Multiomic Insights into Human Health: Gut Microbiomes of Hunter-Gatherer, Agropastoral, and Western Urban Populations.

Societies with exposure to preindustrial diets exhibit improved markers of health. Our study used a comprehensive multi-omic approach to reveal that the gut microbiome of the Ju/'hoansi hunter-gatherers, one of the most remote KhoeSan groups, exhibit a higher diversity and richness, with an abundance of microbial species lost in the western population. The Ju/'hoansi microbiome showed enhanced global transcription and enrichment of complex carbohydrate metabolic and energy generation pathways. The Ju/'hoansi also show high abundance of short-chain fatty acids that are associated with health and optimal immune function. In contrast, these pathways and their respective species were found in low abundance or completely absent in Western populations. Amino acid and fatty acid metabolism pathways were observed prevalent in the Western population, associated with biomarkers of chronic inflammation. Our study provides the first in-depth multi-omic characterization of the Ju/'hoansi microbiome, revealing uncharacterized species and functional pathways that are associated with health.

Enhancing the physician-scientist workforce: evaluating a mentored research program for medical students' research competencies and intentions.

Background: The growing recognition of the need to incorporate scientific discoveries into healthcare decisions underscores an urgency for a robust physician-scientist workforce to advance translational research. Despite the correlation between medical students' research engagement and their academic productivity and success, significant gaps remain in the scientific workforce exacerbated by the "leaky pipeline" phenomenon from medical school to academic medicine, where potential physician-scientists veer away from research careers.The purpose of this study was to assess the effectiveness of a structured mentored research program for enhancing medical students' research competencies and sustaining their interest in research careers, thereby potentially enhancing the physician-scientist workforce. Methods: The Medical Student Research Program (MSRP) implemented at the University of California, Irvine (UCI) was designed to provide comprehensive research training and support to medical students through a series of structured lectures, mentorship by dedicated faculty, and administrative support for research activities. Students were surveyed upon enrollment and one year later to assess the change in research competencies from baseline to follow-up (paired samples t-test), students' intent to use research in clinical practice (paired samples t-test), and their intent to conduct research in the future (McNemar's test and McNemar Bowker test). Results: Preliminary evaluations indicated that the MSRP enhanced students' research competencies and has the potential to enhance medical students' research skills. However, similar to national trends, there was a decrease in students' intentions to engage with research in their future clinical career. Conclusions: Our preliminary findings demonstrate MSRP students' enhanced research competencies during the first year of the program. However, the decline in students' intentions to engage in future research highlights the need for continued innovation in research training programs to sustain future intent to conduct research, in turn helping to address the "leaky pipeline" in the physician-scientist workforce. Future studies should focus on mid and long-term outcomes to fully assess research program impact on the physician-scientist pipeline and on integrating such programs more broadly into medical education.

A real-world longitudinal study implementing digital screening and treatment for distress in inflammatory bowel disease (IBD): The COMPASS-IBD study protocol.

INTRODUCTION: Co-morbid anxiety and depression (distress) in inflammatory bowel disease (IBD) results in poorer outcomes and increased healthcare burden. IBD services require scalable treatment pathways for distress to meet this need. This real-world longitudinal study evaluates the implementation of a new integrated care pathway for distress including: 1) routine mental health screening and 2) therapist-guided, digital CBT tailored to the challenges of living with IBD (compass with adaptations for IBD: COMPASS-IBD) in a UK National Health Service (NHS) large gastroenterology service (∼ 5000 patients). METHODS: We describe a mixed-methods, observational, real-world longitudinal study. Routine mental health screening in the IBD service will identify patients with distress (using pre-defined clinical cut-offs), who will be triaged to determine appropriate treatment pathways (including participation in the COMPASS-IBD study). Participants will receive COMPASS-IBD online for ∼12 weeks (including 6 × 30-min therapist sessions). Key implementation outcomes will assess reach and adoption of the new pathway using aggregate data on uptake of mental health screening, eligibility, and consent rates for COMPASS-IBD, and number of COMPASS-IBD sessions completed. Interviews with patients and healthcare providers will primarily assess acceptability of the new pathway. Potential effectiveness will be assessed using participant questionnaires at pre-intervention, 12-weeks (post-intervention), and 6-month follow-up. The primary effectiveness outcome will be pre-post changes in distress (PHQ-ADS scores). Quantitative data will be summarised using descriptive statistics and qualitative data analysed using reflexive thematic analysis. CONCLUSION: Study findings will inform treatment pathways for co-morbid distress in IBD, and highlight adaptations required to increase future scalability and effectiveness. TRIAL REGISTRATION NUMBER: NCT05330299 (clinicaltrials.gov).

