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Alzheimer's disease is a chronic clinical condition that is predominantly seen in age groups above 60 years. The early detection of the disease through image classification aids in effective diagnosis and suitable treatment. The magnetic resonance imaging (MRI) data on Alzheimer's disease have been collected from Kaggle which is a freely available data source. These datasets are divided into training and validation sets. The present study focuses on training MRI datasets using TinyNet architecture that suits small‐scale image classification problems by overcoming the disadvantages of large convolutional neural networks. The architecture is designed such that convergence time is reduced and overall generalization is improved. Though the number of parameters used in this architecture is lesser than the existing networks, still this network can provide better results. Training MRI datasets achieved an accuracy of 98% with the method used with a 2% error rate and 80% for the validation MRI datasets with a 20% error rate. Furthermore, to validate the model‐supporting data collected from Kaggle and other open‐source platforms, a comparative analysis is performed to substantiate TinyNet's applicability and is projected in the discussion section. Transfer learning techniques are employed to infer the differences and to improve the model's efficiency. Furthermore, experiments are included for fine‐tuning attempts at the TinyNet architecture to assess how the nuances in convolutional neural networks have an impact on its performance. [ABSTRACT FROM AUTHOR]

Background: Lactational breast abscesses are a significant complication of mastitis in breastfeeding women. This study aimed to compare the efficacy and patient outcomes of open drainage versus percutaneous negative pressure suction drainage in the treatment of lactational breast abscesses. Methods: A total of 100 lactating women with diagnosed breast abscesses were randomly assigned to either open drainage or percutaneous negative pressure suction drainage. The study evaluated abscess resolution rates, recurrence rates, time to recovery, pain management, breastfeeding continuation, patient satisfaction, and complication rates. Results: Both groups showed high abscess resolution rates by the one-month follow-up. The percutaneous group had a significantly shorter mean recovery time (12.8 vs. 14.2 days, p=0.04) and lower pain scores at one day and one week postprocedure (p<0.001 and p=0.001, respectively). Patient satisfaction regarding procedure discomfort, cosmetic outcomes, and overall satisfaction was significantly higher in the percutaneous group (p<0.001, p=0.005, and p<0.001, respectively). The incidence of scar formation was lower in the percutaneous group (p=0.05). Conclusion: While both open drainage and percutaneous negative pressure suction drainage are effective for the management of lactational breast abscesses, the percutaneous approach offers advantages in recovery time, pain management, patient satisfaction, and cosmetic outcomes. These findings suggest a preference for the minimally invasive percutaneous method in clinical practice. [ABSTRACT FROM AUTHOR]

Background Patients who undergo spine surgery often experience severe pain postoperatively. Multimodal analgesia inclusive of a regional block provides optimal pain relief. Thoracolumbar interfascial plane (TLIP) block may provide promising analgesia in these patients. Materials Fifty consenting adults aged between 18 and 60 years undergoing elective lumbar spinal surgeries under balanced general anesthesia were divided into two equal groups (group T: received bilateral TLIP block, and group C : received conventional opioid analgesia). All the patients were taken care of by an independent anesthesiologist unaware of the study protocol in the postanesthesia care unit. The postoperative pain was assessed by visual analog scale (VAS). Time to first rescue analgesia, total morphine consumption, complications, and patient satisfaction were also recorded. Results Postoperative mean VAS scores till 12 hours were significantly higher in the control group. The mean time to the first analgesic requirement among group T and group C patients was 404.4 ± 25.1 and 150.2 ± 12.4 minutes, respectively (p < 0.001). Morphine consumptions in 24 hours were also significantly higher in group C (3.36 ± 1.04 vs. 7.84 ± 1.43; p < 0.001). Mean intraoperative fentanyl consumption was significantly more in group C (122.4 ± 16.4 µg and 140.4 ± 21.7 µg; p = 0.001). Complications were similar in both groups. However, patient satisfaction was significantly higher in group T (p < 0.001). Conclusion TLIP block provided superior analgesia, decreased opioid consumption, and improved patient satisfaction as compared with patients receiving standard general anesthesia with opioid analgesics. Hence, TLIP block could be a component of multimodal analgesia in patients undergoing lumbar spine surgeries. CTRI No.: CTRI/2021/03/031682 [ABSTRACT FROM AUTHOR]

Background: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. Methods: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). Results: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60–8.94); p = 0.003; univariate analysis] and [3.30 (1.11–9.82); p = 0.03]; multivariate logistic regression]. Conclusions: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses. [ABSTRACT FROM AUTHOR]

Background Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. Methods Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1–2, 3–4, ≥5); (ii) baseline creatinine clearance (<30, 30–50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. Results Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. Conclusions In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities. [ABSTRACT FROM AUTHOR]

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Aim: To assess and compare the efficacy of dexamethasone ointment with triamcinolone acetonide, the gel form, in the treatment of minor recurrent aphthous stomatitis (RAS). Materials and Methods: This was a randomized clinical trial of 60 patients of either sex with clinically diagnosed RAS who were randomly divided into two groups--the dexamethasone ointment group (Group I) and the triamcinolone acetonide gel group (Group II). Patients were asked to apply the gel three times a day on each ulcer. Estimation of the efficacy of gel was done based on the time required for regression in pain, size, and number of ulcers. Results: The results showed there was a significant difference in size, pain, number, and duration of ulcers in Group I and Group II within 7 days. However, in both groups, no significant difference was noted in the treatment of RAS. Conclusion: Dexamethasone ointment was found to be efficient in this treatment and was safe as evaluated using clinical assessments. [ABSTRACT FROM AUTHOR]

