Four Opportunities To Revitalize The US Biomedical Research Enterprise.

The US biomedical research enterprise is renowned for its historical and ongoing scientific breakthroughs and advancements. Yet its capacity to solve complex health issues, bridge health equity gaps, and strengthen public trust is constrained by the lack of an overarching national vision, fragmented coordination for research funding, and critical workforce recruitment and retention challenges. To improve national health outcomes and retain global competitiveness, the sector must embrace new approaches.

Human Epidermal Growth Factor Receptor 2 Loss Following Treatment with Trastuzumab Deruxtecan in Patients with Metastatic Breast Cancer.

Purpose: Trastuzumab deruxtecan (T-DXd) is currently approved for treating metastatic breast cancer (MBC) which is HER2-positive (immunohistochemistry [IHC] score of 3+ or ISH positivity) or HER2-low (IHC score of 1+ or IHC 2+/ISH negative), as well as for HER2-positive gastric cancer, HER2-mutant lung cancer, and HER2 overexpressing solid tumors. Given the increasing utilization of T-DXd, we sought to determine how HER2 receptor status might change following T-DXd therapy.

Design: We retrospectively reviewed patients with MBC who received T-DXd at The University of Texas MD Anderson Cancer Center.

Functional classification of tauopathy strains reveals the role of protofilament core residues.

Distinct tau amyloid assemblies underlie diverse tauopathies but defy rapid classification. Cell and animal experiments indicate tau functions as a prion, as different strains propagated in cells cause unique, transmissible neuropathology after inoculation. Strain amplification requires compatibility of the monomer and amyloid template.

Prefrontal 5α-reductase 2 mediates male-specific acute stress response.

A key response to acute stress is the increased brain synthesis of the neurosteroid allopregnanolone (AP). Although the rate-limiting step of this reaction is catalyzed by 5α-reductase (5αR), the role of its two primary isoenzymes, 5αR1 and 5αR2, in stress reactivity remains unclear. Here, we found that acute stress led to increased levels of 5αR2, but not 5αR1, in the medial prefrontal cortex (mPFC) of male, but not female, rats.

Would a robot ever get angry enough to attack a person?

"Sunny," the new Apple TV series, explores what happens if robot assistants develop emotions.

Common Comorbidities and a Comparison of 4 Comorbidity Indices in Patients Undergoing Orthopaedic Oncology Surgery.

Background: Comorbidity indices are used to help to estimate patients' length of hospital stay, care costs, outcomes, and mortality. Increasingly, they are considered in reimbursement models. The applicability of comorbidity indices to patients undergoing orthopaedic oncology surgery has not been studied.

Skeletal age assessed by Greulich-Pyle: Intra-observer and inter-observer agreement among male pubertal tennis players.

The assessment of biological maturation is a central topic in pediatric exercise sciences. Skeletal age (SA) reflects changes in each bone of the hand and wrist from initial ossification to the adult state. This study examined intra-observer and inter-examiner agreement is Greulich-Pyle (GP) assessments of SA in 97 male tennis players 8.

Constructs across a hierarchical, dimensional model of psychopathology show differential associations with social and general cognitive ability.

Many psychiatric disorders and associated psychopathology dimensions are related to social cognitive deficits and reduced general cognitive ability. The current study applied a hierarchical, dimensional approach to better understand associations among psychopathology, social cognition, and general cognitive ability. Data were collected from two samples (n = 653), including psychosis-spectrum patients, their first-degree relatives, and individuals from community sources.

Parental divorce's long shadow: Elevated stroke risk among older Americans.

Although studies have investigated the association between adverse childhood experiences and chronic health outcomes including stroke, few studies have investigated the association between parental divorce and stroke among adults with no history of childhood abuse. The objectives of this study were to investigate the association between parental divorce in childhood and stroke in older adulthood among those who did not experience child abuse and to examine whether this association differs between men and women. This study utilized population-based data from the 2022 Behavioral Risk Factor Surveillance System.

Regional changes in cerebral blood flow between the upright and supine posture and over 3 days of bed rest.

A reduction in cerebral blood flow (CBF) has been observed during spaceflight and bed rest. We aimed to examine the magnitude and regional heterogeneity of the decrease in CBF during bed rest compared to posture changes on Earth. Seventeen participants (age, 29 ± 9 years, 7 females) were studied in the upright and supine posture and over 3 days of bed rest.

Sex Differences in Long COVID.

