Predictors of Device-Related Thrombus After Left Atrial Appendage Occlusion: TED-F Score.

Background: Left atrial appendage (LAA) occlusion (LAAO) is performed to prevent LAA thrombus in patients with atrial fibrillation (AF). The risk of device-related thrombus (DRT) on the atrial side of the LAAO device is approximately 4%. Identifying patients at high risk of DRT would enable closer surveillance and more-aggressive anticoagulation to prevent post-LAAO DRT-related stroke.

Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is often resistant to therapy. An immune suppressive tumor microenvironment (TME) and oncogenic mutations in have both been implicated as drivers of resistance to therapy. Mitogen-activated protein kinase (MAPK) inhibition has not yet shown clinical efficacy, likely because of rapid acquisition of tumor-intrinsic resistance.

Escaping the benthos with Coral Reef Arks: effects on coral translocation and fish biomass.

Anthropogenic stressors like overfishing, land based runoff, and increasing temperatures cause the degradation of coral reefs, leading to the loss of corals and other calcifiers, increases in competitive fleshy algae, and increases in microbial pathogen abundance and hypoxia. To test the hypothesis that corals would be healthier by moving them off the benthos, a common garden experiment was conducted in which corals were translocated to midwater geodesic spheres (hereafter called Coral Reef Arks or Arks). Coral fragments translocated to the Arks survived significantly longer than equivalent coral fragments translocated to Control sites (.

Frequency of Persistent Opioid Use 6 Months After Exposure to IV Opioids in the Emergency Department: A Prospective Cohort Study.

Background: As rates of opioid use disorder in the general population have increased, some have questioned whether IV opioids should be used routinely for treatment of acute severe pain in the emergency department (ED).

Objectives: We determined the incidence of persistent opioid use among opioid-naïve patients exposed to IV opioids in the ED.

Methods: This was a prospective observational cohort study conducted in two EDs in the Bronx, NY.

A sequential, multiple-assignment, randomized trial of analgesic strategies for acute musculoskeletal Pain.

Background: Most methodologically rigorous, ED-based, comparative effectiveness analgesic studies completed in the last two decades failed to find a clinically important difference between the comparators. We believe that many of these comparative effectiveness studies were biased towards the null hypothesis because some ED patients with intense pain will respond to relatively mild interventions. We hypothesized that including a run-in period would alter the results of an acute pain RCT.

Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression.

The tumor microenvironment (TME) profoundly influences tumorigenesis, with gene expression in the breast TME capable of predicting clinical outcomes. The TME is complex and includes distinct cancer-associated fibroblast (CAF) subtypes whose contribution to tumorigenesis remains unclear. Here, we identify a subset of myofibroblast CAFs (myCAF) that are senescent (senCAF) in mouse and human breast tumors.

Senescence Defines a Distinct Subset of Myofibroblasts That Orchestrates Immunosuppression in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) therapeutic resistance is largely attributed to a unique tumor microenvironment embedded with an abundance of cancer-associated fibroblasts (CAF). Distinct CAF populations were recently identified, but the phenotypic drivers and specific impact of CAF heterogeneity remain unclear. In this study, we identify a subpopulation of senescent myofibroblastic CAFs (SenCAF) in mouse and human PDAC.

Integrating Palliative Care Into the Management of Genitourinary Malignancies.

Palliative care (PC) plays a critical role in managing the difficulties associated with genitourinary malignancies. Its primary aim is to improve the overall health of patients, provide support to both patients and their caregivers, and help individuals to navigate the complex decisions about treatment and end-of-life care. PC takes a holistic approach to patient care, recognizing that genitourinary malignancies affect multiple aspects of a person's life.

Topical Diclofenac Versus Oral Ibuprofen Versus Diclofenac + Ibuprofen for Emergency Department Patients With Acute Low Back Pain: A Randomized Study.

Study Objective: Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are useful for a variety of musculoskeletal injuries. It is not known whether topical NSAIDs should be used for patients presenting with acute nonradicular musculoskeletal low back pain.

Methods: We conducted a randomized, placebo-controlled double-blind study in which patients 18 to 69 years of age visiting the emergency department (ED) with acute, nontraumatic, nonradicular, musculoskeletal low back pain were randomized at the time of discharge to treatment with 400 mg oral ibuprofen + placebo topical gel, 1% diclofenac topical gel + oral placebo, or 400 mg ibuprofen + 1% diclofenac topical gel.

