Germline Single-Nucleotide Polymorphism Causes Alterations in Mitochondrial Metabolism and Leads to Increased ROS-Mediated DNA Damage in a Murine Model of Human Acute Myeloid Leukemia.

: GFI1-36N represents a single-nucleotide polymorphism (SNP) of the zinc finger protein Growth Factor Independence 1 (GFI1), in which the amino acid serine (S) is replaced by asparagine (N). The presence of the gene variant is associated with a reduced DNA repair capacity favoring myeloid leukemogenesis and leads to an inferior prognosis of acute myeloid leukemia (AML) patients. However, the underlying reasons for the reduced DNA repair capacity in leukemic cells are largely unknown.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

Directed Evolution of AAV9 for Efficient Gene Expression in Cardiomyocytes and .

Adeno-associated viral (AAV) vectors are increasingly used for preclinical and clinical cardiac gene therapy approaches. However, gene transfer to cardiomyocytes poses a challenge due to differences between AAV serotypes in terms of expression efficiency and . For example, AAV9 vectors work well in rodent heart muscle cells but not in cultivated neonatal rat ventricular cardiomyocytes (NRVCMs), necessitating the use of AAV6 vectors for studies.

Mechanistic insights into HPV-positivity in non-smokers and HPV-negativity in smokers with head and neck cancer.

Introduction: Several aspects of the involvement of HPV in the pathogenesis of HPV-associated diseases remain poorly understood including mechanistic aspects of infection and the question of why the majority of HPV-positive HNSCC-patients are non-smokers, whereas HPV-negatives are smokers. Our previous research, based on 1,100 patient samples, hypothesized an explanation for this phenomenon: Smoking induces upregulation of a mucosal protective protein (SLPI), which competes with HPV for binding to Annexin A2 (AnxA2), pivotal for HPV cell entry. Here we investigate the mechanistic aspects of our hypothesis using transfection assays.

Definition of a European pre-vasectomy scoring system to identify patients at risk of vasectomy regret.

Introduction: Vasectomy is a widely used, safe, effective method of permanent contraception and contributes to healthy sexuality.

Aims: We have conducted a 3-step observational clinical study to develop a vasectomy regret risk score and guide patients and clinicians when discussing a vasectomy.

Methods: A 3-step approach has been followed.

DenseSeg: joint learning for semantic segmentation and landmark detection using dense image-to-shape representation.

Purpose: Semantic segmentation and landmark detection are fundamental tasks of medical image processing, facilitating further analysis of anatomical objects. Although deep learning-based pixel-wise classification has set a new-state-of-the-art for segmentation, it falls short in landmark detection, a strength of shape-based approaches.

Methods: In this work, we propose a dense image-to-shape representation that enables the joint learning of landmarks and semantic segmentation by employing a fully convolutional architecture.

Towards a common terminology of ventilation during cardiopulmonary resuscitation.

Manual and mechanical ventilation during cardiopulmonary resuscitation are critical yet poorly understood components of resuscitation care. In recent years, intra-arrest ventilation has been the subject of a growing number of laboratory and clinical investigations. Essential components to accurately interpret or reproduce original investigations are the exact measurement and transparent reporting of key ventilation parameters, such as volumes and airway pressures obtained during ongoing cardiopulmonary resuscitation.

Is the freezing index a valid outcome to assess freezing of gait during turning in Parkinson's disease?

Introduction: Freezing of gait (FOG) is a disabling symptom for people with Parkinson's disease (PwPD). Turning on the spot for one minute in alternating directions (360 turn) while performing a cognitive dual-task (DT) is a fast and sensitive way to provoke FOG. The FOG-index is a widely used wearable sensor-based algorithm to quantify FOG severity during turning.

Serum NfL predicts outcome and secondary autoimmunity in herpes-simplex encephalitis.

Objectives: Herpes simplex virus 1 encephalitis (HSE) is the most common infectious encephalitis in developed countries. We aimed to evaluate the association of serum neurofilament light chain (sNfL) with disease severity, outcome and secondary anti-neuronal autoantibodies in a retrospective cohort study.

Methods: We retrospectively identified 30 patients with HSE and 132 controls (bacterial meningoencephalitis BM n = 27, non-bacterial meningitis NBM n = 33, healthy controls = 72).

Clinical characteristics and BGA-optimized pretest probability of pulmonary embolism in the elderly.

Background: Pulmonary arterial embolism (PE) is not well characterized in elderly patients. In addition, unnecessary computed tomography pulmonary angiography (CTPA) examinations are often performed within this patient group, especially if the pretest probability is low.

Objective: To identify differences in clinical presentation in patients aged ≥80 years compared to patients <80 years and the effect of a BGA-optimized pretest probability to reduce unnecessary CTPAs according to age category.

