First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.

Purpose: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2: ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.

Generative artificial intelligence enables the generation of bone scintigraphy images and improves generalization of deep learning models in data-constrained environments.

Purpose: Advancements of deep learning in medical imaging are often constrained by the limited availability of large, annotated datasets, resulting in underperforming models when deployed under real-world conditions. This study investigated a generative artificial intelligence (AI) approach to create synthetic medical images taking the example of bone scintigraphy scans, to increase the data diversity of small-scale datasets for more effective model training and improved generalization.

Methods: We trained a generative model on Tc-bone scintigraphy scans from 9,170 patients in one center to generate high-quality and fully anonymized annotated scans of patients representing two distinct disease patterns: abnormal uptake indicative of (i) bone metastases and (ii) cardiac uptake indicative of cardiac amyloidosis.

Exploring the Structure-Activity Relationships of Albumin-Targeted Picoplatin-Based Platinum(IV) Prodrugs.

Platinum(II) complexes prevail as first-line treatment for many cancers but are associated with serious side effects and resistance development. Picoplatin emerged as a promising alternative to circumvent GSH-induced tumor resistance by introducing a bulky 2-picoline ligand. Although clinical studies were encouraging, picoplatin did not receive approval.

Human-derived microRNA 21 regulates indole and L-tryptophan biosynthesis transcripts in the gut commensal .

Unlabelled: In the gut, microRNAs (miRNAs) produced by intestinal epithelial cells are secreted into the lumen and can shape the composition and function of the gut microbiome. Crosstalk between gut microbes and the host plays a key role in irritable bowel syndrome (IBS) and inflammatory bowel diseases, yet little is known about how the miRNA-gut microbiome axis contributes to the pathogenesis of these conditions. Here, we investigate the ability of miR-21, a miRNA that we found decreased in fecal samples from IBS patients, to associate with and regulate gut microbiome function.

Clearing the path for whole-mount labeling and quantification of neuron- and vessel-density in adipose tissue.

White adipose tissue (WAT) comprises a plethora of cell types beyond adipocytes forming a regulatory network that ensures systemic energy homeostasis. Intertissue communication is facilitated by metabolites and signaling molecules that are spread by vasculature and nerves. Previous works indicated that WAT responds to environmental cues by adapting the abundance of these "communication routes", however, high intra-tissue heterogeneity questions the informative value of bulk or single cell analyses and underscores the necessity of whole-mount imaging.

Resonant song recognition and the evolution of acoustic communication in crickets.

Cricket song recognition is thought to evolve through modifications of a shared neural network. However, the species has an unusual recognition pattern that challenges this view: females respond to both normal male song pulse periods and periods twice as long. Of the three minimal models tested, only a single-neuron model with an oscillating membrane could explain this unusual behavior.

Risk assessment and prevention of cancer-associated venous thromboembolism in ambulatory patients with solid malignancies.

Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment models and the latest guideline recommendations.

Characterization of patients with clonal mast cells in the bone marrow with clinical significance not otherwise specified.

Background: Systemic mastocytosis (SM) diagnosis requires the presence of 3 minor criteria or 1 major and 1 minor criterion according to the WHO 2016 classification. The aim of this study was to characterize patients with 1 or 2 minor SM criteria including mutation and/or aberrant expression of CD2 and/or CD25 on bone marrow (BM) mast cells (MCs), but without MC activation syndrome (MCAS) criteria.

Methods: We included eligible patients from two countries diagnosed between 2011 and 2021.

Genetic and nongenetic variation of multiple births in Austrian dual-purpose cows.

In recent decades, a general increase in multiple birth (MB) rate has been reported in both dairy and dual-purpose cattle breeds. As there is evidence that MB has negative effects on economically important traits in dairy cows, the aims of this study were to (i) investigate environmental and genetic factors affecting MB rate and (ii) assess the impact of MB on productive and nonproductive traits of the Austrian dual-purpose breeds Pinzgauer and Tyrol Grey. The dataset included 99,141 calvings of 33,791 Pinzgauer and 68,454 calvings of 19,244 Tyrol Grey cows recorded from 2000 to 2022.

Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases.

Autoimmune rheumatic diseases (ARDs) are a heterogeneous group of conditions characterized by excessive and misdirected immune responses against the body's own musculoskeletal tissues. Their exact aetiology remains unclear, with genetic, demographic, behavioural and environmental factors implicated in disease onset. One prominent hypothesis for the initial breach of immune tolerance (leading to autoimmunity) is molecular mimicry, which describes structural or sequence similarities between human and microbial proteins (mimotopes).

Second-line treatment patterns and outcomes in advanced HCC after progression on atezolizumab/bevacizumab.

Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

Clinical Presentation and Course of Pulmonary Involvement in Chronic Nonbacterial Osteomyelitis.

Objective: Pulmonary involvement in chronic nonbacterial osteomyelitis (CNO) is rare. Limited awareness results in diagnostic challenges, especially because malignancy or infection needs to be considered.

Methods: Based on a survey shared among centers participating in the Kerndokumentation Deutsches Rheumaforschungszentrum (Germany), this study investigated clinical and imaging presentations, demographic features, treatment response and outcomes of pulmonary involvement in CNO (pCNO).

