Cell type-dependent role of transforming growth factor-β signaling on postnatal neural stem cell proliferation and migration.

Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents. While it is known transforming growth factor-β signaling is important in embryonic neurogenesis, its role in postnatal neurogenesis remains unclear. In this study, to define the precise role of transforming growth factor-β signaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo, we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-β signaling in neural stem cells in (mGFAPcre-ALK5fl/fl-Ai9) or immature neuroblasts in (DCXcreERT2-ALK5fl/fl-Ai9).

Bone Health and Linear Growth in Children with Familial Hypoparathyroidism Treated with Human Parathyroid Hormone 1-34.

Context: Our study explores the impact of human PTH 1-34 injections (PTH therapy) on growth, areal bone mineral density (BMD), and bone quality (measured by trabecular bone score, TBS) in hypoparathyroidism due to autoimmune polyendocrine syndrome type 1 (APS-1) or an activating variant of the calcium sensing receptor (CaR).

Objective: To assess associations of 1) age and PTH therapy duration with age-standardized Z-scores for height (HAZ), BMD (BMD-Z), and TBS (TBS-Z) in CaR or APS-1, and 2) APS-1 disease severity with BMD-Z and TBS-Z.

Methods: This secondary analysis pooled linear growth and lumbar spine (LS) DXA data from studies of hypoparathyroidism with mean baseline age of 13.

Revised Process for ACNS Guidelines Development.

The development of clinical practice guidelines is an evolving field. In response to the need for consistent, evidence-based medical practice, the American Clinical Neurophysiology Society identified the need to update the Society's guideline development process. The American Clinical Neurophysiology Society Guidelines Committee created an action plan with the goal of improving transparency and rigor for future guidelines and bringing existing guidelines to current standards.

Multivalvular vs single-valve infective endocarditis: a systematic review and meta-analysis.

Background: Infective endocarditis is characterized by the colonization of heart valves by virulent microorganisms. It commonly manifests as involvement of a single heart valve -single-valve infective endocarditis (SIE), while in some patients, two or more heart valves are concomitantly infected -multivalvular infective endocarditis (MIE). The risk of complications and prognosis of MIE as opposed to SIE are unknown.

Modelling a pathological GSX2 variant that selectively alters DNA binding reveals hypomorphic mouse basal ganglia and hindbrain defects.

Gsx2 is a homeodomain transcription factor critical for development of the ventral telencephalon and hindbrain of the mouse. Loss of Gsx2 function results in severe basal ganglia dysgenesis as well as defects in the nucleus tractus solitarius (nTS) of the hindbrain together with respiratory failure at birth. De Mori et al.

Increased serum GM-CSF at diagnosis of biliary atresia is associated with improved biliary drainage.

Background: The immune heterogeneity of biliary atresia (BA) presents a challenge for development of prognostic biomarkers. This study aimed to identify early immune signatures associated with biliary drainage after Kasai Portoenterostomy (KPE).

Methods: Serum samples, liver slides, and clinical data were obtained from patients enrolled in the NIDDK-supported Childhood Liver Disease Research Network.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Anaphylaxis definition, overview, and clinical support tool: 2024 consensus report.

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network (NIAID/FAAN) anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization (WAO) published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Mealtime challenges from the perspectives of adolescents with anorexia nervosa and atypical anorexia nervosa and their caregivers enrolled in family-based treatment.

Objective: This study identified mealtime challenges and emotions experienced during challenges among adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) and their caregivers during the early phase of family-based treatment (FBT).

Method: Caregivers with high expressed emotion (i.e.

Language Mapping With rTMS in Healthy Pediatric Patients.

Purpose: Repetitive transcranial magnetic stimulation (rTMS) is a potentially effective, noninvasive tool for language mapping. However, there is a paucity of data in pediatric patients. In this study, we aimed to map language sites in healthy pediatric participants with navigated rTMS.

The Fas-mediated apoptosis assay: From concept to clinical application.

Abnormal lymphocyte homeostasis underly several Inborn Errors of Immunity (IEoI). In vitro assessment of lymphocyte homeostasis is achieved by specific apoptosis assays reflective of specific homeostasis programs and pathways that are mediated through specific proteins. This review discusses those programs, pathways and proteins and describes the development and use of the in vitro Fas-mediated apoptosis assay, as it relates to the IEoI Autoimmune Lymphoproliferative Syndrome (ALPS) and describes other disorders of lymphocyte homeostasis in the context of other forms of in vitro apoptosis assessment.

Mitigating PM Induced Myocardial Metal Deposition Through Sodium Thiosulfate Resulted in Reduction of Cardiotoxicity and Physiological Recovery From Ischemia-Reperfusion via Mitochondrial Preservation.

The cardiovascular risks linked to PM include calcification in both vasculature and myocardial tissues, leading to structural changes and functional decline. Through the selection of a clinically proven endogenous agent, sodium thiosulfate (STS), capable of addressing PM related cardiac abnormalities, we not only address the absence of effective solutions to mitigate PM toxicity, but also provide evidence for the repurposing potential of STS in ameliorating PM induced cardiac damage. Female Wistar rats were exposed to PM (250 μg/m) for 3 h daily for 21 days.

Environment scan of generative AI infrastructure for clinical and translational science.

