Discovery of new inhibitors of nuclease MRE11.

MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors MU147 and MU1409. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-the-art inhibitor mirin.

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

High-throughput drug screening identifies SMAC mimetics as enhancers of NK cell cytotoxicity in chronic myeloid leukemia.

Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells.

Baseline characteristics and 2-year functional outcome data of patients undergoing an arthroscopic rotator cuff repair in Switzerland, results of the ARCR_Pred study.

The ARCR_Pred study was initiated to document and predict the safety and effectiveness of arthroscopic rotator cuff repair (ARCR) in a representative Swiss patient cohort. In the present manuscript, we aimed to describe the overall and baseline characteristics of the study, report on functional outcome data and explore case-mix adjustment and differences between public and private hospitals. Between June 2020 and November 2021, primary ARCR patients were prospectively enrolled in a multicenter cohort across 18 Swiss and one German orthopedic center.

Exploring associations between the FTO rs9939609 genotype and plasma concentrations of appetite-related hormones in adults with obesity.

Associations between variants in the FTO locus and plasma concentrations of appetite related hormones are inconsistent, and might not work in a dose dependent fashion in people with obesity. Moreover, it is relevant to report meal related plasma concentrations of these hormones in persons with obesity given the growing interest in their pharmacological potential in obesity therapy. We find it clinically relevant to examine associations between the SNP rs9939609 genotypes and homeostatic appetite regulation in individuals with BMI ≥35 kg/m2.

Guardian Knowledge in Primary Congenital Glaucoma: A Cross-Sectional Study.

Prcis: Guardian education level and frequency of surgical interventions are key determinants of knowledge in primary congenital glaucoma, highlighting the need for targeted educational strategies.

Background: Management of congenital glaucoma poses unique challenges, particularly concerning the patient guardians' understanding of the condition, which is crucial for treatment adherence and follow-up compliance. This study aimed to assess guardians' knowledge levels and identify the influencing factors.

Hepatocellular Carcinoma Cells in Humans Exhibit Resistance to Suberoylanilide Hydroxamic Acid (SAHA) Owing to the Diminished Level of Hsa-miR-125a-5p.

Hepatocellular carcinoma (HCC) presents an escalating public health challenge globally. However, drug resistance has emerged as a major impediment to successful HCC treatment, limiting the efficacy of curative interventions. Despite numerous investigations into the diverse impacts of hsa-miR-125a-5p on tumor growth across different cancer types, its specific involvement in chemotherapy resistance in HCC remains elusive.

Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.

Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.

Biochemical and Computational Characterization of Haloalkane Dehalogenase Variants Designed by Generative AI: Accelerating the S2 Step.

Generative artificial intelligence (AI) models trained on natural protein sequences have been used to design functional enzymes. However, their ability to predict individual reaction steps in enzyme catalysis remains unclear, limiting the potential use of sequence information for enzyme engineering. In this study, we demonstrated that sequence information can predict the rate of the S2 step of a haloalkane dehalogenase using a generative maximum-entropy (MaxEnt) model.

The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models.

Recent research has shown that mtDNA-deficient cancer cells (ρ cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1) mice markedly delayed tumor formation after grafting ρ cancer cells.

Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn.

Importance: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

Familial Mediterranean fever with sigmoid colon stricture.

We describe a case of familial Mediterranean fever (FMF) with sigmoid colon stricture. The patient, a woman in her 30 s, had a 12-year history of ileocolitis-type Crohn's disease. The colonoscope could not pass because of the sigmoid colon stricture, and the patient was referred to our hospital with complaints of abdominal pain and fever.

Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations.

Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.

Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.

Tailored Approach to Temporary Mechanical Circulatory Support for Cardiogenic Shock: Strategies to Facilitate Patient Mobilization.

Purpose Of Review: This article discusses a tailored approach to managing cardiogenic shock and temporary mechanical circulatory support (tMCS). We also outline specific mobilization strategies for patients with different tMCS devices and configurations, which can be enabled by this tailored approach to cardiogenic shock management.

Recent Findings: Safe and effective mobilization of patients with cardiogenic shock receiving tMCS can be accomplished.

Patient- and clinician-based evaluation of large language models for patient education in prostate cancer radiotherapy.

