Negative valence in Obsessive-Compulsive Disorder: A worldwide mega-analysis of task-based functional neuroimaging data of the ENIGMA-OCD consortium.

Objective: Obsessive-compulsive disorder (OCD) is associated with altered brain function related to processing of negative emotions. To investigate neural correlates of negative valence in OCD, we pooled fMRI data of 633 individuals with OCD and 453 healthy controls from 16 studies using different negatively-valenced tasks across the ENIGMA-OCD Working-Group.

Methods: Participant data were processed uniformly using HALFpipe, to extract voxelwise participant-level statistical images of one common first-level contrast: negative vs.

Complement activation as a biomarker for platelet-activating antibodies in heparin-induced thrombocytopenia.

Background: Immunoglobulin G antibodies (Abs) to platelet factor 4 (PF4) complexed to heparin (PF4/H) commonly occur after H exposure but cause life-threatening complications of H-induced thrombocytopenia (HIT) in only a few patients. Presently, only platelet activation assays reliably distinguish anti-PF4/H Abs that cause disease (HIT Abs) from those likely to be asymptomatic (AAbs).

Objectives: Recent studies indicate that complement activation is an important serologic property of HIT Abs and is essential for IgG Fc receptor IIA-mediated cellular activation.

Advances in Engineering Myeloid Cells for Cell Therapy Applications.

Myeloid cells, including macrophages, neutrophils, dendritic cells, and myeloid-derived suppressor cells, play crucial roles in the innate immune system, contributing to immune defense, tissue homeostasis, and organ development. They have tremendous potential as therapeutic tools for diseases such as cancer and autoimmune disorders, but harnessing cell engineering strategies to enhance potency and expand applications is challenging. Recent advancements in stem cell research have made it possible to differentiate human embryonic stem cells and induce pluripotent stem cells into various cell types, including myeloid cells, offering a promising new approach to generate myeloid cells for cell therapy.

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.

The Leaky Preexposure Prophylaxis Cascade: Barriers and Facilitators to Preexposure Prophylaxis Uptake and Adherence Among Youth Experiencing Homelessness in the US South, a Mixed Methods Study.

Adherence to preexposure prophylaxis (PrEP) is lower among high-risk populations, including youth experiencing homelessness (YEH). This study determined the feasibility of urine PrEP adherence biomarker testing and examined the barriers and facilitators to PrEP uptake and adherence among YEH. YEH were recruited from a randomized control trial conducted in a large urban setting in southern United States.

Black Carbon Air Pollution and Incident Mortality among the Advance-Aged Adults in China: A Prospective Cohort Study.

Background: We aimed to assess associations between black carbon (BC) and non-accidental mortality among advance-aged adults in China.

Methods: We conducted a prospective cohort study in 22 provinces of Chinese Longitudinal Healthy Longevity Survey. We calculated concentrations of 3-year average BC, fine particulate matter (PM2.

Developing and disseminating an electronic penicillin allergy de-labelling tool using the model for improvement framework.

Background: Many clinicians feel uncomfortable with de-labelling penicillin allergies despite ample safety data. Point of care tools effectively support providers with de-labelling. This study's objective was to increase the number of providers intending to pursue a penicillin oral challenge by 15% by February 2023.

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.

Background: Activated Phosphoinositide 3-Kinase (PI3K) δ Syndrome (APDS), an inborn error of immunity due to upregulation of the PI3K pathway, leads to recurrent infections and immune dysregulation (lymphoproliferation and autoimmunity).

Methods: Clinical and genetic data of 28 APDS patients from 25 unrelated families were collected from fifteen Italian centers.

Results: Patients were genetically confirmed with APDS-1 (n = 20) or APDS-2 (n = 8), with pathogenic mutations in the PIK3CD or PIK3R1 genes.

Identification of circulating risk biomarkers for cognitive decline in a large community-based population in Chongqing China.

Introduction: This study aims to investigate the relationship between blood-based pathologies and established risk factors for cognitive decline in the community-based population of Chongqing, a region with significant aging.

Methods: A total of 26,554 residents aged 50 years and older were recruited. Multinomial logistic regression models were applied to assess the risk factors of cognition levels.

Identification of a Founder GLDN Variant Associated With "Lethal" Arthrogryposis in Nunavik Inuit: Implications for Obstetrical and Long-Term Survivors' Management.

Biallelic variants in GLDN have recently been associated with lethal congenital contracture syndrome 11 (LCCS11), a form of fetal akinesia deformation sequence (FADS) with high neonatal mortality. In this report, we describe five individuals from two Canadian Inuit families originating from different communities in Nunavik all affected with FADS and harboring a rare homozygous missense variant, [NM_181789.4:c.

