Publications by authors named "Shesh Rai"

Background: Socioeconomic status and pollution exposure have been described as risk factors for poor survival in patients with non-small cell lung cancer (NSCLC). However, the relationship between these factors is complex and inadequately studied. This study aimed to evaluate the relationship between environmental and social factors and their impact on survival after NSCLC resection.

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Dysregulated miRNA expression contributes to development of arsenic-induced cutaneous squamous cell carcinoma (cSCC). hsa-miR-186 (miR-186) is overexpressed in arsenical cSCC tissues as well as in preclinical cell line model of arsenical cSCC. Simultaneous miR-186 overexpression and chronic inorganic trivalent arsenite (iAs; 100 nM) exposure transformed human HaCaT cell line preferentially over miR-186 overexpression or iAs exposure alone.

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The Green Heart Project is a controlled, community-based clinical trial to evaluate the effects of increasing greenery on community health. The study was initiated in 2018 in a low-to-middle-income residential area of nearly 30,000 racially diverse residents in Louisville, KY. Community engagement was maintained throughout the project, with feedback integrated into its design and implementation.

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Mutations in protein tyrosine phosphatase non-receptor type 11 ( ) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of mutations, we utilized single-cell DNA sequencing and identified that mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonly mutations. The co-driver role of mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice.

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Research conducted on homogenous populations can lead to biased and misleading findings, impeding the development of effective interventions and treatments for diverse populations. Low participation among minority groups further leads to disparities in access to innovative cancer care and treatment outcomes associated with trial participation. To better understand cancer patients' attitudes and willingness to participate in clinical trials, solid tumor patients attending their clinic visits were invited to complete a survey.

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Carnosine is an endogenous dipeptide that buffers intracellular pH and quenches toxic products of lipid peroxidation. Used as a dietary supplement, it also supports exercise endurance. However, the accumulation and distribution of carnosine after supplementation has not been rigorously evaluated.

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Gene regulation is crucial for cellular function and homeostasis. It involves diverse mechanisms controlling the production of specific gene products and contributing to tissue-specific variations in gene expression. The dysregulation of genes leads to disease, emphasizing the need to understand these mechanisms.

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Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants previously associated with elevated liver enzymes in human cohorts and steatotic liver disease in animal models. We aimed to evaluate the associations between PFAS exposures, and liver enzymes and vibration controlled transient elastography (VCTE) biomarkers of metabolic dysfunction associated steatotic liver disease (MASLD) in adult National Health and Nutrition Examination Survey (NHANES) 2017 to 2018. VCTE was determined by FibroScan.

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Phase IV clinical trials are designed to monitor long-term side effects of medical treatment. For instance, childhood cancer survivors treated with chest radiation and/or anthracycline are often at risk of developing cardiotoxicity during their adulthood. Often the primary focus of a study could be on estimating the cumulative incidence of a particular outcome of interest such as cardiotoxicity.

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Article Synopsis
  • Molecular phylogenetic research focuses on analyzing coding sequences of genes and amino acid sequences to identify mutations and their impact on evolution.
  • Specific amino acids have quantifiable characteristics that can convert these sequences into numerical representations, allowing for a more comprehensive analysis of evolutionary processes beyond just counting mismatches.
  • Advanced analytical techniques, including bivariate wavelet analysis and matrix comparisons, improve the understanding of protein evolution and help resolve discrepancies in taxonomic trees, with automation available in R for further applications.
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Introduction: Stereotactic body radiation therapy (SBRT) is a treatment for patients with early-stage non-small cell lung cancer (ES-NSCLC). Surveillance guidelines vary after treatment. While patients are more likely to locally recur within 2 years of treatment, there remains a paucity of data on the benefit of frequent and long-term surveillance.

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Article Synopsis
  • - The study explores breath analysis as a quick, non-invasive method for detecting COVID-19 by identifying carbonyl compounds related to inflammation and oxidative stress.
  • - A total of 321 participants, including 141 COVID-19 positive individuals (55 during the alpha wave and 86 during the delta wave), were tested using advanced techniques like ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS).
  • - Results showed high accuracy in detecting COVID-19 patients: 98.4% for the alpha wave and 88.3% for the delta wave, suggesting breath analysis could be a viable tool for rapid COVID-19 screening and future respiratory virus outbreaks.
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Introduction: Previous investigations have reported that individuals living in greener neighborhoods have better cardiovascular health. It is unclear whether the effects reported at large geographic scales persist when examined at an intra-neighborhood level. The effects of greenness have not been thoroughly examined using high-resolution metrics of greenness exposure, and how they vary with spatial scales of assessment or participant characteristics.

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Background: Underrepresented minority patients with surgical malignancies experience disparities in outcomes. The impact of provider-based factors, including communication, trust, and cultural competency, on outcomes is not well understood. This study examines modifiable provider-based barriers to care experienced by patients with surgical malignancies.

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Objective(s): To assess the influence of treatment package time (TPT) on overall survival (OS) and event free survival (EFS) in oral cavity cancer (OCC) patients treated with surgery and adjuvant radiation therapy (RT) with or without concurrent chemotherapy (CHT).

Materials/methods: 354 adult OCC patients treated at a single, high-volume center between 2012-2022 with various pathologic risk features were included. TPT was defined as days from surgery to RT completion.

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Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics.

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Article Synopsis
  • * A study on male mice revealed that exposure to Ar1260 led to liver damage and changes in RNA modifications 34 weeks later, affecting numerous liver proteins and their functions.
  • * Specifically, this exposure impacted proteins related to glutathione metabolism and selenoproteins, resulting in increased and decreased levels of various selenoproteins and metals in the liver.
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Article Synopsis
  • - Biological processes, including cancer development, involve both stochastic (random) and deterministic (predictable) changes, but current studies focus mainly on the latter, often overlooking the role of randomness.
  • - This research investigates how chronic arsenic exposure influences gene expression, identifying which genes are affected stochastically versus deterministically during cancer progression.
  • - Findings reveal that chronic arsenic exposure reduces variability in gene expression, leading to a more uniform cell population and highlighting the significance of both types of changes in cancer development and tumor diversity.
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Background: Acute myeloid leukemia (AML) is the malignant proliferation of immature myeloid cells characterized by a block in differentiation. As such, novel therapeutic strategies to promote the differentiation of immature myeloid cells have been successful in AML, although these agents are targeted to a specific mutation that is only present in a subset of AML patients. In the current study, we show that targeting the epigenetic modifier enhancer of zeste homolog 2 (EZH2) can induce the differentiation of immature blast cells into a more mature myeloid phenotype and promote survival in AML murine models.

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Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y.

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Foot-and-mouth disease (FMD) is a severe contagious viral disease of cloven-hoofed animals. In India, a vaccination-based official FMD control programme was started, which got expanded progressively to cover entire country in 2019. The serological tests are used to determine non-structural protein based sero-prevalence rates for properly implementing and assessing the control programme.

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The Green Heart Project is a community-based trial to evaluate the effects of increasing greenery on urban environment and community health. The study was initiated in 2018 in a low-to-middle-income mixed-race residential area of nearly 28,000 residents in Louisville, KY. The 4 square mile area was surveyed for land use, population characteristics, and greenness, and assigned to 8 paired clusters of demographically- and environmentally matched "target" (T) and adjacent "control" (C), clusters.

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Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling of the cytoskeleton, which is a tightly regulated process coordinated by Rho-specific guanine nucleotide exchange factors (GEFs) and the Rho family of small GTPases. Rho-associated kinase (ROCK) promotes assembly of focal adhesions and actin stress fibers by regulating cytoskeleton organization.

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Objectives: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.

Design: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.

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