enterotoxin-claudin pore complex: Models for structure, mechanism of pore assembly and cation permeability.

The pore-forming enterotoxin (CPE), a common cause of foodborne diseases, facilitates Ca influx in enterocytes, leading to cell damage. Upon binding to certain claudins (e.g.

Synthesis, HS releasing properties, antiviral and antioxidant activities and acute cardiac effects of nucleoside 5'-dithioacetates.

Hydrogen sulfide (HS) is an endogenous gasotransmitter with cardioprotective and antiviral effects. In this work, new cysteine-selective nucleoside-HS-donor hybrid molecules were prepared by conjugating nucleoside biomolecules with a thiol-activatable dithioacetyl group. 5'-Dithioacetate derivatives were synthesized from the canonical nucleosides (uridine, adenosine, cytidine, guanosine and thymidine), and the putative 5'-thio metabolites were also produced from uridine and adenosine.

Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.

For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies and neutralize with constant high potency. Comparative analysis of neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational flexibility, with substantial epitope-specific variation of bnAb potency ranging from increased to decreased activity against open, neutralization-sensitive Env. To systematically investigate the impact of variability in Env conformation on bnAb potency we screened 126 JR-CSF point mutants for generalized neutralization sensitivity to weakly neutralizing antibodies (weak-nAbs) depending on trimer opening and plasma from people with chronic HIV-1 infection.

Sustainability of Enzymatic Monomer Synthesis: Evaluation via Comparison of Petrochemical and Enzymatic Alkene Epoxidation by Life Cycle Assessment.

Life cycle assessment (LCA) was used, next to green chemistry concepts, to compare the full environmental impacts of the epoxidation of a bio-based monomer, which can be used for the synthesis of vitrimers. On a laboratory scale, the synthesis of the monomer can either be done via a petrochemical route or via an enzymatic reaction pathway. Both reaction pathways were initially optimized to minimize the impact of suboptimal routes on the sustainability evaluation.

Bi-allelic KICS2 mutations impair KICSTOR complex-mediated mTORC1 regulation, causing intellectual disability and epilepsy.

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.

Governance of Indigenous data in open earth systems science.

In the age of big data and open science, what processes are needed to follow open science protocols while upholding Indigenous Peoples' rights? The Earth Data Relations Working Group (EDRWG), convened to address this question and envision a research landscape that acknowledges the legacy of extractive practices and embraces new norms across Earth science institutions and open science research. Using the National Ecological Observatory Network (NEON) as an example, the EDRWG recommends actions, applicable across all phases of the data lifecycle, that recognize the sovereign rights of Indigenous Peoples and support better research across all Earth Sciences.

Factors associated with the evolution of digit health in Swiss dairy herds in a nationwide digit health program.

The purpose of this study was to investigate the evolution of digit health (DH) on Swiss dairy farms participating in a nationwide DH program and to identify risk factors associated with poor DH. Specially trained claw trimmers recorded disorders of the digits (DOD) electronically during routine trimmings between January 2020 and June 2023. The first part of the study was a non-randomized controlled implementation study, comparing the evolution of DH in 75 herds that received professional on-farm risk assessments as well as veterinary advice with 49 herds that did not.

Properties of Maxentropic DNA Synthesis Codes.

Low-weight codes have been proposed for efficiently synthesizing deoxyribonucleic acid (DNA) for massive data storage, where a multiple of DNA strands are synthesized in parallel. We report on the redundancy and information rate of maxentropic low-weight codes for asymptotically large codeword length. We compare the performance of low-complexity nibble replacement (NR) codes, which are designed to minimize the synthesis time, with the performance of maxentropic low-weight codes.

A modified Radiographic Union Score for Tibia (RUST) scoring system for patella fractures treated with osteosynthesis shows excellent intra und interobserver reliability.

Introduction: Patellar fractures are rare at 1% incidence of all fractures. However, they can cause significant functional impairments due to the patella's role in knee joint extension. Current scoring systems lack objectivity in assessing patellar healing.

Effects of timely case conferencing between general practitioners and specialist palliative care services on symptom burden in patients with advanced chronic disease: results of the cluster-randomised controlled KOPAL trial.

Background: Patients with advanced chronic non-malignant conditions often experience significant symptom burden. Therefore, overcoming barriers to interprofessional collaboration between general practitioners (GPs) and specialist palliative home care (SPHC) teams is essential to facilitate the timely integration of palliative care elements. The KOPAL trial aimed to examine the impact of case conferences between GPs and SPHC teams on symptom burden and pain in patients with advanced chronic heart failure, chronic obstructive pulmonary disease, and dementia.

Efficacy of CTLA-4 checkpoint therapy is dependent on IL-21 signaling to mediate cytotoxic reprogramming of PD-1CD8 T cells.

The mechanisms underlying the efficacy of anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) therapy are incompletely understood. Here, by immune profiling responding PD-1CD8 T (T) cell populations from patients with advanced melanoma, we identified differential programming of T cells in response to combination therapy, from an exhausted toward a more cytotoxic effector program. This effect does not occur with anti-PD-1 monotherapy.

Significant nocturnal wakefulness after sleep onset in metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multisystemic disease with a multifactorial pathogenesis involving dietary, environmental, and genetic factors. Previous mouse models suggested that circadian misalignment may additionally influence its development as it influences metabolism in diverse organs including the liver. Further, data from sleep questionnaires proved sleep-wake disruption in patients with MASLD.

Inverse design of copolymers including stoichiometry and chain architecture.

The demand for innovative synthetic polymers with improved properties is high, but their structural complexity and vast design space hinder rapid discovery. Machine learning-guided molecular design is a promising approach to accelerate polymer discovery. However, the scarcity of labeled polymer data and the complex hierarchical structure of synthetic polymers make generative design particularly challenging.

The zymogenic form of SARS-CoV-2 main protease: A discrete target for drug discovery.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M) autocatalytically releases itself out of the viral polyprotein to form a fully active mature dimer in a manner that is not fully understood. Here, we introduce several tools to help elucidate differences between cis (intramolecular) and trans (intermolecular) proteolytic processing and to evaluate inhibition of precursor M. We found that many mutations at the P1 position of the N-terminal autoprocessing site do not block cis autoprocessing but do inhibit trans processing.

Modified Delphi Procedure to Achieve Consensus for the Concept of a National Curriculum for Minimally Invasive and Robot-assisted Surgery in Germany (GeRMIQ).

The rapid development of minimally invasive surgery (MIS) and robot-assisted surgery (RAS) requires standardized training to ensure high-quality patient care. In Germany, there is currently a lack of a standardized curriculum that teaches these specialized skills. The aim of this study is to find a consensus for the development of a nationwide curriculum for MIS and RAS with the subsequent implementation of the consented content.

Effect of patient-contextual skin images in human- and artificial intelligence-based diagnosis of melanoma: Results from the 2020 SIIM-ISIC melanoma classification challenge.

Background: While the high accuracy of reported AI tools for melanoma detection is promising, the lack of holistic consideration of the patient is often criticized. Along with medical history, a dermatologist would also consider intra-patient nevi patterns, such that nevi that are different from others on a given patient are treated with suspicion.

Objective: To evaluate whether patient-contextual lesion-images improves diagnostic accuracy for melanoma in a dermoscopic image-based AI competition and a human reader study.

Tailored Ni(OH)/CuCo/Ni(OH) Composite Interfaces for Efficient and Durable Urea Oxidation Reaction.

Electrocatalytic urea oxidation reaction is a promising alternative to water oxidation for more efficient hydrogen production due to its significantly lower thermodynamic potential. However, achieving efficient electrochemical urea oxidation remains a formidable challenge, and development of an improved electrocatalyst with an optimal physicochemical and electronic structure toward urea oxidation is desired. This can be accomplished by designing a tailored two-dimensional composite with an abundance of active sites in a favorable electronic environment.

Associations between Psychosocial Working Conditions and Work-Specific Self-Efficacy Beliefs Among Employees Receiving Psychotherapeutic Consultation at Work.

Purpose: By considering work-related aspects during early intervention and treatment of employees with (subclinical) symptoms of common mental disorders, psychotherapeutic consultation at work (PT-W) aims to increase work-specific self-efficacy (SE) to finally reduce sickness absence and contribute to successful return to work. This study, thus, aims to investigate interrelations between working conditions and work-specific SE among employees before receiving PT-W.

Methods: The study uses baseline data of a randomized controlled trial testing the efficacy of PT-W in Germany (n = 535).