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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. 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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6. 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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7. 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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8. 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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12. 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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13. 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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14. 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. 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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17. 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. Initial Invasive or Conservative Strategy for Stable Coronary Disease

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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, 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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 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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 Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall 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 Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, 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, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, 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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20. 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

21. 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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22. 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

23. 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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24. 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

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

Author

Zhang, Yuling, Ren, Hongwei, Liu, Yize, Li, Meiyu, Rasheed, Adnan Hameed, Alias, Hajar, and Duan, Erhong

Subjects
EUTECTICS, QUANTUM chemistry, SOLVENTS, MACHINE learning
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. This review summarizes the current researches involved QC calculations combined experiments, on investigating the microstructure-interactions-physicochemical properties relationship and dissolving behaviour in DESs from the macroscopic and microcosmic perspective. On top of that, the prediction of properties and dissolving ability of DESs through COSMO-RS and Machine Learning Methods are discussed, which have not been thoroughly and intensively researched, but show great potential. Finally, a brief analysis of perspectives and challenges for the future research in this field is presented. [ABSTRACT FROM AUTHOR]

Published
2022
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27. 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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29. INTERVENTIONAL CARDIOLOGIST POINT OF CARE TREATMENT DECISION VERSUS VIRTUAL HEART TEAM RETROSPECTIVE EVALUATION OF MULTIVESSEL CORONARY ARTERY DISEASE: DIFFERENCES OF OPINION

Author

Amiram Gafni, Sumeet Gandhi, Bobby Yanagawa, Kostas Ioannou, Matthew Mercuri, Andre Lamy, Ryan McGreal, Amin Mulji, Jon-David Schwalm, Nandini Gupta, Madhu K. Natarajan, Daniel Pericak, Adel Dyub, Matthew Sibbald, Michael Tsang, and Adnan Hameed

Subjects
Coronary artery disease, medicine.medical_specialty, business.industry, Emergency medicine, Heart team, medicine, Treatment decision making, Cardiology and Cardiovascular Medicine, medicine.disease, business, Point of care
Published
2019
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31. THE EFFECT OF SOIL ACIDIFICATION IN THE AVAILABILITY OF PHOSPHOR ON GROWTH OF CUCUMBER CUCUMIS SATIVUS L. CROP.

Author

AL-Aloosy, Yousif Ahmad Mahmood, AL-Tameemi, Ali Jasim Hadi, and Salman, Adnan Hameed

Subjects
SOIL acidification, SULFURIC acid, PHOSPHORS, AGRICULTURAL productivity, PLANT growth, CUCUMBER growing
Abstract

A field experiment was carried out during the spring season 2016 in a greenhouse affiliated to the Directorate for Plant Protection - Ministry of Agriculture. The objective was to study the effect of phosphor levels and the concentration of sulfuric acid on some of the features of growth of Cucumis sativus L. The experiment was arranged according to the Randomized Complete Block Design (RCBD) in factorial experiment that included four levels of phosphor (0, 25, 50 and 75) kg Pha-1 and three concentrations of sulfuric acid with irrigation water (0, 0.025 N and 0.05 N) symbolized with three replicates. The results showed the superiority of the level of 75 kg P ha-1 and gave the highest values of the available phosphor, nitrogen and potassium in soil 19.54 mg kg -1 and 46 mg kg-1 and 247.2 mg kg-1 respectively. The addition of features of the dry weight for the shoot system is 480.4 gm.plant-1 and the dry weight of the root system is 24.93 gm. plant-1 and the concentration of phosphor in plant is 0.40% and the yield of one plant is 4.88 kg. plant-1 . Also, concentration 0.05N of sulphuric acid is excelled in the concentration of phosphor 18.22 mg kg -1, nitrogen 45.4 mg kg-1 potassium 255.2 mg kg-1 available in the soil and the dry weight of the shoot system 486.4 gm. plant-1 and the dry weight root system 21.0 gm. plant-1 and concentration of phosphor in plant 0.39% and the yield of one plant 4.478 kg plant-1. The interaction treatment has superseded in treatment 75 kg plant-1 + concentration 0.05 N, which gave the highest value 23.20 mg kg-1, 50 mg kg-1 and 265.0 mg kg-1 and 582.3 gm. plant-1 and 26.74 gm. plant-1 and 0.48% and 5.64 kg plant-1 for the phosphor, nitrogen and potassium in plant, dry weight of the root system and shoot system and concentration of phosphor and one plant yield respectively . [ABSTRACT FROM AUTHOR]

Published
2018

33. Comparative genome analysis reveals high-level drug resistance markers in a clinical isolate of Mycobacterium fortuitum subsp. fortuitum MF GZ001

Author

Md Shah Alam, Ping Guan, Yuting Zhu, Sanshan Zeng, Xiange Fang, Shuai Wang, Buhari Yusuf, Jingran Zhang, Xirong Tian, Cuiting Fang, Yamin Gao, Mst Sumaia Khatun, Zhiyong Liu, H. M. Adnan Hameed, Yaoju Tan, Jinxing Hu, Jianxiong Liu, and Tianyu Zhang

Subjects
Mycobacterium fortuitum, morphology, comparative genomic analysis, drug resistance, pathogenesis, Microbiology, QR1-502
Abstract

