Diffuseness of coronary artery disease impacts on immediate hemodynamic and predicted clinical outcomes.

Diffuse coronary artery disease (CAD) impacts the immediate hemodynamic and clinical outcomes of percutaneous coronary intervention (PCI). We evaluated whether the diffuse pattern of CAD derived from angiographic Quantitative flow ratio (QFR) impacts the immediate hemodynamic outcome post-PCI and the medium term predicted vessel-oriented composite endpoint (VOCE). Paired pre-procedure QFRs were assessed in 503 patients and 1022 vessels in the Multivessel TALENT (MVT) trial.

Terbutaline for Management of Relative Bradycardia Post-Orthotopic Heart Transplant: A Single Center Experience.

Background: Vagal nerve denervation during the heart transplant procedure results in higher resting heart rates in these recipients compared to the general population. Relative bradycardia (RB) is a common and often temporary post-operative complication that can be managed with agents like terbutaline; however, little data exist on the efficacy, safety, and necessity of long-term terbutaline use post-heart transplant.

Methods: This was a single-center, retrospective, descriptive study conducted at a large academic medical center investigating oral terbutaline use for RB management in heart transplant recipients.

Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target.

Cardiac fibrosis impairs cardiac function, but no effective clinical therapies exist. To address this unmet need, we employed a high-throughput screening for antifibrotic compounds using human induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts (CFs). Counter-screening of the initial candidates using iPSC-derived cardiomyocytes and iPSC-derived endothelial cells excluded hits with cardiotoxicity.

Effect of sotatercept on circulating proteomics in pulmonary arterial hypertension.

https://bit.ly/3Z5AZJ3

Soybean symbiotic-nodule zonation and cell differentiation are defined by NIN2 signaling and GH3-dependent auxin homeostasis.

Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones.

Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction.

Prolonged tachycardia-a risk factor for cardiovascular morbidity and mortality-can induce cardiomyopathy in the absence of structural disease in the heart. Here, by leveraging human patient data, a canine model of tachycardia and engineered heart tissue generated from human induced pluripotent stem cells, we show that metabolic rewiring during tachycardia drives contractile dysfunction by promoting tissue hypoxia, elevated glucose utilization and the suppression of oxidative phosphorylation. Mechanistically, a metabolic shift towards anaerobic glycolysis disrupts the redox balance of nicotinamide adenine dinucleotide (NAD), resulting in increased global protein acetylation (and in particular the acetylation of sarcoplasmic/endoplasmic reticulum Ca-ATPase), a molecular signature of heart failure.

Trans-vaccenic acid reprograms CD8 T cells and anti-tumour immunity.

Diet-derived nutrients are inextricably linked to human physiology by providing energy and biosynthetic building blocks and by functioning as regulatory molecules. However, the mechanisms by which circulating nutrients in the human body influence specific physiological processes remain largely unknown. Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8 T cell function and anti-tumour immunity in vivo.

Murray law-based quantitative flow ratio to assess left main bifurcation stenosis: selecting the angiographic projection matters.

Murray law-based quantitative flow ratio (µQFR) assesses fractional flow reserve (FFR) in bifurcation lesions using a single angiographic view, enhancing the feasibility of analysis; however, accuracy may be compromised in suboptimal angiographic projections. FFR is a well-validated non-invasive method measuring FFR from coronary computed tomographic angiography (CCTA). We evaluated the feasibility of µQFR in left main (LM) bifurcations, the impact of the optimal/suboptimal fluoroscopic view with respect to CCTA, and its diagnostic concordance with FFR.

Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.

Background: Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. While it is known that danicamtiv increases force and cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode of action are lacking.

Adrenal Neoplasms: Lessons from Adrenal Multidisciplinary Tumor Boards.

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex.

Cold Versus Hot Snare Polypectomy for Small Colorectal Polyps : A Pragmatic Randomized Controlled Trial.

Background: Although cold snare polypectomy (CSP) is considered effective in reducing delayed postpolypectomy bleeding risk, direct evidence supporting its safety in the general population remains lacking.

Objective: To clarify whether CSP would reduce delayed bleeding risk after polypectomy compared with hot snare polypectomy (HSP) in the general population.

Design: Multicenter randomized controlled study.

A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology.

Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS).

Oral cancer induced TRPV1 sensitization is mediated by PAR signaling in primary afferent neurons innervating the cancer microenvironment.

Oral cancer patients report sensitivity to spicy foods and liquids. The mechanism responsible for chemosensitivity induced by oral cancer is not known. We simulate oral cancer-induced chemosensitivity in a xenograft oral cancer mouse model using two-bottle choice drinking and conditioned place aversion assays.

