Heterozygous UBR5 variants result in a neurodevelopmental syndrome with developmental delay, autism, and intellectual disability.

E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.

Deep profiling deconstructs features associated with memory CD8 T cell tissue residence.

Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.

Source Data Verification (SDV) quality in clinical research: A scoping review.

Introduction: The value of Source Data Verification (SDV) has been a common theme in the applied Clinical Translational Science literature. Yet, few published assessments of SDV quality exist even though they are needed to design risk-based and reduced monitoring schemes. This review was conducted to identify reports of SDV quality, with a specific focus on accuracy.

A multidonor class of highly glycan-dependent HIV-1 gp120-gp41 interface-targeting broadly neutralizing antibodies.

Antibodies that target the gp120-gp41 interface of the HIV-1 envelope (Env) trimer comprise a commonly elicited category of broadly neutralizing antibodies (bNAbs). Here, we isolate and characterize VRC44, a bNAb lineage with up to 52% neutralization breadth. The cryoelectron microscopy (cryo-EM) structure of antibody VRC44.

An overview of drug-induced sodium channel blockade and changes in cardiac conduction: Implications for drug safety.

The human voltage-gated sodium channel Na1.5 (hNa1.5/SCN5A) plays a critical role in the initiation and propagation of action potentials in cardiac myocytes, and its modulation by various drugs has significant implications for cardiac safety.

A Genetic Polymorphism Underlying Alternative Reproductive Tactics in Eurycea Salamanders.

Alternative reproductive tactics are discrete, intrasexual differences in reproductive behaviour within a population. In some cases, these complex phenotypes are determined by autosomal supergenes or sex chromosomes-both of which exhibit reduced recombination and thus enable the linked inheritance of co-adapted alleles from multiple loci. Most alternative reproductive tactics in amphibians are plastic (and reversible), environmentally determined and lacking morphological differentiation, but a striking exception is found in the two-lined salamander (Eurycea bislineata) species complex.

Pressure Pain Sensitivity is Independent of Structural Pathology in Patients with Subacromial Pain Syndrome: A Cross-Sectional Analysis.

Objective: To compare localized (primary) and widespread (secondary) hyperalgesia using pressure pain threshold (PPT) of patients with normal imaging findings, rotator cuff tear, or other pathologies.

Design: This was a cross-sectional design with data collected at a single time point.

Setting: This study was performed at two large, urban, academic medical centers.

Curation and reporting of pathogenic genome-wide copy-number variants in a prenatal cell-free DNA screen.

Purpose: Advances in fetal fraction amplification in prenatal cell-free DNA screening now allow for high-resolution detection of copy-number variants (CNVs). However, approaches to interpreting CNVs as part of a primary screen are still evolving and require consensus. Here, we present a conservative, patient-centered framework for reporting fetal CNVs.

Fetal fraction amplification within prenatal cfDNA screening enables detection of genome-wide copy-number variants at enhanced resolution.

Purpose: Clinically significant copy-number variants (CNVs) occur in 1% to 2% of pregnancies and are difficult to detect via prenatal cell-free DNA (cfDNA) screening because of the low fraction of fetal-derived cfDNA in maternal plasma. Here, we use fetal fraction amplification (FFA) and improved computational algorithms to enhance the resolution and sensitivity of CNV detection.

Methods: We implemented and characterized the performance of a hidden Markov model that identifies fetal CNVs.

Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris.

Candida auris is a growing concern due to its resistance to antifungal drugs, particularly amphotericin B (AMB), detected in 30 to 60% of clinical isolates. However, the mechanisms of AMB resistance remain poorly understood. Here we investigated 441 in vitro- and in vivo-evolved C.

Phase 2 Trial of Veliparib, Local Irradiation and Temozolomide in Patients with Newly Diagnosed High-Grade Glioma: A Children's Oncology Group Study.

Background: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy.

