Systemic therapy for patients with metastatic pheochromocytoma and paraganglioma.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors derived from the paraganglia. These tumors frequently secrete excessive amounts of catecholamines leading to cardiovascular and gastrointestinal complications. While all pheochromocytomas and paragangliomas possess the potential for metastasis, actual metastatic occurrences are observed in approximately one third of cases.

Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Hemodialysis: An International, Multicentric Registry.

Background: The net benefit of oral anticoagulation in patients with end-stage renal disease on hemodialysis (HD) is uncertain. In recent years, left atrial appendage closure (LAAC) has emerged as an alternative to oral anticoagulation; however, there is scant evidence of LAAC in patients on HD.

Objectives: This study aimed to assess the feasibility and safety of LAAC in patients on HD.

Improving Nanoparticle Size Estimation from Scanning Transmission Electron Micrographs with a Multislice Surrogate Model.

The computational cost of simulating scanning transmission electron microscopy (STEM) images limits the curation of large enough data sets to train accurate and robust machine learning networks for deep feature extraction from atomically resolved STEM images. For nanoparticle size estimation in particular, a diverse data set is essential due to the large variations in size, shape, crystallinity, orientation, and dynamical diffraction effects in experimental data. To address this, we train a 3D convolutional neural network to predict STEM images from voxelized atomic models, achieving a 100x speed-up compared to traditional multislice simulations while maintaining high image quality.

Development of the fish invitrome for animal-free environmental risk assessment of chemicals.

Given the need to reduce animal testing for environmental risk assessment, we aim to develop a fish invitrome, an alternative fish modular framework capable of predicting chemical toxicity in fish without the use of animals. The central module of the framework is the validated RTgill-W1 cell line assay that predicts fish acute toxicity of chemicals (Organization for Economic Cooperation and Development Test Guideline (OECD TG) 249). Expanding towards prediction of chronic toxicity, the fish invitrome includes two other well-advanced modules for chemical bioaccumulation/biotransformation and inhibition of fish growth.

Localized K63 ubiquitin signaling is regulated by VCP/p97 during oxidative stress.

Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote concerted response mechanisms remain understudied.

Characterization of the N- and C-terminal domain interface of the three main apoE isoforms: A combined quantitative cross-linking mass spectrometry and molecular modeling study.

Apolipoprotein E (apoE) polymorphism is associated with different pathologies such as atherosclerosis and Alzheimer's disease. Knowledge of the three-dimensional structure of apoE and isoform-specific structural differences are prerequisites for the rational design of small molecule structure modulators that correct the detrimental effects of pathological isoforms. In this study, cross-linking mass spectrometry (XL-MS) targeting Asp, Glu and Lys residues was used to explore the intramolecular interactions in the E2, E3 and E4 isoforms of apoE.

Engineering electrogenetic interfaces for mammalian cell control.

Human body cells and our daily electronic devices both communicate information within their distinct worlds by regulating the flow of electrons across specified membranes. While electronic devices depend on the flow of electrons generated by conductive materials to communicate within a digital network, biological systems use ion gradients, created in analog biochemical reactions, to trigger biological data transmission throughout multicellular systems. Electrogenetics is an emerging concept in synthetic biology in which electrons generated by digital electronic devices program customized electron-responsive biological units within living cells.

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.

Safety and efficacy of tamoxifen in non-ambulant patients with Duchenne muscular dystrophy: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (TAMDMD Group B).

Most patients with Duchenne muscular dystrophy (DMD) are non-ambulant. Preserving proximal motor function is crucial, rarely studied. Tamoxifen, a selective oestrogen receptor modulator, reduced signs of muscular pathology in a DMD mouse model.

CompositIA: an open-source automated quantification tool for body composition scores from thoraco-abdominal CT scans.

Background: Body composition scores allow for quantifying the volume and physical properties of specific tissues. However, their manual calculation is time-consuming and prone to human error. This study aims to develop and validate CompositIA, an automated, open-source pipeline for quantifying body composition scores from thoraco-abdominal computed tomography (CT) scans.

Feasibility of generating sagittal radiographs from coronal views using GAN-based deep learning framework in adolescent idiopathic scoliosis.

Background: Minimizing radiation exposure is crucial in monitoring adolescent idiopathic scoliosis (AIS). Generative adversarial networks (GANs) have emerged as valuable tools being able to generate high-quality synthetic images. This study explores the use of GANs to generate synthetic sagittal radiographs from coronal views in AIS patients.

Haemodynamic profiling: when AI tells us what we already know.

Machine learning (ML) algorithms hold significant potential for extracting valuable clinical information from big data, surpassing the processing capabilities of the human brain. However, it would be naïve to believe that ML algorithms can consistently transform data into actionable insights. Clinical studies suggest that in some instances, they tell clinicians what they already know or can plainly see.

Impact of Online Interactive Decision Tools on Women's Decision-Making Regarding Breast Cancer Screening: Systematic Review and Meta-Analysis.

Background: The online nature of decision aids (DAs) and related e-tools supporting women's decision-making regarding breast cancer screening (BCS) through mammography may facilitate broader access, making them a valuable addition to BCS programs.

Objective: This systematic review and meta-analysis aims to evaluate the scientific evidence on the impacts of these e-tools and to provide a comprehensive assessment of the factors associated with their increased utility and efficacy.

Methods: We followed the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and conducted a search of MEDLINE, PsycINFO, Embase, CINAHL, and Web of Science databases from August 2010 to April 2023.

Exploring the Credibility of Large Language Models for Mental Health Support: Protocol for a Scoping Review.

Background: The rapid evolution of large language models (LLMs), such as Bidirectional Encoder Representations from Transformers (BERT; Google) and GPT (OpenAI), has introduced significant advancements in natural language processing. These models are increasingly integrated into various applications, including mental health support. However, the credibility of LLMs in providing reliable and explainable mental health information and support remains underexplored.

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.

Hyperspectral Imaging for High Throughput Optical Spectroscopy of pL Droplets.

Droplet-based microfluidics is a powerful tool for high-throughput analysis of liquid samples with significant applications in biomedicine and biochemistry. Nevertheless, extracting content-rich information from single picolitre-sized droplets at high throughputs remains challenging due to the weak signals associated with these small volumes. Overcoming this limitation would be transformative for fields that rely on high-throughput screening, enabling broader multiparametric analysis.

Tracing the inner edge of the habitable zone with sulfur chemistry.

The circumstellar liquid-water habitable zone guides our search for potentially inhabited exoplanets but remains observationally untested. We show that the inner edge of the habitable zone can now be mapped among exoplanets using their lack of surface water, which, unlike the presence of water, can be unambiguously revealed by atmospheric sulfur species. Using coupled climate-chemistry modeling, we find that the observability of sulfur gases on exoplanets depends critically on the ultraviolet (UV) flux of their host star, a property with wide variation: Most M-dwarfs have a low UV flux and thereby allow the detection of sulfur gases as a tracer of dry planetary surfaces; however, the UV flux of Trappist-1 may be too high for sulfur to disambiguate uninhabitable from habitable surfaces on any of its planets.

REACH assessment of humans exposed to chemicals indirectly via the environment: screening modeling in EUSES versus state of the science.

The assessment of humans indirectly exposed to chemicals via the environment (HvE) is an assessment element of the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation. The European Union System for the Evaluation of Substances (EUSES) is the default screening tool, aimed at prioritizing chemicals for further refinement/higher tier assessment. This review summarizes the approach used in EUSES, evaluates the state of the science in human exposure modeling via the environment, and identifies areas for further research to strengthen the confidence and applicability of EUSES for assessing HvE.

Characterization of language abilities and semantic networks in very preterm children at school-age.

It has been widely assessed that very preterm children (<32 weeks gestational age) present language and memory impairments compared with full-term children. However, differences in their underlying semantic memory structure have not been studied yet. Nevertheless, the way concepts are learned and organized across development relates to children's capacities in retrieving and using information later.