Purification and characterization of a thermophilic NAD-dependent lactate dehydrogenase from Moorella thermoacetica.

Oxidation of lactate under anaerobic dark fermentative conditions poses an energetic problem. The redox potential of the lactate/pyruvate couple is too electropositive to reduce the physiological electron carriers NAD(P) or ferredoxin. However, the thermophilic, anaerobic, and acetogenic model organism Moorella thermoacetica can grow on lactate but was suggested to have a NAD-dependent lactate dehydrogenase (LDH), based on enzyme assays in cell-free extract.

Acetogenesis to ethanologenesis: facilitating NADH oxidation via reductive acetate uptake.

(Homo)acetogens, including Clostridium spp., represent an enigma in metabolic flexibility and diversity. Eubacterium callanderi KIST612 is an acetogen that produces n-butyrate with carbon monoxide (CO) as the carbon and energy source; however, the production route is unknown.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

High-Throughput Effect-Directed Analysis of Androgenic Compounds in Hospital Wastewater: Identifying Effect Drivers through Non-Target Screening Supported by Toxicity Prediction.

The increasing number of contaminants released into the environment necessitates innovative strategies for their detection and identification, particularly in complex environmental matrices like hospital wastewater. Hospital effluents contain both natural and synthetic hormones that might significantly contribute to endocrine disruption in aquatic ecosystems. In this study, HT-EDA has been implemented to identify the main effect-drivers (testosterone, androsterone and norgestrel) from hospital effluent using microplate fractionation, the AR-CALUX bioassay and an efficient data processing workflow.

More micrometastases, more recurrence? The role of qPCR of PSA mRNA in lymph nodes during prostatectomy.

Background And Objectives: Radical prostatectomy is a standard treatment for prostate cancer, yet about 30% of patients experience rising biochemical markers within a decade post-surgery. Pelvic lymph node sampling during prostatectomy assesses potential lymph node metastases, but standard histological assessments, which typically examine only 2-3 tissue sections, often miss occult metastases. This study assesses the effectiveness of qPCR in detecting PSA coding KLK3 mRNA for identifying lymph node metastases post-prostatectomy and explores the correlation between PSA-mRNA and biochemical recurrence.

Periodic Table of Immunomodulatory Elements and Derived Two-Dimensional Biomaterials.

Periodic table of chemical elements serves as the foundation of material chemistry, impacting human health in many different ways. It contributes to the creation, growth, and manipulation of functional metallic, ceramic, metalloid, polymeric, and carbon-based materials on and near an atomic scale. Recent nanotechnology advancements have revolutionized the field of biomedical engineering to tackle longstanding clinical challenges.

Conservation of structural brain connectivity in people with multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. Structures affected in MS include the corpus callosum, connecting the hemispheres. Studies have shown that in mammalian brains, structural connectivity is organized according to a conservation principle, an inverse relationship between intra- and interhemispheric connectivity.

Loneliness and social anxiety in the general population over time - results of a cross-lagged panel analysis.

Background: Loneliness has become a major public health issue of the recent decades due to its severe impact on health and mortality. Little is known about the relation between loneliness and social anxiety. This study aimed (1) to explore levels of loneliness and social anxiety in the general population, and (2) to assess whether and how loneliness affects symptoms of social anxiety and vice versa over a period of five years.

Probing the Protein Kinases' Cysteinome by Covalent Fragments.

Protein kinases are important drug targets, yet specific inhibitors have been developed for only a fraction of the more than 500 human kinases. A major challenge in designing inhibitors for highly related kinases is selectivity. Unlike their non-covalent counterparts, covalent inhibitors offer the advantage of selectively targeting structurally similar kinases by modifying specific protein side chains, particularly non-conserved cysteines.

De-escalating and discontinuing disease-modifying therapies in multiple sclerosis.

The development of disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) has been highly successful in recent decades. It is now widely accepted that early initiation of DMTs after disease onset is associated with a better long-term prognosis. However, the question of when and how to de-escalate or discontinue DMTs remains open and critical.

Head-to-head comparison of palbociclib and ribociclib in first-line treatment of HR-positive/HER2-negative metastatic breast cancer with real-world data from the OPAL registry.

Cyclin-dependent kinase 4/6 inhibitors (CDKIs) in combination with endocrine therapy (ET) are the standard-of-care in the first-line treatment of HR-positive, HER2-negative metastatic breast cancer. In the absence of direct head-to-head trials comparing the efficacy and safety of the different CDKIs, the individual choice of treatment in everyday practice is complex. Inverse probability of treatment weighting was used to emulate a head-to-head comparison of palbociclib +ET (PALBO) and ribociclib +ET (RIBO) in patients recruited into the prospective, observational, multicenter registry platform OPAL (NCT03417115).

NMR resonance assignment of a ligand-binding domain of ephrin receptor A2.

Ephrin receptors regulate intercellular communication and are thus involved in tumor development. Ephrin receptor A2 (EphA2), in particular, is overexpressed in a variety of cancers and is a proven target for anti-cancer drugs. The N-terminal ligand-binding domain of ephrin receptors is responsible for the recognition of their ligands, ephrins, and is directly involved in receptor activation.

Clinical utility of the Fibrosis-4 index for predicting mortality in patients with heart failure with or without metabolic dysfunction-associated steatotic liver disease: a prospective cohort study.

Background: The liver-heart axis potentially influences the risk of mortality in patients with heart failure. We aimed to identify the clinical utility of the fibrosis-4 (FIB-4) index in patients with heart failure for predicting mortality in the context of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Patients with heart failure and a subsample of healthy participants were enrolled in the MyoVasc study (NCT04064450) and followed for nine years.

Cardiac Magnetic Resonance Imaging with Myocardial Strain Assessment Correlates with Cardiopulmonary Exercise Testing in Patients with Pectus Excavatum.

: To evaluate correlations between cardiac magnetic resonance imaging (cMRI) at rest including strain imaging and variables derived from quantitative cardiopulmonary exercise testing using a treadmill in patients with pectus excavatum. : We retrospectively correlated the results of cMRI and cardiopulmonary exercise testing in 17 patients with pectus excavatum, in whom both examinations were performed during their pre-operative clinical evaluation. In addition to cardiac volumetry, we assessed the strain rates of both ventricles using a feature-tracking algorithm of a piece of commercially available post-processing software.

GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci.

The C-terminal PHDVC5HCH tandem domain of NSD2 is a combinatorial reader of unmodified H3K4 and tri-methylated H3K27 that regulates transcription of cell adhesion genes in multiple myeloma.

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding.

Mental health symptoms and burdens after a SARS-CoV-2 infection.

Background: Previous studies have found adverse effects on mental health following infection with SARS-CoV-2. This study investigates whether mental health is also impaired in unknowingly infected individuals. In addition, the relevance of the severity of the infection and the time since the onset of infection were analyzed.

Assessing the impact of two conventional wastewater treatment plants on small streams with effect-based methods.

Sixty percent of discrete surface water bodies in Europe do not meet the requirements for good ecological and chemical status and in Germany, the situation is even worse with over 90% of surface water bodies failing to meet the threshold. In addition to hydromorphological degradation, intensive land use and invasive species, chemical pollution is primarily considered to be responsible for the inadequate ecological status of the water bodies. As a quantitatively important source of micropollutants, wastewater treatment plants (WWTPs) represent an important entry path for chemical stressors.

Intra-individual Differences in Pericoronary Fat Attenuation Index Measurements Between Photon-counting and Energy-integrating Detector Computed Tomography.

Rationale And Objectives: The purpose of this study was to explore intra-individual differences in pericoronary adipose tissue (PCAT) fat attenuation index (FAI) between photon-counting detector (PCD)- and energy-integrating detector (EID)-CT.

Material And Methods: Patients were prospectively enrolled for a PCD-CT research scan within 30 days of EID-CT. Both acquisitions were reconstructed using a Qr36 kernel at 0.

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours.

Cancer immunotherapies with antibodies blocking immune checkpoint molecules are clinically active across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumour progression commonly occurs. Soluble and cell-bound factors in the tumour microenvironment negatively affect cancer immunity.

Amygdala-predominant α-synuclein pathology is associated with exacerbated hippocampal neuron loss in Alzheimer's disease.

Misfolded α-synuclein protein accumulates in 43-63% of individuals with symptomatic Alzheimer's disease. Two main patterns of comorbid α-synuclein pathology have been identified: caudo-rostral and amygdala-predominant. α-Synuclein aggregates have been shown to interact with the transactive response DNA-binding protein 43 (TDP-43) and abnormally phosphorylated tau protein.

Noise causes cardiovascular disease: it's time to act.

Background: Chronic transportation noise is an environmental stressor affecting a substantial portion of the population. The World Health Organization (WHO) and various studies have established associations between transportation noise and cardiovascular disease (CVD), such as myocardial infarction, stroke, heart failure, and arrhythmia. The WHO Environmental Noise Guidelines and recent reviews confirm a heightened risk of cardiovascular incidents with increasing transportation noise levels.

Outcome and management of patients with hepatocellular carcinoma who achieved a complete response to immunotherapy-based systemic therapy.

Background And Aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)-based systemic therapies is unclear.

Approach And Results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.