In the last three years, COVID-19 has impacted the world with back-to-back waves leading to devastating consequences. SARS-CoV-2, the causative agent of COVID-19, was first detected in 2019 and since then has spread to 228 countries. Even though the primary focus of research groups was diverted to fight against COVID-19, yet no dedicated drug has been developed to combat the emergent life-threatening medical conditions. In this study, 35 phytocompounds and 43 drugs were investigated for comparative docking analysis. Molecular docking and virtual screening were performed against SARS-CoV-2 spike glycoprotein of 13 variants using AutoDock Vina tool 1.5.6 and Discovery Studio, respectively, to identify the most efficient drugs. Selection of the most suitable compounds with the best binding affinity was done after screening for toxicity, ADME (absorption, distribution, metabolism and excretion) properties and drug-likeliness. The potential candidates were discovered to be Liquiritin (binding affinities ranging between −7.0 and −8.1 kcal/mol for the 13 variants) and Apigenin (binding affinities ranging between −6.8 and −7.3 kcal/mol for the 13 variants) based on their toxicity and consistent binding affinity with the Spike protein of all variants. The stability of the protein–ligand complex was determined using Molecular dynamics (MD) simulation of Apigenin with the Delta plus variant of SARS-CoV-2. Furthermore, Liquiritin and Apigenin were also found to be less toxic than the presently used drugs and showed promising results based on in silico studies, though, confirmation using in vitro studies is required. This in-depth comparative investigation suggests potential drug candidates to fight against SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal form of interstitial lung disease (ILD) characterized by the absence of a known cause and usual interstitial pneumonitis (UIP) pattern on chest CT imaging and/or histopathology. Distinguishing UIP/IPF from other ILD subtypes is essential given different treatments and prognosis. Lung biopsy is necessary when noninvasive data are insufficient to render a confident diagnosis.Research Question: Can we improve noninvasive diagnosis of UIP be improved by predicting ILD histopathology from CT scans by using deep learning?Study Design and Methods: This study retrospectively identified a cohort of 1,239 patients in a multicenter database with pathologically proven ILD who had chest CT imaging. Each case was assigned a label based on histopathologic diagnosis (UIP or non-UIP). A custom deep learning model was trained to predict class labels from CT images (training set, n = 894) and was evaluated on a 198-patient test set. Separately, two subspecialty-trained radiologists manually labeled each CT scan in the test set according to the 2018 American Thoracic Society IPF guidelines. The performance of the model in predicting histopathologic class was compared against radiologists' performance by using area under the receiver-operating characteristic curve as the primary metric. Deep learning model reproducibility was compared against intra-rater and inter-rater radiologist reproducibility.Results: For the entire cohort, mean patient age was 62 ± 12 years, and 605 patients were female (49%). Deep learning performance was superior to visual analysis in predicting histopathologic diagnosis (area under the receiver-operating characteristic curve, 0.87 vs 0.80, respectively; P < .05). Deep learning model reproducibility was significantly greater than radiologist inter-rater and intra-rater reproducibility (95% CI for difference in Krippendorff's alpha did not include zero).Interpretation: Deep learning may be superior to visual assessment in predicting UIP/IPF histopathology from CT imaging and may serve as an alternative to invasive lung biopsy. [ABSTRACT FROM AUTHOR]

Background and Aim: Proteus bacteria, a key contributor to several gastrointestinal diseases, is known to survive in the wide pH range offered by different locations of the GI tract. The bacterial enzyme Choline TMA Lyase found in several opportunistic gut commensals catalyzes choline conversion to trimethylamine, a precursor of the pro-atherosclerotic metabolite trimethylamine N oxide. This study evaluates the pathogenic potential of Proteus gut bacteria in patients with coronary artery disease. We also sought to create a simple predictive model for assessing risk factors of coronary artery disease using a sample of Indian patients. Materials and Methods: The study included 14 patients with coronary artery disease and 6 controls. Optimal conditions were devised, and standardized protocols were followed to culture Proteus bacteria in vitro and isolate the protein of interest, Choline TMA Lyase. FTIR analysis and UV spectrophotometry were employed to quantify choline and trimethylamine N oxide levels, respectively. Finally, receiver operating characteristic analysis and multivariate logistic regression established the predictive power of the entire model and trimethylamine N oxide. Results: The findings demonstrated an optimum activity of this protein and the bacterial growth in the pH range of 7.4 - 9. Quantitative analysis showed trimethylamine N oxide levels to be significantly higher in coronary artery disease patients (1.81 μM) than in controls (0.86 μM). Conclusion: Optimum activity in the alkaline condition indicates the strong pathological potential of Proteus bacteria in the progression of coronary artery disease. The prediction model can serve as a helpful tool within the medical community to assess the risk factors for coronary artery disease. [ABSTRACT FROM AUTHOR]

Our present study evaluates the performance of wound dressing material fabricated by incorporating silver(Ag) and titanium dioxide(TiO2) nanoparticles(NPs) in xylan/chitosan-based conjugate matrix. The porous nanocomposites were examined for antimicrobial, cell attachment, swelling, protein adsorption, and cytotoxic studies. Nanocomposites exhibited potent antimicrobial response against both gram-negative and gram-positive strains of bacteria. Despite remarkable cellular response, a concentration-dependent cytotoxicity was observed in matrix with high Ag NPs content. Nanoparticles incorporated composites also tuned the pore size, swelling ratio, and protein adsorption tendency of scaffold making them feasible as wound dressing material. [ABSTRACT FROM AUTHOR]

