Clinical value of plasma pTau181 to predict Alzheimer's disease pathology in a large real-world cohort of a memory clinic.

Background: The identification of patients with an elevated risk of developing Alzheimer's disease (AD) dementia and eligible for the disease-modifying treatments (DMTs) in the earliest stages is one of the greatest challenges in the clinical practice. Plasma biomarkers has the potential to predict these issues, but further research is still needed to translate them to clinical practice. Here we evaluated the clinical applicability of plasma pTau181 as a predictive marker of AD pathology in a large real-world cohort of a memory clinic.

HIF-2α drives hepatic Kupffer cell death and proinflammatory recruited macrophage activation in nonalcoholic steatohepatitis.

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow-derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation.

Perturbing TET2 condensation promotes aberrant genome-wide DNA methylation and curtails leukaemia cell growth.

The ten-eleven translocation (TET) family of dioxygenases maintain stable local DNA demethylation during cell division and lineage specification. As the major catalytic product of TET enzymes, 5-hydroxymethylcytosine is selectively enriched at specific genomic regions, such as enhancers, in a tissue-dependent manner. However, the mechanisms underlying this selectivity remain unresolved.

Therapeutic Response of Alopecia Areata-Associated Nail Changes to Baricitinib.

Nail changes are seen in some individuals with alopecia areata, with the most common variants including pitting and trachyonychia. The nail findings are presumed to be due to the same lymphocytic infiltration seen in hair bulbs in individuals with AA. Baricitinib is an immunomodulatory drug that acts as a selective and reversible inhibitor of JAK proteins and is indicated for adult patients with moderate to severe rheumatoid arthritis who have not responded to other disease-modifying antirheumatic drugs.

Adjunctive Intravenous Argatroban or Eptifibatide for Ischemic Stroke.

Background: Intravenous thrombolysis is a standard treatment of acute ischemic stroke. The efficacy and safety of combining intravenous thrombolysis with argatroban (an anticoagulant agent) or eptifibatide (an antiplatelet agent) are unclear.

Methods: We conducted a phase 3, three-group, adaptive, single-blind, randomized, controlled clinical trial at 57 sites in the United States.

RELATIONSHIP BETWEEN TRPM4 RS8104571 GENOTYPE, CIRCULATING TRPM4 AND SUR1, AND CLINICAL OUTCOME FOLLOWING TRAUMATIC BRAIN INJURY.

The variant single nucleotide polymorphism rs8104571 has been associated with poor outcomes following traumatic brain injury (TBI) and is most prevalent in those of African ancestry. This single nucleotide polymorphism (SNP) resides within a gene coding for the TRPM4 protein, which complexes with SUR1 protein to create a transmembrane ion channel and is believed to contribute to cellular swelling and cell death in neurological tissue. Our study evaluates the relationship between circulating TRPM4 and SUR1, rs8104571 genotype, and clinical outcome in TBI patients.

TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy.

Purpose: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.

Methods: TROPHY-U-01 (ClinicalTrials.

Comparison of combined intravenous and intra-arterial thrombolysis with intravenous thrombolysis alone in stroke patients undergoing mechanical thrombectomy: a propensity-matched analysis.

Background: A combination of intravenous (IVT) or intra-arterial (IAT) thrombolysis with mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) has been investigated. However, there is limited data on patients who receive both IVT and IAT compared with IVT alone before MT.

Methods: STAR data from 2013 to 2023 was utilized.

Subsyndromes and symptom clusters: Multilevel factor analysis of behavioral and psychological symptoms of dementia with intensive longitudinal data.

Introduction: Behavioral and psychological symptoms in dementia (BPSD) are dynamic phenomena with a high amount of intraindividual variability. We applied a multilevel framework to identify subsyndromes (between-person factors) that represent clinically relevant profiles of BPSD and identify symptom clusters (within-person factors) that represent contextually driven daily symptom experiences.

Methods: This study used an intensive longitudinal design in which 68 co-residing family caregivers to persons living with dementia were recruited to proxy report on their care recipient's daily symptom experiences of 23 different BPSD for eight consecutive days (n = 443 diaries).

Trimethylamine -Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

Background: Growing evidence indicates that trimethylamine -oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine -oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).

Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites.

Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM).

The development and current directions of a diversity specialty clinic: Implications for multicultural training in psychology.

Addressing systemic injustices and racism in training and clinical service provision are key next steps in clinical science. While the APA Multicultural Guidelines and accreditation standards have long emphasized this need, most graduate programs offer a single course on diversity, equity, and inclusion topics, which is inadequate to train and sustain culturally humble providers and redress systemic injustices and racism within psychology. Few "real-world" examples exist to guide the development of training models.

Brief Review and Primer of Key Terminology for Artificial Intelligence and Machine Learning in Hypertension.

Recent breakthroughs in artificial intelligence (AI) have caught the attention of many fields, including health care. The vision for AI is that a computer model can process information and provide output that is indistinguishable from that of a human and, in specific repetitive tasks, outperform a human's capability. The 2 critical underlying technologies in AI are used for supervised and unsupervised machine learning.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression.

Deep Learning-Based Prediction Modeling of Major Adverse Cardiovascular Events After Liver Transplantation.

Objective: To validate deep learning models' ability to predict post-transplantation major adverse cardiovascular events (MACE) in patients undergoing liver transplantation (LT).

Patients And Methods: We used data from Optum's de-identified Clinformatics Data Mart Database to identify liver transplant recipients between January 2007 and March 2020. To predict post-transplantation MACE risk, we considered patients' demographics characteristics, diagnoses, medications, and procedural data recorded back to 3 years before the LT procedure date (index date).

The intersection of parent questions, child skills, and activity context in informal science, technology, engineering, and math learning.

Adult verbal input occurs frequently during parent-child interactions. However, few studies have considered how parent language varies across informal STEM (science, technology, engineering, and math) activities. In this study, we examined how open and closed parent questions (a) differed across three STEM activities and (b) related to math, science, and vocabulary knowledge in their preschool-aged children.

Gastrointestinal toxicities of proteasome inhibitor therapy.

Purpose: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib.

Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

Background: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used.

Associations of role, area deprivation index, and race with health behaviors and body mass index among localized prostate cancer patients and their partners.

Purpose: To examine the associations of role (localized prostate cancer (PCa) patient vs. their intimate partner), area deprivation index (ADI-higher scores indicating higher neighborhood deprivation levels), and race (Black/African American (AA) vs. White) with health behaviors and body mass index (BMI) among PCa patients and partners.

Aurkin-A, a TPX2-Aurora A small molecule inhibitor disrupts Alisertib-induced polyploidy in aggressive diffuse large B cell lymphoma.

Chemotherapy induced polyploidy is a mechanism of inherited drug resistance resulting in an aggressive disease course in cancer patients. Alisertib, an Aurora Kinase A (AK-A) ATP site inhibitor, induces cell cycle disruption resulting in polyaneuploidy in Diffuse Large B Cell Lymphoma (DLBCL). Propidium iodide flow cytometry was utilized to quantify alisertib induced polyploidy in U2932 and VAL cell lines.

Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial.

Microsatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study.

Development of primary osteoarthritis during aging in genetically diverse UM-HET3 mice.

Background: Primary osteoarthritis (OA) occurs without identifiable underlying causes such as previous injuries or specific medical conditions. Age is a major contributing factor to OA, and as one ages, various joint tissues undergo gradual change, including degeneration of the articular cartilage, alterations in subchondral bone (SCB) morphology, and inflammation of the synovium.

Methods: We investigated the prevalence of primary OA in aged, genetically diverse UM-HET3 mice.