Engineered heart muscle allografts for heart repair in primates and humans.

Cardiomyocytes can be implanted to remuscularize the failing heart. Challenges include sufficient cardiomyocyte retention for a sustainable therapeutic impact without intolerable side effects, such as arrhythmia and tumour growth. We investigated the hypothesis that epicardial engineered heart muscle (EHM) allografts from induced pluripotent stem cell-derived cardiomyocytes and stromal cells structurally and functionally remuscularize the chronically failing heart without limiting side effects in rhesus macaques.

Global meta-analysis shows action is needed to halt genetic diversity loss.

Mitigating loss of genetic diversity is a major global biodiversity challenge. To meet recent international commitments to maintain genetic diversity within species, we need to understand relationships between threats, conservation management and genetic diversity change. Here we conduct a global analysis of genetic diversity change via meta-analysis of all available temporal measures of genetic diversity from more than three decades of research.

The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.

The mycobacterial ABC transporter IrtAB features an ABC exporter fold, yet it imports iron-charged siderophores called mycobactins. Here, we present extensive cryo-EM analyses and DEER measurements, revealing that IrtAB alternates between an inward-facing and an outward-occluded conformation, but does not sample an outward-facing conformation. When IrtAB is locked in its outward-occluded conformation in nanodiscs, mycobactin is bound in the middle of the lipid bilayer at a membrane-facing crevice opening at the heterodimeric interface.

Transient Photoluminescence Reveals the Dynamics of Injected Charge Carriers in Perovskite Light-Emitting Diodes.

Understanding the dynamics of injected charge carriers is crucial for the analysis of the perovskite light-emitting diode (PeLED) operation. The behavior of the injected carriers largely dictates the external quantum efficiency (EQE) roll-off at high current densities and the temperature dependence of the EQE in PeLEDs. However, limitations such as sample capacitance and external circuitry hinder precise control of carrier injection rates, making it challenging to directly track the dynamics of individual carriers.

Predicting falls with ultrasound, physical parameters or fall-risk questions among older adults: A prospective cohort study.

Background: Falls are a significant issue among older adults, leading to morbidity and mortality. Screening for fall risk in the ED is crucial but challenging due to time limitations and patient conditions. Sarcopenia, characterized by muscle loss, is associated with increased fall risk, and ultrasound has been proposed as a non-invasive tool to measure muscle mass in this context.

Recurrence after surgery for clear cell and papillary renal cell carcinoma: Head-to head comparison of validated risk scores.

Introduction: The American Urology Association (AUA) recently introduced in their guidelines a subtype-agnostic, 4-tiered risk classification score to assess oncologic outcomes after surgery in patients with localized renal cell carcinoma (RCC). We provide a head-to-head comparison of the AUA score with 3, internationally validated and EAU recommended, histological-specific models.

Materials And Methods: We retrieved from a prospectively-maintained database 2,560 surgically-treated patients with localized RCC in a single high-volume European center (1987-2023).

Posterior fossa ring-enhancing lesions in the adult immunocompetent host: illustrative cases, systematic review, and proposed diagnostic algorithm.

Purpose: Posterior fossa ring-enhancing lesions (PFREL) in the adult immunocompetent hosts pose a diagnostic challenge. We aimed to evaluate the spectrum of PFREL etiologies and propose a diagnostic algorithm.

Methods: This study involved a retrospective analysis of PFREL cases from our institution (January 2023 to April 2024) and a systematic literature review conducted using Embase and PubMed databases following the PRISMA 2020 guidelines.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Hemodialysis: An International, Multicentric Registry.

Background: The net benefit of oral anticoagulation in patients with end-stage renal disease on hemodialysis (HD) is uncertain. In recent years, left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation; however, there is scant evidence of LAAC in patients on HD.

Objectives: This study aimed to assess the feasibility and safety of LAAC in patients on HD.

Mount Fuji sign in invasive fungal rhinosinusitis.

We report on a fatal case of invasive fungal rhinosinusitis with after lung transplantation. After endoscopic treatment and adjuvant medical therapy with isavuconazole, caspofungin and an investigational antifungal drug, there was a good clinical response with absence of endoscopic and radiographic disease. However, the patient developed disease recurrence, with signs of intracranial involvement on MRI, for which urgent endoscopic sinus surgery was performed and isavuconazole was restarted.

Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (fifth edition).

Hemorrhagic complications associated with regional anesthesia are extremely rare. The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy reviews the published evidence since 2018 and provides guidance to help avoid this potentially catastrophic complication.The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy uses similar methodology as previous editions but is reorganized and significantly condensed.

Occurrence and allele frequencies of genetic variants associated with Varroa drone brood resistance (DBR) in African Apis mellifera subspecies.

The ectoparasite Varroa destructor is a major contributor to the global decline of honeybee colonies (Apis mellifera), especially in the Northern Hemisphere. However, Varroa-resistant honeybee populations have been reported in various regions around the globe, including Europe and Africa. This resistance is primarily attributed to the trait known as Suppressed Mite Reproduction (SMR), which significantly reduces the reproductive success of Varroa mites within these colonies.

The impact of glidant addition on the loss-in-weight feeding of active pharmaceutical ingredients.

