Representation of Women in Atrial Fibrillation Ablation Randomized Controlled Trials: Systematic Review.

Background: Sex inequality in randomized controlled trials (RCTs) related to cardiovascular disease has been observed. This study examined the proportion of women enrolled in atrial fibrillation (AF) ablation RCTs and the potential risks of underrepresentation of women.

Methods And Results: We systematically searched PubMed and Embase for AF ablation RCTs published from 2015 to 2022.

Representation of obesity in contemporary atrial fibrillation ablation randomized controlled trials.

Background: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied.

Objective: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available.

Methods: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022.

Spatial transcriptomics unravels palmitoylation and zonation-dependent gene regulation by AEG-1 in mouse liver.

Obesity-induced metabolic dysfunction-associated steatohepatitis (MASH) leads to hepatocellular carcinoma (HCC). Astrocyte-elevated gene-1/Metadherin (AEG-1/MTDH) plays a key role in promoting MASH and HCC. AEG-1 is palmitoylated at residue cysteine 75 (Cys75) and a knock-in mouse representing mutated Cys75 to serine (AEG-1-C75S) showed activation of MASH- and HCC-promoting gene signature when compared to wild-type littermates (AEG-1-WT).

SPTLC3 Is Essential for Complex I Activity and Contributes to Ischemic Cardiomyopathy.

Background: Dysregulated metabolism of bioactive sphingolipids, including ceramides and sphingosine-1-phosphate, has been implicated in cardiovascular disease, although the specific species, disease contexts, and cellular roles are not completely understood. Sphingolipids are produced by the serine palmitoyltransferase enzyme, canonically composed of 2 subunits, SPTLC1 (serine palmitoyltransferase long chain base subunit 1) and SPTLC2 (serine palmitoyltransferase long chain base subunit 2). Noncanonical sphingolipids are produced by a more recently described subunit, SPTLC3 (serine palmitoyltransferase long chain base subunit 3).

Osteocytes and Paget's Disease of Bone.

Purpose Of Review: To describe the contributions of osteocytes to the lesions in Paget's disease, which are characterized by locally overactive bone resorption and formation.

Recent Findings: Osteocytes, the most abundant cells in bone, are altered in Paget's disease lesions, displaying increased size, decreased canalicular length, incomplete differentiation, and less sclerostin expression compared to controls in both patients and mouse models. Pagetic lesions show increased senescent osteocytes that express RANK ligand, which drives osteoclastic bone resorption.

Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity.

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine-polycytidylic acid (pIC) is a synthetic double-stranded RNA (dsRNA) which directly activates dendritic cells and natural killer cells inhibiting tumor growth.

MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.

Bone metastasis is a frequent and incurable consequence of advanced prostate cancer (PC). An interplay between disseminated tumor cells and heterogeneous bone resident cells in the metastatic niche initiates this process. () is a prometastatic gene expressed in multiple organs, including bone marrow-derived mesenchymal stromal cells (BM-MSCs), under both physiological and pathological conditions.

Osteoclast-derived IGF1 induces RANKL production in osteocytes and contributes to pagetic lesion formation.

We previously reported that measles virus nucleocapsid protein (MVNP) expression in osteoclasts (OCLs) of patients with Paget disease (PD) or targeted to the OCL lineage in MVNP-transgenic mice (MVNP mice) increases IGF1 production in osteoclasts (OCL-IGF1) and leads to development of PD OCLs and pagetic bone lesions (PDLs). Conditional deletion of Igf1 in OCLs of MVNP mice fully blocked development of PDLs. In this study, we examined whether osteocytes (OCys), key regulators of normal bone remodeling, contribute to PD.

Alagille Syndrome and Repeat Oxygenator Failure during Cardiopulmonary Bypass: A Word of Caution.

Alagille syndrome is an autosomal dominant disorder that is caused by heterozygous mutation of JAG1 or NOTCH2 gene that impacts several multisystem organs including but may not be limited to the liver, heart, musculoskeletal, skin, and the eyes. The most common congenital heart defect associated with Alagille syndrome is multilevel right ventricular outflow tract obstruction with multiple central and peripheral branch pulmonary arterial stenoses occurring in up to two-thirds of these patients. We report two cases of Alagille syndrome who underwent extensive pulmonary arterial branch rehabilitation and experienced unusual oxygenator failure during cardiopulmonary bypass (CPB).

Astrocyte Elevated Gene-1 Cys75 -Palmitoylation by ZDHHC6 Regulates Its Biological Activity.

Nonalcoholic fatty liver disease is a major risk factor for hepatocellular carcinoma (HCC). Astrocyte elevated gene-1/Metadherin (AEG-1/MTDH) augments lipid accumulation (steatosis), inflammation, and tumorigenesis, thereby promoting the whole spectrum of this disease process. Targeting AEG-1 is a potential interventional strategy for nonalcoholic steatohepatitis (NASH) and HCC.

Predictive value of interatrial block on electrocardiogram among obese patients undergoing atrial fibrillation ablation.

Background: Determine a predictive value of interatrial block (IAB) on atrial fibrillation (AF) ablation outcomes in obese patients.

Methods: Medical records were retrospectively reviewed for 205 consecutive patients with body mass indices (BMI) ≥ 30 kg/m who underwent initial AF ablation. Evidence of partial IAB defined as P-wave duration (PWD) ≥ 120 ms and advanced IAB with PWD ≥ 120 ms and biphasic or negative P-wave in inferior leads was examined from sinus electrocardiograms (ECGs) within 1-year pre-ablation.