This study reports a comprehensive environmental scan of the generative AI (GenAI) infrastructure in the national network for clinical and translational science across 36 institutions supported by the CTSA Program led by the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH) at the United States. Key findings indicate a diverse range of institutional strategies, with most organizations in the experimental phase of GenAI deployment. The results underscore the need for a more coordinated approach to GenAI governance, emphasizing collaboration among senior leaders, clinicians, information technology staff, and researchers.

Total Anomalous Pulmonary Venous Return, Marfan Syndrome, and Severe Combined Immunodeficiency: A Lethal Combination?

The authors present an exceptionally rare case of a newborn in whom total anomalous pulmonary venous return (TAPVR) had been diagnosed prenatally and in whom genetic testing after neonatal cardiac repair confirmed a missense variant of the gene consistent with Marfan syndrome as well as a gene mutation associated with severe combined immunodeficiency. To the authors' knowledge, this is the first reported case with this unique combination. Neonatal TAPVR repair was undertaken with a good postoperative outcome and survival until the last follow-up.

Investigation of the participation of the TRPV1 receptor in the irritant effect of dithranol in mice.

Dithranol is one of the most effective topical medications for treating plaque psoriasis. However, its clinical use is limited by irritative adverse reactions to the skin, such as oedema, erythema, and pruritus, caused by poorly understood mechanisms. Because TRPV1 activation mediates skin irritation caused by several drugs, we conducted blind and randomised experiments in male and female C57BL/6 mice to elucidate the role of TRPV1 in dithranol-induced irritation.

Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial.

Background: Lerodalcibep, a small binding anti-PCSK9 protein (adnectin), showed effective LDL cholesterol reduction in heterozygous familial hypercholesterolaemia. We aimed to assess the safety and efficacy of lerodalcibep and evolocumab in a globally diverse homozygous familial hypercholesterolaemia population.

Methods: This phase 3, randomised, open-label, crossover, non-inferiority study consisted of two 24-week treatment periods separated by an 8-week washout.

Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial.

Importance: In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective: To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Anterior communicating aneurysm clipping: How I do it.

Up to 40% of intracranial aneurysms arise from the anterior cerebral artery and anterior communicating artery (ACA-ACoA) complex. The vast variability of vessel anomalies and the surrounding critical structures correlate with severe morbidity and mortality rates in case of rupture. In the era of cutting-edge advantages of endovascular procedures, surgical expertise is reducing.

Integrated care for mental health in epilepsy: A systematic review and meta-synthesis by the International League Against Epilepsy Integrated Mental Health Care Pathways Task Force.

Mental health (MH) comorbidities are prevalent among people with epilepsy (PWE), but many experience challenges accessing care. To address this, suggestions have been made to integrate MH care into epilepsy care settings, yet the current approaches, benefits, and implementation determinants to MH care integration are unclear. This review aims to synthesize existing integrated MH care models for PWE to inform the development and planning of future initiatives.

Dynamically changing extracellular matrix stiffness drives Schwann cell phenotype.

Schwann cells (SCs) hold key roles in axonal function and maintenance in the peripheral nervous system (PNS) and are a critical component to the regeneration process following trauma. Following PNS trauma, SCs respond to both physical and chemical signals to modify phenotype and assist in the regeneration of damaged axons and extracellular matrix (ECM). There is currently a lack of knowledge regarding the SC response to dynamic, temporal changes in the ECM brought on by swelling and the development of scar tissue as part of the body's wound-healing process.

Dual Biologic Therapy Induces Remission in Refractory Crohn's Disease With Vedolizumab and Ustekinumab.

Background: Despite advancements in the therapeutic armamentarium for Crohn's disease (CD), biologic and small molecule monotherapies are associated with sub-optimal response and remission rates. Utilizing dual biologic therapy (DBT) holds the potential to increase efficacy in the treatment of refractory or partially responsive CD. Evidence pertaining to this strategy remains limited.

Liver fibrosis classification on trichrome histology slides using weakly supervised learning in children and young adults.

Background: Traditional liver fibrosis staging via percutaneous biopsy suffers from sampling bias and variable inter-pathologist agreement, highlighting the need for more objective techniques. Deep learning models for disease staging from medical images have shown potential to decrease diagnostic variability, with recent weakly supervised learning strategies showing promising results even with limited manual annotation.

Purpose: To study the clustering-constrained attention multiple instance learning (CLAM) approach for staging liver fibrosis on trichrome whole slide images (WSIs) of children and young adults.

Mechanical Thrombectomy in Africa: A Challenging Future.

Mechanical thrombectomy (MT) has revolutionized the management of proximal large vessel occlusions (LVOs) in patients with acute ischemic stroke (AIS), improving long-term outcomes compared to standard treatments. However, despite its success in high-income countries, the widespread implementation of MT in Africa remains limited. With Africa experiencing one of the highest stroke burdens globally, this study examines the barriers impeding the adoption of MT in the region.

Challenges of Engaging Primary Care Providers in Specialized Telementoring Education About Sickle Cell Disease for Sickle Cell Specialists: Results from the Sickle Cell Disease Training and Mentoring Program for Primary Care Providers (STAMP) Project ECHO.

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting approximately 100,000 individuals in the U.S. A lack of knowledgeable providers, particularly for adult patients, has led to a significant number of adults without access to high-quality care.