Ten-year outcomes after DMEK, DSAEK, and PK: insights on graft survival, endothelial cell density loss, rejection and visual acuity.

Fuchs Endothelial Corneal Dystrophy (FECD) is the most frequent indication for corneal transplantation, with Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and penetrating keratoplasty (PK) being viable options. This retrospective study compared 10-year outcomes of these techniques in a large cohort of 2956 first-time keratoplasty eyes treated for FECD at a high-volume corneal transplant center in Germany. While DMEK and DSAEK provided faster visual recovery (median time to BSCVA ≥ 6/12 Snellen: DMEK 7.

KIRA6 is an Effective and Versatile Mast Cell Inhibitor of IgE-mediated Activation.

Mast cell (MC)-driven allergic diseases are constantly expanding and require the development of novel pharmacological MC stabilizers. Allergen/antigen (Ag)-triggered activation via crosslinking of the high-affinity receptor for IgE (FcεRI) is fundamentally regulated by SRC family kinases, for example, LYN and FYN, exhibiting positive and negative functions. We report that KIRA6, an inhibitor for the endoplasmic reticulum stress sensor IRE1α, suppresses IgE-mediated MC activation by inhibiting both LYN and FYN.

Decoding the Digital Pulse: Bibliometric Analysis of 25 Years in Digital Health Research Through the Journal of Medical Internet Research.

Background: As the digital health landscape continues to evolve, analyzing the progress and direction of the field can yield valuable insights. The Journal of Medical Internet Research (JMIR) has been at the forefront of disseminating digital health research since 1999. A comprehensive network analysis of JMIR publications can help illuminate the evolution and trends in digital medicine over the past 25 years.

Evaluating multimodal AI in medical diagnostics.

This study evaluates multimodal AI models' accuracy and responsiveness in answering NEJM Image Challenge questions, juxtaposed with human collective intelligence, underscoring AI's potential and current limitations in clinical diagnostics. Anthropic's Claude 3 family demonstrated the highest accuracy among the evaluated AI models, surpassing the average human accuracy, while collective human decision-making outperformed all AI models. GPT-4 Vision Preview exhibited selectivity, responding more to easier questions with smaller images and longer questions.

Influence of Heart Rate and Change in Wavefront Direction through Pacing on Conduction Velocity and Voltage Amplitude in a Porcine Model: A High-Density Mapping Study.

Background: Understanding the dynamics of conduction velocity (CV) and voltage amplitude (VA) is crucial in cardiac electrophysiology, particularly for substrate-based catheter ablations targeting slow conduction zones and low voltage areas. This study utilizes ultra-high-density mapping to investigate the impact of heart rate and pacing location on changes in the wavefront direction, CV, and VA of healthy pig hearts.

Methods: We conducted in vivo electrophysiological studies on four healthy juvenile pigs, involving various pacing locations and heart rates.

TurboID-Based IRE1 Interactome Reveals Participants of the Endoplasmic Reticulum-Associated Protein Degradation Machinery in the Human Mast Cell Leukemia Cell Line HMC-1.2.

The unfolded protein response is an intricate system of sensor proteins in the endoplasmic reticulum (ER) that recognizes misfolded proteins and transmits information via transcription factors to either regain proteostasis or, depending on the severity, to induce apoptosis. The main transmembrane sensor is IRE1α, which contains cytoplasmic kinase and RNase domains relevant for its activation and the mRNA splicing of the transcription factor XBP1. Mast cell leukemia (MCL) is a severe form of systemic mastocytosis.

Cancer detection rate of breast-MR in supplemental screening after negative mammography in women with dense breasts. Preliminary results of the MA-DETECT-Study after 200 participants.

Background: Due to increased cancer detection rates (CDR), breast MR (breast MRI) can reduce underdiagnosis of breast cancer compared to conventional imaging techniques, particularly in women with dense breasts. The purpose of this study is to report the additional breast cancer yield by breast MRI in women with dense breasts after receiving a negative screening mammogram.

Methods: For this study we invited consecutive participants of the national German breast cancer Screening program with breast density categories ACR C & D and a negative mammogram to undergo additional screening by breast MRI.

Specialized replication mechanisms maintain genome stability at human centromeres.

The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities.

Large Language Models for Therapy Recommendations Across 3 Clinical Specialties: Comparative Study.

Background: As advancements in artificial intelligence (AI) continue, large language models (LLMs) have emerged as promising tools for generating medical information. Their rapid adaptation and potential benefits in health care require rigorous assessment in terms of the quality, accuracy, and safety of the generated information across diverse medical specialties.

Objective: This study aimed to evaluate the performance of 4 prominent LLMs, namely, Claude-instant-v1.

Electroanatomical Conduction Characteristics of Pig Myocardial Tissue Derived from High-Density Mapping.

Background: Ultra-high-density mapping systems allow more precise measurement of the heart chambers at corresponding conduction velocities (CVs) and voltage amplitudes (VAs). Our aim for this study was to define and compare a basic value set for unipolar CV and VA in all four heart chambers and their separate walls in healthy, juvenile porcine hearts using ultra-high-density mapping.

