Posaconazole for Prevention of COVID-19-Associated Pulmonary Aspergillosis in Mechanically Ventilated Patients: A European Multicentre Case-Control Study (POSACOVID).

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA).

Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk.

Adaptive evolution of stress response genes in parasites aligns with host niche diversity.

Background: Stress responses are key the survival of parasites and, consequently, also the evolutionary success of these organisms. Despite this importance, our understanding of the evolution of molecular pathways dealing with environmental stressors in parasitic animals remains limited. Here, we tested the link between adaptive evolution of parasite stress response genes and their ecological diversity and species richness.

Balloon atrioseptostomy for transposition of the great arteries in Europe: characteristics and outcomes.

Introduction And Objectives: Balloon atrial septostomy (BAS) improves oxygenation in neonates with transposition of the great arteries (TGA) and restrictive foramen ovale. Currently, there is a global shortage of dedicated BAS catheters, while new unmarked catheters have recently become available at some European centers. This study aimed to characterize BAS outcomes using the currently available BAS catheters in Europe.

Impact of smoking on biological treatment response in patients from the German Severe Asthma (GAN) Registry.

Background: Clinical studies of biologics in severe asthma exclude smokers or ex-smokers (ExS) with over 10 pack-years (py). Thus, the effectiveness of this therapy in ex-smokers with severe asthma is not well understood.

Objectives: To assess the impact of smoking on clinical efficiency of biologics in patients with severe asthma from the German Asthma Net (GAN), a comprehensive international registry.

The UBR domain of plant Ubr1 homolog PRT6 accommodates basic and hydrophobic amino termini for substrate recognition.

N-degrons are amino-terminal degradation signals. Non-acetylated first residues with bulky side chains were the first discovered N-degrons. In yeast, their ability to destabilize a protein depends on ubiquitin ligase Ubr1, which has a binding site for basic first residues, the UBR box, and one for hydrophobic first residues, the N domain.

Low-grade infections in nonunion of the femur and tibia without clinical suspicion of infection - Incidence, microbiology, treatment, and outcome.

Treatment algorithms for fracture nonunion depend on the presence or absence of bacterial infection. However, it is often impossible to identify infection preoperatively. While some infections may present with clinical signs of infection, low-grade infections lack infection signs and have a clinical presentation similar to aseptic nonunion.

Enhanced Recovery After Surgery for patients undergoing radical cystectomy: Surgeons' perspectives and recommendations ten years after its implementation.

Background And Objectives: Enhanced Recovery After Surgery (ERAS) guidelines for Radical Cystectomy (RC) were published over ten years ago. Aim of this systematic review is to update ERAS recommendations for patients undergoing RC and to give an expert opinion on the relevance of each single ERAS item.

Methods: A systematic review was performed to identify the impact of each single ERAS item on RC outcomes.

Uncertainties around net-zero climate targets have major impact on greenhouse gas emissions projections.

Globally, more than 100 countries have adopted net-zero targets. Most studies agree on how this increases the chance of keeping end-of-century global warming below 2°C. However, they typically make assumptions about net-zero targets that do not capture uncertainties related to gas coverage, sector coverage, sinks, and removals.

Combining an Anterolateral Complex Procedure With Anterior Cruciate Ligament Reconstruction Reduces Graft Reinjury Without Increasing the Rate of Complications: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: Anterolateral ligament reconstruction (ALLR) or lateral extra-articular tenodesis (LET) has been used more frequently in conjunction with anterior cruciate ligament reconstruction (ACLR) in recent years. However, there are still concerns that these procedures may lead to complications such as overconstraint of the lateral compartment, stiffness, infections, tunnel convergence, and other intra- and postoperative complications because of increased surgical time and the need for additional procedures.

Hypothesis/purpose: The lateral extra-articular procedure will reduce the failure rate of reconstructed ACLs without increasing the number of complications.

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion FVIII linked to the D'D3 domain of VWF and two XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab. We hypothesized that the chromogenic (CSA) FVIII assay, specifically calibrated for efanesoctocog using bovine coagulation factors, could provide an accurate assessment of efanesoctocog activity.

Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.

Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.

Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.

Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive.

PTSD and CPTSD in the new ICD-11 - A latent profile analysis.

In the 11th version of the WHO´s International Classification of Diseases, complex post-traumatic stress disorder (CPTSD) is newly recognized as a variant of PTSD, characterized by additional and more severe symptoms and typically arising from prolonged or multiple traumatic experiences. Despite recent research supporting the differentiation between PTSD and CPTSD, studies also identify a third or even a fourth latent profile in trauma patients. This study employs latent profile analysis to identify the number of latent profiles within a clinical trauma population in Germany (N = 588) and aims to investigate their distinct symptomatology.

