Publications by authors named "Merchant M"

Introduction: Wearable health monitors (WHM) offer minimally invasive, ambulatory monitoring of physiological parameters and activity. WHMs are being used increasingly in healthcare but adoption for patients undergoing cancer treatment is limited in part due to a lack of understanding of patient intentions as they receive treatment. The aim of this study explores the patient experience of using WHMs during their cancer pathway, including barriers and enablers of WHM use.

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SARS-CoV-2 variants of concern (VOC) have been associated with increased viral transmission and disease severity. We investigated the mechanisms of pathogenesis caused by variants using a host blood transcriptome profiling approach. We analysed transcriptional signatures of COVID-19 patients comparing those infected with wildtype (wt), alpha, delta or omicron strains seeking insights into infection in Asymptomatic cases.

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  • The study compares 'sawtooth' proton arc therapy (PAT) and static intensity modulated proton therapy (IMPT) in terms of their deliverability at a clinical facility.
  • It evaluates various PAT plans on different types of targets, including abdominal and brain cases, using both step-and-shoot and continuous delivery methods.
  • Results indicate that continuous PAT takes significantly longer in delivery time compared to static IMPT, and while the emulator can model PAT, it shows no evident advantage in beam-on time versus static IMPT, needing further validation.
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Alcohol-associated liver disease (ALD) is a prevalent medical problem with limited effective treatment strategies. Although many biological processes contributing to ALD have been elucidated, a complete understanding of the underlying mechanisms is still lacking. The current study employed a proteomic approach to identify hepatic changes resulting from ethanol (EtOH) consumption and the genetic ablation of the formyl peptide receptor 2 (FPR2), a G-protein coupled receptor known to regulate multiple signaling pathways and biological processes, in a mouse model of ALD.

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  • Alcohol-associated hepatitis (AH) has a high mortality rate and challenges in identifying patients at risk, prompting research into the extracellular matrix as a potential predictor for mortality.
  • Plasma samples from 62 AH patients revealed over 1600 peptide features linked to significant proteins, with notable changes corresponding to disease severity and associated with specific proteases.
  • Three peptides showed strong links to 90-day mortality, leading to a promising noninvasive method for predicting outcomes in AH patients that could enhance current prognostic tools.
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  • Dietary doses of copper, in combination with fructose, impact metabolic dysfunction and contribute to MASLD through the gut-liver axis.
  • A study on rats identified 2847 differentially expressed proteins in the ileum, highlighting specific pathways affected by varying copper levels and fructose.
  • Key findings indicate that different copper-fructose diets uniquely alter pathways related to oxidative stress, arachidonic acid metabolism, and gut barrier integrity, which are crucial for understanding MASLD development.
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Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an effect known as 'FLASH'. This effect has been studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the effect of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used as a biological model to measure DNA damage in response to Very High Energy Electron (VHEE) irradiation at conventional (0.

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The process of end-joining during nonhomologous repair of DNA double-strand breaks (DSBs) after radiation damage is considered. Experimental evidence has revealed that the dynamics of DSB ends exhibit subdiffusive motion rather than simple diffusion with rare directional movement. Traditional models often overlook the rare long-range directed motion.

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Background: Diabetes is the strongest risk factor for cardiovascular disease, and although glycosylated hemoglobin (HbA1c) levels are known to vary by race, no racial and ethnic-specific diagnostic thresholds exist for diabetes in prediction of cardiovascular disease events. The purpose of this study is to determine whether HbA1c thresholds for predicting major adverse cardiovascular events (MACEs) differ among racial and ethnic groups.

Methods And Results: This is a retrospective cohort study of Kaiser Permanente Northern California adult members (n=309 636) with no history of cardiovascular disease who had HbA1c values and race and ethnicity data available between 2014 and 2019.

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Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies.

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Background: Environmental pollutants, including polychlorinated biphenyls (PCBs) have been implicated in the pathogenesis of liver disease. Our group recently demonstrated that PCB126 promoted steatosis, hepatomegaly, and modulated intermediary metabolism in a rodent model of alcohol-associated liver disease (ALD).

Objective: To better understand how PCB126 promoted ALD in our previous model, the current study adopts multiple omics approaches to elucidate potential mechanistic hypotheses.

