Heterozygous variants in AP4S1 are not associated with a neurological phenotype.

Biallelic loss-of-function variants in AP4S1 cause childhood-onset hereditary spastic paraplegia. A recent report suggested that heterozygous AP4S1 variants lead to a syndrome of lower limb spasticity and dysregulation of sphincter function. We critically evaluate this claim against clinical observations in 28 heterozygous carriers of the same AP4S1 variant (NM_007077.

extracellular vesicles alleviate alcohol-induced liver injury in mice by regulating gut microbiota and activating the Nrf-2 signaling pathway.

derived extracellular vesicles (LAB-EVs) are nanosized particles secreted from during fermentation, and therefore exist universally in fermented foods such as yogurt, pickles, and fermented beverages. In this study, three LAB-EVs were prepared using a simple scalable method, and then their structures, compositions, and biosafety properties were characterized. The protective properties and potential mechanisms of action of the LAB-EVs against alcoholic liver disease were studied.

Dispersion-based cognitive intra-individual variability in former American football players: Association with traumatic encephalopathy syndrome, repetitive head impacts, and biomarkers.

Exposure to repetitive head impacts (RHI), such as those experienced in American football, is linked to cognitive dysfunction later in life. Traumatic encephalopathy syndrome (TES) is a proposed clinical syndrome thought to be linked to neuropath-ology of chronic traumatic encephalopathy (CTE), a condition associated with RHI from football. Cognitive intra-individual variability (d-CIIV) measures test-score dispersion, indicating cognitive dysfunction.

Young Adult Perspectives on Treatment Engagement and Family Communication During Psychosis.

Background: Fostering positive relationships with mental health professionals and involving family in treatment can reduce untreated psychosis duration and prevent dropout.

Aims: The present study explores the experiences of young adults with psychosis as they engage in mental health treatment and communicate with family caregivers. Describing their lived experiences would inform the clinical engagement process and pathways to clinical outcomes.

Cytologic, histologic, and clinical correlation of minor mutations in pancreatic cysts.

Background: Major mutations (e.g., KRAS, GNAS, TP53, SMAD4) in pancreatic cyst fluid (PCF) are useful for classifying and risk stratifying certain cyst types, particularly in cases with nondiagnostic cytology.

Clinical progress note: Diagnostic approach to dizziness and vertigo.

Dizziness is a common clinical presentation that incurs huge financial costs. It is frequently misdiagnosed due to a wide differential involving both benign (inner ear disease) and serious (stroke) disorders. Traditional frameworks that emphasize symptom quality (dizziness/lightheadedness/vertigo) lack diagnostic utility.

Minimally Invasive Fixed Prosthodontics: A Narrative Review.

Objective: Minimally invasive dentistry is being widely practiced. The center stone is to be as conservative as possible to minimize unnecessary removal of healthy tooth structure. In prosthodontics the patients have generalized and combined nature of diseases.

NumSimEX: A method using EXX hydrogen exchange mass spectrometry to map the energetics of protein folding landscapes.

Hydrogen exchange mass spectrometry (HXMS) is a powerful tool to understand protein folding pathways and energetics. However, HXMS experiments to date have used exchange conditions termed EX1 or EX2 which limit the information that can be gained compared to the more general EXX exchange regime. If EXX behavior could be understood and analyzed, a single HXMS timecourse on an intact protein could fully map its folding landscape without requiring denaturation.

Adjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk.

Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.

Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD.

Background And Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.

Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included.

Likes and Hashtags: Exploring the Potential Relationship Between Social Media use and the Emotional Wellbeing of Oncology Professionals.

Purpose: To explore the potential relationship between social media (SoMe) and burnout or overall wellbeing within the field of oncology.

Design: A cross-sectional study of adult and pediatric oncology professionals conducted using an anonymous electronic survey. The survey was disseminated through the Children's Oncology Group (COG) and the SWOG Cancer Research Network (SWOG) member listservs.

Longitudinal measures of peripheral optical quality in young children.

Purpose: To assess longitudinal changes in optical quality across the periphery (horizontal meridian, 60°) in young children who are at high (HR) or low risk (LR) of developing myopia, as well as a small subgroup of children who developed myopia over a 3-year time frame.

Methods: Aberrations were measured every 6 months in 92 children with functional emmetropia at baseline. Children were classified into HR or LR based on baseline refractive error and parental myopia.

Irregular sleep-wake rhythm disorder: From the pathophysiologic perspective to the treatment.

Irregular sleep-wake rhythm disorder (ISWRD) is an intrinsic circadian rhythm disorder caused by loss of the brain's circadian regulation, through changes of the input and/or output to the suprachiasmatic nucleus (SCN), or of the SCN itself. Although there are limited prevalence data for this rare disease, ISWRD is associated with neurodegenerative disorders, including the Alzheimer disease (AD) and the Parkinson disease (PD), which will become increasingly prevalent in an aging population. It additionally presents in childhood developmental disorders, psychiatric disorders, and traumatic brain injury (TBI).

Psychometric testing of the caring for the caregiver survey for healthcare providers.

Aim: The purpose of this study was to assess the factorial structure and model fit of the Caring for the Caregiver Scale.

Background: Caregiving is an all-encompassing role that results in negative health consequences. Healthcare providers require specific knowledge and clinical skills to support caregivers with health promotion.

Assessing Lung Cancer Screening Eligibility of Lung Cancer Patients in the Boston Lung Cancer Study: An Analysis of 7,186 Lung Cancer Cases.

Background: To evaluate the proportion of lung cancer patients who would have qualified for lung cancer screening under different eligibility criteria in the Boston Lung Cancer Study (BLCS).

Methods: BLCS participants diagnosed with lung cancer from 1992-2024 were identified for analysis. The proportion of patients who would have qualified for screening under the 2021 U.

The Society of Thoracic Surgeons National Intermacs Database Risk Model for Durable Left Ventricular Assist Device Implantation.

Background: Statistical risk models for durable left ventricular assist device (LVAD) implantation inform candidate selection, quality improvement, and evaluation of provider performance. We developed a 90-day mortality risk model utilizing The Society of Thoracic Surgeons National Intermacs Database (STS Intermacs).

Methods: STS Intermacs was queried for primary durable LVAD implants from 1/ 2019 - 9/2023.

Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.

Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.

Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.

A quantitative intracellular peptide binding assay reveals recognition determinants and context dependence of short linear motifs.

Transient protein-protein interactions play key roles in controlling dynamic cellular responses. Many examples involve globular protein domains that bind to peptide sequences known as Short Linear Motifs (SLiMs), which are enriched in intrinsically disordered regions of proteins. Here we describe a novel functional assay for measuring SLiM binding, called Systematic Intracellular Motif Binding Analysis (SIMBA).

Human organotypic colon in vitro microtissue: unveiling a new window into colonic drug disposition.

The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.

Association of Chronic Limb Ischemia Rutherford Classification with Clinical Outcomes Following Lower Extremity Revascularization.

Introduction: The Rutherford Classification for chronic limb-threatening ischemia (CLTI) is used to categorize peripheral artery disease severity through history and physical examination. This study investigated whether higher Rutherford Classification correlates with worse clinical outcomes and could serve as a predictive tool.

Methods: In this prospective single-center study , 252 patients undergoing lower extremity revascularization were followed for three years (2020-2023).