Optimizing risk stratification for intermediate-risk prostate cancer - the prognostic value of baseline health-related quality of life.

Objective: To investigate the prognostic value of baseline health-related quality of life (HRQOL) for patients with intermediate-risk localized prostate cancer (IR-PCa) undergoing radical prostatectomy (RP).

Methods: 4780 patients with IR-PCa according to NCCN risk stratification were identified from a prospectively maintained database. All patients were treated with RP and had prospectively assessed baseline HRQOL.

A "poly-matter network" conception of biological inheritance.

Here we intend to shift the "DNA- and information-centric" conception of biological inheritance, with the accompanying exclusion of any non-DNA matter, to a "poly-matter network" framework which, in addition to DNA, considers the action of other cellular membranous constituents. These cellular structures, in particular organelles and plasma membranes, express "landscapes" of specific topologies at their surfaces, which may become altered in response to certain environmental factors. These so-called "membranous environmental landscapes" (MELs), which replicate by self-organization / autopoiesis rather than self-assembly, are transferred from donor to acceptor cells by various - vesicular and non-vesicular - mechanisms and exert novel features in the acceptor cells.

Local sleep in songbirds: different simultaneous sleep states across the avian pallium.

Wakefulness and sleep have often been treated as distinct and global brain states. However, an emerging body of evidence on the local regulation of sleep stages challenges this conventional view. Apart from unihemispheric sleep, the current data that support local variations of neural oscillations during sleep are focused on the homeostatic regulation of local sleep, i.

Complementing aculiferan mitogenomics: comparative characterization of mitochondrial genomes of Solenogastres (Mollusca, Aplacophora).

Background: With the advances in high-throughput sequencing and bioinformatic pipelines, mitochondrial genomes have become increasingly popular for phylogenetic analyses across different clades of invertebrates. Despite the vast rise in available mitogenomic datasets of molluscs, one class of aplacophoran molluscs - Solenogastres (or Neomeniomorpha) - is still neglected.

Results: Here, we present six new mitochondrial genomes from five families of Solenogastres (Amphimeniidae, Gymnomeniidae, Proneomeniidae, Pruvotinidae, Simrothiellidae), including the first complete mitogenomes, thereby now representing three of the four traditional orders.

Testing the relationship between preferences for infant-directed speech and vocabulary development: A multi-lab study.

From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants' preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months.

Causal Inference for Continuous Multiple Time Point Interventions.

There are limited options to estimate the treatment effects of variables which are continuous and measured at multiple time points, particularly if the true dose-response curve should be estimated as closely as possible. However, these situations may be of relevance: in pharmacology, one may be interested in how outcomes of people living with-and treated for-HIV, such as viral failure, would vary for time-varying interventions such as different drug concentration trajectories. A challenge for doing causal inference with continuous interventions is that the positivity assumption is typically violated.

CD30 influences germinal center B-cell dynamics and the expansion of IgG1-switched B cells.

Initially, identified as a Hodgkin lymphoma marker, CD30 was subsequently detected on a subset of human B cells within and around germinal centers (GCs). While CD30 expression is typically restricted to a few B cells, expansion of CD30-expressing B cells occurs in certain immune disorders and during viral infections. The role of CD30 in B cells remains largely unclear.

Imaging error reduction in radial cine-MRI with deep learning-based intra-frame motion compensation.

Radial cine-MRI allows for sliding window reconstruction at nearly arbitrary frame rate, promising high-speed imaging for intra-fractional motion monitoring in magnetic resonance guided radiotherapy. However, motion within the reconstruction window may determine the location of the reconstructed target to deviate from the true real-time position (target positioning errors), particularly in cases of fast breathing or for anatomical structures affected by the heartbeat. In this work, we present a proof-of-concept study aiming to enhance radial cine-MR imaging by implementing deep-learning-based intra-frame motion compensation techniques.

Apolipoprotein E aggregation in microglia initiates Alzheimer's disease pathology by seeding β-amyloidosis.

The seeded growth of pathogenic protein aggregates underlies the pathogenesis of Alzheimer's disease (AD), but how this pathological cascade is initiated is not fully understood. Sporadic AD is linked genetically to apolipoprotein E (APOE) and other genes expressed in microglia related to immune, lipid, and endocytic functions. We generated a transgenic knockin mouse expressing HaloTag-tagged APOE and optimized experimental protocols for the biochemical purification of APOE, which enabled us to identify fibrillary aggregates of APOE in mice with amyloid-β (Aβ) amyloidosis and in human AD brain autopsies.

Kinematics of elongate harvestmen chelicerae: Comparative range of motion analyses in extant Ischyropsalis (Dyspnoi, Opiliones).

Chelicerae, the mouthparts of chelicerates, are essential for food processing. Particularly within harvestmen (Opiliones), some species have greatly elongated their tripartite chelicerae and utilize them for mating behavior, defense, and primarily for predation. We investigated two European species, Ischyropsalis muellneri and Ischyropsalis hellwigii, which occupy different niches (caves, forests), exhibit different feeding ecologies (opportunist, specialist), and first and foremost possess different chelicerae morphologies (long and thin, short and robust).

