Protonation effects in protein-ligand complexes - a case study of endothiapepsin and pepstatin A with computational and experimental methods.

Protonation states serve as an essential molecular recognition motif for biological processes. Their correct consideration is key to successful drug design campaigns, since chemoinformatic tools usually deal with default protonation states of ligands and proteins and miss atypical protonation states. The protonation pattern for the Endothiapepsin/PepstatinA (EP/pepA) complex is investigated using different dry lab and wet lab techniques.

Decoding Dual-Functionality in N-doped Defective Carbon: Unveiling Active Sites for Bifunctional Oxygen Electrocatalysis.

Oxygen electrocatalysis plays a pivotal role in energy conversion and storage technologies. The precise identification of active sites for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is crucial for developing an efficient bifunctional electrocatalyst. However, this remains a challenging endeavor.

Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Minimally invasive versus open surgery for nonfunctioning pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

Introduction: Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) have been diagnosed increasingly often but still represent rare pancreatic neoplasms. Surgery is a potentially curative approach for patients with NF-PNETs. In recent years, minimally invasive surgery (MIS) has been applied more frequently for surgical resection of NF-PNETs.

Wilson disease in the USA: epidemiology and real-world patient characteristics based on a retrospective observational health claims study.

Objectives: To describe the epidemiology, patient characteristics and comorbidities in patients with Wilson disease (WD) in the USA.

Design: Retrospective, population-based study.

Setting: The study used the US Komodo claims database containing records regarding medical claims for over 120 million individuals.

Multicentre study conducted across centres in the USA, Europe and Australia to assess the safety and effectiveness of a bilateral hypoglossal nerve stimulation system for the treatment of obstructive sleep apnoea in adults: a protocol for a pivotal, multicentre, open-label, single-arm study.

Introduction: Obstructive sleep apnoea (OSA) is characterised by blood oxygen desaturations and sleep disruptions manifesting undesirable consequences. Existing treatments including oral appliances, positive airway pressure (PAP) therapy and surgically altering the anatomy of the pharynx have drawbacks including poor long-term adherence or often involving irreversible, invasive procedures. Bilateral hypoglossal nerve stimulation (HNS) is a new treatment for managing OSA, and this study is intended to determine whether an HNS system is a safe and effective treatment option for adults with OSA.

Prognostic signature of multimorbidity, geriatric syndromes and resources cluster in older in- and outpatients: a pooled secondary analysis with a 6-month follow-up.

Objective: The prognosis of older adults is strongly influenced by the relation of multifactorial geriatric syndromes (GS) and their health-maintaining counterparts, geriatric resources (GR). The present analysis aimed to identify clusters of comorbidities, GS and GR, and to measure their multidimensional prognostic signature in older patients admitted to different healthcare settings.

Design: Pooled secondary analysis of three longitudinal interventional studies with the 3- and 6-month follow-up data collection on mortality and rehospitalisation.

Frequency, demographics, diagnoses and consultation patterns associated with low-acuity attendances in German emergency departments: a retrospective routine healthcare data analysis from the INDEED project.

Objective: Evidence suggests interventions targeting low-acuity attendances have been hampered by insufficient characterisation of potential target groups. This study aimed to estimate the frequency of low-acuity emergency department (ED) attendances and to provide an overview of their demographic, diagnosis and consultation patterns.

Design: Observational analyses of routine healthcare data.

Determining the feasibility of linked claims and vaccination data for a COVID-19 vaccine pharmacoepidemiological study in Germany-RiCO feasibility study protocol.

Introduction: In Germany, there has been no population-level pharmacoepidemiological study on the safety of the COVID-19 vaccines. One factor preventing such a study so far relates to challenges combining the different relevant data bodies on vaccination with suitable outcome data, specifically statutory health insurance claims data. Individual identifiers used across these data bodies are of unknown quality and reliability for data linkage.

Patient-reported outcome measures for post-COVID-19 condition: a systematic review of instruments and measurement properties.

Objectives: Post-COVID-19 condition (PCC), also referred to as Long COVID, has become an emerging public health issue requiring adequate prevention, treatment and management strategies. Evaluating these strategies from the patients' perspective using patient-reported outcome measures (PROMs) is critical. In this systematic review, we aimed to critically appraise and summarise the quality of existing PROMs for PCC, and to identify PROMs that can be recommended for use in future research.

Which clinical trial designs and statistical approaches have been used in assessments of orphan maintenance by the European Medicines Agency between 2012 and 2022? A cross-sectional study.

Objectives: In the European Union, a new orphan medicinal product must demonstrate 'significant benefit' over approved medicinal products targeting the same indication. To demonstrate a significant benefit, comparisons between the new product and the already approved medicinal products-either directly by a head-to-head comparison within a clinical trial or indirectly as a cross-trial comparison-are necessary. In this study, we investigate the types of trial designs and statistical approaches used for demonstrating a significant benefit of a new orphan medicinal product against approved comparators used between 2012 and 2022.

Temporal Lobe Epilepsy Perturbs the Brain-Wide Excitation-Inhibition Balance: Associations with Microcircuit Organization, Clinical Parameters, and Cognitive Dysfunction.

