Vanzacaftor-tezacaftor-deutivacaftor versus elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials.

Background: The goal of cystic fibrosis transmembrane conductance regulator (CFTR) modulators is to reach normal CFTR function in people with cystic fibrosis. Vanzacaftor-tezacaftor-deutivacaftor restored CFTR function in vitro and in phase 2 trials in participants aged 18 years and older resulting in improvements in CFTR function, as measured by sweat chloride concentrations and lung function as measured by spirometry. We aimed to evaluate the efficacy and safety of vanzacaftor-tezacaftor-deutivacaftor compared with standard of care elexacaftor-tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years and older.

The Potential Of Autologous Patient-Derived Circulating Extracellular Vesicles To Improve Drug Delivery In Rheumatoid Arthritis.

Recognizing the need for innovative therapeutic approaches in the management of autoimmune diseases , our current investigation explores the potential of autologous extracellular vesicles (EVs), derived from blood of rheumatoid arthritis (RA) patients, to serve as therapeutic vectors to improve drug delivery. We found that circulating EVs derived from arthritic mice (Collagen-induced arthritis model) express the joint/synovia homing receptor, αVβ3 integrin. Importantly, both autologous labelled EVs, derived from blood of arthritic mice (Collagen antibody-induced arthritis model) and healthy mice-derived EVs, exhibit targeted migration toward inflamed synovia without infiltrating healthy joints, as demonstrated by an in-vivo imaging system.

Communications needs of family caregivers of geriatric unit residents at end-of-life.

Background And Objective: There is a dearth of literature regarding the communication needs of family caregivers of institutionalized older adults and the degree to which these needs are fulfilled. This study aimed to clarify those needs regarding communication with staff in geriatric facilities during older non-communicative residents' end-of-life.

Research Design And Methods: Personal interviews were conducted with 135 family caregivers from two geriatric medical centers and two nursing homes in Israel.

The impact of body mass index on surgical complications in minimally invasive hysterectomy for uterine fibroids.

Research Question: We aimed to assess the impact of Body Mass Index (BMI) on 30-day postoperative complications in patients undergoing minimally invasive hysterectomy (MIH) for fibroids.

Design: Using data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database (2012-2020), we analyzed major and minor 30-day postoperative complications, stratified by BMI, in patients with uterine fibroids who underwent MIH. Complications were stratified according to the Clavien-Dindo classification.

Migrasome formation is initiated preferentially in tubular junctions by membrane tension.

Migrasomes, the vesicle-like membrane micro-structures, arise on the retraction fibers (RFs), the branched nano-tubules pulled out of cell plasma membranes during cell migration and shaped by membrane tension. Migrasomes form in two steps: a local RF bulging is followed by a protein-dependent stabilization of the emerging spherical bulge. Here we addressed theoretically and experimentally the previously unexplored mechanism of bulging of membrane tubular systems.

The impact of spillover and crossover effects of job stressors on pregnancy rates in couples undergoing in vitro fertilization treatments.

Purpose: Studies have shown mixed findings regarding the impact of stress on the success of fertility treatments. To the best of our knowledge, stress in the context of the workplace has not been investigated to date in relation to the success of fertility treatments. This research investigates the impact of work-related stress and emotional exhaustion experienced by both partners on in vitro fertilization (IVF) treatment outcomes.

FOUR QUESTIONS ABOUT ATRIAL FIBRILLATION IN CARDIAC AMYLOIDOSIS. WHY IS THIS ARRHYTHMIA DIFFERENT FROM ALL OTHER ARRHYTHMIAS?

AF is a common arrhythmia in cardiomyopathy, particularly when congestive heart failure is present. The neurohormonal activation in congestive heart failure may trigger fibrotic and other changes in the left atrium and the atrial stretch associated with heart failure may induce further atrial pathology and/ or directly trigger AF (8). By the time that patients with AF develop extensive fibrosis, the arrhythmia has been shown to be associated with a greater difficulty in maintaining sinus rhythm despite attempted ablation procedures.

Patients with severe mental illness in the general emergency department: Clinical characteristics, quality of care and challenges.

Background: Morbidity and mortality rates are notably higher among individuals with severe mental illnesses (SMI). People with SMI often have lower access to healthcare services, and the medical care they receive is known to be suboptimal. Consequently, treatment in an acute care setting rather than a community setting is more common.

Do we Need to Perform Bone Marrow Examination in all Subjects Suspected of MDS? Evaluation and Validation of Non-Invasive (Web-Based) Diagnostic Algorithm.

Background: Bone marrow examination (BME) is the gold standard of diagnosing myelodysplastic syndromes (MDS).

Problems: it is invasive, painful, causing possible bleeding, inaccurate (aspirate hemodilution), and subjective (inter-observer interpretation discordance). We developed non-invasive diagnostic tools: A logistic regression formula [LeukRes 2018], then a web algorithm using 10 variables (age, gender, Hb, MCV, WBC, ANC, monocytes, PLT, glucose, creatinine) to diagnose/exclude MDS [BldAdv 2021].

Land Use Change Consistently Reduces α- But Not β- and γ-Diversity of Bees.

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e.

De-escalation of surgical and radiation treatment in elderly luminal breast cancer patients, single institution report and review of the evidence.

