Copy Number Variant Does Not Influence Stroke Severity in 2 C57BL/6J Mouse Models nor in Humans: An Exploratory Study.

Background: Contrary to the common belief, the most commonly used laboratory C57BL/6J mouse inbred strain presents a distinctive genetic and phenotypic variability, and for several traits, the genotype-phenotype link remains still unknown. Recently, we characterized the most important stroke survival factor such as brain collateral plasticity in 2 brain ischemia C57BL/6J mouse models (bilateral common carotid artery stenosis and middle cerebral artery occlusion) and observed a Mendelian-like fashion of inheritance of the posterior communicating artery (PcomA) patency. Interestingly, a copy number variant (CNV) spanning locus was reported to segregate in an analogous Mendelian-like pattern in the C57BL/6J colonies of the Jackson Laboratory.

The role of non-respiratory arousals in residual daytime sleepiness in patients with obstructive sleep apnea treated with positive airway pressure: An analysis of the European Sleep Apnea Database registry.

Study Objectives: To assess the impact of the non-respiratory arousal burden at baseline polysomnography (PSG) on residual daytime sleepiness in positive airway pressure (PAP)-treated obstructive sleep apnea (OSA).

Methods: We included OSA patients from the European Sleep Apnea Database registry with available arousal data who had at least 2 treatment follow-up visits. The primary outcome was the Epworth Sleepiness Scale (ESS) score under PAP.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

REVEAL-CP: Selective Screening of Pediatric Patients for Aromatic L-Amino Acid Decarboxylase Deficiency with a Guthrie Card and Structural Modeling of One Index Case.

The main objective of this prospective, multicenter study (REVEAL-CP) was to test children with cerebral palsy-like signs and symptoms for raised 3--methyldopa (3-OMD) blood levels, a biomarker for aromatic L-amino acid decarboxylase deficiency (AADCd). A secondary objective was to characterize the molecular basis for the defective aromatic L-amino acid decarboxylase (AADC) gene product. Patients were identified in pediatric secondary and tertiary care hospitals through database searches and personal communication.

An atlas of transcription initiation reveals regulatory principles of gene and transposable element expression in early mammalian development.

Transcriptional activation of the embryonic genome (EGA) is a major developmental landmark enabling the embryo to become independent from maternal control. The magnitude and control of transcriptional reprogramming during this event across mammals remains poorly understood. Here, we developed Smart-seq+5' for high sensitivity, full-length transcript coverage and simultaneous capture of 5' transcript information from single cells and single embryos.

CT, MRI, and FDG PET/CT in the Assessment of Lymph Node Involvement in Pediatric Hodgkin Lymphoma: An Expert Consensus Definition by an International Collaboration on Staging Evaluation and Response Criteria Harmonization for Children, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL).

Staging of pediatric Hodgkin lymphoma is currently based on the Ann Arbor classification, incorporating the Cotswold modifications and the Lugano classification. The Cotswold modifications provide guidelines for the use of CT and MRI. The Lugano classification emphasizes the importance of CT and PET/CT in evaluating both Hodgkin lymphoma and non-Hodgkin lymphoma but focuses on adult patients.

Haplotype Phasing of Biallelic WNT10B Variants Using Long-Read Sequencing in Split-Hand/Foot Malformation Syndrome.

Split-hand/foot malformation syndrome (SHFM) is a congenital limb malformation that is both clinically and genetically heterogeneous. Variants in WNT10B are known to cause an autosomal recessive form of SHFM. Here, we report a patient born to unrelated parents who was found to be a compound heterozygote for missense variants in WNT10B: c.

Systematic evaluation of adhesives for implant fixation in multimodal functional brain MRI.

Objective: Invasive multimodal fMRI in rodents is often compromised by susceptibility artifacts from adhesives used to secure cranial implants. We hypothesized that adhesive type, shape, and field strength significantly affect susceptibility artifacts, and systematically evaluated various adhesives.

Materials And Methods: Thirty-one adhesives were applied in constrained/unconstrained geometries and imaged with T2*-weighted EPI at 7.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Prevalence and characteristics of microspurs in patients with spontaneous intracranial hypotension compared to the general population.

Background And Purpose: In patients diagnosed with spontaneous intracranial hypotension (SIH), microspurs are considered the culprit lesion in most ventral dural leaks (type I). The imaging characteristics of discogenic spurs, and their prevalence in the general population has not been reported in the literature.

Materials And Methods: This observational case-control study was conducted comparing the prevalence and characteristics of discogenic microspurs between SIH patients with a type I leak treated at a tertiary hospital between 2013 and 2023 and an age-and sex matched cohort of trauma patients.

Kinetic Oscillation Stimulation for the Preventive Treatment of Chronic Migraine: A Randomized, Double-Blind, Sham-Controlled Trial.

Background And Objectives: The Chordate System administers kinetic oscillation stimulation (K.O.S) into the nasal cavity thereby potentially modulating the activity of trigemino-autonomic reflex.

Extended clinical phenotypes and treatment modalities in 32 JAGN1-deficient patients. A multicenter study by EBMT IEWP.

JAGN1 (Jagunal-homolog1) is a ER-resident transmembrane protein which is part of the early secretory pathway and granulocyte colony-stimulating factor receptor mediated signaling. Autosomal recessively inherited variants in the JAGN1 gene lead to congenital neutropenia, early-onset bacterial infections, aphthosis and skin abscesses due to aberrant differentiation and maturation of neutrophils. In addition, bone metabolism disorders and a syndromic phenotype, including facial features, short stature and neurodevelopmental delay, have been reported in affected patients.