Background:Political cartoons have become a significant part of all newspapers. There is a clear distinction between the requirements, perception, and understanding of political cartoons amongst the younger and older generation. Thus, it is important to understand this difference in perception so that such content can be created which spikes the interest of both generations. Objectives: The present research is based on assessing the difference in perception of the younger and older generation on Indian political cartoons in everyday editorials. Methods:Quantitative analysis has been conducted using a structured quantitative questionnaire. For analysing the data, SPSS 23.0 has been used as the statistical software. For descriptive analysis, frequency analysis has been conducted. Further, pie charts have been used to describe the data. For inferential analysis, an independent sample t-test has been used. Results:The analysis of the data stated that a significant difference exists in the perception of the younger and older generation on political cartoons in everyday editorials. Conclusions: Thechange in perception of the younger generation should be admitted by the editorials. The present research can be used as a basis by the daily editorials and steps should be taken to draw the attention of the newer generation towards political cartoons. [ABSTRACT FROM AUTHOR]

AIM: The aim of the study is to compare the effectiveness of electrical stimulation, myofascial release (MFR), and conventional physiotherapy over acupuncture points (GB21, SI14) on the upper trapezius in female basketball players. METHODOLOGY: The study included 30 patients with unilateral myofascial trigger points (MTrPs) present on acupuncture points GB2l (midway between shoulder and vertebral column) and SI14 (3 cm lateral to lower border of spinous process of first thoracic vertebra) on the upper trapezius, between the age group of 18 and 30 years. The patients were allotted alternatively to Group A, Group B, and Group C, respectively. Preparticipation evaluation was done. Group A received electrical stimulation with exercise, Group B received MFR with exercise, and Group C received cold pack with exercise. Posttreatment evaluation is conducted on the 7th day of treatment. RESULTS: The results showed that Group B has significant decrease in pain and increase in lateral bending of the cervical spine to the opposite side at posttest values as compared to Group A and Group C. CONCLUSION: All three groups have got beneficial effects in reducing pain intensity and increasing lateral bending of the cervical spine to the opposite side. Group B shows more significant effect in decrease in pain and increase in lateral bending of the cervical spine to the opposite side in female basketball players with MTrP over acupoints GB21, SI14 on the upper trapezius. [ABSTRACT FROM AUTHOR]

Background: In India and other low- and middle-income countries, multiple family and community members are influential in caregivers' perceptions of vaccination. Existing literature indicates the primary caregiver, typically the mother, is instrumental in vaccine decision-making, but this may vary in contexts. We investigated the role of stakeholders in India who influence caregivers' vaccination perceptions, as this is essential to developing strategies to promote vaccine acceptance and improve uptake.Methods: This research was conducted in 2019 in Mewat District in Haryana, an area in India with extremely low vaccination coverage. We conducted six focus group discussions with 60 participants in the following categories: fathers of children under-5 years old, expectant mothers, mothers-in-law, community health workers, and community influencers such as locally elected officials and religious leaders.Results: Our results highlighted four themes that influence vaccine uptake. First, while caregivers associated vaccination with reductions in specific diseases, they also noted that vaccination services brought broad health gains, including improved nutrition, antenatal guidance, and social support. Second, community health workers critically influenced, positively or negatively, caregivers' vaccination perceptions. Third, community health workers faced gaps in their education such as limited training on vaccine side-effects, placing them at a disadvantage when dealing with families. Finally, we found that mothers-in-law, fathers, and religious leaders influence caregivers' perceptions of vaccination.Conclusions: Communication of broader benefits of vaccines and vaccination services by community health workers could be impactful in increasing vaccine acceptance. Vaccine uptake could potentially be improved by facilitating community health workers' ownership over vaccine acceptance and uptake by involving them in the design and implementation of interventions to target mothers and mothers-in-law. A 'bottom-up' approach, leveraging community health workers' knowledge to design interventions, and giving a voice to key members of the household and society beyond mothers alone, may sustain health improvement in low vaccine coverage areas. [ABSTRACT FROM AUTHOR]

The risk of diabetes is higher in South Asians compared to the general population. As a result of migration during the twentieth-century postindependence, the South Asian diaspora is incredibly vast. We examined the diabetes prevalence between groups of the South Asian diaspora based on their distinct migration patterns. Population-based health care and immigration administrative data were used to compare crude and standardized diabetes prevalence between immigrants from nine regions of the South Asian diaspora and the non-immigrant population. Diabetes prevalence across groups were also stratified by gender. There were 199,003 South Asian immigrants; 33,882 (crude prevalence of 17.0%) of whom had a diagnosis of diabetes. The nine subgroups varied significantly in the prevalence of diabetes after adjusting for age, sex and income: Sri Lanka 24.3%, Pakistan 22.2%, Fiji 21.5%, Bangladesh 20.7%, the Caribbean 20.4%, India 16.0%, East Africa 13.8%, South Africa 10.8%, and the Middle East 9.6% in comparison to the non-immigrant population 17.8%. Higher prevalence was evident among men compared with women in each subgroup with the exception of Pakistan. Diabetes prevalence is not uniform among South Asians. Our findings highlight potential impacts of their unique migration histories on the risk and burden of diabetes, and move beyond a one size fits all approach in the South Asian population of Ontario to develop targeted interventions. [ABSTRACT FROM AUTHOR]

