Biology subjects

Shah, U. A.

Publications and source records attributed to Shah, U. A..

4 recordsLinked to original sources

bioRxiv2026

Dietary fiber intake associates with improved survival and microbiomecomposition in allogeneic hematopoietic cell transplantation

Diet is linked to changes in gut microbiota and metabolite production with clinical relevance in several disease settings, although these effects remain poorly defined. We performed prospective, real-time diet monitoring (37,929 food items, 3,837 patient days) and longitudinal microbiome and metabolite profiling (1,230 fecal samples) in a clinical cohort of 173 patients undergoing allogeneic hematopoietic cell transplantation. Patients with pre-transplant fiber intake above the cohort average had significantly improved overall survival (p=0.014) and reduced incidence of grades 2-4 acute graft-versus-host disease (GVHD) (p=0.032) post-transplant. Those consuming insoluble fiber had increased microbial diversity, enriched butyrate-producing taxa, and depleted Enterococcus. Those who developed lower gastrointestinal GVHD had reduced fecal butyrate levels. In a GVHD preclinical model, we confirmed that a fiber-enriched diet increased survival, cecal butyrate, and regulatory-to-conventional T cell ratio. Thus, we demonstrated that dietary fiber has clinical significance as a modifiable factor with microbiome-mediated effects.

cancer biology↗

bioRxiv2025

Correlating High-dimensional longitudinal microbial features with time-varying outcomes with FLORAL

Correlating time-dependent patient characteristics and matched microbiome samples can identify biomarkers in longitudinal microbiome studies. Existing approaches typically repeat a pre-specified modeling approach for all taxonomic features, followed by a multiple testing adjustment step for false discovery rate (FDR) control. In this work, we develop an alternative strategy of using log-ratio penalized generalized estimating equations, which directly models the longitudinal patient characteristic of interest as the outcome variable and treats microbial features as high-dimensional compositional covariates. A cross validation procedure is developed for variable selection and model selection among different working correlation structures. In extensive simulations, the proposed method achieved superior sensitivity over the state-of-the-art methods with robustly controlled FDR. In the analyses of correlating longitudinal dietary intake, bloodstream infection status, and microbial features from matched samples of cancer patients, the proposed method effectively identified gut health indicators and clinically relevant microbial markers, showing robust utilities in real-world applications. The method is implemented under the open-source R package FLORAL, which is available at (https://vdblab.github.io/FLORAL/).

bioinformatics↗

bioRxiv2021

GN1, Glucosamine Analog, attenuate the neuronal hyperactivity of c-fos gene in Adjuvant-Induced Arthritis in Rats

The anti-inflammatory and anti-arthritic activity of GN1 (6-hydroxymethyl-3-(1-methylene-allylamino)-tetrahydro-pyran-2,4,5-triol), an analog of glucoseamine was investigated in the adjuvant induced arthritis (AIA) in rats. It was observed that the highly increased hind paw swelling was significantly reduced (p <0.001) with no noticeable retardation of body weight in the GN1 treated arthritic rats as compared to arthritic control rats. The histopathological analysis of isolated rat joints by scaling system classification of different stages appear in arthritic inflammatory lesion development, disclosed the suppressive effect in the inflammation processing in the GN1 treated animals. Different predictive markers such as TNF-, nitric oxide IL-1{beta}, peroxide and glutathione were also determined in the serum samples of the treated and non-treated arthritic rats in order to measure the intensity of inflammation. Our results show that GN-1 treatment in arthritic groups demonstrated marked reduction in c-fos expression. Results also revealed that GN1 significantly reduces the peroxide production (p < 0.002) and both the pro-inflammatory cytokines TNF- (p < 0.015) and IL-1{beta} (p < 0.001) in the arthritic rats receiving this treatment. Although, nitric oxide formation was found to be less than the arthritic control, but this reduction was not significant. The level of glutathione was significantly increased in GN1 treated arthritic rats (p < 0.037). These observations suggest that GN1 may help in reducing the inflammation and have anti-arthritic properties.

pharmacology and toxicology↗

bioRxiv2020

Accelerated single cell seeding in relapsed multiple myeloma

The malignant progression of multiple myeloma is characterized by the seeding of cancer cells in different anatomic sites followed by their clonal expansion. It has been demonstrated that this spatial evolution at varying anatomic sites is characterized by genomic heterogeneity. However, it is unclear whether each anatomic site at relapse reflects the expansion of pre-existing but previously undetected disease or secondary seeding from other sites. Furthermore, genomic evolution over time at spatially distinct sites of disease has not been investigated in a systematic manner. To address this, we interrogated 25 samples, by whole genome sequencing, collected at autopsy from 4 patients with relapsed multiple myeloma and demonstrated that each site had a unique evolutionary trajectory characterized by distinct single and complex structural variants and copy number changes. By analyzing the landscape of mutational signatures at these sites and for an additional set of 125 published whole exomes collected from 51 patients, we demonstrate the profound mutagenic effect of melphalan and platinum in relapsed multiple myeloma. Chemotherapy-related mutagenic processes are known to introduce hundreds of unique mutations in each surviving cancer cell. These mutations can be detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature linked to chemotherapy exposure thus representing a unique single-cell genomic barcode linked to a discrete time window in each patients life. We leveraged this concept to show that multiple myeloma systemic seeding is accelerated at clinical relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high dose melphalan therapy and autologous stem cell transplant.

cancer biology↗