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1. The Effect of Chemical Fertilization Time on NPK Pannaes Contents and Yield of New Date Palm Breading for Three Cultivars

Author: Adnan Hameed, Iman Kassiem, Waleed Fleh Hassan, and Harth Adnan Moter
Subjects: time, pannaes, new date palm breading, Agriculture, Plant culture, SB1-1110, Botany, QK1-989
Abstract: An experiment was conducted during 2014 growing season at Al –Rabi date palm station/Zafaraniah /Baghdad to study the effect of chemical fertilization time on NPK pannaes contents, offsets number and yield of new date palm breading for Barhee, Zahdee and Kathrawee Mandly cultivars . There are five chemical fertilization times first time (march and September) second time (march, April and September) third time (march, April ,May and September) forth time(march, April ,May, June and September) and the last time in September , an experiment was growing under drip irrigation. The results show that a significant increases in nitrogen and phousphors pannas contents in September , it were 1.33 , 0.226 mg.kg-1 dry mater for nitrogen and phousphors respectly ,the highest value of nitrogen pannas content had record in Zahdee cultivar it was 1.36 mg N.kg-1 dry mater , the highest value of nitrogen pannas content had record in Kathrawee Mandly cultivar fertilized in September it was 0.247 mgP.kg-1 dry mater . There were a significant increases in potassium pannas content in forth time , it were 1.262 mgK.kg-1 dry mater ,the highest value of potassium pannas content had record in Zahdee cultivar fertilized in forth time it was 1.20 mg K.kg-1 dry mater, although results show a significant increase in yield in second time , it was 13.78 kg.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar it was 13.85 kg.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar fertilized in second time it was 15.67 kg.tree-1, although results show a significant increase in off sheet number in first time , it was 9.56 offsheet.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar it was 9.17 offsheet.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar fertilized in first time it was 14.33 offsheet.tree-1.
Published: 2017
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2. The Effect of Chemical Fertilization Time on NPK Pannaes Contents and Yield of New Date Palm Breading for Three Cultivars

Author: Waleed Fleh Hassan, Adnan Hameed Salman, Iman Kassiem Mohamed, and Harth Adnan Moter
Subjects: Agriculture, Plant culture, SB1-1110, Botany, QK1-989
Abstract: An experiment was conducted during 2014 growing season at Al –Rabi date palm station/Zafaraniah /Baghdad to study the effect of chemical fertilization time on NPK pannaes contents,offsets number and yield of new date palm breading for Barhee, Zahdee and Kathrawee Mandly cultivars . There are five chemical fertilization times first time (march and September) second time (march, April and September) third time (march, April ,May and September) forth time(march, April ,May, June and September) and the last time in September , an experiment was growing under drip irrigation. The results show that a significant increases in nitrogen and phousphors pannas contents in September , it were 1.33 , 0.226 mg.kg-1 dry mater for nitrogen and phousphors respectly ,the highest value of nitrogen pannas content had record in Zahdee cultivar it was 1.36 mg N.kg-1 dry mater , the highest value of nitrogen pannas content had record in Kathrawee Mandly cultivar fertilized in September it was 0.247 mgP.kg-1 dry mater .There were a significant increases in potassium pannas content in forth time , it were 1.262 mgK.kg-1 dry mater ,the highest value of potassium pannas content had record in Zahdee cultivar fertilized in forth time it was 1.20 mg K.kg-1 dry mater, although results show a significant increase in yield in second time , it was 13.78 kg.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar it was 13.85 kg.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar fertilized in second time it was 15.67 kg.tree-1, although results show a significant increase in off sheet number in first time , it was 9.56 offsheet.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar it was 9.17 offsheet.tree-1 , the highest value of yield had record in Kathrawee Mandly cultivar fertilized in first time it was 14.33 offsheet.tree-1.
Published: 2018

3. EmbB and EmbC regulate the sensitivity of Mycobacterium abscessus to echinomycin

Author: Jing He, Yamin Gao, Jingyun Wang, H. M. Adnan Hameed, Shuai Wang, Cuiting Fang, Xirong Tian, Jingran Zhang, Xingli Han, Yanan Ju, Yaoju Tan, Junying Ma, Jianhua Ju, Jinxing Hu, Jianxiong Liu, and Tianyu Zhang
Subjects: echinomycin, EmbB, EmbC, functional compensation, Mycobacterium abscessus, Microbiology, QR1-502
Abstract: Abstract Treatment of Mycobacterium abscessus (Mab) infections is very challenging due to its intrinsic resistance to most available drugs. Therefore, it is crucial to discover novel anti‐Mab drugs. In this study, we explored an intrinsic resistance mechanism through which Mab resists echinomycin (ECH). ECH showed activity against Mab at a minimum inhibitory concentration (MIC) of 2 µg/ml. A ΔembC strain in which the embC gene was knocked out showed hypersensitivity to ECH (MIC: 0.0078–0.0156 µg/ml). The MICs of ECH‐resistant strains screened with reference to ΔembC ranged from 0.25 to 1 µg/ml. Mutations in EmbB, including D306A, D306N, R350G, V555I, and G581S, increased the Mab's resistance to ECH when overexpressed in ΔembC individually (MIC: 0.25–0.5 µg/ml). These EmbB mutants, edited using the CRISPR/Cpf1 system, showed heightened resistance to ECH (MIC: 0.25–0.5 µg/ml). The permeability of these Mab strains with edited genes and overexpression was reduced, as evidenced by an ethidium bromide accumulation assay, but it remained significantly higher than that of the parent Mab. In summary, our study demonstrates that ECH exerts potent anti‐Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH. Mutation in EmbB may partially compensate for a loss of EmbC function.
Published: 2024
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4. A novel non-invasive murine model for rapidly testing drug activity via inhalation administration against Mycobacterium tuberculosis

Author: Xirong Tian, Yamin Gao, Chunyu Li, Wanli Ma, Jingran Zhang, Yanan Ju, Jie Ding, Sanshan Zeng, H. M. Adnan Hameed, Htin Lin Aung, Nanshan Zhong, Gregory M. Cook, Jinxing Hu, and Tianyu Zhang
Subjects: inhalation administration, autoluminescence, tuberculosis, murine model, chemotherapy, Therapeutics. Pharmacology, RM1-950
Abstract: The efficacy of many compounds against Mycobacterium tuberculosis is often limited when administered via conventional oral or injection routes due to suboptimal pharmacokinetic characteristics. Inhalation-based delivery methods have been investigated to achieve high local therapeutic doses in the lungs. However, previous models, typically employing wild-type M. tuberculosis strains, were intricate, time-consuming, labor-intensive, and with poor reproducibility. In this study, we developed an autoluminescence-based inhalation administration model to evaluate drug activity by quantifying relative light units (RLUs) emitted from live mice infected with autoluminescent M. tuberculosis. This novel approach offers several advantages: (1) it eliminates the need for anesthesia in mice during administration and simplifies the instrument manipulation; (2) it is cost-effective by utilizing mice instead of larger animals; (3) it shortens the time from several months to 16 or 17 days for obtaining result; (4) it is non-invasive by directly measuring the live RLUs of mice as a surrogate marker for colony-forming units for in vivo drug activity testing; (5) up to six mice can be administrated daily and simultaneously, even 2–3 times/day; (6) results are relatively objective and reproducible results minimizing human factors. Proof-of-concept experiments demonstrated that inhalable rifampicin, isoniazid, and ethambutol showed anti-M. tuberculosis activity at concentrations as low as 0.5, 0.5, and 0.625 mg/mL, respectively, as evidenced by comparing the live RLUs of mice. Furthermore, consistency between RLUs and colony-forming units of the autoluminescent M. tuberculosis in lungs reaffirms the reliability of RLUs as an indicator of drug efficacy, highlighting the potential of this approach for accurately assessing anti-M. tuberculosis activity in vivo. This autoluminescence-based, non-invasive inhalation model offers a substantial reduction in the time, effort, and cost required for evaluating the efficacy of screening new drugs and repurposing old drugs in vivo via inhalation administration.
Published: 2025
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5. Towards predicting individual treatment response in patients with multiple sclerosis

Author: Al-Araji, Sarmad Adnan Hameed
Abstract: This thesis demonstrates an observational predominantly retrospective study of nearly 2000 consecutive relapsing remitting multiple sclerosis (RRMS) patients recruited after initiating disease modifying therapies (DMTs); glatiramer acetate, dimethyl fumarate, fingolimod, natalizumab or ocrelizumab, in the National Health Service at the National Hospital for Neurology and Neurosurgery and followed up for a period of two years. Due to the heterogeneity of onset, diagnosis, classification, treatment response and prognosis, it is difficult to predict outcomes in MS patients. Machine learning has been evolving in the medical field over the last two decades and we have therefore reviewed the literature on the use of machine learning (ML) in MS diagnosis, classification, progression and prediction. Despite the enormous application on ML in the field of MS in the last 10 years, we found limited studies that have focused on predicting the response to DMTs that could assist clinicians in choosing the best treatment for MS patients. We therefore explored the association of routinely available clinical and radiological variables in predicting NEDA (no evidence of disease activity) at the group-level in our separate cohorts. We found that baseline variables including older age at MS onset, lower number of previous DMTs, lower number of relapses in the previous 12 months, lower number of new and/or Gd-enhancing MRI brain lesions, and lower EDSS score showed significant association of achieving NEDA in most cohorts. Whilst these factors are associated with clinical response at the group-level, we are unable to make clinically useful predictions of treatment response at the individual-level. We therefore built a Bayesian modelling framework optimal for estimating individual-level uncertainty in predicting NEDA. We combined all cohorts and built five predicting models with increasing complexity. The most comprehensive model with 12 clinical and radiological predictors showed the best accuracy, reaching 73% and 69%, in predicting individualised NEDA at 1 and 2 years, respectively. Finally, since there have been no head-to-head phase III clinical trials comparing multiple DMTs with variable efficacy, we conducted a pilot study to compare the clinical and radiological effectiveness of five different DMTs in our real-world cohort using propensity score adjustment. Although ocrelizumab showed slightly better outcomes, considering the limitations of this study, including the observational and retrospective nature of the study, different therapies used over two decades and the small sample size, further larger studies and using propensity score matching are needed in the absence of randomised controlled trials.
Published: 2023

6. Investigating the role of MAB_1915 in intrinsic resistance to multiple drugs in Mycobacterium abscessus

Author: Buhari Yusuf, Shuai Wang, Md Shah Alam, Jingran Zhang, Zhiyong Liu, Ziwen Lu, Jie Ding, Gift Chiwala, Yamin Gao, Cuiting Fang, Shahzad Akbar Khan, Xirong Tian, Md Mahmudul Islam, H. M. Adnan Hameed, Dmitry A. Maslov, Nanshan Zhong, Jinxing Hu, and Tianyu Zhang
Subjects: Mycobacterium abscessus, MAB_1915, fatty acid-CoA ligase, cell envelope permeability, intrinsic drug resistance, Microbiology, QR1-502
Abstract: ABSTRACT The increasing clinical significance of Mycobacterium abscessus is owed to its innate high-level, broad-spectrum resistance to antibiotics and therefore rapidly evolves as an important human pathogen. This warrants the identification of novel targets for aiding the discovery of new drugs or drug combinations to treat M. abscessus infections. This study is inspired by the drug-hypersensitive profile of a mutant M. abscessus (U14) with transposon insertion in MAB_1915. We validated the role of MAB_1915 in intrinsic drug resistance in M. abscessus by constructing a selectable marker-free in-frame deletion in MAB_1915 and complementing the mutant with the same or extended version of the gene and then followed by drug susceptibility testing. Judging by the putative function of MAB_1915, cell envelope permeability was studied by ethidium bromide accumulation assay and susceptibility testing against dyes and detergents. In this study, we established genetic evidence of the role of MAB_1915 in intrinsic resistance to rifampicin, rifabutin, linezolid, clarithromycin, vancomycin, and bedaquiline. Disruption of MAB_1915 has also been observed to cause a significant increase in cell envelope permeability in M. abscessus. Restoration of resistance is observed to depend on at least 27 base pairs upstream of the coding DNA sequence of MAB_1915. MAB_1915 could therefore be associated with cell envelope permeability, and hence its role in intrinsic resistance to multiple drugs in M. abscessus, which presents it as a novel target for future development of effective antimicrobials to overcome intrinsic drug resistance in M. abscessus.IMPORTANCEThis study reports the role of a putative fadD (MAB_1915) in innate resistance to multiple drugs by M. abscessus, hence identifying MAB_1915 as a valuable target and providing a baseline for further mechanistic studies and development of effective antimicrobials to check the high level of intrinsic resistance in this pathogen.
Published: 2024
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7. Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis

Author: Md Mahmudul Islam, Md Shah Alam, Zhiyong Liu, Mst Sumaia Khatun, Buhari Yusuf, H. M. Adnan Hameed, Xirong Tian, Chiranjibi Chhotaray, Rajesh Basnet, Haftay Abraha, Xiaofan Zhang, Shahzad Akbar Khan, Cuiting Fang, Chunyu Li, Sohel Hasan, Shouyong Tan, Nanshan Zhong, Jinxing Hu, and Tianyu Zhang
Subjects: cross-resistance, drug resistance, mechanism of action, molecular diagnostic, regimens, treatment, Medicine (General), R5-920
Abstract: Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) Mtb strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against Mtb strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the Rv0678, pepQ, Rv1979c, and atpE genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against Mtb can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB.
Published: 2024
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8. Amino acid 17 in QRDR of Gyrase A plays a key role in fluoroquinolones susceptibility in mycobacteria

Author: Shuai Wang, Jingran Zhang, H. M. Adnan Hameed, Jie Ding, Ping Guan, Xiange Fang, Jiacong Peng, Biyi Su, Shangming Ma, Yaoju Tan, Gregory M. Cook, Guoliang Zhang, Yongping Lin, Nanshan Zhong, Jinxing Hu, Jianxiong Liu, and Tianyu Zhang
Subjects: fluoroquinolone, mycobacteria, intrinsic resistance, gene editing, Mycobacterium abscessus, Microbiology, QR1-502
Abstract: ABSTRACT The polymorphism at amino acid 17 of quinolone resistance-determining region of GyrA has been stated with a potential role in fluoroquinolone susceptibility in different mycobacterial species. However, no study has provided dependable evidence so far. Here, we verified that gene-edited Mycobacterium abscessus mutants bearing Ser/Gly at this position were more susceptible to fluoroquinolones than their parent strain and the revertant that supports mycobacteria containing Ser/Gly at this position were more susceptible to fluoroquinolones than those containing Ala. IMPORTANCE Fluoroquinolones (FQs) play a key role in the treatment regimens against tuberculosis and non-tuberculous mycobacterial infections. However, there are significant differences in the sensitivities of different mycobacteria to FQs. In this study, we proved that this is associated with the polymorphism at amino acid 17 of quinolone resistance-determining region of Gyrase A by gene editing. This is the first study using CRISPR-associated recombination for gene editing in Mycobacterium abscessus to underscore the contribution of the amino acid substitutions in GyrA to FQ susceptibilities in mycobacteria.
Published: 2023
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9. Economic Consequences Based on Reversible and Irreversible Degradation of PV Park in the Harsh Climate Conditions of Iraq

Author: Mohammed Adnan Hameed, David Daßler, Qais Matti Alias, Roland Scheer, and Ralph Gottschalg
Subjects: MENA, reliability, PV systems, soiling, economic impact, LCOE, Technology
Abstract: Photovoltaic (PV) system reliability and durability investigations are essential for industrial maturity and economic success. Recently, PV systems received much interest in Iraq due to many reasons—for instance, power shortage, global warming and pollution. Despite this interest, the precise economic implications of PV system reliability in harsh climates like Iraq remain uncertain. This work assesses the economic implications of PV system component reliability and soiling in Iraq using field experience and historical data. This study identifies the most common failure modes of PV systems installed in Iraq and similar climatic regions, and also ranks their severity. Simulations explore scenarios of PV module degradation rates, inverter lifetimes, soiling rates, and cleaning intervals, revealing that soiling has the most detrimental effect, with cleaning frequency leading to Levelized Cost of Electricity (LCOE) losses of over 30%, depending on the location. Inverter lifetime contributes to LCOE losses between 4 and 6%, depending on the PV system’s location. This study also evaluates the impact of tilt angle as a mitigation strategy for reducing soiling loss and its economic implications, finding that installing PV modules at higher tilt angles could reduce the economic impact of soiling by approximately 4.4%. Additionally, the optimal cleaning strategy identified is fully automated dry cleaning with robots, outperforming other strategies economically. Overall, the findings highlight that the LCOE in Iraq is relatively high compared to the global weighted average for utility-scale PV systems, primarily due to high soiling and degradation rates. The LCOE varies within the country, influenced by different degradation rates. This study aims to assist PV stakeholders in Iraq and the Middle East and North Africa (MENA) region in accurately estimating solar bankability; moreover, increasing reliability by minimizing the technical and financial risks by considering key parameters specific to these regions.
Published: 2024
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10. Clinical and therapeutic characteristics and medical cost of managing cancer patients in Al-Anbar, Iraq: A cross-sectional study

Author: Adnan Hameed, Hameed, Naser, Abdallah Y, and Mudheher Talib, Nabeel
Published: 2022
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11. Rapid visualized assessment of drug efficacy in live mice with a selectable marker-free autoluminescent Klebsiella pneumoniae

Author: Tian, Xirong, Gao, Yamin, Wang, Shuai, Adnan Hameed, H.M., Yu, Wei, Fang, Cuiting, Zhang, Jingran, Tan, Yaoju, Cao, Zhizhong, Guan, Ping, Hu, Jinxing, Liu, Jianxiong, Zhong, Nanshan, and Zhang, Tianyu
Published: 2021
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12. Experimental and numerical investigations of heat transfer enhancement in shell and helically microtube heat exchanger using nanofluids

Author: Rasheed, Adnan Hameed, Alias, Hajar Binti, and Salman, Sami Dawood
Published: 2021
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13. Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for Mycobacterium ulcerans

Author: Yamin Gao, H.M. Adnan Hameed, Yang Liu, Lingmin Guo, Cuiting Fang, Xirong Tian, Zhiyong Liu, Shuai Wang, Zhili Lu, Md Mahmudul Islam, and Tianyu Zhang
Subjects: Mycobacterium ulcerans, Buruli ulcer, Electron transport chain, QcrB, Chemotherapy, TB47, Therapeutics. Pharmacology, RM1-950
Abstract: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with rifampin–streptomycin or rifampin–clarithromycin daily for 8 weeks recommended by World Health Organization (WHO). These options are lengthy with severe side effects. A new anti-tuberculosis drug, TB47, targeting QcrB in cytochrome bc1:aa3 complex is being developed in China. TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M. ulcerans strain. High-level TB47-resistant spontaneous M. ulcerans mutants were selected and their qcrB genes were sequenced. The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model. Here, we show that TB47-containing oral 3-drug regimens can completely cure BU in ≤2 weeks for daily use or in ≤3 weeks given twice per week (6 doses in total). All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice. This is the first report of double mutations in QcrB in mycobacteria. In summary, TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance. Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants.
Published: 2021
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14. Prevalence and molecular characterization of amikacin resistance among Mycobacterium tuberculosis clinical isolates from southern China

Author: Md Mahmudul Islam, Yaoju Tan, H.M. Adnan Hameed, Yang Liu, Chiranjibi Chhotaray, Xiaoyin Cai, Zhiyong Liu, Zhili Lu, Shuai Wang, Xingshan Cai, Biyi Su, Xinjie Li, Shouyong Tan, Jianxiong Liu, and Tianyu Zhang
Subjects: Amikacin, Tuberculosis, Mutation, Resistance, Injectable drug, Susceptibility testing, Microbiology, QR1-502
Abstract: Objectives: Amikacin is the only second-line injectable antituberculosis (anti-TB) drug still recommended for multidrug-resistant tuberculosis (MDR-TB) treatment when a short MDR-TB regimen is designed. Mutations in rrs and eis are reported to be associated with resistance to amikacin. In this study, we investigated the incidence of rrs, eis, tap and whiB7 mutations in amikacin-resistant Mycobacterium tuberculosis clinical isolates to find the proportion of different mutations related to amikacin resistance. Methods: A total of 395 clinical isolates of M. tuberculosis were used for phenotypic drug susceptibility testing (DST) to 10 drugs with the Löwenstein–Jensen (L–J) method. We sequenced rrs, eis, tap and whiB7 genes in 178 M. tuberculosis clinical isolates (89 amikacin-resistant isolates and 89 of 306 amikacin-susceptible isolates). Results: Our data showed that 22.53% (89/395) M. tuberculosis clinical isolates were resistant to amikacin. Of the 89 amikacin-resistant isolates, 89.89% (80/89) were MDR-TB, of which 12.36% (11/89) were pre-extensively drug-resistant TB (pre–XDR-TB) and 77.53% (69/89) were XDR-TB. The rrs mutations were found in 82% (73/89) in amikacin-resistant M. tuberculosis clinical isolates. The A1401G alteration in the rrs gene was the most dominant mutation (80.90%; 72/89). Five mutations were detected as new in rrs, tap and whiB7. Notably, 13.48% (12/89) amikacin-resistant isolates had no known mutation in these genes. Conclusions: Our data reveal that the rrs mutation is a predominant molecular marker of amikacin resistance in southern China. Analysis of the rrs gene mutations will significantly reduce the time and cost to diagnose amikacin resistance in TB patients. Other unknown amikacin resistance mechanism(s) exist.
Published: 2020
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15. Comparative Analysis of Whole-Genome and Methylome Profiles of a Smooth and a Rough Mycobacterium abscessus Clinical Strain

