Deep Learning-Enabled Assessment of Right Ventricular Function Improves Prognostication After Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Right ventricular (RV) function has a well-established prognostic role in patients with severe mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and is typically assessed using echocardiography-measured tricuspid annular plane systolic excursion. Recently, a deep learning model has been proposed that accurately predicts RV ejection fraction (RVEF) from 2-dimensional echocardiographic videos, with similar diagnostic accuracy as 3-dimensional imaging. This study aimed to evaluate the prognostic value of the deep learning-predicted RVEF values in patients with severe MR undergoing TEER.

Impact of Atrial Fibrillation Diagnosis-to-Ablation Time on 24-Month Efficacy and Safety Outcomes in the Cryo Global Registry.

Background And Aims: Early rhythm-control therapy in atrial fibrillation (AF) results in higher freedom from atrial arrhythmia (AA) recurrence and improved cardiovascular outcomes. The optimal timing of Cryoballoon ablation (CBA) is unknown.

Methods: We evaluated AA recurrence and procedure-related complications of early vs.

Olanzapine/Samidorphan Effects on Weight Gain: An Individual Patient Data Meta-Analysis of Phase 2 and 3 Randomized Double-Blind Studies.

To evaluate weight change with a combination of olanzapine and samidorphan (OLZ/SAM) versus olanzapine by pooling data across clinical studies. This study was an individual patient data (IPD) meta-analysis of clinical trial data. EMBASE, MEDLINE, and PsycInfo were searched for randomized clinical trials (≥12 weeks) in adults with schizophrenia or bipolar I disorder in which weight change from baseline was the primary or secondary end point.

AA-Stacked Hydrogen-Substituted Graphdiyne for Enhanced Lithium Storage.

Graphdiyne (GDY) has been considered a promising electrode material for application in electrochemical energy storage. However, studies on GDY featuring an ordered interlayer stacking are lacking, which is supposed to be another effective way to increase lithium binding sites and diffusion pathways. Herein, we synthesized a hydrogen-substituted GDY (HsGDY) with a highly-ordered AA-stacking structure via a facile alcohol-thermal method.

Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses.

Cytochrome P450 (CYP) 3A4 plays a major role in drug metabolism. Its activity could be determined by non-invasive and cost-effective assays, such as breath analysis, for the personalised monitoring of drug response. For the first time, we identify an isotopically unlabelled CYP3A4 substrate, tolterodine that leads to the formation of a non-toxic volatile metabolite, acetone, which could potentially be applied to monitor CYP3A4 activity in humans.

Transcriptional activation and coactivator binding by yeast Ino2 and human proto-oncoprotein c-Myc.

Basic helix-loop-helix domains in yeast regulatory proteins Ino2 and Ino4 mediate formation of a heterodimer which binds to and activates expression of phospholipid biosynthetic genes. The human proto-oncoprotein c-Myc (Myc) and its binding partner Max activate genes important for cellular proliferation and contain functional domains structure and position of which strongly resembles Ino2 and Ino4. Since Ino2-Myc and Ino4-Max may be considered as orthologs we performed functional comparisons in yeast.

Transport and inhibition of the sphingosine-1-phosphate exporter SPNS2.

Sphingosine-1-phosphate (S1P) is a signaling lysolipid critical to heart development, immunity, and hearing. Accordingly, mutations in the S1P transporter SPNS2 are associated with reduced white cell count and hearing defects. SPNS2 also exports the S1P-mimicking FTY720-P (Fingolimod) and thereby is central to the pharmacokinetics of this drug when treating multiple sclerosis.

Age- and sex-specific differences in myocardial sympathetic tone and left ventricular remodeling following myocardial injury.

Background: Presentations and outcomes of acute myocardial infarction (MI) differ between women and men, with the worst outcomes being reported in younger women. Mental stress induced ischemia and sympathetic activation have been suggested to play a prominent role in the pathogenesis of MI in younger women, however, the impact of sex hormones on these parameters remains unknown.

Methods: The effect of sex hormones and age on myocardial infarct size and myocardial sympathetic activity (MSA) was assessed in male and female, as well as young (4-6 months) and aged (20-22 months) FVB/N mice (n = 106, 60 gonadectomized and 46 sham-operated animals) who underwent in vivo [C]meta-hydroxyephedrine ([C]mHED) positron emission tomography (PET) and cardiac magnetic resonance (CMR) imaging 24 h after a 30 min myocardial ischemic injury.

