Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

The MyLungHealth study protocol: a pragmatic patient-randomised controlled trial to evaluate a patient-centred, electronic health record-integrated intervention to enhance lung cancer screening in primary care.

Introduction: Early lung cancer screening (LCS) through low-dose CT (LDCT) is crucial but underused due to various barriers, including incomplete or inaccurate patient smoking data in the electronic health record and limited time for shared decision-making. The objective of this trial is to investigate a patient-centred intervention, MyLungHealth, delivered through the patient portal. The intervention is designed to improve LCS rates through increased identification of eligible patients and informed decision-making.

Modified Delphi expert elicitation of the clinical and economic burden of obstructive hypertrophic cardiomyopathy in England and Northern Ireland.

Objective: To estimate the resource use of patients with obstructive hypertrophic cardiomyopathy (HCM), stratified by New York Heart Association (NYHA) class, in the English and Northern Irish healthcare systems via expert elicitation.

Design: Modified Delphi framework methodology.

Setting: UK HCM secondary care centres (n=24).

Temporal Lobe Epilepsy Perturbs the Brain-Wide Excitation-Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction.

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models.

Experimental Investigation of Cadmium Isotope Fractionation during Adsorption on Montmorillonite and Kaolinite.

Cadmium (Cd) isotopes have recently emerged as novel tracers of Cd sources and geochemical processes. Widespread clay minerals play a key role in Cd migration due to their strong adsorption capacity, but the mechanism of Cd isotope fractionation during adsorption onto clay minerals is poorly understood. Here, we experimentally investigated the adsorption mechanisms of Cd on montmorillonite (2:1) and kaolinite (1:1) by using extended X-ray absorption fine structure (EXAFS) spectroscopy.

Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: a comparative neuroimaging analysis.

Background: Psychostimulants and nonstimulants have partially overlapping pharmacological targets on attention-deficit/hyperactivity disorder (ADHD), but whether their neuroimaging underpinnings differ is elusive. We aimed to identify overlapping and medication-specific brain functional mechanisms of psychostimulants and nonstimulants on ADHD.

Methods: After a systematic literature search and database construction, the imputed maps of separate and pooled neuropharmacological mechanisms were meta-analyzed by Seed-based Mapping toolbox, followed by large-scale network analysis to uncover potential coactivation patterns and meta-regression analysis to examine the modulatory effects of age and sex.

Pediatric Supracondylar Humerus and Diaphyseal Femur Fractures: A Comparative Analysis of Chat Generative Pretrained Transformer and Google Gemini Recommendations Versus American Academy of Orthopaedic Surgeons Clinical Practice Guidelines.

Objective: Artificial intelligence (AI) chatbots, including chat generative pretrained transformer (ChatGPT) and Google Gemini, have significantly increased access to medical information. However, in pediatric orthopaedics, no study has evaluated the accuracy of AI chatbots compared with evidence-based recommendations, including the American Academy of Orthopaedic Surgeons clinical practice guidelines (AAOS CPGs). The aims of this study were to compare responses by ChatGPT-4.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Role of preconception nutrition supplements in maternal anemia and intrauterine growth: a systematic review and meta-analysis of randomized controlled trials.

Background: Impaired intrauterine growth, a significant global health problem, contributes to a higher burden of infant morbidity and mortality, mainly in resource-poor settings. Maternal anemia and undernutrition, two important causes of impaired intrauterine growth, are prioritized by global nutrition targets of 2030. We synthesized the evidence on the role of preconception nutrition supplements in reducing maternal anemia and improving intrauterine growth.

North American avian species that migrate in flocks show greater long-term non-breeding range shift rates.

Background: Many species are exhibiting range shifts associated with anthropogenic change. For migratory species, colonisation of new areas can require novel migratory programmes that facilitate navigation between independently-shifting seasonal ranges. Therefore, in some cases range-shifts may be limited by the capacity for novel migratory programmes to be transferred between generations, which can be genetically and socially mediated.

Rapid implementation of open-access pandemic education for global frontline healthcare workers.

Background: The recent global pandemic posed extraordinary challenges for healthcare systems. Frontline healthcare workers required focused, immediate, practical, evidence-based instruction on optimal patient care modalities as knowledge evolved around disease management.

Objective: This course was designed to provide knowledge to protect healthcare workers; combat disease spread; and improve patient outcomes.

A phase 2 randomized, placebo-controlled trial of inulin for the prevention of gut pathogen colonization and infection among patients admitted to the intensive care unit for sepsis.

Background: Patients admitted to the intensive care unit (ICU) often have gut colonization with pathogenic bacteria and such colonization is associated with increased risk for death and infection. We conducted a trial to determine whether a prebiotic would improve the gut microbiome to decrease gut pathogen colonization and decrease downstream risk for infection among newly admitted medical ICU patients with sepsis.

Methods: This was a randomized, double-blind, placebo-controlled trial of adults who were admitted to the medical ICU for sepsis and were receiving broad-spectrum antibiotics.

Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial.

Background: Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations.

Objective: To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination.

An exploratory analysis of differences in serum protein expression by sex in patients with systemic sclerosis associated interstitial lung disease.

Background: Systemic sclerosis (SSc) is a rare connective tissue disease, frequently affecting the skin, lungs, and pulmonary vasculature. Approximately 30-50% of SSc patients develop interstitial lung disease (SSc-ILD), with 30-35% of related deaths attributed to it. Even though men are less likely to develop systemic sclerosis, they have a higher incidence of SSc-ILD than women, and they tend to develop it at a younger age with a higher mortality rate.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.

Prevalence and Temporal Trends of Attention Deficit Hyperactivity Disorder Medication Fills During Pregnancy and Breastfeeding in Denmark.

Background And Objectives: Females of reproductive age are increasingly using attention deficit hyperactivity disorder (ADHD) medication, but its use during pregnancy and breastfeeding is largely unknown. The aim of this study is to examine the prevalence of ADHD medication fills during pregnancy and breastfeeding, including characteristics of these females and cohort differences over time.

Methods: We conducted a descriptive study using Danish nationwide registers.

Assays of Platelet SNARE-actin Interactions.

The actin cytoskeleton serves an important, but poorly characterized, role in controlling granule exocytosis. The dynamic nature of actin remodeling allows it to act both as a barrier to prevent indiscriminate granule release and as a facilitator of membrane fusion. In its capacity to promote exocytosis, filamentous actin binds to components of the exocytotic machinery through actin binding proteins, but also through direct interactions with SNAREs.

Investigating Complexin-Membrane Interactions Using NMR and Optical Methods.

Complexins are a family of small presynaptic proteins that regulate neurotransmitter release at nerve terminals and are highly conserved in evolution. While direct interactions with SNARE proteins are critical for all complexin functions, binding of their disordered C-terminal domains (CTD) to membranes, especially to synaptic vesicle membranes, is essential for the ability of complexin to inhibit vesicle release. Furthermore, while some complexin CTDs possess an endogenous affinity for membranes, other complexin isoforms are subject to lipidation at their C-termini, which is presumed to confer additional membrane binding.

Lifetime risk and projected burden of dementia.

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.

Pain management in percutaneous nephrolithotomy - an approach rooted in pathophysiology.

Pain related to percutaneous nephrolithotomy (PCNL) is multifactorial and poorly elucidated. However, understanding the pathophysiology of pain can enable a practical approach to pain management, which can be tailored to each patient. A number of potential mechanisms underlie pain perception in PCNL, and these mechanisms can be leveraged at various points on the perioperative care pathway.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.