Author: Chiranjibi Chhotaray, Shuai Wang, Yaoju Tan, Amjad Ali, Muhammad Shehroz, Cuiting Fang, Yang Liu, Zhili Lu, Xingshan Cai, H. M. Adnan Hameed, Md Mahmudul Islam, Goverdhan Surineni, Shouyong Tan, Jianxiong Liu, and Tianyu Zhang
Subjects: mycobacterium abscessus, smrt sequencing, comparative genomics, whole genome sequencing, methylation, single nucleotide variation, Genetics, QH426-470
Abstract: Mycobacterium abscessus is a fast growing Mycobacterium species mainly causing skin and respiratory infections in human. M. abscessus is resistant to numerous drugs, which is a major challenge for the treatment. In this study, we have sequenced the genomes of two clinical M. abscessus strains having rough and smooth morphology, using the single molecule real-time and Illumina HiSeq sequencing technology. In addition, we reported the first comparative methylome profiles of a rough and a smooth M. abscessus clinical strains. The number of N4-methylcytosine (4mC) and N6-methyladenine (6mA) modified bases obtained from smooth phenotype were two-fold and 1.6 fold respectively higher than that of rough phenotype. We have also identified 4 distinct novel motifs in two clinical strains and genes encoding antibiotic-modifying/targeting enzymes and genes associated with intracellular survivability having different methylation patterns. To our knowledge, this is the first report about genome-wide methylation profiles of M. abscessus strains and identification of a natural linear plasmid (15 kb) in this critical pathogen harboring methylated bases. The pan-genome analysis of 25 M. abscessus strains including two clinical strains revealed an open pan genome comprises of 7596 gene clusters. Likewise, structural variation analysis revealed that the genome of rough phenotype strain contains more insertions and deletions than the smooth phenotype and that of the reference strain. A total of 391 single nucleotide variations responsible for the non-synonymous mutations were detected in clinical strains compared to the reference genome. The comparative genomic analysis elucidates the genome plasticity in this emerging pathogen. Furthermore, the detection of genome-wide methylation profiles of M. abscessus clinical strains may provide insight into the significant role of DNA methylation in pathogenicity and drug resistance in this opportunistic pathogen.
Published: 2020
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16. Advances in the development of molecular genetic tools for Mycobacterium tuberculosis

Author: Chhotaray, Chiranjibi, Tan, Yaoju, Mugweru, Julius, Islam, Md Mahmudul, Adnan Hameed, H.M., Wang, Shuai, Lu, Zhili, Wang, Changwei, Li, Xinjie, Tan, Shouyong, Liu, Jianxiong, and Zhang, Tianyu
Published: 2018
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17. Survival After Invasive or Conservative Management of Stable Coronary Disease

Author: Judith S. Hochman, Rebecca Anthopolos, Harmony R. Reynolds, Sripal Bangalore, Yifan Xu, Sean M. O’Brien, Stavroula Mavromichalis, Michelle Chang, Aira Contreras, Yves Rosenberg, Ruth Kirby, Balram Bhargava, Roxy Senior, Ann Banfield, Shaun G. Goodman, Renato D. Lopes, Radosław Pracoń, José López-Sendón, Aldo Pietro Maggioni, Jonathan D. Newman, Jeffrey S. Berger, Mandeep S. Sidhu, Harvey D. White, Andrea B. Troxel, Robert A. Harrington, William E. Boden, Gregg W. Stone, Daniel B. Mark, John A. Spertus, David J. Maron, Shari Esquenazi-Karonika, Margaret Gilsenan, Ewelina Gwiszcz, Patenne Mathews, Samaa Mohamed, Anna Naumova, Arline Roberts, Kerrie VanLoo, Ying Lu, Zhen Huang, Samuel Broderick, Luis Guzmán, Joseph Selvanayagam, Gabriel Steg, Jean-Michel Juliard, Rolf Doerr, Matyas Keltai, Boban Thomas, Tali Sharir, Eugenia Nikolsky, Aldo P. Maggioni, Shun Kohsaka, Jorge Escobedo, Olga Bockeria, Claes Held, Leslee J. Shaw, Lawrence Phillips, Daniel Berman, Raymond Y. Kwong, Michael H. Picard, Bernard R. Chaitman, Ziad Ali, James Min, G.B. John Mancini, Jonathon Leipsic, Graham Hillis, Suku Thambar, Majo Joseph, John Beltrame, Irene Lang, Herwig Schuchlenz, Kurt Huber, Kaatje Goetschalckx, Whady Hueb, Paulo Ricardo Caramori, Alexandre de Quadros, Paola Smanio, Claudio Mesquita, João Vitola, José Marin-Neto, Expedito Ribeiro da Silva, Rogério Tumelero, Marianna Andrade, Alvaro Rabelo Alves, Frederico Dall’Orto, Carisi Polanczyk, Estevão Figueiredo, Andrew Howarth, Gilbert Gosselin, Asim Cheema, Kevin Bainey, Denis Phaneuf, Ariel Diaz, Pallav Garg, Shamir Mehta, Graham Wong, Andy Lam, James Cha, Paul Galiwango, Amar Uxa, Benjamin (Ben) Chow, Adnan Hameed, Jacob Udell, Magdy Hamid, Marie Hauguel-Moreau, Alain Furber, Pascal Goube, Philippe-Gabriel Steg, Gilles Barone-Rochette, Christophe Thuaire, Michel Slama, Georg Nickenig, Raffi Bekeredjian, P. Christian Schulze, Bela Merkely, Geza Fontos, András Vértes, Albert Varga, Ajit Kumar, Rajesh G. Nair, Purvez Grant, Cholenahally Manjunath, Nagaraja Moorthy, Santhosh Satheesh, Ranjit Kumar Nath, Gurpreet Wander, Johann Christopher, Sudhanshu Dwivedi, Abraham Oomman, Atul Mathur, Milind Gadkari, Sudhir Naik, Eapen Punnoose, Ranjan Kachru, Upendra Kaul, Arthur Kerner, Giuseppe Tarantini, Gian Piero Perna, Emanuela Racca, Andrea Mortara, Lorenzo Monti, Carlo Briguori, Gianpiero Leone, Roberto Amati, Mauro Salvatori, Antonio Di Chiara, Paolo Calabro, Marcello Galvani, Stefano Provasoli, Keiichi Fukuda, Shintaro Nakano, Aleksandras Laucevicius, Sasko Kedev, Ahmad Khairuddin, Robert Riezebos, Jorik Timmer, Spencer Heald, Ralph Stewart, Walter Mogrovejo Ramos, Marcin Demkow, Tomasz Mazurek, Jarozlaw Drozdz, Hanna Szwed, Adam Witkowski, Nuno Ferreira, Fausto Pinto, Ruben Ramos, Bogdan Popescu, Calin Pop, Leo Bockeria, Elena Demchenko, Alexander Romanov, Leonid Bershtein, Ahmed Jizeeri, Goran Stankovic, Svetlana Apostolovic, Nada Cemerlic Adjic, Marija Zdravkovic, Branko Beleslin, Milica Dekleva, Goran Davidovic, Terrance Chua, David Foo, Kian Keong Poh, Mpiko Ntsekhe, Alessandro Sionis, Francisco Marin, Vicente Miró, Montserrat Gracida Blancas, José González-Juanatey, Francisco Fernández-Avilés, Jesús Peteiro, Jose Enrique Castillo Luena, Johannes Aspberg, Mariagrazia Rossi, Srun Kuanprasert, Sukit Yamwong, Nicola Johnston, Patrick Donnelly, Andrew Moriarty, Ahmed Elghamaz, Sothinathan Gurunathan, Nikolaos Karogiannis, Benoy N. Shah, Richard H.J. Trimlett, Michael B. Rubens, Edward D. Nicol, Tarun K. Mittal, Reinette Hampson, Reto Gamma, Mark De Belder, Thuraia Nageh, Steven Lindsay, Kreton Mavromatis, Todd Miller, Subhash Banerjee, Harmony Reynolds, Khaled Nour, and Peter Stone
Subjects: Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract: Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85–1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63–0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08–1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04894877.
Published: 2023
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18. Quantum Chemical and Experimental Insight into Structure, Physicochemical Properties and Dissolving Behavior of Deep Eutectic Solvents

Author: Yuling Zhang, Hongwei Ren, Yize Liu, Meiyu Li, Adnan Hameed Rasheed, Hajar Alias, and Erhong Duan
Subjects: Computational Theory and Mathematics, Physical and Theoretical Chemistry, Computer Science Applications
Abstract: During the past decade, deep eutectic solvents (DESs), emerging as green, versatile and adjustable alternatives to traditional solvents, have attracted intensive interests and immense research in various research fields. Especially DESs show quite a remarkable potential dissolving capability, due to their ability to donate as well as accept protons and electrons. A thorough and deep understanding of the microstructure, interactions and dissolving mechanism within DESs plays a key role in acquiring a task-specific DES. Quantum chemistry (QC) calculations provide structure-property-function relationship based on the molecular description and make up for the limitations of the current experimental techniques, showing promises for DESs screening and design. This paper summarizes the current research involving QC calculations and combined experiments, on investigating the structure, physicochemical properties and dissolving capability of DESs from the macroscopic and microcosmic perspective. This paper highlights and discusses the dissolving mechanism of various compounds in DESs, covering the recent successes in applying QC calculations to select the appropriate DESs as dissolving media. Furthermore, a brief analysis of perspectives and challenges for the future research in this field is presented. It is expected that this paper will inspire the future development of DESs from synthesis design to various designated applications.
Published: 2022
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19. Biometric indices and size at first sexual maturity of eight alien fish species from Bangladesh

Author: Hossain, Md. Yeamin, Hossen, Md. Alomgir, Islam, Md. Mahmudul, Uddin Pramanik, Md. Nasir, Nawer, Fairuz, Paul, Alok Kumar, Adnan Hameed, H.M., Rahman, Md. Mosaddequr, Kaushik, Gitartha, and Bardoloi, Sabitry
Published: 2016
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20. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author: Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine Shelley, Christophe Laure, Christophe Thuaire, Christopher Kinsey, Christopher McFarren, Christopher Spizzieri, Christopher Travill, Chun-Chieh Liu, Chung-Lieh Hung, Chunguang Li, Chun-Ho Yun, Chunli Xia, Ciarra Heard, Cidney Schultz, Clare Venn-Edmonds, Claudia P Hochberg, Claudia Wegmayr, Claudia Cortés, Claudia Escobar, Cláudia Freixo, Claudio T Mesquita, Clemens T Kadalie, Colin Berry, Constance Philander, Corine Thobois, Costantino Costantini, Courtney Page, Craig Atkinson, Craig Barr, Craig Paterson, Cristina Bare, Cynthia Baumann, Cynthia Burman, Dalisa Espinosa, Damien Collison, Dan Deleanu, Dan Elian, Dan Gao, Dana Oliver, Daniel P Vezina, Daniel O'Rourke, Daniele Komar, Danielle Schade, Darrel P Francis, Dastan Malaev, David A Bull, David E Winchester, David P Faxon, David Booth, David Cohen, David DeMets, David Foo, David Schlichting, David Taggart, David Waters, David Wohns, Davis Vo, Dawid Teodorczyk, Dawn Shelstad, Dawn Turnbull, Dayuan Li, Dean Kereiakes, Deborah O'Neill, Deborah Yip, Debra K Johnson, Debra Dees, Deepak L Bhatt, Deepika Gopal, Deepti Kumar, Deirdre Mattina, Deirdre Murphy, Delano R Small, Delsa K Rose, Dengke Jiang, Denis Carl Phaneuf, Denise Braganza, Denise Fine, Derek Cyr, Desiree Tobin, Diana Cukali, Diana Parra, Diane Camara, Diane Minshall Liu, Diego Adrián Vences, Diego Franca de Cunha, Dimitrios Stournaras, Dipti Patel, Dongze Li, Donna Exley, Dorit Grahl, Dragana Stanojevic, Duarte Cacela, Dwayne S G Conway, E Pinar Bermudez, Eapen Punnoose, Edgar L Tay, Edgar Karanjah, Edoardo Verna, Eduardo Hernandez-Rangel, Edward D Nicol, Edward O McFalls, Edward T Martin, Edyta Kaczmarska, Ekaterina I Lubinskaya, Elena A Demchenko, Elena Refoyo Salicio, Eli Feen, Elihú Durán-Cortés, Elisabeth M Janzen, Elise L Hannemann, Elise van Dongen, Elissa Restelli Piloto, Eliza Kaplan, Elizabeta Srbinovska Kostovska, Elizabeth Capasso-Gulve, Elizabeth Congdon, Elizabeth Ferguson, Elizaveta V Zbyshevskaya, Ellen Magedanz, Ellie Fridell, Ellis W Lader, Elvin Kedhi, Emanuela Racca, Emilie Tachot, Emily DeRosa, Encarnación Alonso-Álvarez, Eric Nicollet, Eric Peterson, Erick Alexánderson Rosas, Erick Donato Morales, Erin Orvis, Ermina Moga, Estelle Montpetit, Estevao Figueiredo, Eugene Passamani, Eugenia Nikolsky, Eunice Yeoh, Evgeniy I Kretov, Ewa Szczerba, Ewelina Wojtala, Expedito Eustáquio Ribeiro Silva, F Marin Ortuño, Fabio R Farias, Fabio Fimiani, Fabrizio Rolfo, Fa-Chang Yu, Fadi Hage, Fadi Matar, Fahim Haider Jafary, Fang Feng, Fang Liu, Fatima Ranjbaran, Fatima Rodriguez, Fausto J Pinto, Fauzia Rashid, Federica Ramani, Fei Wang, Fernanda Igansi, Filipa Silva, Filippo Ottani, Fiona Haines, Firas Al Solaiman, Flávia Egydio, Flavio Lyra, Florian Egger, Fran Farquharson, Frances Laube, Francesc Carreras Costa, Francesca de Micco, Francesca Bianchini, Francesca Pezzetta, Francesca Pietrucci, Francesco Orso, Francesco Pisano, Francis Burt, Francisca Patuleia Figueiras, Francisco Fernandez-Aviles, Francois Pierre Mongeon, Frans Van de Werf, Franziska Guenther, Fraser N Witherow, Fred Mohr, Frederico Dall'Orto, Fumiyuki Otsuka, G De La Morena, G Karthikeyan, Gabor Dekany, Gabor Kerecsen, Gabriel Galeote, Gabriel Grossmann, Gabriel Vorobiof, Gabriela Sanchez de Souza, Gabriela Guzman, Gabriela Zeballos, Gabriele Gabrielli, Gabriele Jakl-Kotauschek, Gail A Shammas, Gail Brandt, Gang Chen, Gary E Lane, Gary J Luckasen, Gautam Sharma, Gelmina Mikolaitiene, Gennie Yee, Georg Nickenig, George E Revtyak, George J Juang, Gerald Fletcher, Gerald Leonard, Gerard Patrick Devlin, Gerard Esposito, Gergely Ágoston, Gervasio Lamas, Geza Fontos, Ghada Mikhail, Gia Cobb, Gian Piero Perna, Gianpiero Leone, Giles Roditi, Gilles Barone-Rochette, Girish Mishra, Giuseppe Tarantini, Glenda Wong, Glenn S Hamroff, Glenn Rayos, Gong Cheng, Gonzalo Barge-Caballero, Goran Davidović, Goran Stankovic, Gordana Stevanovic, Grace Jingyan Wang, Grace M Young, Graceanne Wayser, Graciela Scaro, Graham S Hillis, Graham Wong, Grazyna Anna Szulczyk, Gregor Simonis, Gregory Kumkumian, Gretchen Ann Peichel, Grzegorz Gajos, Gudrun Steinmaurer, Guilherme G Rucatti, Guilherme Portugal, Guilhermina Cantinho Lopes, Guillem Pons Lladó, Gunnar Frostfelt, Gurpreet S Wander, Gurpreet Gulati, Gustavo Pucci, Hafidz Abd Hadi, Haibo Zhang, Haitao Wang, Halina Marciniak, Han Chen, Hanan Kerr, Hani Najm, Hanna Douglas, Hannah Phillips, Hao Dai, Haojian Dong, Haqeel Jamil, Harikrishnan Sivadasanpillai, Harry Suryapranata, Hassan Reda, Hayley Pomeroy, Heather Barrentine, Heather Golden, Heather Hurlburt, Heidi Wilson, Helen C Tucker, Helene Abergel, Hemalata Siddaram, Hermine Osseni, Herwig Schuchlenz, Hesong Zeng, Hicham Skali, Hilda Solomon, Hollie Horton, Holly Hetrick, Holly Little, Holly Park, Hongjie Chi, Hossam Mahrous, Howard A Levite, Hristo Pejkov, Huajun Li, Hugo Bloise-Adames, Hugo Marques, Hui Zhong, Hui-Min Zhang, Humayrah Hashim, Hung-I Yeh, Hussien El Fishawy, Ian Webb, Iftikhar Kullo, Igor O Grazhdankin, Ihab Hamzeh, Ikraam Hassan, Ikuko Ueda, Ileana L Pina, Ilona Tamasauskiene, Ilse Bouwhuis, Imran Arif, Ina Wenzelburger, Inês Zimbarra Cabrita, Ines Rodrigues, Inga H Robbins, Inga Soveri, Ingela Schnittger, Iqbal Karimullah, Ira M Dauber, Iram Rehman, Irena Peovska Mitevska, Irene Marthe Lang, Irina Subbotina, Irma Kalibataite-Rutkauskiene, Irni Yusnida, Isabel Estela Carvajal, Isabella C Palazzo, Isabelle Hogan, Isabelle Roy, Ishba Syed, Ishita Tejani, Ivan A Naryshkin, Ivana Jankovic, Iwona Niedzwiecka, J David Knight, Jacek Kusmierek, Jackie M White, Jackie Chow, Jacob Udell, Jacqueline E Tamis-Holland, Jacqueline Fannon, Jacquelyn A Quin, Jacquelyn Do, Jaekyeong Heo, Jakub Maksym, James E Davies, James H O'Keefe Jr, James J Jang, James Cha, James Harrison, James Hirsch, James Stafford, James Tatoulis, Jamie Rankin, Jan Henzel, Jan Orga, Jana Tancredi, Janaina Oliveira, Jane Burton, Jane Eckstein, Jane Marucci, Janet P Knight, Janet Blount, Janet Halliday, Janetta Kourzenkova, Janitha Raj, Jan-Malte Sinning, Jaqueline Pozzibon, Jaroslaw Drozdz, Jaroslaw Karwowski, Jason D Glover, Jason Loh Kwok, Jason T Call, Jason Linefsky, Jassira Gomes, Jati Anumpa, Javier J Garcia, Javier Courtis, Jay Meisner, K Jayakumar, Jayne Scales, Jean E Denaro, Jean Michel Juliard, Jean Ho, Jeanette K Stansborough, Jean-Michel Juliard, Jeanne Russo, Jeannette J M Schoep, Jeet Thambyrajah, Jeff Leimberger, Jeffery A Breall, Jeffrey A Kohn, Jeffrey C Milliken, Jeffrey Anderson, Jeffrey Blume, Jeffrey Kanters, Jeffrey Lorin, Jeffrey Moses, Jelena J Stepanovic, Jelena Celutkiene, Jelena Djokic, Jelena Stojkovic, Jenne M Jose, Jenne Manchery, Jennifer A Mull, Jennifer H Czerniak, Jennifer L Stanford, Jennifer Gillis, Jennifer Horst, Jennifer Isaacs, Jennifer Langdon, Jennifer Thomson, Jennifer Tomfohr, Jennifer White, Jen-Yuan Kuo, Jeremy Rautureau, Jerome Fleg, Jessica Berg, Jessica Rodriguez, Jessica Waldron, Jhina Patro, Jia Li, Jiajia Mao, Jiamin Liu, Jian'an Wang, Jianhua Li, Jianxin Zhang, Jie Qi, Jihyun Lyo, Jill Marcus, Jim Blankenship, Jing Zhang, Jingjing Liu, Jing-Yao Fan, Jiun-Yi Li, Jiwan Pradhan, Jiyan Chen, J M Rivera Caravaca, Jo Evans, Joan Garcia Picart, Joan Hecht, Joanna Jaroch, Joanna Zalewska, Joanne Kelly, Joanne Taaffe, João Reynaldo Abbud, João V Vitola, Joaquín V Peñafiel, Jocelyne Benatar, Jody Bindeman, Joe Sabik, Joel Klitch, Johann Christopher, Johannes Aspberg, John D Friedman, John F Beltrame, John F Heitner, John Joseph Graham, John R Davies, John Doan, John Kotter, John Kurian, John Mukai, John Pownall, Jolanta Sobolewska, Jon Kobashigawa, Jonathan L Goldberg, Jonathan W Bazeley, Jonathan Byrne, Jonathan Himmelfarb, Jonathan Leipsic, Jonean Thorsen, Jorge F Trejo Gutierrez, Jorge Escobedo, Jorik Timmer, José A Ortega-Ramírez, José Antonio Marin-Neto, Jose D Salas, Jose Enrique Castillo, Jose Francisco Saraiva, José J Cuenca-Castillo, Jose L Diez, José Luis Narro Villanueva, José Luiz da Vieira, José M Flores-Palacios, Jose Ramon Gonzalez, Jose Seijas Amigo, Jose Fragata, Josep Maria Padró, Josheph F X McGarvey Jr, Joseph Hannan, Joseph Sacco, Joseph Sweeny, Joseph Wiesel, Josephine D Abraham, Joshua P Loh, Joy Burkhardt, Joyce R White, Joyce Riestenberg-Smith, Judit Sebo, Judith L Meadows, Judith Wright, Judy Mae Foltz, Judy Hung, Judy Otis, Juergen Stumpf, Jui-Peng Tsai, Julia S Dionne, Julia de Aveiro Morata, Julie Bunke, Julie Morrow, Julio César Figal, Jun Fujita, Jun Jiang, Junhua Li, Junqing Yang, Juntima Euathrongchit, Jyotsna Garg, K Manjula Rani, K Preethi, Kaatje Goetschalckx, Kai Eggers, Kamalakar Surineni, Kanae Hirase, T R Kapilamoorthy, Karen Calfas, Karen Gratrix, Karen Hallett, Karen Hultberg, Karen Nugent, Karen Petrosyan, Karen Swan, Karolina Kryczka, Karolina Wojtczak-Soska, Karolina Wojtera, Karsten Lenk, Karthik Ramasamy, Katarzyna Łuczak, Katarzyna Malinowska, Kate Pointon, Kate Robb, Katherine Martin, Kathleen Claes, Kathryn Carruthers, Kathy E Siegel, Katia Drouin, Katie Fowler-Lehman, Kavita Rawat, Kay Rowe, Keiichi Fukuda, Keith A A Fox, Ken Mahaffey, Kendra Unterbrink, Kenneth Giedd, Kerrie Van Loo, Kerry Lee, Kerstin Bonin, Kevin R Bainey, Kevin T Harley, Kevin Anstrom, Kevin Chan, Kevin Croce, Kevin Landolfo, Kevin Marzo, Keyur Patel, Khaled Abdul-Nour, Khaled Alfakih, Khaled Dajani, Khaled Ziada, Khaula Baloch, Khrystyna Kushniriuk, Kian-Keong Poh, Kim F Ireland, Kim Holland, Kimberly Ann Byrne, Kimberly E Halverson, Kimberly Elmore, Kimberly Miller-Cox, Kiran Reddy, Kirsten J Quiles, Kirsty Abercrombie, Klaus Matschke, Konrad Szymczyk, Koo Hui Chan, Kotiboinna Preethi, Kozhaya Sokhon, Krissada Meemuk, Kristian Thygesen, Kristin M Salmi, Kristin Newby, Kristina Wippler, Kristine Arges, Kristine Teoh, Krystal Etherington, Krystyna Łoboz-Grudzień, Krzysztof W Reczuch, Krzysztof Bury, Krzysztof Drzymalski, Krzysztof Kukuła, Kuo-Tzu Sung, Kurt Huber, Ladda Douangvila, Lance Sullenberger, Larissa Miranda Trama, Laszlone Matics, Laura Drew, Laura Flint, Laura Keinaite, Laura Sarti, Laurel Kolakaluri, Lawrence M Phillips, Lawrence Friedman, Lawrence Phillips, Lazar Velicki, Leah Howell, Leandro C Maranan, Leanne Cox, Ledjalem Daba, Lei Zhang, Lekshmi Dharmarajan, Leo Bockeria, Leonardo Pizzol Caetano, Leonardo Bridi, Leonid L Bershtein, Leszek Sokalski, Li Hai Yan, Li Li, Lia Nijmeijer, Lidia Sousa, Lihong Xu, Lihua Zhang, Lili Zhang, Lilia Schiavi, Lilian Mazza Barbosa, Lillian L Khor, Lina Felix-Stern, Linda L Hall, Linda M Hollenweger, Linda Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C 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Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira 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Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, 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Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits
Subjects: Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract: BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
Published: 2020
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21. Characterization of Genetic Variants Associated with Rifampicin Resistance Level in Mycobacterium tuberculosis Clinical Isolates Collected in Guangzhou Chest Hospital, China