Implications for the diagnosis of aspiration and aspergillosis in critically ill patients with detection of galactomannan in broncho-alveolar lavage fluids.

Invasive infections with Aspergillus fumigatus in ICU patients are linked to high morbidity and mortality. Diagnosing invasive pulmonary aspergillosis (IPA) in non-immunosuppressed patients is difficult, as Aspergillus antigen (galactomannan [GM]) may have other causes. This retrospective study analyzed 160 ICU surgical patients with positive GM in broncho-alveolar lavage fluid (BALF), classifying them based on AspICU criteria for suspected IPA (pIPA) or aspiration.

Maintenance treatment with trofosfamide in patients with advanced soft tissue sarcoma - a retrospective single-centre analysis.

Background: The prognosis of patients with advanced soft tissue sarcoma (STS) remains dismal. Trofosfamide (TRO) has been proposed as a well-tolerated oral maintenance therapy. This retrospective analysis aims to determine the value of this therapy.

Real-world psoriasis treatment patterns and disease burden in Germany, with a focus on biologics and apremilast: data from a German statutory health insurance database.

Background: Psoriasis is a chronic, systemic, inflammatory skin disease, with increasing prevalence; however, few studies have reported real-world prescription patterns and healthcare burden.

Objectives: This retrospective, observational cohort study used statutory health insurance claims data (January 2014-December 2019) to estimate prevalence/incidence of moderate-to-severe psoriasis in Germany. Patient characteristics, treatment patterns/compliance, and healthcare resource utilization (HCRU)/costs were evaluated, focusing on apremilast and anti-interleukin (IL), and anti-tumor necrosis factor (TNF) biologics.

Global Perspectives on Returning Genetic Research Results in Parkinson Disease.

Background And Objectives: In the era of precision medicine, genetic test results have become increasingly relevant in the care of patients with Parkinson disease (PD). While large research consortia are performing widespread research genetic testing to accelerate discoveries, debate continues about whether, and to what extent, the results should be returned to patients. Ethically, it is imperative to keep participants informed, especially when findings are potentially actionable.

Molecular dynamics simulations to decipher the hotspots at the allosteric site of human 5-lipoxygenase.

Human 5-lipoxygenase (LOX) is a non-heme, Fe-containing LOX which catalyses the conversion of arachidonic acid (AA) to leukotriene A (LTA). LTA is subsequently converted to cysteinyl-LTs and LTB that cause bronchoconstriction and act as chemotactic and chemokinetic agent on human leukocytes, respectively. Leukotrienes play significant roles in inflammation in asthma, cardiovascular diseases, allergic rhinitis, atopic dermatitis, inflammatory bowel disease, rheumatoid arthritis, psoriasis and many more.

Human Brucellosis in the Rural and Urban Population of Pakistan: Seroprevalence, Risk Factors, and Clinical Manifestations.

Brucella spp. is the bacterium responsible for brucellosis, a zoonotic infection that affects humans. This disease poses significant health challenges and contributes to poverty, particularly in developing countries.

The Diverse Binding Modes Explain the Nanomolar Levels of Inhibitory Activities Against 1-Deoxy-d-Xylulose 5-Phosphate Reductoisomerase from Exhibited by Reverse Hydroxamate Analogs of Fosmidomycin with Varying -Substituents.

It is established that reverse hydroxamate analogs of fosmidomycin inhibit the growth of by inhibiting 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the second enzyme of the non-mevalonate pathway, which is absent in humans. Recent biochemical studies have demonstrated that novel reverse fosmidomycin analogs with phenylalkyl substituents at the hydroxamate nitrogen exhibit inhibitory activities against DXR at the nanomolar level. Moreover, crystallographic analyses have revealed that the phenyl moiety of the -phenylpropyl substituent is accommodated in a previously unidentified subpocket within the active site of DXR.

Cycle Effects Are Not Universal: A Case Study of Urinary C-Reactive Protein Concentrations in Rural Polish and Polish American Samples.

Objectives: We need to better understand how the menstrual cycle interacts with other biological systems, such the inflammation and immune response. One way to study this interaction is through C-reactive protein (CRP). Studies of CRP concentrations across the menstrual cycle have been inconsistent.

