Deciphering the Genetic Architecture of Parkinson's Disease in India.

The genomic landscape of the Indian population, particularly for age-related disorders like Parkinson's disease (PD) remains underrepresented in global research. Genetic variability in PD has been studied predominantly in European populations, offering limited insights into its role within the Indian population. To address this gap, we conducted the first pan-India genomic survey of PD involving 4,806 cases and 6,364 controls, complemented by a meta-analysis integrating summary statistics from a multi-ancestry PD meta-analysis (N=611,485).

Evaluation of pharmacy student empathy toward patients living with Alzheimer's disease and related dementias and caregivers following a dementia simulation.

Alzheimer's Disease and Related Dementias (ADRD) is a leading cause of death in the United States, with national goals in place to improve the quality of care provided to this population. With little available literature on empathy training for pharmacy students in caring for patients living with ADRD, this study outlined the implementation process of an immersive sensory experience, the Virtual Dementia Tour (VDT), into a Doctor of Pharmacy curriculum and evaluated the impact of the experience on pharmacy students' empathy for persons living with ADRD. After completing the VDT, quantitative analysis demonstrated a significant reduction in the pharmacy students' ability to capably complete tasks and relax, and a positive change in their perceptions of the need for improved care for persons living with ADRD.

The Neurodegenerative Disease Knowledge Portal: Propelling Discovery Through the Sharing of Neurodegenerative Disease Genomic Resources.

Although large-scale genetic association studies have proven useful for the delineation of neurodegenerative disease processes, we still lack a full understanding of the pathologic mechanisms of these diseases, resulting in few appropriate treatment options and diagnostic challenges. To mitigate these gaps, the Neurodegenerative Disease Knowledge Portal (NDKP) was created as an open-science initiative with the aim to aggregate, enable analysis, and display all available genomic datasets of neurodegenerative disease, while protecting the integrity and confidentiality of the underlying datasets. The portal contains 218 genomic datasets, including genotyping and sequencing studies, of individuals across 10 different phenotypic groups, including neurologic conditions such as Alzheimer disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson disease.

Pediatric endoscopic ultrasound-guided liver biopsy: 3-year experience.

Objectives: Liver biopsy is the gold standard for diagnosing and staging liver diseases. Endoscopic ultrasound-guided liver biopsy (EUS-LB) has been reported in adults with equivalent or better safety profiles than percutaneous liver biopsies. The aim of this study was to retrospectively assess the safety and efficacy of EUS-LB in pediatric patients.

CARDBiomedBench: A Benchmark for Evaluating Large Language Model Performance in Biomedical Research: A novel question-and-answer benchmark designed to assess Large Language Models' comprehension of biomedical research, piloted on Neurodegenerative Diseases.

Backgrounds: Biomedical research requires sophisticated understanding and reasoning across multiple specializations. While large language models (LLMs) show promise in scientific applications, their capability to safely and accurately support complex biomedical research remains uncertain.

Methods: We present , a novel question-and-answer benchmark for evaluating LLMs in biomedical research.

Large-scale genetic characterization of Parkinson's disease in the African and African admixed populations.

Elucidating the genetic contributions to Parkinson's disease (PD) etiology across diverse ancestries is a critical priority for the development of targeted therapies in a global context. We conducted the largest sequencing characterization of potentially disease-causing, protein-altering and splicing mutations in 710 cases and 11,827 controls from genetically predicted African or African admixed ancestries. We explored copy number variants (CNVs) and runs of homozygosity (ROHs) in prioritized early onset and familial cases.

T1 signal intensity ratio variability based on sampling strategies in the pancreas of children and young adults.

Purpose: T1-weighted signal intensity ratios (SIR) comparing pancreas to spleen (SIRps) or muscle (SIRpm) can semiquantitatively assess T1 signal change associated with pancreatitis. However, there is no standardized methodology for generating these ratios. We set out to determine the impact of MRI sequence as well as region of interest (ROI) location, shape, and size on T1 SIR.

Long-read sequencing of hundreds of diverse brains provides insight into the impact of structural variation on gene expression and DNA methylation.