Excitation-inhibition (E/I) imbalance is theorized as a key mechanism in the pathophysiology of epilepsy, with ample research focusing on elucidating its cellular manifestations. However, few studies investigate E/I imbalance at the macroscale, whole-brain level, and its microcircuit-level mechanisms and clinical significance remain incompletely understood. Here, the Hurst exponent, an index of the E/I ratio, is computed from resting-state fMRI time series, and microcircuit parameters are simulated using biophysical models.

Solvent-Dependent Reactivity of Fe(CO) under Superacidic and Oxidative Conditions.

Herein, we report the solvent-dependent reactivity of Fe(CO) toward AsF in either anhydrous HF or liquid SO. The reaction of Fe(CO) with the superacid HF/AsF leads to the protonation of the iron center and allows for the first-time structural characterization of [FeH(CO)] in the solid state, representing one of the most acidic transition metal hydride complexes to ever be isolated and structurally characterized. In the aprotic but oxidation-stable solvent SO, Fe(CO) is oxidized and dimerized to [Fe(CO)], which is isoelectronic with well-known Mn(CO).

The Value of Multidisciplinary Neuro-oncological Tumor Boards to Increase the Accuracy of FET PET for Identifying Brain Tumor Relapse.

Purpose: Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes.

Patients And Methods: In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment.

Multiple Contrast Tests in the Presence of Partial Heteroskedasticity.

This paper proposes a general approach for handling multiple contrast tests for normally distributed data in the presence of partial heteroskedasticity. In contrast to the usual case of complete heteroskedasticity, the treatments belong to subgroups according to their variances. Treatments within these subgroups are homoskedastic, whereas treatments of different subgroups are heteroskedastic.

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges.

Risk prediction tools for pressure injury occurrence: an umbrella review of systematic reviews reporting model development and validation methods.

Background: Pressure injuries (PIs) place a substantial burden on healthcare systems worldwide. Risk stratification of those who are at risk of developing PIs allows preventive interventions to be focused on patients who are at the highest risk. The considerable number of risk assessment scales and prediction models available underscores the need for a thorough evaluation of their development, validation, and clinical utility.

Investigating the impact of microbiome-changing interventions on food decision-making: MIFOOD study protocol.

Background: Obesity is a multifactorial disease reaching pandemic proportions with increasing healthcare costs, advocating the development of better prevention and treatment strategies. Previous research indicates that the gut microbiome plays an important role in metabolic, hormonal, and neuronal cross-talk underlying eating behavior. We therefore aim to examine the effects of prebiotic and neurocognitive behavioral interventions on food decision-making and to assay the underlying mechanisms in a Randomized Controlled Trial (RCT).

Insights into the lemon (Citrus limon) epiphytic microbiome: impact of the biocontrol yeast Clavispora lusitaniae 146.

Background: Postharvest lemons are affected by several fungal infections, and as alternatives to chemical fungicides for combating these infections, different microbial biocontrol agents have been studied, with the Clavispora lusitaniae 146 strain standing out. Although strain 146 has proven to be an effective agent, the influence of a microbial biological control agent on the postharvest lemon microbiome has not been studied until now. Thus, this study aimed to evaluate how the epiphytic microbiome of postharvest lemons is affected by the application of the biocontrol yeast C.

Assessment of a novel unidirectional mid-term absorbable barbed suture versus a competitor barbed suture for vaginal cuff closure after gynaecology surgery, study protocol of a randomized controlled trial - BARHYSTER.

Background: Total laparoscopic hysterectomy (TLH) is nowadays the standard to treat benign and malignant disease occurring in the uterus, but the number of robotic-assisted surgeries is increasing worldwide. To facilitate the handling of sutures in a bi- and tri-dimensional plane, a new type of suture material has been developed, named barbed sutures, which are in use in different indications. In comparison to conventional suture materials, the barbs anchor the suture in the tissue, provide tissue approximation and prevent slippage without the need for knot tying.

Improving 10-year cardiovascular risk prediction in patients with type 2 diabetes with metabolomics.

Background: Existing cardiovascular risk prediction models still have room for improvement in patients with type 2 diabetes who represent a high-risk population. This study evaluated whether adding metabolomic biomarkers could enhance the 10-year prediction of major adverse cardiovascular events (MACE) in these patients.

Methods: Data from 10,257 to 1,039 patients with type 2 diabetes from the UK Biobank (UKB) and the German ESTHER cohort, respectively, were used for model derivation, internal and external validation.

Gut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation.

Background: The conversion of primary bile acids to secondary bile acids by the gut microbiota has been implicated in colonic inflammation. This study investigated the role of gut microbiota related bile acid metabolism in colonic inflammation in both patients with inflammatory bowel disease (IBD) and a murine model of dextran sulfate sodium (DSS)-induced colitis.

Methods: Bile acids in fecal samples from patients with IBD and DSS-induced colitis mice, with and without antibiotic treatment, were analyzed using ultraperformance liquid chromatography-mass spectrometry (UPLC-MS).