IntroductionInfections caused by non-tuberculosis mycobacteria are significantly worsening across the globe. M. fortuitum complex is a rapidly growing pathogenic species that is of clinical relevance to both humans and animals. This pathogen has the potential to create adverse effects on human healthcare.MethodsThe MF GZ001 clinical strain was collected from the sputum of a 45-year-old male patient with a pulmonary infection. The morphological studies, comparative genomic analysis, and drug resistance profiles along with variants detection were performed in this study. In addition, comparative analysis of virulence genes led us to understand the pathogenicity of this organism.ResultsBacterial growth kinetics and morphology confirmed that MF GZ001 is a rapidly growing species with a rough morphotype. The MF GZ001 contains 6413573 bp genome size with 66.18 % high G+C content. MF GZ001 possesses a larger genome than other related mycobacteria and included 6156 protein-coding genes. Molecular phylogenetic tree, collinearity, and comparative genomic analysis suggested that MF GZ001 is a novel member of the M. fortuitum complex. We carried out the drug resistance profile analysis and found single nucleotide polymorphism (SNP) mutations in key drug resistance genes such as rpoB, katG, AAC(2')-Ib, gyrA, gyrB, embB, pncA, blaF, thyA, embC, embR, and iniA. In addition, the MF GZ001strain contains mutations in iniA, iniC, pncA, and ribD which conferred resistance to isoniazid, ethambutol, pyrazinamide, and para-aminosalicylic acid respectively, which are not frequently observed in rapidly growing mycobacteria. A wide variety of predicted putative potential virulence genes were found in MF GZ001, most of which are shared with well-recognized mycobacterial species with high pathogenic profiles such as M. tuberculosis and M. abscessus.DiscussionOur identified novel features of a pathogenic member of the M. fortuitum complex will provide the foundation for further investigation of mycobacterial pathogenicity and effective treatment.

Published
2023
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34. 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
Mycobacterium abscessus, intrinsic resistance, MAB_0189c, permeability, Microbiology, QR1-502
Abstract

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 MAB_0189c encoding a putative arabinosyltransferase C was found to be disrupted, using a newly developed highly-efficient strategy combining next-generation sequencing and multiple PCR. Furthermore, selectable marker-free deletion of MAB_0189c recapitulated the hypersensitive phenotype. Disruption of MAB_0189c resulted in an inability to synthesize lipoarabinomannan and markedly enhanced its cell envelope permeability. Complementing MAB_0189c or M. tuberculosis embC restored the resistance phenotype. Importantly, treatment of M. abscessus with ethambutol, a first-line antituberculosis drug targeting arabinosyltransferases of M. tuberculosis, largely sensitized M. abscessus to multiple antibiotics in vitro. We finally tested activities of six selected drugs using a murine model of sustained M. abscessus infection and found that linezolid, rifabutin, and imipenem were active against the MAB_0189c deletion strain. These results identified MAB_0189 as a crucial determinant of intrinsic resistance of M. abscessus, and optimizing inhibitors targeting MAB_0189 might be a strategy to disarm the intrinsic multiple antibiotic resistance of M. abscessus. IMPORTANCE Mycobacterium abscessus is intrinsically resistant to most antibiotics, and treatment of its infections is highly challenging. The mechanisms of its intrinsic resistance remain not fully understood. Here we found a transposon mutant hypersensitive to a variety of drugs and identified the transposon inserted into the MAB_0189c (orthologous embC coding arabinosyltransferase, EmbC) gene by using a newly developed rapid and efficient approach. We further verified that the MAB_0189c gene played a significant role in its intrinsic resistance by decreasing the cell envelope permeability through affecting the production of lipoarabinomannan in its cell envelope. Lastly, we found the arabinosyltransferases inhibitor, ethambutol, increased activities of nine selected drugs in vitro. Knockout of MAB_0189c made M. abscessus become susceptible to 3 drugs in mice. These findings indicated that potential powerful M. abscessus EmbC inhibitor might be used to reverse the intrinsic resistance of M. abscessus to multiple drugs.

Published
2022
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35. The compound TB47 is highly bactericidal against Mycobacterium ulcerans in a Buruli ulcer mouse model

Author

Yang Liu, Yamin Gao, Jianxiong Liu, Yaoju Tan, Zhiyong Liu, Chiranjibi Chhotaray, Huofeng Jiang, Zhili Lu, Gift Chiwala, Shuai Wang, Gaelle Makafe, Md Mahmudul Islam, H. M. Adnan Hameed, Xingshan Cai, Changwei Wang, Xinjie Li, Shouyong Tan, and Tianyu Zhang

Subjects
Science
Abstract

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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36. Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains

Author

H. M. Adnan Hameed, Md Mahmudul Islam, Chiranjibi Chhotaray, Changwei Wang, Yang Liu, Yaoju Tan, Xinjie Li, Shouyong Tan, Vincent Delorme, Wing W. Yew, Jianxiong Liu, and Tianyu Zhang

Subjects
Mycobacterium tuberculosis, drug resistance, molecular, comorbidities, therapeutic, drug targets, Microbiology, QR1-502
Abstract

Tuberculosis (TB) is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting scenarios of multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and total drug-resistant tuberculosis (TDR-TB), due to number of resistance pathways, alongside some apparently obscure ones. Recent advances in the understanding of the molecular/ genetic basis of drug targets and drug resistance mechanisms have been steadily made. Intriguing findings through whole genome sequencing and other molecular approaches facilitate the further understanding of biology and pathology of M. tuberculosis for the development of new therapeutics to meet the immense challenge of global health.

Published
2018
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