Importance: A substantial number of individuals worldwide experience long COVID, or post-COVID condition. Other postviral and autoimmune conditions have a female predominance, but whether the same is true for long COVID, especially within different subgroups, is uncertain.

Objective: To evaluate sex differences in the risk of developing long COVID among adults with SARS-CoV-2 infection.

Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Oral vs Intravenous Antibiotics for Fracture-Related Infections: The POvIV Randomized Clinical Trial.

Importance: Fracture-related infection (FRI) is a serious complication following fracture fixation surgery. Current treatment of FRIs entails debridement and 6 weeks of intravenous (IV) antibiotics. Lab data and retrospective clinical studies support use of oral antibiotics, which are less expensive and may have fewer complications than IV antibiotics.

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Perception of Quality of Life by Primary Caregivers of Children with Congenital Zika Syndrome: a Cross-Sectional Study.

Objective: The study aimed to evaluate the quality of life (QoL) of caregivers of children diagnosed with CZS and to assess the association of findings with socioeconomic and CZS-associated variables.

Methods: This was a cross-sectional, quantitative study, carried out over three days of multidisciplinary care for patients with CZS. Sixty-four participants underwent a quality of life assessment using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in Portuguese.

Long-term effects of combined exposures to simulated microgravity and galactic cosmic radiation on the mouse lung: sex-specific epigenetic reprogramming.

Most studies on the effects of galactic cosmic rays (GCR) have relied on terrestrial irradiation using spatially homogeneous dose distributions of mono-energetic beams comprised of one ion species. Here, we exposed mice to novel beams that more closely mimic GCR, namely, comprising poly-energetic ions of multiple species. Six-month-old male and female C57BL/6J mice were exposed to 0 Gy, 0.

The use of cervical interfacet devices and related clinical outcomes.

Purpose: The purpose of this study was to investigate the outcomes of minimally invasive PCF using an interfacet joint fusion cage.

Methods: The inclusion criteria consisted of patients who underwent a PCF using an interfacet device (Cavux, Providence Medical Technology Inc.) at a single institution and were at least 6 months postoperative.

regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice.

The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct strains might lead to functional differences in the gut microbiome.

Sexual trauma and compulsive sexual behavior in young men and women: A network analysis involving two samples.

Background And Aims: Sexual trauma is associated with multiple negative health and social conditions, including compulsive sexual behavior. The present study examined network structures involving sexual trauma history, psychological distress (defined as depression and/or anxiety symptoms), substance use, transactional sex, and compulsive sexual behavior. Prior network analysis work in this area is limited.

Preventing inappropriate signals pre- and post-ligand perception by a toggle switch mechanism of ERECTA.

Dynamic control of signaling events requires swift regulation of receptors at an active state. By focusing on the Arabidopsis ERECTA (ER) receptor kinase, which perceives peptide ligands to control multiple developmental processes, we report a mechanism preventing inappropriate receptor activity. The ER C-terminal tail (ER_CT) functions as an autoinhibitory domain: Its removal confers higher kinase activity and hyperactivity during inflorescence and stomatal development.

CD44-Mediated Metabolic Rewiring is A Targetable Dependency of IDH-Mutant Leukemia.

Recurrent IDH mutations catalyze NADPH-dependent production of oncometabolite R-2HG for tumorigenesis. IDH inhibition provides clinical response in a subset of acute myeloid leukemia (AML) cases; however, most patients develop resistance, highlighting the need for more effective IDH-targeting therapies. By comparing transcriptomic alterations in isogenic leukemia cells harboring CRISPR base-edited IDH mutations, we identify the activation of adhesion molecules including CD44, a transmembrane glycoprotein, as a shared feature of IDH-mutant leukemia, consistent with elevated CD44 expression in IDH-mutant AML patients.

Closed-loop ventilation and oxygenation with decision support fluid resuscitation to treat major burn injury with smoke induced acute respiratory distress syndrome.

Introduction: The understanding of the interaction of closed-loop control of ventilation and oxygenation, specifically fraction of inspired oxygen (FiO2) and positive end-expiratory pressure (PEEP), and fluid resuscitation after burn injury and acute lung injury from smoke inhalation is limited. We compared the effectiveness of FiO2, PEEP, and ventilation adjusted automatically using adaptive support ventilation (ASV) and decision support fluid resuscitation based on urine output in a clinically relevant conscious ovine model of lung injury secondary to combined smoke inhalation and major burn injury.

Methods: Sheep were subjected to burn and smoke inhalation injury under deep anesthesia and analgesia.