Williams-Beuren Syndrome and Epilepsy: A Retrospective Analysis of 589 Patients.

Although many reports have described the characteristics of Williams-Beuren syndrome, few specifically analyzed epilepsy in patients with Williams-Beuren syndrome. In this retrospective study, we map the prevalence, types, and prognosis of epileptic seizures in a large cohort of 589 patients with Williams-Beuren syndrome, as well as associations between deletions of the membrane-associated guanylate kinase inverted-2-gene (2 gene), which is associated with infantile spasms (IS), and epilepsy in patients with Williams-Beuren syndrome.Our findings indicate that the incidence of epilepsy in patients with Williams-Beuren syndrome is approximately 1.

How does an intervention work?-English Version : Development of an effect model for a complex intervention to prevent recurring or persistent pain using the example of PAIN 2.0.

In addition to the usual evaluation approach (usually a clinical randomized trial in the sense of the question: does an intervention work), complex interventions require further systematic investigations to prove their effectiveness. The role of the context in which the intervention is delivered is essential here, as is consideration of the question of why an intervention works (or does not work). Detailed recommendations exist for the planning and implementation of effectiveness studies on complex interventions, to which interdisciplinary multimodal pain therapy undoubtedly belongs.

Retrospective analysis of amantadine response and predictive factors in intensive care unit patients with non-traumatic disorders of consciousness.

Background: Disorders of consciousness (DoC) in non-traumatic ICU-patients are often treated with amantadine, although evidence supporting its efficacy is limited.

Methods: This retrospective study analyzed non-traumatic DoC-patients treated with amantadine between January 2016 and June 2021. Data on patient demographics, clinical characteristics, treatment specifications, and outcomes were extracted from electronic medical records.

Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Genomic reanalysis of a pan-European rare-disease resource yields new diagnoses.

Genetic diagnosis of rare diseases requires accurate identification and interpretation of genomic variants. Clinical and molecular scientists from 37 expert centers across Europe created the Solve-Rare Diseases Consortium (Solve-RD) resource, encompassing clinical, pedigree and genomic rare-disease data (94.5% exomes, 5.

Specific selection of stimulation-responsive γδ T-cells utilizing a short-term activation assay.

T cells expressing the γδ T-cell receptor (TCR) represent a numerically small proportion of total T cells. Unlike αβ T cells they are activated by non-peptide antigens independently of MHC-presentation. γδ T cells have been recognized as a favorable prognostic marker across different tumor entities.

Repeat Procedures After Pulsed Field Ablation for Atrial Fibrillation: MANIFEST-REDO Study.

Background: Initial clinical studies of pulsed field ablation (PFA) to treat atrial fibrillation (AF) indicated a >90% durability rate of pulmonary vein isolation (PVI). However, these studies were largely conducted in single centers and involved a limited number of operators. The electrophysiological findings and outcomes in patients undergoing repeat ablation after an initial PF ablation for AF are incompletely understood.

Incidence and predictors of weaning failure from veno-arterial extracorporeal membrane oxygenation therapy in patients with cardiogenic shock.

Aims: This study aimed to investigate incidence and predictors of weaning failure and in-hospital death after successful weaning from veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in patients with cardiogenic shock (CS).

Methods And Results: Overall, 685 patients with CS treated with VA-ECMO from 23 tertiary care centres in 7 countries were analysed (median age 57 [interquartile range 49-66] years, 542 [79.1%] male, median lactate 7.

Idecabtagene vicleucel or ciltacabtagene autoleucel for relapsed or refractory multiple myeloma: An international multicenter study.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM), but direct comparisons are lacking. Leveraging an international multicenter RRMM cohort, we compared the outcome of ide-cel ( = 162) versus cilta-cel ( = 42). Co-primary efficacy endpoints of the study were overall response rate (ORR) and progression-free survival (PFS).

Empowering personalized oncology: evolution of digital support and visualization tools for molecular tumor boards.

Background: Molecular tumor boards (MTBs) play a pivotal role in personalized oncology, leveraging complex data sets to tailor therapy for cancer patients. The integration of digital support and visualization tools is essential in this rapidly evolving field facing fast-growing data and changing clinical processes. This study addresses the gap in understanding the evolution of software and visualization needs within MTBs and evaluates the current state of digital support.

Instruments for Evaluating Undergraduate Medical Education in Complementary and Integrative Medicine: A Systematic Review.

The provision of courses in complementary and integrative medicine (CIM) varies widely between medical schools. To effectively improve CIM education, it is essential to use robust evaluation instruments that measure the impact of different educational interventions. This review aimed to identify and critically appraise qualitative and quantitative instruments used to evaluate CIM courses in undergraduate medical education.

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis.

Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval.