Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.

The mechanisms underlying cooperative activation and inactivation of myocardial force extend from local, near-neighbor interactions involving troponin-tropomyosin regulatory units (RU) and crossbridges (XB) to more global interactions across the sarcomere. To better understand these mechanisms in the hearts of small and large mammals, we undertook a simplified mathematical approach to assess the contribution of three types of near-neighbor cooperative interactions, i.e.

Competition between Halogen Atom and Ring of Halobenzenes as Hydrogen Bond Electron Donor Sites.

A halobenzene molecule contains several sites that are capable of acting in an electron-donating capacity within a H-bond.  One set of such sites comprise the lone electron pairs of the halogen (X) atoms on the periphery of the ring.  The π-electron system above the ring plane can also fulfill this function in many cases.

Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity.

Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.

Natural and Bioengineered Extracellular Vesicles in Diagnosis, Monitoring and Treatment of Cancer.

Extracellular vesicles (EVs) are cell derived nanovesicles which are implicated in both physiological and pathological intercellular communication, including the initiation, progression, and metastasis of cancer. The exchange of biomolecules between stromal cells and cancer cells via EVs can provide a window to monitor cancer development in real time for better diagnostic and interventional strategies. In addition, the process of secretion and internalization of EVs by stromal and cancer cells in the tumor microenvironment (TME) can be exploited for delivering therapeutics.

Rethinking gender differences: An investigation of comorbid psychopathology and alcohol use disorder in veterans.

Background: While men have been found to drink more alcohol and have higher rates of alcohol-related mortality, women tend to experience higher rates of alcohol-related consequences, including psychological comorbidities and worse alcohol use disorder (AUD) outcomes. However, gender differences in comorbid psychopathology and associations with AUD outcomes among veterans are less well understood.

Methods: Veterans (N = 126; 32 women) receiving inpatient treatment for AUD completed baseline clinical measures including the Beck Depression Inventory-II, Beck Anxiety Inventory, Early Life Stress Questionnaire, and PTSD Checklist for DSM-5.

The Changing pathogenesis of liver cancer in Hawaii over three decades.

Background: Worldwide trends support the increasing contribution of hepatic steatosis on the incidence of hepatocellular carcinoma (HCC). This study investigates if similar changes are seen in Hawaii, where the incidence of HCC is higher than most of the United States. Methods; This is a retrospective study of 1651 patients diagnosed with HCC (1991-2023) that includes 60-70% of Hawaii's HCC cases.

An IgM Cleaving Enzyme for Clearance of Anti-Pig Xenoreactive Antibodies in a Nonhuman Primate Model.

Background: The removal of preformed antibodies with cleaving enzyme like IdeS (Imlifidase) has demonstrated therapeutic potential in organ transplantation for sensitized recipients. However, preformed xenoreactive antibodies (XAbs) against porcine glycans are predominantly IgM and considered detrimental in pig-to-human xenotransplantation.

Methods: Recombinant IceM, an endopeptidase cleaving IgM, was generated in Escherichia coli.

Hotspots and global trends in research of host immune response in periodontitis: A bibliometric analysis.

Background: The host immune response plays a major role in the pathogenesis of periodontitis. A bibliometric study can be crucial to understanding the different processes involved in this area; however, to our knowledge, it has not been published until now. Therefore, a bibliometric analysis was conducted to assess research hotspots and global trends in scientific articles about the immune response in periodontitis published between 1952 and 2023.

Operation of spinal sensorimotor circuits controlling phase durations during tied-belt and split-belt locomotion after a lateral thoracic hemisection.

Locomotion is controlled by spinal circuits that interact with supraspinal drives and sensory feedback from the limbs. These sensorimotor interactions are disrupted following spinal cord injury. The thoracic lateral hemisection represents an experimental model of an incomplete spinal cord injury, where connections between the brain and spinal cord are abolished on one side of the cord.

Mindful self-compassion for lung cancer (MSC-LC): Incorporating perspectives of lung cancer patients, clinicians, and researchers to create an adapted intervention to reduce lung cancer stigma.

Background: Stigma is a pervasive and distressing problem experienced frequently by lung cancer patients, and there is a lack of psychosocial interventions that target the reduction of lung cancer stigma. Mindful self-compassion (MSC) is an empirically supported intervention demonstrated to increase self-compassion and reduce feelings of shame and distress in non-cancer populations. However, there are several anticipated challenges for delivering MSC to lung cancer patients, and modifications may be needed to improve acceptability, appropriateness, and feasibility.

Need of the hour: A service failure recovery reorientation for U.S. hospitals.

Issue: Many hospitals in the United States are facing significant postpandemic operational challenges largely as a result of increasing demand for health care services. Operational issues increase the risk of service failures. Improving the patient experience after service failures may lead to better outcomes for both patients and hospitals.

Dendritic alterations precede age-related dysphagia and nucleus ambiguus motor neuron death.

Motor neurons (MNs) within the nucleus ambiguus innervate the skeletal muscles of the larynx, pharynx and oesophagus, which are essential for swallow. Disordered swallow (dysphagia) is a serious problem in elderly humans, increasing the risk of aspiration, a key contributor to mortality. Despite this importance, very little is known about the pathophysiology of ageing dysphagia and the relative importance of frank muscle weakness compared to timing/activation abnormalities.