Author: HM Adnan Hameed, Cuiting Fang, Zhiyong Liu, Yanan Ju, Xingli Han, Yamin Gao, Shuai Wang, Gift Chiwala, Yaoju Tan, Ping Guan, Jinxing Hu, Xiaoli Xiong, Jiacong Peng, Yongping Lin, Muzammal Hussain, Nanshan Zhong, Dmitry A Maslov, Gregory M Cook, Jianxiong Liu, and Tianyu Zhang
Subjects: Pharmacology, Infectious Diseases, Infection and Drug Resistance, Pharmacology (medical)
Abstract: HM Adnan Hameed1â 4&ast;, Cuiting Fang1â 4&ast;, Zhiyong Liu,1â 3 Yanan Ju,1â 3 Xingli Han,1â 4 Yamin Gao,1â 4 Shuai Wang,1â 3,5 Gift Chiwala,1â 4 Yaoju Tan,6 Ping Guan,6 Jinxing Hu,6 Xiaoli Xiong,1â 3 Jiacong Peng,3,7 Yongping Lin,3,7 Muzammal Hussain,4 Nanshan Zhong,3,7,8 Dmitry A Maslov,9 Gregory M Cook,10,11 Jianxiong Liu,6 Tianyu Zhang1â 4 1State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, Peopleâs Republic of China; 2China-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, Peopleâs Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases, Guangzhou, Peopleâs Republic of China; 4University of Chinese Academy of Sciences (UCAS), Beijing, Peopleâs Republic of China; 5National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third Peopleâs Hospital, Shenzhen, Peopleâs Republic of China; 6State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Peopleâs Republic of China; 7State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Peopleâs Republic of China; 8Guangzhou National Laboratory, Guangzhou, Peopleâs Republic of China; 9Laboratory of Bacterial Genetics, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia; 10Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand; 11Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand&ast;These authors contributed equally to this workCorrespondence: Tianyu Zhang, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Room A207, 190 Kaiyuan Ave, Science Park, Huangpu District, Guangzhou, 510530, Peopleâs Republic of China, Tel +86-2032015270, Email zhang_tianyu@gibh.ac.cn Jianxiong Liu, Guangzhou Chest Hospital, 62 Hengzhigang Road, Yuexiu District, Guangzhou, Peopleâs Republic of China, Tel +86-2083595977, Email ljxer64@qq.comObjective: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in the rpoB gene. We aimed to investigate the prevalence of mutations pattern in the entire rpoB gene of Mycobacterium tuberculosis clinical isolates and their association with resistance level to RIF.Methods: Among 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmed Mtb strains was performed via the proportion method and Bactec MGIT 960 system. GeneXpert MTB/RIF and sanger sequencing facilitated in genetic characterization, whereas the MICs of RIF were determined by Alamar blue assay.Results: We found 150/175 (85.71%) RIF-resistant strains (MIC: 4 to > 64 Î¼g/mL) of which 57 were MDR and 81 pre-XDR TB. Genetic analysis identified 17 types of mutations 146/150 (97.33%) within RRDR (codons 426â 452) of rpoB, mainly at L430 (P), D435 (V, E, G, N), H445 (N, D, Y, R, L), S450 (L, F) and L452 (P). D435V 12/146 (8.2%), H445N 16/146 (10.9%), and S450L 70/146 (47.94%) were the most frequently encountered mutations. Mutations Q432K, M434V, and N437D are rarely identified in RRDR. Deletions at (1284â 1289 CCAGCT), (1295â 1303 AATTCATGG), and insertion at (1300â 1302 TTC) were detected within RRDR of three RIFR strains for the first time. We detected 47 types of mutations and insertions/deletions (indels) outside the RRDR. Four RIFR strains were detected with only novel mutations/indels outside the RRDR. Two of the four had (K274Q + C897 del + I491M) and (A286V + L494P), respectively. The other two had (G1687del + P454L) and (TT1835-6 ins + I491L) individually. Compared with phenotypic characterization, diagnostic sensitivities of GeneXpert MTB/RIF and sequencing analysis were 95.33% (143/150), and 100% (150/150) respectively.Conclusion: Our findings underscore the key role of RRDR mutations and the contribution of non-RRDR mutations in rapid molecular diagnosis of RIFR clinical isolates. Such insights will support early detection of disease and recommend the appropriate anti-TB regimens in high-burden settings.Keywords: rifampicin-resistance, Mycobacterium tuberculosis, rpoB, GeneXpert MTB/RIF, resistance-determining region
Published: 2022

22. Quantum Chemical and Experimental Insight into Structure, Physicochemical Properties and Dissolving Behavior of Deep Eutectic Solvents

Author: Zhang, Yuling, primary, Ren, Hongwei, additional, Liu, Yize, additional, Li, Meiyu, additional, Rasheed, Adnan Hameed, additional, Alias, Hajar, additional, and Duan, Erhong, additional
Published: 2022
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23. Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for Mycobacterium ulcerans

Author: Yang Liu, Mahmudul Islam, Tianyu Zhang, H.M. Adnan Hameed, Shuai Wang, Zhili Lu, Yamin Gao, Lingmin Guo, Zhiyong Liu, Xirong Tian, and Cuiting Fang
Subjects: Buruli ulcer, Drug, TB47, medicine.medical_treatment, media_common.quotation_subject, Mutant, Drug resistance, Clofazimine, 03 medical and health sciences, 0302 clinical medicine, medicine, Chemotherapy, General Pharmacology, Toxicology and Pharmaceutics, 030304 developmental biology, media_common, 0303 health sciences, biology, Mycobacterium ulcerans, business.industry, lcsh:RM1-950, biology.organism_classification, medicine.disease, Virology, lcsh:Therapeutics. Pharmacology, QcrB, Murine model, 030220 oncology & carcinogenesis, Electron transport chain, Original Article, business, medicine.drug
Abstract: Buruli ulcer (BU), caused by Mycobacterium ulcerans, is currently treated with rifampin–streptomycin or rifampin–clarithromycin daily for 8 weeks recommended by World Health Organization (WHO). These options are lengthy with severe side effects. A new anti-tuberculosis drug, TB47, targeting QcrB in cytochrome bc1:aa3 complex is being developed in China. TB47-containing regimens were evaluated in a well-established murine model using an autoluminescent M. ulcerans strain. High-level TB47-resistant spontaneous M. ulcerans mutants were selected and their qcrB genes were sequenced. The in vivo activities of TB47 against both low-level and high-level TB47-resistant mutants were tested in BU murine model. Here, we show that TB47-containing oral 3-drug regimens can completely cure BU in ≤2 weeks for daily use or in ≤3 weeks given twice per week (6 doses in total). All high-level TB47-resistant mutants could only be selected using the low-level mutants which were still sensitive to TB47 in mice. This is the first report of double mutations in QcrB in mycobacteria. In summary, TB47-containing regimens have promise to cure BU highly effectively and prevent the emergence of drug resistance. Novel QcrB mutations found here may guide the potential clinical molecular diagnosis of resistance and the discovery of new drugs against the high-level resistant mutants., Graphical abstract Novel regimens containing TB47, a QcrB inhibitor, cure Buruli ulcer in a murine model within 14 days or with only 6 doses. TB47 was active against the low-level TB47-resistant mutants but inactive against the high-level ones in which double mutations in QcrB were first found.Image 1
Published: 2021

24. Thermophysical Properties for ZnO-Water Nanofluid: Experimental Study

Author: Sami D. Salman, Hajar Alias, and Adnan Hameed Rasheed
Subjects: Materials science, 020209 energy, Mechanical Engineering, chemistry.chemical_element, 02 engineering and technology, Zinc, Condensed Matter Physics, Viscosity, Nanofluid, Thermal conductivity, 020401 chemical engineering, chemistry, Chemical engineering, Mechanics of Materials, 0202 electrical engineering, electronic engineering, information engineering, General Materials Science, 0204 chemical engineering
Abstract: This paper presents the thermophysical properties of zinc oxide nanofluid that have been measured for experimental investigation. The main contribution of this study is to define the heat transfer characteristics of nanofluids. The measuring of these properties was carried out within a range of temperatures from 25 °C to 45 °C, volume fraction from 1 to 2 %, and the average nanoparticle diameter size is 25 nm, and the base fluid is water. The thermophysical properties, including viscosity and thermal conductivity, were measured by using Brookfield rotational Viscometer and Thermal Properties Analyzer, respectively. The result indicates that the thermophysical properties of zinc oxide nanofluid increasing with nanoparticle volume fraction increasing, as well as the thermophysical properties of zinc oxide nanofluid affected by the change in temperature.
Published: 2021
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25. Arabinosyltransferase C Mediates Multiple Drugs Intrinsic Resistance by Altering Cell Envelope Permeability in Mycobacterium abscessus

Author: Shuai Wang, Xiaoyin Cai, Wei Yu, Sheng Zeng, Jingran Zhang, Lingmin Guo, Yamin Gao, Zhili Lu, H. M. Adnan Hameed, Cuiting Fang, Xirong Tian, Buhari Yusuf, Chiranjibi Chhotaray, M. D. Shah Alam, Buchang Zhang, Honghua Ge, Dmitry A. Maslov, Gregory M. Cook, Jiacong Peng, Yongping Lin, Nanshan Zhong, Guoliang Zhang, and Tianyu Zhang
Subjects: Mice, Knockout, Microbiology (medical), Mycobacterium abscessus, General Immunology and Microbiology, Ecology, Physiology, Antitubercular Agents, Linezolid, Mycobacterium Infections, Nontuberculous, Microbial Sensitivity Tests, Cell Biology, Permeability, Anti-Bacterial Agents, Imipenem, Mice, Infectious Diseases, Rifabutin, Genetics, Animals, Humans, Tuberculosis, Pentosyltransferases, Ethambutol
Abstract: Mycobacterium abscessus is an emerging human pathogen leading to significant morbidity and even mortality, intrinsically resistant to almost all the antibiotics available and so can be a nightmare. Mechanisms of its intrinsic resistance remain not fully understood. Here, we selected and confirmed an M. abscessus transposon mutant that is hypersensitive to multiple drugs including rifampin, rifabutin, vancomycin, clofazimine, linezolid, imipenem, levofloxacin, cefoxitin, and clarithromycin. The gene
Published: 2022
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26. Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis

Author: Matthew B. McNeil, Chen-Yi Cheung, Natalie J. E. Waller, Cara Adolph, Cassandra L. Chapman, Noon E. J. Seeto, William Jowsey, Zhengqiu Li, H. M. Adnan Hameed, Tianyu Zhang, and Gregory M. Cook
Subjects: Microbiology (medical), Infectious Diseases, Immunology, Microbiology
Abstract: Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respiratory inhibitors have been shown to have synergistic or synthetic lethal interactions, suggesting that combinations of bioenergetic inhibitors could drastically shorten treatment times. Realizing the full potential of this unique target space requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest interactions and potential in a clinical setting. In this review, we discuss (i) chemical-interaction, (ii) genetic-interaction and (iii) chemical-genetic interaction studies to explore the consequences of inhibiting multiple mycobacterial respiratory components. We provide potential mechanisms to describe the basis for the strongest interactions. Finally, whilst we place an emphasis on interactions that occur with existing bioenergetic inhibitors, by highlighting interactions that occur with alternative respiratory components we envision that this information will provide a rational to further explore alternative proteins as potential drug targets and as part of unique drug combinations.
Published: 2022
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27. Clinical and therapeutic characteristics and medical cost of managing cancer patients in Al-Anbar, Iraq: A cross-sectional study

Author: Hameed Adnan Hameed, Abdallah Y Naser, and Nabeel Mudheher Talib
Subjects: Pharmacology, Pharmaceutical Science
Abstract: Cancer is a complex disease that is one of the leading causes of death. This study aimed to investigate the clinical and therapeutic characteristics, as well as the medical cost of managing adult cancer patients in Al-Anbar city in Iraq from the patient's perspective.This was a prospective cross-sectional study that was carried out at the Al-Anbar Oncology Centre between September and December 2021. Direct medical cost data includes the cost of treatment, healthcare professional visits, laboratory tests, and surgery. Furthermore, patients were contacted and asked to estimate the direct non-medical costs (transportation costs) connected with their disease, as well as describe side effects of their cancer therapy. Logistic regression was used to identify variables associated with higher cancer management costs.This study included 500 patients in total. The median overall management cost is 2,765.0 $ (IQR: 3,888.7$). The median cancer management cost differed statistically significantly depending on the stage of the disease, with stage two patients having a lower median cost than other patients (p 0.05). Patients suffering from colon and brain cancer having significantly higher costs (p ≤ 0.05). The median duration of disease was 1.0 year (IQR: 1.0 year). More than half the patients (65.4 %) were at stages three and four. Breast cancer (among females), ovarian cancer (among females), and lymphoma were the most common types of cancer, accounting for 53.9 %, 10.5 %, and 8.6 %, respectively. Almost all patients (99.8 %) were undergoing chemotherapy. More than half of the patients (64.8 %) had surgery to manage their disease, and 16.6 % had radiotherapy as part of their treatment plan. The most widely utilized chemotherapy therapeutic classes were antimicrotubular and platinum analogues with 34.0 % and 33.6 %, respectively. The most common cancer therapy side effects were nausea and vomiting, hair loss, and appetite loss, with 85.2 %, 75.2 %, and 54.2 %, respectively.Breast cancer (in females), ovarian cancer (in females), and lymphoma are the most common types of cancer in Iraq. More research on the risk factors for these types of cancer is needed. Furthermore, additional economic studies from other perspectives are required to highlight the economic burden of cancer in Iraq.
Published: 2022

28. Phenotypic and Genotypic Characterization of Streptomycin-Resistant Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates in Southern China

Author: Xinjie Li, Tianyu Zhang, Yaoju Tan, Nanshan Zhong, Yamin Gao, Mahmudul Islam, Lingmin Guo, Wing Wai Yew, Shouyong Tan, Shuai Wang, Xiaoyin Cai, Chiranjibi Chhotaray, Zhiyong Liu, Zhili Lu, H.M. Adnan Hameed, Xingshan Cai, Yang Liu, and Jianxiong Liu
Subjects: Microbiology (medical), Pharmacology, 0303 health sciences, Tuberculosis, 030306 microbiology, medicine.drug_class, Immunology, Antibiotics, Biology, medicine.disease, biology.organism_classification, Microbiology, Phenotype, Multiple drug resistance, Mycobacterium tuberculosis, 03 medical and health sciences, Streptomycin, Genotype, medicine, Multidrug-Resistant Mycobacterium tuberculosis, 030304 developmental biology, medicine.drug
Abstract: Streptomycin (STR) is the first antibiotic used in the treatment of tuberculosis (TB) and the earliest antituberculosis drug with acquired resistance developed by Mycobacterium tuberculosis. The hi...
Published: 2020
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29. Characterization of Genetic Variants Associated with Rifampicin Resistance Level in

Author: H M Adnan, Hameed, Cuiting, Fang, Zhiyong, Liu, Yanan, Ju, Xingli, Han, Yamin, Gao, Shuai, Wang, Gift, Chiwala, Yaoju, Tan, Ping, Guan, Jinxing, Hu, Xiaoli, Xiong, Jiacong, Peng, Yongping, Lin, Muzammal, Hussain, Nanshan, Zhong, Dmitry A, Maslov, Gregory M, Cook, Jianxiong, Liu, and Tianyu, Zhang
Abstract: Rifampicin (RIF)-resistance, a surrogate marker for multidrug-resistant tuberculosis (TB), is mediated by mutations in theAmong 465 clinical isolates collected from the Guangzhou Chest Hospital, drug-susceptibility of 175 confirmedWe found 150/175 (85.71%) RIF-resistant strains (MIC: 4 to64 µg/mL) of which 57 were MDR and 81 pre-XDR TB. Genetic analysis identified 17 types of mutations 146/150 (97.33%) within RRDR (codons 426-452) ofOur findings underscore the key role of RRDR mutations and the contribution of non-RRDR mutations in rapid molecular diagnosis of RIF
Published: 2022

30. Insight Into Novel Anti-tuberculosis Vaccines by Using Immunoinformatics Approaches

Author: Zafran Khan, Daniya Ualiyeva, Obed Boadi Amissah, Sanjeep Sapkota, H. M. Adnan Hameed, and Tianyu Zhang
Subjects: Microbiology (medical), Microbiology
Abstract: Tuberculosis (TB), an infectious disease, has been a leading cause of morbidity and mortality for decades. The causative agent of TB is the Mycobacterium tuberculosis (Mtb) which can infects various parts of the body, mainly the lungs in pulmonary TB cases. Mycobacterium bovis Bacillus Calmette–Guerin (BCG) is the only approved vaccine for TB, but its efficiency to combat pulmonary TB is limited. Multidrug-resistant (MDR) TB and extensive drug-resistant (XDR) TB requires the evolution of more potent vaccines. Therefore, this research aims to generate a universal TB subunit vaccine using advanced immunoinformatics techniques. In generating a novel multiepitope subunit vaccine, we selected the conserved and experimentally confirmed antigens Rv0058, Rv0101, and Rv3343. After a rigorous evaluation, the top candidates from predicted Helper T-lymphocytes (HTL), Cytotoxic T-lymphocytes (CTL), and B-cell epitopes were considered potential vaccine candidates. Immunogenicity was enhanced by the addition of an adjuvant to the ultimate construct of the vaccine. B-cell epitopes predictions guaranteed the eventual induction of a humoral response. Thereafter, dynamics simulations and molecular docking validated the vaccine-receptor complex’s stability and high affinity for the immune receptor TLR-3. Also, immune simulations revealed the significantly elevated levels of immunoglobulins such as IgM, cytokines such as interleukin-2, helper T (Th) cells, and cytotoxic T-cell populations. These results agreed with the actual inflammatory response and showed rapid antigen clearance after manifold exposure. Finally, the E. coli K12 strain was confirmed via in-silico cloning for quality expression. Nevertheless, in vivo experiments should be performed to validate the safety of the proposed vaccine and its inherent ability to prevent TB infection.
Published: 2022

31. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab

Author: Emil Hagström, P. Gabriel Steg, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Nicolas Danchin, Rafael Diaz, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Evangelos Liberopoulos, Nikolaus Marx, Jennifer McGinniss, Garen Manvelian, Robert Pordy, Michel Scemama, Harvey D. White, Andreas M. Zeiher, Gregory G. Schwartz, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S Nieminen, Vakhtang Chumburidze, Pablo Carlos, Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J Dalby, José Tuñón, H. Asita de Silva, Ulf Landmesser, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B Schiavi, Marcelo Garrido, Andrés F Alvarisqueta, Sonia A Sassone, Anselmo P Bordonava, Alberto E Alves De Lima, Jorge M Schmidberg, Ernesto A Duronto, Orlando C Caruso, Leonardo P Novaretto, Miguel Angel Hominal, Oscar R Montaña, Alberto Caccavo, Oscar A Gomez Vilamajo, Alberto J Lorenzatti, Luis R Cartasegna, Gustavo A Paterlini, Ignacio J Mackinnon, Guillermo D Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R Codutti, Horacio O Jure, Julio OE Bono, Adrian D Hrabar, Julio A Vallejos, Rodolfo A Ahuad Guerrero, Federico Novoa, Cristian A Patocchi, Cesar J Zaidman, Maria E Giuliano, Ricardo D Dran, Marisa L Vico, Gabriela S Carnero, Pablo N Guzman, Juan C Medrano Allende, Daniela F Garcia Brasca, Miguel H Bustamante Labarta, Sebastian Nani, Eduardo DS Blumberg, Hugo R Colombo, Alberto Liberman, Victorino Fuentealba, Hector L Luciardi, Gabriel D Waisman, Mario A Berli, Ruben O Garcia Duran, Horacio G Cestari, Hugo A Luquez, Jorge A Giordano, Silvia S 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Blok, William Sheldon, Masoud M Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun (Tom) Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O’Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Jean- Francois Tamby, Melanie Verrier, Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. 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McClanahan, Roe, Matthew T., Blicharski, Tomasz, Bystryk, Leszek, Szpajer, Michal, Korol, Marek, Czerski, Tomasz, Gniot, Jacek, Lubinski, Andrzej, Gorny, Jerzy, Franek, Edward, Raczak, Grzegorz, Vogel, Robert, Szwed, Hanna, Monteiro, Pedro, Mesquita Bastos, Jose, Pereira, Helder H., Morais, Joao, Seixo, Filipe, Mendonça, Carlos, Botelho, Ana, Caetano, Francisca, Minescu, Bogdan, Chaitman, Bernard, Istratoaie, Octavian, Tesloianu, Dan N., Dorobantu, Maria, Cristian, Gabriel, Dumitrescu, Silviu, Podoleanu, Cristian Gc, Constantinescu, Mircea Ca, Bengus, Cristina M., Militaru, Constantin, Rosu, Doina, Kelsey, Sheryl F., Parepa, Irinel R., Matei, Adrian V., Alexandru, Tom M., Malis, Mihaela, Coman, Ioan, Shvarts, Yury, Orlikova, Olga, Kobalava, Zhanna, Barbarash, Olga L., Markov, Valentin, Olsson, Anders G., Lyamina, Nadezhda, Gordienko, Alexander, Zrazhevsky, Konstantin, Vishnevsky, Alexander Y., Gurevich, Victor, Stryuk, Raisa, Lomakin, Nikita V., Bokarev, Igor, Khlevchuk, Tatiana, Shalaev, Sergey, Rouleau, Jean-Lucien, Khaisheva, Larisa, Chizhov, Petr, Viktorova, Inna, Osokina, Natalya, Shchekotov, Vladimir, Akatova, Evgenia, Chumakova, Galina, Libov, Igor, Voevoda, Mikhail I., Tretyakova, Tatyana V., Simoons, Maarten L., Baranov, Evgeny, Shustov, Sergey, Yakushin, Sergey, Gordeev, Ivan, Khasanov, Niiaz, Reshetko, Olga, Sotnikova, Tatiana, Molchanova, Olga, Nikolaev, Konstantin, Gapon, Liudmila, Alexander, Karen, Baranova, Elena, Kosmachova, Elena, Karpov, Yuriy, Karpov, Yuri, Povzun, Anton, Egorova, Liudmila, Tyrenko, Vadim V., Ivanov, Igor G., Ilya, Masterov, Kanorsky, Sergey, Meloni, Chiara, Simic, Dragan, Ivanovic, Nikola, Davidovic, Goran, Tasic, Nebojsa, Asanin, Milika R., Stojic, Stevo, Apostolovic, Svetlana R., Ilic, Stevan, Tosic, Biljana Putnikovic, Stankovic, Aleksandar, Rosenson, Robert, Arandjelovic, Aleksandra, Radovanovic, Slavica, Todic, Branislava, Ristic, Arsen D., Balinovac, Jovan, Dincic, Dragan V., Seferovic, Petar, Karadzic, Ana, Dodic, Slobodan, Dimkovic, Sinisa, Sijbrands, Eric J. G., Jakimov, Tamara, Poh, Kian-Keong, Yee Ong, Hean, Tang I-Shing, Justin, Micko, Karol, Nociar, Jan, Pella, Daniel, Fulop, Peter, Hranai, Marian, Palka, Juraj, Tricoci, Pierluigi, Mazur, Juraj, Majercák, Ivan, Dzupina, Andrej, Fazekas, František, Gonsorcik, Jozef, Bugan, Viliam, Murin, Jan, Selecky, Juraj, Kamensky, Gabriel, Strbova, Jaroslava, Alexander, John H., Smik, Rudolf, Dukat, Andrej, Olexa, Peter, Žuran, Ivan, Poklukar, Janez, Šuligoj, Nataša Černič, Cevc, Matija, Fras, Zlatko, Cyster, Henry P., Ranjith, Naresh, Armaganijan, Luciana, Corbett, Clive, Bayat, Junaid, Makoali Makotoko, Ellen, du Toit Theron, Hendrik, Kapp, Ilse E., de V Basson, Matthys M., Lottering, Hanlie, Van Aswegen, Dina, Van Zyl, Louis J., Sebastian, Peter J., Bagai, Akshay, Pillay, Thayabran, Saaiman, Jan A., Commerford, Patrick J., Cassimjee, Soraya, Riaz, Garda, Ebrahim, Iftikhar O., Sarvan, Mahomed, Mynhardt, Joseph H., Dalby, Anthony J., Reuter, Helmuth, Bahit, Maria Cecilia, Moodley, Rajendran, Vida, Manuel, Fillat, Angel R. 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Matthew, Worner Diz, Fernando, Garcia-Dorado, David, Iñiguez, Andres, Gonzalez-Juanatey, Jose R., Portales, Javier Fernandez, Murillo, Fernando Civeira, Pericas, Laia Matas, Zamorano, Jose Luis, De Mora Martin, Manuel, Cortada, Jordi Bruguera, Clifton, Shaun, Alonso Martin, Joaquin J., Serrano Antolin, Jose Maria, De Berrazueta Fernández, José R., Vázquez de Prada, José Antonio, Díaz Fernández, Jose Francisco, García Lledó, José Alberto, Cosín Sales, Juan, Rodriguez, Javier Botas, Tragant, Gabriel Gusi, Benedicto, Amparo, DeVore, Adam D., Gonzalez-Juanatey, Carlos, Camprubí Potau, Mercedes, Perez, Ignacio Plaza, De La Tassa, César Morís, Rincon, Pablo Loma-Osorio, Recena, Javier Balaguer, Escudier, Juan M., Payeras, Antonio Coca, Orcajo, Norberto Alonso, Constantine, Godwin, Deloatch, Shalonda, Haniffa, Ruvaiz, Tissera, Nirmali, Amarasekera, Stanley, Ponnamperuma, Chandrike, Fernando, Nimali, Fernando, Kaputella, Jayawardena, Jayanthimala, Wijeyasingam, Santharaj, Ranasinghe, Gotabhaya, Ekanayaka, Ruvan, Dickey, Sheila, Mendis, Sepalika, Senaratne, Vajira, Mayurathan, Gnanamoorthy, Rajapaksha, Ajantha, Sirisena, Thilak, Herath, Jagath I., Amarasena, Naomali, Berglund, Stefan, Rasmanis, Gundars, Hagström, Emil, Dombrowski, Keith, Vedin, Ola, Witt, Nils, Mourtzinis, Georgios, Nicol, Peter, Hansen, Ole, Romeo, Stefano, Jensen, Steen Agergaard, Torstensson, Ingemar, Ahremark, Ulf, Sundelin, Torbjörn, Ducrocq, Grégory, Moccetti, Tiziano, Müller, Christian, Mach, Francois, Binde, Ronald, Landmesser, Ulf, Gämperli, Oliver, Chiang, Chern-En, Tsai, Wei-Chuan, Ueng, Kwo-Chang, Lai, Wen-Ter, Eapen, Zubin, Liu, Ming-En, Hwang, Juey-Jen, Yin, Wei-Hsian, Hsieh, I.-Chang, Hsieh, Ming-Jer, Hsiang Lin, Wei, Kuo, Jen-Yuan, Huang, Tsuei-Yuan, Fang, Chih-Yuan, Kaewsuwanna, Pinij, Endsley, Patricia, Soonfuang, Wasant, Jintapakorn, Woravut, Sukonthasarn, Apichard, Sritara, Piyamitr, Wongpraparut, Nattawut, Sastravaha, Krisada, Sansanayudh, Nakarin, Kehasukcharoen, Wirash, Piyayotai, Dilok, Chotnoparatpat, Paiboon, Eppinger, Arleen, Camsari, Ahmet, Kultursay, Hakan, Guneri, Sema, Mutlu, Bulent, Ersanli, Murat, Demirtas, Mustafa, Kirma, Cevat, Ural, Ertan, Koldas, Lale, Karpenko, Oleksandr, Harrison, Robert W., Prokhorov, Alexander, Vakaluyk, Ihor, Myshanych, Halyna, Reshotko, Dmytro, Batushkin, Valeriy, Rudenko, Leonid, Kovalskyi, Ihor, Kushnir, Mykola, Tseluyko, Vira, Mostovoy, Yuriy, Hess, Connie Ng, Stanislavchuk, Mykola, Kyiak, Yulian, Karpenko, Yuriy, Malynovsky, Yaroslav, Klantsa, Andriy, Kutniy, Oles, Amosova, Ekaterina, Tashchuk, Viktor, Leshchuk, Oleh, Parkhomenko, Alexander, Hlatky, Mark A., Rishko, Mykola, Kopytsya, Mykola, Yagensky, Andriy, Vatutin, Mykola, Bagriy, Andriy, Barna, Olga M., Ushakov, Olexiy, Dzyak, Georgiy, Goloborodko, Borys, Rudenko, Anatolii, Jordan, Joseph Dedrick, Zheleznyy, Volodymyr, Trevelyan, Jasper, Zaman, Azfar, Lee, Kaeng, Moriarty, Andrew, Aggarwal, Rajesh K., Clifford, Piers, Wong, Yuk-ki, Iqbal, Syed Mr, Subkovas, Eduardas, Knowles, Joshua W., Braganza, Denise, Sarkar, David, Storey, Robert, Griffiths, Huw, Mcclure, Sam, Muthusamy, Rangasamy, Smith, Simon, Kurian, John, Levy, Terry, Barr, Craig, Kolls, Bradley J., Kadr, Honer, Gerber, Robert, Simaitis, Audrius, Soran, Handrean, Brodison, Adrian, Ayaz, Mohammad, Cheema, Muhammad, Oliver, Richard, Thackray, Simon, Mudawi, Telal, Kong, David F., Rahma, Gohar, Sultan, Ayyaz, Reynolds, Timothy, Sharman, David, Spriging, David, Butler, Rob, Wilkinson, Peter, Lip, Gregory Yh, Ossei-Gerning, Nicholas, Vardi, Gil, Leonardi, Sergio, Baldari, Duccio, Brabham, David, Treasure Ii, Charles, Dahl, Charles, Palmer, Bruce, Wiseman, Alan, Khan, Abul, Puri, Sanjeev, Mohart, Ann Elizabeth, Ince, Carlos, Lillis, Linda, Flores, Enrique, Wright, Scott, Cheng, Shi-Chi, Rosenberg, Michael, Rogers, William, Kosinski, Edward, Forgosh, Les, Waltman, Jonathan, Shoukfeh, Mohammad, Dagher, Georges, Lopes, Renato D., Cambier, Patrick, Lieber, Ira, Kumar, Priya, East, Cara, Krichmar, Perry, Hasan, Mian, White, Lindsey, Knickelbine, Thomas, Haldis, Thomas, Gillespie, Eve, Maron, David J., Amidon, Thomas, Suh, David, Arif, Imran, Abdallah, Mouhamad, Akhter, Faiq, Carlson, Eric, D'Urso, Michael, El-Ahdab, Fadi, Nelson, William, Moriarty, Katie, Mahaffey, Kenneth W., Harris, Barry, Cohen, Steven, Carter, Luther, Doty, Daniel, Sabatino, Kenneth, Haddad, Tariq, Rao, Sunder, Mulkay, Angel, Jovin, Ion, Klancke, Kim, Marcus, Jill, Malhotra, Vinay, Devarapalli, Sai K., Koren, Michael, Chandna, Harish, Dodds Iii, George, Goraya, Tauqir, Bengston, James, Janik, Matthew, Moran, Joseph, Sumner, Andrew, Mathews, Robin, Kobayashi, John, Davis, William, Yazdani, Shahram, Pasquini, John, Thakkar, Maitreya, Vedere, Amarnath, Leimbach, Wayne, Rider, James, Fenton, Sarah, Singh, Narendra, Mehta, Rajendra H., Shah, Anil V., Moriarty, Patrick M., Janosik, Denise, Pepine, Carl, Berman, Brett, Gelormini, Joseph, Daniels, Christopher, Richard, Kerensky, Keating, Friederike, Kondo, Nicholas I., Mentz, Robert J., Shetty, Sanjay, Levite, Howard, Waider, Winfried, Takata, Theodore, Abu-Fadel, Mazen, Shah, Vipul, Aggarwal, Rahul, Kumar, Anil, Hattler, Brack, Do, Rose, Moreira, Humberto Graner, Link, Chad, Bortnick, Anna, Kinzfogl Iii, George, Ghitis, Arnold, Larry, John, Teufel, Edward, Kuhlman, Peter, Mclaurin, Brent, Zhang, Wenwu, Thew, Stephen, Patel, Chetan B., Abbas, Jalal, White, Matthew, Islam, Othman, Subherwal, Sumeet, Ranadive, Nandkishore, Vakili, Babak, Gring, Christian, Henderson, David, Schuchard, Timothy, Farhat, Naim, Pereira, Sabrina Bernardez, Kline, Geoffrey, Mahal, Sharan, Whitaker, Jack, Speirs, Shawn, Andersen, Rolf, Daboul, Nizar, Horwitz, Phillip, Zahr, Firas, Ponce, George, Jafar, Zubair, Perkins, Lynn, Mcgarvey, Joseph, Panchal, Vipul, Voyce, Stephen, Blok, Thomas, Sheldon, William, Azizad, Masoud M., Schmalfuss, Carsten, Picone, Mark, Pederson, Robert, Herzog, William, Povsic, Thomas J., Friedman, Keith, Lindsey, Jason, Timothy, Eichenlaub, Leonard, Parilak, Lepor, Norman, El Shahawy, Mahfouz, Weintraub, Howard, Irimpen, Anand, Alonso, Alvaro, May, Wade, Puymirat, Etienne, Christopher, Daniels, Galski, Thomas, Chu, Alan, Mody, Freny, Ramin, Ebrahimi, Hodes, Zachary, Rossi, Joseph, Rose, Gregory, Fairlamb, James, Lambert, Charles, Raisinghani, Ajit, Abbate, Antonio, Vetrovec, George, King, Marilyn, Carey, Charles, Gerber, Jaime, Younis, Liwa, Park, Hyeun Tom, Vidovich, Mladen, Knutson, Thomas, Jones, William Schuyler, Friedman, Dennis, Chaleff, Fred, Loussararian, Arthur, Rozeman, Phillip, Kimmelstiel, Carey, Kuvin, Jeffrey, Silver, Kevin, Foster, Malcolm, Tonnessen, Glen, Espinoza, Andrey, Shah, Bimal R., Amlani, Mohamadali, Wali, Andreas, Malozzi, Christopher, Jong, Geert T., Massey, Clara, Wattanakit, Keattiyoat, O'Donnell, Philip J., Singal, Dinesh, Jaffrani, Naseem, Banuru, Sridhar, Sherwood, Matthew W., Fisher, Daniel, Xenakis, Mark, Perlmutter, Neal, Bhagwat, Ravi, Strader, James, Blonder, Ronald, Akyea-Djamson, Ayim, Labroo, Ajay, Lee, Kwan, Marais, H. John, Stringfellow, Kenya, Claxton, Edmund, Weiss, Robert, Kathryn, Rohr, Berk, Martin, Rossi, Peter, Joshi, Parag, Khera, Amit, Khaira, Ajit S., Kumkumian, Greg, Lupovitch, Steven, Sujjavanich, Darin, Purow, Joshua, Welka, Stephen, Hoffman, David, Fischer, Stuart, Soroka, Eugene, Eagerton, Donald, Pancholy, Samir, Ray, Michael, Erenrich, Norman, Farrar, Michael, Toma, Mustafa, Pollock, Stewart, French, William J., Diamantis, Steve, Guy, Douglas, Gimple, Lawrence, Neustel, Mark, Schwartz, Steven, Pereira, Edward, Albert, Seals, Spriggs, Douglas, Trotter, Charlene, Strain, Janet, Mittal, Suneet, Vo, Anthony, Chane, Majed, Hall, Jason, Vijay, Nampalli, Lotun, Kapildeo, Lester, F. Martin, Nahhas, Ahed, Pope, Theodore, van Diepen, Sean F. 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Andreas M, Roe, Matthew T, Mahaffey, Kenneth W, Edelberg, Jay M, Sasiela, William J, Aylward, Philip E, Lopes, Renato D, Gotcheva, Nina N, Nieminen, Markku S, Laucevičius, Aleksandras, Correa Flores, Roger M, Sy, Rody G, Ristic, Arsen D, Dalby, Anthony J, de Silva, H Asita, Ray, Kausik K, Moriarty, Patrick M, Kelsey, Sheryl F, Olsson, Anders G, Simoons, Maarten L, Sijbrands, Eric J G, Alexander, John H, Brennan, J Matthew, DeVore, Adam D, Harrison, Robert W, Hlatky, Mark A, Knowles, Joshua W, Kolls, Bradley J, Kong, David F, Maron, David J, Mehta, Rajendra H, Mentz, Robert J, Patel, Chetan B, Povsic, Thomas J, Shah, Bimal R, Sherwood, Matthew W, van Diepen, Sean F P, Wilson, Matthew D, Schiavi, Lilia B, Alvarisqueta, Andrés F, Sassone, Sonia A, Bordonava, Anselmo P, Alves De Lima, Alberto E, Schmidberg, Jorge M, Duronto, Ernesto A, Caruso, Orlando C, Novaretto, Leonardo P, Montaña, Oscar R, Gomez Vilamajo, Oscar A, Lorenzatti, Alberto J, Cartasegna, Luis R, Paterlini, Gustavo A, Mackinnon, Ignacio J, Caime, Guillermo D, Codutti, Oscar R, Jure, Horacio O, Hrabar, Adrian D, Vallejos, Julio A, Ahuad Guerrero, Rodolfo A, Patocchi, Cristian A, Zaidman, Cesar J, Giuliano, Maria E, Dran, Ricardo D, Vico, Marisa L, Carnero, Gabriela S, Guzman, Pablo N, Medrano Allende, Juan C, Garcia Brasca, Daniela F, Bustamante Labarta, Miguel H, Colombo, Hugo R, Luciardi, Hector L, Waisman, Gabriel D, Berli, Mario A, Garcia Duran, Ruben O, Cestari, Horacio G, Luquez, Hugo A, Giordano, Jorge A, Saavedra, Silvia S, Waites, Jonathon H, Arstall, Margaret A, Rogers, James F, Oqueli Flores, Romulo E, Lehman, Sam J, Garrahy, Paul J, Carroll, Patrick A, Wolf, Luc De, Nicolau, Jose C, Giorgeto, Flavio E, Silva, Ricardo P, Abrantes, José Antonio M, Bodanese, Luiz C, Michalaros, Yorghos L, Eliaschewitz, Freddy G, Vidotti, Maria H, Leaes, Paulo E, Botelho, Roberto V, Manenti, Euler Roberto F Fernandes, Precoma, Dalton B, Moura Jorge, Jose C, Silveira, Jose A, Neto, Jose A Marin, Feitosa, Gilson S, Ritt, Luiz Eduardo F, de Souza, Juliana A, Todorov, Georgi V, Nikolov, Fedya P, Velcheva, Elena S, Tzekova, Maria L, Benov, Haralambi O, Petranov, Stanislav L, Tumbev, Haralin S, Shehova-Yankova, Nina S, Markov, Dimitar T, Raev, Dimitar H, Mollov, Mihail N, Kichukov, Kostadin N, Ilieva-Pandeva, Katya A, Mincheva, Valentina M, Lazov, Petar V, Dimov, Bojidar I, Prieto, Juan C, Raffo, Carlos A, Luna Botia, Diana C, De Salazar, Dora I Molina, Bonfanti, Alberto J Cadena, Barrera Silva, Sandra I, Garcia Lozada, Henry J, Coronel Arroyo, Julian A, Accini Mendoza, Jose L, Fernandez Ruiz, Ricardo L, Quintero Ossa, Alvaro M, Manzur Jatin, Fernando G, Urina Triana, Miguel A, Trujillo, Angela M Fernandez, Poulsen, Steen H, Bang, Lia E, Hove, Jens D, Kristensen, Kjeld S, Lomholdt, Jens D, Klausen, Ib C, Fausto Ovando, Sergio R, Arango Benecke, Juan L, Rodriguez De Leon, Edgar R, Premchand, Rajendra K, Abhyanakar, Atul D, Govinda, Ravishankar A, Patil, Sachin N, Joshi, Abhijeet B, Pothineni, Ramesh B, Monteiro, Minguel R, Iyengar, Shamanna S, Fulwani, Mahesh C, Chopra, Vijay K, Goyal, Naresh K, Manakshe, Gajendra V, Pellegrin, Annamaria De, De Cesare, Nicoletta B, Piatti, Piermarco, Luca, Giuseppe De, Leo, Alessandro De, Petrulionienė, Žaneta, Šakalytė, Gintarė, Šlapikas, Rimvydas, Liew, Houng B, Breedveld, Robert W, Wiersma, Jacobijne J, Troquay, Roland PTh, Viergever, Eric P, Bartels, Gerard L, Cornel, Jan H, Bos, Robert J, Van Der Zwaan, Coenraad C, Groenemeijer, Bjorn E, Willems, Frank F, Munk, Peter S, Calderon Ticona, Jorge R, Durand Velasquez, Julio R, Negron Miguel, Sandra A, Sanabria Perez, Enrique S, Carrion Chambilla, Jesus M, Chavez Ayala, Carlos A, Castillo Leon, Reynaldo P, Vargas GonzalesC, Rolando J, Hernandez Zuniga, Jose D, Camacho Cosavalente, Luis A, Bravo Mannucci, Jorge E, Llerena Navarro, Nassip C, Roldan Concha, Yudy M, Rodriguez Chavez, Víctor E, Anchante Hernandez, Henry A, Zea Nunez, Carlos A, Sy, Rosa Allyn G, Morales, Dante D, Pereira, Helder H, Tesloianu, Dan N, Bengus, Cristina M, Parepa, Irinel R, Matei, Adrian V, Alexandru, Tom M, Barbarash, Olga L, Vishnevsky, Alexander Y, Lomakin, Nikita V, Voevoda, Mikhail I, Tretyakova, Tatyana V, Tyrenko, Vadim V, Ivanov, Igor G, Asanin, Milika R, Apostolovic, Svetlana R, Dincic, Dragan V, Cyster, Henry P, Kapp, Ilse E, de V Basson, Matthys M, Aswegen, Dina Van, Van Zyl, Louis J, Sebastian, Peter J, Saaiman, Jan A, Commerford, Patrick J, Ebrahim, Iftikhar O, Mynhardt, Joseph H, Fillat, Angel R Cequier, Cruz Fernández, Jose M, Gonzalez-Juanatey, Jose R, Alonso Martin, Joaquin J, De Berrazueta Fernández, José R, Escudier, Juan M, Herath, Jagath I, Hsieh, I-Chang, Barna, Olga M, Aggarwal, Rajesh K, Wong, Yuk-Ki, Devarapalli, Sai K, Shah, Anil V, Kondo, Nicholas I, Azizad, Masoud M, Jong, Geert T, O'Donnell, Philip J, Marais, H John, Khaira, Ajit S, French, William J, Lester, F Martin, Sundram, P Sandy, Gilbert, John M, Schmedtje, John F, Colhoun, Helen M, Dempsey, Michael A, and McClanahan, Mark A
Subjects: Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use, Anticholesteremic Agents/adverse effects, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], prevention & control, heart disease risk factors, diagnosis [Cardiovascular Diseases], Antibodies, Monoclonal, Humanized, PCSK9 inhibitors, acute coronary syndrome, apolipoproteins B, LDL cholesterol, Antibodies, acute coronary syndrome, LDL, drug therapy [Atherosclerosis], Risk Factors, Physiology (medical), therapeutic use [Hydroxymethylglutaryl-CoA Reductase Inhibitors], Monoclonal, Humans, Cardiac and Cardiovascular Systems, Humanized, Cardiovascular Diseases/diagnosis, Apolipoproteins B, Kardiologi, diagnosis [Acute Coronary Syndrome], Anticholesteremic Agents, PCSK9 inhibitors, apolipoproteins B, cholesterol, LDL, cholesterol, Atherosclerosis/drug therapy, Cholesterol, LDL, Atherosclerosis, Acute Coronary Syndrome/diagnosis, drug therapy, Cholesterol, Treatment Outcome, Cardiovascular Diseases, Heart Disease Risk Factors, epidemiology, adverse effects [Anticholesteremic Agents], Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine
Abstract: Circulation : an official journal of the American Heart Association / ed.-in-chief Ephraim Donosco 146(9), 657-672 (2022). doi:10.1161/CIRCULATIONAHA.121.057807, Published by Ovid, [Erscheinungsort nicht ermittelbar]
Published: 2022
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32. Probiotics encapsulated gastroprotective cross-linked microgels: Enhanced viability under stressed conditions with dried apple carrier

