Bi-allelic deleterious variants in SNAPIN, which encodes a retrograde dynein adaptor, cause a prenatal-onset neurodevelopmental disorder.

Fetal brain anomalies identified by prenatal ultrasound and/or magnetic resonance imaging represent a considerable healthcare burden with ∼1-2/1,000 live births. To identify the underlying etiology, trio prenatal exome sequencing or genome sequencing (ES/GS) has emerged as a comprehensive diagnostic paradigm with a reported diagnostic rate up to ∼32%. Here, we report five unrelated families with six affected individuals that presented neuroanatomical, craniofacial, and skeletal anomalies, all harboring rare, bi-allelic deleterious variants in SNAPIN, which encodes SNARE-associated protein.

KIF13B controls ciliary protein content by promoting endocytic retrieval and suppressing release of large extracellular vesicles from cilia.

Dynamic control of ciliary membrane protein content is crucial for the organelle's homeostasis and signaling function and involves removal of ciliary components by intraflagellar transport (IFT) and BBSome-mediated export, endocytic retrieval, and/or extracellular vesicle (EV) shedding. We report that the kinesin-3 motor KIF13B regulates ciliary protein composition and EV shedding in cultured kidney epithelial cells, with effects that vary over time. In early stages of ciliation, Kif13b cells aberrantly accumulate polycystin-2 (PC2) within cilia and release large EVs enriched with CCDC198 and the centriole distal appendage protein CCDC92, which also localizes to the ciliary tip.

Multi-modal image analysis for large-scale cancer tissue studies within IMMUcan.

In cancer research, multiplexed imaging allows detailed characterization of the tumor microenvironment (TME) and its link to patient prognosis. The integrated immunoprofiling of large adaptive cancer patient cohorts (IMMUcan) consortium collects multi-modal imaging data from thousands of patients with cancer to perform broad molecular and cellular spatial profiling. Here, we describe and compare two workflows for multiplexed immunofluorescence (mIF) and imaging mass cytometry (IMC) developed within IMMUcan to enable the generation of standardized data for cancer tissue analysis.

Investigating Learning Effects Through the Implementation of Teledermatology Consultations Among General Practitioners in Germany: Mixed Methods Process Evaluation.

Background: The increasing prevalence of dermatological diseases will pose a growing challenge to the health care system and, in particular, to general practitioners (GPs) as the first point of contact for these patients. In many countries, primary care physicians are supported by teledermatology services.

Objective: The aim of this study was to detect learning effects and gains among GPs through teledermatology consultations (TCs) in daily practice.

Associations between common mental disorders and vaccination readiness against seasonal influenza and Covid-19 of chronically ill adult patients in primary care - a systematic review.

Background: Chronically ill are advised to receive annual vaccinations against Covid-19 and seasonal influenza. Furthermore, chronically ill show an increased prevalence of comorbid common mental disorders (CMDs), like depression, anxiety, and somatoform disorders. With vaccination rates remaining insufficient among these vulnerable patients, prior research assumes an association between CMDs and vaccination readiness.

Cytoskeletal disruption-induced calcium dysregulation drives cell death in anti-IgLON5 disease.

Anti-IgLON5 disease is an autoimmune encephalitis with more chronic presentation including memory decline, sleep disorder, bulbar symptoms and movement disorder. Post-mortem brains of patients with anti-IgLON5 disease show neurodegeneration with tau deposition sparking interest in this 'acquired tauopathy' as a disease model for neurodegeneration, yet mechanisms of neurodegeneration remain unknown. Using a reductionist human iPSC-derived neuron-antibody model, we applied proteomics approach, electrophysiology and live cell imaging.

Inferior Vena Cava Ultrasound to Guide Decongestion in Acute Decompensated Heart Failure: A Randomized Controlled Trial.

Background: Residual congestion at hospital discharge after an episode of acute decompensated heart failure (ADHF) is associated with poor prognosis. There is no consensus on how optimal decongestion should be assessed.

Objectives: This study aims to determine whether decongestive therapy guided by ultrasound measurements of inferior vena cava (IVC) diameters leads to greater reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels from baseline to hospital discharge as compared with decongestion treatment guided by clinical assessment alone.

Calprotectin and neurofilament serum levels correlate with treatment response in myasthenia gravis under intensified therapy-A pilot study.

Objective: New therapeutic options have recently emerged for patients with highly active, acetylcholine receptor antibody-positive (AChR-Ab) generalized myasthenia gravis (gMG), including fast-acting, endplate-protective agents such as complement C5 inhibitors (C5-I) and neonatal Fc receptor inhibitors (FcRn-I). However, objective biomarkers beyond clinical scoring systems are lacking to guide individualized treatment decisions.

Methods: In this exploratory, prospective real-world study, we assessed serum calprotectin (sCLP) and serum neurofilament light chain (sNfL) levels in a total of 22 AChR-Ab gMG patients, who were treatment-naïve for either C5-I or FcRn-I.

Trends in cell collection and apheresis practices: Insights from a cross-sectional study on the use of Spectra Optia in collection and transplant centers.

Background: This study, conducted among collection and transplant centers in France, Germany, Japan, the United Kingdom (UK), and the United States (USA), aimed to better understand current trends, challenges, and future directions in cell collection and apheresis practices, focusing on the Spectra Optia™ Apheresis System.

Methods: This cross-sectional study was conducted from July to November 2023 among facilities using the Spectra Optia™ Apheresis System, which could also be using other comparable cell collection technologies, with expertise in cell collection and therapeutics. Respondents completed an online questionnaire.

EndoChat: Grounded multimodal large language model for endoscopic surgery.

Recently, Multimodal Large Language Models (MLLMs) have demonstrated their immense potential in computer-aided diagnosis and decision-making. In the context of robotic-assisted surgery, MLLMs can serve as effective tools for surgical training and guidance. However, there is still a deficiency of MLLMs specialized for surgical scene understanding in endoscopic procedures.

Skin safety of 233 nm far UV-C ex vivo and in vivo - Pilot study for evaluating different populations and multiple exposures.

Nosocomial infections remain a major healthcare challenge, underlining the demand for antimicrobial technologies. Far UV-C (200-235 nm) has emerged as a safer alternative to traditional 254 nm UV-C for microbial reduction on skin and wounds but also in occupied spaces due to its strong germicidal properties and minimal skin penetration. However, studies on humans remain limited.

Do functional gut parameters predict enteral autonomy and chronic cholestasis in pediatric intestinal failure?

Background & Aims: Parenteral nutrition (PN) dependency in patients with intestinal failure (IF) can lead to complications including liver disease. Therefore, IF management strives to wean patients off PN. In adult IF, chronic cholestasis is predicted by the functional gut parameters citrulline (CIT) and enteroendocrine fibroblast growth factor 19 (FGF19), which inhibits hepatic bile salt synthesis.

Shenqi Wan inhibits cellular senescence to alleviate renal fibrosis by modulating the AQP1/TGF-β1/ITPR1 axis.

Background: Renal fibrosis is a common terminal pathway for various CKDs. Shenqi Wan (SQW) can reduce the development of renal fibrosis and may be associated with aquaporin 1 (AQP1) as discovered previously.

Purpose: The mechanism of SQW in mitigating the progression of renal fibrosis and alleviating CKD was analyzed.

Origins and objectives of computational diversity in sensory populations.

Populations of sensory neurons are not homogeneous. Even neighboring neurons located in the same brain area can process identical stimuli in significantly different ways. Retinal ganglion cells (RGCs) are a prominent example of such heterogeneity - they exhibit diverse properties whose computational role and purpose remain mysterious.

Anomalous hydration of glycolipid ohmline revealed by surface-specific vibrational spectroscopy.

Glycolipids are key structural and functional components of biological membranes, yet their interfacial hydration behavior remains poorly understood. Here, we use vibrational heterodyne-detected sum-frequency generation (HD-SFG) spectroscopy to probe the molecular structure of the air-water interface formed by monolayers of ohmline, a glycolipid bearing a lactose headgroup and carrying no formal charge. Upon electrolyte addition, we observe a striking reorientation of interfacial water and a reversal of the HD-SFG signal, indicative of apparent surface charging by an otherwise neutral headgroup.

Together and beyond: A systematic review on characteristics and efficacy of transdiagnostic psychotherapeutic group-based interventions for children and adolescents.

Transdiagnostic group interventions address the limitations of youth mental health care services, including the disorder-specific nature of existing treatments and the limited capacity of individual psychotherapies. This review synthesizes the 1) characteristics, applications, parental involvement, patient and public involvement (PPI), and 2) data on efficacy, adherence, safety and treatment satisfaction evidence of transdiagnostic group interventions for children and adolescents. Following PRISMA guidelines, a preregistered systematic literature search identified 6845 publications on transdiagnostic in-person group-based interventions for children and adolescents (mean age ≤ 18 years).

CRISPR/Cas9-mediated editing of COQ4 in induced pluripotent stem cells: A model for investigating COQ4-associated human coenzyme Q deficiency.

Pathogenic variants in the gene COQ4 cause primary coenzyme Q deficiency, which is associated with symptoms ranging from early epileptic encephalopathy up to adult-onset ataxia-spasticity spectrum disease. We genetically modified commercially available wild-type iPS cells by using a CRISPR/Cas9 approach to create heterozygous and homozygous isogenic cell lines carrying the disease-causing COQ4 variants c.458C > T, p.

The Plant of Many Scents: Unraveling the Odorant Composition of Selected CBD Hemp Cultivars.

This study presents the first comprehensive sensory-guided investigation into the odor-active compounds of dried hemp ( L.) flowers. Using gas chromatography-olfactometry (GC-O) in combination with aroma extract dilution analysis (AEDA), 52 odor-active compounds were identified across six cannabidiol-rich cultivars.

Health Inequity in People with Cystic Fibrosis: Can We Close the Gap?

Background Although advances in care have improved cystic fibrosis (CF) outcomes in higher-income countries (HICs), the situation remains alarming in lower-income countries (LICs). Methods People with CF (pwCF) enrolled in the European Cystic Fibrosis Society Patient Registry (ECFSPR) and carrying at least one F508del variant allele were evaluated in 2017 and in 2022 for predicted percent forced expiratory volume (ppFEV1), underweight status, and chronic Pseudomonas aeruginosa (Pa) infection, according to the gross national income (GNI) per capita divided into three terciles (low-income countries, LICs; middle-income countries, MICs; and high-income countries, HICs). Survival was evaluated in the periods 2013-2017 and 2018-2022.

The efficacy, safety and predictability of transepithelial versus mechanical or alcohol-assisted photorefractive keratectomy - a meta-analysis.

Topic: The aim of this study was to assess the meta-analysis of the studies comparing transepithelial photorefractive keratectomy (TransPRK) to classical photorefractive keratectomy (PRK) (mechanical or alcohol-assisted).

Clinical Relevance: While PRK is a well-established procedure, TransPRK, a newer, minimally invasive technique may reduce surgery time and improve patient outcomes. Comparing these techniques helps optimize surgical choices.

Mechanotransduction mechanisms in human erythrocytes: Fundamental physiology and clinical significance.

The hallmarks of mechanosensitive ion channels have been observed for half a century in various cell lines, although their mechanisms and molecular identities remained unknown until recently. Identification of the bona fide mammalian mechanosensory Piezo channels resulted in an explosion of research exploring the translation of mechanical cues into biochemical signals and dynamic cell morphology responses. One of the Piezo isoforms - Piezo1 - is integral in the erythrocyte (red blood cell; RBC) membrane.

Catalytic Asymmetric (-)-Carbonyl-Ene Type Cyclizations.

The carbonyl-ene reaction between aldehydes and olefins constitutes a perfectly atom economic approach to homoallylic alcohols with concomitant C-C bond formation. However, the scope of catalytic asymmetric intermolecular versions is currently limited to activated substrates, while of the two intramolecular types only catalytic asymmetric (-)-carbonyl-ene type cyclizations can be considered mature. The corresponding (-)-cyclizations would arguably find equal utility in chemical synthesis but remain underdeveloped.

Participant Satisfaction, Effectiveness, and Safety With a Novel Dual-Applicator Cryolipolysis System: A Prospective, Multicountry Study.

Background: Cryolipolysis is an effective, well-tolerated noninvasive subcutaneous fat reduction treatment.

Objective: Assess participant satisfaction, effectiveness, and safety of a dual-applicator cryolipolysis system that can deliver simultaneous treatments.

Materials And Methods: Adult participants received treatment to the abdomen/flanks (midsection).

Incretin Signaling Neighborhoods and Adverse Drug Reactions.

In light of the success of blockbuster drugs for type 2 diabetes and obesity based on the GLP-1 hormone, drugmakers have concentrated their efforts on developing new and improved variations that address the route of administration, dosing, pathway selectivity, or polypharmacology. While some of these modifications have demonstrated improved efficacy in clinical studies and offered exciting opportunities for treating other diseases, drug-induced shifts to the conformational landscape of target receptors may have consequences for side effects. Our review summarizes advances in the understanding of the biochemistry, pharmacogenomics, and molecular pharmacology of incretins and their cognate receptors.