How and why funders support engaged research.

Research that better aligns policy, practice, and research communities is gaining momentum around the world. This includes engaged research strategies that bring partners, and their diverse perspectives and kinds of knowledge, together to shape research agendas with on-the-ground-needs and to create dynamic problem-solving processes. These approaches aim to generate more equitable and effective solutions to societal challenges.

Comparing integrative ventilatory and renal acid-base acclimatization in lowlanders and Tibetan highlanders during ascent to 4,300 m.

With over 14 million people living above 3,500 m, the study of acclimatization and adaptation to high altitude in human populations is of increasing importance, where exposure to high altitude (HA) imposes a blood oxygenation and acid-base challenge. A sustained and augmented hypoxic ventilatory response protects oxygenation through ventilatory acclimatization, but elicits hypocapnia and respiratory alkalosis. A subsequent renally mediated compensatory metabolic acidosis corrects pH toward baseline values, with a high degree of interindividual variability.

Pöschl Reformations Created from High-Resolution Noncontrast Enhanced CT Head Exams Can Be Used to Detect and Classify Superior Semicircular Canal Abnormalities.

Objective: To compare the diagnostic capability of Pöschl reformations created from temporal bone CT (TBCT) and high-resolution noncontrast CT head exams (HR-NECTH) to detect and classify superior semicircular canal (SSC) abnormalities.

Study Design: Retrospective case review.

Setting: Tertiary referral center.

A Survey of Sedation Practices for Adolescents and Young Adults With Acute Lymphoblastic Leukemia Undergoing Lumbar Puncture.

Purpose: Lumbar puncture is a frequently performed procedure for patients undergoing treatment for acute lymphoblastic leukemia. This brief procedure is frequently performed with sedation in young patients but with only local anesthesia in adults. Adolescent and young adult patients may be cared for by physicians with different training backgrounds and sedation preferences, making the utilization of sedation for lumbar punctures variable among providers.

Glaucoma Screening and Referral Risk Factors in a High-Risk Population: Follow-up Study of the Manhattan Vision Screening Study (NYC-SIGHT).

Prcis: Community-based eye health screenings that incorporated fundus photography and optometric exams in a high-risk NYC population effectively identified a higher than average number of participants that required an in-office glaucoma evaluation.

Purpose: To report glaucoma screening rates and risk factors associated with referral for in-office glaucoma evaluation in the Manhattan Vision Screening and Follow-up Study (NYC-SIGHT).

Methods: In this 5-year, cluster-randomized clinical trial, eligible individuals aged 40 and older were recruited from affordable housing developments and senior centers.

gneSeqCOO: a novel method for classifying diffuse large B-cell lymphoma cell of origin based on bulk tumor RNA sequencing profiles.

The cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations.

Screening the human miRNA interactome reveals coordinated up-regulation in melanoma, adding bidirectional regulation to miRNA networks.

Cellular protein expression is coordinated posttranscriptionally by an intricate regulatory network. The current presumption is that microRNAs (miRNAs) work by repression of functionally related targets within a system. In recent work, up-regulation of protein expression via direct interactions of messenger RNA with miRNA has been found in dividing cells, providing an additional mechanism of regulation.

The punctuated evolution of the Venusian atmosphere from a transition in mantle convective style and volcanic outgassing.

A key question in the planetary sciences centers on the divergence between the sibling planets, Venus and Earth. Venus currently does not operate with plate tectonics, and its thick atmosphere has led to extreme greenhouse conditions. It is unknown if this state was set primordially or if Venus was once more Earth-like.

Beyond Increasing Sample Sizes: Optimizing Effect Sizes in Neuroimaging Research on Individual Differences.

Linking neurobiology to relatively stable individual differences in cognition, emotion, motivation, and behavior can require large sample sizes to yield replicable results. Given the nature of between-person research, sample sizes at least in the hundreds are likely to be necessary in most neuroimaging studies of individual differences, regardless of whether they are investigating the whole brain or more focal hypotheses. However, the appropriate sample size depends on the expected effect size.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Using the PROMOTE Screener to Identify Psychosocial Risk Factors for Prenatal Substance Use.

Introduction: There is an urgent need to improve the identification of psychosocial vulnerabilities in clinical practice (eg, stress, unstable living conditions) and examine their contribution to prenatal substance use, especially for legal substances such as alcohol, tobacco, and recently, cannabis.

