Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis.

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign.

Stimulation of histamine H-receptors produces a positive inotropic effect in the human atrium.

There is a controversy whether histamine H-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H-receptor in the heart (H-TG).

Semantic Integration Demands Modulate Large-Scale Network Interactions in the Brain.

The ability to integrate semantic information into the context of a sentence is essential for human communication. Several studies have shown that the predictability of a final keyword based on the sentence context influences semantic integration on the behavioral, neurophysiological, and neural level. However, the architecture of the underlying network interactions for semantic integration across the lifespan remains unclear.

Effects of postoperative physical exercise rehabilitation on cardiorespiratory fitness, functional capacity and quality of life in patients with colorectal, breast, and prostate cancer - a systematic review and meta-analysis.

Purpose: The reduced cardiorespiratory fitness (CRF) and functional capacity following surgical procedures and during cancer treatments is a major risk factor for morbidity and mortality among patients with cancer. We aimed to assess the impact of endurance and combined resistance exercise interventions during the postoperative rehabilitation period for patients with colorectal, breast, and prostate cancer.

Methods: A systematic search was conducted in MEDLINE Pubmed, Web of Science, and Cochrane Library until October 2023 for randomized controlled trials that assessed exercise interventions (aerobic/endurance; resistance or combined training) on postoperative patients with cancer.

Sense of coherence, subjective burden, and anxiety and depression symptoms in caregivers of people with dementia: Causal dynamics unveiled by a longitudinal cohort study in Europe.

Background: Sense of coherence (SOC) is a disposition to perceive things as comprehensible, manageable and meaningful. Lower SOC is associated with subjective burden and psychological morbidity in family caregivers, including in dementia. However, the evidence-base mainly comprises small-scale or cross-sectional studies.

Compulsive sexual behavior, sexual functioning problems, and their linkages to substance use among German medical students: exploring the role of sex and trauma exposure.

Sexual problems relevant to psychotherapy, such as compulsive sexual behavior (CSB) and sexual functioning problems (SFP), have been related to harmful substance use in several studies. Substance use is prevalent among medical students (MS) and is often considered a maladaptive coping strategy for stress, as well as a risk factor for mental health issues. Sexual problems and substance use share trauma exposure and post-traumatic symptoms as risk factors for their development.

Built-in selection or confounder bias? Dynamic Landmarking in matched propensity score analyses.

Background: Propensity score matching has become a popular method for estimating causal treatment effects in non-randomized studies. However, for time-to-event outcomes, the estimation of hazard ratios based on propensity scores can be challenging if omitted or unobserved covariates are present. Not accounting for such covariates could lead to treatment estimates, differing from the estimate of interest.

Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.

In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.

Eplerenone, a mineralocorticoid receptor inhibitor, reduces cirrhosis associated changes of hepatocyte glucose and lipid metabolism.

Background: Recent studies suggest a contribution of intrahepatic mineralocorticoid receptor (MR) activation to the development of cirrhosis. As MR blockade abrogates the development of cirrhosis and hypoxia, common during the development of cirrhosis, can activate MR in hepatocytes. But, the impact of non-physiological hepatic MR activation is unknown.

Dissection of RET p.M918T-driven progression of hereditary vs. sporadic medullary thyroid cancer.

Background: Whether inherited in the context of multiple endocrine neoplasia 2B at germline level or acquired in a lifetime, all RET p.M918T (RET c.2753T>C) mutations should activate the RET tyrosine kinase receptor alike, with similar degrees of medullary thyroid cancer (MTC) progression when disparities in disease onset and multifocal growth are accounted for.

Intron retention of an adhesion GPCR generates 1TM isoforms required for 7TM-GPCR function.

Adhesion G protein-coupled receptors (aGPCRs) are expressed in all organs and are involved in various mechanobiological processes. They are heavily alternatively spliced, forecasting an extraordinary molecular structural diversity. Here, we uncovered the existence of unconventional single-transmembrane (1TM)-containing ADGRL/Cirl proteins devoid of the conventional GPCR layout (i.

Subsequent Thyroid Carcinomas in Children and Adolescents Registered in the German MET Consortium (1997-2023).

Among childhood cancer survivors, the cumulative incidence rate of differentiated thyroid carcinomas (DTCs) is estimated to be 8-11%. Although the association of DTC with prior radiotherapy is well-studied, the association with chemotherapy remains less understood. Most studies focused on young adults, leaving a knowledge gap on subsequent DTC occurring in childhood and adolescence.

A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.

BTZ043 is an 8-nitro-1,3-benzothiazin-4-one with potency against multidrug-resistant . Low solubility and hepatic metabolism are linked to poor oral bioavailability. Amorphous drug nanoparticles (ADN) were formulated to improve the bioavailability.

Crystallization of -Alkanes under Anisotropic Nanoconfinement in Lipid Bilayers.

Understanding crystallization behavior is integral to the design of pharmaceutical compounds for which the pharmacological properties depend on the crystal forms achieved. Very often, these crystals are based on hydrophobic molecules. One method for delivering crystal-forming hydrophobic drugs is by means of lipid nanoparticle carriers.