Background: This study aims to evaluate the capabilities and limitations of large language models (LLMs) for providing patient education for men undergoing radiotherapy for localized prostate cancer, incorporating assessments from both clinicians and patients.

Methods: Six questions about definitive radiotherapy for prostate cancer were designed based on common patient inquiries. These questions were presented to different LLMs [ChatGPT‑4, ChatGPT-4o (both OpenAI Inc.

Strategies to enhance management of HER2-positive breast cancer in the elderly: an expert consensus perspective.

Therapeutic decision-making for older patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer highlights the importance of a comprehensive geriatric assessment (CGA). This assessment considers the functional status, comorbidities, and relevant conditions of the patient, and allows for an estimation of life expectancy, but it does not facilitate individualized treatment plans. There are also other challenges to consider related to the cardiac toxicity of the treatments and the under-representation of older patients in clinical trials.

Evaluating smartphone-based 3D imaging techniques for clinical application in oral and maxillofacial surgery: A comparative study with the vectra M5.

Purpose: This study aimed to clarify the applicability of smartphone-based three-dimensional (3D) surface imaging for clinical use in oral and maxillofacial surgery, comparing two smartphone-based approaches to the gold standard.

Methods: Facial surface models (SMs) were generated for 30 volunteers (15 men, 15 women) using the Vectra M5 (Canfield Scientific, USA), the TrueDepth camera of the iPhone 14 Pro (Apple Inc., USA), and the iPhone 14 Pro with photogrammetry.

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.

Analytical review of facial nerve palsy following SARS-CoV-2 vaccination: comprehensive assessment.

Purpose: The SARS-CoV-2 vaccination has reduced COVID-19 infection, though facial nerve palsy (FNP) has emerged as a notable side effect of the vaccine. We evaluated the current literature on the clinical presentation and outcomes of FNP related to COVID-19 vaccination.

Methods: A comprehensive search of seven databases was conducted for studies up to January 2023.

Endoglin as a predictive biomarker for pemetrexed sensitivity in non-small-cell lung cancer: a cellular study.

Objective: Based on our previous research, which demonstrated that elevated plasma endoglin (ENG) levels in lung cancer patients were associated with a better prognosis, increased sensitivity to pemetrexed, and enhanced tumor suppression, this study aims to validate these findings at the cellular level. The focus is on membrane and extracellular ENG and their influence on drug response and tumor cell behavior in non-small cell lung cancer (NSCLC) cells.

Methods: The correlation between ENG expression and pemetrexed-induced cytotoxicity in eight human non-squamous subtype NSCLC cell lines was analyzed.

Tracking clonal and plasmid transmission in colistin- and carbapenem-resistant .

The surveillance of mobile genetic elements facilitating the spread of antimicrobial resistance genes has been challenging. Here, we tracked both clonal and plasmid transmission in colistin- and carbapenem-resistant using short- and long-read sequencing technologies. We observed three clonal transmissions, all containing Incompatibility group (Inc) L plasmids and New Delhi metallo-beta-lactamase , although not co-located on the same plasmid.

Coronary atherosclerosis in athletes: emerging concepts and preventive strategies.

There should be no assumption that an athlete is immune to coronary artery disease (CAD), even when traditional cardiovascular (CV) risk factors appear well-managed. Excelling in certain aspects of health does not equate to total CV protection. Recent data from cardiac imaging studies have raised the possibility that long-term, high-volume, high-intensity endurance exercise is associated with coronary atherosclerosis.

Carotid artery atherosclerosis: mechanisms of instability and clinical implications.

Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability.

Preservation of the azygos vein versus ligation of the azygos vein during primary surgical repair of congenital esophageal atresia.

Background: Esophageal atresia is one of the most common life-threatening congenital malformations and is defined as an interruption in the continuity of the esophagus with or without fistula to the trachea or bronchi. Definitive treatment is surgical ligation of the fistula if present and esophageal end-to-end anastomosis of the two pouches, thereby reconstructing the continuity of the esophagus. During this procedure, the surgeon may choose to either ligate or preserve the azygos vein, a major draining vein for the esophagus and surrounding structures, but no definitive consensus on the matter exists.