FAM43A coordinates mtDNA replication and mitochondrial biogenesis in response to mtDNA depletion.

Mitochondrial retrograde signaling (MRS) pathways relay the functional status of mitochondria to elicit homeostatic or adaptive changes in nuclear gene expression. Budding yeast have "intergenomic signaling" pathways that sense the amount of mitochondrial DNA (mtDNA) independently of oxidative phosphorylation (OXPHOS), the primary function of genes encoded by mtDNA. However, MRS pathways that sense the amount of mtDNA in mammalian cells remain poorly understood.

Cross-Sectional Comparison of Structural MRI Markers of Impairment in a Diverse Cohort of Older Adults.

Neurodegeneration is presumed to be the pathological process measure most proximal to clinical symptom onset in Alzheimer Disease (AD). Structural MRI is routinely collected in research and clinical trial settings. Several quantitative MRI-based measures of atrophy have been proposed, but their low correspondence with each other has been previously documented.

Predictors of Arrhythmia Recurrence After Cryoballoon Ablation for Persistent Atrial Fibrillation: A Sub-Analysis of the Cryo Global Registry.

Introduction: Freedom from recurrences of atrial tachyarrhythmia (ATA) is suboptimal after pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (PsAF). This sub-analysis from the Cryo Global Registry sought to investigate predictors of ablation success after PVI using cryoballoon ablation (CBA) for PsAF.

Methods And Results: ATA recurrence was defined as ≥ 30 s recurrence of atrial fibrillation, atrial flutter or atrial tachycardia after a 90-day blanking period and through 12-months.

Opportunistic assessment of steatotic liver disease in lung cancer screening eligible individuals.

Background: Steatotic liver disease (SLD) is a potentially reversible condition but often goes unnoticed with the risk for end-stage liver disease.

Purpose: To opportunistically estimate SLD on lung screening chest computed tomography (CT) and investigate its prognostic value in heavy smokers participating in the National Lung Screening Trial (NLST).

Material And Methods: We used a deep learning model to segment the liver on non-contrast-enhanced chest CT scans of 19,774 NLST participants (age 61.

Accelerated Destruction of Passive Film and Microbial Corrosion of 316L Stainless Steel via Extracellular Electron Transfer.

The dense passive film on 316L stainless steel is the key in its corrosion resistance. Its interactions with an electroactive biofilm are critical in deciphering microbial corrosion. Herein, an in-depth investigation using genetic manipulations and addition of an exogenous electron mediator found that extracellular electron transfer (EET) mediated by the electroactive S.

Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.

Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC.

Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.

This proceedings article summarizes the inaugural "T Cells in the Brain" symposium held at Columbia University. Experts gathered to explore the role of T cells in neurodegenerative diseases. Key topics included characterization of antigen-specific immune responses, T cell receptor (TCR) repertoire, microbial etiology in Alzheimer's disease (AD), and microglia-T cell crosstalk, with a focus on how T cells affect neuroinflammation and AD biomarkers like amyloid beta and tau.

Phytochemical-Based Drug Discovery for Breast Cancer: Combining Virtual Screening and Molecular Dynamics to Identify Novel Therapeutics.

Maternal Embryonic Leucine Zipper Kinase (MELK), a pivotal signaling protein, plays a crucial role in various physiological processes such as cell growth, survival, and differentiation. There is currently a growing interest in MELK as a promising therapeutic target for multiple cancers, including triple-negative breast cancer (TNBC). Exploring MELK as a target offers a prospective strategy to impede cancer progression and enhance the efficacy of conventional anticancer therapies.

Current practices by Alzheimer's Disease Research Centers to remunerate research participants.

Introduction: Recent guidance from the National Alzheimer's Coordinating Center (NACC) recommends remuneration for all Alzheimer's disease (AD) research participants. Given AD research recruitment challenges, we assessed the remuneration practices at Alzheimer's Disease Research Centers (ADRCs).

Methods: We surveyed 37 ADRCs about remuneration for longitudinal research participants.

Understanding Types of Stigma Experienced in Black Women Living With HIV in Baltimore, Maryland: A Mixed Methods Study.

Aim: To understand how Black or African American women living with HIV (WLH) experience different types of stigma in their daily lives.

Design: Secondary analysis of quantitative and qualitative data from a recent clinical trial in Baltimore, Maryland.

Methods: Quantitative data were collected in the baseline survey, and qualitative data were gathered during 6-month follow-up focus group and individual interviews.

Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States.

Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities.

Multi-center evaluation of the Alinity m HR HPV assay with liquid-based cytology cervical specimens in the United States.

Incorporating molecular testing for human papillomavirus (HPV) into the screening of cervical specimens can improve risk stratification and, in turn, patient management. Infection with a high-risk (HR) HPV genotype is associated with greater risk for persistent infection, viral integration, and progression of cervical neoplasia. Current guidelines consider HPV 16 or HPV 18 clinically actionable with referral to colposcopy; however, 12 Other HR HPV genotypes have been associated with cervical cancer risk, suggesting a benefit of extended genotyping.