Sex-Dependent Efficacy of Sphingosine-1-Phosphate Receptor Agonist FTY720 in Mitigating Huntington's Disease.

Huntington's disease (HD) is a debilitating neurodegenerative disorder characterized by severe motor deficits, cognitive decline and psychiatric disturbances. An early and significant morphological hallmark of HD is the activation of astrocytes triggered by mutant huntingtin, leading to the release of inflammatory mediators. Fingolimod (FTY), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist is used to treat multiple sclerosis (MS), a neuroinflammatory disease, and has shown therapeutic promise in other neurological conditions.

Reduced elastin in multiple myeloma niche promotes cell proliferation.

Multiple myeloma (MM) malignant plasma cells accumulate in the bone marrow (BM) where their interactions with the microenvironment promote disease progression and drug resistance. Previously, we have shown that bone marrow mesenchymal stem cells (BM-MSCs) (MM and normal donors- ND) derived extracellular matrix (ECM) affected MM cell lines differentially with a pro-MM effect attributed to MM-MSCs' ECM. Here we studied the composition of BM-MSC's ECM (ND versus MM) with focus on elastin (ELN).

WEE1 Confers Resistance to KRAS Inhibitors in Non-Small Cell Lung Cancer.

KRAS inhibitors sotorasib and adagrasib have been approved for the treatment of KRAS-mutant non-small cell lung cancer (NSCLC). However, the efficacy of single-agent treatments is limited, presumably due to multiple resistance mechanisms. To overcome these therapeutic limitations, combination strategies that potentiate the antitumor efficacy of KRAS inhibitors must be developed.

Research Article: The prediction of the analgesic placebo response is moderated by outward-focused attention: a sham, randomized clinical trial of chronic back pain patients.

The within-subject variability (WSV) of pain-intensity reports has gained attention as a predictor of the placebo response but has demonstrated mixed results. We hypothesized that participants' inward- and outward-directed attention will moderate WSV's prediction of the analgesic placebo response. In this sham randomized clinical trial (protocol number NCT05994118); placebo response was induced in chronic back-pain patients (n=113) through a saline injection plus verbal suggestion.

Simplifying coronary artery disease risk stratification: development and validation of a questionnaire-based alternative comparable to clinical risk tools.

Background: Coronary artery disease (CAD) comprises one of the leading causes of morbidity and mortality both in the European population and globally. All established clinical risk stratification scores and models require blood lipids and physical measurements. The latest reports of the European Commission suggest that attracting health professionals to collect these data can be challenging, both from a logistic and cost perspective, which limits the usefulness of established models and makes them unsuitable for population-wide screening in resource-limited settings, i.

Cryopreserved sperm among patients with Oligoasthenoteratozoospermia.

Objectives: This study investigates sperm utilization and disposal patterns in Oligoasthenoteratozoospermia (OAT) patients undergoing long-term sperm storage. OAT is a major contributor to male infertility. Cryopreservation is a common practice as a "fertility insurance" in case of further deterioration until azoospermia.

Ocular and Systemic Abnormalities in Punctal Agenesis.

Background: Punctal agenesis (PA) is a rare congenital anomaly that can occur in isolation or as part of an underlying syndrome. The benefit of genetic assessment in individuals with PA and clinical features that should prompt molecular workup has not been systematically studied. The aim of this study was to identify ocular and extraocular features associated with PA and determine its association with an underlying syndrome.

Characteristics and Outcomes of Over a Million Patients with Inflammatory Bowel Disease in Seven Countries: Multinational Cohort Study and Open Data Resource.

Background And Aims: Observational healthcare data are an important tool for delineating patients' inflammatory bowel disease (IBD) journey in real-world settings. However, studies that characterize IBD cohorts typically rely on a single resource, apply diverse eligibility criteria, and extract variable sets of attributes, making comparison between cohorts challenging. We aim to longitudinally describe and compare IBD patient cohorts across multiple geographic regions, employing unified data and analysis framework.

Safety of vaginal breech delivery following an unsuccessful external cephalic version: a comparative study.

Objective: To determine whether patients undergoing a trial of labor with a breech presentation following a failed attempt of external cephalic version (ECV) are at increased risk of adverse maternal and neonatal outcomes.

Methods: This retrospective cohort study was conducted at a single university-affiliated medical center. The study group comprised women with singleton pregnancies at term, categorized into three groups: those who underwent a failed external cephalic version (ECV) and subsequently attempted a trial of breech delivery (Breech-failed-ECV group), those who attempted an assisted vaginal breech delivery without a prior ECV attempt (Breech-no-ECV group), and those with vertex presentation following a successful ECV (Vertex-ECV).

Evaluation of enterochromaffin-like cell hyperplasia can help categorize patients with Helicobacter-negative atrophic gastritis.