Whole-genome sequencing-based genetic diversity, transmission dynamics, and drug-resistant mutations in Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia.

Background: Extrapulmonary tuberculosis (EPTB) refers to a form of Tuberculosis (TB) where the infection occurs outside the lungs. Despite EPTB being a devastating disease of public health concern, it is frequently overlooked as a public health problem. This study aimed to investigate genetic diversity, identify drug-resistance mutations, and trace ongoing transmission chains. Methods: A cross-sectional study was undertaken on individuals with EPTB in western Ethiopia. In this study, whole-genome sequencing (WGS) was employed to analyze Mycobacterium tuberculosis (MTB) samples obtained from EPTB patients. Out of the 96 genomes initially sequenced, 89 met the required quality standards for genetic diversity, and drug-resistant mutations analysis. The data were processed using robust bioinformatics tools. Results: Our analysis reveals that the majority (87.64%) of the isolates can be attributed to Lineage-4 (L4), with L4.6.3 and L4.2.2.2 emerging as the predominant sub-lineages, constituting 34.62% and 26.92%, respectively. The overall clustering rate and recent transmission index (RTI) were 30 and 17.24%, respectively. Notably, 7.87% of the isolates demonstrated resistance to at least one anti-TB drug, although multi-drug resistance (MDR) was observed in only 1.12% of the isolates. Conclusions: The genetic diversity of MTBC strains in western Ethiopia was found to have low inter-lineage diversity, with L4 predominating and exhibiting high intra-lineage diversity. The notably high clustering rate in the region implies a pressing need for enhanced TB infection control measures to effectively disrupt the transmission chain. It's noteworthy that 68.75% of resistance-conferring mutations went undetected by both GeneXpert MTB/RIF and the line probe assay (LPA) in western Ethiopia. The identification of resistance mutations undetected by both GeneXpert and LPA, along with the detection of mixed infections through WGS, emphasizes the value of adopting WGS as a high-resolution approach for TB diagnosis and molecular epidemiological surveillance.

Comparative genomics of Deinococcus radiodurans: unveiling genetic discrepancies between ATCC 13939K and BAA-816 strains.

The Deinococcus genus is renowned for its remarkable resilience against environmental stresses, including ionizing radiation, desiccation, and oxidative damage. This resilience is attributed to its sophisticated DNA repair mechanisms and robust defense systems, enabling it to recover from extensive damage and thrive under extreme conditions. Central to Deinococcus research, the D. radiodurans strains ATCC BAA-816 and ATCC 13939 facilitate extensive studies into this remarkably resilient genus. This study focused on delineating genetic discrepancies between these strains by sequencing our laboratory's ATCC 13939 specimen (ATCC 13939K) and juxtaposing it with ATCC BAA-816. We uncovered 436 DNA sequence differences within ATCC 13939K, including 100 single nucleotide variations, 278 insertions, and 58 deletions, which could induce frameshifts altering protein-coding genes. Gene annotation revisions accounting for gene fusions and the reconciliation of gene lengths uncovered novel protein-coding genes and refined the functional categorizations of established ones. Additionally, the analysis pointed out genome structural variations due to insertion sequence (IS) elements, underscoring the D. radiodurans genome's plasticity. Notably, ATCC 13939K exhibited a loss of six ISDra2 elements relative to BAA-816, restoring genes fragmented by ISDra2, such as those encoding for α/ß hydrolase and serine protease, and revealing new open reading frames, including genes imperative for acetoin decomposition. This comparative genomic study offers vital insights into the metabolic capabilities and resilience strategies of D. radiodurans.

Pangenome and genomic signatures linked to the dominance of the lineage-4 of Mycobacterium tuberculosis isolated from extrapulmonary tuberculosis patients in western Ethiopia.