Structural variants (SVs) drive gene expression in the human brain and are causative of many neurological conditions. However, most existing genetic studies have been based on short-read sequencing methods, which capture fewer than half of the SVs present in any one individual. Long-read sequencing (LRS) enhances our ability to detect disease-associated and functionally relevant structural variants (SVs); however, its application in large-scale genomic studies has been limited by challenges in sample preparation and high costs.

Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis.

Background/objectives: Genetic variants in PRSS1 encoding human cationic trypsinogen are associated with hereditary pancreatitis. The clinically frequent variants exert their pathogenic effect by increasing intrapancreatic trypsin activity, while a distinct subset of variants causes disease via mutation-induced trypsinogen misfolding and endoplasmic reticulum (ER) stress. Here, we report a novel misfolding PRSS1 variant.

Endoscopic cystostomy and biliary sphincterotomy for choledochoceles: A pediatric case series.

Management of choledochoceles (type III choledochal cysts) in children varies. We highlight the potential role of endoscopic management of choledochoceles with cystostomy and biliary sphincterotomy through a series of three successfully treated pediatric patients aged 12-13 at our tertiary center. Patients presented with symptoms including abdominal pain and pancreatitis.

The p.L1795F variant causes Parkinson's disease in the European population.

Pathogenic variants in the gene represent the most common cause of autosomal dominant Parkinson's disease (PD) worldwide. We identified the p.L1795F variant in 14 White/European ancestry PD patients, including two families with multiple affected carriers and seven additional affected individuals with familial PD using genotyping and sequencing data from more than 50,000 individuals through GP2, AMP-PD, PDGENEration, and CENTOGENE.

Liberal Fluid Resuscitation is Associated with Improved Outcomes in Pediatric Acute Pancreatitis.

Objective: To evaluate outcomes of children from an observational cohort registry of index acute pancreatitis (AP) admissions managed with different types and rates of intravenous fluid therapy.

Study Design: Patients with index admission of AP between 2013 and 2023 were included. Those who received >1.

NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations.

Background: Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.

Objective: We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.

Methods: We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples.

Cluster Buster: A Machine Learning Algorithm for Genotyping SNPs from Raw Data.

Genotyping single nucleotide polymorphisms (SNPs) is fundamental to disease research, as researchers seek to establish links between genetic variation and disease. Although significant advances in genome technology have been made with the development of bead-based SNP genotyping and Genome Studio software, some SNPs still fail to be genotyped, resulting in "no-calls" that impede downstream analyses. To recover these genotypes, we introduce Cluster Buster, a genotyping neural network and visual inspection system designed to improve the quality of neurodegenerative disease (NDD) research.

Role of Hyaluronic acid and its chemical derivatives in immunity during homeostasis, cancer and tissue regeneration.

Over the last few decades, scientists have recognized the critical role that various components of the extracellular matrix (ECM) play in maintaining homeostatic immunity. Besides, dysregulation in the synthesis or degradation levels of these components directly impacts the mechanisms of immune response during tissue injury caused by tumor processes or the regeneration of the tissue itself in the event of damage. ECM is a complex network of protein compounds, proteoglycans and glycosaminoglycans (GAGs).

Early Access for Medicines in ITALY: The Case of Ruxolitinib for Patients with Graft-Versus-Host Disease.

After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those with important unfmet needs for whom it may be necessary and ethical to ensure access. The objective of this study was to evaluate the use of ruxolitinib for patients with graft-versus-host disease (GvHD) after EMA approval at the University Hospital of Catania.

Deciphering Drug Resistance: Investigating the Emerging Role of Hyaluronan Metabolism and Signaling and Tumor Extracellular Matrix in Cancer Chemotherapy.

Hyaluronan (HA) has gained significant attention in cancer research for its role in modulating chemoresistance. This review aims to elucidate the mechanisms by which HA contributes to chemoresistance, focusing on its interactions within the tumor microenvironment. HA is abundantly present in the extracellular matrix (ECM) and binds to cell-surface receptors such as CD44 and RHAMM.

Magnetic resonance imaging T1 mapping of the liver, pancreas and spleen in children.

Purpose: To characterize T1 relaxation times of the pancreas, liver, and spleen in children with and without abdominal pathology.

Methods: This retrospective study included pediatric patients (< 18-years-old). T1 mapping was performed with a Modified Look-Locker Inversion Recovery sequence.