Background: De-intensification of anti-cancer therapy without significantly affecting outcomes is an important goal. Omission of axillary surgery or breast radiation is considered a reasonable option in elderly patients with early-stage breast cancer and good prognostic factors. Data on avoidance of both axillary surgery and radiation therapy (RT) is scarce and inconclusive.

Key shifts in frontoparietal network activity in Parkinson's disease.

We aimed to study the effect of Parkinson's disease (PD) and motor-cognitive load on the interplay between activation level and spatial complexity. To that end, 68 PD patients and 30 controls underwent electroencephalography (EEG) recording while executing visual single- and dual- Go/No-go tasks. The EEG underwent source localization, followed by parcellation of the neural activity into 116 regions of interest.

Radiological markers of CSF α-synuclein aggregation in Parkinson's disease patients.

Alpha-synuclein (αS) aggregation is a widely regarded hallmark of Parkinson's disease (PD) and can be detected through synuclein amplification assays (SAA). This study investigated the association between cerebrospinal fluid (CSF) radiological measures in 41 PD patients (14 iPD, 14 GBA1-PD, 13 LRRK2-PD) and 14 age-and-sex-matched healthy controls. Quantitative measures including striatal binding ratios (SBR), whole-brain and deep gray matter volumes, neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter (WM) diffusion-tensor imaging (DTI) were calculated.

Multi-Planar Cervical Motion Dataset: IMU Measurements and Goniometer.

This data descriptor presents a comprehensive and replicable dataset and method for calculating the cervical range of motion (CROM) utilizing quaternion-based orientation analysis from Delsys inertial measurement unit (IMU) sensors. This study was conducted with 14 participants and analyzed 504 cervical movements in the Sagittal, Frontal and Horizontal planes. Validated against a Universal Goniometer and tested for reliability and reproducibility.

Transoral approach for hilo-parenchymal submandibular stones: outcomes and predictors of success.

Objective: To evaluate the efficacy and safety of transoral surgical management for complex submandibular gland (SMG) stones.

Study Design: A retrospective cohort study of 240 patients treated for sialolithiasis between 2015 and 2018, focusing on 57 cases of SMG stones that underwent stone removal procedures. Treatment methods, success rates, and complications were analyzed using Kaplan-Meier analysis, Cox proportional hazards regression, and multiple logistic regression.

The role of non-invasive stress testing in the diagnosis of coronary microvascular disease.

Background: Angina with non-obstructive coronary artery disease (ANOCA) is commonly observed in patients with stable angina undergoing coronary angiography. Current guidelines recommend non-invasive stress testing as the first step in diagnosing coronary microvascular disease (CMD). This study aims to evaluate the diagnostic value of non-invasive stress testing in patients invasively diagnosed with CMD.

Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.

Novel bimanual haptic simulator for epidural loss-of-resistance detection: a pilot study assessing movement strategies and performance across anesthesiologist experience levels.

Background: Correct identification of the epidural space requires extensive training for technical proficiency. This study explores a novel bimanual haptic simulator designed for the precise insertion of an epidural needle based on loss-of-resistance (LOR) detection, providing realistic dual-hand force feedback.

Methods: The simulator, equipped with two haptic devices connected to a Tuohy needle and an LOR syringe, was designed to simulate the tissues' resistive forces felt by the user during the procedure, offer anatomical variability and record detailed performance metrics for personalized feedback.

Disentangling Sources of Momentum Fluctuations in Xe+Xe and Pb+Pb Collisions with the ATLAS Detector.

High-energy nuclear collisions create a quark-gluon plasma, whose initial condition and subsequent expansion vary from event to event, impacting the distribution of the eventwise average transverse momentum [P([p_{T}])]. Disentangling the contributions from fluctuations in the nuclear overlap size (geometrical component) and other sources at a fixed size (intrinsic component) remains a challenge. This problem is addressed by measuring the mean, variance, and skewness of P([p_{T}]) in ^{208}Pb+^{208}Pb and ^{129}Xe+^{129}Xe collisions at sqrt[s_{NN}]=5.

Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.

Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.

Small bowel duplication cyst in the pediatric population-when to operate?

Introduction: AIM: The aim of the study is to determine the optimal timing for surgery in patients with small bowel duplications.

Methods: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with small bowel duplications from 2013 until 2024 in a single tertiary medical center, was performed. Patients' demographics, duplication size and location, pathological results, and clinical outcomes were collected.

Development of a reference standard to assign bacterial versus viral infection etiology using an all-inclusive methodology for comparison of novel diagnostic tool performance.

Background: Diagnostic test evaluation requires a reference standard. We describe an approach for creating a reference standard for acute infection using unrestricted adjudication and apply it to compare biomarker tools.

Methods: Adults and children with suspected acute infection enrolled in three prospective studies at emergency departments and urgent cares were included.

Eosinopenia in bronchiectasis: A novel biomarker for morbidity and mortality.

Background: The paradigm of bronchiectasis is shifting away from its exclusive characterization as a neutrophilic condition. Patients with bronchiectasis and high eosinophil levels have been found to have a specific phenotype, but the clinical effect of eosinopenia remains unclear.

Method: A retrospective, single-center, observational study was conducted at a tertiary medical center.