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Poor Prognostic Factors and Unmet Needs in Rheumatoid Arthritis.

Prognostic factors in rheumatoid arthritis relate to several aspects, such as prediction of joint damage and loss of function or prediction of response to a particular therapy. Since many decades, it is well established that high disease activity, especially exemplified by swollen joint counts and acute phase reactants, is associated with progression of joint damage. In addition, rheumatoid factor (RF) positive patients, but not patients with anti-citrullinated peptide antibodies (ACPA) are particularly prone to high disease activity and joint destruction.

Multicenter In-House Evaluation of an Amplicon-Based Next-Generation Sequencing Panel for Comprehensive Molecular Profiling.

Background: Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods.

Methods: This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors.

Ovarian cancer staging and follow-up: updated guidelines from the European Society of Urogenital Radiology female pelvic imaging working group.

Objective: To provide up-to-date European Society of Urogenital Radiology (ESUR) guidelines for staging and follow-up of patients with ovarian cancer (OC).

Methods: Twenty-one experts, members of the female pelvis imaging ESUR subcommittee from 19 institutions, replied to 2 rounds of questionnaires regarding imaging techniques and structured reporting used for pre-treatment evaluation of OC patients. The results of the survey were presented to the other authors during the group's annual meeting.

Precision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review.

Introduction: Liquid biopsy as a non-invasive method to investigate cancer biology and monitor residual disease has gained significance in clinical practice over the years. Whilst its applicability in carcinomas is well established, the low incidence and heterogeneity of bone and soft tissue sarcomas explains the less well-established knowledge considering liquid biopsy in these highly malignant mesenchymal neoplasms.

Materials And Methods: A systematic literature review adhering to the PRISMA guidelines initially identified 920 studies, of whom 68 original articles could be finally included, all dealing with clinical applicability of liquid biopsy in sarcoma.

Postgraduate medical education in obstetrics and gynecology in Switzerland in comparison to Germany and Austria: the results of an international survey.

Background: There is frequent academic exchange between Switzerland, Germany and Austria, facilitated by the common language. Additionally, the postgraduate training curricula in obstetrics and gynecology show some similarities. We aimed to compare self-perceived level of ability, availability of simulation training and teaching and feedback culture among residents in obstetrics and gynecology in Switzerland, Germany, and Austria.

UBIQUITIN-CONJUGATING ENZYME34 mediates pyrophosphatase AVP1 turnover and regulates abiotic stress responses in Arabidopsis.

Understanding the molecular mechanisms of abiotic stress responses in plants is instrumental for the development of climate-resilient crops. Key factors in abiotic stress responses, such as the proton- pumping pyrophosphatase (AVP1), have been identified, but their function and regulation remain elusive. Here, we explored the post-translational regulation of AVP1 by the ubiquitin-conjugating enzyme UBC34 and its relevance in the salt stress and phosphate starvation responses of Arabidopsis (Arabidopsis thaliana).

Molecular Stratification of Light-Chain Cardiac Amyloidosis With F-Florbetapir and Ga-FAPI-04 for Enhanced Prognostic Precision.

Background: Cardiac involvement in amyloid light chain (AL) amyloidosis significantly influences prognosis, necessitating timely diagnosis and meticulous risk stratification.

Objectives: This prospective study aimed to delineate the molecular phenotypes of AL cardiac amyloidosis (AL-CA) by characterizing fibro-amyloid deposition using F-florbetapir and gallium-68-labeled fibroblast activation protein inhibitor-04 (Ga-FAPI-04) positron emission tomography (PET)/computed tomography (CT) imaging. The authors also proposed a novel molecular stratification methodology for prognosis.

Decreased Structural Connectivity Between Thalamic Nuclei and Hippocampus in Temporal Lobe Epilepsy-A Diffusion Tensor Imaging-Based Study.

Background: Temporal lobe epilepsy (TLE) can lead to structural brain abnormalities, with thalamus atrophy being the most common extratemporal alteration. This study used probabilistic tractography to investigate the structural connectivity between individual thalamic nuclei and the hippocampus in TLE.

Methods: Thirty-six TLE patients who underwent pre-surgical 3 Tesla magnetic resonance imaging (MRI) and 18 healthy controls were enrolled in this study.