In recent years, continuous manufacturing (CM) has become increasingly popular in the pharmaceutical industry for the production of oral solid dosage (OSD) forms. Most of the newly developed active pharmaceutical ingredients (APIs) nowadays are extremely cohesive and sticky with a mean particle size particle of <100μm, a wide particle size distribution (PSD) and a high tendency to agglomerate, making them difficult to accurately dose using loss-in-weight equipment during CM. In this research paper, the effect of various glidants on the volumetric and gravimetric feeding of several APIs was assessed.

PathwayPilot: A User-Friendly Tool for Visualizing and Navigating Metabolic Pathways.

Metaproteomics, the study of collective proteomes in environmental communities, plays a crucial role in understanding microbial functionalities affecting ecosystems and human health. Pathway analysis offers structured insights into the biochemical processes within these communities. However, no existing tool effectively combines pathway analysis with peptide- or protein-level data.

Characterization of the N- and C-terminal domain interface of the three main apoE isoforms: A combined quantitative cross-linking mass spectrometry and molecular modeling study.

Apolipoprotein E (apoE) polymorphism is associated with different pathologies such as atherosclerosis and Alzheimer's disease. Knowledge of the three-dimensional structure of apoE and isoform-specific structural differences are prerequisites for the rational design of small molecule structure modulators that correct the detrimental effects of pathological isoforms. In this study, cross-linking mass spectrometry (XL-MS) targeting Asp, Glu and Lys residues was used to explore the intramolecular interactions in the E2, E3 and E4 isoforms of apoE.

Cochlear implantation and cognitive function in the older adult population: current state of the art and future perspectives.

Objectives: Hearing loss is associated with increased cognitive decline and incident dementia in older adults. Given the rapidly rising incidence of dementia, management of modifiable risk factors such as hearing loss, is essential to mitigate the impact on the individual and society in general. In this narrative review, we discuss the current state-of-art with respect to studying cognitive function before and after cochlear implantation in the elderly population.

Number is more than meets the eye: Unveiling segmentation mechanisms in numerosity perception with visual illusions.

Animals and humans possess an adaptive ability to rapidly estimate approximate numerosity, yet the visual mechanisms underlying this process remain poorly understood. Evidence suggests that approximate numerosity relies on segmented perceptual units modulated by grouping cues, with perceived numerosity decreasing when objects are connected by irrelevant lines, independent of low-level features. However, most studies have focused on physical objects.

Otolaryngological manifestations of cystic fibrosis in children: A systematic review.

Purpose: Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population. Otolaryngological manifestations pose a significant impact on the quality of life of children with CF. The primary aim of this review is to provide a state of the art update of current literature on the otolaryngological manifestations of CF in children.

Metabolic profiling of Achillea millefolium from the Chernobyl exclusion zone reveals the adaptive strategies to low-dose chronic radiation exposure.

The radionuclide contamination of the environment is an abiotic stress factor that influences biological systems. Plants growing in contaminated areas for many generations provide a unique opportunity to study adaptive strategies aimed at maintaining homeostasis under elevated radiation levels. Using non-targeted metabolomics approaches, we investigated the metabolomic profiles of Achillea millefolium L.

Stability of antipsychotic biomarkers for wastewater-based epidemiology.

Wastewater-based epidemiology (WBE) offers a promising approach by providing objective data on antipsychotic drug consumption within a population that can be used to monitor abuse, misuse, and regional prescription patterns. However, accurate estimations depend on knowing the stability of drug biomarkers. This study provides a comprehensive analysis of the stability of 11 antipsychotic biomarkers (parent drugs and their metabolites) in influent wastewater, using a series of experiments mimicking in-sewer transport (in-sewer setup and deconjugation) and in-sample stability (benchtop, frozen cartridge, long-term sample storage, and freeze-thaw).

Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B).

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model.

Efficacy, immunogenicity, and safety of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine.

Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%).

Oral Regimens for Rifampin-Resistant, Fluoroquinolone-Susceptible Tuberculosis.

Background: For decades, poor treatment options and low-quality evidence plagued care for patients with rifampin-resistant tuberculosis. The advent of new drugs to treat tuberculosis and enhanced funding now permit randomized, controlled trials of shortened-duration, all-oral treatments for rifampin-resistant tuberculosis.

Methods: We conducted a phase 3, multinational, open-label, randomized, controlled noninferiority trial to compare standard therapy for treatment of fluoroquinolone-susceptible, rifampin-resistant tuberculosis with five 9-month oral regimens that included various combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C), and pyrazinamide (Z).

The TOXIN knowledge graph: supporting animal-free risk assessment of cosmetics.

The European Union's ban on animal testing for cosmetic products and their ingredients, combined with the lack of validated animal-free methods, poses challenges in evaluating their potential repeated-dose organ toxicity. To address this, innovative strategies like Next-Generation Risk Assessment (NGRA) are being explored, integrating historical animal data with new mechanistic insights from non-animal New Approach Methodologies (NAMs). This paper introduces the TOXIN knowledge graph (TOXIN KG), a tool designed to retrieve toxicological information on cosmetic ingredients, with a focus on liver-related data.

Frequency, financial impact, and factors associated with cost outliers in intensive care units: a cohort study in Belgium.

Objective: This study aimed to explore the association between high outliers and intensive care unit admissions and to identify the factors contributing to high intensive care unit costs.

Methods: This retrospective cohort study used data from 17 Belgian hospitals from 2018 and 2019. The study focused on the 10 most frequently admitted diagnosis-related groups in the intensive care unit.