Pregnancy & cardiovascular disease: the PREG-CVD-HH registry.

Background: Cardiovascular disease (CVD) remains the leading cause of death in pregnant and peripartal women in western countries. Physiological changes during pregnancy can lead to cardiovascular complications in the mother; women with pre-existing heart disease may not tolerate these changes well, increasing their susceptibility to adverse cardiovascular outcomes during pregnancy. The aim of this study is to characterize pregnancy-induced changes in cardiac function, biomarker concentrations and cardiovascular outcomes in women with CVD during pregnancy at a tertiary care hospital in Germany.

Impulsivity behaviors and white matter mediate the relationship between genetic risk for cannabis use disorder and early cannabis use in adolescents.

Background And Aim: Cannabis use disorder (CUD) is strongly influenced by genetic factors; however the mechanisms underpinning this association are not well understood. This study investigated whether a polygenic risk score (PRS) based on a genome-wide association study for CUD in adults predicts cannabis use in adolescents and whether the association can be explained by inter-individual variation in structural properties of brain white matter or risk-taking behaviors.

Design And Setting: Longitudinal and cross-sectional analyses using data from the IMAGEN cohort, a European longitudinal study integrating genetic, neuroimaging and behavioral measures.

Non-Caucasian Race/Ethnicity Predisposes to Unfavorable Stage and Grade at Upper Tract Urothelial Carcinoma Diagnosis.

Objective: To test whether race/ethnicity affects stage or grade distribution at upper tract urothelial carcinoma (UTUC) diagnosis.

Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database 2004-2020, UTUC patients were identified. Multivariable logistic regression models tested for the association between race/ethnicity and stage as well as grade at diagnosis according to renal pelvis vs.

Divergent roles of mA in orchestrating brown and white adipocyte transcriptomes and systemic metabolism.

N-methyladenosine (mA) is among the most abundant mRNA modifications, yet its cell-type-specific regulatory roles remain unclear. Here we show that mA methyltransferase-like 14 (METTL14) differentially regulates transcriptome in brown versus white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. In humans and mice with insulin resistance, METTL14 expression differs significantly from BAT and WAT in the context of its correlation with insulin sensitivity.

Neutrophil Extracellular Traps (NETs) as a Potential Target for Anti-Aging: Role of Therapeutic Apheresis.

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms.

Towards a better understanding of sorption of persistent and mobile contaminants to activated carbon: Applying data analysis techniques with experimental datasets of limited size.

The complex sorption mechanisms of carbon adsorbents for the diverse group of persistent, mobile, and potentially toxic contaminants (PMs or PMTs) present significant challenges in understanding and predicting adsorption behavior. While the development of quantitative predictive tools for adsorbent design often relies on extensive training data, there is a notable lack of experimental sorption data for PMs accompanied by detailed sorbent characterization. Rather than focusing on predictive tool development, this study aims to elucidate the underlying mechanisms of sorption by applying data analysis methods to a high-quality dataset.

A BODIPY-Containing Covalent Organic Framework as a Highly Porous Photosensitizer for Environmental Remediation and Pollutants Adsorption.

The direct incorporation of borondipyrromethene (BODIPY) subunits into the structural backbone of covalent organic frameworks (COFs) gives facile access to porous photosensitizers but is still a challenging task. Here, we introduce β-ketoenamine-linked BDP-TFP-COF, which crystallizes in AA-stacking mode with hcb topology. A comprehensive characterization reveals high crystallinity and enhanced stability in a variety of solvents, excellent mesoporosity (SA=1042 m g), broad light absorption in the visible region, and red emission upon the exfoliation of few-layer COF nanosheets.

Insights into Interlayer Dislocation Augmented Zinc-Ion Storage Kinetics in MoS Nanosheets for Rocking-Chair Zinc-Ion Batteries with Ultralong Cycle-Life.

Increasing attention to sustainability and cost-effectiveness in energy storage sector has catalyzed the rise of rechargeable Zinc-ion batteries (ZIBs). However, finding replacement for limited cycle-life Zn-anode is a major challenge. Molybdenum disulfide (MoS), an insertion-type 2D layered material, has shown promising characteristics as a ZIB anode.

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.