Publications by authors named "Jagadeesh K"
Cost effectiveness of obstructive sleep apnea therapies: a systematic review and meta-analysis of cost utility studies.
Expert Rev Pharmacoecon Outcomes Res
January 2025
Objectives: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by recurrent episodes of nocturnal breathing cessation resulting from upper airway collapse. Given the absence of a comprehensive review of the cost-effectiveness of OSA treatments, we undertook an extensive systematic review and meta-analysis to calculate the pooled incremental net benefit (INBp).
Methods: A systematic search of PubMed, Embase, Scopus, and Tufts cost-effectiveness analysis registry was conducted.
Successful pregnancy relies directly on the placenta's complex, dynamic, gene-regulatory networks. Disruption of this vast collection of intercellular and intracellular programs leads to pregnancy complications and developmental defects. In the present study, we generated a comprehensive, spatially resolved, multimodal cell census elucidating the molecular architecture of the first trimester human placenta.
View Article and Find Full Text PDFBackground: Regional citrate anticoagulation (RCA) has emerged as a treatment modality that reduces bleeding risk and filter clotting. With initial experience of using RCA with continuous renal replacement therapy (CRRT), we have formulated a working protocol based on published literature.
Objective: The study aimed to evaluate the protocol for routine use of RCA during CRRT requiring anticoagulation and evaluation of filter life.
Article Synopsis
- Single-cell RNA sequencing (scRNA-seq) is a valuable technique for understanding how gene variations affect RNA expression in individual cells, and allele-specific expression (ASE) analysis enhances this understanding by focusing on genetic differences at the RNA level.* -
- The study reveals that using single-nucleus RNA-seq (snRNA-seq) can improve analysis of ASE due to increased intronic reads, which are more likely to contain genetic variants, and demonstrates how experimental factors like RNA source and sequencing depth can influence the effectiveness of these analyses.* -
- The researchers developed new computational tools and compared their ASE methods against traditional expression quantitative trait locus (eQTL) analysis in a Parkinson's disease study, finding that ASE analysis was
Aim And Background: Sarcopenia is a substantial contributor to intensive care unit (ICU)-acquired weakness and is associated with significant short- and long-term outcomes. It can, however, be mitigated by providing appropriate nutrition. Indirect calorimetry (IC) is believed to be the gold standard in determining caloric targets in the dynamic environment of critical illness.
View Article and Find Full Text PDFEssential medicines or drugs are recognized as highly cost-effective components within contemporary healthcare, demonstrating significant potential for improving health outcomes. The provision of essential medicines directly impacts the functioning of healthcare facilities, resulting in financial hardship. This review aims to fill knowledge gaps by examining obstacles hindering access and utilization of essential medicines in India.
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- - Methods for linking regulatory elements to genes using single-cell RNA-seq and ATAC-seq multiome data have varied success due to differences in handling noise and genomic distance, leading to inconsistent results.
- - The new framework, pgBoost, combines multiple linking strategies and incorporates genomic distance, resulting in significantly better identification of SNP-gene relationships, especially over larger distances compared to existing methods.
- - pgBoost demonstrates superior performance in connecting SNPs to genes validated by CRISPR and GWAS data, revealing important links that other methods failed to identify, especially when focused on specific cell types.
Article Synopsis
- Developed a new method called SCENT for mapping enhancer-gene relationships using single-cell data to improve understanding of genetic influences on diseases.
- Successfully applied SCENT to over 120,000 single cells, creating 23 detailed enhancer-gene maps specific to different cell types.
- These maps revealed likely causal genes associated with various diseases, helping to connect genetic variants to their functional roles in human health.
Head and neck cancers (HNCs) present a significant global health burden, especially in India, where oral cavity cancers, notably affecting the tongue, are prevalent. A substantial portion of global HNCs (57.5%) is concentrated in Asia, India contributing with 30%.
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- The study aims to identify important cell types linked to various brain diseases by combining genome-wide association studies (GWAS) with detailed cell data from scATAC-seq and scRNA-seq.
- Researchers analyzed data from 28 brain-related conditions and found key fetal and adult brain cell types associated with those diseases using scATAC-seq and scRNA-seq methodologies.
- Significant findings include specific cell types associated with conditions such as major depressive disorder and schizophrenia, enhancing our understanding of brain diseases and guiding future research.
The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here we mapped expression quantitative trait loci (eQTLs) for classical HLA genes across 1,073 individuals and 1,131,414 single cells from three tissues.
View Article and Find Full Text PDFSpeciation leads to adaptive changes in organ cellular physiology and creates challenges for studying rare cell-type functions that diverge between humans and mice. Rare cystic fibrosis transmembrane conductance regulator (CFTR)-rich pulmonary ionocytes exist throughout the cartilaginous airways of humans, but limited presence and divergent biology in the proximal trachea of mice has prevented the use of traditional transgenic models to elucidate ionocyte functions in the airway. Here we describe the creation and use of conditional genetic ferret models to dissect pulmonary ionocyte biology and function by enabling ionocyte lineage tracing (FOXI1-Cre::ROSA-TG), ionocyte ablation (FOXI1-KO) and ionocyte-specific deletion of CFTR (FOXI1-Cre::CFTR).