Methods: We conducted a single-arm, non-randomized phase 2 clinical trial to determine whether treatment with veliparib and radiotherapy, followed by veliparib and temozolomide, improves progression-free survival in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features.

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial.

rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo are WHO-prequalified vaccination regimens against Ebola virus disease (EVD). Challenges associated with measuring long-term clinical protection warrant the evaluation of immune response kinetics after vaccination.

Tarsal coalition resection in children: Is it effective?

Tarsal coalitions in children are a group of disorders that typically present as a rigid flatfoot deformity. Operative treatment generally consists of resecting the coalition alone or resection plus flatfoot reconstructive procedures. The purpose of this study was to evaluate the rate and risk factors for complications, including infection, recurrence, and reoperation, following the surgical management of tarsal coalitions in children.

A novel simulation to prepare maternal caregivers of children diagnosed with a critical congenital heart defect.

Purpose: The purpose of this feasibility study was to determine the effectiveness of an interprofessional led low-fidelity simulation program over three timepoints on maternal caregivers' perceived stress, sense of competence and discharge readiness for care of critical congenital heart disease (CCHD) infants requiring neonatal cardiac surgery.

Design And Methods: The Perceived Stress Scale (PSS) was administered to simulation and non-intervention groups at three timepoints: prenatal period, Cardiac Acute Care Unit (CACU) transfer, and rooming-in. Parental Sense of Competence (PSOC) was measured at timepoint two and three, and Readiness for Hospital Discharge (RDHS) was measured at timepoint three for the simulation group.

Breast ultrasound knobology and the knobology of twinkling for marker detection.

Breast ultrasound utilizes various scanning techniques to acquire optimal images for diagnostic evaluation. During interventional procedures, such as ultrasound-guided biopsies or preoperative localizations, knowledgeable and purposeful scanning adjustments are critical for successfully identifying the targeted mass or biopsy marker or clip. While most ultrasound scanning parameters are similar across different vendors, detailed descriptions specifically addressing the scanning parameters-often referred to as "knobology"- for breast ultrasound is at best limited in the literature.

Persistent Threat Avoidance Following Negative Reinforcement Is Not Associated with Elevated State Anxiety.

Obsessive-compulsive disorder (OCD) is a debilitating illness consisting of obsessions and compulsions. OCD severity and treatment response are correlated with avoidant behaviors thought be performed to alleviate obsession-related anxiety. However, little is known about either the role of avoidance in the development of OCD or the interplay between anxiety states and avoidance behaviors.

Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques.

An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%-77% breadth (geometric mean 50% inhibitory dilution [ID] ∼100) on a 208-strain panel.

Chemical Composition and Crystallization Behavior of Oil and Fat Blends for Spreadable Fat Applications.

To meet the expectations of European consumers, who prioritize agro-environmental factors and local resources, the substitution of fats (palm, coconut, shea) and achieving a balanced fatty acid profile in spreadable fats are gaining more attention. The crystallization at 4 °C of a lipid blend composed of rapeseed oil, anhydrous dairy fats, and emulsifiers was studied using a multi-scale approach (DSC and X-ray diffraction techniques) to understand the emergence of polymorphic structures. Although the addition of PUFA from rapeseed oil reduces the atherogenicity and thrombogenicity indices in the blend, controlling the cooling kinetics influences the shapes (needles and spherulites) and sizes of the crystalline structures (small crystals form at a cooling rate of 1 °C min, while larger crystals form at higher rates of 5 and 10 °C min).

Meta-analysis: The utility of the anterior quadratus lumborum block in abdominal surgery.

Background: Regional anesthesia is routinely used in Enhanced Recovery After Surgery pathways to improve post-operative recovery times. No consensus has been reached on optimal block type. This study reviews the current literature as it pertains to the anterior quadratus lumborum (aQL) block in all abdominal surgeries, as well as its efficacy compared to the transversus abdominis plane (TAP) block.