BACKGROUND: The lineage 4 (L4) of Mycobacterium tuberculosis (MTB) is not only globally prevalent but also locally dominant, surpassing other lineages, with lineage 2 (L2) following in prevalence. Despite its widespread occurrence, factors influencing the expansion of L4 and its sub-lineages remain poorly understood both at local and global levels. Therefore, this study aimed to conduct a pan-genome and identify genomic signatures linked to the elevated prevalence of L4 sublineages among extrapulmonary TB (EPTB) patients in western Ethiopia. METHODS: A cross-sectional study was conducted at an institutional level involving confirmed cases of extrapulmonary tuberculosis (EPTB) patients from August 5, 2018, to December 30, 2019. A total of 75 MTB genomes, classified under lineage 4 (L4), were used for conducting pan-genome and genome-wide association study (GWAS) analyses. After a quality check, variants were identified using MTBseq, and genomes were de novo assembled using SPAdes. Gene prediction and annotation were performed using Prokka. The pan-genome was constructed using GET_HOMOLOGUES, and its functional analysis was carried out with the Bacterial Pan-Genome Analysis tool (BPGA). For GWAS analysis, Scoary was employed with Benjamini-Hochberg correction, with a significance threshold set at p-value ≤ 0.05. RESULTS: The analysis revealed a total of 3,270 core genes, predominantly associated with orthologous groups (COG) functions, notably in the categories of '[R] General function prediction only' and '[I] Lipid transport and metabolism'. Conversely, functions related to '[N] Cell motility' and '[Q] Secondary metabolites biosynthesis, transport, and catabolism' were primarily linked to unique and accessory genes. The pan-genome of MTB L4 was found to be open. Furthermore, the GWAS study identified genomic signatures linked to the prevalence of sublineages L4.6.3 and L4.2.2.2. CONCLUSIONS: Apart from host and environmental factors, the sublineage of L4 employs distinct virulence factors for successful dissemination in western Ethiopia. Given that the functions of these newly identified genes are not well understood, it is advisable to experimentally validate their roles, particularly in the successful transmission of specific L4 sublineages over others.

Temporal dynamics and genomic programming of plasma cell fates.

Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Here, using a model antigen in mice, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response. Clonal tracing using single-cell RNA sequencing and B cell antigen receptor sequencing in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveals a new PC transition state that gives rise to functionally competent PC precursors. The latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived PCs, based on extended antigen encounters in the GC.

An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.

Major alteration of Lung Microbiome and the Host Reaction in critically ill COVID-19 Patients with high viral load.

Background: Patients with COVID-19 under invasive mechanical ventilation are at higher risk of developing ventilator-associated pneumonia (VAP), associated with increased healthcare costs, and unfavorable prognosis. The underlying mechanisms of this phenomenon have not been thoroughly dissected. Therefore, this study attempted to bridge this gap by performing a lung microbiota analysis and evaluating the host immune responses that could drive the development of VAP. Materials and methods: In this prospective cohort study, mechanically ventilated patients with confirmed SARS-CoV-2 infection were enrolled. Nasal swabs (NS), endotracheal aspirates (ETA), and blood samples were collected initially within 12 hours of intubation and again at 72 hours post-intubation. Plasma samples underwent cytokine and metabolomic analyses, while NS and ETA samples were sequenced for lung microbiome examination. The cohort was categorized based on the development of VAP. Data analysis was conducted using RStudio version 4.3.1. Results: In a study of 36 COVID-19 patients on mechanical ventilation, significant differences were found in the nasal and pulmonary microbiome, notably in Staphylococcus and Enterobacteriaceae, linked to VAP. Patients with VAP showed a higher SARS-CoV-2 viral load, elevated neutralizing antibodies, and reduced inflammatory cytokines, including IFN-δ, IL-1ß, IL-12p70, IL-18, IL-6, TNF-α, and CCL4. Metabolomic analysis revealed changes in 22 metabolites in non-VAP patients and 27 in VAP patients, highlighting D-Maltose-Lactose, Histidinyl-Glycine, and various phosphatidylcholines, indicating a metabolic predisposition to VAP. Conclusions: This study reveals a critical link between respiratory microbiome alterations and ventilator-associated pneumonia in COVID-19 patients, with elevated SARS-CoV-2 levels and metabolic changes, providing novel insights into the underlying mechanisms of VAP with potential management and prevention implications.

Population-level comparisons of gene regulatory networks modeled on high-throughput single-cell transcriptomics data.

