Characterization of lipophilicity and blood partitioning of pyrrolizidine alkaloids and their N-oxides in vitro and in silico for toxicokinetic modeling.

Lipophilicity and blood partitioning are important determinants for predicting toxicokinetics using physiologically-based toxicokinetic (PBTK) modeling. In this study, the logarithm of the -octanol:water partition coefficient (log) and the blood-to-plasma concentration ratio ( ) were for the first time experimentally determined for the pyrrolizidine alkaloids (PAs) intermedine, lasiocarpine, monocrotaline, retrorsine and their -oxides (PANOs). Validated assays for log (miniaturized shake-flask method) and (LC-MS/MS-based depletion assay) determination were compared to an ensemble of models.

Decoding lysosome communication.

Lysosome interaction with other organelles may be linked to pulmonary hypertension.

The role of expansion and adaptability of face-space for individual differences in face identity processing.

Individuals can strongly vary in their ability to process face identity. Understanding the mechanisms driving these differences is important for theoretical development, and in clinical and applied contexts. Here we investigate the role of face-space properties in relation to individual face identity processing skills.

Amino-substituted Azoxybenzenes as Potential Redox-Active Catholyte Materials.

Aryl diazenes, particularly azobenzenes (AB), represent a versatile class of compounds with significant historical and practical relevance, ranging from dyes to molecular machines, solar thermal and electrochemical storage. Their oxygen-substituted counterparts, azoxybenzenes (AOB), share structural similarities but have been less explored, especially in energy storage applications. This study investigates the redox properties of AOB, comparing them to AB, and evaluates their potential as redox-active materials for energy storage systems.

Lymph Node Staging and Treatment in Pediatric Patients With Soft Tissue Sarcomas: A Consensus Opinion from the Children's Oncology Group, European paediatric Soft tissue sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe.

Accurate staging of nodal involvement in pediatric sarcoma patients is important to determine correct systemic and local therapy, with the goal to reduce subsequent recurrences. However, differences in lymph node staging strategies, definitions, and treatment protocols between the Children's Oncology Group (COG), European paediatric Soft tissue sarcoma Study Group (EpSSG), and the Cooperative Weichteilsarkom Studiengruppe (CWS) complicate comparisons. In this article, we aim to establish internationally recognized recommendations for lymph node assessment and treatment of children and adolescents diagnosed with rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) according to the Consensus Conference Standard Operating Procedure methodology.

Medication patterns and potentially inappropriate medication in patients with metastatic breast cancer: results of the BRE-BY-MED study.

Background: The treatment of metastatic breast cancer (mBC) focuses on prolonging patient survival, providing adequate symptom management, and maintaining quality of life (QoL). This includes supportive therapy to prevent or treat potential side effects and handle comorbidities. The combination of mBC therapy, supportive therapy, and treatment for comorbidities increases the risk for polypharmacy, potential drug-drug interactions (pDDI), potentially inappropriate medication (PIM), and potentially missing drugs (pMD).

Evaluating pulmonary stenosis and regurgitation impact on cardiac strain and strain rate in a porcine model via magnetic resonance feature tracking.

Background: Pulmonary stenosis (PS) is common in congenital heart disease and an integral finding in Tetralogy of Fallot (TOF). Pulmonary regurgitation (PR) is more commonly found following surgery in repaired TOF. We aimed to evaluate the haemodynamic effects of PS and PR on cardiac physiology in a porcine model using cardiac magnetic resonance-based feature tracking (CMR-FT) deformation imaging.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Temporal variation in nutritional status and preoperative anemia among patients with retroperitoneal soft tissue sarcoma: a retrospective longitudinal cohort study.

Purpose: Optimal management of retroperitoneal soft tissue sarcoma (RPS) often requires extensive tumor resections, frequently involving gastrointestinal organs. The impact of these procedures on the nutritional status and hemoglobin (Hb) levels of RPS patients remain unexplored. In this study, we aimed to evaluate preoperative nutritional status as well as the prevalence of anemia in RPS patients, and to investigate longitudinal changes throughout the disease course in order to identify potential strategies for prehabilitation.

Tolerance to land-use changes through natural modulations of the plant microbiome.

Land-use changes threaten ecosystems and are a major driver of species loss. Plants may adapt or migrate to resist global change, but this can lag behind rapid anthropogenic changes to the environment. Our data show that natural modulations of the microbiome of grassland plants in response to experimental land-use change in a common garden directly affect plant phenotype and performance, thus increasing plant tolerance.

Real-World-Evidence of Digital Health Applications (DiGAs) in Rheumatology: Insights from the DiGAReal Registry.

Introduction: Prescribable digital health applications (DiGAs) present scalable solutions to improve patient self-management in rheumatology, however real-world evidence is scarce. Therefore, we aimed to assess the effectiveness, usage, and usability of DiGAs prescribed by rheumatologists, as well as patient satisfaction.

Methods: The DiGAReal registry includes adult patients with rheumatic conditions who received a DiGA prescription.

CT, MRI, and FDG PET/CT in the Assessment of Lymph Node Involvement in Pediatric Hodgkin Lymphoma: An Expert Consensus Definition by an International Collaboration on Staging Evaluation and Response Criteria Harmonization for Children, Adolescent, and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL).

Staging of pediatric Hodgkin lymphoma is currently based on the Ann Arbor classification, incorporating the Cotswold modifications and the Lugano classification. The Cotswold modifications provide guidelines for the use of CT and MRI. The Lugano classification emphasizes the importance of CT and PET/CT in evaluating both Hodgkin lymphoma and non-Hodgkin lymphoma but focuses on adult patients.

Centromere positioning orchestrates telomere bouquet formation and the initiation of meiotic differentiation.

Accurate gametogenesis requires the establishment of the telomere bouquet, an evolutionarily conserved, 3D chromosomal arrangement. In this spatial configuration, telomeres temporarily aggregate at the nuclear envelope during meiotic prophase, which facilitates chromosome pairing and recombination. The mechanisms governing the assembly of the telomere bouquet remain largely unexplored, primarily due to the challenges in visualizing and manipulating the bouquet.

A Systematic Targeted Genetic Screen Identifies Proteins Involved in Cytoadherence of the Malaria Parasite P. falciparum.

Immediately after invading their chosen host cell, the mature human erythrocyte, malaria parasites begin to export an array of proteins to this compartment, where they initiate processes that are prerequisite for parasite survival and propagation, including nutrient import and immune evasion. One consequence of these activities is the emergence of novel adhesive phenotypes that can lead directly to pathology in the human host. To identify parasite proteins involved in this process, we used modern genetic tools to target genes encoding 15 exported parasite proteins, selected by an in silico workflow.

Impact of invasive infections on clinical outcomes in acute pancreatitis: early predictive factors and implications for prophylactic anti-infective therapy.

Background: The use of antibiotic therapy in acute pancreatitis remains controversial and is currently recommended only for confirmed infections of peripancreatic necrosis. However, reliable early predictors of septic complications and unfavorable outcomes are substantially lacking.

Methods: Patients with acute pancreatitis were retrospectively reviewed and divided into two groups: one with a septic course defined by pathogen detection [GERM(+)] and one without [GERM(-)].

Safety and Efficacy of Thrombectomy for Distal Medium Vessel Occlusions of the Middle Cerebral Artery.

Purpose: Mechanical thrombectomy (MT) for distal medium vessel occlusions (DMVOs) in the middle cerebral artery (MCA) is less established than for large vessel occlusions. This study evaluates the safety and efficacy of MT in DMVOs, comparing it with M1-segment occlusions.

Materials And Methods: This retrospective study analyzed 218 patients who underwent MT for isolated M1 (n=123) or distal M2+M3 (n=35) occlusions between January 2020 and August 2023.

Effects of a Preoperative Psychological Expectation-focused Intervention in Patients Undergoing Valvular Surgery - the Randomized Controlled ValvEx (valve patients' expectations) Study.

Background: Many patients experience a reduced quality of life for months after heart surgery. Besides medical factors, psychological factors such as preoperative expectations influence the recovery process. The ValvEx study investigated whether an expectation-focused preoperative intervention before heart valve surgery would i) increase positive realistic expectations, ii) reduce preoperative anxiety and iii) improve the postoperative recovery process.

Management Measures and Trends of Biological Invasions in Europe: A Survey-Based Assessment of Local Managers.

Biological invasions are a major threat to biodiversity, ecosystem functioning and nature's contributions to people worldwide. However, the effectiveness of invasive alien species (IAS) management measures and the progress toward achieving biodiversity targets remain uncertain due to limited and nonuniform data availability. Management success is usually assessed at a local level and documented in technical reports, often written in languages other than English, which makes such data notoriously difficult to collect at large geographic scales.

ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY.

Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent.

Screening for transcriptomic associations with Swine Inflammation and Necrosis Syndrome.

Background: The recently identified swine inflammation and necrosis syndrome (SINS) affects tail, ears, teats, coronary bands, claws and heels of affected individuals. The primarily endogenous syndrome is based on vasculitis, thrombosis, and intimal proliferation, involving defence cells, interleukins, chemokines, and acute phase proteins and accompanied by alterations in clinical chemistry, metabolome, and liver transcriptome. The complexity of metabolic alterations and the influence of the boar led to hypothesize a polygenic architecture of SINS.

Influence of drought stress on phosphorus dynamics and maize growth in tropical ecosystems.

Drought has a significant impact on ecosystem functions, especially on the biogeochemical cycling of phosphorus (P), which is a crucial nutrient for plant growth and productivity. Despite its importance, the effects of different drought scenarios on soil P cycling and availability remain poorly understood in previous studies. This study simulated drought conditions in tropical soils using maize as a test crop under varying field capacity (FC) levels (100%, 80%, 60%, 40%, and 20%) over a 60-day pot experiment.

Effect of Application Mode and Aging on Microtensile Bond Strength of Universal Adhesives to Enamel of Primary Teeth.

Background: Limited reports are available regarding bonding of universal adhesives to primary teeth' enamel.

Aim: To evaluate the effect of application mode and aging on microtensile bond strength (μTBS) of universal adhesives to primary enamel.

Design: Ninety-six human primary molars were randomly assigned to three groups: SU: Scotchbond Universal (3M); CU: Clearfil Universal Bond Quick (Kuraray Noritake); iBU: iBond Universal (Heraeus Kulzer), then subdivided according to phosphoric acid etching time into three subgroups (SG): SG1: 0s; SG2: 15s; SG3: 30s.