Background: miRNAs are promising biomarkers in oncology as their small size makes them less susceptible to degradation than mRNA in FFPE tissue. We aimed to derive a hypoxia-associated miRNA signature for bladder cancer.Methods: Taqman miRNA array cards identified miRNA seed genes induced under hypoxia in bladder cancer cell lines. A signature was derived using feature selection methods in a TCGA BLCA training data set. miRNA expression data were generated for 190 tumours from the BCON Phase 3 trial and used for independent validation.Results: A 14-miRNA hypoxia signature was derived, which was prognostic for poorer overall survival in the TCGA BLCA cohort (n = 403, p = 0.001). Univariable analysis showed that the miRNA signature predicted an overall survival benefit from having carbogen-nicotinamide with radiotherapy (HR = 0.30, 95% CI 0.094-0.95, p = 0.030) and performed similarly to a 24-gene mRNA signature (HR = 0.47, 95% CI 0.24-0.92, p = 0.025). Combining the signatures improved performance (HR = 0.26, 95% CI 0.08-0.82, p = 0.014) with borderline significance for an interaction test (p = 0.065). The interaction test was significant for local relapse-free survival LRFS (p = 0.033).Conclusion: A 14-miRNA hypoxia signature can be used with an mRNA hypoxia signature to identify bladder cancer patients benefitting most from having carbogen and nicotinamide with radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Axillary dissection is one of the important components of modified radical mastectomy (MRM). The present study was conducted to compare surgical outcomes by using monopolar electrocautery and ultrasonic dissector for axillary dissection in MRM. Methods: A parallel randomised controlled single blinded study was conducted with a sample size of 70 patients who were randomised into two groups. One group underwent MRM using ultrasonic dissector (Group A) and the other one using electrocautery (Group B). Intra- and post-operative outcomes were compared. Results: Group A had an average operating time of 30.86 min, which was statistically less than that of Group B. The mean mop count and the daily drain output in Group A were less as compared to Group B and the differences were statistically significant. Drain was removed early in Group A as compared to Group B. However, post-operative pain scores and seroma formation were not statistically significant among the two groups. Conclusion: Ultrasonic dissector group had significantly lesser intra-operative bleeding, operating time and post-operative drain output when compared to electrocautery group. However, the two groups had no significant difference in post-operative pain scores and seroma formation. [ABSTRACT FROM AUTHOR]

Objectives: Coronary artery disease (CAD), also known as ischemic heart disease or atherosclerotic cardiovascular disease (CVD), is one of the major causes of morbidity and mortality globally and has contributed to about 80% of sudden deaths. There have been advancements in the diagnosis and treatment of CAD, some of which are still going on to improve patient care, however, there is a dearth of information regarding the various challenges the patients go through after being diagnosed with CAD and so a qualitative study was conducted on cardiac patients in Mauritius to shine a light on the various aspects of life affected by CAD. This is the first qualitative study conducted on cardiac patients in Mauritius. Material and Methods: A phenomenological qualitative study was performed on 12 patients who were diagnosed with CAD, at the Cardiac Unit of Victoria Hospital, Mauritius. By the use of NVivo 12 (Windows) Plus software, after it was transcribed, codes/nodes and themes were generated. Results: Twenty-five different codes were inferred from the study done and from the respective codes, eight main themes were established. The main themes drawn from the study were as follows: Emotional factors, risk factors, optimistic factors, support, awareness of your health, consequences, lifestyle modifications, and the healthcare system. Conclusion: An event of CAD is an experience with multifaceted influences on innumerable aspects of the patient’s life. The study illuminated the immense sufferings and emotional bearings of those patients who were living with heart disease. They expressed their overbearing, insecurities, and a loss of control over various aspects of their lives. This study provided various thought-provoking themes that emerged after transcribing the qualitative interviews. It also highlighted the various challenges faced by patients and how the beliefs of patients with CAD were vital to sustaining them. Family support is a vital aspect in keeping the patient both motivated to follow their treatment and emotionally grounded [ABSTRACT FROM AUTHOR]

Background: The Government of Bihar (GoB) in India, the Bill and Melinda Gates Foundation and several non-governmental organisations launched the Ananya program aimed to support the GoB to improve reproductive, maternal, newborn and child health and nutrition (RMNCHN) statewide. Here we summarise changes in indicators attained during the initial two-year pilot phase (2012-2013) of implementation in eight focus districts of approximately 28 million population, aimed to inform subsequent scale-up.Methods: The quasi-experimental impact evaluation included statewide household surveys at two time points during the pilot phase: January-April 2012 ("baseline") including an initial cohort of beneficiaries and January-April 2014 ("midline") with a new cohort. The two arms were: 1) eight intervention districts, and 2) a comparison arm comprised of the remaining 30 districts in Bihar where Ananya interventions were not implemented. We analysed changes in indicators across the RMNCHN continuum of care from baseline to midline in intervention and comparison districts using a difference-in-difference analysis.Results: Indicators in the two arms were similar at baseline. Overall, 40% of indicators (20 of 51) changed significantly from baseline to midline in the comparison districts unrelated to Ananya; two-thirds (n = 13) of secular indicator changes were in a direction expected to promote health. Statistically significant impact attributable to the Ananya program was found for 10% (five of 51) of RMNCHN indicators. Positive impacts were most prominent for mother's behaviours in contraceptive utilisation.Conclusions: The Ananya program had limited impact in improving health-related outcomes during the first two-year period covered by this evaluation. The program's theories of change and action were not powered to observe statistically significant differences in RMNCHN indicators within two years, but rather aimed to help inform program improvements and scale-up. Evaluation of large-scale programs such as Ananya using theory-informed, equity-sensitive (including gender), mixed-methods approaches can help elucidate causality and better explain pathways through which supply- and demand-side interventions contribute to changes in behaviour among the actors involved in the production of population-level health outcomes. Evidence from Bihar indicates that deep structural constraints in health system organisation and delivery of interventions pose substantial limitations on behaviour change among health care providers and beneficiaries.Study Registration: ClinicalTrials.gov number NCT02726230. [ABSTRACT FROM AUTHOR]