Single-cell technologies enable high-resolution studies of phenotype-defining molecular mechanisms. However, data sparsity and cellular heterogeneity make modeling biological variability across single-cell samples difficult. Here we present SCORPION, a tool that uses a message-passing algorithm to reconstruct comparable gene regulatory networks from single-cell/nuclei RNA-sequencing data that are suitable for population-level comparisons by leveraging the same baseline priors. Using synthetic data, we found that SCORPION outperformed 12 existing gene regulatory network reconstruction techniques. Using supervised experiments, we show that SCORPION can accurately identify differences in regulatory networks between wild-type and transcription factor-perturbed cells. We demonstrate SCORPION's scalability to population-level analyses using a single-cell RNA-sequencing atlas containing 200,436 cells from colorectal cancer and adjacent healthy tissues. The differences between tumor regions detected by SCORPION are consistent across multiple cohorts as well as with our understanding of disease progression, and elucidate phenotypic regulators that may impact patient survival.

Structural and Functional Characterization of Obesumbacterium proteus Phytase: A Comprehensive In-Silico Study.

Phytate, also known as myoinositol hexakisphosphate, exhibits anti-nutritional properties and possesses a negative environmental impact. Phytase enzymes break down phytate, showing potential in various industries, necessitating thorough biochemical and computational characterizations. The present study focuses on Obesumbacterium proteus phytase (OPP), indicating its similarities with known phytases and its potential through computational analyses. Structure, functional, and docking results shed light on OPP's features, structural stability, strong and stable interaction, and dynamic conformation, with flexible sidechains that could adapt to different temperatures or specific functions. Root Mean Square fluctuation (RMSF) highlighted fluctuating regions in OPP, indicating potential sites for stability enhancement through mutagenesis. The systematic approach developed here could aid in enhancing enzyme properties via a rational engineering approach. Computational analysis expedites enzyme discovery and engineering, complementing the traditional biochemical methods to accelerate the quest for superior enzymes for industrial applications.

Unmasking the Enigma of Weil's Disease: A Case Report.

We present the case of a 37-year-old male with Weil's disease, a severe form of leptospirosis, who presented without typical ecological risk factors. Initially manifesting as weakness, muscle aches, and fever, the patient rapidly deteriorated, necessitating ICU admission due to septic shock and respiratory failure. Despite initial diagnostic challenges, including normal initial imaging and inconclusive laboratory findings, a presumptive diagnosis of leptospirosis was made using Modified Faine's criteria. Empirical antibiotic treatment with doxycycline led to significant clinical improvement, highlighting the importance of early recognition and treatment in severe cases of leptospirosis. This case underscores the need for heightened clinical suspicion and the use of diagnostic scoring systems, even in atypical presentations, to facilitate timely intervention and improve patient outcomes.

Extraction of nano-crystalline cellulose for development of aerogel: Structural, morphological and antibacterial analysis.

In the present decades, nanocellulose has been very popular in the field of nanotechnology and is receiving much attention from researchers because of its advantageous physicochemical properties, high aspect ratio, and high specific strength and modulus. The available non-eco-friendly conventional methods for the extraction of nano-crystalline cellulose (NCC) use highly concentrated chemicals and are time-consuming as well. The present adopted cost-effective method for the extraction of nano-crystalline cellulose involves minimum usage of chemicals and is environmentally friendly and relatively fast compared to other conventional methods. The nano-crystalline cellulose from sisal (NCC-S) fibers were extracted by steam explosion-assisted mild concentrated chemical treatments followed by mechanical grinding. The Dynamic light scattering (DLS) and Transmission electron microscopy (TEM) characterization confirmed the size of extracted NCC-S. A high aspect ratio was observed as 19.23, which signifies it could be a promising reinforcing material in developing nanocomposites for advanced applications. An increase in crystallinity and the removal of amorphous materials for NCC-S were confirmed by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analysis, respectively. Antibacterial study shows that NCC-S did not show any antibacterial properties against E. coli and S. aureus. The calculated yield of extracted nanocellulose was about 50 %. The aerogel with a porosity of 95.1 % and a density of 0.075 g/cm3 was prepared by vacuum freeze-drying method using extracted nanocellulose and chitosan. The cross-linking network structure and thermal stability of the aerogel were also confirmed by FTIR and TGA analysis respectively.

From Stress Tolerance to Virulence: Recognizing the Roles of Csps in Pathogenicity and Food Contamination.