View Article and Find Full Text PDFThe human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation, and cancer. While coding variation in genes has been extensively documented, regulatory genetic variation modulating expression levels has not been comprehensively investigated. Here, we mapped expression quantitative trait loci (eQTLs) for classical genes across 1,073 individuals and 1,131,414 single cells from three tissues, using personalized reference genomes to mitigate technical confounding.
View Article and Find Full Text PDFSrinivasan S, Kumar PG, Govil D, Gupta S, Kumar V, Pichamuthu K, . Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S7-S12.
View Article and Find Full Text PDFBoth common and rare genetic variants influence complex traits and common diseases. Genome-wide association studies have identified thousands of common-variant associations, and more recently, large-scale exome sequencing studies have identified rare-variant associations in hundreds of genes. However, rare-variant genetic architecture is not well characterized, and the relationship between common-variant and rare-variant architecture is unclear.
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- - We studied 1,130 E3 ligases and their roles in the inflammatory response of primary dendritic cells using Perturb-seq, revealing their significant impact on different types of dendritic cells and macrophages.
- - E3 ligases and their adaptors work together but interact with different substrate recognition adaptors, influencing various processes in dendritic cell development and function.
- - A deep learning model named comβVAE was developed to predict outcomes of new E3 ligase combinations, showing that the E3 regulatory network is linked to genetic variations and abnormal gene expression in immune-related human diseases.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most treatment refractory and lethal malignancies. The diversity of endothelial cell (EC) lineages in the tumor microenvironment (TME) impacts the efficacy of antineoplastic therapies, which in turn remodel EC states and distributions. Here, we present a single-cell resolution framework of diverse EC lineages in the PDAC TME in the context of neoadjuvant chemotherapy, radiotherapy, and losartan.
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- Genome-wide association studies help identify genes linked to diseases, but the specific cell types involved are often unclear.
- The study introduces sc-linker, a framework that combines single-cell RNA-sequencing data and genetic information to uncover how genes impact diseases through particular cell types.
- Findings revealed important connections between specific cell types and diseases, such as certain neurons in depression and immune cell programs in autoimmune diseases, shedding light on potential therapeutic targets.
Several biobanks, including UK Biobank (UKBB), are generating large-scale sequencing data. An existing method, SAIGE-GENE, performs well when testing variants with minor allele frequency (MAF) ≤ 1%, but inflation is observed in variance component set-based tests when restricting to variants with MAF ≤ 0.1% or 0.
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- Single-cell RNA sequencing (scRNA-seq) has been enhanced by a new method called single-cell disease relevance score (scDRS), which connects genetic risk for diseases to individual cells without needing predefined cell types.
- scDRS was tested on 74 diseases using 1.3 million single-cell profiles from various tissues, with results confirming existing cell-type-disease links while also revealing new subpopulations tied to specific diseases.
- The analysis showed that genes linked to the scDRS score are significantly associated with important drug targets and genetic diseases, suggesting that this technique could help in drug development and understanding disease mechanisms.
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with limited treatment options, and current methods for understanding its molecular characteristics are inadequate.
- Researchers used advanced techniques, including single-nucleus RNA sequencing and digital spatial profiling, to analyze 43 PDAC tumors, revealing key cellular subtypes and their interactions.
- They identified new malignant cell programs linked to poor outcomes and established three distinct multicellular communities, providing insights that could improve patient stratification in clinical trials and guide targeted therapies.
In addition to statin therapy, Ezetimibe, a non-statin lipid-modifying agent, is increasingly used to reduce low-density lipoprotein cholesterol and atherosclerotic cardiovascular disease risk. Literature suggests the clinical effectiveness of Ezetimibe plus statin (EPS) therapy; however, primary evidence on its economic effectiveness is inconsistent. Hence, we pooled incremental net benefit to synthesise the cost-effectiveness of EPS therapy.
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- - Disease-associated SNPs are mainly regulatory and often do not point directly to target genes, complicating the understanding of their effects on diseases.
- - The researchers developed a heritability-based combined S2G strategy (cS2G) that merges results from seven different linking strategies, achieving better performance in predicting gene associations with common diseases compared to individual methods.
- - The cS2G approach was applied to data from the UK Biobank to predict over 5,000 causal SNP-gene-disease connections and found that a small percentage of genes accounted for a significant portion of the SNP-related heritability across diseases.
Objectives: The bone quantity and quality determine the prosthetic success outcome. This research was performed to evaluate the bone density for insertion of pterygoid implants in edentulous and dentulous participants with cone-beam computed tomography (CBCT).
Materials And Methods: CBCT evaluation was done for 66 dentate and edentulous patients for pterygoid implants at the pterygomaxillary region.