Author: Muhammad Afzaal, Farhan Saeed, Huda Ateeq, Muhammad Nadeem Akhtar, Ali Imran, Aftab Ahmed, Muhammad Aamir, Fakhar Islam, Iqra Yasmin, Yasir Abbas Shah, Muzzamal Hussain, Adnan Hameed, Roshan Kumar, and Chinaza Godswill Awuchi
Subjects: encapsulation, viability, gastroprotective microgels, apple snack, antacid, probiotics, Food Science
Abstract: In the current study, Lactobacillus acidophilus was encapsulated in sodium alginate and whey protein isolate, with the addition of antacids CaCO3 or Mg(OH)2. The obtained microgels were observed by scanning electron microscopy. Encapsulated and free probiotics were subjected to vitality assay under stressed conditions. Furthermore, dried apple snack was evaluated as a carrier for probiotics for 28 days. A significant (p ≤ .05) effect of antacid with an encapsulating agent was observed under different stressed conditions. During exposure to simulated gastrointestinal conditions, there were observations of 1.24 log CFU and 2.17 log CFU, with corresponding 0.93 log CFU and 2.63 log CFU decrease in the case of SA + CaCO3 and WPI + CaCO3 respectively. Likewise, high viability was observed under thermal and refrigerated conditions for probiotics encapsulated with SA + CaCO3. In conclusion, the results indicated that alginate microgels with CaCO3 are effective in prolonging the viability of probiotics under stressed conditions.
Published: 2022

33. Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant Mycobacterium tuberculosis Clinical Isolates in Southern China

Author: Shuai Wang, Cuiting Fang, Zhiyong Liu, Wing Wai Yew, Tianyu Zhang, Mahmudul Islam, Shouyong Tan, Hm Adnan Hameed, Nanshan Zhong, Jianxiong Liu, Yaoju Tan, Zhili Lu, and Chiranjibi Chhotaray
Subjects: 0301 basic medicine, Pharmacology, Genetics, Tuberculosis, 030106 microbiology, Drug resistance, Biology, Pyrazinamide, medicine.disease, biology.organism_classification, Frameshift mutation, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, PncA, Genotype, medicine, Pharmacology (medical), Multidrug-Resistant Mycobacterium tuberculosis, 030212 general & internal medicine, medicine.drug
Abstract: Objective Pyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA + upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis. Methods Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates. Results Our data showed that among 448 M. tuberculosis clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drug-resistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZAR isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncA-Rv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZAR. Compared with phenotypic data, 84.38% (227/269) PZAR strains with mutations in pncA + upstream region exhibited 83.64% sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48% (4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74% (2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C-114del) in upstream of pncAwt nullified the effect of A-11G mutation and induced positive PZase activity, divergent from five PZase negative A-11G PZAR mutants. Twenty-six PZAR strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms. Conclusion Our study revealed that PZAR rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA + UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance.
Published: 2020
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34. Phenotypic and genotypic characterization of levofloxacin- and moxifloxacin-resistant Mycobacterium tuberculosis clinical isolates in southern China