Baseline Microglial Activation Correlates With Brain Amyloidosis and Longitudinal Cognitive Decline in Alzheimer Disease.

Background And Objectives: This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.

Methods: Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation.

Protocol to measure contraction, calcium, and action potential in human-induced pluripotent stem cell-derived cardiomyocytes.

Multiple strategies have been developed to efficiently differentiate human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Here, we describe a protocol for measuring three key functional parameters of hiPSC-CMs, including contractile function, calcium (Ca) handling, and action potential. For complete details on the use and execution of this protocol, please refer to Zhang et al.

LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamic Effects of the Anti-EL (Endothelial Lipase) Antibody MEDI5884 in Patients With Stable Coronary Artery Disease.

Objective: Functional HDL (high-density lipoprotein) particles that facilitate cholesterol efflux may be cardioprotective. EL (endothelial lipase) hydrolyzes phospholipids promoting catabolism of HDL and subsequent renal excretion. MEDI5884 is a selective, humanized, monoclonal, EL-neutralizing antibody.

Cathepsin S Evokes PAR-Dependent Pain in Oral Squamous Cell Carcinoma Patients and Preclinical Mouse Models.

Oral squamous cell carcinoma (SCC) pain is more prevalent and severe than pain generated by any other form of cancer. We previously showed that protease-activated receptor-2 (PAR) contributes to oral SCC pain. Cathepsin S is a lysosomal cysteine protease released during injury and disease that can activate PAR.

Clonally expanded, GPR15-expressing pathogenic effector T2 cells are associated with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by the recruitment of eosinophils to the esophagus, resulting in chronic inflammation. We sought to understand the cellular populations present in tissue biopsies of patients with EoE and to determine how these populations are altered between active disease and remission. To this end, we analyzed cells obtained from esophageal biopsies, duodenal biopsies, and peripheral blood of patients with EoE diagnosed with active disease or remission with single-cell RNA and T cell receptor (TCR) sequencing.

Asthma-COPD overlap: current understanding and the utility of experimental models.

Pathological features of both asthma and COPD coexist in some patients and this is termed asthma-COPD overlap (ACO). ACO is heterogeneous and patients exhibit various combinations of asthma and COPD features, making it difficult to characterise the underlying pathogenic mechanisms. There are no controlled studies that define effective therapies for ACO, which arises from the lack of international consensus on the definition and diagnostic criteria for ACO, as well as scant and data.

Measurement of single-diffractive dijet production in proton-proton collisions at with the CMS and TOTEM experiments.

Measurements are presented of the single-diffractive dijet cross section and the diffractive cross section as a function of the proton fractional momentum loss and the four-momentum transfer squared . Both processes and , i.e.

A review of biosensor technologies for blood biomarkers toward monitoring cardiovascular diseases at the point-of-care.

Cardiovascular diseases (CVDs) cause significant mortality globally. Notably, CVDs disproportionately negatively impact underserved populations, such as those that are economically disadvantaged and often located in remote regions. Devices to measure cardiac biomarkers have traditionally been focused on large instruments in a central laboratory but the development of affordable, portable devices that measure multiple cardiac biomarkers at the point-of-care (POC) are needed to improve clinical outcomes for patients, especially in underserved populations.

Search for physics beyond the standard model in events with jets and two same-sign or at least three charged leptons in proton-proton collisions at .

A data sample of events from proton-proton collisions with at least two jets, and two isolated same-sign or three or more charged leptons, is studied in a search for signatures of new physics phenomena. The data correspond to an integrated luminosity of at a center-of-mass energy of , collected in 2016-2018 by the CMS experiment at the LHC. The search is performed using a total of 168 signal regions defined using several kinematic variables.

Study of central exclusive production in proton-proton collisions at and 13TeV.

Central exclusive and semiexclusive production of pairs is measured with the CMS detector in proton-proton collisions at the LHC at center-of-mass energies of 5.02 and 13TeV. The theoretical description of these nonperturbative processes, which have not yet been measured in detail at the LHC, poses a significant challenge to models.

The Impact of Coronary Physiology on Contemporary Clinical Decision Making.

Physiological assessment of coronary artery disease (CAD) has become one of the cornerstones of decision making for myocardial revascularization, with a large body of evidence supporting the benefits of using fractional flow reserve and other pressure-based indexes for functional assessment of coronary stenoses. Furthermore, physiology allows the identification of specific vascular dysfunction mechanisms in patients without obstructive CAD. Currently, more than 10 modalities of functional coronary assessment are available, although the overall adoption of these physiological tools, of either intracoronary or image-based nature, is still low.