Late Glacial summer paleohydrology across Central Europe.

It is generally accepted that a weakening of the North Atlantic thermohaline circulation caused the Younger Dryas cooling. Although the role of seasonality was emphasized previously, this aspect is rarely considered yet, and it remains elusive how this impacted hydroclimate during winters and summers across Central Europe. Here, we coupled biomarker-based δO and δH from Bergsee in southern Germany to reconstruct deuterium excess as a proxy for evaporation history from the Bølling-Allerød to the Preboreal.

Feasibility of implementing a decision aid for advanced cancer patients in a comprehensive cancer centers' outpatient setting: Valuable lessons learned.

Background: Decision aids (DAs) have been proposed as tools to empower patients in decision-making. However, implementing DA for decisions in advanced cancer is challenging. This study focuses on perspectives of oncologists and other healthcare providers on the hindering and facilitating factors for implementing a customizable DA.

MS -Pushing the Limits for Biomolecular Mass Spectrometry.

Electrospray mass spectrometry has become indispensable in many disciplines including the classic "omics" techniques such as proteomics or lipidomics, as well as other life science applications in molecular, cellular, and structural biology. However, a limiting factor that often arises for the detection of biomolecular analytes is their poor ionization efficiency in the ion source. Here, we present an add-on device for the electrospray source, termed MS (MS Spectral Impurity Eliminator & Value Enhancer), which is placed between the electrospray needle and the cone of the mass spectrometer.

Low income, being without employment, and living alone: how they are associated with cognitive functioning-Results from the German national cohort (NAKO).

Aim was to investigate to what extent cognitive functioning differs by three socioeconomic conditions: low income, being without employment, and living alone. A total of N = 158,144 participants of the population-based German National Cohort (NAKO) provided data on socioeconomic conditions and completed cognitive tests. Multivariable confounder-adjusted regression analyses indicated that cognitive functioning was lower in those with low income (b = -0.

Benefits and harms associated with the use of AI-related algorithmic decision-making systems by healthcare professionals: a systematic review.

Background: Despite notable advancements in artificial intelligence (AI) that enable complex systems to perform certain tasks more accurately than medical experts, the impact on patient-relevant outcomes remains uncertain. To address this gap, this systematic review assesses the benefits and harms associated with AI-related algorithmic decision-making (ADM) systems used by healthcare professionals, compared to standard care.

Methods: In accordance with the PRISMA guidelines, we included interventional and observational studies published as peer-reviewed full-text articles that met the following criteria: human patients; interventions involving algorithmic decision-making systems, developed with and/or utilizing machine learning (ML); and outcomes describing patient-relevant benefits and harms that directly affect health and quality of life, such as mortality and morbidity.

Echocardiographic Predictors of Ventricular Arrhythmias in Patients With Left Ventricular Assist Devices and Implantable Cardioverter-Defibrillator.

Aim: To evaluate the predictive value of preoperative echocardiographic parameters for occurrence of VAs in patients with preexisting ICD undergoing LVAD implantation.

Methods And Results: All consecutive patients (n = 264) with previous ICD who underwent LVAD surgery between May 2011 and December 2019 at our institution were included. The patients were predominantly male (89%) with NICM (59%) and a mean age of 59 ± 10 years.

Drug-Dependent Inhibitory Effects on Corneal Epithelium Structure, Cell Viability, and Corneal Wound Healing by Local Anesthetics.

Local anesthetics are commonly used in ophthalmic surgery. However, their use can affect the healing process. This study aimed to investigate the potential impact of anesthetic substances at clinically relevant concentrations and incubation times (3 min), specifically oxybuprocaine (OBPC, 0.

GrandQC: A comprehensive solution to quality control problem in digital pathology.

Histological slides contain numerous artifacts that can significantly deteriorate the performance of image analysis algorithms. Here we develop the GrandQC tool for tissue and multi-class artifact segmentation. GrandQC allows for high-precision tissue segmentation (Dice score 0.

Novel travel time aware metapopulation models and multi-layer waning immunity for late-phase epidemic and endemic scenarios.

In the realm of infectious disease control, accurate modeling of the transmission dynamics is pivotal. As human mobility and commuting patterns are key components of communicable disease spread, we introduce a novel travel time aware metapopulation model. Our model aims to enhance estimations of disease transmission.

Cost-effectiveness-analysis of oral health remotivation and reinstruction in nursing homes in a cluster-randomized controlled trial.

Objectives: We conducted a cluster-randomized-controlled trial (cRCT) in 18 German nursing homes (NH) to evaluate the cost-effectiveness of reinstruction and remotivation of nursing staff by dental assistants (DAs) over 13 months.

Methods: In the intervention arm, dentists examined NH residents, identified oral health conditions, and prescribed individualized oral care interventions. Nursing staff delivered these interventions, with regular follow-up support from DAs (reinstruction and remotivation).