Biomedical subjects

Mitesh Patel

Publications and source records attributed to Mitesh Patel.

8 recordsLinked to original sources

PubMed2026

Reference-Free Microsatellite Instability Detection from Tumor Sequencing Using Intrasample Variability Modeling.

Microsatellite instability (MSI) is a predictive biomarker in several tumor types. However, many next-generation sequencing-based callers require matched normal samples, reference panels, or pretrained models, limiting their portability across assays and sequencing centers. We developed PROMIS (PROfiling of Microsatellite InStability), a tumor-only, reference-free pipeline that uses a discrete mixture model to characterize intrasample repeat-length distributions at predefined microsatellite loci. Locus-level classifications are then aggregated into a continuous MSI score. We benchmarked PROMIS in colorectal (CRC), endometrial (UCEC), and gastric (STAD) cancers from The Cancer Genome Atlas. PROMIS achieved an overall area under the receiver operating characteristic curve (AUC) of 0.995 and cohort-specific AUCs of 1.00 in CRC and stomach adenocarcinoma and 0.999 in uterine corpus endometrial carcinoma, comparable to established tools despite not using matched normals or pretrained models. Subsampling demonstrated robust performance with substantially fewer loci. In silico dilution showed progressively reduced MSI-microsatellite-stable discrimination, with the pooled AUC declining from 0.83 at 10% tumor fraction to 0.53 at 1%. At low tumor fractions, tumor-type-specific baseline microsatellite variability increasingly influenced PROMIS scores. Finally, in prostate and CRC cell-free DNA cohorts, including Illumina TSO500 data and an 18-gene panel, PROMIS yielded MSI scores concordant with orthogonal tissue- and panel-based classifications across the evaluated Illumina-based sequencing contexts. Accordingly, the present validation should be considered limited to Illumina-based sequencing platforms. PROMIS is intended to complement existing genomic profiling workflows by enabling MSI assessment from sequencing data already generated for broader molecular analyses. Prospective clinical validation remains necessary before clinical implementation.

Journal Article↗

PubMed2026

Tumor microbial burden drives immune responses through regulation of Interferon signaling.

Tumor microbes are increasingly recognized for modulating tumor behavior and therapy responses. Intratumoral microbial burden (ITMB) analysis across cancers revealed regulation of immune pathways, and activated mast cells, mostly in colorectal (CRC) and gastric (STAD) cancers. High ITMB CRC leads to interferon regulation and is associated with improved outcomes in advanced disease. Single-cell sequencing revealed induction of interferon-related genes (IRGs) within microbes-containing human CRC. GI-luminal mismatch repair deficiency (MMRd) tumors had higher ITMB than proficient tumors (MMRp). In a rectal MMRd cohort with 100% remission after immune checkpoint blockade (ICB), tumor microbes and microbes-containing mast cells increased. In ICB-sensitive syngeneic murine MMRd tumor models, local tumor microbial depletion, impaired ICB efficacy while downregulating IFN signaling. Forced upregulation of IRGs in ADAR1-deficient cancer cells restored immunotherapy responses during microbial ablation. These data highlight dynamic interplay between ITMB, host defense, and immunogenicity which seems key to determine therapy responses.

Journal Article↗

PubMed2006

Histopathologic and immunohistochemical features of fatal influenza virus infection in children during the 2003-2004 season.

BACKGROUND: The Centers for Disease Control and Prevention enhanced national surveillance for influenza-associated deaths among children because of early reports of pediatric deaths during the 2003-2004 influenza season. METHODS: We studied lung and upper airway specimens from 47 case patients who died who had at least 1 positive result for influenza virus tests using hematoxylin and eosin, special stains for bacteria and fungi, and immunohistochemical (IHC) assays for influenza A and B viruses and other potential viral and bacterial respiratory pathogens. RESULTS: Nineteen (40%) of the 47 patients were <or=2 years old, and 26 (55%) were female. Influenza IHC testing identified type A antigens in 26 patients and type B antigens in 1 patient. Influenza antigens were observed focally in bronchoepithelial cells and mucous glands of trachea, bronchi, and larger bronchioli, showing submucosal mononuclear inflammatory infiltrates. IHC assays were the only confirmatory diagnostic test for 5 patients (11%). Significant life-threatening pathological conditions that could be considered the cause of death were present in 36 patients (77%) and included diffuse alveolar damage (12 cases), extensive secondary pneumonia (11 cases), extensive intraalveolar hemorrhage (10 cases), viral pneumonitis (10 cases), myocarditis (6 cases), and meningoencephalitis (1 case). For 9 patients with bronchopneumonia, a bacterial or fungal etiology was determined with IHC assay (3 Staphylococcus infections, 3 group A streptococci infections, 1 Streptococcus pneumoniae infection, 1 Bordetella pertussis infection, and 1 Aspergillus infection). CONCLUSIONS: IHC assays are useful for the diagnosis of influenza and bacterial pneumonia. This study underscores the importance of performing autopsies to identify the causes of death in patients with influenza infection.

Adolescent↗

PubMed2006

Transmission of lymphocytic choriomeningitis virus by organ transplantation.

BACKGROUND: In December 2003 and April 2005, signs and symptoms suggestive of infection developed in two groups of recipients of solid-organ transplants. Each cluster was investigated because diagnostic evaluations were unrevealing, and in each a common donor was recognized. METHODS: We examined clinical specimens from the two donors and eight recipients, using viral culture, electron microscopy, serologic testing, molecular analysis, and histopathological examination with immunohistochemical staining to identify a cause. Epidemiologic investigations, including interviews, environmental assessments, and medical-record reviews, were performed to characterize clinical courses and to determine the cause of the illnesses. RESULTS: Laboratory testing revealed lymphocytic choriomeningitis virus (LCMV) in all the recipients, with a single, unique strain of LCMV identified in each cluster. In both investigations, LCMV could not be detected in the organ donor. In the 2005 cluster, the donor had had contact in her home with a pet hamster infected with an LCMV strain identical to that detected in the organ recipients; no source of LCMV infection was found in the 2003 cluster. The transplant recipients had abdominal pain, altered mental status, thrombocytopenia, elevated aminotransferase levels, coagulopathy, graft dysfunction, and either fever or leukocytosis within three weeks after transplantation. Diarrhea, peri-incisional rash, renal failure, and seizures were variably present. Seven of the eight recipients died, 9 to 76 days after transplantation. One recipient, who received ribavirin and reduced levels of immunosuppressive therapy, survived. CONCLUSIONS: We document two clusters of LCMV infection transmitted through organ transplantation.

Adult↗

PubMed2006

On the nitrile effect in L-rhamnopyranosylation.

It is shown that the use of 5% acetonitrile or propionitrile in dichloromethane functions to increase the beta-selectivity of a number of L-rhamnopyranosylation reactions conducted by the thioglycoside method with activation by the 1-benzenesulfinyl piperidine/trifluoromethanesulfonic anhydride couple. The use of more significant quantities of acetonitrile or propionitrile results in the formation of complex reaction mixtures containing little coupled product, but from which Ritter-type products can be isolated.

Acetonitriles↗

PubMed2005

Facile dearomatizing radical arylation of furan and thiophene.

In the presence of catalytic diphenyl diselenide, reduced in situ to benzeneselenol, tributyltin hydride and V-70 promote the addition of aryl iodides to furan and thiophene. The adduct radicals are trapped by the selenol to give the 2-aryl-2,3-dihydro and 2-aryl-2,5-dihydro heterocyclic products. When the iodide is an o-iodophenol, a cyclization follows the radical addition and provides bridged bicyclic acetals. [reaction: see text]

Journal Article↗

PubMed2003

Cosmological constraints on bulk neutrinos.

Recent models invoking extra space-like dimensions inhabited by (bulk) neutrinos are shown to have significant cosmological effects if the size of the largest extra dimension is R greater, similar 1 fm. We consider effects on cosmic microwave background anisotropies, big bang nucleosynthesis, deuterium and 6Li photoproduction, diffuse photon backgrounds, and structure formation. The resulting constraints can be stronger than either bulk graviton overproduction constraints or laboratory constraints.

Journal Article↗

PubMed2003

Prevalence of tuberculosis infection among children in slums of Ahmedabad.

Children below 15 yrs. of age without BCG scar were chosen for the tuberculin testing. Total 210 children were tested in 30 selected clusters (7 children in each cluster). Median age of the surveyed children was 6.33. Prevalence of infection in children was found to be 30.4% as 64 children out of 210 showed positive result (had induration > or = 10mm in size). Average ARI in the 0-14 yrs of age group was 5.4%. Tuberculosis is still one of the commonest problems in the urban slums. It is important to evaluate the epidemiology of tuberculosis in the changing face of century.

Adolescent↗