A green bioanalytical spectrofluorimetric approach for estimation of Avapritinib anti-tumor drug; application to quality control and clinical studies.

Aims: Gastrointestinal stromal tumors (GISTs) account for about 80% of the mesenchymal tumors of the GI tract. About 5000-6000 patients are diagnosed in the United States (US) alone, and up to 14.5 cases per million discovered in Europe annually.

Patient centered medication treatment for opioid use disorder in rural Vermont: a qualitative study.

Background: Opioid-related fatal overdoses are occurring at historically high levels and increasing each year. Accessible social and financial support are imperative to the initiation and success of treatment for Opioid Use Disorder (OUD). Medications for Opioid Use Disorder (MOUD) offer effective treatment but there are many more people with untreated OUD than receiving evidence-based medication.

Impact of driver licensing renewal policies on older driver crash involvement and injury rates in 13 states, 2000-2019.

Background: Motor vehicle crashes are the second leading cause of injury death among adults aged 65 and older in the U.S., second only to falls.

Eating disorders in minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the UK: a scoping review.

Background: Historically, eating disorder (ED) research has largely focused on White girls and women, with minority ethnic populations underrepresented. Most research exploring EDs in minority ethnic populations has been conducted in the United States (US). The aim of this scoping review, the first of its kind, was to systematically examine research on disordered eating and EDs among minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the United Kingdom (UK), four countries with shared sociocultural and healthcare characteristics.

The interaction of tPA with NMDAR1 drives neuroinflammation and neurodegeneration in α-synuclein-mediated neurotoxicity.

The thrombolytic protease tissue plasminogen activator (tPA) is expressed in the CNS, where it regulates diverse functions including neuronal plasticity, neuroinflammation, and blood-brain-barrier integrity. However, its role in different brain regions such as the substantia nigra (SN) is largely unexplored. In this study, we characterize tPA expression, activity, and localization in the SN using a combination of retrograde tracing and β-galactosidase tPA reporter mice.

Phosphorylation of Bok at Ser-8 blocks its ability to suppress IPR-mediated calcium mobilization.

Background: Bok is a poorly characterized Bcl-2 protein family member with roles yet to be clearly defined. It is clear, however, that Bok binds strongly to inositol 1,4,5-trisphosphate (IP) receptors (IPRs), which govern the mobilization of Ca from the endoplasmic reticulum, a signaling pathway required for many cellular processes. Also known is that Bok has a highly conserved phosphorylation site for cAMP-dependent protein kinase at serine-8 (Ser-8).

Alternative 3' UTR polyadenylation is disrupted in the rNLS8 mouse model of ALS/FTLD.

Recent research has highlighted widespread dysregulation of alternative polyadenylation in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Here, we identify significant disruptions to 3` UTR polyadenylation in the ALS/FTLD-TDP mouse model rNLS8 that correlate with changes in gene expression and protein levels through the re-analysis of published RNA sequencing and proteomic data. A subset of these changes are shared with TDP-43 knock-down mice suggesting depletion of endogenous mouse TDP-43 is a contributor to polyadenylation dysfunction in rNLS8 mice.

Correlation of sarcopenia with progression of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease: a study from two cohorts in China and the United States.

Objective: The objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18-59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis.

Methods: The study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis.

The association between neutrophil to high-density lipoprotein cholesterol ratio and gallstones: a cross-sectional study.

Objective: Several studies have discussed the relationship between cholesterol and gallstones, and high-density lipoprotein cholesterol (HDL-C) as a representative of this has been addressed in various diseases. The metric neutrophil to high-density lipoprotein cholesterol ratio (NHR) derived from HDL-C has attracted much attention. The purpose of this article is to examine the relationship between NHR and gallstones in a population of American adults.

Rapid identification of bacterial select agents using loop-mediated isothermal amplification.

Background: Point of need diagnostics provide efficient testing capability for remote or austere locations, decreasing the time to answer by minimizing travel or sample transport requirements. Loop-mediated isothermal amplification (LAMP) is an appealing technology for point-of-need diagnostics due to its rapid analysis time and minimal instrumentation requirements.

Methods: Here, we designed and optimized nine LAMP assays that are sensitive and specific to targeted bacterial select agents including Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella spp.

Blood absolute lymphocyte count and trajectory are important in understanding severe COVID-19.

Background: Low blood absolute lymphocyte count (ALC) may predict severe COVID-19 outcomes. Knowledge gaps remain regarding the relationship of ALC trajectory with clinical outcomes and factors associated with lymphopenia.

Methods: Our post hoc analysis of the Therapeutics for Inpatients with COVID-19 platform trial utilized proportional hazards models to assess relationships between Day (D) 0 lymphopenia (ALC < 0.

Dynamic X-ray Microtomography vs. Laser-Doppler Vibrometry: A Comparative Study.

