Nuclear p62 condensates stabilize the promyelocytic leukemia nuclear bodies by sequestering their ubiquitin ligase RNF4.

Liquid-liquid phase separation has emerged as a crucial mechanism driving the formation of membraneless biomolecular condensates, which play important roles in numerous cellular processes. These condensates, found both in the nucleus and cytoplasm, are formed through multivalent, low-affinity interactions between various molecules. P62-containing condensates serve, among other functions, as proteolytic hubs for the ubiquitin-proteasome system.

Performance of Plasma Biomarkers Combined with Structural MRI to Identify Candidate Participants for Alzheimer's Disease-Modifying Therapy.

Background: Recently, two monoclonal antibodies that lower amyloid plaques have shown promising results for the treatment of Mild Cognitive Impairment (MCI) and mild dementia due to Alzheimer's disease (AD). These treatments require the identification of cognitively impaired older adults with biomarker evidence of AD pathology using CSF biomarkers or amyloid-PET. Previous studies showed plasma biomarkers (plasma Aβ42/Aβ40 and p-tau181) and hippocampal volume from structural MRI correlated with brain amyloid pathology.

Early Detection of Ovarian Cancer Using Cell-Free DNA Fragmentomes and Protein Biomarkers.

There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.

Posttraumatic Stress Disorder Symptom Clusters, Exposure to Potentially Morally Injurious Events, and Aggression Among Army Veterans.

Objective: Very few studies have examined the association between posttraumatic stress disorder (PTSD) symptom clusters and aggression since the change in PTSD diagnosis criteria a decade ago. Furthermore, these studies have used measures based on PTSD criteria of the DSM-IV. The current study therefore examines the association between PTSD symptom clusters, exposure to potentially morally injurious events (PMIEs), and various types of aggression following the change in PTSD criteria and in accordance with the criteria of the DSM-5-TR.

Selective Enhancer Gain-of-Function Deregulates MYC Expression in Multiple Myeloma.

MYC deregulation occurs in the majority of multiple myeloma cases and is associated with progression and worse prognosis. Enhanced MYC expression occurs in about 70% of patients with multiple myeloma, but it is known to be driven by translocation or amplification events in only ∼40% of myelomas. Here, we used CRISPR interference to uncover an epigenetic mechanism of MYC regulation whereby increased accessibility of a plasma cell-type-specific enhancer leads to increased MYC expression.

AI-Derived Left Ventricular Mass From Noncontrast Cardiac CT: Correlation With Contrast CT Angiography and CMR.

Background: Noncontrast computed tomography (CT) scans are not used for evaluating left ventricle myocardial mass (LV mass), which is typically evaluated with contrast CT or cardiovascular magnetic resonance imaging (CMR).

Objectives: The purpose of the study was to assess the feasibility of LV mass estimation from standard, ECG-gated, noncontrast CT using an artificial intelligence (AI) approach and compare it with coronary CT angiography (CTA) and CMR.

Methods: We enrolled consecutive patients who underwent coronary CTA, which included noncontrast CT calcium scanning and contrast CTA, and CMR.

Effect of Masking Secondary to the COVID-19 Pandemic on Functional Capacity Improvement in Cardiac Rehabilitation.

Purpose: Given the difficulty to perform exercise training wearing a mask, we examined differences in functional capacity improvement between masking during the coronavirus disease 2019 (COVID-19) pandemic and non-masking prior to the pandemic for patients undergoing cardiac rehabilitation (CR).

Methods: Records of 660 patients who underwent and completed ≥ 18 sessions of CR in 2018 (n = 318, non-masking) and in 2022 (n = 342, masking) at an academic health system were analyzed. The primary outcome was post-CR change in functional capacity in metabolic equivalents (MET) measured by exercise stress test.

The Clinical Nurse Specialist: Maximizing Return on Investment.

The United States health care system is facing an unprecedented nursing shortage, increasing complexity of care, and fewer experienced nurse mentors. These factors contribute to a cycle of burnout, turnover, decreased quality and safety, and a worsening financial bottom line. Improving these contributing factors depends on our ability to mitigate the structural causes of burnout and turnover.

