A systematic pipeline of protein structure selection for computer-aided drug discovery: A case study on T790M/L858R mutant EGFR structures.

Virtual screening (VS) is a routine method to evaluate chemical libraries for lead identification. Therefore, the selection of appropriate protein structures for VS is an essential prerequisite to identify true actives during docking. But the presence of several crystal structures of the same protein makes it difficult to select one or few structures rationally for screening.

Determinants of initiation, continuation and cessation of smokeless tobacco use among pregnant and lactating women: a qualitative study from low-income communities in urban India.

Smokeless tobacco (SLT) consumption increases the risk of cardiovascular diseases and cancer and leads to adverse reproductive health outcomes among women and newborns. This study examines the factors associated with initiation, continuation and cessation of SLT use among women in the reproductive age so as to formulate and include prevention and cessation interventions from its inception. The study was conducted in urban low-income communities in India.

Identification of Bile Acid-Derived Chemical Chaperone(s) Targeting E46K-Mutated Alpha-Synuclein Protein to Treat Parkinson's Disease: Molecular Modelling, Docking, ADME, and Simulation Studies.

Aggregated α-synuclein (α-syn) present inside small cytoplasmic inclusions in the substantia nigra region marks the major pathological hallmark of Parkinson's disease (PD) and makes it an attractive target for the drug development process. Certain small-molecule chaperones (such as DCA, UDCA, TUDCA) presented the ability to prevent misfolding and aggregation of α-syn as well as to disentangle mature α-syn amyloid fibrils. However, due to toxicity constraints, these small molecules could not be translated into clinical settings.

A pharmacokinetic study to correlate the hypoglycemic effect of phlorizin in rats: Identification of metabolites as inhibitors of sodium/glucose cotransporters.

Phlorizin (PRZ) is a natural product that belongs to a class of dihydrochalcones. The unique pharmacological property of PRZ is to block glucose absorption or reabsorption through specific and competitive inhibitors of the sodium/glucose cotransporters (SGLTs) in the intestine (SGLT1) and kidney (SGLT2). This results in glycosuria by inhibiting renal reabsorption of glucose and can be used as an adjuvant treatment for type 2 diabetes.

How Does Tobacco Use Affect the Cognition of Older Adults? A Propensity Score Matching Analysis Based on a Large-Scale Survey.

Introduction: Tobacco is a well-established risk factor for cancer, but its association with other morbidities needs consideration. The low-income and middle-income countries (LMICs) with unprecedented demographic transformation lack evidence on tobacco use and its impact on cognitive health.

Aims And Methods: Using a propensity score matching approach, we utilized data from the Longitudinal Ageing Study of India.

Liquid Biopsies: Emerging role and clinical applications in solid tumours.

Late detection and lack of precision diagnostics are the major challenges in cancer prevention and management. Biomarker discovery in specific cancers, especially at the pre-invasive stage, is vital for early diagnosis, positive treatment response, and good disease prognosis. Traditional diagnostic measures require invasive procedures such as tissue excision using a needle, an endoscope, and/or surgical resection which can be unsafe, expensive, and painful.

Comparison of HPV 16/18 Genotyping and p16/Ki67 Dual Staining for Detection of High-Grade Cervical Lesion in Patients with Low-Grade Cervical Smears.

Objective: To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN).

Methods: In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy.

Transcriptome wide functional analysis of HBx expressing human hepatocytes stimulated with endothelial cell cross-talk.

Identification of genes dysregulated during the hepatitis B virus (HBV)-host cell interaction adds to the understanding of underlying molecular mechanisms and aids in discovering effective therapies to improve prognosis in hepatitis B virus (HBV)-infected individuals. Through bioinformatics analyses of transcriptomics data, this study aimed to identify potential genes involved in the cross-talk of human hepatocytes expressing the HBV viral protein HBx with endothelial cells. Transient transfection of HBV viral gene X (HBx) was performed in THLE2 cells using pcDNA3 constructs.

Alteration of oral bacteriome of smokeless tobacco users and their association with oral cancer.

Smokeless tobacco (SLT) is certainly one of the major risk factors associated with oral cancer. Disruption of oral microbiota-host homeostasis contributes to the progression of oral cancer. Here, we profiled SLT users' oral bacterial composition and inferred their functions by sequencing 16S rDNA V-V region and PICRUSt2, respectively.

Insights from establishing a high throughput viral diagnostic laboratory for SARS-CoV-2 RT-PCR testing facility: challenges and experiences.

: The World Health Organization declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Identifying the infected people and isolating them was the only measure that was available to control the viral spread, as there were no standardized treatment interventions available. Various public health measures, including vaccination, have been implemented to control the spread of the virus worldwide.

Impact of the COVID-19 pandemic on an online cancer screening training programme for healthcare providers in the public sector in India: learnings from a hub and spoke model perspective.

Introduction: This article elicits our experiences and strategic approaches to ensure the sustainability of the online capacity-building programmes for healthcare providers (HCPs) in comprehensive cancer screening through the 'Hub and Spoke' model during the coronavirus disease (COVID-19) pandemic.

Methods: During the first wave of COVID-19, training for three cohorts of medical officers (MO) (Batch-A) was ongoing (May-December 2020). The Indian health system abruptly shifted focus towards containing the COVID-19 spread, leading to new challenges in conducting training courses.

Artificial Intelligence-driven Digital Cytology-based Cervical Cancer Screening: Is the Time Ripe to Adopt This Disruptive Technology in Resource-constrained Settings? A Literature Review.

Cervical cancer is still a public health scourge in the developing countries due to the lack of organized screening programs. Though liquid-based cytology methods improved the performance of cervical cytology, the interpretation still suffers from subjectivity. Artificial intelligence (AI) algorithms have offered objectivity leading to better sensitivity and specificity of cervical cancer screening.

Prevalence of Cigarette Smoking and its Related Factors among Students in Iran: A Meta-Analysis.

Background: Smoking is a preventable cause of morbidity and mortality with an increasing prevalence in developing countries. The present systematic review and meta-analysis aimed to estimate the prevalence of smoking among college and high school students in Iran.

Materials And Methods: Databases of Scopus, PubMed, Web of Science, Google Scholar, SID, and MagIran were searched with no time limitation.

Meta-Analysis of 49 SNPs Covering 25,446 Cases and 41,106 Controls Identifies Polymorphisms in Hormone Regulation and DNA Repair Genes Associated with Increased Endometrial Cancer Risk.

Endometrial cancer (EC) is among the most common gynecological disorders globally. As single nucleotide polymorphisms (SNPs) play an important role in the causation of EC, therefore, a comprehensive meta-analysis of 49 SNPs covering 25,446 cases and 41,106 controls was performed to identify SNPs significantly associated with increased EC risk. PubMed was searched to identify case control studies and meta-analysis was performed to compute the pooled odds ratio (OR) at 95% confidence interval (CI).

Tracking district-level performance in the context of achieving zero indigenous case status by 2027.

India has committed to zero indigenous malaria cases by 2027 and elimination by 2030. Of 28 states and 8 union territories of India, eleven states were targeted to reach the elimination phase by 2020. However, state-level epidemiology indicates that several states of India may not be on the optimum track, and few goals set in National Framework for Malaria Elimination (NFME) for 2020 remain to be addressed.

Asking physicians how best to implement cervical cancer prevention services in India: A qualitative study from Mysore.

Cervical cancer is the second most common cancer among Indian women. Screening is an effective prevention strategy, but achieving high screening rates depend upon identifying barriers at multiple levels of healthcare delivery. There is limited research on understanding the perspectives of providers who deliver cancer prevention services.

Role of identified proteins in the proteome profiles of CDK4/6 inhibitor-resistant breast cancer cell lines.

Abemaciclib (Ab) and palbociclib (Pb) are CDK4/6 inhibitors used to cure advanced breast cancer (BC). However, acquired resistance is a major challenge. The molecular mechanisms and signature proteins of therapy resistance for Ab and Pb drugs need to be explored.

Fungal Community Composition and Function Associated with Loose Smokeless Tobacco Products.

Smokeless tobacco products (STPs) contain several microbial communities which are responsible for the formation of carcinogens, like tobacco-specific nitrosamine (TSNAs). A majority of STPs are sold in loose/unpackaged form which can be loaded with a diverse microbial population. Here, the fungal population and mycotoxins level of three popular Indian loose STPs, Dohra, Mainpuri Kapoori (MK), and loose leaf-chewing tobacco (LCT) was examined using metagenomic sequencing of ITS1 DNA segment of the fungal genome and LC-MS/MS, respectively.

Household transmission dynamics of COVID-19 among residents of Delhi, India: a prospective case-ascertained study.

Objective: The aim of this study was to observe the secondary infection rate and transmission dynamics of COVID-19 among household contacts, and their associations with various factors across four dimensions of interaction.

Methods: This was a case-ascertained study among unvaccinated household contacts of a laboratory-confirmed COVID-19 case in New Delhi between December 2020 and July 2021. For this study, 99 index cases and their 316 household contacts were interviewed and sampled (blood and oro-nasal swab) on days 1, 7, 14, and 28.

Challenges in setting up a primary human papillomavirus-DNA testing facility in a lower and middle income country: lessons learned from a pilot programme.

Introduction: Detection of high-risk human papillomavirus (hrHPV) is the most sensitive test for the screening of cervical cancer. Although most high-income countries have adopted this strategy in their screening programme, there are a lot of barriers in low and middle-income countries (LMICs) in setting up this facility for screening. The lessons learned based on this experience can be useful for other LMICs in their first steps to integrate HPV testing into a screening programme.

In-Silico molecular screening of natural compounds as a potential therapeutic inhibitor for Methicillin-resistant Staphylococcus aureus inhibition.

Methicillin-resistant Staphylococcus aureus (MRSA) is a life-threatening superbug causing infectious diseases such as pneumonia, endocarditis, osteomyelitis, etc. Conventional antibiotics are ineffective against MRSA infections due to their resistance mechanism against the antibiotics. The Penicillin Binding Protein (PBP2a) inhibits the activity of antibiotics by hydrolyzing the β-lactam ring.

Recent advances in the area of plant-based anti-cancer drug discovery using computational approaches.

Phytocompounds are a well-established source of drug discovery due to their unique chemical and functional diversities. In the area of cancer therapeutics, several phytocompounds have been used till date to design and develop new drugs. One of the desired interests of pharmaceutical companies and researchers globally is that new anti-cancer leads are discovered, for which phytocompounds can be considered a valuable source.

Forecasting most deleterious nsSNPs in human gene and their cumulative impact on biophysical features of the protein using approaches.

In women, the uterine cervix and corpus uteri are two main suspects, playing a major role in cancer-associated-mortality. Immunologically, Toll-like receptors (TLRs) associated with the innate immune system, can recognize pathogens and induce immune responses against pathogens. Cellularly, TLR9 expression occurs in immune system cells including macrophages, natural killer cells, dendritic cells, and other antigen-presenting cells.