The implementation of intrathecal morphine for caesarean delivery into clinical practice, and assessment of its impact on patient-reported quality of recovery using the ObsQoR-10-Dutch scale.

Background: Optimising a mother's quality of recovery following caesarean delivery is of paramount importance as it facilitates maternal care of the newborn and affects physical, psychological and emotional well being. Intrathecal morphine (ITM) reduces postoperative pain and may improve quality of recovery: however its widespread use is limited.

Objective: To assess the effects of implementing ITM for caesarean delivery on postoperative quality of recovery.

Cognitive Outcomes After Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression: Résultats cognitifs après la stimulation magnétique transcrânienne pour le traitement de la dépression chez les personnes âgées.

Background: Late-life depression (LLD) is often accompanied by cognitive impairment, which may persist despite antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) is an efficacious treatment for depression, with potential benefits on cognitive functioning. However, research on cognitive effects is inconclusive, relatively sparse in LLD, and predominantly focused on group-level cognitive changes.

Determination of Trends Underlying Aspartic Acid Isomerization in Intact Proteins Reveals Unusually Rapid Isomerization of Tau.

Spontaneous chemical modifications in long-lived proteins can potentially change protein structure in ways that impact proteostasis and cellular health. For example, isomerization of aspartic acid interferes with protein turnover and is anticorrelated with cognitive acuity in Alzheimer's disease. However, few isomerization rates have been determined for Asp residues in intact proteins.

Virtual diversity and the value-ladenness of science.

Collins, Evans, and Reyes-Galindo develop the concept of interactional expertise into the idea of virtual diversity. They thereby provide a strong case against the epistemic barriers established by identity politics. This commentary questions, however, whether virtual diversity can incorporate the critique of institutional power that Wynne has argued is at the center of tensions between lay publics and scientific establishments.

Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda.

Background: Lenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1.

Screening of Coulombic Interactions To Achieve a Higher Power Factor in Conjugated Polymers.

Thermoelectric properties of conducting polymers typically suffer from molecular chain disordering, as charge transport is predominantly controlled by morphology. This is especially more problematic when counterions are introduced to tune the carrier concentration for optimal thermoelectric performance, which disturbs the morphology further. In this work, we introduce a new avenue for enhancing thermoelectric properties without needing to regulate the morphology, namely, by controlling the coulombic interaction between polarons and counterions.

Scientific and Regulatory Policy Committee Points to Consider: Proposal and Recommendations to Reduce Euthanasia of Control Nonhuman Primates in Nonclinical Toxicity Studies.

Nonhuman primates (NHPs) have been and remain a highly valuable animal model with an essential role in translational research and pharmaceutical drug development. Based on current regulatory guidelines, the nonclinical safety of novel therapeutics should be evaluated in relevant nonclinical species, which commonly includes NHPs for biotherapeutics. Given the practical and ethical limitations on availability and/or use of NHPs and in line with the widely accepted guiding "3Rs" (replace, reduce, and refine) principles, many approaches have been considered to optimize toxicity study designs to meaningfully reduce the number of NHPs used.

High-impact Chronic Pain in a Cohort of Urologic Chronic Pelvic Pain Syndrome Patients: A Retrospective MAPP Research Network Study.

Objectives: An emerging concept in the chronic pain literature, high-impact chronic pain (HICP), refers to pain that occurs very frequently and results in major disruption of daily life. Previous epidemiologic investigations have noted that lower educational attainment, age, and race appear to be associated with the frequency of HICP, but condition-specific investigations of HICP have been less common.

Methods: Here we investigate HICP status and its clinical/demographic correlates in the Multidisciplinary Approach to the study of chronic Pelvic Pain research network Symptom Pattern Study.

Exploring the Social Media Discussion of Breast Cancer Treatment Choices: Quantitative Natural Language Processing Study.

Background: Early-stage breast cancer has the complex challenge of carrying a favorable prognosis with multiple treatment options, including breast-conserving surgery (BCS) or mastectomy. Social media is increasingly used as a source of information and as a decision tool for patients, and awareness of these conversations is important for patient counseling.

Objective: The goal of this study was to compare sentiments and associated emotions in social media discussions surrounding BCS and mastectomy using natural language processing (NLP).

Evaluation of the Femoral Condyle Radius of Curvature at the Chondral Surface Shows Significant Correlation With the Anterior-Posterior Length.

Background: Accurate donor-recipient matching of the femoral condyle radius of curvature (ROC) in osteochondral allograft (OCA) transplantation may aid in minimizing articular surface incongruities. Matching linear femorotibial dimensions, such as the femoral condyle anterior-posterior length (APL), femoral condyle width (lateral-medial length, LML), femoral hemicondyle width (HCW), and tibial plateau width (TPW), can provide similar results if they correlate well with ROC. This study investigates the relationship between femorotibial dimensions and ROC at the cartilage surface using magnetic resonance imaging (MRI).

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.