Association of SGLT2 Inhibitor Initiation and PSA Response in Prostate Cancer.

Introduction: Non-castrating therapies are an unmet clinical need for patients with advanced prostate cancer. To maximize quality of life and prioritize cardiovascular health, we investigated SGLT2 inhibitors as a non-castrating therapy in patients with prostate cancer.

Materials And Methods: We conducted a retrospective analysis of patients with either local or biochemically recurrent prostate cancer who initiated therapy with an SGLT2 inhibitor without concurrent androgen deprivation therapy.

SHIP-1 regulates the differentiation and function of Tregs via inhibiting mTORC1 activity.

Cell metabolism is crucial for orchestrating the differentiation and function of regulatory T cells (Tregs). However, the underlying mechanism that coordinates cell metabolism to regulate Treg activity is not completely understood. As a pivotal molecule in lipid metabolism, the role of SHIP-1 in Tregs remains unknown.

Do Caregivers Value the New Antiamyloid Treatments for Alzheimer's Disease More Than Home-Based Care?

Objective: The new antiamyloid medications Lecanemab (Leqembi) and donanemab (Kisunla) are the first disease-modifying treatments for Alzheimer's disease (AD) to receive full FDA approval. However, some commentators question whether the drugs' benefits outweigh their risks, burdens, and costs to patients. This study assessed the perceived value of these medications by asking caregivers of persons with AD to compare them to a widely used intervention in AD management: home-based care.

Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes.

Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection.

Clinical and biochemical footprints of inherited metabolic diseases: XVII. Dysmorphisms.

Dysmorphisms, or physical abnormalities in appearance, can vary in frequency and severity among individuals with inherited metabolic disorders (IMD). The prevalence of dysmorphisms in these disorders can range from rare occurrences to more common features, depending on the specific disorder and its genetic characteristics. It is important to note that not all individuals with IMDs will exhibit dysmorphic features, and the presence of such features may vary widely among different types of metabolic disorders.

An expert consensus statement on biomarkers of ageing for use in intervention studies.

Biomarkers of ageing serve as important outcome measures in longevity-promoting interventions. However, there is limited consensus on which specific biomarkers are most appropriate for human intervention studies. This work aimed to address this need by establishing an expert consensus on biomarkers of ageing for use in intervention studies via the Delphi method.

Clinical Applications of Bone Marrow CD34 Immunohistochemistry (BM CD34 IHC) Assay: International Council for Standardization in Hematology (ICSH) Guidelines.

Introduction: Investigation of bone marrow (BM) trephine biopsies and/or clot sections by CD34 immunohistochemistry (IHC) testing has been used by pathologists for several decades, and its clinical value has been well established with QBEND10 being the most frequently used primary antibody (Ab) clone. However, most other parameters related to the IHC protocol as well as the readout vary widely between clinical laboratories and in the published literature. The ICSH Working Group having reviewed the published evidence has established guidelines that will help to harmonize performance and reporting of CD34 IHC on BM biopsies.

Limbic system synaptic dysfunctions associated with prion disease onset.

Misfolding of normal prion protein (PrP) to pathological isoforms (prions) causes prion diseases (PrDs) with clinical manifestations including cognitive decline and mood-related behavioral changes. Cognition and mood are linked to the neurophysiology of the limbic system. Little is known about how the disease affects the synaptic activity in brain parts associated with this system.

Bacterial intragenic inversions: a new layer of diversity.

DNA inversions in bacteria were known to create diversity through intergenic or partial intergenic changes. Now, Chanin, West, et al. reveal intragenic inversions, enabling single genes to encode multiple protein variants via sequence recoding or truncation - an unexpected mechanism for expanding protein diversity without increasing genome size.

Chromosome X-wide common variant association study in autism spectrum disorder.

Autism spectrum disorder (ASD) displays a notable male bias in prevalence. Research into rare (<0.1) genetic variants on the X chromosome has implicated over 20 genes in ASD pathogenesis, such as MECP2, DDX3X, and DMD.

β-actin function in platelets and red blood cells can be performed by γ-actin and is therefore independent of actin isoform protein sequence.

Actin is an essential component of the cytoskeleton in every eukaryotic cell. Cytoplasmic β-and γ-actin are over 99% identical to each other at the protein level, but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence.

Molecular basis for plasma membrane recruitment of PI4KA by EFR3.

The lipid kinase phosphatidylinositol 4 kinase III α (PI4KIIIα/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B.

Cardiovascular complications in vascular connective tissue disorders after COVID-19 infection and vaccination.

Background: COVID-19 infection and vaccination have been reported to confer an elevated risk for cardiovascular events (CVE). We sought to determine whether individuals with an underlying vascular connective tissue disorder including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), or vascular Ehlers Danlos syndrome (vEDS) are at increased risk for cardiac events after COVID-19 infection or vaccination.

Methods: 325 respondents self-reported data through a cross-sectional, web-based survey available from 22 November 2021, through 15 March 2022 regarding COVID-19 illness and vaccinations, the occurrence of any CVE, and adverse events following vaccination.

Expression, Purification, and In Vitro Analysis of Myosin.