Author: H.M. Adnan Hameed, Chiranjibi Chhotaray, Mahmudul Islam, Shouyong Tan, Jianxiong Liu, Tianyu Zhang, Zhiyong Liu, Nanshan Zhong, Yaoju Tan, Yamin Gao, Lingmin Guo, Wing Wai Yew, and Shuai Wang
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, Tuberculosis, biology, business.industry, 030106 microbiology, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, medicine.disease, biology.organism_classification, DNA gyrase, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, 030104 developmental biology, Levofloxacin, Moxifloxacin, Multiplex polymerase chain reaction, Genotype, medicine, Original Article, business, Cross-resistance, medicine.drug
Abstract: Background: Levofloxacin (LVX) and Moxifloxacin (MXF) are the cornerstones for treatment of multidrug-resistant tuberculosis (MDR-TB). China is one of the highest MDR- and fluoroquinolones (FQ)- resistant TB burdens countries. DNA gyrase encoded by gyr genes is the main target of FQ in Mycobacterium tuberculosis (MTB). The prevalence and molecular characterization of LVX- and MXF-resistant MTB strains from southern China were examined in this study. Methods: Drug susceptibility testing (DST) of 400 MTB clinical isolates was evaluated by proportion method on Lowenstein-Jensen (LJ) medium against ten drugs. The sequencing of entire gyrA and gyrB genes and multiplex PCR were performed to distinguish the prevalence of mutant types in Beijing and non-Beijing genotypes. Results: Three hundred and twenty-one out of four hundred (80.25%) drug-resistant isolates (resistant > one drug) were categorized as 83/321 (25.80%) MDR, 174/321 (54.20%) pre-XDR and 64/321 (19.93%) XDR-MTB. Overall, 303/400 (75.75%) LVX- and 292/400 (73.00%) MXF-resistant (R) MTB strains were identified. Two hundred seventy-one out of three hundred and three (89.43%) resistant strains carried mutations in gyrA and 91/303 (30.03%) in gyrB . Interestingly, 18 novel mutations were detected in gyrA and gyrB genes. Mutations at (A90, D94) and (T500, G510, G512) frequently existed in QRDR(s) of gyrA and gyrB respectively in 286/400 (71.50%) LVX R MXF R strains. The novel mutations in- and out-side the QRDR of gyrA (L105R, A126E, M127K, D151T, V165A) and gyrB (D461H, N499S, G520A) increased the sensitivity and consistency of genotypic tests. Notably, 25 LVX R MXF R strains were found with unknown resistance mechanisms. Conclusions: Mutations in QRDR(s) were concomitantly associated with Beijing and non-Beijing genotypes. The prevalence of resistance and cross-resistance between LVX and MXF in MTB isolates from southern China was immensely higher than other countries. Our valuable findings provide the substantial implications to improve the reliability of genotypic diagnostic tests relying on potential resistance conferring mutations in entire gyr genes.
Published: 2019
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35. Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Author: Gregory G. Schwartz, Michael Szarek, Vera A. Bittner, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Ulf Landmesser, Patricio López-Jaramillo, Garen Manvelian, Robert Pordy, Michel Scemama, Peter R. Sinnaeve, Harvey D. White, Ph Gabriel Steg, P.h. Gabriel Steg, Deepak L. Bhatt, Robert A. Harrington, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Corinne Hanotin, Guillaume Lecorps, Angèle Moryusef, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Steen Hvitfeldt Poulsen, Margus Viigimaa, Markku S. Nieminen, Nicolas Danchin, Vakhtang Chumburidze, Nikolaus Marx, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Rody G. Sy, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Jan Murin, Zlatko Fras, Anthony J. Dalby, José Tuñón, H. Asita de Silva, Emil Hagström, Christian Müller, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean F.P. van Diepen, Matthew D. Wilson, Andrew Tze-Kay Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. Cartasegna, Gustavo A. Paterlini, Ignacio J. Mackinnon, Guillermo D. Caime, Marcos Amuchastegui, Oscar Salomone, Oscar R. Codutti, Horacio O. Jure, Julio O.E. Bono, Adrian D. Hrabar, Julio A. Vallejos, Rodolfo A. Ahuad Guerrero, Federico Novoa, Cristian A. Patocchi, Cesar J. Zaidman, Maria E. Giuliano, Ricardo D. Dran, Marisa L. Vico, Gabriela S. Carnero, Pablo N. Guzman, Juan C. Medrano Allende, Daniela F. Garcia Brasca, Miguel H. Bustamante Labarta, Sebastian Nani, Eduardo D.S. Blumberg, Hugo R. Colombo, Alberto Liberman, Victorino Fuentealba, Hector L. Luciardi, Gabriel D. Waisman, Mario A. Berli, Ruben O. Garcia Duran, Horacio G. Cestari, Hugo A. Luquez, Jorge A. Giordano, Silvia S. Saavedra, Gerardo Zapata, Osvaldo Costamagna, Susana Llois, Jonathon H. Waites, Nicholas Collins, Allan Soward, Chris L.S. Hii, James Shaw, Margaret A. Arstall, John Horowitz, Daniel Ninio, James F. Rogers, David Colquhoun, Romulo E. Oqueli Flores, Philip Roberts-Thomson, Owen Raffel, Sam J. Lehman, Constantine Aroney, Steven G.M. Coverdale, Paul J. Garrahy, Gregory Starmer, Mark Sader, Patrick A. Carroll, Ronald Dick, Robert Zweiker, Uta Hoppe, Kurt Huber, Rudolf Berger, Georg Delle-Karth, Bernhard Frey, Dirk Faes, Kurt Hermans, Bruno Pirenne, Attilio Leone, Etienne Hoffer, Mathias C.M. Vrolix, Luc De Wolf, Bart Wollaert, Marc Castadot, Karl Dujardin, Christophe Beauloye, Geert Vervoort, Harry Striekwold, Carl Convens, John Roosen, Emanuele Barbato, Marc Claeys, Frank Cools, Ibrahim Terzic, Fahir Barakovic, Zlatko Midzic, Belma Pojskic, Emir Fazlibegovic, Azra Durak-Nalbantic, Mehmed Kulić, Dusko Vulic, Adis Muslibegovic, Boris Goronja, Gilmar Reis, Luciano Sousa, Jose C. Nicolau, Flavio E. Giorgeto, Ricardo P. Silva, Lilia Nigro Maia, Rafael Rech, Paulo R.F. Rossi, Maria José A.G. Cerqueira, Norberto Duda, Renato Kalil, Adrian Kormann, José Antonio M. Abrantes, Pedro Pimentel Filho, Ana Priscila Soggia, Mayler O.N. de Santos, Fernando Neuenschwander, Luiz C. Bodanese, Yorghos L. Michalaros, Freddy G. Eliaschewitz, Maria H. Vidotti, Paulo E. Leaes, Roberto V. Botelho, Sergio Kaiser, Euler Roberto F. Fernandes Manenti, Dalton B. Precoma, Jose C. Moura Jorge, Pedro Silva, Jose A. Silveira, Wladmir Saporito, Jose A. Marin Neto, Gilson S. Feitosa, Luiz Eduardo F. Ritt, Juliana A. de Souza, Fernando Costa, Weimar K.S.B. Souza, Helder J.L. Reis, Leandro Machado, José Carlos Aidar Ayoub, Georgi V. Todorov, Fedya P. Nikolov, Elena S. Velcheva, Maria L. Tzekova, Haralambi O. Benov, Stanislav L. Petranov, Haralin S. Tumbev, Nina S. Shehova-Yankova, Dimitar T. Markov, Dimitar H. Raev, Mihail N. Mollov, Kostadin N. Kichukov, Katya A. Ilieva-Pandeva, Raya Ivanova, Maryana Gospodinov, Valentina M. Mincheva, Petar V. Lazov, Bojidar I. Dimov, Manohara Senaratne, James Stone, Jan Kornder, Stephen Pearce, Danielle Dion, Daniel Savard, Yves Pesant, Amritanshu Pandey, Simon Robinson, Gilbert Gosselin, Saul Vizel, Gordon Hoag, Ronald Bourgeois, Anne Morisset, Eric Sabbah, Bruce Sussex, Simon Kouz, Paul MacDonald, Ariel Diaz, Nicolas Michaud, David Fell, Raymond Leung, Tycho Vuurmans, Christopher Lai, Frank Nigro, Richard Davies, Gustavo Nogareda, Ram Vijayaraghavan, John Ducas, Serge Lepage, Shamir Mehta, James Cha, Robert Dupuis, Peter Fong, Sohrab Lutchmedial, Josep Rodes-Cabau, Hussein Fadlallah, David Cleveland, Thao Huynh, Iqbal Bata, Adnan Hameed, Cristian Pincetti, Sergio Potthoff, Juan C. Prieto, Monica Acevedo, Arnoldo Aguirre, Margarita Vejar, Mario Yañez, Guillermo Araneda, Mauricio Fernandez, Luis Perez, Paola Varleta, Fernando Florenzano, Laura Huidobro, Carlos A. Raffo, Claudia Olivares, Leonardo Nahuelpan, Humberto Montecinos, Jiyan Chen, Yugang Dong, Weijian Huang, Jianzhong Wang, Shi'An Huang, Zhuhua Yao, Xiang Li, Lan Cui, Wenhua Lin, Yuemin Sun, Jingfeng Wang, Jianping Li, Xuelian Zhang, Hong Zhu, Dandan Chen, Lan Huang, Shaohong Dong, Guohai Su, Biao Xu, Xi Su, Xiaoshu Cheng, Jinxiu Lin, Wenxia Zong, Huanming Li, Yi Feng, Dingli Xu, Xinchun Yang, Yuannan Ke, Xuefeng Lin, Zheng Zhang, Zeqi Zheng, Zhurong Luo, Yundai Chen, Chunhua Ding, Yi Zhong, Yang Zheng, Xiaodong Li, Daoquan Peng, Shuiping Zhao, Ying Li, Xuebo Liu, Meng Wei, Shaowen Liu, Yihua Yu, Baiming Qu, Weihong Jiang, Yujie Zhou, Xingsheng Zhao, Zuyi Yuan, Ying Guo, Xiping Xu, Xubo Shi, Junbo Ge, Guosheng Fu, Feng Bai, Weiyi Fang, Xiling Shou, Xiangjun Yang, Jian'An Wang, Meixiang Xiang, Yingxian Sun, Qinghua Lu, Ruiyan Zhang, Jianhua Zhu, Yizhou Xu, Zhongcai Fan, Tianchang Li, Chun Wu, Nicolas Jaramillo, Gregorio Sanchez Vallejo, Diana C. Luna Botia, Rodrigo Botero Lopez, Dora I. Molina De Salazar, Alberto J. Cadena Bonfanti, Carlos Cotes Aroca, Juan Diego Higuera, Marco Blanquicett, Sandra I. Barrera Silva, Henry J. Garcia Lozada, Julian A. Coronel Arroyo, Jose L. Accini Mendoza, Ricardo L. Fernandez Ruiz, Alvaro M. Quintero Ossa, Fernando G. Manzur Jatin, Aristides Sotomayor Herazo, Jeffrey Castellanos Parada, Rafael Suarez Arambula, Miguel A. Urina Triana, Angela M. Fernandez Trujillo, Maja Strozzi, Siniša Car, Melita Jerić, Davor Miličić, Martina Lovrić Benčić, Hrvoje Pintarić, Đeiti Prvulović, Jozica Šikić, Viktor Peršić, Dean Mileta, Kresimir Štambuk, Zdravko Babić, Vjekoslav Tomulic, Josip Lukenda, Stanka Mejic-Krstulovic, Boris Starcevic, Jindrich Spinar, David Horak, Zdenek Velicka, Josef Stasek, David Alan, Vilma Machova, Ales Linhart, Vojtech Novotny, Vladimir Kaucak, Richard Rokyta, Robert Naplava, Zdenek Coufal, Vera Adamkova, Ivo Podpera, Jiri Zizka, Zuzana Motovska, Ivana Marusincova, Premysl Svab, Petr Heinc, Jiri Kuchar, Petr Povolny, Jiri Matuska, Steen H. Poulsen, Bent Raungaard, Peter Clemmensen, Lia E. Bang, Ole May, Morten Bøttcher, Jens D. Hove, Lars Frost, Gunnar Gislason, John Larsen, Peter Betton Johansen, Flemming Hald, Peter Johansen, Jørgen Jeppesen, Tonny Nielsen, Kjeld S. Kristensen, Piotr Maria Walichiewicz, Jens D. Lomholdt, Ib C. Klausen, Peter Kaiser Nielsen, Flemming Davidsen, Lars Videbaek, Mai Soots, Veiko Vahula, Anu Hedman, Üllar Soopõld, Kaja Märtsin, Tiina Jurgenson, Arved Kristjan, Heikki Huikuri, Juhani Airaksinen Pierre Coste, Emile Ferrari, Olivier Morel, Gilles Montalescot, Jacques Machecourt, Gilles Barone-Rochette, Jacques Mansourati, Yves Cottin, Florence Leclercq, Abdelkader Belhassane, Nicolas Delarche, Franck Boccara, Franck Paganelli, Jérôme Clerc, Francois Schiele, Victor Aboyans, Vincent Probst, Jacques Berland, Thierry Lefèvre, Bernard Citron, Irakli Khintibidze, Tamaz Shaburishvili, Zurab Pagava, Ramaz Ghlonti, Zaza Lominadze, George Khabeishvili, Rayyan Hemetsberger, Kemala Edward, Ursula Rauch-Kröhnert, Matthias Stratmann, Karl-Friedrich Appel, Ekkehard Schmidt, Heyder Omran, Christoph Stellbrink, Thomas Dorsel, Emmanouil Lianopoulos, Hans Friedrich Vöhringer, Roger Marx, Andreas Zirlik, Detlev Schellenberg, Thomas Heitzer, Ulrich Laufs, Christian Werner, Stephan Gielen, Sebastian Nuding, Bernhard Winkelmann, Steffen Behrens, Karsten Sydow, Mahir Karakas, Gregor Simonis, Thomas Muenzel, Nikos Werner, Stefan Leggewie, Dirk Böcker, Rüdiger Braun-Dullaeus, Nicole Toursarkissian, Michael Jeserich, Matthias Weißbrodt, Tim Schaeufele, Joachim Weil, Heinz Völler, Johannes Waltenberger, Mohammed Natour, Susanne Schmitt, Dirk Müller-Wieland, Stephan Steiner, Lothar Heidenreich, Elmar Offers, Uwe Gremmler, Holger Killat, Werner Rieker, Sotiris Patsilinakos, Athanasios Kartalis, Athanassios Manolis, Dimitrios Sionis, Geargios Chachalis, Ioannis Skoumas, Vasilios Athyros, Panagiotis Vardas, Frangkiskos Parthenakis, John Lekakis, Apostolos Hatzitolios, Sergio R. Fausto Ovando, Juan L. Arango Benecke, Edgar R. Rodriguez De Leon, Bryan P.Y. Yan, David C.W. Siu, Tibor Turi, Bela Merkely, Imre Ungi, Geza Lupkovics, Lajos Nagy, András Katona, István Édes, Gábor Müller, Iván Horvath, Tibor Kapin, Zsolt Szigeti, József Faluközy, Mukund Kumbla, Manjinder Sandhu, Sharath Annam, Naveen Reddy Proddutur, Reddy Regella, Rajendra K. Premchand, Ajaykumar Mahajan, Sudhir Pawar, Atul D. Abhyanakar, Prafulla Kerkar, Ravishankar A. Govinda, Abraham Oomman, Dhurjati Sinha, Sachin N. Patil, Dhiman Kahali, Jitendra Sawhney, Abhijeet B. Joshi, Sanjeev Chaudhary, Pankaj Harkut, Santanu Guha, Sanjay Porwal, Srimannarayana Jujjuru, Ramesh B. Pothineni, Minguel R. Monteiro, Aziz Khan, Shamanna S. Iyengar, Jasprakash Singh Grewal, Manoj Chopda, Mahesh C. Fulwani, Aparna Patange, Patil Sachin, Vijay K. Chopra, Naresh K. Goyal, Rituparna Shinde, Gajendra V. Manakshe, Nitin Patki, Sumeet Sethi, Vengatesh Munusamy, Sunil Karnaand Sunil Thanvi, Srilakshmi Adhyapak, Chandrakant Patil, Ulhas Pandurangi, Rishabh Mathur, Jugal Gupta, Suhas Kalashetti, Ajit Bhagwat, Bagirath Raghuraman, Shiv Kumar Yerra, Prasant Bhansali, Rohidas Borse, Patil Rahul, Srihari Das, Vinay Kumar, Jabir Abdullakutty, Shireesh Saathe, Priya Palimkar, Jabir Abdullkutty, Shireesh Sathe, Shaul Atar, Michael Shechter, Morris Mosseri, Yaron Arbel, Chorin Ehud, Havakuk Ofer, Chaim Lotan, Uri Rosenschein, Amos Katz, Yaakov Henkin, Adi Francis, Marc Klutstein, Eugenia Nikolsky, Robert Zukermann, Yoav Turgeman, Majdi Halabi, Alon Marmor, Ran Kornowski, Michael Jonas, Offer Amir, Yonathan Hasin, Yoseph Rozenman, Shmuel Fuchs, Vered Zvi, Osamah Hussein, Dov Gavish, Zvi Vered, Yoseph Caraco, Mazen Elias, Naveh Tov, Efrat Wolfovitz, Michael Lishner, Nizar Elias, Giancarlo Piovaccari, Annamaria De Pellegrin, Raffaella Garbelotto, Gabriele Guardigli, Valgimigli Marco, Giovanni Licciardello, Carla Auguadro, Filippo Scalise, Claudio Cuccia, Alessandro Salvioni, Giuseppe Musumeci, Michelle Senni, Paolo Calabrò, Salvatore Novo, Pompilio Faggiano, Marco Metra, Nicoletta B. De Cesare, Sergio Berti, Claudio Cavallini, Enrico Puccioni, Marcello Galvani, Maurizio Tespili, Piermarco Piatti, Michela Palvarini, Giuseppe De Luca, Roberto Violini, Alessandro De Leo, Zoran Olivari, Pasquale Perrone Filardi, Maurizio Ferratini, Vittorio Racca, Kazuoki Dai, Yuji Shimatani, Haruo Kamiya, Kenji Ando, Yoshihiro Takeda, Yoshihiro Morino, Yoshiki Hata, Kazuo Kimura, Koichi Kishi, Ichiro Michishita, Hiroki Uehara, Toshinori Higashikata, Atsushi Hirayama, Keiji Hirooka, Yasuji Doi, Satoru Sakagami, Shuichi Taguchi, Akihiro Koike, Hiroyuki Fujinaga, Shinji Koba, Ken Kozuma, Tomohiro Kawasaki, Yujiro Ono, Masatoshi Shimizu, Yousuke Katsuda, Atsuyuki Wada, Toshiro Shinke, Junya Ako, Kenshi Fujii, Toshiyuki Takahashi, Tomohiro Sakamoto, Koichi Nakao, Yutaka Furukawa, Hiroshi Sugino, Ritsu Tamura, Toshiaki Mano, Masaaki Uematsu, Noriaki Utsu, Kashima Ito, Takuya Haraguchi, Katsuhiko Sato, Yasunori Ueda, Akira Nishibe, Kazuteru Fujimoto, Motomaru Masutani, Jung Han Yoon, Hack-Lyoung Kim, Hun Sik Park, In-Ho Chae, Moo Hyun Kim, Myung Ho Jeong, Seungwoon Rha, Chongjin Kim, Hae Young Kim, Taekjong Hong, Seung-Jea Tahk, Youngkwon Kim, Arija Busmane, Natalija Pontaga, Aldis Strelnieks, Iveta Mintale, Iveta Sime, Zaneta Petrulioniene, Roma Kavaliauskiene, Ruta Jurgaitiene, Gintare Sakalyte, Rimvydas Slapikas, Sigute Norkiene, Nerijus Misonis, Aleksandras Kibarskis, Raimondas Kubilius, Stojko Bojovski, Nensi Lozance, Aleksandar Kjovkaroski, Snezana Doncovska, Tiong Kiam Ong, Sazzli Kasim, Oteh Maskon, Balachandran Kandasamy, Houng B. Liew, Wan Mohd Izani Wan Mohamed, Armando García Castillo, Jorge Carrillo Calvillo, Pedro Fajardo Campos, Juan Carlos Núñez Fragoso, Edmundo Alfredo Bayram Llamas, Marco Antonio Alcocer Gamba, Jaime Carranza Madrigal, Luis Gerardo González Salas, Enrique López Rosas, Belinda González Díaz, Eduardo Salcido Vázquez, Alfredo Nacoud Ackar, Guillermo Antonio Llamas Esperón, Carlos Rodolfo Martínez Sánchez, María Guerrero De Leon, Rodrigo Suarez Otero, Guillermo Fanghänel Salmón, Jesús Antonio Pérez Ríos, José Angel Garza Ruíz, Robert W. Breedveld, Margriet Feenema-Aardema, Alida Borger-Van Der Burg, Pieter A.M. Hoogslag, Harry Suryapranata, Antonius Oomen, Paulus Van Haelst, Margriet Feenema-Aradema, Jacobijne J. Wiersma, Dirk Basart, Ruud M.A. Van Der Wal, Peter Zwart, Pascalle Monraats, Henricus Van Kesteren, Ioannis Karalis, Johan Jukema, Gerardus J.E. Verdel, Bart R.G. Brueren, Roland PTh Troquay, Eric P. Viergever, Nadea Y.Y. Al-Windy, Gerard L. Bartels, Jan H. Cornel, Walter R.M. 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Bravo Mannucci, Javier Heredia Landeo, Nassip C. Llerena Navarro, Yudy M. Roldan Concha, Víctor E. Rodriguez Chavez, Henry A. Anchante Hernandez, Carlos A. Zea Nunez, Walter Mogrovejo Ramos, Arthur Ferrolino, Rosa Allyn G. Sy, Louie Tirador, Generoso Matiga, Raul Martin Coching, Alisa Bernan, Gregorio Rogelio, Dante D. Morales, Edgar Tan, Dennis Jose Sulit, Adrian Wlodarczak, Krystyna Jaworska, Grzegorz Skonieczny, Lidia Pawlowicz, Pawel Wojewoda, Benita Busz-Papiez, Janusz Bednarski, Aleksander Goch, Pawel Staneta, Elzbieta Dulak, Krzysztof Saminski, Wlodzimierz Krasowski, Wanda Sudnik, Aleksander Zurakowski, Marcin Skorski, Roman Lysek, Beata Miklaszewicz, Jacek Kubica, Jan Andrzej Lipko, Edyta Kostarska-Srokosz, Marek Piepiorka, Anna Drzewiecka, Ryszard Sciborski, Arkadiusz Stasiewski, Tomasz Blicharski, Leszek Bystryk, Michal Szpajer, Marek Korol, Tomasz Czerski, Ewa Mirek-Bryniarska, Jacek Gniot, Andrzej Lubinski, Jerzy Gorny, Edward Franek, Grzegorz Raczak, Hanna Szwed, Pedro Monteiro, Jose Mesquita Bastos, Helder H. Pereira, Dinis Martins, Filipe Seixo, Carlos Mendonça, Ana Botelho, Francisca Caetano, Bogdan Minescu, Octavian Istratoaie, Dan N. Tesloianu, Gabriel Cristian, Silviu Dumitrescu, Cristian G.C. Podoleanu, Mircea C.A. Constantinescu, Cristina M. Bengus, Constantin Militaru, Doina Rosu, Irinel R. Parepa, Adrian V. Matei, Tom M. Alexandru, Mihaela Malis, Ioan Coman, Rodica Stanescu-Cioranu, Doina Dimulescu, Yury Shvarts, Olga Orlikova, Zhanna Kobalava, Olga L. Barbarash, Valentin Markov, Nadezhda Lyamina, Alexander Gordienko, Konstantin Zrazhevsky, Alexander Y. Vishnevsky, Victor Gurevich, Raisa Stryuk, Nikita V. Lomakin, Igor Bokarev, Tatiana Khlevchuk, Sergey Shalaev, Larisa Khaisheva, Petr Chizhov, Inna Viktorova, Natalya Osokina, Vladimir Shchekotov, Evgenia Akatova, Galina Chumakova, Igor Libov, Mikhail I. Voevoda, Tatyana V. Tretyakova, Evgeny Baranov, Sergey Shustov, Sergey Yakushin, Ivan Gordeev, Niiaz Khasanov, Olga Reshetko, Tatiana Sotnikova, Olga Molchanova, Konstantin Nikolaev, Liudmila Gapon, Elena Baranova, Zaur Shogenov, Elena Kosmachova, Yuriy Karpov, Anton Povzun, Liudmila Egorova, Vadim V. Tyrenko, Igor G. Ivanov, Masterov Ilya, Sergey Kanorsky, Dragan Simic, Nikola Ivanovic, Goran Davidovic, Nebojsa Tasic, Milika R. Asanin, Stevo Stojic, Svetlana R. Apostolovic, Stevan Ilic, Biljana Putnikovic Tosic, Aleksandar Stankovic, Aleksandra Arandjelovic, Slavica Radovanovic, Branislava Todic, Jovan Balinovac, Dragan V. Dincic, Petar Seferovic, Ana Karadzic, Slobodan Dodic, Sinisa Dimkovic, Tamara Jakimov, Kian-Keong Poh, Hean Yee Ong, Justin Tang I-Shing, Karol Micko, Jan Nociar, Daniel Pella, Peter Fulop, Marian Hranai, Juraj Palka, Juraj Mazur, Ivan Majercák, Andrej Dzupina, František Fazekas, Jozef Gonsorcik, Viliam Bugan, Juraj Selecky, Gabriel Kamensky, Jaroslava Strbova, Rudolf Smik, Andrej Dukat, Peter Olexa, Ivan Žuran, Janez Poklukar, Nataša Černič Šuligoj, Matija Cevc, Henry P. Cyster, Naresh Ranjith, Clive Corbett, Junaid Bayat, Ellen Makoali Makotoko, Hendrik du Toit Theron, Ilse E. Kapp, Matthys M. de V Basson, Hanlie Lottering, Dina Van Aswegen, Louis J. Van Zyl, Peter J. Sebastian, Thayabran Pillay, Jan A. Saaiman, Patrick J. Commerford, Soraya Cassimjee, Garda Riaz, Iftikhar O. Ebrahim, Mahomed Sarvan, Joseph H. Mynhardt, Helmuth Reuter, Rajendran Moodley, Manuel Vida, Angel R. Cequier Fillat, Vicente Bodí Peris, Francisco Fuentes Jimenez, Francisco Marín, Jose M. Cruz Fernández, Rafael Jesus Hidalgo Urbano, Blas Gil-Extremera, Pablo Toledo, Fernando Worner Diz, David Garcia-Dorado, Andres Iñiguez, José Tuñón Fernández, Jose R. Gonzalez-Juanatey, Javier Fernandez Portales, Fernando Civeira Murillo, Laia Matas Pericas, Jose Luis Zamorano, Manuel De Mora Martin, Jordi Bruguera Cortada, Joaquin J. Alonso Martin, Jose Maria Serrano Antolin, José R. De Berrazueta Fernández, José Antonio Vázquez de Prada, Jose Francisco Díaz Fernández, José Alberto García Lledó, Juan Cosín Sales, Javier Botas Rodriguez, Gabriel Gusi Tragant, Amparo Benedicto, Carlos Gonzalez-Juanatey, Mercedes Camprubí Potau, Ignacio Plaza Perez, César Morís De La Tassa, Pablo Loma-Osorio Rincon, Javier Balaguer Recena, Juan M. Escudier, Antonio Coca Payeras, Norberto Alonso Orcajo, Pedro Valdivielso, Godwin Constantine, Ruvaiz Haniffa, Nirmali Tissera, Stanley Amarasekera, Chandrike Ponnamperuma, Nimali Fernando, Kaputella Fernando, Jayanthimala Jayawardena, Santharaj Wijeyasingam, Gotabhaya Ranasinghe, Ruvan Ekanayaka, Sepalika Mendis, Vajira Senaratne, Gnanamoorthy Mayurathan, Ajantha Rajapaksha, Thilak Sirisena, Jagath I. Herath, Naomali Amarasena, Stefan Berglund, Gundars Rasmanis, Ola Vedin, Nils Witt, Georgios Mourtzinis, Peter Nicol, Ole Hansen, Stefano Romeo, Steen Agergaard Jensen, Ingemar Torstensson, Ulf Ahremark, Torbjörn Sundelin, Tiziano Moccetti, Francois Mach, Ronald Binde, Oliver Gämperli, Wei-Chuan Tsai, Kwo-Chang Ueng, Wen-Ter Lai, Ming-En Liu, Juey-Jen Hwang, Wei-Hsian Yin, I-Chang Hsieh, Ming-Jer Hsieh, Wei Hsiang Lin, Jen-Yuan Kuo, Tsuei-Yuan Huang, Chih-Yuan Fang, Pinij Kaewsuwanna, Wasant Soonfuang, Woravut Jintapakorn, Apichard Sukonthasarn, Nattawut Wongpraparut, Krisada Sastravaha, Nakarin Sansanayudh, Wirash Kehasukcharoen, Dilok Piyayotai, Paiboon Chotnoparatpat, Ahmet Camsari, Hakan Kultursay, Bulent Mutlu, Murat Ersanli, Mustafa Demirtas, Cevat Kirma, Ertan Ural, Lale Koldas, Oleksandr Karpenko, Alexander Prokhorov, Ihor Vakaluyk, Halyna Myshanych, Dmytro Reshotko, Valeriy Batushkin, Leonid Rudenko, Ihor Kovalskyi, Mykola Kushnir, Vira Tseluyko, Yuriy Mostovoy, Mykola Stanislavchuk, Yulian Kyiak, Yuriy Karpenko, Yaroslav Malynovsky, Andriy Klantsa, Oles Kutniy, Ekaterina Amosova, Viktor Tashchuk, Oleh Leshchuk, Mykola Rishko, Mykola Kopytsya, Andriy Yagensky, Mykola Vatutin, Andriy Bagriy, Olga M. Barna, Olexiy Ushakov, Georgiy Dzyak, Borys Goloborodko, Anatolii Rudenko, Volodymyr Zheleznyy, Jasper Trevelyan, Azfar Zaman, Kaeng Lee, Andrew Moriarty, Rajesh K. Aggarwal, Piers Clifford, Yuk-Ki Wong, Syed M.R. Iqbal, Eduardas Subkovas, Denise Braganza, David Sarkar, Robert Storey, Huw Griffiths, Sam Mcclure, Rangasamy Muthusamy, Simon Smith, John Kurian, Terry Levy, Craig Barr, Honer Kadr, Robert Gerber, Audrius Simaitis, Handrean Soran, Anthony Mathur, Adrian Brodison, Mohammad Ayaz, Muhammad Cheema, Richard Oliver, Simon Thackray, Telal Mudawi, Gohar Rahman, Ayyaz Sultan, Timothy Reynolds, David Sharman, null david Sprigings, Rob Butler, Peter Wilkinson, Gregory Y.H. Lip, Julian Halcox, Sean Gallagher, Nicholas Ossei-Gerning, Gil Vardi, Duccio Baldari, David Brabham, Charles Treasure, Charles Dahl, Bruce Palmer, Alan Wiseman, Abul Khan, Sanjeev Puri, Ann Elizabeth Mohart, Carlos Ince, Enrique Flores, Scott Wright, Shi-Chi Cheng, Michael Rosenberg, William Rogers, Edward Kosinski, Les Forgosh, Jonathan Waltman, Misal Khan, Mohammad Shoukfeh, Georges Dagher, Patrick Cambier, Ira Lieber, Priya Kumar, Cara East, Perry Krichmar, Mian Hasan, Lindsey White, Thomas Knickelbine, Thomas Haldis, Eve Gillespie, Thomas Amidon, David Suh, Imran Arif, Mouhamad Abdallah, Faiq Akhter, Eric Carlson, Michael D'Urso, Fadi El-Ahdab, William Nelson, Katie Moriarty, Barry Harris, Steven Cohen, Luther Carter, Daniel Doty, Kenneth Sabatino, Tariq Haddad, Amir Malik, Sunder Rao, Angel Mulkay, Ion Jovin, Kim Klancke, Vinay Malhotra, Sai K. Devarapalli, Michael Koren, Harish Chandna, George Dodds, Tauqir Goraya, James Bengston, Matthew Janik, Joseph Moran, Andrew Sumner, John Kobayashi, William Davis, Shahram Yazdani, John Pasquini, Maitreya Thakkar, Amarnath Vedere, Wayne Leimbach, James Rider, Sarah fenton, Narendra Singh, Anil V. Shah, Denise Janosik, Carl Pepine, Brett Berman, Joseph Gelormini, Christopher Daniels, Kerensky Richard, Friederike Keating, Nicholas I. Kondo, Sanjay Shetty, Howard Levite, Winfried Waider, Theodore Takata, Mazen Abu-Fadel, Vipul Shah, Rahul Aggarwal, Mark Izzo, Anil Kumar, Brack Hattler, Rose Do, Chad Link, Anna Bortnick, George Kinzfogl, Arnold Ghitis, John Larry, Edward Teufel, Peter Kuhlman, Brent Mclaurin, Wenwu Zhang, Stephen Thew, Jalal Abbas, Matthew White, Othman Islam, Sumeet Subherwal, Nandkishore Ranadive, Babak Vakili, Christian Gring, David Henderson, Timothy Schuchard, Naim Farhat, Geoffrey Kline, Sharan Mahal, Jack Whitaker, Shawn Speirs, Rolf Andersen, Nizar Daboul, Phillip Horwitz, Firas Zahr, George Ponce, Zubair Jafar, Joseph Mcgarvey, Vipul Panchal, Stephen Voyce, Thomas Blok, William Sheldon, Masoud M. Azizad, Carsten Schmalfuss, Mark Picone, Robert Pederson, William Herzog, Keith Friedman, Jason Lindsey, Rosemary Nowins, Eichenlaub Timothy, Parilak Leonard, Norman Lepor, Mahfouz El Shahawy, Howard Weintraub, Anand Irimpen, Alvaro Alonso, Wade May, Daniels Christopher, Thomas Galski, Alan Chu, Freny Mody, Ebrahimi Ramin, Zachary Hodes, Joseph Rossi, Gregory Rose, James Fairlamb, Charles Lambert, Ajit Raisinghani, Antonio Abbate, George Vetrovec, Marilyn King, Charles Carey, Jaime Gerber, Liwa Younis, Hyeun Park, Mladen Vidovich, Thomas Knutson, Dennis Friedman, Fred Chaleff, Arthur Loussararian, Phillip Rozeman, Carey Kimmelstiel, Jeffrey Kuvin, Kevin Silver, Malcolm Foster, Glen Tonnessen, Andrey Espinoza, Mohamadali Amlani, Andreas Wali, Christopher Malozzi, Geert T. Jong, Clara Massey, Keattiyoat Wattanakit, Philip J. O'Donnell, Dinesh Singal, Naseem Jaffrani, Sridhar Banuru, Daniel Fisher, Mark Xenakis, Neal Perlmutter, Ravi Bhagwat, James Strader, Ronald Blonder, Ayim Akyea-Djamson, Ajay Labroo, Kwan Lee, H. John Marais, Edmund Claxton, Robert Weiss, Rohr Kathryn, Martin Berk, Peter Rossi, Parag Joshi, Amit Khera, Ajit S. Khaira, Greg Kumkumian, Steven Lupovitch, Joshua Purow, Stephen Welka, David Hoffman, Stuart Fischer, Eugene Soroka, Donald Eagerton, Samir Pancholy, Michael Ray, Norman Erenrich, Michael Farrar, Stewart Pollock, William J. French, Steve Diamantis, Douglas Guy, Lawrence Gimple, Mark Neustel, Steven Schwartz, Edward Pereira, Seals Albert, Douglas Spriggs, Janet Strain, Suneet Mittal, Anthony Vo, Majed Chane, Jason Hall, Nampalli Vijay, Kapildeo Lotun, F. Martin Lester, Ahed Nahhas, Theodore Pope, Paul Nager, Rakesh Vohra, Mukesh Sharma, Riyaz Bashir, Hinan Ahmed, Michael Berlowitz, Robert Fishberg, Robert Barrucco, Eric Yang, Michael Radin, Daniel Sporn, Dwight Stapleton, Steven Eisenberg, Joel Landzberg, Martin Mcgough, Samir Turk, Michael Schwartz, P. Sandy Sundram, Diwakar Jain, Mark Zainea, Carlos Bayron, Ronald Karlsberg, Suhail Dohad, Henry Lui, William Keen, Donald Westerhausen, Sandeep Khurana, Himanshu Agarwal, Jessica Birchem, William Penny, Mark Chang, Sherrill Murphy, John Henry, Branislav Schifferdecker, John M Gilbert, Gopal Chalavarya, Charles Eaton, John F. Schmedtje, Stuart Christenson, Imran Dotani, Douglas Denham, Alexander Macdonell, Paul Gibson, Aref Rahman, Tammam Al Joundi, Nizar Assi, Gary Conrad, Purushotham Kotha, Michael Love, Gregory Giesler, Howard Rubenstein, Dawood Gamil, Laura Akright, Justine Krawczyk, Joanne Cobler, Terry Wells, James Welker, Robert Foster, Richard Gilmore, Jay Anderson, Douglas Jacoby, Bill Harris, Geraldine Gardner, Ramprasad Dandillaya, Kishor Vora, John Kostis, John Hunter, David Laxson, Eric Ball, Flavia Egydio, Anelise Kawakami, Janaina Oliveira, Julianna Wozniak, Alexander Matthews, Caroline Ratky, Janine Valiris, Lisa Berdan, Anita Hepditch, Kirby Quintero, Tyrus Rorick, Melissa Westbrook, Andrea Pascual, Carla Rovito, Madeleine Bezault, Elodie Drouet, Tabassome Simon, Caroline Alsweiler, Anne Luyten, Julie Butters, Liddy Griffith, Michelle Shaw, Lena Grunberg, Shahidul Islam, Marie-France Brégeault, Nathalie Bougon, Douglas Faustino, Sylvie Fontecave, Judith Murphy, Melanie Verrier, null Veronique Agnetti, Dorthe Andersen, Emmy Badreddine, Mhamed Bekkouche, Cecile Bouancheau, Imane Brigui, Maddy Brocklehurst, Joseph Cianciarulo, Dawn Devaul, Szilvia Domokos, Cecile Gache, Caroline Gobillot, Severine Guillou, Jan Healy, Megan Heath, Gayatri Jaiwal, Carine Javierre, Julien Labeirie, Myriam Monier, Ulises Morales, Asmaa Mrabti, Bicky Mthombeni, Betim Okan, Lucile Smith, Jennifer Sheller, Sebastien Sopena, Valerie Pellan, Fadela Benbernou, Nafissa Bengrait, Maud Lamoureux, Katarina Kralova, Raphael Bejuit, Anthony Coulange, Christelle Berthou, Jérôme Repincay, Christelle Lorenzato, Alexis Etienne, Valerie Gouet, Virginie Loizeau, Mickael Normand, Anne Ourliac, Christelle Rondel, Antony Adamo, Pascale Beltran, Pauline Barraud, Helene Dubois-Gache, Benjamin Halle, Lamia Metwally, Maxime Mourgues, Marc Sotty, Marion Vincendet, Raluca Cotruta, Zhu Chengyue, Dominique Fournie-Lloret, Christine Morrello, Aurelie Perthuis, Patrick Picault, Isabelle Zobouyan, Helen M. Colhoun, Michael A. Dempsey, Mark A. McClanahan, Masira, and Laucevičius, Aleksandras
Subjects: Male, Acute coronary syndrome, medicine.medical_specialty, Cardiac & Cardiovascular Systems, Randomization, PCSK9 inhibitor, LOW-DENSITY-LIPOPROTEIN, Antibodies, Monoclonal, Humanized, acute coronary syndrom, Placebo, Gastroenterology, lipoprotein(a), Internal medicine, medicine, Humans, Low-density lipoprotein cholesterol, Aged, Alirocumab, RISK, low-density lipoprotein cholesterol, Science & Technology, biology, business.industry, PCSK9, PCSK9 Inhibitors, Hazard ratio, ALIROCUMAB, acute coronary syndrome, Cholesterol, LDL, Lipoprotein(a), Middle Aged, EFFICACY, medicine.disease, Cardiovascular Diseases, CARDIOVASCULAR-DISEASE, SAFETY, Cardiovascular System & Cardiology, biology.protein, Female, lipids (amino acids, peptides, and proteins), STATIN, low-density lipoprotein, cholesterol PCSK9 inhibitor, CORONARY, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine, Mace
Abstract: Digital, Background Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402), Ciencias Médicas y de la Salud
Published: 2021
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36. Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine, and Linezolid in a Murine Model of Tuberculosis

