Genetic Predisposition to Hippocampal Atrophy and Risk of Amnestic Mild Cognitive Impairment and Alzheimer's Dementia.

Background: There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.

Methods: Participants were drawn from the population-based HELIAD cohort.

Stipulations of cell and gene therapy and the ties to biomanufacturing.

Cell and gene therapy (CGT) products are emerging and innovative biopharmaceuticals that hold promise for treating diseases that are otherwise beyond the scope of conventional medicines. The evolution of CGT from a research idea to a promising therapeutic product is due to the complementary advancements across various scientific disciplines. First, the innovations and advancements in gene editing and delivery technology have provided fundamental tools to manipulate genes and cells for therapeutic pursuits.

Structural Characterization of the Platinum Nanoparticle Hydrogen-Evolving Catalyst Assembled on Photosystem I by Light-Driven Chemistry.

Directed assembly of abiotic catalysts onto biological redox protein frameworks is of interest as an approach for the synthesis of biohybrid catalysts that combine features of both synthetic and biological materials. In this report, we provide a multiscale characterization of the platinum nanoparticle (NP) hydrogen-evolving catalysts that are assembled by light-driven reductive precipitation of platinum from an aqueous salt solution onto the photosystem I protein (PSI), isolated from cyanobacteria as trimeric PSI. The resulting PSI-NP assemblies were analyzed using a combination of X-ray energy-dispersive spectroscopy (XEDS), high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), small-angle X-ray scattering (SAXS), and high-energy X-ray scattering with atomic pair distribution function (PDF) analyses.

Interest in Injectable and Oral PrEP for HIV Prevention Among Women and Men Who Inject Drugs.

Background: People who inject drugs (PWID) are at increased risk for human immunodeficiency virus (HIV). Women who inject are a particularly vulnerable group. Preexposure prophylaxis (PrEP) is effective, but access and uptake has been limited.

Prescribing Psychostimulants for the Treatment of Stimulant Use Disorder: Navigating the Federal Legal Landscape.

Stimulant use disorder (StUD) is a rapidly growing concern in the United States, with escalating rates of death attributed to amphetamines and cocaine. No medications are currently approved for StUD treatment, leaving clinicians to navigate off-label medication options. Recent studies suggest that controlled prescription psychostimulants such as dextroamphetamine, methylphenidate, and modafinil are associated with reductions in self-reported stimulant use, craving, and depressive symptoms.

Tangential Versus Segmental Portomesenteric Venous Resection During Pancreatoduodenectomy for Pancreatic Cancer: An International Multicenter Cohort Study on Surgical and Oncological Outcome.

Objective: To investigate whether tangential versus segmental portomesenteric venous resection (PVR) impacts surgical and oncological outcome in patients undergoing pancreatoduodenectomy for pancreatic cancer with portomesenteric vein (PMV) involvement.

Summary Background Data: Current comparative studies on tangential versus segmental PVR as part of pancreatoduodenectomy for pancreatic cancer include all degrees of PMV involvement, including cases where tangential PVR may not be a feasible approach, limiting the clinical applicability.

Methods: International retrospective study in 10 centers from 5 countries, including all consecutive patients after pancreatoduodenectomy with PVR for pancreatic cancer with ≤180° PMV involvement on cross-sectional imaging at diagnosis (2014-2020).

Long-term safety and efficacy of ritlecitinib in adults and adolescents with alopecia areata and at least 25% scalp hair loss: Results from the ALLEGRO-LT phase 3, open-label study.

Background: ALLEGRO-LT is an ongoing, long-term, open-label, multicentre, phase 3 study of ritlecitinib in adults and adolescents with alopecia areata (AA).

Objectives: To evaluate ritlecitinib safety and efficacy through Month 24 in patients with AA and ≥25% scalp hair loss.

Methods: ALLEGRO-LT enrolled rollover patients who previously received study intervention in either ALLEGRO phase 2a or 2b/3 studies and de novo patients who had not received treatment in either study.

Directed Acyclic Graphs in Decision-Analytic Modeling: Bridging Causal Inference and Effective Model Design in Medical Decision Making.

Our commentary proposes the application of directed acyclic graphs (DAGs) in the design of decision-analytic models, offering researchers a valuable and structured tool to enhance transparency and accuracy by bridging the gap between causal inference and model design in medical decision making.The practical examples in this article showcase the transformative effect DAGs can have on model structure, parameter selection, and the resulting conclusions on effectiveness and cost-effectiveness.This methodological article invites a broader conversation on decision-modeling choices grounded in causal assumptions.

Measuring the effects of motion corruption in fetal fMRI.

Irregular and unpredictable fetal movement is the most common cause of artifacts in in utero functional magnetic resonance imaging (fMRI), affecting analysis and limiting our understanding of early functional brain development. The accurate detection of corrupted functional connectivity (FC) resulting from motion artifacts or preprocessing, instead of neural activity, is a prerequisite for reliable and valid analysis of FC and early brain development. Approaches to address this problem in adult data are of limited utility in fetal fMRI.

Association Between Cardiometabolic Comorbidity Burden and Outcomes in Heart Failure.

Background: Cardiometabolic comorbidities such as obesity, diabetes, and hypertension are highly prevalent in heart failure (HF). We aimed to examine the association between severity of cardiometabolic comorbidities and hospitalization in patients with HF.

