The genetic architecture of differentiating behavioral and emotional problems in early life.

Background: Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.

Real-world effectiveness and safety of bulevirtide monotherapy for up to 96 weeks in patients with HDV-related cirrhosis.

Background And Aims: Bulevirtide (BLV) 2 mg/day is EMA approved for treatment of compensated chronic hepatitis due to Delta virus (HDV) infection, however real-life data in large cohorts of patients with cirrhosis are lacking.

Methods: Consecutive HDV-infected patients with cirrhosis starting BLV 2 mg/day since September 2019 were included in a European retrospective multicenter real-life study (SAVE-D). Patient characteristics before and during BLV treatment were collected.

Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial.

Background: Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.

Methods: This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America.

Functional optimality underpins the repeated evolution of the extreme "saber-tooth" morphology.

"Saber teeth"-elongate, blade-like canines-are a classic example of convergence, having evolved repeatedly throughout mammalian history. Within canine teeth, there is a trade-off between the aspects of shape that improve food fracture and those that increase tooth strength. Optimal morphologies strike a balance between these antagonistic functional criteria.

Neuropsychological awareness in pediatrics (NAP): Proposal of a new cognitive self-report questionnaire for pediatric multiple sclerosis patients.

Background: Self-perception of cognitive functioning in pediatric MS (pedMS) needs to be evaluated with specific questionnaires, currently lacking. This study aimed to develop a self-reportwhich investigates cognitive status in pedMS.

Methods: Twenty-seven pedMS patients (mean age±standard deviation=15 years±1.

A first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.

Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.

Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.

Gut microbiome and immune checkpoint inhibitor toxicity.

Background: Multiple studies have suggested that gut microbiome may influence immune checkpoint inhibitor (ICI) efficacy, but its association with immune-related adverse events (irAEs) is less well studied. In this prospective cohort study, we assessed whether gut microbiome composition at start, or changes during ICI, are associated with severe irAEs.

Methods: Stool samples of cancer patients treated with anti-PD-1 ± anti-CTLA-4 were analyzed using 16S rRNA gene sequencing and metagenomic shotgun sequencing.

Aptamer-molecularly imprinted polymer sensors for the detection of bacteria in water.

Bacteria pose a significant threat to human health as they can cause diseases and outbreaks; therefore rapid, easy, and specific detection of bacteria in a short time is crucial. Various methods such as polymerase chain reaction and enzyme-linked immunosorbent assay have been developed for bacteria detection. However, most of these methods require sample preparation, trained personnel, and 2-4 days for identification.

A qualitative exploration of the enablers of and barriers to conformance with antibiotic withdrawal periods on smallholding, peri-urban pig farms in Kiambu County, Kenya.

Non-conformance with antibiotic withdrawal period guidelines represents a food safety concern, with potential for antibiotic toxicities and allergic reactions as well as selecting for antibiotic resistance. In the Kenyan domestic pig market, conformance with antibiotic withdrawal periods is not a requirement of government legislation and evidence suggests that antibiotic residues may frequently be above recommended limits. In this study, we sought to explore enablers of and barriers to conformance with antibiotic withdrawal periods for pig farms supplying a local independent abattoir in peri-urban Nairobi.

Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn.

Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

Concomitant Usage of H1-Antihistamines and Immune Checkpoint Inhibitors on Cancer Patient Survival.

Purpose: Recent research (Li et al. 2021) suggests an upregulated expression and activation of H1 receptors on macrophages in the tumor microenvironment, and concomitant H1-antihistamine use is associated with improved overall survival in patients with lung and skin cancers receiving immunotherapy. Therefore, we retrospectively evaluated the impacts of H1-antihistamine use in cancer patients during immunotherapy.

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.

Outbreak of perichondritis associated with ear piercings and a contaminated water system.

In September 2023, the UK Health Security Agency's (UKHSA) South West Health Protection Team received notification of patients with perichondritis. All five cases had attended the same cosmetic piercing studio and a multi-disciplinary outbreak control investigation was subsequently initiated. An additional five cases attending the same studio were found.

Investigating the presence of surgical learning in the Timing of Primary Surgery for cleft palate randomised trial.

Background/aims: When conducting a randomised controlled trial in surgery, it is important to consider surgical learning, where surgeons' familiarity with one, or both, of the interventions increases during the trial. If present, learning may compromise trial validity. We demonstrate a statistical investigation into surgical learning within a trial of cleft palate repair.

Prediction accuracy of discrete choice experiments in health-related research: a systematic review and meta-analysis.

Background: Discrete choice experiments (DCEs) are increasingly used to inform the design of health products and services. It is essential to understand the extent to which DCEs provide reliable predictions outside of experimental settings in real-world decision-making situations. We aimed to compare the prediction accuracy of stated preferences with real-world choices, as modelled from DCE data.

Therapeutic Dilemmas Arising From a Serpentine Thrombus Across a Patent Foramen Ovale in a Patient With Dilated Cardiomyopathy.

A thrombus straddling a patent foramen ovale (TSPFO) is a rare condition that presents significant health risks, including stroke or myocardial infarction, and can be life-threatening if not promptly addressed. We report the case of a 42-year-old female with morbid obesity who presented with sudden shortness of breath due to a bilateral pulmonary embolism. Imaging revealed a thrombus extending from the right atrium to the left atrium through the patent foramen ovale (PFO).

Renal Clear Cell Carcinoma Masquerading As Brain Arteriovenous Malformation: A Case Report and Review of the Literature.

Cerebral arteriovenous malformations (AVMs) are tangles of abnormal vessels with early arteriovenous (AV) shunting that can lead to intracerebral hemorrhage, seizures, neurologic deficit, or headache. To date, only a few cases of carcinomas metastasizing to pre-existing cerebral AVMs have been reported in the literature. However, renal clear cell carcinoma (RCC) brain metastases that exhibit early AV shunting, where AVM pathology is not present, are extremely rare.

Complex and Bidirectional Interplay Between Marital Quality, Catastrophizing, Psychological Dysfunction, and Quality of Life in Married Malay Women With Disorder of Gut-Brain Interactions.

Background: Disorders of gut-brain interactions (DGBI) affect more women, and marital quality may have been a factor that explains clinical manifestations of DGBI-however, the mechanism is unclear. This study aimed to elucidate supported relationships between DGBI with marital quality and clinical attributes in married Malay women.

Methods: This cross-sectional study involved married Malay women with functional dyspepsia (FD), irritable bowel syndrome (IBS), and FD-IBS overlap per Rome IV criteria.

Capacity and Capability for Nursing, Midwifery and Allied Health Professional Principal Investigator Roles in Healthcare Research: A National Survey.

Aims: To understand the current capacity and capability for nursing, midwifery and allied health professional (NMAHP) principal investigator roles in England.

Design: Quantitative online survey.

Methods: Online national quantitative survey across England analysed using descriptive statistics.