Monitoring ETI effects over 1.7 years in an infant treated in utero, via breast milk and granules by repeated faecal elastase measurements.

Pancreatic insufficiency is a major complication of cystic fibrosis (CF), which traditionally has been managed with pancreatic enzyme replacement therapy in the vast majority of CF patients, even in the era of highly effective cystic fibrosis transmembrane conductance regulator modulator (CFTRm) therapy. We report on a 1.7 year old male infant with CF who was exposed to ETI both in utero and postpartum, via breast milk and oral granules.

A Systematic Review and Meta-analysis of the Clinical Impact of Prophylactic Quinolones with Adjuvant Bacillus Calmette-Guérin Instillation for Non-muscle-invasive Bladder Cancer.

Background And Objective: Bacillus Calmette-Guérin (BCG) reduces disease recurrence and progression in intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). BCG-associated adverse events during instillations are common, leading to treatment cessation. Prophylactic use of quinolones in conjunction with BCG instillations is one approach for reducing BCG-associated adverse events.

New Artisse intrasaccular device for intracranial aneurysm treatment: short term clinical and angiographic result from the prospective registry INSPIRE-A.

Background: Intrasaccular devices have broadened treatment options for wide necked aneurysms. This study presents the preliminary experience with the Artisse 2.0 device.

Low-coverage whole genome sequencing of low-grade dysplasia strongly predicts advanced neoplasia risk in ulcerative colitis.

Background: The risk of developing advanced neoplasia (AN; colorectal cancer and/or high-grade dysplasia) in ulcerative colitis (UC) patients with a low-grade dysplasia (LGD) lesion is variable and difficult to predict. This is a major challenge for effective clinical management.

Objective: We aimed to provide accurate AN risk stratification in UC patients with LGD.

Starfield's 4Cs of NCD management in primary healthcare: a conceptual framework development from a case study of 19 countries.

Introduction: Faced with a backdrop of an increasing chronic disease burden from an ageing global population compounded with rising healthcare costs, health systems are required to implement cost-effective, safe and equitable care through efficient service delivery models. One approach to achieving this is through Starfield's 4Cs of primary healthcare (PHC), which delineates the key attributes of a high-performing PHC system that upholds the pillars of care coordination, first contact of care, continuity of care and comprehensive care. Therefore, this study aims to explore and elucidate the key themes and subthemes related to and extending beyond Starfield's 4Cs of PHC by integrating findings from a comprehensive literature review and a qualitative study.

Prolonged mechanical ventilation in critically ill patients: six-month mortality, care pathways, and quality of life.

Background: There is limited knowledge about long-term mortality, care pathways and health-related quality of life (HrQoL) among intensive care unit (ICU) patients receiving prolonged mechanical ventilation (PMV).

Research Question: What are the long-term mortality, care pathways, and HrQoL of patients receiving invasive PMV, stratified by weaning success?

Study Design: and methods: We conducted a secondary analysis of patients from the cluster-randomised controlled Enhanced Recovery after Intensive Care trial who were treated in two ICU clusters and received invasive PMV (≥21 days via endotracheal tube/tracheostomy or ≥four days via tracheostomy). Data on weaning success, mortality, care place transitions, readmissions, and HrQoL were collected for six months after ICU discharge.

Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.

Unassembled and partially assembled subunits of multi-protein complexes have emerged as major quality control clients, particularly under conditions of imbalanced gene expression such as stress, aging, and aneuploidy. The factors and mechanisms that eliminate such orphan subunits to maintain protein homeostasis are incompletely defined. Here, we show that the UBR4-KCMF1 ubiquitin ligase complex is required for the efficient degradation of multiple unrelated orphan subunits from the chaperonin, proteasome cap, proteasome core, and a protein targeting complex.

Glycans of parasitic nematodes - from glycomes to novel diagnostic tools and vaccines.

Nematodes, commonly known as roundworms, are among the most prevalent and diverse multicellular organisms on Earth, belonging to the large phylum Nematoda. In addition to free-living species, many nematodes are parasitic, infecting plants, animals, and humans. Nematodes possess a wide array of genes responsible for carbohydrate metabolism and glycosylation.

Timing in orthopaedic surgery - Rethinking traditional myths with a critical perspective.

Purpose: Standard operating procedures aim to achieve a standardized and assumedly high-quality therapy. However, in orthopaedic surgery, the aspect of temporal urgency is often based on surgical tradition and experience. At a time of evidence-based medicine, it is necessary to question these temporal guidelines.

Characterization of children with early onset pediatric multiple sclerosis.

Background: Early onset pediatric multiple sclerosis (EOPMS) provides an early window of opportunity to understand the mechanisms leading to MS.

Objective: To investigate clinical, laboratory and imaging differences between children with early onset pediatric MS (<11 years, EOPMS) and late onset pediatric MS (≥11 years, LOPMS).

Methods: Mostly prospectively collected data of children with MS including clinical presentation, MRI at onset, time to second relapse, relapse rate, treatment history, and CSF markers were eligible.

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.

Structural transitions of ionic microgel solutions driven by circularly polarized electric fields.

In this work, a theoretical approach is developed to investigate the structural properties of ionic microgels induced by a circularly polarized (CP) electric field. Following a similar study on chain formation in the presence of linearly polarized fields [T. Colla , , 2018, , 4321-4337], we propose an effective potential between microgels which incorporates the field-induced interactions a static, time averaged polarizing charge at the particle surface.

Simultaneous Unbinned Differential Cross-Section Measurement of Twenty-Four Z+jets Kinematic Observables with the ATLAS Detector.

Z boson events at the Large Hadron Collider can be selected with high purity and are sensitive to a diverse range of QCD phenomena. As a result, these events are often used to probe the nature of the strong force, improve Monte Carlo event generators, and search for deviations from standard model predictions. All previous measurements of Z boson production characterize the event properties using a small number of observables and present the results as differential cross sections in predetermined bins.

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.

Tetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.

Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.

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.

Vulvar inspection at the time of cervical cancer screening: European Society of Gynaecological Oncology (ESGO), International Society for the Study of Vulvovaginal Disease (ISSVD), European College for the Study of Vulval Disease (ECSVD), and European Federation for Colposcopy (EFC) consensus statements.

Background: Vulvar squamous cell carcinoma incidence is increasing, especially among women under 60, largely attributed to human papillomavirus infections. Precursor pre-invasive vulvar lesions are frequently underdiagnosed. Routine vulvar inspection during cervical cancer screening could offer an opportunity for the detection of these lesions.

Minimally invasive compared to open surgery in patients with low-risk cervical cancer following simple hysterectomy: An exploratory analysis from the Gynegologic Cancer Intergroup/Canadian Cancer Trials Group CX.5/SHAPE trial.

Objective: The Laparoscopic Approach to Cervical Cancer trial demonstrated that minimally invasive radical hysterectomy was associated with worse disease-free survival and overall survival among women with early-stage cervical cancer. It is unknown whether this applies to patients with low-risk disease following simple hysterectomy.

Methods: Among patients who underwent simple hysterectomy in the Simple Hysterectomy And PElvic node assessment trial, univariate and multivariate Cox models were used to assess the association of minimally invasive versus open surgery with clinical outcomes, including pelvic and extra-pelvic recurrence-free survival, overall recurrence-free survival, and overall survival.

Identical Fe-N Sites with Different Reactivity: Elucidating the Effect of Support Curvature.

Detailed atomic-scale understanding is a crucial prerequisite for rational design of next-generation single-atom catalysts (SACs). However, the sub-ångström precision needed for systematic studies is challenging to achieve on common SACs. Here, we present a two-dimensional (2D) metal-organic system featuring Fe-N single-atom sites, where the metal-organic structure is modulated by 0.

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.

Identifying segment-specific barriers to ordering environmentally sustainable plant-based meat dishes in restaurants.

Eating less meat when dining out can help mitigate climate change. Plant-based meats can facilitate the transition to a more environmentally sustainable tourism sector. However, uptake of these products remains low.

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.