Estrogen receptor 1 (ESR1, which encodes estrogen receptor-alpha) is a key driver gene for the initiation and progression of hormone receptor-positive breast cancer. Estrogen receptor-alpha (ER) is expressed in up to 70% of cases, and patients are routinely treated with endocrine therapies. However, the development of resistance over time is common and occurs in one-third of ER-positive breast tumors, leading to disease progression and death. X-box binding protein 1 (XBP1), a key component of the unfolded protein response (UPR) and ER signaling pathway, generates a positive feedback regulatory loop that leads to increased expression of XBP1 and ER in luminal breast cancer. In this review, we highlight new insights into the mechanisms of crosstalk between XBP1 and ER signaling and its clinical implications. Next, we describe the key signaling nodes that play an important role in XBP1-mediated endocrine resistance in breast cancer. Further, we discuss XBP1 gene mutations in breast cancer and the role of these mutations in the emergence of endocrine resistance and response to treatment. Finally, we discuss the current state and future directions for targeting XBP1 in combination with standard endocrine therapy to improve clinical outcomes in endocrine-resistant breast cancer patients. [ABSTRACT FROM AUTHOR]

This article serves as an epilogue to the special issue curated by Claire Bénit-Gbaffou and Sarah Charlton with a focus on state power and the concept of informality. In my reflection, I examine the specificity of statecraft in the context of postcolonial government. In particular, I analyse political potency as a relationship between the state and subaltern subjects. Also at stake in this paper is the question of comparative and transnational analysis. In what ways can concepts generated through the study of processes of urban informality in India speak to the production of illegality and the reproduction of rule in South Africa? [ABSTRACT FROM AUTHOR]

This study makes an inter comparison of ocean state of the Tropical Indian Ocean (TIO) in different ocean reanalyses such as global ocean data assimilation system (GODAS), ensemble coupled data assimilation (ECDA), ocean reanalysis system 4 (ORAS4) and simple ocean data assimilation (SODA) with reference to the in-situ buoy observations, satellite observed sea surface temperature (SST), EN4 analysis and ocean surface current analysis real time (OSCAR). Analysis of mean state of SST and sea surface salinity (SSS) reveals that ORAS4 is better comparable with satellite observations as well as EN4 analysis, and is followed by SODA, ECDA and GODAS. The surface circulation in ORAS4 is closer to OSCAR compared to the other reanalyses. However mixed layer depth (MLD) is better simulated by SODA, followed by ECDA, ORAS4 and GODAS. Seasonal evolution of error indicates that the highest deviation in SST and MLD over the TIO exists during spring and summer in GODAS. Statistical analysis with concurrent data of EN4 for the period of 1980-2010 supports that the difference and standard deviation (variability strength) ratio for SSS and MLD is mostly greater than one. In general the strength of variability is overestimated by all the reanalyses. Further comparison with in-situ buoy observations supports that MLD errors over the equatorial Indian Ocean (EIO) and the Bay of Bengal are higher than with EN4 analysis. Overall ORAS4 displays higher correlation and lower error among all reanalyses with respect to both EN4 analysis and buoy observations. Major issues in the reanalyses are the underestimation of upper ocean stability in the TIO, underestimation of surface current in the EIO, overestimation of vertical shear of current and improper variability in different oceanic variables. To improve the skill of reanalyses over the TIO, salinity vertical structure and upper ocean circulation need to be better represented in reanalyses. [ABSTRACT FROM AUTHOR]

Background: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial.Methods: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy. Immunohistochemistry for HIF-1α, CAIX and GLUT1 was performed on tissue microarrays and assessed by two scorers (one pathologist). Prognostic analysis of disease-free survival (DFS) used Kaplan-Meier and Cox regression.Results: Biobank and outcome data were available for 203 out of 216 randomised patients. High CAIX expression was associated with worse DFS (hazard ratio 2.28, 95% confidence interval: 1.44-3.59, P<0.001). Hypoxia-inducible factor-1α and GLUT1 were not prognostic. Carbonic anhydrase IX remained prognostic in multivariable analysis.Conclusions: The VorteX-Biobank contains tissue with linked outcome data and is an important resource for research. This study confirms hypoxia is linked to poor prognosis in STS and suggests that CAIX may be the best known marker. However, overlap between single marker positivity was poor and future work will develop an STS hypoxia gene signature to account for tumour heterogeneity. [ABSTRACT FROM AUTHOR]

This study compares procedural complications and clinical outcomes between subintimal crossing versus intraluminal crossing during endovascular treatment of infrainguinal peripheral artery chronic total occlusions (CTO). We identified 1335 CTO interventions in 1001 patients from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry from January 2005 to October 2015. Outcomes included 30-day and 12-month all-cause death, non-fatal myocardial infarction or stroke, peripheral artery stent, or vessel, thrombosis (ST), need for any target limb endovascular or surgical revascularization, target limb major amputation and procedural complications. A subintimal crossing technique was necessary in 388 lesions (27% overall in 1335 lesions; 34% (n=351) in 1023 femoropopliteal lesions, and 12% (n=37) in 312 infrapopliteal lesions, p<0.01) with a lower procedural (p<0.01) and technical (p<0.01) success than the intraluminal in both femoropopliteal and infrapopliteal interventions. There were no significant differences in procedural complications, major adverse cardiac events, or clinically driven target limb revascularization at 1 year between the two groups, except a higher residual dissection rate in the subintimal crossing group than the intraluminal group in femoropopliteal target vessels (p = 0.04). [ABSTRACT FROM AUTHOR]