Methods: We used the Rhythmia Mapping System to create electroanatomical maps of four pig hearts in sinus rhythm.

Integrated clinical case discussions - a fully student-organized peer-teaching program on internal medicine.

Background: In response to students´ poor ratings of emergency remote lectures in internal medicine, a team of undergraduate medical students initiated a series of voluntary peer-moderated clinical case discussions. This study aims to describe the student-led effort to develop peer-moderated clinical case discussions focused on training cognitive clinical skill for first and second-year clinical students.

Methods: Following the Kern Cycle a didactic concept is conceived by matching cognitive learning theory to the competence levels of the German Medical Training Framework.

Capitalizing on paradoxical activation of the mitogen-activated protein kinase pathway for treatment of Imatinib-resistant mast cell leukemia.

Prevention of fatal side effects during cancer therapy of cancer patients with high-dosed pharmacological inhibitors is to date a major challenge. Moreover, the development of drug resistance poses severe problems for the treatment of patients with leukemia or solid tumors. Particularly drug-mediated dimerization of RAF kinases can be the cause of acquired resistance, also called "paradoxical activation.

Basal Cell Carcinoma of the Head and Neck-A Retrospective Single-Centre Comparison of the Recurrence Rate after R0 or R1 Resection.

The treatment guidelines for basal cell carcinoma (BCC) postulate complete surgical excision using microscopically controlled resection (MOHS) as the gold standard. The need to obtain a small safety margin in the complex anatomical area of the head and neck is very challenging due to the individual characteristics (localization, histology, and size) of tumors and the fact that the postoperative loss of quality of life depends on the surgical defect size. The R1 status is histopathologically defined when the safety margin is less than 1 mm even if there are no tumor cells actually infiltrating the resection margin.

Influence of Viscose Fibre Geometry on the Structure-Property Relationships of High-Density Polyethylene Composites.

This study investigated the influence of viscose fibre (VF) geometry on the microstructures and resulting properties of high-density polyethylene (HDPE) composites. Seven types of viscose fibres varying in cross-section shape, linear density, and length were pelletised, compounded into HDPE with a twin-screw extruder, and injection moulded. The microstructures of the composites were characterised by investigating their cross-sections and by extracting the fibres and measuring their lengths using optical microscopy (OM).

Endoplasmic Reticulum Homeostasis Regulates TLR4 Expression and Signaling in Mast Cells.

The endoplasmic reticulum (ER) is a dynamic organelle that responds to demand in secretory proteins by undergoing expansion. The mechanisms that control the homeostasis of ER size and function involve the activation of the unfolded protein response (UPR). The UPR plays a role in various effector functions of immune cells.

The pattern of epistaxis recurrence in patients taking prophylactic acetylsalicylic acid (ASA) from a 10 year cohort.

Objectives: Epistaxis is the most common otolaryngological emergency and one-third of epistaxis patients regularly take low-dose acetylsalicylic acid (ASA) for the prevention of cardiovascular disease (CVD). The shift in contemporary guidelines identifies little benefit of ASA intake in patients who have not previously had an infarction. Existing evidence confirms ASA intake as a factor for severe epistaxis, while the evidence concerning its impact on recurrence is ambiguous.

Enrichment of centromeric DNA from human cells.

Centromeres are key elements for chromosome segregation. Canonical centromeres are built over long-stretches of tandem repetitive arrays. Despite being quite abundant compared to other loci, centromere sequences overall still represent only 2 to 5% of the human genome, therefore studying their genetic and epigenetic features is a major challenge.

Erythropoietin Enhances Post-ischemic Migration and Phagocytosis and Alleviates the Activation of Inflammasomes in Human Microglial Cells.

Recombinant human erythropoietin (rhEPO) has been shown to exert anti-apoptotic and anti-inflammatory effects after cerebral ischemia. Inflammatory cytokines interleukin-1β and -18 (IL-1β and IL-18) are crucial mediators of apoptosis and are maturated by multiprotein complexes termed inflammasomes. Microglia are the first responders to post-ischemic brain damage and are a main source of inflammasomes.

Perspective-Electrochemical Sensors for Neurotransmitters and Psychiatrics: Steps toward Physiological Mental Health Monitoring.

Therapeutic monitoring of neurotransmitters (NTs) and psychiatric medications is essential for the diagnosis and treatment of mental illness. However, in-vivo monitoring of NTs in humans as well as continuous physiological monitoring of psychiatrics have yet to be realized. In pursuit of this goal, there has been a plethora of work to develop electrochemical sensors for both in-vivo NT monitoring as well as in-vitro detection of psychiatric medications.

CENP-B-mediated DNA loops regulate activity and stability of human centromeres.

Chromosome inheritance depends on centromeres, epigenetically specified regions of chromosomes. While conventional human centromeres are known to be built of long tandem DNA repeats, much of their architecture remains unknown. Using single-molecule techniques such as AFM, nanopores, and optical tweezers, we find that human centromeric DNA exhibits complex DNA folds such as local hairpins.