To understand the mechanics and kinetic properties of cytoskeletal molecular motors such as myosin, typically the motor of interest needs to be expressed and purified and then analyzed using a range of in vitro-based assays. In this chapter, we describe how to express and purify myosin using the insect cell system, how to characterize the purified protein by mass photometry and negative-stain EM to assess its quality, and how to perform in vitro assays in which fluorescently labeled myosin walks along actin tracks, including a brief description of adapting these assays for MINFLUX imaging.

Relationship of Sex and Diagnosis With Symptoms and Illness Impact in Urologic Chronic Pelvic Pain; A Mapp Network Analysis.

Objective: To assess differences in clinical presentation and illness impact in men and women presenting with urologic chronic pelvic pain syndrome (UCPPS) and between men diagnosed with interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods: 356 men and 605 women from six sites across the United States were assessed using a comprehensive set of demographic, symptom, and illness impact measures. Multivariable regression analyses examined differences between men and women and between men previously diagnosed with CP/CPPS or IC/BPS.

Multilevel Mediators on the Associations of Neighborhood Social Environmental Factors and Severity of Metabolic Syndrome: The Jackson Heart Study.

Background: Neighborhood characteristics serve as risk factors for metabolic syndrome (MetS). However, the intermediary factors linking this relationship remain understudied. Thus, we investigated the sex-specific mediating role of C-reactive protein, physical activity (PA), and perceived stress in the associations of perceived neighborhood social environment (PNSE) with MetS severity among Black adults.

Growth hormone secretagogue receptor and cannabinoid receptor type 1 intersection in the mouse brain.

The growth hormone secretagogue receptor (GHSR) and the cannabinoid receptor type 1 (CB1R) are G-protein coupled receptors highly expressed in the brain and involved in critical regulatory processes, such as energy homeostasis, appetite control, reward, and stress responses. GHSR mediates the effects of both ghrelin and liver-expressed antimicrobial peptide 2, while CB1R is targeted by cannabinoids. Strikingly, both receptors mediate their effects by acting on common brain areas and their individual roles have been well characterized.

Predicting the tumor microenvironment composition and immunotherapy response in non-small cell lung cancer from digital histopathology images.

Immune checkpoint inhibitors (ICI) have become integral to treatment of non-small cell lung cancer (NSCLC). However, reliable biomarkers predictive of immunotherapy efficacy are limited. Here, we introduce HistoTME, a novel weakly supervised deep learning approach to infer the tumor microenvironment (TME) composition directly from histopathology images of NSCLC patients.

Disrupting Notch signaling related HES1 in myeloid cells reinvigorates antitumor T cell responses.

Background: Tumor-associated macrophages (TAMs) are immunosuppressive cells within the tumor microenvironment (TME) that hinder anti-tumor immunity. Notch signaling is a pathway crucial for TAM differentiation and function. Here, we investigate the role of HES1, a downstream target of Notch signaling, in TAM-mediated immunosuppression and explore its potential as a target for cancer immunotherapy.

Replicating RNA vaccine confers durable immunity against Crimean Congo hemorrhagic fever virus challenge in mice.

Spread by Hyalomma genus ticks, Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic disease endemic throughout Southern and Eastern Europe, Asia, and Africa. To date, there are no widely approved vaccines for CCHFV and treatment for disease is largely supportive. Due to this lack of intervention, the WHO lists CCHFV as a high-priority pathogen.

Tackling algorithmic bias and promoting transparency in health datasets: the STANDING Together consensus recommendations.

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups.

Is the impact of spontaneous movements on early visual cortex species specific?

Recent studies in non-human primates do not find pronounced signals related to the animal's own body movements in the responses of neurons in the visual cortex. This is notable because such pronounced signals have been widely observed in the visual cortex of mice. Here, we discuss factors that may contribute to the differences observed between species, such as state, slow neural drift, eccentricity, and changes in retinal input.

Lipid levels increase to the normal range after nonmyeloablative hematopoietic cell transplantation for sickle cell disease.

Background: Individuals with sickle cell disease (SCD) have a unique type of dyslipidemia characterized by low total cholesterol (TC), low low-density lipoprotein cholesterol (LDL-c), low high-density lipoprotein cholesterol (HDL-c), and normal triglycerides (TG). This lipid state is theorized to be cardioprotective against atherosclerosis. In SCD, hematopoietic cell transplant (HCT) offers a potentially curative therapy.

Pediatric Transplant and Cellular Therapy Consortium RESILIENT Conference on Pediatric Chronic Graft-Versus-Host Disease Survivorship After Hematopoietic Cell Transplantation: Part I. Phases of Chronic GVHD, Supportive Care, and Systemic Therapy Discontinuation.

Current literature lacks details on the impact of pediatric chronic graft-versus-host disease (cGVHD) on long-term survivorship after allogeneic hematopoietic cell transplantation (HCT). Nonetheless, cGVHD remains a leading cause of post-transplant morbidity and mortality in children and adolescents, which is particularly relevant given the longer life-expectancy after HCT (measured in decades) compared to older adults. To address this knowledge gap, leaders of the Pediatric Transplant and Cellular Therapy Consortium convened a multidisciplinary taskforce of experts in pediatric cGVHD and HCT late effects known as RESILIENT after Chronic GVHD (Research and Education towards Solutions for Late effects to Innovate, Excel, and Nurture after cGVHD).