Objectives: Atrophic gastritis (AG) is characterized by atrophy of gastric glands-in particular, oxyntic glands-in the setting of chronic inflammation; it is often autoimmune. The diagnosis is confirmed by immunohistochemistry (IHC) for gastrin (to confirm biopsy site), and pathologists often use IHC for neuroendocrine markers to evaluate for enterochromaffin-like cell hyperplasia (ECL-H). The utility of neuroendocrine staining is unclear, and we undertook this study to determine whether ECL pattern provided any additional information in cases of Helicobacter-negative AG.

Computational Analysis of MDR1 Variants Predicts Effect on Cancer Cells via their Effect on mRNA Folding.

The P-glycoprotein efflux pump, encoded by the MDR1 gene, is an ATP-driven transporter capable of expelling a diverse array of compounds from cells. Overexpression of this protein is implicated in the multi-drug resistant phenotype observed in various cancers. Numerous studies have attempted to decipher the impact of genetic variants within MDR1 on P-glycoprotein expression, functional activity, and clinical outcomes in cancer patients.

Photobiomodulation Treatment for Second-Degree Burn Treatment-A Double-Blinded Controlled Pilot Trial.

Photobiomodulation (PBM) is a technology that has gained much attention in recent years regarding its potential application for stimulating wound healing, alleviating pain, reducing inflammation, and aiding in the restoration of function. Due to a scarcity of evidence in the literature regarding PBM for the treatment of burns, our objective of this study was to test whether treatment with PBM in hospitalized patients with second-degree burns accelerated recovery. A double-blind controlled study was conducted on nine patients with up to 15% second-degree burns who were hospitalized at Hadassah-Hebrew University Medical Center, Ein Kerem Campus, Jerusalem Israel, between July 2022 and November 2022.

Resolving the bone - optimizing decalcification in spatial transcriptomics and molecular pathology.

Bone tissue poses critical roadblocks for spatial transcriptomics and molecular pathology due to a combination of its dense, calcified matrix and inadequate preservation of biomolecules in conventional decalcification. Decalcification is a complex and nuanced histological process to concomitantly preserve nucleic acids, proteins, and tissue architecture, ensuring molecular integrity for downstream assays. However, commonly used agents like formic and hydrochloric acids, while efficient, can degrade biomolecules to varying extents, complicating assays such as PCR, sequencing, immunohistochemistry, and hybridization.

Exploring Midwives' and Nurse-Midwives' Professional Identity and How Midwifery May Be Best Represented in the Public Realm: A Global Convergent Parallel Mixed-Methods Study.

Aims: With respect to midwives and nurse-midwife populations (1) measure and (2) explore professional identity and (3) explore how the midwifery profession may be best represented in the public realm.

Design: Convergent Parallel Mixed-Methods Design.

Methods: A web-based survey was used to collect data from 860 midwives and nurse-midwives from 102 countries between February and July 2022.

The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.

Isocitrate dehydrogenase (IDH)-mutant gliomas are the most common malignant primary brain tumors in young adults. This condition imposes a substantial burden on patients and their caregivers, marked by neurocognitive deficits and high mortality rates due to tumor progression, coupled with significant morbidity from current treatment modalities. Although surgery, radiation therapy, and chemotherapy improve survival, these treatments can adversely affect cognitive function, quality of life, finances, employment status, and overall independence.

Hope is Not a Strategy: Key Lessons from COVID-19 for Future Health Crises.

Introduction: The COVID-19 pandemic disrupted global economies, social structures, and public health systems. However, Denmark stood out as an exception, maintaining steady life expectancy during this period. This raises important questions about the factors that strengthened the Danish healthcare system and society against the pandemic's challenges.

Toward workforce integration: enhancements in adaptive behaviors and social communication skills among autistic young adults following vocational training course.

Background: Cognitively able autistic adults demonstrate low rates of employment due to social and vocational challenges. The current study aimed to examine changes in various areas among autistic young adults who participated in the 'Roim Rachok' ('Looking Ahead' in Hebrew) Training Course (RRTC). The course prepares young autistic adults for integration into military service as vocational soldiers.

Tradeoffs and synergy between material cycles and greenhouse gas emissions: Opportunities in a rapidly growing housing stock.

Management of building materials' stocks and flows is a major opportunity for circularity and de-carbonization. We examine the relationship between material consumption and associated greenhouse gas (GHG) emissions under different scenarios in Israel, a developed country with an already high population density that expects tremendous growth in its housing stock by 2050. We created scenarios of varying housing unit sizes and additional material efficiency practices: fabrication yield, lifetime extension, material substitution, recycling, and their combination, resulting in 18 scenarios.

New eye tracking metrics system: the value in early diagnosis of autism spectrum disorder.

Background: Eye tracking (ET) is emerging as a promising early and objective screening method for autism spectrum disorders (ASD), but it requires more reliable metrics with enhanced sensitivity and specificity for clinical use.

Methods: This study introduces a suite of novel ET metrics: Area of Interest (AOI) Switch Counts (ASC), Favorable AOI Shifts (FAS) along self-determined pathways, and AOI Vacancy Counts (AVC), applied to toddlers and preschoolers diagnosed with ASD. The correlation between these new ET metrics and Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) scores via linear regression and sensitivity and specificity of the cut-off scores were assessed to predict diagnosis.