Melanoma differentiation associated gene-9/syndecan binding protein promotes hepatocellular carcinoma.

Background And Aims: The oncogene Melanoma differentiation associated gene-9/syndecan binding protein (MDA-9/SDCBP) is overexpressed in many cancers, promoting aggressive, metastatic disease. However, the role of MDA-9 in regulating hepatocellular carcinoma (HCC) has not been well studied.

Approach And Results: To unravel the function of MDA-9 in HCC, we generated and characterized a transgenic mouse with hepatocyte-specific overexpression of MDA-9 (Alb/MDA-9).

Blunted Amphetamine-induced Reinforcing Behaviors and Transporter Downregulation in Knock-in Mice Carrying Alanine Mutations at Threonine-258 and Serine-259 of Norepinephrine Transporter.

Altered amine transporter function, phosphorylation, and association with interacting proteins are evident in animals with a history of psychostimulant exposure. Our previous studies have shown that the Thr258/Ser259 motif in the norepinephrine transporter (NET) is involved in amphetamine (AMPH)-mediated NET regulation and behavior. However, the neurobiological consequences of in vivo Thr258/Ser259-dependent NET regulation in an intact animal model are unclear.

The National Cardiovascular Data Registry Data Quality Program 2020: JACC State-of-the-Art Review.

The National Cardiovascular Data Registry is a group of registries maintained by the American College of Cardiology Foundation. These registries are used by a diverse constituency to improve the quality and outcomes of cardiovascular care, to assess the safety and effectiveness of new therapies, and for research. To achieve these goals, registry data must be complete and reliable.

Roadmap to a more useful and usable electronic health record.

Background: A decade after the Health Information Technology for Economic and Clinical Health (HITECH) Act, electronic health records (EHRs) largely remain poorly designed and contribute to clinician burnout.

Objective: The purpose of this study was to understand clinicians' wants, needs, and perceived barriers imposed by the EHR; implement best practices in user-centered design; and create a clinician-centered EHR framework validated via a functional EHR prototype.

Methods: Usability evaluations were performed using a simulated patient with a complex clinical scenario.

Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein.

Melanoma differentiation associated gene-7/interleukin-24 (MDA-7/IL-24), a secreted protein of the IL-10 family, was first identified more than two decades ago as a novel gene differentially expressed in terminally differentiating human metastatic melanoma cells. MDA-7/IL-24 functions as a potent tumor suppressor exerting a diverse array of functions including the inhibition of tumor growth, invasion, angiogenesis, and metastasis, and induction of potent "bystander" antitumor activity and synergy with conventional cancer therapeutics. MDA-7/IL-24 induces cancer-specific cell death through apoptosis or toxic autophagy, which was initially established in vitro and in preclinical animal models in vivo and later in a Phase I clinical trial in patients with advanced cancers.

Dissecting the Balance Between Metabolic and Oncogenic Functions of Astrocyte-Elevated Gene-1/Metadherin.

Obesity is an enormous global health problem, and obesity-induced nonalcoholic steatohepatitis (NASH) is contributing to a rising incidence and mortality for hepatocellular carcinoma (HCC). Increase in de novo lipogenesis and decrease in fatty acid β-oxidation (FAO) underlie hepatic lipid accumulation in NASH. Astrocyte-elevated gene-1/metadherin (AEG-1) overexpression contributes to both NASH and HCC.

Who researches organised crime? A review of organised crime authorship trends (2004-2019).

This article presents a review of organised crime authorship for all articles published in Trends in Organized Crime and Global Crime between 2004 and 2019 (N = 528 articles and 627 individual authors). The results of this review identify a field dominated by White men based in six countries, all in the Global North. Little collaboration occurs; few studies are funded, and few researchers specialise in the area.

Capturing in-field root system dynamics with RootTracker.

Optimizing root system architecture offers a promising approach to developing stress tolerant cultivars in the face of climate change, as root systems are critical for water and nutrient uptake as well as mechanical stability. However, breeding for optimal root system architecture has been hindered by the difficulty in measuring root growth in the field. Here, we describe the RootTracker, a technology that employs impedance touch sensors to monitor in-field root growth over time.

The Role of Computer Skills in Personal Health Record Adoption Among Patients With Heart Disease: Multidimensional Evaluation of Users Versus Nonusers.

Background: In the era of precision medicine, it is critical for health communication efforts to prioritize personal health record (PHR) adoption.

Objective: The objective of this study was to describe the characteristics of patients with heart disease that choose to adopt a PHR.

Methods: A total of 79 patients with chronic cardiovascular disease participated in this study: 48 PHR users and 31 nonusers.

Novelty-induced hyperactivity and suppressed cocaine induced locomotor activation in mice lacking threonine 53 phosphorylation of dopamine transporter.

Dopamine (DA) transporter (DAT) is dynamically regulated by several protein kinases and the Thr53 phosphorylation of DAT (pT53-DAT) is documented in heterologous cell models and in rat brain. However, the role of endogenous pT53-DAT in living animals has never been addressed. Here we generated and studied the pT53-lacking DAT mouse model (DAT-Ala53) by CRISPR/Cas9 technology.

Engineering T Cells to Express Tumoricidal MDA-7/IL24 Enhances Cancer Immunotherapy.

Antigen-specific immunotherapy can be limited by induced tumor immunoediting (e.g., antigen loss) or through failure to recognize antigen-negative tumor clones.