Methods: We conducted a retrospective chart review of 1842 patients who completed the PROMOTE screening instrument during their first prenatal visit to outpatient clinics of a New York State health system in 6/2019-11/2020. The PROMOTE includes 18 core items to assess psychosocial vulnerabilities including the NIDA Quick Screen assessing past year substance use.

Satisfaction, user experiences, and initial efficacy of a technology-supported self-management intervention (iSMART) to improve post-stroke functioning: a remoted randomized controlled trial.

Background: Self-management interventions empower individuals to manage their chronic conditions and daily life after stroke. However, traditional in-person self-management interventions often face transportation and geographical barriers. Digital interventions may offer a solution to address this gap.

Development of novel patient-reported outcome instruments to assess atopic dermatitis-associated dyspigmentation and xerosis in patients with skin of colour.

Background: The prevalence and burden of atopic dermatitis (AD) are disproportionately high in individuals with skin of colour (SOC). Previous research shows that risk for xerosis and/or dyspigmentation is heightened in this population and may be more bothersome. However, there are no patient-reported instruments developed specifically for these disease sequelae in patients with SOC.

Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.

The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.

IL-21 shapes the B cell response in a context-dependent manner.

The T-cell-derived cytokine IL-21 is crucial for germinal center (GC) responses, but its precise role in B cell function has remained elusive. Using IL-21 receptor (Il21r) conditional knockout mice and ex vivo culture systems, we demonstrate that IL-21 has dual effects on B cells. While IL-21 induced apoptosis in a STAT3-dependent manner in naive B cells, it promoted the robust proliferation of pre-activated B cells, particularly IgG1 B cells.

Restrictive Versus Liberal Transfusion in Symptomatic Coronary Artery Disease and Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials.

Background: In patients with coronary artery disease (CAD) and/or myocardial infarction (MI), anemia is associated with an increased risk of adverse cardiovascular (CV) outcomes. Transfusion goals in such patients remain unclear.

Study Question: A meta-analysis of the available randomized controlled trials (RCTs) was conducted comparing restrictive and liberal transfusion strategies in patients with symptomatic CAD/MI.

The Difficulties of Treating Complement-3-Mediated Glomerulopathy.

Background: C3 glomerulopathy (C3G) is a rare disease affecting the complement alternative pathway, categorized into dense deposit disease and C3 glomerulonephritis. Dense deposit disease predominantly affects younger individuals, while C3 glomerulonephritis tends to manifest in older populations. The diseases are characterized by dysregulation of the complement alternative pathway, leading to the deposition of complement components in the glomeruli and subsequent renal dysfunction.

Self-Perceptions of Aging and Physical Activity in Older Adults with Arthritis: Impact of General Health.

How negative self-perceptions of aging relate to physical activity (PA) in older adults with arthritis is unclear. We examined whether general health mediated the relationship between Awareness of Age-Related change (AARC) losses and PA. We analyzed baseline data from a randomized controlled trial of a PA intervention for adults ≥60 years who self-reported PA, AARC, general health, pain, and social support.

Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in mice.

Exposure to ionizing radiation (IR), both low-LET (e.g., X-rays, γ rays) and high-LET (e.

Long-Term Safety and Efficacy with Roflumilast Cream 0.15% in Patients Aged ≥6 Years with Atopic Dermatitis: A Phase 3 Open-Label Extension Trial.

Safety and efficacy of roflumilast cream 0.15% for atopic dermatitis (AD) were demonstrated in two 4-week phase 3 trials. Evaluate long-term safety, tolerability, and efficacy of roflumilast cream 0.

IP6K1 rewires LKB1 signaling to mediate hyperglycemic endothelial senescence.

Diabetes is a major risk factor for cardiovascular disease, but the molecular mechanisms underlying diabetic vasculopathy have been elusive. Here we report that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by rewiring the liver kinase B1 (LKB1) signaling from activating the adenosine monophosphate-activated protein kinase (AMPK) pathway to the p53 pathway. We found that hyperglycemia upregulated IP6K1, which disrupts the Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein (CHIP)-mediated LKB1 degradation, leading to increased expression levels of LKB1.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

Clubhouse Partnerships with Clinical Services: Current Status and Barriers to Integration.

The Clubhouse model of psychosocial rehabilitation has supported the recovery of people with serious mental illness for over 75 years, but many of the roughly 350 Clubhouses are not well-integrated into the larger health care system, limiting their reach. This article examines Clubhouses' and psychiatric providers' interactions and experiences to understand the nature of and barriers to partnerships. The directors of Clubhouses affiliated with Clubhouse International were surveyed, examining their attitudes and practices around collaboration with psychiatric providers.