Chirag J Patel

Targeting gut microbiota has shown promise to prevent experimental acute kidney injury (AKI). However, this has not been studied in relation to accelerating recovery and preventing fibrosis. Here, we found that modifying gut microbiota with an antibiotic administered after severe ischemic kidney injury in mice, particularly with amoxicillin, accelerated recovery. These indices of recovery included increased glomerular filtration rate, diminution of kidney fibrosis, and reduction of kidney profibrotic gene expression...

BACKGROUND: Risk for COVID-19 positivity and hospitalization due to diverse environmental and sociodemographic factors may change as the pandemic progresses. METHODS: We investigated the association of 360 exposures sampled before COVID-19 outcomes for participants in the UK Biobank, including 9268 and 38,837 non-overlapping participants, sampled at July 17, 2020 and February 2, 2021, respectively. The 360 exposures included clinical biomarkers (e.g., BMI), health indicators (e...

Monkeypox virus (MPXV) was confirmed in May 2022 and designated a global health emergency by WHO in July 2022. MPX virions are big, enclosed, brick-shaped, and contain a linear, double-stranded DNA genome as well as enzymes. MPXV particles bind to the host cell membrane via a variety of viral-host protein interactions. As a result, the wrapped structure is a potential therapeutic target. DeepRepurpose, an artificial intelligence-based compound-viral proteins interaction framework, was used via a transfer learning setting to prioritize a set of FDA approved and investigational drugs which can potentially inhibit MPXV viral proteins...

BACKGROUND: Post-treatment Lyme disease syndrome (PTLDS) is used to describe Lyme disease patients who have the infection cleared by antibiotic but then experienced persisting symptoms of pain, fatigue, or cognitive impairment. Currently, little is known about the cause or epidemiology of PTLDS. METHODS: We conducted a data-driven study with a large nationwide administrative dataset, which consists of more than 98 billion billing and 1.4 billion prescription records between 2008 and 2016, to identify unique aspects of PTLDS that could have diagnostic and etiologic values...

PURPOSE: To understand the benefits of COVID-19 vaccination (Covishield, Covaxin) on clinical features and outcome of COVID-19 during the third wave in India. MATERIALS AND METHODS: The primary study aim was to describe the clinical profile and outcome of COVID-19 regarding their vaccination and to identify risk factors for disease progression in vaccinated patients. This was a prospective observational multicentric study of COVID-19 attended by Infectious Disease physicians during January 15, 2022 to February 15, 2022...

BACKGROUND: Traditional management of olfactory neuroblastoma (ONB) includes margin-negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be overtreating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes. METHODS: This retrospective, multi-institutional cohort study examined clinical covariates associated with occult intracranial involvement...

INTRODUCTION: Contrast-enhanced MRI is routinely performed as part of preoperative work-up for patients with Colorectal Cancer Liver Metastases (CRLM). Radiomic biomarkers depicting the characteristics of CRLMs in MRI have been associated with overall survival (OS) of patients, but the reproducibility and clinical applicability of these biomarkers are limited due to the variations in MRI protocols between hospitals. METHODS: In this work, we propose a generalizable radiomic model for predicting OS of CRLM patients who received preoperative chemotherapy and delayed-phase contrast enhanced (DPCE) MRIs prior to hepatic resection...

Physical activity improves quality of life and protects against age-related diseases. With age, physical activity tends to decrease, increasing vulnerability to disease in the elderly. In the following, we trained a neural network to predict age from 115,456 one week-long 100Hz wrist accelerometer recordings from the UK Biobank (mean absolute error = 3.7±0.2 years), using a variety of data structures to capture the complexity of real-world activity. We achieved this performance by preprocessing the raw frequency data as 2,271 scalar features, 113 time series, and four images...

The National Health and Nutrition Examination Survey (NHANES) provides data on the health and environmental exposure of the non-institutionalized US population. Such data have considerable potential to understand how the environment and behaviors impact human health. These data are also currently leveraged to answer public health questions such as prevalence of disease. However, these data need to first be processed before new insights can be derived through large-scale analyses. NHANES data are stored across hundreds of files with multiple inconsistencies...

OBJECTIVE: Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity. RESEARCH DESIGN AND METHODS: Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T2D and BMI and 2) area-level socioeconomic risk (educational attainment) measures. The primary analysis included 26,737 participants of European genetic ancestry in MGBB with replication in UKB (N = 223,843), as well as in participants of non-European ancestry (MGBB N = 3,468; UKB N = 7,459)...

We studied pathogenic gene mutations and tumor mutation burden (TMB) in visible low grade dysplastic lesions in patients with inflammatory bowel disease (IBD). The dysplastic lesions with histologically normal mucosa in the background (group 1) were compared with dysplastic lesions occurring either in a background of chronic active colitis (group 2) or associated with synchronous carcinomas regardless of the status of the background mucosa (group 3). The TMB in group 3 was consistently higher in comparison to the group 1 and group 2 lesions, although the difference was not statistically significant...

T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming and regulation. By using [U-13 C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8+ T cell effector differentiation and function. Mechanistically, GOT1 enhances proliferation by maintaining intracellular redox balance and serine-mediated purine nucleotide biosynthesis. Further, GOT1 promotes the glycolytic programming and cytotoxic function of cytotoxic T lymphocytes via posttranslational regulation of HIF protein, potentially by regulating the levels of α-ketoglutarate...

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes...

The mechanistic target of rapamycin is an essential regulator of T cell metabolism and differentiation. In this study, we demonstrate that serum- and glucocorticoid-regulated kinase 1 (SGK1), a downstream node of mechanistic target of rapamycin complex 2 signaling, represses memory CD8+ T cell differentiation. During acute infections, murine SGK1-deficient CD8+ T cells adopt an early memory precursor phenotype leading to more long-lived memory T cells. Thus, SGK1-deficient CD8+ T cells demonstrate an enhanced recall capacity in response to reinfection and can readily reject tumors...

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is significantly impacting human lives, overburdening the healthcare system and weakening global economies. Plant-derived natural compounds are being largely tested for their efficacy against COVID-19 targets to combat SARS-CoV-2 infection. The SARS-CoV-2 Main protease (Mpro ) is considered an appealing target because of its role in replication in host cells. We curated a set of 7809 natural compounds by combining the collections of five databases viz Dr Duke's Phytochemical and Ethnobotanical database, IMPPAT, PhytoHub, AromaDb and Zinc...

BACKGROUND: Proper advance care planning (ACP) documentation both improves patient care and is increasingly seen as a marker of high quality by governmental payers. The transition of most medical documentation to electronic health records (EHR) allows for ACP documents to be rapidly disseminated across diverse ambulatory practice settings. At the same time, the complexity and heterogeneity of the EHR, as well as the multiple potential storage locations for documentation, may lead to confusion and inaccessibility...

The mechanistic target of rapamycin is an essential regulator of T cell metabolism and differentiation. In this study, we demonstrate that serum- and glucocorticoid-regulated kinase 1 (SGK1), a downstream node of mechanistic target of rapamycin complex 2 signaling, represses memory CD8+ T cell differentiation. During acute infections, murine SGK1-deficient CD8+ T cells adopt an early memory precursor phenotype leading to more long-lived memory T cells. Thus, SGK1-deficient CD8+ T cells demonstrate an enhanced recall capacity in response to reinfection and can readily reject tumors...

BACKGROUND: Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. METHODS: Here we phenotyped 28 individuals from 17 families with pathogenic FOXP2 -only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German...

Exposing cancer cells to alternating electric fields of 100-300 kHz frequency and 1-4 V/cm strength has been shown to significantly reduce cancer growth in cell culture and in human patients. This form of anti-cancer therapy is more commonly referred to as tumor treating fields (TTFields), a novel treatment modality that has been approved by the U.S. Food and Drug Administration for use in patients with glioblastoma and malignant pleural mesothelioma. Pivotal trials in other solid organ cancer trials are underway...

The choices of participants in nephrology research genomics studies about receiving additional findings (AFs) are unclear as are participant factors that might influence those choices. Methods : Participant choices and factors potentially impacting decisions about AFs were examined in an Australian study applying research genomic testing following uninformative diagnostic genetic testing for suspected monogenic kidney disease. Results : 93% of participants (195/210) chose to receive potential AFs. There were no statistically significant differences between those consenting to receive AFs or not in terms of gender ( p = 0...