Biomedical subjects

Bharat Thyagarajan

Publications and source records attributed to Bharat Thyagarajan.

7 recordsLinked to original sources

PubMed2026

Validation of an integrated metagenomic pipeline combining optimized wet-lab processing and tiered reporting for CSF pathogen detection.

UNLABELLED: Metagenomic next-generation sequencing (mNGS) in the infectious disease diagnostic space has been gaining traction and is popular for aiding in the diagnosis of central nervous system infections. However, many challenges and obstacles remain in making this technology a gold standard for infectious disease diagnostic testing. One major challenge is being able to distinguish between the clinically relevant organisms from background contamination. We performed a validation study for mNGS on cerebrospinal fluid (CSF) that utilized positive clinical samples and contrived samples that incorporated a bioinformatics pipeline that can better distinguish between background contamination and clinically relevant organisms and used a three-tiered reporting algorithm meant to decrease the inherent subjectivity that comes with interpreting and reporting data from clinical metagenomic sequencing. The validation of this assay and category-based reporting pipeline revealed an overall concordance of 91.8%, with a sensitivity of 100% and a specificity of 72.4%. In addition, we improved the detection of clinically relevant RNA viruses to almost 100% in the CSF by modifying the wet lab processing of the sample. This bioinformatics pipeline with a category-based reporting algorithm will provide more confidence in reporting microorganisms detected with this technology, mNGS, and improving patient care. IMPORTANCE: Metagenomic next-generation sequencing (mNGS) can offer a broad, unbiased approach for the detection of infectious pathogens and has shown promise in diagnosing central nervous system infections. Despite its potential, clinical implementation remains limited by challenges in distinguishing clinically relevant organisms from background contamination. This study validated an mNGS assay for cerebrospinal fluid that incorporates an optimized bioinformatics pipeline with a three-tiered reporting algorithm designed to reduce subjectivity and enhance diagnostic confidence. The assay also has improved detection of clinically relevant RNA viruses through modified wet-lab processing. These findings support the clinical utility of a structured, category-based reporting approach for mNGS, advancing its reliability as a diagnostic tool in infectious disease testing.

Metagenomics↗

PubMed2025

Prevalence and causes of anemia among older adults in India: findings from wave 2 of the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD).

Anemia among older adults aged ≥ 60 years is a well-described risk factor that increases the risk of falls, cardiovascular diseases, and mortality. In India, objectively measured national estimates of anemia prevalence and the causes of anemia among older adults are lacking. The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) collected venous blood samples from a nationally representative sample of 3,252 individuals in wave 2 of the study. Out of these, 3,009 samples were used to estimate national prevalence and regional differences in anemia prevalence and its underlying causes. Anemia was defined as hemoglobin < 13 mg/dl in males and < 12 mg/dl in females and further categorized into nutritional and non-nutritional anemia based on several nutritional (ferritin, Vitamin B12, and folate), inflammatory (ferritin, C-reactive protein), and renal (serum creatinine) biomarkers. The overall national anemia prevalence was 49.92%. Anemia prevalence was significantly higher among women (53.9%) than men (45.8%). Among those with anemia, nutritional anemia was found in 63.5% of the respondents, with isolated iron deficiency anemia being the most common cause (51.8%). Among the non-nutritional category, anemia of chronic disease was the most common type (31.4%). About 10% of all anemia cases could not be classified into either category using the available data. Regional differences were seen with the highest prevalence of anemia in Assam, West Bengal, Jharkhand, and Odisha, and the lowest prevalence (< 30%) in Jammu & Kashmir and Haryana. Multivariate adjustment showed that age, sex, and region of residence are independently associated with anemia status. The study provides valuable insights into the overall anemia prevalence among older adults in India, its underlying causes, and regional differences to lay a strong foundation for making informed decisions toward anemia control in India.

Humans↗

PubMed2025

Heterogeneity of Apolipoprotein B Levels Among Hispanic or Latino Individuals Residing in the US.

IMPORTANCE: Apolipoprotein B (apoB) distribution and its implications as an atherosclerotic cardiovascular disease (ASCVD) risk-enhancing factor among individuals of diverse Hispanic or Latino backgrounds have not been described. OBJECTIVE: To describe the distribution of apoB in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) cohort and to characterize associations of baseline sociodemographic and clinical variables with apoB and self-identified Hispanic or Latino background. DESIGN, SETTING, AND PARTICIPANTS: The HCHS/SOL was a prospective, population-based cohort study of diverse Hispanic or Latino adults living in the US who were recruited and screened between March 2008 and June 2011. Sampling weights were used to generate a population-based sample of Hispanic or Latino participants aged 18 to 74 years who resided in 4 US metropolitan areas (Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California). ApoB concentration was measured in participants from the HCHS/SOL, and apoB tertiles were compared across demographic groups, including self-identified Hispanic or Latino background. Median percentage continental genetic ancestry (West African, Amerindian, and European) was compared across apoB tertiles. EXPOSURE: ApoB measured in mg/dL from serum or plasma using an immunoturbidimetric assay. MAIN OUTCOMES AND MEASURES: ApoB tertiles were determined, and traditional lipids were evaluated across apoB tertiles. ApoB and traditional lipid measurements were assessed across ASCVD risk categories. Additionally, scatterplots were created to observe correlations between apoB and low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. RESULTS: Overall mean (SD) apoB concentration was 99.8 (0.4) mg/dL, with male participants displaying significantly higher mean levels than female participants (102.4 vs 97.4 mg/dL, respectively). Mean (SD) participant age was 41.1 (0.8) years, and 8376 participants (51.9%) were female. ApoB levels were higher among older age groups. There was significant heterogeneity in mean apoB concentrations across self-identified Hispanic or Latino background groups, ranging from 95.1 mg/dL in Dominican individuals to 104.8 mg/dL in Cuban individuals. The prevalence of elevated apoB (≥130 mg/dL) was greater across higher predicted ASCVD risk categories. Among participants with a 10-year predicted ASCVD risk of 7.5% or higher, 26.5% had an elevated apoB. Median West African ancestry was lower across higher tertiles of apoB. CONCLUSIONS AND RELEVANCE: In this cohort study among participants from the HCHS/SOL, elevated apoB was present in one-quarter of a diverse cohort study of Hispanic or Latino individuals who were at intermediate or high predicted ASCVD risk. Differences in apoB distribution among Hispanic or Latino individuals may have important implications for apoB's use in ASCVD risk assessment.

Adolescent↗

PubMed2006

No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study.

BACKGROUND: Genetic variation in DNA repair may contribute to differences in the susceptibility of several cancers. We evaluated two polymorphisms in the base excision repair pathway (BER) (XRCC1; Arg194Trp and Arg399Gln) and one polymorphism in the double strand DNA repair pathway (XRCC3; Thr241Met) for their association with breast cancer risk. METHODS: The association was analyzed in a nested case control study of 460 breast cancer cases and 324 cancer-free controls within the Iowa Women's Health Cohort. DNA was obtained from blood samples or paraffin embedded tissues (PET) and all samples were genotyped by one of three genotyping platforms-PCR-RFLP, PCR-INVADER, or Sequenom. RESULTS: None of the three polymorphisms studied were significantly associated with breast cancer risk (XRCC1: Arg194Trp (OR=1.21, 95% CI: 0.78-1.88); Arg399Gln (OR=1.20, 95% CI: 0.80-1.79); XRCC3: Thr241Met (OR=1.04, 95% CI: 0.76-1.41). CONCLUSIONS: These results suggest that independently these polymorphisms of XRCC1 and XRCC3 genes do not contribute significantly to the genetic susceptibility of breast cancer.

Aged↗

PubMed2006

Plasma fibrinogen and lung function: the CARDIA Study.

BACKGROUND: We hypothesized that fibrinogen, as a marker of chronic inflammation, is inversely associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) in healthy persons. METHODS: The CARDIA cohort started in 1985 and included black and white men and women, aged 18-30, from the general population. Spirometry testing conducted at years 5 and 10 [FVC, FEV(1), and their ratio (FEV(1)/FVC)] was studied relative to plasma fibrinogen levels measured at year 5 (cross-sectional n = 4,040) and at year 7 (longitudinal n = 3,001), controlling for race, sex, age, height, smoking, asthma, body mass index, physical activity, birth control pill use, and alcohol intake. RESULTS: In cross-sectional analyses, FVC at year 5 was lower by 166 ml (95% confidence interval 116-216 ml) in the highest vs lowest year 5 fibrinogen quartile. At year 10, holding year 5 FVC and change in fibrinogen (year 7-year 5) constant, the difference in FVC between the highest and the lowest year 5 fibrinogen quartiles widened by 67 ml (95% CI 31-103 ml). The corresponding differences for FEV(1) were 166 ml (95% CI 146-253 ml) at year 5 and 45 ml (95% CI 11-80 ml) widening by year 10. The FEV(1)/FVC ratio was unrelated to plasma fibrinogen. CONCLUSION: These findings are consistent with the hypothesis that fibrinogen, possibly as a marker for chronic low-grade inflammation, is associated with modest deterioration of lung function in healthy young adults.

Adolescent↗

PubMed2004

CYP1B1 and CYP19 gene polymorphisms and breast cancer incidence: no association in the ARIC study.

We conducted a nested case control study of 178 incident breast cancer cases and 356 controls in the Atherosclerosis Risk in Communities study. We evaluated the association between breast cancer and Val432Leu polymorphism in the CYP1B1 gene and the tetranucleotide repeats in intron 4 of the CYP19 gene. After adjustment for height, age at menopause, age at menarche, BMI, HRT, and alcohol intake, carriers of the Val/Leu or Val/Val genotype had a 1.45 fold (95% CI 0.85-2.47) greater odds of breast cancer than Leu/Leu carriers. There was no association of the breast cancer with any individual CYP19 allele. Compared to individuals homozygous with the 167 allele, odds ratios were close to 1.0 for the 167 heterozygous genotype and for the remaining tetranucleotide repeats combined. Our data shows no association between breast cancer and the Leu432Val polymorphism of the CYP1B1 gene or the tetranucleotide repeats of the CYP19 gene.

Aromatase↗

PubMed2003

What motivates minorities to participate in research?

This study investigates factors that facilitate and impede minority participation in medical and scientific research studies. Four focus group sessions involving 18 participants aged 18 to 55 years were conducted. Participants, all members of minority groups, were asked a series of questions about why minorities in the Twin Cities area might or might not participate in medical research. Focus group participants indicated they would be willing to participate as research subjects if study findings were shored with them and their primary care physician and if results would benefit their community. Participants cited 4 major barriers to their participation in research: limited knowledge of health studies, mistrust of researchers, limited community involvement in the design of health studies, and use of invasive procedures. Results from this study suggest that researchers seeking to include minority subjects need to use more participatory or community-centered approaches to research.

Adolescent↗