Leveraging Single-Cell Multi-Omics to Decode Tumor Microenvironment Diversity and Therapeutic Resistance.

Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior.

Safety and Efficacy of Thrombectomy for Distal Medium Vessel Occlusions of the Middle Cerebral Artery.

Purpose: Mechanical thrombectomy (MT) for distal medium vessel occlusions (DMVOs) in the middle cerebral artery (MCA) is less established than for large vessel occlusions. This study evaluates the safety and efficacy of MT in DMVOs, comparing it with M1-segment occlusions.

Materials And Methods: This retrospective study analyzed 218 patients who underwent MT for isolated M1 (n=123) or distal M2+M3 (n=35) occlusions between January 2020 and August 2023.

ENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY.

Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent.

T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice.

Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance.

Floating-embedded stems reduce tibial stress shielding in total knee revision arthroplasty.

Background: Total knee arthroplasty (TKA) is one of the most common orthopaedic procedures and the number of patients which undergo TKA will continue to rise in the coming years. Consecutively, the number of necessary revision surgeries will increase. One of the main reasons for revision surgery is aseptic loosening because of a so-called stress-shielding effect.

Echocardiography of the right heart in pulmonary arterial hypertension: insights from the ULTRA RIGHT VALUE study.

Aims: Outcome in pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to increased afterload. Echocardiography is easily available to assist bedside evaluation of the RV. However, no agreement exists about the feasibility and most relevant measurements.

Proximal Femur Fractures: Evaluating the Necessity of On-Call Surgery.

The decision of the Joint Federal Committee on the treatment of hip fractures stipulates that proximal femur fractures must be treated within the first 24 h. This leads to organizational and personnel difficulties in day-to-day care. Therefore, we investigated the question at what times of day we operate to maintain this timeline and whether there is a difference in the outcome for the patients according to treatment hours.

Assessment of decision-making with locally run and web-based large language models versus human board recommendations in otorhinolaryngology, head and neck surgery.

Introduction: Tumor boards are a cornerstone of modern cancer treatment. Given their advanced capabilities, the role of Large Language Models (LLMs) in generating tumor board decisions for otorhinolaryngology (ORL) head and neck surgery is gaining increasing attention. However, concerns over data protection and the use of confidential patient information in web-based LLMs have restricted their widespread adoption and hindered the exploration of their full potential.

GOLD grade-specific characterization of COPD in the COSYCONET multi-center trial: comparison of semiquantitative MRI and quantitative CT.

Objectives: We hypothesized that semiquantitative visual scoring of lung MRI is suitable for GOLD-grade specific characterization of parenchymal and airway disease in COPD and that MRI scores correlate with quantitative CT (QCT) and pulmonary function test (PFT) parameters.

Methods: Five hundred ninety-eight subjects from the COSYCONET study (median age = 67 (60-72)) at risk for COPD or with GOLD1-4 underwent PFT, same-day paired inspiratory/expiratory CT, and structural and contrast-enhanced MRI. QCT assessed total lung volume (TLV), emphysema, and air trapping by parametric response mapping (PRM, PRM) and airway disease by wall percentage (WP).

Deep CRISPR mutagenesis characterizes the functional diversity of TP53 mutations.

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells.

The Diagnostic Accuracy of an Electrocardiogram in Pulmonary Hypertension and the Role of "R V1, V2 + S I, aVL - S V1".

: Pulmonary hypertension (PH) can cause characteristic electrocardiographic (ECG) changes due to right ventricular hypertrophy and/or strain. The aims of the present study were to explore the diagnostic accuracy of ECG parameters for the diagnosis of PH, applying the recently adjusted mean pulmonary artery pressure (mPAP) threshold of >20 mmHg, and to determine the role of "R V1, V2 + S I, aVL - S V1". : Between July 2012 and November 2023, 100 patients without PH, with pulmonary arterial hypertension, or with chronic thromboembolic pulmonary hypertension were retrospectively enrolled.

Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.

Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways.

The impact of white matter lesions and subclinical cerebral ischemia on postoperative cognitive training outcomes after heart valve surgery: A randomized clinical trial.

Background: White matter lesions and subclinical cerebral ischemia (SCI) are described as risk factors for postoperative cognitive decline (POCD) following cardiac surgery. This report aims to investigate the effect of brain lesions on postoperative cognitive training outcomes.

Methods: In a randomized, treatment-as-usual controlled trial, elderly patients scheduled for elective heart valve surgery participated.

Digital Transformation of Rheumatology Care in Germany: Cross-Sectional National Survey.

Background: In recent years, health care has undergone a rapid and unprecedented digital transformation. In many fields of specialty care, such as rheumatology, this shift is driven by the growing number of patients and limited resources, leading to increased use of digital health technologies (DHTs) to maintain high-quality clinical care. Previous studies examined user acceptance of individual DHTs in rheumatology, such as telemedicine, video consultations, and mHealth.