Be it for lab studies or real-life situations, bacteria are constantly exposed to a myriad of physical or chemical stresses that selectively allow the tolerant to survive and thrive. In response to environmental fluctuations, the expression of cold shock domain family proteins (Csps) significantly increases to counteract and help cells deal with the harmful effects of stresses. Csps are, therefore, considered stress adaptation proteins. The primary functions of Csps include chaperoning nucleic acids and regulating global gene expression. In this review, we focus on the phenotypic effects of Csps in pathogenic bacteria and explore their involvement in bacterial pathogenesis. Current studies of csp deletions among pathogenic strains indicate their involvement in motility, host invasion and stress tolerance, proliferation, cell adhesion, and biofilm formation. Through their RNA chaperone activity, Csps regulate virulence-associated genes and thereby contribute to bacterial pathogenicity. Additionally, we outline their involvement in food contamination and discuss how foodborne pathogens utilize the stress tolerance roles of Csps against preservation and sanitation strategies. Furthermore, we highlight how Csps positively and negatively impact pathogens and the host. Overall, Csps are involved in regulatory networks that influence the expression of genes central to stress tolerance and virulence.

HLA sequencing identifies novel associations and suggests clinical relevance of DPB1*04:01 in ANCA-associated Granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease. Major contributions of HLA genes have been reported; however, HLA typing-based diagnosis or risk prediction in GPA has not been established. We have performed a sequencing-based HLA genotyping in a north Indian GPA cohort and controls to identify clinically relevant novel associations. PR3-ANCA-positive 40 GPA patients and 40 healthy controls from north India were recruited for the study. Targeted sequencing of HLA-A,-B,-C,-DRB1,-DQB1, and -DPB1 was performed. Allelic and haplotypic associations were tested. Molecular docking of susceptibility HLA alleles with reported super-antigen epitopes was performed. The association of substituted amino acids located at the antigen-binding domain of HLA was evaluated. Genetic association of five HLA-alleles was identified in GPA. The novel association was identified for C*15:02 (p = 0.04; OR = 0.27(0.09-0.88)). The strongest association was observed for DPB1*04:01 (p < 0.0001; OR = 6.2(3.08-11.71)), previously reported in European studies. 35 of 40 GPA subjects had at least one DPB1*04:01 allele, and its significant risk was previously not reported from the Indian population. Significantly associated haplotypes DRB1*03:01-DQB1*02:01-DPB1*04:01 (p = 0.02; OR = 3.46(1.11-12.75)) and DRB1*07:01-DQB1*02:02-DPB1*04:01 (p = 0.04; OR = 3.35(0.95-14.84)) were the most frequent in GPA patients. Ranging from 89 % to 100 % of GPA patients with organ involvement can be explained by at least one DPB1*04:01 allele. A strong interaction between the HLA and three epitopes of the reported super antigen TSST-1 of Staphylococcus aureus was confirmed. Our study highlighted the potential applicability of HLA typing for screening and diagnosis of GPA. A large multi-centric study and genotype-phenotype correlation analysis among GPA patients will enable the establishment of HLA-typing based GPA diagnosis.

Indian Academy of Pediatrics Revised Guidelines on Evaluation, Prevention and Management of Childhood Obesity.

JUSTIFICATION: The last guidelines for pediatric obesity were released in 2004 by Indian Academy of Pediatrics (IAP). Since then, there has been an alarming increase in prevalence and a significant shift in our understanding in the pathogenesis, risk factors, evaluation, and management of pediatric obesity and its complications. Thus, it was decided to revise and update the previous recommendations. OBJECTIVES: To review the existing literature on the burden of childhood obesity and its underlying etiology and risk factors. To recommend evaluation of childhood obesity and suggest optimum prevention and management strategies of childhood obesity. PROCESS: The following IAP chapters (Pediatric and Adolescent Endocrinology, Infant and Young Child feeding, Nutrition, Non-Communicable Disease and Adolescent Health Academy) were invited to nominate members to become part of the writing committee. The Committee held discussions on various aspects of childhood obesity through online meetings between February and August, 2023. Recommendations were then formulated, which were analyzed, revised and approved by all members of the Committee. RECOMMENDATIONS: Exogenous or primary obesity accounts for the majority of cases of childhood obesity. It is important to differentiate it from endogenous or secondary obesity as evaluation and management changes depending on the cause. In Indian, in children under 5 years of age, weight for length/height using WHO charts, and in children 5-18 years, BMI using IAP 2015 charts is used to diagnose overweight and obesity. Waist circumference should be routinely measured in all overweight and obese children and plotted on India specific charts, as it is a key measure of cardio-metabolic risk. Routine evaluation for endocrine causes is not recommended, except in short and obese children with additional diagnostic clues. All obese children more than ten years old should be evaluated for comorbidities like hypertension, dyslipidemia, hyperglycemia and non-alcoholic fatty liver disease/metabolic dysfunction associated steatotic liver disease (NAFLD/ MASLD). Prevention and management of childhood obesity mainly involves healthy diet practices, daily moderate to vigorous physical activity and reduced screen time. Pharmacotherapy may be offered as an addition to lifestyle interventions only in cases of class 3 obesity or if there are any life-threatening comorbidities. Finally, surgical management may be offered in children older than 12 years of age with class 2 obesity and associated comorbidities or class 3 obesity with/without comorbidities, only after failure of a proper trial of intense lifestyle modifications and pharmacotherapy for at least 6 months.