Unveiling the mechanical role of radial fibers in meniscal tissue: Toward structural biomimetics.

The meniscus tissue is crucial for knee joint biomechanics and is frequently susceptible to injuries resulting in early-onset osteoarthritis. Consequently, the need for meniscal substitutes spurs ongoing development. The meniscus is a composite tissue reinforced with circumferential and radial collagenous fibers; the mechanical role of the latter has yet to be fully unveiled.

Astrocytic glutamate transport is essential for the memory-enhancing effects of 17β-estradiol in ovariectomized mice.

Infusion of 17β-estradiol (E) into the dorsal hippocampus (DH) of ovariectomized (OVX) mice enhances memory consolidation, an effect that depends on rapid phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Astrocytic glutamate transporter 1 (GLT-1) modulates neurotransmission via glutamate uptake from the synaptic cleft. However, little is known about the contribution of DH astrocytes, and astrocytic glutamate transport, to the memory-enhancing effects of E.

Digoxin initiation after an acute heart failure episode and its association with post-discharge outcomes: an international multicenter analysis.

Digoxin is commonly used to treat acute heart failure (AHF), especially in patients with concurrent atrial fibrillation (AF). Nonetheless, there is little consensus about in which patients digoxin should be given, the proper time for digoxin initiation, and whether digoxin initiation is associated with improved outcomes. We investigated factors related to digoxin initiation after an episode of AHF and whether patients receiving digoxin presented better short-term outcomes.

Avoidance and Rumination as Predictors of Substance Use, Mental Health, and Pain Outcomes Among People Living With HIV.

Pain, substance use, and mental health conditions are common among people living with HIV (PLWH), and avoidance and rumination may influence the co-occurrence of these conditions. The present study examined longitudinal associations between avoidance/rumination and pain outcomes, anxiety, anger, and substance use among PLWH. Participants (N = 187) with chronic pain and depressive symptoms completed self-report assessments over a 1-year period.

Cell-surface Milieu Remodeling in Human Dendritic Cell Activation.

Dendritic cells (DCs) are specialized sentinel and APCs coordinating innate and adaptive immunity. Through proteins on their cell surface, DCs sense changes in the environment, internalize pathogens, present processed Ags, and communicate with other immune cells. By combining chemical labeling and quantitative mass spectrometry, we systematically profiled and compared the cell-surface proteomes of human primary conventional DCs (cDCs) in their resting and activated states.

Cell-free and extracellular vesicle microRNAs with clinical utility for solid tumors.

As cutting-edge technologies applied for the study of body fluid molecular biomarkers are continuously evolving, clinical applications of these biomarkers improve. Diverse forms of circulating molecular biomarkers have been described, including cell-free DNA (cfDNA), circulating tumor cells (CTCs), and cell-free microRNAs (cfmiRs), although unresolved issues remain in their applicability, specificity, sensitivity, and reproducibility. Translational studies demonstrating the clinical utility and importance of cfmiRs in multiple cancers have significantly increased.

Targeting the muscarinic M1 receptor with a selective, brain-penetrant antagonist to promote remyelination in multiple sclerosis.

Multiple sclerosis (MS) is a chronic and debilitating neurological disease that results in inflammatory demyelination. While endogenous remyelination helps to recover function, this restorative process tends to become less efficient over time. Currently, intense efforts aimed at the mechanisms that promote remyelination are being considered promising therapeutic approaches.

Characterization of early non-responders within behavioral weight loss treatment.

Objective: Given that low early (4 weeks) weight loss (WL) predicts longer-term WL, the purpose of this study was to identify factors associated with poor early WL.

Methods: 438 adults with overweight/obesity participating in an Internet-delivered behavioral WL program provided weights at baseline and 4 weeks. Participants were stratified by percent WL at 4 weeks: LOW: <2% WL, MEDIUM: 2 to <4% WL, HIGH: ≥4% WL and groups were compared on baseline variables (demographics, physical activity, and psychosocial measures) and 4-week intervention adherence.