Transforming literature screening: The emerging role of large language models in systematic reviews.

Systematic reviews (SR) synthesize evidence-based medical literature, but they involve labor-intensive manual article screening. Large language models (LLMs) can select relevant literature, but their quality and efficacy are still being determined compared to humans. We evaluated the overlap between title- and abstract-based selected articles of 18 different LLMs and human-selected articles for three SR.

An untargeted metabolomics approach to evaluate enzymatically deconjugated steroids and intact steroid conjugates in urine as diagnostic biomarkers for adrenal tumors.

Objectives: Urinary steroid profiling after hydrolysis of conjugates is an emerging tool to differentiate aggressive adrenocortical carcinomas (ACC) from benign adrenocortical adenomas (ACA). However, the shortcomings of deconjugation are the lack of standardized and fully validated hydrolysis protocols and the loss of information about the originally conjugated form of the steroids. This study aimed to evaluate the quality of the deconjugation process and investigate novel diagnostic biomarkers in urine without enzymatic hydrolysis.

Why CEOs need advanced education and training for optimizing decisions in the development of innovative medicinal products? justification and recommendation.

Chief executives have been educated and trained how to handle business, to take executive decisions, and take care of financial and human resources in favor of the company they are leading. CEOs (chief executive officers) of innovative pharmaceutical businesses, among others, have only seldomly been trained to understand the immense time periods involved between decisions and their moment of impact, and the skills and languages used by their internal and external R&D (research and development) staff. R&D staff and regulators, however, have undergone full training, and are usually capable of understanding each other across their various specialties (among them compound finding, quality, safety, efficacy, efficiency, risk assessment and management).

BLOOD PROTEOMICS AND MULTIMODAL RISK PROFILING of human volunteers after incision injury: a translational study for advancing Personalized Pain Management After Surgery.

A significant number of patients develop chronic pain after surgery, but prediction of those who are at risk is currently not possible. Thus, prognostic prediction models that include bio-psycho, social and physiological factors in line with the complex nature of chronic pain would be urgently required. Here, we performed a translational study in male volunteers before an experimental incision injury.

Exploring pyrazolines as potential inhibitors of NSP3-macrodomain of SARS-CoV-2: synthesis and in silico analysis.

COVID-19 has proved to be a global health crisis during the pandemic, and the emerging JN.1 variant is a potential threat. Therefore, finding alternative antivirals is of utmost priority.

A Robust NSCLC Biomarker- Mir-7-5p: Its In-Silico Validation and Potential SPR-Based Probe for Detection.

MicroRNA abundance as a particular biomarker for precisely identifying cancer metastases has emerged in recent years. The expression levels of miRNA are analyzed to get insights into cancer tissue detection and subtypes. Similar to other cancer types, the miRNA shows high levels of target mRNA dysregulation in association with non-small cell lung carcinoma (NSCLC).

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Machine Learning identifies remodeling patterns in human lung extracellular matrix.

Organ function depends on the three-dimensional integrity of the extracellular matrix (ECM). The structure resulting from the location and association of ECM components is a central regulator of cell behavior, but a dearth of matrix-specific analysis keeps it unresolved. Here, we deploy a high-resolution, 3D ECM mapping method and design a machine-learning powered pipeline to detect and characterize ECM architecture during health and disease.

Neuropsychological profiles of patients suffering from hallucinogen persisting perception disorder (HPPD): A comparative analysis with psychedelic-using and non-using controls.

Classic psychedelics like LSD and psilocybin are showing promising effects in treating certain psychiatric disorders. Despite their low toxicity and lack of an addictive potential, in some individuals, psychedelics can be associated with persisting psychological harms. Hallucinogen Persisting Perception Disorder (HPPD) is one of those complications, a rare disorder characterized by enduring perceptual symptoms without impaired reality control.

Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation.

Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC).

Critical assessment of commercially available microtitre panels for antimicrobial susceptibility testing of veterinary pathogens.

Antimicrobial susceptibility testing (AST) in the veterinary sector by broth microdilution is mainly based on commercially available microtitre plates with specific panels. A critical review of commercially available microtitre panels identified AST panels that fulfil the requirements for obtaining reliable AST results by covering the necessary antimicrobial concentrations for both clinical breakpoints as well as quality control (QC) ranges for approved QC strains. However, there are AST panels in which these prerequisites are only in part fulfilled, and some AST panels that do not fulfil the aforementioned criteria at all.

Bone quality relies on hyaluronan synthesis - Insights from mice with complete knockout of hyaluronan synthase expression.

Bone consists of a complex mineralised matrix that is maintained by a controlled equilibrium of synthesis and resorption by different cell types. Hyaluronan (HA) is an important glycosaminoglycan in many tissues including bone. Previously, the importance of HA synthesis for bone development during embryogenesis has been shown.

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).

Key Pathophysiological Role of Skeletal Muscle Disturbance in Post COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Accumulated Evidence.

Background: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.

Why are we still in need for novel anti-obesity medications?

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery.

Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly.

Effectiveness of spinal cord stimulation in diabetic patients with chronic limb-threatening ischemia: small cohort study.

Background: Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease (PAD). Patients with diabetes mellitus (DM) have a faster progression of PAD and a fourfold increased risk of CLTI compared to patients without DM. Epidural spinal cord stimulation (SCS) has been used as a method to improve microcirculation, relieve ischemic pain and reduce the number of amputations in patients with PAD.

Spotlight on the 2024 ESC/EACTS management of atrial fibrillation guidelines: 10 novel key aspects.

Atrial fibrillation (AF) remains the most common cardiac arrhythmia worldwide and is associated with significant morbidity and mortality. The European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) have recently released the 2024 guidelines for the management of AF. This review highlights 10 novel aspects of the ESC/EACTS 2024 Guidelines.

Combination of FSH and testosterone could enhance activation of primordial follicles and growth of activated follicles in 1-day-old mice ovaries cultured for 12 days.

Treatment with follicle-stimulating hormone (FSH) and testosterone (T2) and their combination have been observed to be influential on ovarian follicles of 1-day-old mice ovaries cultured for 8 days. Given that extension of the culture period could positively impact the development of follicles in cultured ovaries, the present study was conducted to evaluate the main and interaction effects of FSH by T2 on the development of ovarian follicles in 1-day-old mice ovaries cultured for 12 days. One-day-old mice ovaries were initially cultured with base medium for 4 days; thereafter, different hormonal treatments were added to the culture media, and the culture was continued for 8 additional days until day 12.

A new human autologous hepatocyte/macrophage co-culture system that mimics drug-induced liver injury-like inflammation.

The development of in vitro hepatocyte cell culture systems is crucial for investigating drug-induced liver injury (DILI). One prerequisite for monitoring DILI related immunologic reactions is the extension of primary human hepatocyte (PHH) cultures towards the inclusion of macrophages. Therefore, we developed and characterized an autologous co-culture system of PHH and primary human hepatic macrophages (hepM) (CoC1).