Author: Xirong Tian, Shah Alam, Zhili Lu, Gift Chiwala, Nanshan Zhong, H.M. Adnan Hameed, Shuai Wang, Wei Yu, Gregory M. Cook, Tianyu Zhang, D. A. Maslov, and Buhari Yusuf
Subjects: Drug, Tuberculosis, media_common.quotation_subject, Antitubercular Agents, Drug resistance, Pharmacology, Clofazimine, chemistry.chemical_compound, Mice, In vivo, Levofloxacin, medicine, Animals, Pharmacology (medical), Experimental Therapeutics, media_common, Mice, Inbred BALB C, Drug candidate, business.industry, Significant difference, Linezolid, Mycobacterium tuberculosis, Pyrazinamide, medicine.disease, Regimen, Disease Models, Animal, Infectious Diseases, chemistry, Murine model, business, medicine.drug
Abstract: Toxicity and inconvenience associated with the use of injectable drug-containing regimens for tuberculosis (TB) have made all-oral regimens a preferred alternative. Widespread resistance to fluoroquinolones and pyrazinamide makes it essential to identify new drug candidates and study their effects on current regimens for TB. TB47 is a pyrazolo[1,5-a]pyridine-3-carboxamide with powerful synergistic in vitro and in vivo activities against mycobacteria, especially with clofazimine. Here, we investigated the bactericidal and sterilizing activities of novel oral regimens containing TB47 + clofazimine + linezolid, and the potential roles of levofloxacin and/or pyrazinamide in such drug combinations. Using a well-established mouse model, we assessed the effect of these regimens on bacterial burden in the lung during treatment and relapse (4 months after stopping treatment + immunosuppression). Our findings indicate that the TB47 + clofazimine + linezolid + pyrazinamide, with/without levofloxacin, regimens had fast-acting (4 months) sterilizing activity and no relapse was observed. When pyrazinamide was excluded from the regimen, treatment times were longer (5-6 months) to achieve sterilizing conditions. We propose that TB47 + clofazimine + linezolid can form a highly sterilizing block for use as an alternative pan-TB regimen.
Published: 2021

37. A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line anti-tuberculosis regimen

Author: Yaoju Tan, Ping Guan, Nanshan Zhong, Jinxing Hu, Julius Mugweru, Gift Chiwala, Tianyu Zhang, Jianxiong Liu, Petuel Ndip Ndip Bate, Buhari Yusuf, Shouyong Tan, Bangxing Wang, H.M. Adnan Hameed, Shahzad Akbar Khan, Cuiting Fang, and Zhiyong Liu
Subjects: Tuberculosis, medicine.medical_treatment, Recombinant drug-resistant BCG, Ag85B, Antitubercular Agents, RM1-950, Drug resistance, Levofloxacin, Mice, SCID, Immune system, In vivo, Drug Resistance, Bacterial, Medicine, Animals, Amikacin, Tuberculosis, Pulmonary, Pharmacology, Chemotherapy, Antigens, Bacterial, Mice, Inbred BALB C, Vaccines, Synthetic, Drug-resistant tuberculosis, biology, Virulence, business.industry, General Medicine, Mycobacterium tuberculosis, Therapeutic vaccine, Rv2628, medicine.disease, Mycobacterium bovis, Pyrazinamide, Vaccination, Regimen, Disease Models, Animal, Immunology, Prothionamide, biology.protein, BCG Vaccine, Therapeutics. Pharmacology, Antibody, business, Plasmids
Abstract: Drug-resistant tuberculosis (DR-TB) poses a new threat to global health; to improve the treatment outcome, therapeutic vaccines are considered the best chemotherapy adjuvants. Unfortunately, there is no therapeutic vaccine approved against DR-TB. Our study assessed the therapeutic efficacy of a recombinant drug-resistant BCG (RdrBCG) vaccine in DR-TB. We constructed the RdrBCG overexpressing Ag85B and Rv2628 by selecting drug-resistant BCG strains and transformed them with plasmid pEBCG or pIBCG to create RdrBCG-E and RdrBCG-I respectively. Following successful stability testing, we tested the vaccine’s safety in severe combined immune deficient (SCID) mice that lack both T and B lymphocytes plus immunoglobulins. Finally, we evaluated the RdrBCG’s therapeutic efficacy in BALB/c mice infected with rifampin-resistant M. tuberculosis and treated with a second-line anti-TB regimen. We obtained M. bovis strains which were resistant to several second-line drugs and M. tuberculosis resistant to rifampin. Notably, the exogenously inserted genes were lost in RdrBCG-E but remained stable in the RdrBCG-I both in vitro and in vivo. When administered adjunct to a second-line anti-TB regimen in a murine model of DR-TB, the RdrBCG-I lowered lung M. tuberculosis burden by 1 log10. Furthermore, vaccination with RdrBCG-I adjunct to chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG-I showed almost the same virulence as its parent BCG Tice strain in SCID mice. Our findings suggested that the RdrBCG-I was stable, safe and effective as a therapeutic vaccine. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.
Published: 2021

38. A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line tuberculosis regimen

Author: Ping Guan, Julius Mugweru, Buhari Yusuf, Nanshan Zhong, Jinxing Hu, Zhiyong Liu, Yaoju Tan, Tianyu Zhang, Petuel Ndip Ndip Bate, Jianxiong Liu, Shouyong Tan, Gift Chiwala, Shahzad Akbar Khan, H.M. Adnan Hameed, Cuiting Fang, and Bangxing Wang
Subjects: Tuberculosis, biology, business.industry, Isoniazid, Drug resistance, biology.organism_classification, medicine.disease, Chemotherapy regimen, Mycobacterium tuberculosis, Vaccination, Regimen, Immunology, Medicine, business, Pathogen, medicine.drug
Abstract: Drug-resistant tuberculosis (DR-TB) results from infection by Mycobacterium tuberculosis strains resistant to at least rifampin or isoniazid. To improve the treatment outcome in DR-TB, therapeutic vaccines are considered an ideal choice as they can enhance pathogen clearance and minimize disease sequelae. To date, there is no therapeutic vaccine reported to be effective when combined with a chemotherapy regimen against DR-TB. The only available TB vaccine, the M. bovis BCG (BCG) is susceptible to several anti-TB drugs hence not a perfect option for therapeutic vaccination. Herein, we developed a recombinant BCG (RdrBCG) overexpressing Ag85B and Rv2628 with resistance to selected anti-TB drugs. When administered three times adjunct to a second-line anti-TB regimen in a classical murine model of DR-TB, the RdrBCG lowered lung M. tuberculosis colony-forming units by 1 log10. Furthermore, vaccination with the RdrBCG adjunct to TB chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG maintained the exogenously inserted genes and showed almost the same virulence as its parent BCG Tice strain in severe combined immune-deficient mice. All these suggested that the RdrBCG was stable, safe and effective. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.
Published: 2021
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39. Comparison of Heart Team vs Interventional Cardiologist Recommendations for the Treatment of Patients With Multivessel Coronary Artery Disease

Author: Dominic Parry, Victor Chu, Shamir R. Mehta, Madhu K. Natarajan, Omid Salehian, Irene Cybulsky, Amin Mulji, Richard P. Whitlock, Natalia Pinilla, Adel Dyub, Adnan Hameed, J-D Schwalm, Lloyd Semelhago, Nicholas Valettas, Sanjit S. Jolly, Mathew Mercuri, Ahmed Alshatti, Matthew Sibbald, Sumeet Gandhi, Andre Lamy, Michael B. Tsang, Saeed Darvish-Kazem, Dan Pericak, Nandini Gupta, Tej Sheth, Kostas Ioannou, Bobby Yanagawa, Craig Ainsworth, Li Zhang, James L. Velianou, Amiram Gafni, and Douglas Wright
Subjects: Male, medicine.medical_specialty, Cross-sectional study, medicine.medical_treatment, Concordance, health care facilities, manpower, and services, Clinical Decision-Making, education, Cardiology, Coronary Artery Disease, Revascularization, Coronary artery disease, Coronary artery bypass surgery, Cardiologists, Percutaneous Coronary Intervention, Internal medicine, health services administration, medicine, Humans, cardiovascular diseases, Practice Patterns, Physicians', Coronary Artery Bypass, health care economics and organizations, Aged, Original Investigation, Patient Care Team, Interventional cardiology, business.industry, Research, Percutaneous coronary intervention, Heart, General Medicine, Middle Aged, medicine.disease, Stenosis, Online Only, Cross-Sectional Studies, Practice Guidelines as Topic, Female, business
Abstract: Key Points Question Do treatments recommended by a heart team differ from those recommended by an original treating interventional cardiologist for patients with multivessel coronary artery disease? Findings In this cross-sectional study of 245 patients with multivessel coronary artery disease, heart team treatment recommendations indicated moderate agreement (with discordance in 30% of cases) with the original treating interventional cardiologist. Unanimous decisions within the heart team and agreement between the heart team interventional cardiologist and the original treating interventional cardiologist were less frequent in this subset of cases, while interventional cardiologist recommendations for angioplasty and medication therapy were more frequent. Meaning The study’s findings indicated that heart team recommendations differed from those of the original treating interventional cardiologist in approximately one-third of cases; this subset of cases was associated with a greater number of divergent opinions between interventional cardiologists and within the heart team., Importance Although the heart team approach is recommended in revascularization guidelines, the frequency with which heart team decisions differ from those of the original treating interventional cardiologist is unknown. Objective To examine the difference in decisions between the heart team and the original treating interventional cardiologist for the treatment of patients with multivessel coronary artery disease. Design, Setting, and Participants In this cross-sectional study, 245 consecutive patients with multivessel coronary artery disease were recruited from 1 high-volume tertiary care referral center (185 patients were enrolled through a screening process, and 60 patients were retrospectively enrolled from the center’s database). A total of 237 patients were included in the final virtual heart team analysis. Treatment decisions (which comprised coronary artery bypass grafting, percutaneous coronary intervention, and medication therapy) were made by the original treating interventional cardiologists between March 15, 2012, and October 20, 2014. These decisions were then compared with pooled-majority treatment decisions made by 8 blinded heart teams using structured online case presentations between October 1, 2017, and October 15, 2018. The randomized members of the heart teams comprised experts from 3 domains, with each team containing 1 noninvasive cardiologist, 1 interventional cardiologist, and 1 cardiovascular surgeon. Cases in which all 3 of the heart team members disagreed and cases in which procedural discordance occurred (eg, 2 members chose coronary artery bypass grafting and 1 member chose percutaneous coronary intervention) were discussed in a face-to-face heart team review in October 2018 to obtain pooled-majority decisions. Data were analyzed from May 6, 2019, to April 22, 2020. Main Outcomes and Measures The Cohen κ coefficient between the treatment recommendation from the heart team and the treatment recommendation from the original treating interventional cardiologist. Results Among 234 of 237 patients (98.7%) in the analysis for whom complete data were available, the mean (SD) age was 67.8 (10.9) years; 176 patients (75.2%) were male, and 191 patients (81.4%) had stenosis in 3 epicardial coronary vessels. A total of 71 differences (30.3%; 95% CI, 24.5%-36.7%) in treatment decisions between the heart team and the original treating interventional cardiologist occurred, with a Cohen κ of 0.478 (95% CI, 0.336-0.540; P = .006). The heart team decision was more frequently unanimous when it was concordant with the decision of the original treating interventional cardiologist (109 of 163 cases [66.9%]) compared with when it was discordant (28 of 71 cases [39.4%]; P, This cross-sectional study examines the differences in treatment decisions between a heart team and an original treating interventional cardiologist for patients with multivessel coronary artery disease.
Published: 2020

40. Design, synthesis, andin vitrobiological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors ofMycobacterium tuberculosis

Author: Goverdhan Surineni, Yamin Gao, Mahmudul Islam, Zhiyong Liu, Chiranjibi Chhotaray, Tianyu Zhang, H.M. Adnan Hameed, Muzammal Hussain, and Zhili Lu
Subjects: Pharmacology, Benzimidazole, Tuberculosis, biology, 010405 organic chemistry, Organic Chemistry, Pharmaceutical Science, Biological activity, medicine.disease, biology.organism_classification, Condensation reaction, 01 natural sciences, Biochemistry, Combinatorial chemistry, In vitro, 0104 chemical sciences, Mycobacterium tuberculosis, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, chemistry, Drug Discovery, medicine, Molecular Medicine, Cytotoxicity, Biological evaluation
Abstract: Tuberculosis (TB) has become one of the most significant public health problems in recent years. Antibiotic therapy remains the mainstay of TB control strategies, but the increasing resistance of mycobacterial species has heightened alarm, requiring the development of novel drugs in order to improve treatment outcomes. Here, as an effort to identify novel and effective antitubercular agents, we designed and synthesized a series of novel substituted benzimidazolallylidenehydrazinylmethylthiazole derivatives via a multi-component molecular hybridization approach with single molecular architecture. Our design strategy involved assembling the antitubercular pharmacophoric fragments benzimidazole, 2-aminothiazole and substituted α,β-unsaturated ketones via condensation reactions. All the newly synthesized compounds were fully characterized via NMR and mass spectral data and evaluated for in vitro biological activity against the H37Ra strain of Mycobacterium tuberculosis. From the biological evaluation data, we identified some effective compounds, of which 8g and 7e were the most active ones (both having MIC values of 2.5 μg mL-1). In addition, compound 8g exhibited a lower cytotoxicity profile. We conceive that compound 8g may serve as a chemical probe of interest for further lead optimization studies with the general aim of developing novel and effective antitubercular agents.
Published: 2019
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41. Assessment of Clofazimine and TB47 Combination Activity against Mycobacterium abscessus Using a Bioluminescent Approach

Author: Xingshan Cai, Yuanyuan Cao, Yaoju Tan, Peipei Zhou, Shuai Wang, H.M. Adnan Hameed, Sheng Zeng, Yang Liu, Tianyu Zhang, Jianxiong Liu, Xiaoyun Lu, Guoliang Zhang, Eric L. Nuermberger, Huancai Yin, Mahmudul Islam, and Julius Mugweru
Subjects: Drug, Luminescence, media_common.quotation_subject, Mycobacterium Infections, Nontuberculous, Microbial Sensitivity Tests, Pharmacology, Mycobacterium abscessus, Clofazimine, Electron Transport, Recombinases, Electron Transport Complex III, Mice, 03 medical and health sciences, Bacterial Proteins, In vivo, Clarithromycin, Drug Resistance, Multiple, Bacterial, medicine, Animals, Experimental Therapeutics, Pharmacology (medical), Enzyme Inhibitors, Amikacin, 030304 developmental biology, media_common, Mice, Inbred BALB C, Roxithromycin, 0303 health sciences, biology, 030306 microbiology, business.industry, Optical Imaging, Drug Synergism, bacterial infections and mycoses, Antimicrobial, biology.organism_classification, Anti-Bacterial Agents, Drug Combinations, Infectious Diseases, Female, Genetic Engineering, business, medicine.drug
Abstract: Mycobacterium abscessus is intrinsically resistant to most antimicrobial agents. The emerging infections caused by M. abscessus and the lack of effective treatment call for rapid attention. Here, we intended to construct a selectable marker-free autoluminescent M. abscessus strain (designated UAlMab) as a real-time reporter strain to facilitate the discovery of effective drugs and regimens for treating M. abscessus. The UAlMab strain was constructed using the dif/Xer recombinase system. In vitro and in vivo activities of several drugs, including clofazimine and TB47, a recently reported cytochrome bc(1) inhibitor, were assessed using UAlMab. Furthermore, the efficacy of multiple drug combinations, including the clofazimine and TB47 combination, were tested against 20 clinical M. abscessus isolates. The UAlMab strain enabled us to evaluate drug efficacy both in vitro and in live BALB/c mice in a real-time, noninvasive fashion. Importantly, although TB47 showed marginal activity either alone or in combination with clarithromycin, amikacin, or roxithromycin, the drug markedly potentiated the activity of clofazimine, both in vitro and in vivo. This study demonstrates that the use of the UAlMab strain can significantly facilitate rapid evaluation of new drugs and regimens. The clofazimine and TB47 combination is effective against M. abscessus, and dual/triple electron transport chain (ETC) targeting can be an effective therapeutic approach for treating mycobacterial infections.
Published: 2020
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42. Phenotypic and Genotypic Characterization of Streptomycin-Resistant Multidrug-Resistant

Author: Md Mahmudul, Islam, Yaoju, Tan, H M Adnan, Hameed, Chiranjibi, Chhotaray, Zhiyong, Liu, Yang, Liu, Zhili, Lu, Shuai, Wang, Xiaoyin, Cai, Yamin, Gao, Xingshan, Cai, Lingmin, Guo, Xinjie, Li, Shouyong, Tan, Wing Wai, Yew, Nanshan, Zhong, Jianxiong, Liu, and Tianyu, Zhang
Subjects: China, Genotype, Genes, Bacterial, Tuberculosis, Multidrug-Resistant, Antitubercular Agents, Streptomycin, Humans, Microbial Sensitivity Tests, Mycobacterium tuberculosis
Abstract: Streptomycin (STR) is the first antibiotic used in the treatment of tuberculosis (TB) and the earliest antituberculosis drug with acquired resistance developed by
Published: 2020

43. Comparative Analysis of Whole-Genome and Methylome Profiles of a Smooth and a Rough

Author: Chiranjibi, Chhotaray, Shuai, Wang, Yaoju, Tan, Amjad, Ali, Muhammad, Shehroz, Cuiting, Fang, Yang, Liu, Zhili, Lu, Xingshan, Cai, H M Adnan, Hameed, Md Mahmudul, Islam, Goverdhan, Surineni, Shouyong, Tan, Jianxiong, Liu, and Tianyu, Zhang
Subjects: single nucleotide variation, Epigenome, whole genome sequencing, Phenotype, Polymorphism, Genetic, Mycobacterium abscessus, SMRT sequencing, comparative genomics, methylation, DNA Methylation, Genome, Bacterial, Genome Report
Abstract: Mycobacterium abscessus is a fast growing Mycobacterium species mainly causing skin and respiratory infections in human. M. abscessus is resistant to numerous drugs, which is a major challenge for the treatment. In this study, we have sequenced the genomes of two clinical M. abscessus strains having rough and smooth morphology, using the single molecule real-time and Illumina HiSeq sequencing technology. In addition, we reported the first comparative methylome profiles of a rough and a smooth M. abscessus clinical strains. The number of N4-methylcytosine (4mC) and N6-methyladenine (6mA) modified bases obtained from smooth phenotype were two-fold and 1.6 fold respectively higher than that of rough phenotype. We have also identified 4 distinct novel motifs in two clinical strains and genes encoding antibiotic-modifying/targeting enzymes and genes associated with intracellular survivability having different methylation patterns. To our knowledge, this is the first report about genome-wide methylation profiles of M. abscessus strains and identification of a natural linear plasmid (15 kb) in this critical pathogen harboring methylated bases. The pan-genome analysis of 25 M. abscessus strains including two clinical strains revealed an open pan genome comprises of 7596 gene clusters. Likewise, structural variation analysis revealed that the genome of rough phenotype strain contains more insertions and deletions than the smooth phenotype and that of the reference strain. A total of 391 single nucleotide variations responsible for the non-synonymous mutations were detected in clinical strains compared to the reference genome. The comparative genomic analysis elucidates the genome plasticity in this emerging pathogen. Furthermore, the detection of genome-wide methylation profiles of M. abscessus clinical strains may provide insight into the significant role of DNA methylation in pathogenicity and drug resistance in this opportunistic pathogen.
Published: 2019

44. Detection of Novel Gene Mutations Associated with Pyrazinamide Resistance in Multidrug-Resistant

Author: Hm Adnan, Hameed, Yaoju, Tan, Md Mahmudul, Islam, Zhili, Lu, Chiranjibi, Chhotaray, Shuai, Wang, Zhiyong, Liu, Cuiting, Fang, Shouyong, Tan, Wing Wai, Yew, Nanshan, Zhong, Jianxiong, Liu, and Tianyu, Zhang
Subjects: drug resistance, tuberculosis, molecular diagnosis, frameshift deletion, novel mutations, Original Research, pyrazinamidase
Abstract: Objective Pyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA+ upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis. Methods Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates. Results Our data showed that among 448 M. tuberculosis clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drug-resistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZAR isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncA-Rv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZAR. Compared with phenotypic data, 84.38% (227/269) PZAR strains with mutations in pncA+ upstream region exhibited 83.64% sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48% (4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74% (2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C−114del) in upstream of pncAwt nullified the effect of A−11G mutation and induced positive PZase activity, divergent from five PZase negative A−11G PZAR mutants. Twenty-six PZAR strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms. Conclusion Our study revealed that PZAR rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA+ UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/zW3IJ-ZxTmk
Published: 2019

