Gene therapy for inborn errors of immunity: current clinical progress.

Hematopoietic stem cell transplant has been the single curative treatment for inborn errors of immunity (IEI) and is recommended for the most severe IEI conditions, such as severe combined immunodeficiency (SCID). However, adverse outcomes primarily due to histocompatibility differences between the donor and the patient are still of concern. Progress in genetic and molecular mechanisms, as well as new technology to insert DNA sequences in cell genomes has allowed the development of strategies to treat genetic diseases by correcting the gene defect in patients' cells.

Historical Demography and Species Distribution Models Shed Light on Speciation in Primates of Northeast India.

Past climate change is one of the important factors influencing primate speciation. Populations of various species could have risen or declined in response to these climatic fluctuations. Northeast India harbors a rich diversity of primates, where such fluctuations can be implicated.

Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants.

Background: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear.

Method And Results: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program.

Impact of Tumor Stage on Oncologic Outcomes of High-grade Bacillus Calmette-Guérin Unresponsive Non-muscle-invasive Bladder Cancer Undergoing Bladder-sparing Therapies.

Background And Objective: Current data on bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) do not differentiate outcomes by clinical stage. The purpose of this study is to investigate the role of tumor stage in oncologic outcomes in BCG-unresponsive NMIBC undergoing bladder-sparing therapies.

Methods: Demographic and outcome data for patients with BCG-unresponsive NMIBC were reviewed at ten institutions.

From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.

Despite significant advances in its management, AF remains a major healthcare burden affecting millions of individuals. Rhythm control with antiarrhythmic drugs or catheter ablation has been shown to improve symptoms and outcomes in AF patients, but current treatment options have limited efficacy and/or significant side-effects. Novel mechanism-based approaches could potentially be more effective, enabling improved therapeutic strategies for managing AF.

Acute respiratory distress syndrome (ARDS): from mechanistic insights to therapeutic strategies.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome of acute hypoxic respiratory failure caused by diffuse lung inflammation and edema. ARDS can be precipitated by intrapulmonary factors or extrapulmonary factors, which can lead to severe hypoxemia. Patients suffering from ARDS have high mortality rates, including a 28-day mortality rate of 34.

Adverse outcomes in monochorionic twins with amniotic fluid abnormalities without TTTS: A Case-Control study.

Objective: Monochorionic diamniotic (MCDA) twins with amniotic fluid abnormalities that do not meet criteria for twin-twin transfusion syndrome (TTTS) concern physicians and families. This study aimed to describe the natural history of amniotic fluid abnormalities.

Methods: In this retrospective case-control study, TTTS screening ultrasounds and clinical records throughout all MCDA twin gestations were reviewed between 2018 and 2022 at a tertiary fetal care center.

Crises in Antimicrobial Stewardship: Misuse of Clarithromycin for Therapy.

is a class I carcinogen that infects more than 100 million individuals in the United States. Antimicrobial therapy for has typically been prescribed empirically rather than based on susceptibility testing. Until recently, therapeutic recommendations have generally ignored the principles of antibiotic stewardship.

Maintenance therapy with a P2Y12 receptor inhibitor after cangrelor in patients with acute coronary syndrome. The ELECTRA-SIRIO 2 investigators' viewpoint.

According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within 30 minutes before the end of infusion in the case of a LD of prasugrel.

Aerodigestive Sequelae and Triple Endoscopy after Congenital Tracheoesophageal Fistula Repair in Children.

Unlabelled: Children post-tracheoesophageal fistula (TEF) repair may present with chronic respiratory and gastrointestinal symptoms that can affect quality of life.

Objective: To identify factors associated with positive findings on triple endoscopy following neonatal TEF repair.

Study Design: Case series with retrospective review of patients.

The African Initiative for Bioinformatics Online Training in Neurodegenerative Diseases (AI-BOND): Investing in the next generation of African neuroscientists.

Unlabelled: Neurodegenerative disorders, including Alzheimer's disease and AD-related dementias (AD/ADRD), pose significant challenges to health care systems globally, particularly in Africa. With the advances in medical technology and research capabilities, especially in next-generation sequencing and imaging, vast amounts of data have been generated from AD/ADRD research. Given that the greatest increase in AD/ADRD prevalence is expected to occur in Africa, it is critical to establish comprehensive bioinformatics training programs to help African scientists leverage existing data and collect additional information to untangle AD/ADRD heterogeneity in African populations.