Methods: In a retrospective electronic health record-based cohort of adults 18 with HF, we categorized individuals based on the number of severe cardiometabolic comorbidities, including hypertension, diabetes, and obesity.

Alternative driver pathways in peripheral nerve sheath tumors - including DICER1 and/or KRAS alterations.

DICER1-associated sarcoma is an emerging entity, defined by either somatic or germline dicer 1, ribonuclease III (DICER1) mutations and sharing characteristic morphologic features irrespective of the site of origin. In addition to the DICER1 driver mutation, concurrent genomic alterations, including tumor protein 53 (TP53) inactivation and RAS pathway activation, are frequently detected. Tumors that morphologically resemble malignant peripheral nerve sheath tumor (MPNST) have rarely been reported among DICER1 sarcomas and often pose diagnostic challenges.

Genomic sequencing in diverse and underserved pediatric populations: parent perspectives on understanding, uncertainty, psychosocial impact, and personal utility of results.

Purpose: Limited evidence evaluates parents' perceptions of their child's clinical genomic sequencing (GS) results, particularly among individuals from medically underserved groups. Five Clinical Sequencing Evidence-Generating Research (CSER) consortium studies performed GS in children with suspected genetic conditions with high proportions of individuals from underserved groups to address this evidence gap.

Methods: Parents completed surveys of perceived understanding, personal utility, and test-related distress after GS result disclosure.

Structural insights into the role of the prosegment binding loop in a papain-superfamily cysteine protease from Treponema denticola.

Periodontal diseases afflict 20-50% of the global population and carry serious health and economic burdens. Chronic periodontitis is characterized by inflammation of the periodontal pocket caused by dysbiosis. This dysbiosis is coupled with an increase in the population of Treponema denticola, a spirochete bacterium with high mobility and invasivity mediated by a number of virulence factors.

Increasing Contraception Documentation in an Academic Rheumatology Clinic: A Quality Improvement Approach.

Objective: This quality improvement initiative aimed to increase the rate of provider screening and documentation of contraception use for reproductive-aged women seen in an academic rheumatology fellows' clinic to >50% by 24 weeks, with sustained improvement at one year.

Methods: With a multidisciplinary team, we devised and implemented six interventional cycles over 24 weeks informed by key stakeholder survey responses. The primary outcome measure was the percentage of eligible visits with contraception information documented in the structured electronic health record field.

MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration.

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL.

Patient-Reported Fatigue Associated with Joint Histopathology in Rheumatoid Arthritis.

Objective: Fatigue is important for patients with rheumatoid arthritis (RA) but is poorly understood. We sought to study associations of fatigue with clinical features, disease activity, and synovial histology.

Methods: Patients meeting the American College of Rheumatology/EULAR 1987 and/or 2010 RA criteria were recruited before elective total joint replacement.

Immunotherapy-based neoadjuvant treatment and complication rates after radical cystectomy.

Objective: To assess 30- and 90-day postoperative complication rates in patients who underwent robot-assisted radical cystectomy (RARC) after receiving novel immunotherapy-based neoadjuvant treatment.

Methods: A bi-centre analysis was conducted in patients who underwent RARC with intracorporeal urinary diversion and who received an immunotherapy-based neoadjuvant regimen between 2017 and 2023. Complications were classified using the Clavien-Dindo system.

Annular Closure Device Reduces Symptomatic Reherniation Rates: Results of a Meta-analysis.

The scope of existing annular closure device (ACD) studies examining long-term follow-up data is limited. There is a paucity of studies that report and analyze recent outcomes data following ACD use. We sought to summarize the available long-term follow-up data on postoperative outcomes of the Barricaid (Intrinsic Therapeutics) ACD.

A Pilot Study of the Gut Microbiota in Spine Fusion Surgery Patients.

Background: The microbiome has been identified as a contributor to bone quality. As skeletal health is critical to success of orthopedic surgery, the gut microbiome may be a modifiable factor associated with postoperative outcomes. For spine fusion surgery in particular, bone formation and sufficient bone mineral density are essential for successful outcomes.

Exploring the presence and roles of humility when experiencing situations of uncertainty.

Background: Uncertainty is a pervasive challenge in clinical practice. Whereas the importance of humility in navigating uncertainty has been discussed, empirical research on how humility is practiced or expressed (i.e.

Changes in multidisciplinary perceptions of trauma video review following implementation of a novel program: let us go to the tape.

Background: Trauma video review (TVR) is an evolving technology that can be used to measure technical and non-technical aspects of trauma care leading to meaningful improvements. Only 30% of centers currently use TVR, with non-users citing medicolegal concerns, staff discomfort with recording, and resource constraints as barriers to implementation. Multiple studies have shown established TVR programs are well-perceived by staff.

Murine model of cross-IgE sensitization and cross-anaphylactic reactions among multiple group food allergens.

Rationale: Approximately 32 million people in the United States suffer from food allergies. Some food groups, such as legumes - peanuts, tree nuts, fish, and shellfish, have a high risk of cross-reactivity. However, the murine model of multiple food group cross-reactivity is limited.

Therapeutic potential of short-chain fatty acids for acute lung injury: a systematic review and meta-analysis of preclinical animal studies.

Background: Short-chain fatty acids (SCFAs), derived from the fermentation of dietary fiber by intestinal commensal bacteria, have demonstrated protective effects against acute lung injury (ALI) in animal models. However, the findings have shown variability across different studies. It is necessary to conduct a comprehensive evaluation of the efficacy of these treatments and their consistency.