Insights into the Potential Role of Plasmids in the Versatility of the Genus Pantoea.

In the past two decades, 25 different species of the genus Pantoea within the Enterobacteriaceae family, have been isolated from different environmental niches. These species have a wide range of biological roles. Versatility in functions and hosts indicate that this genus has undergone extensive genetic diversification, which can be attributed to the different extra-chromosomal genetic elements or plasmids found across this genus. We have analyzed the functions of these plasmids and categorized them into four major groups for a better understanding of their future applications. The first and second group includes plasmids that contribute to genetic diversification and pathogenicity, respectively. The third group comprises cryptic plasmids of Pantoea. The last group includes plasmids that play a role in the metabolic versatility of the genus Pantoea. We have analyzed the data available up to May 2023 from two databases (viz; NCBI and PLSDB). In our analysis we have found a vast gap in knowledge. Complete gene annotations are available for only a few of the plasmids. This review highlights these challenges as an avenue for future research.

Seasonal variation of the quality of groundwater resources for human consumption and industrial purposes in the central plain zone of Punjab, India.

Due to environmental pollution, climate change, and anthropogenic activities, the judicious use and regular assessment of the quality of groundwater for industrial, agricultural, and drinking purposes had gained a lot of attention across the globe. To assess the seasonal suitability of groundwater based on hydrochemistry and different quality indices, groundwater samples were collected and analyzed for different physicochemical parameters. Our findings indicated that the pH, electrical conductivity (EC), total dissolved solids (TDS), total hardness (TH), and calcium ion (Ca2+) content of groundwater were within acceptable limits of WHO and Bureau of Indian Standards (BIS) guidelines for drinking water. However, chloride content exceeded the acceptable levels, accounting for about 29.1% during the pre-monsoon and 15.3% during the post-monsoon period. Based on the water quality index (WQI), none of the water samples were deemed unsuitable for drinking purposes. However, when considering the synthetic pollution index (SPI), 100% of the samples were categorized as moderately polluted during both the pre-monsoon and post-monsoon periods. For industrial purpose suitability, 39.8 and 30.6% of the water samples had high corrosion tendency for pre-monsoon and post-monsoon seasons, respectively. Additionally, 77.5-93.4% of the total water samples were slightly affected by salinization on the basis of Revelle index. Generally, the groundwater quality for drinking purposes meets the WHO and BIS guidelines, with high corrosion potential for industrial use and slight salinization concerns in the area.

Patterns of Electrocardiographic Abnormalities in Children with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM.

Temporal dynamics and genomic programming of plasma cell fates.

Affinity-matured plasma cells (PCs) of varying lifespans are generated through a germinal center (GC) response. The developmental dynamics and genomic programs of antigen-specific PC precursors remain to be elucidated. Using a model antigen, we demonstrate biphasic generation of PC precursors, with those generating long-lived bone marrow PCs preferentially produced in the late phase of GC response. Clonal tracing using scRNA-seq+BCR-seq in spleen and bone marrow compartments, coupled with adoptive transfer experiments, reveal a novel PC transition state that gives rise to functionally competent PC precursors. The latter undergo clonal expansion, dependent on inducible expression of TIGIT. We propose a model for the proliferation and programming of precursors of long-lived PCs, based on extended antigen encounters followed by reduced antigen availability.