Segmentation of the iliac crest from CT-data for virtual surgical planning of facial reconstruction surgery using deep learning.

Background And Objectives: For the planning of surgical procedures involving the bony reconstruction of the mandible, the autologous iliac crest graft, along with the fibula graft, has become established as a preferred donor region. While computer-assisted planning methods are increasingly gaining importance, the necessary preparation of geometric data based on CT imaging remains largely a manual process. The aim of this work was to develop and test a method for the automated segmentation of the iliac crest for subsequent reconstruction planning.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors.

Analyzing the TotalSegmentator for facial feature removal in head CT scans.

Background: Facial recognition technology in medical imaging, particularly with head scans, poses privacy risks due to identifiable facial features. This study evaluates the use of facial recognition software in identifying facial features from head CT scans and explores a defacing pipeline using TotalSegmentator to reduce re-identification risks while preserving data integrity for research.

Methods: 1404 high-quality renderings from the UCLH EIT Stroke dataset, both with and without defacing were analysed.

Immune correlates of early clearance of Mycobacterium tuberculosis among tuberculosis household contacts in Indonesia.

Some individuals, even when heavily exposed to an infectious tuberculosis patient, do not develop a specific T-cell response as measured by interferon-gamma release assay (IGRA). This could be explained by an IFN-γ-independent adaptive immune response, or an effective innate host response clearing Mycobacterium tuberculosis (Mtb) without adaptive immunity. In heavily exposed Indonesian tuberculosis household contacts (n = 1347), a persistently IGRA negative status was associated with presence of a BCG scar, and - especially among those with a BCG scar - with altered innate immune cells dynamics, higher heterologous (Escherichia coli-induced) proinflammatory cytokine production, and higher inflammatory proteins in the IGRA mitogen tube.

Minimum 10-Year Clinical and Functional Outcomes, and Return to Sport After Sternoclavicular Joint Reconstruction for Sternoclavicular Joint Instability.

Background: Sternoclavicular joint (SCJ) instability can lead to pain, reduced function, and an inability to perform sports and activities of daily living. Reconstruction of the SCJ using hamstring autograft in a figure-of-8 configuration has demonstrated good outcomes at short- and midterm follow-ups, but there is a paucity of literature on long-term outcomes.

Purpose: To evaluate the long-term clinical and functional outcomes after SCJ reconstruction, with a focus on return to sport, instability recurrence, and revision surgery.

AI allows pre-screening of FGFR3 mutational status using routine histology slides of muscle-invasive bladder cancer.

Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10-15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.

Impact of genetic test interpretation on a missense variant in Cohen syndrome.

Introduction: Cohen syndrome (CS) is an early-onset pediatric neurodevelopmental disorder characterized by postnatal microcephaly and intellectual disability. An accurate diagnosis for individuals with CS is crucial, particularly for their caretakers and future prospects. CS is predominantly caused by rare homozygous or compound heterozygous pathogenic variants in the vacuolar protein sorting-associated 13B () gene, which disrupt protein translation and lead to a loss of function (LoF) of the encoded VPS13B protein.

Further evidence of biallelic NAV3 variants associated with recessive neurodevelopmental disorder with dysmorphism, developmental delay, intellectual disability, and behavioral abnormalities.

Neuron navigators (NAVs) are cytoskeleton-associated proteins well known for their role in axonal guidance, neuronal migration, and neurite growth necessary for neurodevelopment. Neuron navigator 3 (NAV3) is one of the three NAV proteins highly expressed in the embryonic and adult brain. However, the role of the NAV3 gene in human disease is not well-studied.

αFAP-specific nanobodies mediate a highly precise retargeting of modified AAV2 capsids thereby enabling specific transduction of tumor tissues.

Due to the refractiveness of tumor tissues to adeno-associated virus (AAV) transduction, AAV vectors are poorly explored for cancer therapy delivery. Here, we aimed to engineer AAVs to target tumors by enabling the specific engagement of fibroblast activation protein (FAP). FAP is a cell surface receptor distinctly upregulated in the reactive tumor stroma, but rarely expressed in healthy tissues.

Modulation of Haemostatic Balance in Combined von Willebrand Disease and Antithrombin Deficiency: A Comprehensive Family Study.

Introduction: Maintaining the balance between procoagulant and anticoagulant factors is essential for effective haemostasis. Emerging evidence suggests a modulation of bleeding tendency by factors in the anticoagulant and fibrinolytic systems.

Aim: This study investigates the clinical and laboratory characteristics of a family with combined von Willebrand disease (VWD) and antithrombin (AT) deficiency.

Sonographic bleb visualisation after PAUL glaucoma implant surgery.

Background/aims: Bleb characteristics in the area around the plate following glaucoma drainage device (GDD) surgery are difficult to evaluate on slit lamp examination. Ultrasound sonography could be used for more detailed visualisation. The aim of this study was to describe bleb configuration after PAUL glaucoma implant (PGI) surgery and evaluate the possible correlation with intraocular pressure (IOP) in order to derive new markers for evaluating GDD function.

Metastasis Detection Using True and Artificial T1-Weighted Postcontrast Images in Brain MRI.

Objectives: Small lesions are the limiting factor for reducing gadolinium-based contrast agents in brain magnetic resonance imaging (MRI). The purpose of this study was to compare the sensitivity and precision in metastasis detection on true contrast-enhanced T1-weighted (T1w) images and artificial images synthesized by a deep learning method using low-dose images.

Materials And Methods: In this prospective, multicenter study (5 centers, 12 scanners), 917 participants underwent brain MRI between October 2021 and March 2023 including T1w low-dose (0.