Using a clinical decision support system to reduce excess driving pressure: the ALARM trial.

Background: Patients at need for ventilation often are at risk of acute respiratory distress syndrome (ARDS). Although lung-protective ventilation strategies, including low driving pressure settings, are well known to improve outcomes, clinical practice often diverges from these strategies. A clinical decision support (CDS) system can improve adherence to current guidelines; moreover, the potential of a CDS to enhance adherence can possibly be further increased by combination with a nudge type intervention.

Association between changes in genital immune markers and vaginal microbiome transitions in bacterial vaginosis.

Bacterial vaginosis (BV), characterized by an imbalance in the vaginal microbiota, is a prevalent condition among women of reproductive age and a risk factor for human immunodeficiency virus, sexually transmitted infections, and preterm birth. BV is generally considered to induce mucosal inflammation, but the specific pathways and cell types involved are not well characterized. This prospective study aimed to assess associations between microbial changes and mucosal immune responses in BV patients.

Caring around and through medical tests in primary care: On the role of care in the diagnostic process.

Primary care is characterised by a broad understanding of health and illness. Due to the high degree of diagnostic uncertainty in primary care, medical tests play a lesser role in this domain than in specialist medicine. However, medical testing is also becoming increasingly important in primary care, raising questions about how these technologies are integrated into everyday practice.

The cost of fear: Impairments of decision-making in specific phobia.

Background: Decision-making processes may play a pivotal role in the etiology and maintenance of specific phobia. However, empirical evidence is limited. This study examined whether decision-making is only impaired in presence of fear-related stimuli or whether general impairments exist but are more pronounced in the presence of fear-related stimuli.

The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) of the European Association for Cardio-Thoracic Surgery Fourth report: Focus on standardized outcome ratios.

Objectives: This fourth report aimed to provide insights into patient characteristics, outcomes, and standardized outcome ratios of patients implanted with durable Mechanical Circulatory Support across participating centers in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) registry.

Methods: All registered patients receiving durable mechanical circulatory support up to August 2024 were included. Expected number of events were predicted using penalized logistic regression.

Aspirin Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis Among Patients With Post-Thrombotic Syndrome: The Multicenter, Multinational, Randomized, Open-label ARIVA Trial.

Background: In patients with post-thrombotic syndrome (PTS), stent recanalization of iliofemoral veins or the inferior vena cava can restore venous patency and improve functional outcomes. The risk of stent thrombosis is particularly increased during the first 6 months after intervention. The ARIVA trial tested whether daily aspirin 100 mg plus rivaroxaban 20 mg is superior to rivaroxaban 20 mg alone to prevent stent thrombosis within 6 months after stent placement for PTS.

Co-Producing Peritoneal Dialysis Nursing Sensitive Indicators for Quality Care: A Multinational Consensus Building Design.

Background: Nursing sensitive indicators are a way of measuring aspects of patient care that are most affected by the actions of the nurse. Despite the existence of nursing sensitive indicators, these are largely not suitable to measure peritoneal dialysis nursing practice.

Objective: This project aimed to co-develop a set of peritoneal dialysis nursing-sensitive indicators.

Secondary amputation: a qualitative study of quality of life in patients after primary limb salvage surgery and after later ablative sarcoma treatment.

Objective: This study focuses on how patients experience the time following amputation after primary limb salvage surgery due to musculoskeletal malignancies. Limb salvage is state of the art in the treatment of musculoskeletal tumours. Nonetheless, in some cases, limb salvage can become problematic over time, resulting in poorer limb function and septic outcomes.

The bronchoalveolar lavage fluid as a marker for pulmonary fibrosis in diffuse parenchymal lung diseases.

Introduction: Diffuse parenchymal lung diseases (DPLD) cover heterogeneous types of lung disorders. Among many pathological phenotypes, pulmonary fibrosis is the most devastating and represents a characteristic sign of idiopathic pulmonary fibrosis (IPF). Despite a poor prognosis brought by pulmonary fibrosis, there are no specific diagnostic biomarkers for the initial development of this fatal condition.

Long-term outcomes in five patients with autoimmune pulmonary alveolar proteinosis treated with molgramostim inhalation solution.

Autoimmune pulmonary alveolar proteinosis (aPAP), which accounts for >90% of all cases of PAP, is a rare lung disease mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies that block GM-CSF signalling, leading to reduced surfactant clearance causing abnormal accumulation of alveolar surfactant and impaired gas exchange [1-3]. The current standard of care for aPAP is whole-lung lavage (WLL), which is invasive, resource intensive, carries procedural risk, does not address the underlying cause of disease and often must be repeated regularly [4]. Hence, there is a therapeutical need to address the underlying pathophysiology of the disease.

Number of children and dementia risk: a causal mediation analysis using data from the HUNT study linked with national registries in Norway.

Background: Childlessness, as well as having a high number of children, has been reported to be associated with an elevated risk of dementia compared to having 2-3 children. The mechanisms underlying these relationships are not well understood and may be mediated by different midlife risk factors. We examined the mediating role of various factors on the relationship between the number of children and dementia risk.