Structure-based discovery of first inhibitors targeting the helicase activity of human PIF1.

PIF1 is a conserved helicase and G4 DNA binding and unwinding enzyme, with roles in genome stability. Human PIF1 (hPIF1) is poorly understood, but its functions can become critical for tumour cell survival during oncogene-driven replication stress. Here we report the discovery, via an X-ray crystallographic fragment screen (XChem), of hPIF1 DNA binding and unwinding inhibitors.

Frontoparietal network integrity supports cognitive function in pre-symptomatic frontotemporal dementia: Multimodal analysis of brain function, structure, and perfusion.

Introduction: Genetic mutation carriers of frontotemporal dementia can remain cognitively well despite neurodegeneration. A better understanding of brain structural, perfusion, and functional patterns in the pre-symptomatic stage could inform accurate staging and potential mechanisms.

Methods: We included 207 pre-symptomatic genetic mutation carriers and 188 relatives without mutations.

Circulating miRNAs and Machine Learning for Lateralizing Primary Aldosteronism.

Background: Distinguishing between unilateral and bilateral primary aldosteronism, a major cause of secondary hypertension, is crucial due to different treatment approaches. While adrenal venous sampling is the gold standard, its invasiveness, limited availability, and often difficult interpretation pose challenges. This study explores the utility of circulating microRNAs (miRNAs) and machine learning in distinguishing between unilateral and bilateral forms of primary aldosteronism.

DNA methylation-array interlaboratory comparison trial demonstrates highly reproducible paediatric CNS tumour classification across 13 international centres.

Aims: DNA methylation profiling, recently endorsed by the World Health Organisation (WHO) as a pivotal diagnostic tool for brain tumours, most commonly relies on bead arrays. Despite its widespread use, limited data exist on the technical reproducibility and potential cross-institutional differences. The LOGGIC Core BioClinical Data Bank registry conducted a prospective laboratory comparison trial with 12 international laboratories to enhance diagnostic accuracy for paediatric low-grade gliomas, focusing on technical aspects of DNA methylation data generation and profile interpretation under clinical real-time conditions.

Interdisciplinary Animal Research Ethics-Challenges, Opportunities, and Perspectives.

Can nonhuman animals be used for the benefit of humans in a scientifically and morally justified manner and, if yes, how? Based on our own experiences as scholars from various academic backgrounds, we argue that this question can only be answered as an interdisciplinary and international endeavor, considering insights from research ethics and animal ethics as well as scientific and legal aspects. The aim of this article is to contribute to the foundation of the emerging field of animal research ethics. In doing so, we describe the following seven phases of animal research experiments: ethical, legal and social presumptions (phase 0), planning (phase I), review (phase II), conduct of experiments (phase III), publication/dissemination (phase IV), further exploitation of results (phase V), and evaluation (phase VI).

Association of the Single Nucleotide Polymorphisms rs11556218, rs4778889, rs4072111, and rs1131445 of the Interleukin-16 Gene with Ovarian Cancer.

Single nucleotide polymorphisms (SNPs) of the IL-16 gene have been reported to influence the risk of several cancers, but their role in ovarian cancer (OC) has not been studied. Using the restriction fragment length polymorphism (PCR-RFLP) method, we examined four IL-16 SNPs: rs11556218 (T > G), rs4778889 (T > C), rs4072111 (C > T), and rs1131445 (T > C) in blood samples from 413 women of Central European descent, including 200 OC patients and 213 healthy controls. Among the patients, 62% were postmenopausal, 84.

Carbon dioxide fertilization enhanced carbon sink offset by climate change and land use in Amazonia on a centennial scale.

The Amazon, the Earth's largest tropical forest, plays a critical role in the global carbon cycle, acting as a significant carbon sink. Recent studies, however, indicate a decline in its carbon sequestration capacity due to climate variability, intensive deforestation, and fires. This study aims to examine the impacts of these factors on the carbon dynamics of the Amazon over a centennial scale based on dynamic global vegetation models (DGVMs) of Trendy-v11.

Polypharmacological profiling across protein target families and cellular pathways using the multiplexed cell-based assay platform safetyProfiler reveals efficacy, potency and side effects of drugs.

Selectivity profiling is key for assessing the pharmacological properties of multi-target drugs. We have developed a cell-based and barcoded assay encompassing ten druggable targets, including G protein-coupled receptors (GPCRs), receptor tyrosine kinases (RTKs), nuclear receptors, a protease as well as their key downstream pathways and profiled 17 drugs in living cells for efficacy, potency, and side effects. Notably, this multiplex assay, termed safetyProfiler assay, enabled the simultaneous assessment of multiple target and pathway activities, shedding light on the polypharmacological profile of compounds.