Improving Automated Deep Phenotyping Through Large Language Models Using Retrieval Augmented Generation.

Background: Diagnosing rare genetic disorders relies on precise phenotypic and genotypic analysis, with the Human Phenotype Ontology (HPO) providing a standardized language for capturing clinical phenotypes. Traditional HPO tools, such as Doc2HPO and ClinPhen, employ concept recognition to automate phenotype extraction but struggle with incomplete phenotype assignment, often requiring intensive manual review. While large language models (LLMs) hold promise for more context-driven phenotype extraction, they are prone to errors and "hallucinations," making them less reliable without further refinement.

Comparison of predicted and actual dermatitis generated from computed tomography images and dose distribution maps.

Anticipating the onset, location and severity of radiation dermatitis before radiotherapy can aid in dermatological care. This study developed a method for creation of a prediction diagram for dermatitis and conducted a comparative verification between the prediction diagram and actual patient condition. The prediction diagram involved converting skin doses into 2 Gy fractionated equivalent doses using α/β of 10.

Efficacy of probiotics regimens for Helicobacter pylori eradication: A systematic review, pairwise, and network meta-analysis of randomized controlled trials.

Background: Helicobacter pylori (H. pylori) infection increases the risks of chronic gastritis, peptic ulcer diseases, and the incidence of gastric cancer. However, antibiotic resistance and adverse effects led to the emergence of alternative treatments such as probiotics supplementation.

Association of circulating ketone bodies with cognitive performance and dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods: Associations of plasma KB with incident dementia and cognitive performances were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000-02) and detailed cognitive testing at Exam 5 (2010-2012,  = 4392), Exam 6 (2016-2018,  = 1838), and in MESA-MIND (2019-2021,  = 2060).

Antibiotic-associated neutropenia is marked by the depletion of intestinal and associated metabolites in pediatric patients.

Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics.

Updates in pharmacotherapy of obesity.

Obesity is now recognized as a chronic, progressive condition requiring early intervention and long-term management to achieve health benefits and improve metabolic risk factors. The main objective of obesity pharmacotherapy is weight loss and weight loss maintenance. There is increasing acceptance of anti-obesity medications as an adjunct to lifestyle modifications and/or surgery.

Immediate Versus Staged Complete Revascularization for Patients With ST-Segment-Elevation Myocardial Infarction and Multivessel Disease: A Network Meta-Analysis of Randomized Trials.

Background: The comparative outcomes with immediate, staged in-hospital, and staged out-of-hospital complete revascularization for patients with ST-segment-elevation myocardial infarction and multivessel disease remain unclear.

Methods And Results: An electronic search of MEDLINE, SCOPUS, and Cochrane databases was performed through August 2023 for randomized trials evaluating immediate, staged in-hospital, and staged out-of-hospital complete revascularization for patients with ST-segment-elevation myocardial infarction and multivessel disease. The primary outcome was major adverse cardiac events (MACEs).

Love of life and flourishing in Turkish youth: mediating effects of optimism and hope.

The concept of love of life, which refers to a positive attitude towards one's own life, care for it and attachment to it, has recently captured the attention of researchers in the field of positive psychology. Despite its growing importance, there is a lack of research investigating the underlying mechanisms through which love of life impacts the flourishing and well-being of individuals. For the first time, the present study examined the mediating roles of optimism and hope in the association between love of life and flourishing in Turkish youth.

Persistent Na current couples spreading depolarization to seizures in gain of function mice.

Spreading depolarization (SD) is a slowly propagating wave of massive cellular depolarization that transiently impairs the function of affected brain regions. While SD typically arises as an isolated hemispheric event, we previously reported that reducing M-type potassium current (I) by ablation of in forebrain excitatory neurons results in tightly coupled spontaneous bilateral seizure-SD complexes in the awake mouse cortex. Here we find that enhanced persistent Na current due to gain-of-function (GOF) mutations in (N1768D/+, hereafter D/+) produces a similar compound cortical excitability phenotype.

Mutant NPM1 marginally impacts ribosome footprint in acute myeloid leukemia cells.

Background: -mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild-type NPM1 is known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute to leukemogenesis and leukemia maintenance in -mutated AML. However, this hypothesis has never been investigated.

Birth outcomes following bictegravir exposure during pregnancy.

Objective: Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy.

Design: We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery.