bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prosurvival IL-7–Stimulated Weak Strength of mTORC1-S6K Controls T Cell Memory via Transcriptional FOXO1–TCF1–Id3 and Metabolic AMPKα1–ULK1–ATG7 Pathways
Authors: Xu Aizhang , Leary Scot C , Islam Md Fahmid , Wu Zhaojia , Bhanumathy Kalpana Kalyanasundaram , Ara Anjuman , Chibbar Rajni , Fleywald Andrew , Ahmed Khawaja Ashfaque , Xiang Jim 
Published: December 2021

Abstract
CD8+ memory T (TM) cells play a critical role in immune defense against infection. Two common γ-chain family cytokines, IL-2 and IL-7, although triggering the same mTORC1–S6K pathway, distinctly induce effector T (TE) cells and TM cells, respectively, but the underlying mechanism(s) remains elusive. In this study, we generated IL-7R-/and AMPKα1-knockout (KO)/OTI mice. By using genetic and pharmaceutical tools, we demonstrate that IL-7 deficiency represses expression of FOXO1, TCF1, p-AMPKα1 (T172), and p-ULK1 (S555) and abolishes T cell memory differentiation in IL-7R KO T cells after Listeria monocytogenesis rLmOVA infection. IL-2– and IL-7–stimulated strong and weak S6K (IL-2/S6Kstrong and IL-7/S6Kweak) signals control short-lived IL-7R−CD62L−KLRG1+ TE and long-term IL-7R+CD62L+KLRG1− TM cell formations, respectively. To assess underlying molecular pathway(s), we performed flow cytometry, Western blotting, confocal microscopy, and Seahorse assay analyses by using the IL-7/S6Kweak–stimulated TM (IL-7/TM) and the control IL-2/S6Kstrong–stimulated TE (IL-2/TE) cells. We determine that the IL-7/S6Kweak signal activates transcriptional FOXO1, TCF1, and Id3 and metabolic p-AMPKα1, p-ULK1, and ATG7 molecules in IL-7/TM cells. IL-7/TM cells upregulate IL-7R and CD62L, promote mitochondria biogenesis and fatty acid oxidation metabolism, and show long-term cell survival and functional recall responses. Interestingly, AMPKα1 deficiency abolishes the AMPKα1 but maintains the FOXO1 pathway and induces a metabolic switch from fatty acid oxidation to glycolysis in AMPKα1 KO IL-7/TM cells, leading to loss of cell survival and recall responses. Taken together, our data demonstrate that IL-7–stimulated weak strength of mTORC1–S6K signaling controls T cell memory via activation of transcriptional FOXO1–TCF1–Id3 and metabolic AMPKα1–ULK1–ATG7 pathways. This (to our knowledge) novel finding provides a new mechanism for a distinct IL-2/IL-7 stimulation model in T cell memory and greatly impacts vaccine development.
Prediction of Cardiovascular Risk among Healthcare Professionals using Atherosclerotic Cardiovascular Disease Risk Score in a Tertiary Care Hospital in Aurangabad, India
Authors: Naik Manjiri R. , Jacob Rohit Manoj , Reddy Sanjana P. 
Published: December 2021

Background:
The current scenario of long working hours, sedentary lifestyle, and occupational stress has led to an increased prevalence of noncommunicable risk factors among the medical fraternity. Hence, determining the risk of developing atherosclerotic cardiovascular disease (ASCVD) has become highly essential to curb the predisposing factors leading to it.

Objectives:
The objectives of the study are to cluster the cardiovascular risk factors among healthcare professionals and to estimate the ASCVD Risk Score among healthcare professionals of a teaching hospital in Aurangabad.

Methods:
A population of 200 subjects were considered for the study. Cardiovascular risk factors such as age, race, gender, diabetes mellitus, antihypertensive medications, dyslipidemia, alcohol consumption, smoking, family history of hypertension, physical activity, waist circumference (central obesity), obesity, and stress/mental status were studied. Assessing each of its prevalence to predict the risk of cardiovascular disease using ASCVD Risk Score formed the crux of the study.

Results:
On assessing the risk factors in all subjects, it was found that type 2 diabetes mellitus (34.6%), dyslipidemia (32%), and hypertension (22.09%) were predominantly seen among majority of the healthcare professionals. The average lifetime ASCVD Score among healthcare professionals was 57.8%. It was observed that as age advances, the risk of developing an ASCVD also increased.

Conclusion:
Utilizing a simple tool such as the ASCVD Risk Score Calculator can not only predict the risk of ASCVD but can also help initiate preventive strategies and prolong the life of a medico!
Effect of leukotriene receptor antagonist therapy in bronchial asthma — A prospective, preliminary, hospital-based, randomized study in rural Konaseema, Andhra Pradesh
Authors: Bathula Bhargav Prasad , Bandela Pandit Vinodh , Ravikumar Pentakota , Duvvuri Bhima Sankar , Polimati Subba Rao 
Published: December 2021

BACKGROUND:
The role of leukotriene receptor antagonist is well documented in the management of chronic asthma. However, the efficacy in acute asthma is not yet established.

AIM AND OBJECTIVES:
This study was designed to evaluate the clinical efficacy of oral montelukast as an add-on drug to the standard therapy of the acute attack of bronchial asthma.

MATERIALS AND METHODS:
A prospective, institutional-based, single-blinded, randomized control study was done. A total of 100 (aged between 18 and 60 years) participants diagnosed with acute exacerbations due to bronchial asthma were enrolled in the study. They were divided into study and control groups randomly. The study group patients were treated with 10 mg of montelukast once in a day for 4 weeks as an add-on drug, whereas the control group received only standard medication of acute bronchial asthma (as per Global Initiative for Asthma guidelines). All the participants were monitored at baseline to every week for a month.

RESULTS:
All the 100 participants were assessed finally without any dropouts. The baseline characteristics were noted similarly in both groups. The mean age was 35.46 + 13.17 years in the control and 37.86 + 14.43 years in the study group. Majority were males in both the groups. At the end of the 4 weeks of oral montelukast administration, there was improvement in forced expiratory volume in 1 s (FEV1) and peak expiratory flow rate at 2 weeks and 1 month. On many occasions, there was a strong improvement in FEV1 and other clinical parameters after continuous treatment with beta-2 agonists and parenteral corticosteroids for patients with acute asthma. Even though there was no improvement in FEV1/forced vital capacity ratio among both the groups at 2 weeks and 4 weeks, statistically significant improvement was seen between 2 weeks to 1 month on baseline parameters.

CONCLUSION:
Administration of oral montelukast 10 mg as an add-on drug to standard therapy may help in quick recovery from acute bronchial asthma and relapse.
The study of fractional exhaled nitric oxide in newly diagnosed cases of bronchial asthma and chronic obstructive pulmonary disease
Authors: Lakshmi V. , Meshram Priti , Kumar Ujjwal , Pujari Vishwanath , Sagar Pinkutty 
Published: December 2021

INTRODUCTION:
Fractional exhaled nitric oxide (FENO) is a measurement of fractional nitric oxide (NO) concentration in exhaled breath. It is a quantitative, noninvasive, simple, and safe method to measure airway inflammation for the assessment of airways diseases.

OBJECTIVE:
The study was conducted at the tertiary care hospital to study the FENO levels in newly diagnosed patients of bronchial asthma and chronic obstructive pulmonary disease (COPD).

MATERIALS AND METHODS:
A total number of 105 patients were included in the study, diagnosed based on pulmonary function test and symptomatology. FENO levels were measured using Medisoft FENO machine, and the results were analyzed.

RESULTS AND CONCLUSIONS:
We found that both COPD and bronchial asthma are more prevalent among males. FENO levels were higher in bronchial asthma patients as compared to COPD patients. In bronchial asthma, FENO levels were higher in patients with very severe obstruction, and in COPD, patients with mild obstruction had slightly higher FENO values.
Diagnostic accuracy of respiratory impedance parameters to detect airflow obstruction in adults
Authors: De Sajal 
Published: December 2021

OBJECTIVE:
The present study was aimed to evaluate the diagnostic accuracy of impedance parameters to detect airflow obstruction and the severity of airflow obstruction in adults.

METHODS:
The spirometry parameters (forced expiratory volume in 1 s [FEV1], forced vital capacity [FVC], FEV1/FVC, FVC3/FVC, and FEF25-75) and respiratory impedance parameters (R5, R19, R5-19, and X5) measured by forced oscillation technique of consecutive 299 adults (male: 186) were included in the present analysis. The Spearman correlation coefficient (ρ) was used to assess the correlations of impedance parameters with spirometry indices. The area under the curve (AUC) was used to assess respiratory impedance parameters' diagnostic accuracy.

RESULTS:
The mean age of the study population was 54.1 ± 12.3 years, and 99 individuals (33%) had airflow obstruction (FEV1/FVC < 0.70) in spirometry. All spirometry indices (% of predicted) showed a weak negative correlation with R5, R19, R5-19, and weak positive correlation with X5. The R5 >142% predicted and X5 >136% predicted had the maximum AUC (0.75) with a sensitivity of up to 56% and specificity up to 86% to identify airflow obstruction. The impedance parameters showed low concordance with the severity of airflow obstruction.

CONCLUSION:
Respiratory impedance parameters had insufficient sensitivity to diagnose airflow obstruction and the severity of obstruction in adults. Thus, impedance parameters cannot a substitute for spirometry in diagnosing obstructive lung function.
Drug repurposing for identification of potential inhibitors against SARS-CoV-2 spike receptor-binding domain
Authors: Behera Santosh Kumar , Mahapatra Namita , Tripathy Chandra Sekhar , Pati Sanghamitra 
Published: December 2021

Background & objectives:
The world is currently under the threat of coronavirus disease 2019 (COVID-19) infection, caused by SARS-CoV-2. The objective of the present investigation was to repurpose the drugs with potential antiviral activity against receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein among 56 commercially available drugs. Therefore, an integrative computational approach, using molecular docking, quantum chemical calculation and molecular dynamics, was performed to unzip the effective drug-target interactions between RBD and 56 commercially available drugs.

Methods:
The present in silico approach was based on information of drugs and experimentally derived crystal structure of RBD of SARS-CoV-2 S protein. Molecular docking analysis was performed for RBD against all 56 reported drugs using AutoDock 4.2 tool to screen the drugs with better potential antiviral activity which were further analysed by other computational tools for repurposing potential drug or drugs for COVID-19 therapeutics.

Results:
Drugs such as chalcone, grazoprevir, enzaplatovir, dolutegravir, daclatasvir, tideglusib, presatovir, remdesivir and simeprevir were predicted to be potentially effective antiviral drugs against RBD and could have good COVID-19 therapeutic efficacy. Simeprevir displayed the highest binding affinity and reactivity against RBD with the values of −8.52 kcal/mol (binding energy) and 9.254 kcal/mol (band energy gap) among all the 56 drugs under investigation.

Interpretation & conclusions:
In the current investigation, simeprevir was identified as the potential antiviral drug based on the in silico findings in comparison to remdesivir, favipiravir and other 53 drugs. Further, laboratory and clinical investigations are needed to be carried out which will aid in the development of quick therapeutics designed for COVID-19.
First seroprevalence report of scrub typhus from the tribal belts of the Nilgiris district, Tamil Nadu, India
Authors: Paulraj Philip Samuel , Renu Govindarajan , Ranganathan Krishnamoorthi , Leo Victor Jerald , Veeramanoharan Rajamannar 
Published: December 2021

Background & objectives:
Scrub typhus, an acute febrile Rickettsial disease is caused by the bacterial pathogen Orientia tsutsugamushi which is spread by the bite of infected chigger mite vectors belonging to the family Trombiculidae. A study was undertaken to find out the prevalence of scrub typhus among the indigenous population from Nilgiris, Tamil Nadu.

Methods:
This study was conducted among 214 patients with fever of unknown aetiology and a recent history of febrile illness attending the Nilgiris Adivasi Welfare Association medical facilities available at Nilgiris district, Tamil Nadu. Serum samples were tested for scrub typhus IgM enzyme-linked immunosorbent assay.

Results:
Overall, 13 (6.07%) of the 214 samples tested were positive for scrub typhus. This is the first seroprevalence report of scrub typhus from the indigenous people belonging to Irula, Kurumba, Paniyar, and Kota tribes from the Nilgiris district, Tamil Nadu.

Interpretation & conclusions:
Early diagnosis and effective management will protect this indigenous population from this disease. This report would help in creating awareness regarding scrub typhus infection among clinicians and public health authorities in the region and take appropriate measures for treatment and control.
Health-related quality of life in patients with chronic obstructive pulmonary disease
Authors: Kharbanda Sidharth , Anand R. 
Published: December 2021

Background & objectives:
Chronic obstructive pulmonary disease (COPD) adversely affects various functional and structural domains of the lungs, in addition to having an array of extra-pulmonary effects which affect overall well-being of a patient. This study was aimed at measuring the health-related quality of life (HRQOL) in COPD patients and relating the severity of disease and other factors with the degree of impairment of HRQOL.

Methods:
This cross-sectional study was conducted on 100 individuals with established COPD aged 45 yr or above. COPD severity was graded based on the Global Initiative for Obstructive Lung Disease (GOLD) staging system. Pulmonary function test was carried out as per the American Thoracic Society and European Respiratory Society task force standardised lung function testing guidelines. The quality of life was measured using the COPD-specific version of the St. George's Respiratory Questionnaire (SGRQ). The three component scores (activity, impact and symptoms) and the total score were compared across the various categories of age, gender and COPD grades. Using multivariable linear regression analysis, the relationship between COPD grades and various component scores, adjusting for age and gender, was determined.

Results:
The mean total SGRQ Classification score was found to be 48.5±17.1. There was a significant increase in the symptom, activity and impact component scores and the total scores of the participants with worsening of COPD grade. The activity, impact component scores and total score showed an increasing trend with age. However, the values of these three scores were lower in participants in the age group of 56-65 yr in comparison to those in the 45-55 yr age group. There was a significant increase in the symptom component score with increasing age across the study population. The difference in the various scores between males and females was not significant.

Interpretation & conclusions:
HRQOL is impaired in patients with COPD, and it deteriorates with increasing severity of the disease. The onset of COPD at a younger age has a much more significant deterioration of HRQOL, due to the early onset of symptoms and complications. These findings call for better early care and integration of pulmonary rehabilitation programmes into current health policies.
Phylogenetic classification of the whole-genome sequences of SARS-CoV-2 from India & evolutionary trends
Authors: Potdar Varsha , Vipat Veena , Ramdasi Ashwini , Jadhav Santosh , Pawar-Patil Jayashri , Walimbe Atul , Patil Sucheta S. , Choudhury Manohar L. , Shastri Jayanthi , Agrawal Sachee , Pawar Shailesh , Lole Kavita , Abraham Priya , Cherian Sarah 
Published: December 2021

Background & objectives:
Several phylogenetic classification systems have been devised to trace the viral lineages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, inconsistency in the nomenclature limits uniformity in its epidemiological understanding. This study provides an integration of existing classifications and describes evolutionary trends of the SARS-CoV-2 strains circulating in India.

Methods:
The whole genomes of 330 SARS-CoV-2 samples were sequenced using next-generation sequencing (NGS). Phylogenetic and sequence analysis of a total of 3014 Indian SARS-CoV-2 sequences from 20 different States/Union Territories (January to September 2020) from the Global Initiative on Sharing All Influenza Data (GISAID) database was performed to observe the clustering of Nextstrain and Phylogenetic Assignment of Named Global Outbreak LINeages (Pangolin) lineages with the GISAID clades. The identification of mutational sites under selection pressure was performed using Mixed Effects Model of Evolution and Single-Likelihood Ancestor Counting methods available in the Datamonkey server.

Results:
Temporal data of the Indian SARS-CoV-2 genomes revealed that except for Uttarakhand, West Bengal and Haryana that showed the circulation of GISAID clade O even after July 2020, the rest of the States showed a complete switch to GR/GH clades. Pangolin lineages B.1.1.8 and B.1.113 identified within GR and GH clades, respectively, were noted to be indigenous evolutions. Sites identified to be under positive selection pressure within these clades were found to occur majorly in the non-structural proteins coded by ORF1a and ORF1b.

Interpretation & conclusions:
This study interpreted the geographical and temporal dominance of SARS-CoV-2 strains in India over a period of nine months based on the GISAID classification. An integration of the GISAID, Nextstrain and Pangolin classifications is also provided. The emergence of new lineages B.1.1.8 and B.1.113 was indicative of host-specific evolution of the SARS-CoV-2 strains in India. The hotspot mutations such as those driven by positive selection need to be further characterized.
Modelling the spread of SARS-CoV-2 pandemic - Impact of lockdowns & interventions
Authors: Agrawal Manindra , Kanitkar Madhuri , Vidyasagar M. 
Published: December 2021

Background & objectives:
To handle the current COVID-19 pandemic in India, multiple strategies have been applied and implemented to slow down the virus transmission. These included clinical management of active cases, rapid development of treatment strategies, vaccines computational modelling and statistical tools to name a few. This article presents a mathematical model for a time series prediction and analyzes the impact of the lockdown.

Methods:
Several existing mathematical models were not able to account for asymptomatic patients, with limited testing capability at onset and no data on serosurveillance. In this study, a new model was used which was developed on lines of susceptible-asymptomatic-infected-recovered (SAIR) to assess the impact of the lockdown and make predictions on its future course. Four parameters were used, namely β, γ, η and ε. β measures the likelihood of the susceptible person getting infected, and γ denotes recovery rate of patients. The ratio β/γ is denoted by R0 (basic reproduction number).

Results:
The disease spread was reduced due to initial lockdown. An increase in γ reflects healthcare and hospital services, medications and protocols put in place. In Delhi, the predictions from the model were corroborated with July and September serosurveys, which showed antibodies in 23.5 and 33 per cent population, respectively.

Interpretation & conclusions:
The SAIR model has helped understand the disease better. If the model is correct, we may have reached herd immunity with about 380 million people already infected. However, personal protective measures remain crucial. If there was no lockdown, the number of active infections would have peaked at close to 14.7 million, resulted in more than 2.6 million deaths, and the peak would have arrived by June 2020. The number of deaths with the current trends may be less than 0.2 million.
Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates
Authors: Mukhopadhyay Labanya , Yadav Pragya D. , Gupta Nivedita , Mohandas Sreelekshmy , Patil Deepak Y. , Shete-Aich Anita , Panda Samiran , Bhargava Balram 
Published: December 2021

Background & objectives:
The COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission, with a few vaccines having progressed to advanced stages of clinical trials. The aim of this systematic review was to compare immunogenicity and protective efficacy of various SARS-CoV-2 vaccine candidates tested in non-human primate (NHP) models.

Methods:
Literature on effect of SARS-CoV-2 vaccines in NHP models reported on PubMed and preprint platforms (medRxiv and bioRxiv) till October 22, 2020, was searched with the following terms: coronavirus vaccine, COVID-19 vaccine, SARS-CoV-2 vaccine, nonhuman primate, and rhesus macaque.

Results:
Our search yielded 19 studies, which reported immune response elicited by 18 vaccine candidates in NHP. All the vaccines induced detectable neutralizing antibody (NAb) titres in the serum of vaccinated animals, with some showing effective viral clearance from various organs. The vaccinated animals also showed nil to mild histopathological changes in their lungs compared to placebo groups in the trials that performed necropsy.

Interpretation & conclusions:
Our findings highlighted onset of quick immunogenicity and protective efficacy of mRNA-1273, followed by Ad26.CoV2.S, NVX-CoV2373, BNT162b2, RBD and BBV152 vaccine candidates in preclinical trials as compared to the others. NHP data also showed correlation with clinical trial data available for a few vaccines. Preclinical trials of COVID-19 vaccine candidates in NHPs yielded promising results, with some candidates faring better than others.
The regulatory effect of cabazitaxel on epithelial-mesenchymal transition in metastatic prostate cancer
Authors: Eryilmaz Isil Ezgi , Eskiler Gamze Guney , Egeli Unal , Cecener Gulsah 
Published: December 2021

ABSTRACT

Introduction:
Epithelial-mesenchymal transition (EMT) is a critical mechanism that promotes cancer cells to metastasis. Therefore, EMT regulation has become an important target in anticancer therapy approaches in recent years. However, in metastatic prostate cancer (PC), the EMT regulatory effect has not fully understood for cabazitaxel (Cbx), a third line taxane-based chemotherapeutic for metastatic castration-resistant PC.

Aim:
In this study, we investigated the antimetastatic and EMT-regulatory effects of Cbx on hormone-sensitive metastatic PC cells.

Materials and Methods:
The anticancer effects of Cbx were assessed by WST-1 and Annexin V analysis. The antimetastatic effect of Cbx was evaluated by wound healing and quantitative reverse transcription polymerase chain reaction through EMT-mesenchymal-to-epithelial transition (MET) markers as well as EMT-repressor microRNAs (miRNAs) in Cbx-treated LNCaP cells.

Results:
Our results showed that, in addition to its apoptotic and anti-migratory activities, Cbx exhibited the EMT-repressor effects through the prominent downregulation of matrix metalloproteinase-9 and Snail levels as EMT-promoting factors, and the significant upregulation of the certain miRNAs, including miR-205, miR-524, and miR-124, which play a role in EMT-repressing by targeting regulators of the EMT-associated genes.

Conclusion:
Although further evaluations are needed to improve the findings, we showed that, in addition to its classical taxane function, Cbx has a regulatory effect on EMT-MET cycling in hormone-sensitive metastatic PC.