Prospective multi-centre analysis of rural trauma team development training for medical trainees and traffic law enforcement professionals in Uganda: an interrupted time series study.

Background: Research shows that trauma team formation could potentially improve effectiveness of injury care in rural settings. The aim of this study was to determine the feasibility of rural trauma team training amongst medical trainees and traffic law enforcement professionals in Uganda.

Methods: Prospective multi-centre interrupted time series analysis of an interventional training based on the 4th edition of rural trauma team development course of the American College of Surgeons.

AI-based analysis of fetal growth restriction in a prospective obstetric cohort quantifies compound risks for perinatal morbidity and mortality and identifies previously unrecognized high risk clinical scenarios.

Background: Fetal growth restriction (FGR) is a leading risk factor for stillbirth, yet the diagnosis of FGR confers considerable prognostic uncertainty, as most infants with FGR do not experience any morbidity. Our objective was to use data from a large, deeply phenotyped observational obstetric cohort to develop a probabilistic graphical model (PGM), a type of "explainable artificial intelligence (AI)", as a potential framework to better understand how interrelated variables contribute to perinatal morbidity risk in FGR.

Methods: Using data from 9,558 pregnancies delivered at ≥ 20 weeks with available outcome data, we derived and validated a PGM using randomly selected sub-cohorts of 80% (n = 7645) and 20% (n = 1,912), respectively, to discriminate cases of FGR resulting in composite perinatal morbidity from those that did not.

Niche-derived Semaphorin 4A safeguards functional identity of myeloid-biased hematopoietic stem cells.

Somatic stem cell pools comprise diverse, highly specialized subsets whose individual contribution is critical for the overall regenerative function. In the bone marrow, myeloid-biased hematopoietic stem cells (myHSCs) are indispensable for replenishment of myeloid cells and platelets during inflammatory response but, at the same time, become irreversibly damaged during inflammation and aging. Here we identify an extrinsic factor, semaphorin 4A (Sema4A), which non-cell-autonomously confers myHSC resilience to inflammatory stress.

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.

Outside-in engineering of cadherin endocytosis using a conformation strengthening antibody.

P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.

Strength and durability of indirect protection against SARS-CoV-2 infection through vaccine and infection-acquired immunity.

Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning.

From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS).

The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive therapeutic outcomes and are associated with the entropy of EEG signals. Healthy individuals (N = 11) were administered 1 mg and 25 mg psilocybin 4-weeks apart.

Precession modulates the poleward expansion of atmospheric circulation to the Arctic Ocean.

Under sustained global warming, Arctic climate is projected to become more responsive to changes in North Pacific meridional heat transport as a result of teleconnections between low and high latitudes, but the underlying mechanisms remain poorly understood. Here, we reconstruct subarctic humidity changes over the past 400 kyr to investigate the role of low-to-high latitude interactions in regulating Arctic hydroclimate. Our reconstruction is based on precipitation-driven sediment input variations in the Subarctic North Pacific (SANP), which reveal a strong precessional cycle in subarctic humidity under the relatively low eccentricity variations that dominated the past four glacial-interglacial cycles.

Engaging Patients in Discussions About Medication Deprescribing.

Background: Deprescribing, intentional medication discontinuation or dose reduction, can reduce potentially inappropriate medication use and medication-related harms. Engaging patients in deprescribing discussions may increase likelihood of deprescribing and promote shared decision-making.

Objective: To examine the impact of patient-directed educational brochures on patient engagement and deprescribing discussions with primary care providers (PCPs).

Prevalence of Moral Injury in Nationally Representative Samples of Combat Veterans, Healthcare Workers, and First Responders.

Background: Moral injury affects a variety of populations who make ethically complex decisions involving their own and others' well-being, including combat veterans, healthcare workers, and first responders. Yet little is known about occupational differences in the prevalence of morally injurious exposures and outcomes in nationally representative samples of such populations.

Objective: To examine prevalence of potentially morally injurious event (PMIE) exposure and clinically meaningful moral injury in three high-risk groups.

Sources of Microstructure in Mammalian Cochlear Responses.

Quasiperiodic fluctuations with frequency are observed in a variety of responses that either originate from or strongly depend on the cochlea's active mechanics. These spectral microstructures are unique and stable features of individual ears and have been most thoroughly studied in behavioral hearing thresholds and otoacoustic emissions (OAEs). While the exact morphology of the microstructure patterns may differ across measurement types, the patterns are interrelated and are thought to depend on common mechanisms.

Bridging Gaps: Enhancing Sleep and Health Disparities in Latino Families with Young Adults with Autism Using a Culturally Adapted Intervention.

The present study examined the effects of a culturally adapted intervention, ¡Iniciando! la Adultez, on sleep and health-related quality of life (HRQoL) in Latino young adults with autism spectrum disorder (ASD) and their Spanish-speaking parents. The intervention targeted the transition to adulthood, a period associated with increased challenges in sleep and HRQoL, particularly for underserved Latino populations. Participants included 26 young adults and 38 parents who completed assessments at baseline and post-treatment.

AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.

Therapeutic efficacy and safety of adeno-associated virus (AAV) liver gene therapy depend on capsid choice. To predict AAV capsid performance under near-clinical conditions, we established side-by-side comparison at single-cell resolution in human livers maintained by normothermic machine perfusion. AAV-LK03 transduced hepatocytes much more efficiently and specifically than AAV5, AAV8 and AAV6, which are most commonly used clinically, and AAV-NP59, which is better at transducing human hepatocytes engrafted in immune-deficient mice.

An evaporite sequence from ancient brine recorded in Bennu samples.

Evaporation or freezing of water-rich fluids with dilute concentrations of dissolved salts can produce brines, as observed in closed basins on Earth and detected by remote sensing on icy bodies in the outer Solar System. The mineralogical evolution of these brines is well understood in regard to terrestrial environments, but poorly constrained for extraterrestrial systems owing to a lack of direct sampling. Here we report the occurrence of salt minerals in samples of the asteroid (101955) Bennu returned by the OSIRIS-REx mission.

Copper-dependent halogenase catalyses unactivated C-H bond functionalization.

Carbon-hydrogen (C-H) bonds are the foundation of essentially every organic molecule, making them an ideal place to do chemical synthesis. The key challenge is achieving selectivity for one particular C(sp)-H bond. In recent years, metalloenzymes have been found to perform C(sp)-H bond functionalization.

Warming and cooling catalyse widespread temporal turnover in biodiversity.

Turnover in species composition through time is a dominant form of biodiversity change, which has profound effects on the functioning of ecological communities. Turnover rates differ markedly among communities, but the drivers of this variation across taxa and realms remain unknown. Here we analyse 42,225 time series of species composition from marine, terrestrial and freshwater assemblages, and show that temporal rates of turnover were consistently faster in locations that experienced faster temperature change, including both warming and cooling.

Dynamic flow control through active matter programming language.

Cells use 'active' energy-consuming motor and filament protein networks to control micrometre-scale transport and fluid flows. Biological active materials could be used in dynamically programmable devices that achieve spatial and temporal resolution that exceeds current microfluidic technologies. However, reconstituted motor-microtubule systems generate chaotic flows and cannot be directly harnessed for engineering applications.

A manifesto for a globally diverse, equitable, and inclusive open science.

The field of psychology has rapidly transformed its open science practices in recent years. Yet there has been limited progress in integrating principles of diversity, equity and inclusion. In this Perspective, we raise the spectre of Questionable Generalisability Practices and the issue of MASKing (Making Assumptions based on Skewed Knowledge), calling for more responsible practices in generalising study findings and co-authorship to promote global equity in knowledge production.

Oxidation state of bioavailable dissolved organic matter influences bacterioplankton respiration and growth efficiency.

Oxygen consumption by oceanic microbes can predict respiration (CO production) but requires an assumed respiratory quotient (RQ; ΔO/ΔCO). Measured apparent RQs (ARQs) can be impacted by various processes, including nitrification and changes in dissolved organic matter (DOM) composition, leading to discrepancies between ARQ and actual RQ. In DOM remineralization experiments conducted in the eastern North Atlantic Ocean, ARQs averaged 1.

Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.

Blood transfusion plays a vital role in modern medicine, but frequent shortages occur. Ex vivo manufacturing of red blood cells (RBCs) from universal donor cells offers a potential solution, yet the high cost of recombinant cytokines remains a barrier. Erythropoietin (EPO) signaling is crucial for RBC development, and EPO is among the most expensive media components.

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data.

In the analysis of spatially resolved transcriptomics data, detecting spatially variable genes (SVGs) is crucial. Numerous computational methods exist, but varying SVG definitions and methodologies lead to incomparable results. We review 34 state-of-the-art methods, classifying SVGs into three categories: overall, cell-type-specific, and spatial-domain-marker SVGs.

Disorders of Muscle Mass and Tone.

Muscle disease has various clinical manifestations that range from exertional and non-exertional rhabdomyolysis, fasciculations, weakness, rigidity, stiffness, gait abnormalities, poor performance, and alterations in muscle mass and tone. Neurogenic disorders and non-neurogenic disorders such as primary muscle disease can cause muscle atrophy and changes in muscle tone. Myotonic disorders can have a genetic (eg, inherited channelopathies) or acquired (eg, electrolyte derangements) origin.

Genetics of Muscle Disease.

In the field of equine muscle disorders, many conditions have a genetic basis. Therefore, genetic testing is an important part of the diagnostic evaluation. Validated genetic tests are currently available for 5 equine muscle disorders: hyperkalemic periodic paralysis, malignant hyperthermia, glycogen branching enzyme disease, type 1 polysaccharide storage myopathy, and myosin heavy chain myopathy.