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  • * 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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  • Uninfected alligators have strong genes that help them fight off infections, while uninfected mice focus more on digestion and energy.
  • When mice are injected with bacteria, they get really sick and can even die.
  • But when alligators are injected with a lot of the same bacteria, they don't get sick and even clear their stomachs quickly, showing they use energy to boost their immune system without getting more tired.
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Wildfires are a global natural phenomenon. In North America, wildfires have not only become more frequent, but also more severe and longer in duration, a trend ascribed to climate change combined with large fuel stores left from modern fire suppression. The intensification of wildfire activity has significant implications for planetary health and public health, as exposure to fine particulate matter (PM) in wildfire smoke is linked to adverse health effects.

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Background: This phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD-L1 inhibition, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer (PSROC).

Methods: Patients with PSROC who had received one or two prior treatment lines were treated with 28-day cycles of cobimetinib 60 mg daily (days 1-21) plus niraparib 200 mg daily (days 1-28) with or without atezolizumab 840 mg (days 1 and 15).

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Gut microbiota function has numerous effects on humans and the diet humans consume has emerged as a pivotal determinant of gut microbiota function. Here, a new concept that gut microbiota can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) trained human gut Akkermansia muciniphila (A.

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The identification of VHL-binding proteolysis targeting chimeras (PROTACs) that potently degrade the BRM protein (also known as SMARCA2) in SW1573 cell-based experiments is described. These molecules exhibit between 10- and 100-fold degradation selectivity for BRM over the closely related paralog protein BRG1 (SMARCA4). They also selectively impair the proliferation of the H1944 "BRG1-mutant" NSCLC cell line, which lacks functional BRG1 protein and is thus highly dependent on BRM for growth, relative to the wild-type Calu6 line.

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Unlabelled: Alcohol-related hepatitis (AH) is plagued with high mortality and difficulty in identifying at-risk patients. The extracellular matrix undergoes significant remodeling during inflammatory liver injury that can be detected in biological fluids and potentially used for mortality prediction. EDTA plasma samples were collected from AH patients (n= 62); Model for End-Stage Liver Disease (MELD) score defined AH severity as moderate (12-20; n=28) and severe (>20; n=34).

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Protein S-acylation is a reversible post-translational modification (PTM). It is present on diverse proteins and has important roles in regulating protein function. Aminolysis with hydroxylamine is widely used in the global identification of the PTM.

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Chimeric antigen receptor T cells (CAR-Ts) have remarkable efficacy in liquid tumors, but limited responses in solid tumors. We conducted a Phase I trial (NCT02107963) of GD2 CAR-Ts (GD2-CAR.OX40.

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Every year substandard and falsified (SF) artemisinin derivative-based antimalarials are responsible for the loss of 450 000 deaths and billions of GBP. The lack of infrastructure and funds to support pharmaceutical quality control in many low-and-middle-income countries contributes to this problem. This work assesses fitness for purpose of voltammetric methods for identification and quantification of artemether in the presence of excipients.

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The induction and repair of DNA double-strand breaks (DSBs) are critical factors in the treatment of cancer by radiotherapy. To investigate the relationship between incident radiation and cell death through DSB induction many in silico models have been developed. These models produce and use custom formats of data, specific to the investigative aims of the researchers, and often focus on particular pairings of damage and repair models.

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To assess skin color change in alligators, we maintained animals in differently lighted environments and also measured skin colors in an ontogenetic series of wild animals. Juvenile alligators maintained in black enclosures exhibited a gradual lightening of skin color when shifted to white enclosures, and these observed changes were reversible. A histological examination of the skins of alligators maintained in dark tanks showed that the dermis exhibited a dense layer of pigmented cells, while samples from the same animals in light environments exhibited a more diffuse pigmented layer.

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  • - The study identifies zotiraciclib (ZTR) as a potent treatment for IDH-mutant gliomas, showing it selectively inhibits their growth through a targeted approach.
  • - ZTR works by suppressing key proteins involved in cell function, leading to mitochondrial dysfunction, reduced NAD+ production, and increased oxidative stress.
  • - These findings have prompted a clinical trial (NCT05588141) to explore the effectiveness of ZTR in treating patients with IDH-mutant gliomas, reflecting a move toward precision medicine.
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