Purpose: There are challenges in understanding the biomechanics of the human middle ear, and established methods for studying this system show significant limitations. In this study, we evaluate a novel dynamic imaging technique based on synchrotron X-ray microtomography designed to assess the biomechanical properties of the human middle ear by comparing it to laser-Doppler vibrometry (LDV).

Methods: We examined three fresh-frozen temporal bones (TB), two donated by white males and one by a Black female, using dynamic synchrotron-based X-ray microtomography for 256 and 512 Hz, stimulated at 110 dB and 120 dB sound pressure level (SPL).

2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-Induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

A multi-site feasibility study of a stepped-care telehealth intervention for depression and anxiety in post-treatment cancer survivors at community cancer clinics (WF-30917CD).

Purpose: This feasibility study estimated accrual, retention, adherence, and summarized preliminary efficacy data from a stepped-care telehealth intervention for cancer survivors with moderate or severe levels of anxiety and/or depressive symptoms.

Methods: Participants were randomized to intervention or enhanced usual care (stratified by symptom severity). In the intervention group, those with moderate symptoms received a cognitive-behavioral therapy (CBT) workbook/6 bi-weekly check-in calls (low intensity) and severe symptoms received the workbook/12 weekly therapy sessions (high intensity).

In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

Social Vulnerability and Biological Aging in New York City: An Electronic Health Records-Based Study.

Chronological age is not an accurate predictor of morbidity and mortality risk, as individuals' aging processes are diverse. Phenotypic age acceleration (PhenoAgeAccel) is a validated biological age measure incorporating chronological age and biomarkers from blood samples commonly used in clinical practice that can better reflect aging-related morbidity and mortality risk. The heterogeneity of age-related decline is not random, as environmental exposures can promote or impede healthy aging.

Multiplex genome editing eliminates lactate production without impacting growth rate in mammalian cells.

The Warburg effect, which describes the fermentation of glucose to lactate even in the presence of oxygen, is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production in cells for bioprocessing have failed as lactate dehydrogenase is essential for cell growth. Here, we effectively eliminate lactate production in Chinese hamster ovary and in the human embryonic kidney cell line HEK293 by simultaneous knockout of lactate dehydrogenases and pyruvate dehydrogenase kinases, thereby removing a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA.

Telehealth Modality Usage by US Physicians in 2022.

Background: The growth of telehealth care delivery during the COVID-19 pandemic highlighted its potential to enhance access to care and improve patient outcomes. As the healthcare landscape moves toward a new equilibrium in care delivery, few studies have examined physician usage of specific telehealth modalities.

Objective: To understand telehealth usage differences among modalities and across subgroups of physicians.

Trends in Co-morbid Dementia and Chronic Kidney Disease.

Background: Little is known about the population of Medicare beneficiaries with both chronic kidney disease (CKD) and Alzheimer's disease and related dementias (ADRD).

Methods: Using data from Medicare fee-for-service (FFS) beneficiaries aged 65 and over identified through 2011-2019 Master Beneficiary Summary File (MBSF), we estimated the size, growth, and racial-ethnic characteristics of the ADRD and CKD populations. Individuals were classified as having ADRD and CKD based on CMS Chronic Conditions Data Warehouse (CCW) indicators in the MBSF Chronic Conditions file.

A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.

Background: Based on preclinical data showing addition of CDK4/6 inhibitors to gemcitabine was synergistic, ribociclib was evaluated in combination with gemcitabine to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT).

Methods: In this single arm multicohort phase I trial, we evaluated the safety and efficacy of ribociclib plus gemcitabine in patients with advanced solid tumors. Patients received gemcitabine intravenously on days 1 and 8 followed by ribociclib days 8-14, with treatment repeated every 3 weeks.

Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.

Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.

Stable centromere association of the yeast histone variant Cse4 requires its essential N-terminal domain.

Chromosome segregation relies on kinetochores that assemble on specialized centromeric chromatin containing a histone H3 variant. In budding yeast, a single centromeric nucleosome containing Cse4 assembles at a sequence-defined 125 bp centromere. Yeast centromeric sequences are poor templates for nucleosome formation in vitro, suggesting the existence of mechanisms that specifically stabilize Cse4 nucleosomes in vivo.

Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping.

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls.

Co-targeting of metabolism using dietary and pharmacologic approaches reduces breast cancer metastatic burden.

Patients with metastatic breast cancer face reduced quality of life and increased mortality rates, necessitating more effective anti-cancer strategies. Building on previous research that identified metastatic-niche-specific metabolic vulnerabilities, we investigated how a ketogenic diet enhances estrogen receptor (ER)-positive liver metastatic breast cancer's response to Fulvestrant (Fulv) treatment. Using in vitro cell lines and in vivo xenograft metastasis mouse models, we examined the molecular mechanisms of combining ER targeting with a ketogenic diet.

Motor cortical neuronal hyperexcitability associated with α-synuclein aggregation.

ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.