Escaping malnutrition by shifting habitats: A driver of three-spined stickleback invasion in Lake Constance.

Fatty acids, and especially long-chain polyunsaturated fatty acids, are biologically important components in the metabolism of vertebrates, including fish. Essential fatty acids (EFA) are those that in a given animal cannot be synthesized or modified from precursors and must therefore be acquired via the diet. Because EFAs are often unevenly distributed in nature, this requirement may drive species to make behavioral or ecological adaptations to avoid malnutrition.

Fibrosis induced by resident macrophages has divergent roles in pancreas inflammatory injury and PDAC.

Tissue-resident macrophages (TRMs) are long-lived cells that maintain locally and can be phenotypically distinct from monocyte-derived macrophages. Whether TRMs and monocyte-derived macrophages have district roles under differing pathologies is not understood. Here, we showed that a substantial portion of the macrophages that accumulated during pancreatitis and pancreatic cancer in mice had expanded from TRMs.

Reprint of: COVID-19 messaging in U.S. state parks: Extensions of the outdoor recreation strategies and practices framework unmasked by the pandemic.

Unlabelled: U.S. state parks are a considerable part of the nation's recreation landscape.

Tumor-associated fibrosis impairs immune surveillance and response to immune checkpoint blockade in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths. Immune checkpoint blockade has improved survival for many patients with NSCLC, but most fail to obtain long-term benefit. Understanding the factors leading to reduced immune surveillance in NSCLC is critical in improving patient outcomes.

The therapy frequency of antibiotics and phenotypical resistance of in calf rearing sites in Germany.

Introduction: The association between antibiotic use and the occurrence of resistant bacteria is a global health problem and is subject to enormous efforts at national and international levels. Within the scope of the study "KAbMon", the resistance situation as well as the use of antibiotics in calf rearing farms in Germany was investigated. We hypothesized that the levels of resistance are associated with certain calf keeping farm types, such as pre-weaned calf farms, animal groups, and therapy frequency.

Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity.

Chronic activation of inflammatory pathways and suppressed interferon are hallmarks of immunosuppressive tumors. Previous studies have shown that CD11b integrin agonists could enhance anti-tumor immunity through myeloid reprograming, but the underlying mechanisms remain unclear. Herein we find that CD11b agonists alter tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling and activating interferon gene expression simultaneously.

Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer.

Intratumoral T-cell dysfunction is a hallmark of pancreatic tumors, and efforts to improve dendritic cell (DC)-mediated T-cell activation may be critical in treating these immune therapy unresponsive tumors. Recent evidence indicates that mechanisms that induce dysfunction of type 1 conventional DCs (cDC1) in pancreatic adenocarcinomas (PDAC) are drivers of the lack of responsiveness to checkpoint immunotherapy. However, the impact of PDAC on systemic type 2 cDC2 development and function has not been well studied.

Induction of cancer neoantigens facilitates development of clinically relevant models for the study of pancreatic cancer immunobiology.

Neoantigen burden and CD8 T cell infiltrate are associated with clinical outcome in pancreatic ductal adenocarcinoma (PDAC). A shortcoming of many genetic models of PDAC is the lack of neoantigen burden and limited T cell infiltrate. The goal of the present study was to develop clinically relevant models of PDAC by inducing cancer neoantigens in KP2, a cell line derived from the KPC model of PDAC.

Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action?

Introduction: Current treatment options for major depressive disorder (MDD) have limited efficacy and are associated with adverse effects. Recent studies investigating the antidepressant effect of serotonergic psychedelics-also known as classic psychedelics-have promising preliminary results with large effect sizes. In this context, we conducted a review of the putative neurobiological underpinnings of the mechanism of antidepressant action of these drugs.

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex.

Coral Reef Arks: An In Situ Mesocosm and Toolkit for Assembling Reef Communities.

Coral reefs thrive and provide maximal ecosystem services when they support a multi-level trophic structure and grow in favorable water quality conditions that include high light levels, rapid water flow, and low nutrient levels. Poor water quality and other anthropogenic stressors have caused coral mortality in recent decades, leading to trophic downgrading and the loss of biological complexity on many reefs. Solutions to reverse the causes of trophic downgrading remain elusive, in part because efforts to restore reefs are often attempted in the same diminished conditions that caused coral mortality in the first place.