Patient Support in Obstructive Sleep Apnoea by a Large Language Model - ChatGPT 4o on Answering Frequently Asked Questions on First Line Positive Airway Pressure and Second Line Hypoglossal Nerve Stimulation Therapy: A Pilot Study.

Purpose: Obstructive sleep apnoea (OSA) is a common disease that benefits from early treatment and patient support in order to prevent secondary illnesses. This study assesses the capability of the large language model (LLM) ChatGPT-4o to offer patient support regarding first line positive airway pressure (PAP) and second line hypoglossal nerve stimulation (HGNS) therapy.

Methods: Seventeen questions, each regarding PAP and HGNS therapy, were posed to ChatGPT-4o.

Mixed-methods process evaluation of a proactive approach to healthcare in Parkinson's disease-ParkProReakt: a protocol of a hybrid efficacy-implementation study.

Introduction: People with Parkinson's disease (PwPD) experience a wide range of motor and non-motor symptoms that have a significant impact on their health and quality of life. Effective care management for PwPD involves monitoring symptoms at home, involving specialised multidisciplinary care providers and enhancing self-management skills. This study protocol describes the process evaluation within a randomised clinical trial to assess the implementation and its impact on patient health outcomes of ParkProReakt-a proactive, multidisciplinary, digitally supported care model for community-dwelling PwPD.

Differentiating Benign from Malignant Causes of Splenomegaly: Is Acoustic Radiation Force Impulse Elastography Helpful?

Purpose: To evaluate the ability of acoustic radiation force impulse (ARFI) elastography in differentiating benign from malignant etiologies of splenomegaly based on differences in splenic stiffness.

Materials And Methods: Between September 2020 and November 2022, we evaluated 40 patients with splenomegaly-defined by a splenic long axis greater than 13 cm and/or a short axis greater than 6 cm, without visible focal or infiltrative mass lesions-using abdominal ultrasound at our university hospital. Each patient also underwent a standardized ARFI elastographic assessment of the enlarged spleen, with data collected prospectively.

Minimally Invasive Mitral Valve Repair with Intercostal Cryoablation: A Case Report.

 Minimally invasive lateral thoracotomies may cause severe postoperative pain and discomfort. We describe an intraoperative intercostal cryo-neuronal pain block as one possibility for postoperative pain relief.  A 63-year-old male patient underwent minimally invasive mitral valve repair.

Impact of absolute values and changes in meteorological and air quality conditions on community-acquired pneumonia in Germany.

Community-acquired pneumonia (CAP) is a major global health concern as it is a leading cause of morbidity, mortality and economic burden to the health care systems. In Germany, more than 15,000 people die every year from CAP. Climate change is altering weather patterns, and it may influence the probability and severity of CAP.

Adult-onset status epilepticus in patients with COQ8A coenzyme Q10 deficiency: A case series.

This case series describes the clinical features, diagnostic challenges, treatment approaches, and outcomes of three adult patients with COQ8A-related CoQ10 deficiency presenting with focal status epilepticus, who were effectively treated at the Department of Neurology, Philipps University Marburg, Marburg, Germany. The patients, all from consanguineous families with the first two being siblings, presented with a late onset of the disease, characterized by progressive cerebellar ataxia and epilepsy, with clinical deterioration and focal status epilepticus occurring in adulthood. The first patient exhibited myoclonic status, while the second and third patients presented with bilateral tonic-clonic seizures followed by focal status epilepticus manifesting with cortical blindness.

Quantification of Different Types of Waste and Batteries Associated With the Widespread Usage of Continuous Glucose Monitoring Systems.

Background: People with diabetes benefit from continuous glucose monitoring (CGM) systems. A downside of these valuable aids for diabetes management is the generation of a tremendous amount of waste. This study aimed to quantify this CGM-related waste.

Endosonography in head and neck imaging and surgery.

This CME article explores the evolving role of endosonography in otorhinolaryngology and head and neck surgery. Endosonography offers significant potential to improve imaging inside the upper respiratory tract, particularly with advancements in probe technology and imaging resolution. The article will describe the sonoanatomy of the oral cavity, pharynx, and larynx and the selection of probes and scanning techniques used for the various anatomical sites.

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity.

Visual detection of pulselessness by carotid artery sonography - A prospective observational study among medical students.

Aim: This cross-sectional study aimed to determine whether medical students with little to no ultrasound experience could correctly distinguish between 'pulsation present' and 'no pulsation present' after a short introductory video on the subject using ultrasound videos of the common carotid artery (CCA).

Methods: Ultrasound videos (B-mode, M-mode, and Color Doppler) of pulsatile (systolic blood pressure 70-80 mmHg) and non-pulsatile (cardiopulmonary bypass surgery, clamped aorta) CCA were created. These were demonstrated to the medical students for a period of ten seconds - corresponding to the duration of the manual pulse palpation during cardiopulmonary resuscitation (CPR).