Optimal Medical Therapy for Heart Failure and Integrated Care in Patients With Atrial Fibrillation: A Report From the ESC-EHRA EORP Atrial Fibrillation Long-Term General Registry.

Background: Heart failure (HF) often occurs in patients with atrial fibrillation (AF), with a major impact on prognosis. Few data are available on the effect of integrated treatment strategies to improve prognosis in patients with AF. We aimed to evaluate the association between HF (according to left ventricular ejection fraction [LVEF]), HF optimal medical therapy and adherence to the Atrial Fibrillation Better Care pathway, and major outcomes in patients with AF.

Exploratory Analysis of Upper Facial Muscle Interplay During Emotional Expressions: Magnetic Resonance Imaging (MRI) Insights from Young, Caucasian, Toxin-naïve Individuals.

Background: Understanding the interplay of muscle activity in the upper face is crucial as it can significantly impact the effectiveness and safety of aesthetic treatments. Traditional injection algorithms typically focus on the general 2D and 3D anatomy of muscles, often neglecting the areas where muscles exert the greatest force during facial expressions.

Objectives: To analyze the location of greatest morphological change in upper facial muscles procerus muscle (PM), corrugator supercilia muscle (CSM), orbicularis oculi muscle (OOM) and frontalis muscle (FM) during various facial expressions.

On the consequences of intra-operative release versus over-tensioning of the posterior cruciate ligament in total knee arthroplasty.

Intra-operative tensioning of the posterior cruciate ligament (PCL) in total knee arthroplasty (TKA) is commonly based on the surgeon's experience, resulting in a possibly loose or overly tight PCL. To date, the consequences of different PCL tensioning scenarios for the post-operative biomechanics of the knee remain unclear. Using a comprehensive musculoskeletal modelling approach that allows predictive joint kinematic and kinetic balance, we assessed variations in the movement and loading patterns of the knee as well as changes in ligament and muscle forces during walking in response to systematic variations in the PCL reference strain.

Fluoromethyl Triflate and Fluoromethyl Fluorosulfonate: Easily Accessible and Powerful Fluoromethylation Reagents.

Fluoromethyl triflate (superfluoromethyl, SFM, FCH2OSO2CF3) and fluoromethyl fluorosulfonate (magic fluoromethyl, MFM, FCH2OSO2F) are two easily synthesized, highly effective and non-ozone depleting fluoromethylation reagents. They are analogous to the well-known and widely used methylation re-agents CH3OSO2CF3 and CH3OSO2F. Both SFM and MFM have been fully characterized by multinuclear NMR spectroscopy (1H, 13C, 17O, 19F, 33S).

Radiographic Progression in Patients with Rheumatoid Arthritis in Clinical Remission or Low Disease Activity: Results from a Swiss National Registry (SCQM).

The therapeutic aim for rheumatoid arthritis (RA) is to control disease activity and prevent radiographic progression. Various clinical scores are used to assess disease activity in RA patients. The DAS 28 score can define states of low disease activity (LDA) and remission.

Primary care in rural areas: a qualitative study on medical students' images and experiences of working in rural areas in southern Germany.

Background: Rural areas are increasingly moving back into the focus of social research, especially in the context of health care. As the shortage of general practitioners (GP) in rural areas is a significant challenge in Germany, there are several programs to counteract underuse effectively, acutely, and sustainably. One of those programs is 'Beste Landpartie Allgemeinmedizin' (BeLA), which was developed to strengthen primary care in rural areas and to sustainably promote young doctors to work as general practitioners in rural regions through didactical and financial support.

Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy.

Background: Distal sensorimotor polyneuropathy (DSPN) is a common neurological disorder in elderly adults and people with obesity, prediabetes and diabetes and is associated with high morbidity and premature mortality. DSPN is a multifactorial disease and not fully understood yet.

Methods: Here, we developed the Interpretable Multimodal Machine Learning (IMML) framework for predicting DSPN prevalence and incidence based on sparse multimodal data.

Advancing the personalized advantage index (PAI): a systematic review and application in two large multi-site samples in anxiety disorders.

Background: The Personalized Advantage Index (PAI) shows promise as a method for identifying the most effective treatment for individual patients. Previous studies have demonstrated its utility in retrospective evaluations across various settings. In this study, we explored the effect of different methodological choices in predictive modelling underlying the PAI.

Enduring effects of psychotherapy, antidepressants and their combination for depression: a systematic review and meta-analysis.

Introduction: Although depressive disorders are frequently associated with relapses, the sustained efficacy of therapies after their termination has been insufficiently investigated.

Objective: The aim of this study was to evaluate the current evidence of enduring effects of psychotherapy, antidepressants and their combination after the end of treatment.

Methods: PubMed and PsychINFO were systematically screened according to PRISMA guidelines (except for preregistration).

DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma.

Background: Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs.

MRgRT real-time target localization using foundation models for contour point tracking and promptable mask refinement.

This study aimed to evaluate two real-time target tracking approaches for magnetic resonance imaging (MRI) guided radiotherapy (MRgRT) based on foundation artificial intelligence (AI) models. Approach: The first approach used a point-tracking model that propagates points from a reference contour. The second approach used a video-object-segmentation model, based on Segment Anything Model 2 (SAM2).

Tertiary lymphoid structures in pancreatic cancer are structurally homologous, share gene expression patterns and B-cell clones with secondary lymphoid organs but show increased T-cell activation.

Tertiary lymphoid structures (TLS) in cancer are considered ectopic hotspots for immune activation that are similar to lymphoid follicles in secondary lymphoid organs (SLO). This study elucidates shared and TLS/SLO-specific features in pancreatic ductal adenocarcinoma (PDAC). TLS abundance was related to superior survival and T-cell abundance in 110 treatment-naïve PDAC samples, underlining their clinical relevance.

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer.

Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ().

Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib.

Impact of fixation duration on messenger RNA detectability in human formalin-fixed paraffin-embedded brain tissue.

Technologies to study mRNA in post-mortem human brain samples have greatly advanced our understanding of brain pathologies. With ongoing improvements, particularly in formalin-fixed paraffin-embedded tissue, these technologies will continue to enhance our knowledge in the future. Despite various considerations for tissue and mRNA quality, such as pre-mortem health status and RNA integrity, the impact of the tissue fixation time has not been addressed in a systemic fashion yet.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Clinical results of autologous fat transfer for basal thumb arthritis with a minimum of three years' follow-up.

Aims: In the treatment of basal thumb osteoarthritis (OA), intra-articular autologous fat transplantation has become of great interest within recent years as a minimally invasive and effective alternative to surgical intervention with regard to pain reduction. This study aims to assess its long-term effectiveness.

Methods: Patients diagnosed with stage one to three OA received a single intra-articular autologous fat transplantation.

EPA guidance on lifestyle interventions for adults with severe mental illness: A meta-review of the evidence.

There is growing interest in lifestyle interventions as stand-alone and add-on therapies in mental health care due to their potential benefits for both physical and mental health outcomes. We evaluated lifestyle interventions focusing on physical activity, diet, and sleep in adults with severe mental illness (SMI) and the evidence for their effectiveness. To this end, we conducted a meta-review and searched major electronic databases for articles published prior to 09/2022 and updated our search in 03/2024.

Differential energetic profile of signal processing in central vestibular neurons.

Background: Energetic aspects of neuronal activity have become a major focus of interest given the fact that the brain among all organs dominates the oxygen consumption. At variance with the importance of neuroenergetics, the knowledge about how electrical activity and metabolism is correlated in defined neuronal populations is still rather scarce.

Results: We have estimated the ATP consumption in the two physiologically well characterized populations of frog central vestibular neurons, with tonic and phasic firing patterns, respectively.

SAM-III aptamer enables detection of enzymatic SAM analogue generation.

-Adenosyl-L-methionine (SAM) is crucial for methylation and tightly controlled in cells. We examined SAM-III riboswitch response to 17 SAM analogues and used a Spinach/SAM aptasensor to monitor their enzymatic formation . Most SAM analogues were recognized, unless they featured an -substituted benzyl ring, indicating potential regulatory effects SAM riboswitches.

Synergistic role of Rubisco inhibitor release and degradation in photosynthesis.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) exhibits catalytic promiscuity, resulting in error-prone reactions and the formation of inhibitory sugar phosphates. Specifically, Xylulose-1,5-bisphosphate (XuBP) acts as an inhibitor by binding to the active site of Rubisco, thereby impairing its catalytic function. Thermolabile Rubisco activase (Rca) facilitates the release of such inhibitors, including XuBP, by remodelling Rubisco.