Bolstering connectedness through peer support: Randomized-controlled trial of a web-based peer support program for adolescents with inflammatory bowel disease.

Background: Inflammatory bowel disease (IBD) is a chronic autoimmune disease often diagnosed during adolescence. IBD negatively impacts all aspects of health-related quality of life, resulting in physical, emotional, social, school, and work functioning challenges. Adolescents have identified the need for peer support in managing their disease and promoting positive health outcomes.

Clinical and genetic characteristics of RANBP2 mutations in children with acute necrotizing encephalopathy.

Background: This study investigated RANBP2 mutations in children with acute necrotizing encephalopathy (ANE) and conducted a systematic review of the differences in clinical characteristics between with or without RANBP2 mutations.

Methods: Whole-exome sequencing was performed on 19 pediatric ANE patients at Beijing Children's Hospital affiliated to Capital Medical University between 2017 and 2020. A systematic literature review was also conducted on the clinical characteristics and spectrum analysis of RANBP2 mutations.

E3 ubiquitin ligase ITCH-mediated proteasomal degradation of WBP2 sensitizes breast cancer cells to chemotherapy through restraining AMOTL2/c-JUN axis.

Our study had demonstrated that WW domain-binding protein 2 (WBP2) conferred chemoresistance in breast cancer (BC). However, the underlying mechanism remains unclear. Herein, a decreased expression of itchy E3 ubiquitin protein ligase (ITCH) was observed in drug-resistant BC tissues which negatively regulated the expression of WBP2.

Molecular insights into trauma: A framework of epigenetic pathways to resilience through intervention.

Experiences of complex trauma and adversity, especially for children, are ongoing global crises necessitating adaptation. Bioadaptability to adversity and its health consequences emphasizes the dynamism of adaptation to trauma and the potential for research to inform intervention strategies. Epigenetic variability, particularly DNA methylation, associates with chronic adversity while allowing for resilience and adaptability.

International Multicenter Cohort Study on Beta-Blocker-Free Treatment Strategies for Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, potentially life-threatening genetic heart disease. Nonselective beta-blockers (BBs) are highly effective in reducing CPVT-triggered arrhythmic events. However, some patients suffer from unacceptable BB side effects and might require strategies without a BB.

Loss of hepatocyte Usp53 protects mice from a form of xenobiotic-induced liver injury.

Background: Ubiquitin-specific protease 53 (USP53) deficiency is associated with familial intrahepatic cholestasis in which serum gamma-glutamyl transferase (GGT) activity is relatively low. However, how USP53 deficiency contributes to cholestasis is obscure. No animal model has been reported.

Parental Perspectives on Pediatric Surgical Recovery: Narrative Analysis of Free-Text Comments From a Postoperative Survey.

Background: Qualitative experience data can inform health care providers how to best support families during pediatric postoperative recovery. Patient experience data can also provide actionable information to guide health care quality improvement; positive feedback can confirm the efficacy of current practices and systems, while negative comments can identify areas for improvement.

Objective: This study aimed to understand families' perspectives regarding their children's surgical recovery using qualitative patient experience data (free-text comments) from a prospective cohort study conducted within a larger study developing a postoperative-outcome risk stratification model.

Plasmapheresis for extracorporeal membrane oxygenation (ECMO)-induced hemolysis in infants.

Background: Intravascular hemolysis is a known complication of extracorporeal membrane oxygenation (ECMO). Characterized by elevated plasma-free hemoglobin (PFH), intravascular hemolysis is associated with cytotoxic effects leading to renal replacement therapy (RRT), longer ECMO runs, and mortality. Therapeutic plasma exchange (TPE) in tandem with ECMO was described as a therapy for various pathologic conditions, but there are no Extracorporeal Life Support Organization (ELSO) guidelines for the treatment of ECMO-induced hemolysis.

A national cross-sectional survey of health literacy of caregivers attending Canadian pediatric emergency departments.

Background: Health literacy assessment is key to better meeting family needs and developing informed strategies to promote positive health outcomes for children. The objective of this study was to describe the health literacy of caregivers who use Canadian pediatric emergency departments and relate it to demographic and visit-specific variables.

Methods: This study utilized a descriptive, cross-sectional survey design with medical record review.

Introduction to immunology and immune disorders.

The body has a collection of physical barriers to prevent infection, but once these are overcome, we rely on our immune systems to protect us against a wide variety of infections. The complex mechanisms through which this is achieved are grouped into two lines of defense called the "innate" and "adaptive" immune systems. The innate immune system provides a rapid and tailored response to infection or injury often associated with inflammation.