Background: Postmortem examination is indispensable to ascertain the cause of an unnatural death and as such is mandatory by the law. From ages, traditional autopsy (TA) has proved its worth in establishing the cause of death in the deceased despite some inherent difficulties and challenges and has enjoyed an insurmountable status. The increasing use of application of the modern-day radiology for postmortem examination has however opened a new arena overcoming some of the difficulties of the TA. There are conflicting reports in the published literature regarding superiority of one modality of the postmortem over the other. Objective: The objective of this study was to compare the findings of postmortem computed tomography (CT) scan and TA in the victims of traumatic deaths and to analyze whether postmortem CT can be used to replace TA. Materials and Methods: All patients with a history of trauma that were declared brought dead on arrival in the emergency department were subjected to full-body CT scan. An experienced radiologist reported the findings of CT scan. Subsequently, a forensic expert subjected the patients to TA. The physician who performed autopsy was blinded to the findings of CT scan and vice versa. An individual who was not part of the radiology or forensic team then entered the findings of CT scan and autopsy in a predesigned Pro forma. An unbiased assessor finally compared the findings of the two modalities and analyzed the results. McNemar's test was used to ascertain the level of significance between the findings reported by these two modalities considering P = 0.05 as statistically significant. The agreement or disagreement on cause of death reported by these two modalities was also assessed. Results: About 95% of the deceased were males. The mean age of the corpses was 35 years (range 16–67 years). CT was found superior in picking up most of the bony injuries, air-containing lesions, hemothorax, and hemoperitoneum. However, autopsy was found more sensitive for soft-tissue and solid visceral injuries. Both modalities were equally helpful in identifying extremity fractures. Statistically significant agreement (>95%) on cause of death by both modalities was not achieved in any patient of trauma. Conclusion: Postmortem CT scan is promising in reporting injuries in traumatic deaths and can significantly complement the conventional autopsy. However, at present, it cannot be considered as a replacement for TA. [ABSTRACT FROM AUTHOR]

Background: Lipid peroxidation is a major consequence of oxidative stress and can be evaluated via malondialdehyde (MDA) levels. The present study aims to assess MDA levels in the saliva of patients with chronic periodontitis (CP) and acute coronary syndrome (ACS) and establish their correlation with periodontal clinical parameters, serum high-sensitivity C-reactive protein (hsCRP), and plasma fibrinogen.Methods: The study enrolled 64 patients stratified into four age- and sex-matched groups: both ACS and CP, ACS only, CP only, and healthy controls. All patients were examined, periodontal clinical parameters were recorded, and saliva and blood samples were collected. Salivary MDA levels were measured using a spectrophotometric assay. A quantitative turbidimetric test was used for the measurement of serum hsCRP levels, and plasma fibrinogen levels were determined using an automated analyzer.Results: Salivary MDA levels were significantly higher in patients with both ACS and CP than in those with only ACS or only CP and healthy controls (P <0.05). There were significant positive correlations between salivary MDA levels and periodontal clinical parameters as well as biomarkers for cardiovascular events (P <0.001).Conclusions: To our knowledge, this study is the first to investigate salivary MDA levels in patients with ACS and their correlations with serum hsCRP and plasma fibrinogen levels. The results indicate that salivary MDA levels could be a biomarker for cardiovascular and/or periodontal disease. [ABSTRACT FROM AUTHOR]

Microwave absorbers have emerged as an indispensable industrial apparatus in today's world, owing to their multitude of uses, both civil as well as military. This paper focuses on the use of three evolutionary algorithms, namely, particle swarm optimization, bat algorithm and cuckoo search algorithm for the purpose of obtaining optimal designs of seven layer microwave absorbers over a wide frequency range, and both cases of normal and oblique incidence. The resultant optimal designs are compared in terms of maximum reflection coefficient and total thickness with those presented in existing literature. [ABSTRACT FROM AUTHOR]

Highlights: [•] Br− can stabilize the zwitterionic form of arginine in an isolated cluster. [•] Zwitterionic and canonical minima are very close in energy for Br−·Arg. [•] The canonical tautomer is lower in energy for the Cl−·Arg cluster. [•] Conformation is crucial in determining canonical vs zwitterion relative energies. [•] Comparison to experiment suggests that messenger tagged IR experiments are vital. [ABSTRACT FROM AUTHOR]

The main objective of this work is the accurate measurement of uranium in the potable water sources of Muktsar district of Punjab, India. In the present work, a laser fluorimetry technique was used for the analysis of uranium. Inductively coupled plasma mass spectrometry (ICPMS) technique was also applied to verify and compare the uranium content analyzed using laser technique. About 16 samples from waterworks, bore wells, and hand pumps that supply the drinking water to local population were collected for this purpose. An indigenous laser fluorimeter supplied by RRCAT, Indore was employed for the analysis. Uranium concentrations obtained were in the range from 0 to 10 μg L in ten samples, 11-30 μg L in three samples, and more than 100 μg L in three samples namely Channu ground water, Warning Khera pump, and Killanwale village hand pump. The USEPA guideline value for uranium in safe drinking water is 30 μg L. Also, a data comparison with similar studies carried out in other countries is presented. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness and safety of cefpodoxime and ciprofloxacin for the treatment of mild to moderate cases of acute exacerbation of chronic suppurative otitis media (AECSOM). Materials and Methods: Adult patients diagnosed with AECSOM were screened and patients fulfilling the inclusion criteria were randomized to receive either cefpodoxime 200 mg twice daily or ciprofloxacin 500 mg twice daily orally for 7 days. The primary outcome of this randomized, open-labeled, phase IV clinical trial (Registration Number - CTRI/2011/10/002079) was clinical success rate at day 14 visit and the secondary outcome was incidence of adverse events (AEs). Forty-six patients were enrolled: 23 in the cefpodoxime group and 23 in the ciprofloxacin group. Results: The clinical success rates were 95.6% in the cefpodoxime group versus 90.9% in the ciprofloxacin group. These rates are comparable, but no statistically significant difference was observed between the groups. Few mild and self-limiting AEs were observed and the tolerability of both the drugs was also good. Conclusion: The results of this randomized, open-labeled phase IV clinical trial showed that a 7-day course of cefpodoxime is therapeutically comparable to ciprofloxacin in terms of both clinical effectiveness and safety for the treatment of patients with AECSOM. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the rate and level of microbial contamination of silver and non-silver (control) barrel contact lens storage cases in vivo.Methods: A prospective, single-centre, randomized, double blinded, crossover study was conducted to evaluate the efficacy of silver and control barrel cases used with an Oxipol™-based disinfecting solution over a two-month period. Lens cases were collected, and the frequency, type and level of microbial contamination evaluated using viable culture and standard identification methods. Questionnaires were used to assess the contact lens-related hygiene compliance of the participants.Results: Forty eight daily contact lens wearers completed the study. Overall, 27 % of silver and 35 % control lens cases (P > 0.05) were contaminated, predominantly with Gram-positive bacteria. Only, 12 % of participants had good compliance, with 46 % having average compliance and 43 % poor compliance. Compliance score was not associated with level of microbial contamination. However, the use of hydrogel lenses in combination with silver cases compared to non-silver barrel cases resulted significantly greater numbers of bacteria colonising cases.Conclusion: The present investigation demonstrated that the use of silver barrel cases does not reduce the overall rate and level of bacterial contamination, but that using hydrogel lenses in combination with silver cases resulted in higher numbers of bacteria isolated from cases. [ABSTRACT FROM AUTHOR]

Passport is considered as the first line of security in any country from external affairs. It marks out a person citizenship and also plays an important role in economic as well as security advancement of a country. However, these days many terrorist activities are taking place with the help of forged passport by manipulating one's identity due to which it is not only pointing out flaws in one's country security capabilities but also creating antisocial relationships with other countries. In this review security feature of passports of different countries were compared with the security features of Indian passport and examined how strong or weak it is from them. As we know in today's world producing a forged passport is easier than before so study of the security features plays an important role among the forensic document experts. Passports of countries such as Sri Lanka, Maldives and Tanzania were taken and their security features were studied. [ABSTRACT FROM AUTHOR]

Purpose: Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site.Methods and Materials: A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive.Results: Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed.Conclusions: A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Many muscle-invasive bladder cancers are hypoxic, which limits the efficacy of radiation therapy. Hypoxia modification using carbogen and nicotinamide has been tested in a phase 3 trial, Bladder Carbogen Nicotinamide. We present mature follow-up data with biomarker predictions of outcomes.Methods and Materials: Bladder Carbogen Nicotinamide is a prospective, phase 3, multicenter, randomized, 2-arm, nonblinded clinical trial. Participants were randomized to receive radical radiation therapy (RT; control arm) alone or with the addition of carbogen (98% O2; 2% CO2) and nicotinamide (CON). Patients with muscle-invasive or high-grade non-muscle invasive bladder cancer were included. Tumor tissue was collected at entry and was analyzed for tumor necrosis, hypoxia (24-gene signature), and basal and luminal tumor molecular subtypes. Overall survival (OS) and disease-free survival and relationships with biomarker status outcomes are analyzed using multivariable Cox regression and log-rank analysis.Results: We analyzed 333 patients with a median follow-up of 10.3 years. The 10-year OS rates were 30% (95% confidence interval [CI], 0.23-0.39) in RT + CON patients and 24% (95% CI, 0.18-0.33) in the RT-alone patients (hazard ratio [HR], 0.80; 95% CI, 0.61-1.04; P = .08). The greatest benefit from CON was seen in patients with tumor necrosis (n = 79; 5-year OS, 53% vs. 33% in patients without tumor necrosis; HR, 0.59; 95% CI, 0.36-0.99; P = .04). Cases with a high hypoxia gene score (n = 75) had a 5-year OS rate of 51%, compared to 34% for a low score (HR, 0.64; 95% CI, 0.38-1.08; P = .09); those with the basal molecular subtype (n = 70) had a 5-year OS rate of 58%, compared to 38% for those with the luminal subtype (HR, 0.58; 95% CI, 0.32-1.06; P = .08).Conclusions: Although the improvement in long-term OS in the whole population is not statistically significant, patients selected by necrosis and high hypoxia gene score benefitted from hypoxia modification. [ABSTRACT FROM AUTHOR]

Early events in an experimental model of mesothelioma development include increased levels of editing in double-stranded RNA (dsRNA). We hypothesised that expression of endogenous retroviruses (ERV) contributes to dsRNA formation and type-I interferon signaling. ERV and interferon stimulated genes (ISGs) expression were significantly higher in tumor compared to non-tumor samples. 12 tumor specific ERV ("MesoERV1-12") were identified and verified by qPCR in mouse tissues. "MesoERV1-12" expression was lower in mouse embryonic fibroblasts (MEF) compared to mesothelioma cells. "MesoERV1-12" levels were significantly increased by demethylating agent 5-Aza-2'-deoxycytidine treatment and were accompanied by increased levels of dsRNA and ISGs. Basal ISGs expression was higher in mesothelioma cells compared to MEF and was significantly decreased by JAK inhibitor Ruxolitinib, by blocking Ifnar1 and by silencing Mavs. "MesoERV7" promoter was demethylated in asbestos-exposed compared to sham mice tissue as well as in mesothelioma cells and MEF upon 5-Aza-CdR treatment. These observations uncover novel aspects of asbestos-induced mesothelioma whereby ERV expression increases due to promoter demethylation and is paralleled by increased levels of dsRNA and activation of type-I IFN signaling. These features are important for early diagnosis and therapy. [ABSTRACT FROM AUTHOR]

Levodopa-induced dyskinesia (LID) poses a significant health care challenge for Parkinson's disease (PD) patients. Amantadine is currently the only drug proven to alleviate LID. Although its efficacy in treating LID is widely assumed to be mediated by blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, our experiments demonstrate that at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ channel type 2 (Kir2) channels in striatal spiny projection neurons (SPNs) - not NMDA receptors. In so doing, amantadine enhances dendritic integration of excitatory synaptic potentials in SPNs and enhances - not antagonizes - the induction of long-term potentiation (LTP) at excitatory, axospinous synapses. Taken together, our studies suggest that the alleviation of LID in PD patients is mediated by diminishing the disparity in the excitability of direct- and indirect-pathway SPNs in the on state, rather than by disrupting LTP induction. This insight points to a pharmacological approach that could be used to effectively ameliorate LID and improve the quality of life for PD patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effectiveness of palliative pelvic radiation therapy (PRT) in patients with bladder cancer and identify factors associated with treatment outcome.Methods and Materials: Patients with bladder cancer receiving PRT were identified retrospectively from 2 cancer centers between 2014 and 2017. Patients were stratified by age, stage, performance status, comorbidities, previous chemotherapy, previous radiation therapy, and radiation therapy protocol. Patients were followed up at 6 weeks after radiation therapy (RT). Median overall survival (mOS) from the last fraction of RT was calculated. Death within 30 days of RT or noncompletion of treatment were considered as futile treatment.Results: Two hundred forty-one patients were identified as receiving PRT. A variety of RT protocols were used: 8 Gy in 1 fraction (11%), 21 Gy in 3 fractions (15%), 20 Gy in 5 fractions (18%), 36 Gy in 6 fractions (36%), and 27.5 to 30 Gy in 8 to 10 fractions (18%). Thirty-eight percent of patients were of poor performance status (Eastern Cooperative Oncology Group performance status ≥3), and 46.5% had significant comorbidities (Adult Comorbidity Evaluation-27 ≥2). The mOS from the last fraction of RT was 153 days (0-1289 days). The 30-day mortality after radiation therapy was 18% (n = 44), and the rate of incomplete planned radiation therapy treatment was 14% (n = 33). First follow-up information was available in 62% (n = 150) of patients. Median time to this follow-up was 49 days (14-238 days). At first follow-up at about 6 weeks after the last fraction of radiation therapy, symptoms were reported in 150 of 200 (75%) living patients; 80 of 150 (53%) patients reported improvement in symptoms after treatment. There were significant differences in mOS with stage, performance status, and comorbidities.Conclusions: One in 4 patients either did not complete the planned RT course or died within 30 days of treatment. These patients were unlikely to have received maximal benefit from treatment but may have experienced side effects, making treatment futile. Patients with good performance status and earlier stage disease survived longer. Patient selection and comprehensive assessment are crucial in selecting appropriate patients for treatment. [ABSTRACT FROM AUTHOR]

Purpose: Outcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.Methods and Materials: CHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions. Toxicity was assessed using clinician-reported outcome (CRO) and patient-reported outcome questionnaires. Participants were categorized as aged < 75 years or ≥ 75 years. Outcomes were compared by age group.Results: Of 3216 patients, 491 (15%) were aged ≥ 75 years. There was no difference in biochemical or clinical failure rates between the groups aged < 75 years and ≥ 75 years for any of the fractionation schedules. In the group aged ≥ 75 years, biochemical or clinical failure-free rates favored hypofractionation, and at 5 years, they were 84.7% for 74 Gy, 91% for 60 Gy, and 87.7% for 57 Gy. The incidence of CRO (grade 3) acute bowel toxicity was 2% in both age groups. The incidence of grade 3 acute bladder toxicity was 8% in patients aged < 75 years and 7% in those aged ≥ 75 years. The 5-year cumulative incidence of CRO grade ≥ 2 late bowel side effects was similar in both age groups. However, in the group aged ≥ 75 years, there was a suggestion of a higher cumulative incidence of bowel bother (small or greater) with 60 Gy compared with 74 Gy and 57 Gy. Patient-reported bladder bother was slightly higher in the group aged ≥ 75 years than the group aged < 75 years, and there was a suggestion of a lower cumulative incidence of bladder bother with 57 Gy compared with 74 Gy and 60 Gy in patients aged ≥ 75 years, which was not evident in those aged < 75 years.Conclusions: Hypofractionated radiation therapy appears to be well tolerated and effective in men aged ≥ 75 years. The 57-Gy schedule has potential advantages in that it may moderate long-term side effects without compromising treatment efficacy in this group. [ABSTRACT FROM AUTHOR]