45. Prevalence and molecular characterization of amikacin resistance among Mycobacterium tuberculosis clinical isolates from southern China

Author: Zhili Lu, Chiranjibi Chhotaray, Tianyu Zhang, Shuai Wang, Xinjie Li, Jianxiong Liu, H.M. Adnan Hameed, Biyi Su, Mahmudul Islam, Xiaoyin Cai, Yaoju Tan, Yang Liu, Shouyong Tan, Xingshan Cai, and Zhiyong Liu
Subjects: 0301 basic medicine, Microbiology (medical), China, Tuberculosis, Resistance, 030106 microbiology, Immunology, Injectable drug, Microbial Sensitivity Tests, Gene mutation, medicine.disease_cause, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, 0302 clinical medicine, Kanamycin, Drug Resistance, Multiple, Bacterial, Prevalence, Immunology and Allergy, Medicine, Humans, 030212 general & internal medicine, Capreomycin, Gene, Amikacin, Mutation, biology, business.industry, Incidence (epidemiology), bacterial infections and mycoses, biology.organism_classification, medicine.disease, QR1-502, carbohydrates (lipids), Regimen, Susceptibility testing, business, medicine.drug
Abstract: Objectives Amikacin is the only second-line injectable antituberculosis (anti-TB) drug still recommended for multidrug-resistant tuberculosis (MDR-TB) treatment when a short MDR-TB regimen is designed. Mutations in rrs and eis are reported to be associated with resistance to amikacin. In this study, we investigated the incidence of rrs, eis, tap and whiB7 mutations in amikacin-resistant Mycobacterium tuberculosis clinical isolates to find the proportion of different mutations related to amikacin resistance. Methods A total of 395 clinical isolates of M. tuberculosis were used for phenotypic drug susceptibility testing (DST) to 10 drugs with the Lowenstein–Jensen (L–J) method. We sequenced rrs, eis, tap and whiB7 genes in 178 M. tuberculosis clinical isolates (89 amikacin-resistant isolates and 89 of 306 amikacin-susceptible isolates). Results Our data showed that 22.53% (89/395) M. tuberculosis clinical isolates were resistant to amikacin. Of the 89 amikacin-resistant isolates, 89.89% (80/89) were MDR-TB, of which 12.36% (11/89) were pre-extensively drug-resistant TB (pre–XDR-TB) and 77.53% (69/89) were XDR-TB. The rrs mutations were found in 82% (73/89) in amikacin-resistant M. tuberculosis clinical isolates. The A1401G alteration in the rrs gene was the most dominant mutation (80.90%; 72/89). Five mutations were detected as new in rrs, tap and whiB7. Notably, 13.48% (12/89) amikacin-resistant isolates had no known mutation in these genes. Conclusions Our data reveal that the rrs mutation is a predominant molecular marker of amikacin resistance in southern China. Analysis of the rrs gene mutations will significantly reduce the time and cost to diagnose amikacin resistance in TB patients. Other unknown amikacin resistance mechanism(s) exist.
Published: 2019

46. The Effects of Secondary Pneumonia on the Curative Efficacy of Multidrug-resistant Tuberculosis: A Retrospective Cohort Study

Author: TAN, Shou Yong, LIANG, Zhuo Zhi, Chiwala, Gift, KUANG, Hao Bin, HUANG, Zhi Pei, QIN, Hong Juan, LI, Yan, LI, Yan Qiong, Adnan Hameed, H.M., and ZHANG, Tian Yu
Published: 2018
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47. Rapid, serial, non-invasive quantification of Pseudomonas aeruginosa in live mice with a selectable marker-free autoluminescent strain

Author: Jianxiong Liu, Yaoju Tan, Wei Yu, Lingmin Guo, Zhizhong Cao, Nanshan Zhong, Shuai Wang, Ping Guan, Jinxing Hu, Mahmudul Islam, Tianyu Zhang, Xiaoyin Cai, Jingran Zhang, H.M. Adnan Hameed, Xirong Tian, Sanjeep Sapkota, Gao Yamin, Sheng Zeng, Zhiyong Liu, Shahzad Akbar Khan, Cuiting Fang, and Zafran Khan
Subjects: medicine.drug_class, Antibiotics, Biomedical Engineering, Biophysics, Biosensing Techniques, Microbial Sensitivity Tests, 02 engineering and technology, Biology, medicine.disease_cause, 01 natural sciences, Microbiology, Mice, Levofloxacin, In vivo, Electrochemistry, medicine, Animals, Pseudomonas Infections, Biapenem, Selectable marker, Polymyxin B, Pseudomonas aeruginosa, 010401 analytical chemistry, General Medicine, 021001 nanoscience & nanotechnology, Anti-Bacterial Agents, 0104 chemical sciences, Amikacin, 0210 nano-technology, Biotechnology, medicine.drug
Abstract: Pseudomonas aeruginosa is an increasingly prevalent pathogen that has become a serious health concern due to an increasing incidence of multidrug-resistant (MDR) hospital-acquired infections. The emergence of MDR-P. aeruginosa coupled with shrinking antibiotic pipelines has increased the demand for new antimicrobials and therapeutics. An effective tool for drug screening both in vitro and in vivo can facilitate the discovery of drugs and regimens for treating P. aeruginosa infection. Here, for the first time, we combined the mini-Tn7 system and Xer/dif recombinase system to construct a stable and selectable marker-free autoluminescent P. aeruginosa (SfAlPa) by one step. Afterwards, in vitro and in vivo activities of several antibiotics including amikacin, biapenem, levofloxacin and polymyxin B were assessed using SfAlPa. This study demonstrated that the use of SfAlPa could significantly facilitate rapid real-time evaluating the activities of compounds. Compared to prevailing methods, this method reduces the time, effort, animals and costs consumed in the discovery of new drugs against P. aeruginosa. Additionally, the methodology described in this study could be easily modified for construction of selectable marker-free reporter strain in other Gram-negative bacteria.
Published: 2020
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48. Numerical Study of the Heat Transfer Behavior in Helical Microcoil Tube

Author: Adnan Hameed Rasheed, Hajar Alias, and Sami D. Salman
Subjects: Work (thermodynamics), Finite volume method, Partial differential equation, Materials science, Convective heat transfer, business.industry, Reynolds number, Mechanics, Computational fluid dynamics, Physics::Fluid Dynamics, symbols.namesake, Heat transfer, Heat exchanger, symbols, business
Abstract: This work introduces a numerical study of the convective heat transfer of helical micro coils tube heat exchanger coil. It tested for both circle and elliptical geometry with 18 mm pitch and diameter of copper pipes. It is very difficult and time-consuming if these analyses could be carried out experimentally. Water is used as a working fluid by using 80 C for hot water and 25 C for cold water. The Reynolds number selected in the range of 200 to 1800 for hot water, while specified 5000 for cold water. ANSYS-FLUENT 18.0 has been used to investigate the heat transfer behavior. In computational fluid dynamics (CFD), the partial differential equations was represented by using the finite volume method (FVM) in the form of algebraic equations and the Navier-Stokes equations were solved by using a numerical procedure which is the Semi Implicit Method for Pressure-Linked Equations (SIMPLE) algorithm. The elementary results observed a proportionality relationship between the heat transfer and the Reynolds number raised values. Also, the circular configuration present maximum heat transfer performance and the maximum values are 5.6, 3.42 for Thermal performance factor and Nuselte number respectively at Reynolds number 1800.
Published: 2020
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49. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model

Author: Huofeng Jiang, Yang Liu, Tianyu Zhang, Jianxiong Liu, Zhiyong Liu, Gift Chiwala, Shouyong Tan, Yamin Gao, Gaëlle Guiewi Makafe, Shuai Wang, Mahmudul Islam, Yaoju Tan, Xingshan Cai, Zhili Lu, Chiranjibi Chhotaray, H.M. Adnan Hameed, Xinjie Li, and Changwei Wang
Subjects: 0301 basic medicine, Buruli ulcer, Tuberculosis, Science, General Physics and Astronomy, 02 engineering and technology, Biology, medicine.disease_cause, Article, General Biochemistry, Genetics and Molecular Biology, Microbiology, Electron Transport Complex III, Mice, 03 medical and health sciences, chemistry.chemical_compound, In vivo, Immunopathology, medicine, Animals, lcsh:Science, Mycolactone, Buruli Ulcer, Multidisciplinary, Mycobacterium ulcerans, Toxin, General Chemistry, 021001 nanoscience & nanotechnology, medicine.disease, biology.organism_classification, In vitro, Anti-Bacterial Agents, 030104 developmental biology, chemistry, Mutation, lcsh:Q, 0210 nano-technology
Abstract: Buruli ulcer (BU) is an emerging infectious disease that causes disfiguring skin ulcers. The causative agent, Mycobacterium ulcerans, secretes toxin called mycolactone that triggers inflammation and immunopathology. Existing treatments are lengthy and consist of drugs developed for tuberculosis. Here, we report that a pyrazolo[1,5-a]pyridine-3-carboxamide, TB47, is highly bactericidal against M. ulcerans both in vitro and in vivo. In the validated mouse model of BU, TB47 alone reduces M. ulcerans burden in mouse footpads by more than 2.5 log10 CFU compared to the standard BU treatment regimen recommended by the WHO. We show that mutations of ubiquinol-cytochrome C reductase cytochrome subunit B confer resistance to TB47 and the dissimilarity of CydABs from different mycobacteria may account for their differences in susceptibility to TB47. TB47 is highly potent against M. ulcerans and possesses desirable pharmacological attributes and low toxicity that warrant further assessment of this agent for treatment of BU., Combination therapy for Buruli ulcer (BU) is suboptimal. Here, Liu et al. show that the candidate drug TB47 has potent bactericidal activity against Mycobacterium ulcerans in vitro and in a mouse model, which underscores its potential for shortening the course of BU and treating other mycobacterial diseases.
Published: 2019
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50. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author: Kausik K Ray, Helen M Colhoun, Michael Szarek, Marie Baccara-Dinet, Deepak L Bhatt, Vera A Bittner, Andrzej J Budaj, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Virginie Loizeau, Renato D Lopes, Angèle Moryusef, Jan Murin, Robert Pordy, Arsen D Ristic, Matthew T Roe, José Tuñón, Harvey D White, Andreas M Zeiher, Gregory G Schwartz, Philippe Gabriel Steg, Gregory G. Schwartz, Ph. Gabriel Steg, Deepak L. Bhatt, Vera A. Bittner, Shaun G. Goodman, Robert A. Harrington, J. Wouter Jukema, Harvey D. White, Andreas M. Zeiher, Pierluigi Tricoci, Matthew T. Roe, Kenneth W. Mahaffey, Jay M. Edelberg, Guillaume Lecorps, William J. Sasiela, Jean-François Tamby, Philip E. Aylward, Heinz Drexel, Peter Sinnaeve, Mirza Dilic, Renato D. Lopes, Nina N. Gotcheva, Juan-Carlos Prieto, Huo Yong, Patricio López-Jaramillo, Ivan Pećin, Zeljko Reiner, Petr Ostadal, Margus Viigimaa, Markku S. Nieminen, Vakhtang Chumburidze, Nikolaus Marx, Nicolas Danchin, Evangelos Liberopoulos, Pablo Carlos Montenegro Valdovinos, Hung-Fat Tse, Robert Gabor Kiss, Denis Xavier, Doron Zahger, Marco Valgimigli, Takeshi Kimura, Hyo Soo Kim, Sang-Hyun Kim, Andrejs Erglis, Aleksandras Laucevicius, Sasko Kedev, Khalid Yusoff, Gabriel Arturo Ramos López, Marco Alings, Sigrun Halvorsen, Roger M. Correa Flores, Andrzej Budaj, Joao Morais, Maria Dorobantu, Yuri Karpov, Arsen D. Ristic, Terrance Chua, Zlatko Fras, Anthony J. Dalby, H. Asita de Silva, Emil Hagström, Ulf Landmesser, Chern-En Chiang, Piyamitr Sritara, Sema Guneri, Alexander Parkhomenko, Kausik K. Ray, Patrick M. Moriarty, Robert Vogel, Bernard Chaitman, Sheryl F. Kelsey, Anders G. Olsson, Jean-Lucien Rouleau, Maarten L. Simoons, Karen Alexander, Chiara Meloni, Robert Rosenson, Eric J.G. Sijbrands, John H. Alexander, Luciana Armaganijan, Akshay Bagai, Maria Cecilia Bahit, J. Matthew Brennan, Shaun Clifton, Adam D. DeVore, Shalonda Deloatch, Sheila Dickey, Keith Dombrowski, Grégory Ducrocq, Zubin Eapen, Patricia Endsley, Arleen Eppinger, Robert W. Harrison, Connie Ng Hess, Mark A. Hlatky, Joseph Dedrick Jordan, Joshua W. Knowles, Bradley J. Kolls, David F. Kong, Sergio Leonardi, Linda Lillis, David J. Maron, Jill Marcus, Robin Mathews, Rajendra H. Mehta, Robert J. Mentz, Humberto Graner Moreira, Chetan B. Patel, Sabrina Bernardez-Pereira, Lynn Perkins, Thomas J. Povsic, Etienne Puymirat, William Schuyler Jones, Bimal R. Shah, Matthew W. Sherwood, Kenya Stringfellow, Darin Sujjavanich, Mustafa Toma, Charlene Trotter, Sean Van Diepen, Matthew D. Wilson, Andrew T. Yan, Lilia B. Schiavi, Marcelo Garrido, Andrés F. Alvarisqueta, Sonia A. Sassone, Anselmo P. Bordonava, Alberto E. Alves De Lima, Jorge M. Schmidberg, Ernesto A. Duronto, Orlando C. Caruso, Leonardo P. Novaretto, Miguel Angel Hominal, Oscar R. Montaña, Alberto Caccavo, Oscar A. Gomez Vilamajo, Alberto J. Lorenzatti, Luis R. 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Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, O, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, R, Clifford, P, Wong, Y, Iqbal, S, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Smith, S, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Ayaz, M, Cheema, M, Oliver, R, Thackray, S, Mudawi, T, Rahman, G, Sultan, A, Sharman, D, Sprigings, D, Butler, R, Wilkinson, P, Lip, G, Halcox, J, Gallagher, S, Ossei-Gerning, N, Vardi, G, Baldari, D, Brabham, D, Treasure II, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, A, Ince, C, Flores, E, Wright, S, Cheng, S, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Cambier, P, Lieber, I, Kumar, P, East, C, Krichmar, P, Hasan, M, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Amidon, T, Suh, D, Arif, I, Abdallah, M, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Moriarty, K, Harris, B, Cohen, S, Carter, L, Doty, D, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, S, Koren, M, Chandna, H, Dodds III, G, Goraya, T, Bengston, J, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Fenton, S, Singh, N, Shah, A, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Richard, K, Keating, F, Kondo, N, Shetty, S, Levite, H, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Izzo, M, Kumar, A, Hattler, B, Do, R, Link, C, Bortnick, A, Kinzfogl III, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Islam, O, Subherwal, S, Ranadive, N, Vakili, B, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Zahr, F, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, M, Schmalfuss, C, Picone, M, Pederson, R, Herzog, W, Friedman, K, Lindsey, J, Nowins, R, Timothy, E, Leonard, P, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, Alonso, A, May, W, Christopher, D, Galski, T, Chu, A, Mody, F, Ramin, E, Hodes, Z, Rossi, J, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, Vetrovec, G, King, M, Carey, C, Gerber, J, Younis, L, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Kuvin, J, Silver, K, Foster, M, Tonnessen, G, Espinoza, A, Amlani, M, Wali, A, Malozzi, C, Jong, G, Massey, C, Wattanakit, K, O'Donnell, P, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Blonder, R, Akyea-Djamson, A, Labroo, A, Marais, H, Claxton, E, Weiss, R, Kathryn, R, Berk, M, Joshi, P, Khera, A, Khaira, A, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Erenrich, N, Farrar, M, Pollock, S, French, W, Diamantis, S, Guy, D, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Albert, S, Spriggs, D, Strain, J, Mittal, S, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, F, Nahhas, A, Pope, T, Nager, P, Vohra, R, Sharma, M, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Stapleton, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, P, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Dohad, S, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Henry, J, Schifferdecker, B, Gilbert, J, Chalavarya, G, Eaton, C, Schmedtje, J, Christenson, S, Dotani, I, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Assi, N, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Gamil, D, Akright, L, Krawczyk, J, Cobler, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bregeault, M, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Chengyue, Z, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, Dempsey, M, Mcclanahan, M, ODYSSEY OUTCOMES Comm Investigato, and Ege Üniversitesi
Subjects: Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, STATIN THERAPY, blood-glucose, Endocrinology, Diabetes and Metabolism, GUIDELINES, PCSK9, 0302 clinical medicine, Endocrinology, GENETIC-VARIANTS, Cardiovascular Disease, Diabetes Complication, Aged Antibodies, Monoclonal, Humanized / therapeutic use* Cardiovascular Diseases / blood Cardiovascular Diseases / prevention & control* Diabetes Complications / blood Diabetes Complications / prevention & control* Female Humans Male Middle Aged Substances, Clinical endpoint, Medicine, guidelines, 030212 general & internal medicine, Prediabetes, Myocardial infarction, myocardial-infarction, genetic-variants, statin therapy, risk, pcsk9, association, liraglutide, evolocumab, RISK, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, BLOOD-GLUCOSE, ASSOCIATION, Middle Aged, Cardiovascular Diseases, Female, Life Sciences & Biomedicine, Human, medicine.medical_specialty, Acute coronary syndrome, PCSK9 inhibitor, acute coronary syndrome, lipoprotein(a), low-density lipoprotein cholesterol, 030209 endocrinology & metabolism, Antibodies, Monoclonal, Humanized, Diabetes Complications, Endocrinology & Metabolism, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Aged, Alirocumab, diabetes, PCSK9, hyperlipidemia, Science & Technology, ODYSSEY OUTCOMES Committees and Investigators, business.industry, Unstable angina, EVOLOCUMAB, medicine.disease, MYOCARDIAL-INFARCTION, LIRAGLUTIDE, Human medicine, business
Abstract: Doi, Yasuji/0000-0002-8368-0827; galvani, marcello/0000-0001-5897-667X; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Sherwood, Matthew/0000-0002-4305-5883; Malynovsky, Yaroslav V/0000-0002-9118-1104; Viktorova, vic-inna@mail.ru I.A./0000-0001-8728-2722; bastos, jose/0000-0002-9526-3123; Yang, Eric H/0000-0003-4889-7454; Rudenko, Anatoliy Viktorovich/0000-0003-1099-1613; Novotny, Vojtech/0000-0003-3521-9945; Nikolaev, Konstantin/0000-0003-4601-6203; Reshetko, Olga/0000-0003-3107-7636; Leonardi, Sergio/0000-0002-4800-6132; Muenzel, Thomas/0000-0001-5503-4150; Ushakov, Alexei V/0000-0002-7020-4442; Tse, Hung Fat/0000-0002-9578-7808; Podoleanu, Cristian/0000-0001-9987-2519; Raffel, Owen C/0000-0001-5470-7050; Khasanov, Niiaz/0000-0002-7760-0763; Chumakova, Galina A/0000-0002-2810-6531; Ersanli, Murat/0000-0003-1847-3087; cornel, jan hein/0000-0002-1006-2112; Abbate, Antonio/0000-0002-1930-785X; Racca, Vittorio/0000-0002-4465-3789; Urina-Triana, Miguel A/0000-0001-6003-4622; Rasputina, Lesia/0000-0003-1230-4039; Racca, Vittorio/0000-0002-4465-3789; Reis, Gilmar/0000-0002-4847-1034; Sandhu, Manjinder/0000-0003-2538-2079; Keskin, Kudret/0000-0002-9049-1530; PAREPA, IRINEL/0000-0002-7571-9015; Manakshe, Gajendra/0000-0002-4983-4271; Nicolau, Jose C/0000-0002-9680-3689; Strelnieks, Aldis/0000-0003-3493-2562; Budaj, Andrzej/0000-0002-6395-2098; Marin, Francisco/0000-0001-7246-7708; Wongpraparut, Nattawut/0000-0002-1541-3313; Yuan, Zuyi/0000-0002-4141-0298; Jeong, Myung Ho/0000-0003-2424-810X; Mostovoy, Yuriy/0000-0002-7041-1230; Pepine, Carl/0000-0002-6011-681X; Lopez-Jaramillo, Patricio/0000-0002-9122-8742; Garcia-Lledo, Alberto/0000-0002-8986-2584; Tesloianu, Nicolae-Dan/0000-0002-1007-3022; Kosmacheva, Elena/0000-0001-8600-0199; Kunz Sebba Barroso Souza, Weimar/0000-0002-1265-1930; Katz, Amos/0000-0003-0422-934X; Tunon, Jose/0000-0002-1373-0999; Acevedo, Monica/0000-0002-7989-6633; Hove, Jens/0000-0002-5600-5623; Yakushin, Sergey/0000-0001-7202-742X; Gonzalez Juanatey, Jose Ramon/0000-0001-9681-3388; Lyamina, Nadezhda/0000-0001-6939-3234; Aylward, Philip/0000-0002-5358-8552; Apostolovic, Svetlana/0000-0001-9015-297X; Airaksinen, Juhani/0000-0002-0193-568X; Nahhas, Prof. Dr. Ahmed/0000-0002-2887-8187; Barbarash, Olga/0000-0002-4642-3610, WOS: 000475553300016, PubMed: 31272931, Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1.4-1.8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1: 1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0.65-1.30 mmol/L. in this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA(1c) or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. the primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials. gov, number NCT01663402. Findings At study baseline, 5444 patients (28.8%) had diabetes, 8246 (43.6%) had prediabetes, and 5234 (27.7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2.20-2.28 mmol/L), after 4 months' treatment with alirocumab (0.80 mmol/L), or after 4 months' treatment with placebo (2.25-2.28 mmol/L). in the placebo group, the incidence of the primary endpoint over a median of 2.8 years was greater in patients with diabetes (16.4%) than in those with prediabetes (9.2%) or normoglycaemia (8.5%); hazard ratio (HR) for diabetes versus normoglycaemia 2.09 (95% CI 1.78-2.46, p, Sanofi; Regeneron Pharmaceuticals, Sanofi and Regeneron Pharmaceuticals.
Published: 2019
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