Vanzacaftor-tezacaftor-deutivacaftor for children aged 6-11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial.

Background: In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor-tezacaftor-deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor-tezacaftor-deutivacaftor in children with cystic fibrosis aged 6-11 years.

Fetal imaging, phenotyping, and genomic testing in modern prenatal diagnosis.

Genetic tests available in the prenatal setting have expanded rapidly with next generation sequencing, and fetal imaging can detect a breadth of many structural and functional abnormalities. To identify a fetal genetic disease, deep phenotyping is increasingly important to generate a differential diagnosis, choose the most appropriate genetic tests, and inform the results of those tests. The Human Phenotype Ontology (HPO) organizes and defines the features of human disease to support deep phenotyping, and ongoing efforts are being made to improve the scope of the HPO to comprehensively include fetal phenotypes.

Long-term studies should provide structure for inclusive education and professional development.

Long-term studies are critical for ecological understanding, but they are underutilized as inclusive opportunities for training ecologists. We use our perspective from the Año Nuevo elephant seal programme along with surveys from community members to propose that long-term studies could be better leveraged to promote inclusive education and professional development in ecology. Drawing on our experiences as mentors and mentees, we demonstrate how long-term studies can use their resources, including rich data, robust logistics and extensive professional networks, to improve recruitment and retention of diverse groups of trainees.

Implementing digital respiratory technologies for people with respiratory conditions: A protocol for a scoping review.

The value of 'data-enabled', digital healthcare is evolving rapidly, as demonstrated in the COVID-19 pandemic, and its successful implementation remains complex and challenging. Harmonisation (within/between healthcare systems) of infrastructure and implementation strategies has the potential to promote safe, equitable and accessible digital healthcare, but guidance for implementation is lacking. Using respiratory technologies as an example, our scoping review process will capture and review the published research between 12th December 2013 to 12th December 2023.

Can people with longstanding bulimia nervosa suffer from severe and enduring eating disorder? A qualitative study.

Objectives: To interview a series of individuals with bulimia nervosa of longstanding to establish their symptoms and examine the suggestion, using qualitative analysis, that the term "Severe and Enduring Bulimia Nervosa (SEED-BN)" might be appropriate and helpful.

Methods: 12 participants with Bulimia Nervosa, one male, were interviewed with the help of an interview guide. Interviews were recorded and transcribed.

Efficient reinterpretation of rare disease cases using Exomiser.

Whole genome sequencing has transformed rare disease research; however, 50-80% of rare disease patients remain undiagnosed after such testing. Regular reanalysis can identify new diagnoses, especially in newly discovered disease-gene associations, but efficient tools are required to support clinical interpretation. Exomiser, a phenotype-driven variant prioritisation tool, fulfils this role; within the 100,000 Genomes Project (100kGP), diagnoses were identified after reanalysis in 463 (2%) of 24,015 unsolved patients after previous analysis for variants in known disease genes.

Two decades of three-dimensional movement data from adult female northern elephant seals.

Northern elephant seals (Mirounga angustirostris) have been integral to the development and progress of biologging technology and movement data analysis, which continue to improve our understanding of this and other species. Adult female elephant seals at Año Nuevo Reserve and other colonies along the west coast of North America were tracked annually from 2004 to 2020, resulting in a total of 653 instrument deployments. This paper outlines the compilation and curation process of these high-resolution diving and location data, now accessible in two Dryad repositories.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2024: imaging immediately after neoadjuvant therapy in soft tissue sarcoma, soft tissue tumor surveillance, and the role of interventional radiology.

Objectives: An update of the first European Society of Musculoskeletal Radiology (ESSR) consensus on soft tissue tumor imaging in 2015 became necessary due to technical advancements, further insights into specific entities, and the revised WHO classification (2020) and AJCC staging system (2017). The third part of the revised guidelines covers algorithms and techniques beyond initial imaging: (1) Imaging after neoadjuvant therapy in soft tissue sarcoma, (2) sarcoma surveillance, and (3) special aspects, including surveillance of non-malignant entities and the role of interventional radiology.

Materials And Methods: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries.

Brain endothelial permeability, transport, and flow assessed over 10 orders of magnitude using the in situ brain perfusion technique.

Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.

Intrinsic-dimension analysis for guiding dimensionality reduction and data fusion in multi-omics data processing.

Multi-omics data have revolutionized biomedical research by providing a comprehensive understanding of biological systems and the molecular mechanisms of disease development. However, analyzing multi-omics data is challenging due to high dimensionality and limited sample sizes, necessitating proper data-reduction pipelines to ensure reliable analyses. Additionally, its multimodal nature requires effective data-integration pipelines.

The European Diploma in Musculoskeletal Radiology: Webinar Program of the ESSR.

The European Diploma in Musculoskeletal Radiology (EDiMSK) is a recognized European qualification of excellence for musculoskeletal (MSK) radiologists. Webinars have become a vital component of electronic learning. This article introduces European Society of Musculoskeletal Radiology members to its webinar program that offers an additional source of direct interactive learning from renowned MSK radiologists.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

European Diploma in Musculoskeletal Radiology: Oral Part of the Exam.

The European Diploma in Musculoskeletal Radiology (EDiMSK) is a recognized European qualification of excellence for musculoskeletal (MSK) radiologists. The EDiMSK confirms proof of knowledge of MSK radiology in addition to any national qualifications certifying competency. The examination is conducted in English and consists of both a written and an oral part.

IsopretGO-analysing and visualizing the functional consequences of differential splicing.

Gene Ontology overrepresentation analysis (GO-ORA) is a standard approach towards characterizing salient functional characteristics of sets of differentially expressed genes (DGE) in RNA sequencing (RNA-seq) experiments. GO-ORA compares the distribution of GO annotations of the DGE to that of all genes or all expressed genes. This approach has not been available to characterize differential alternative splicing (DAS).

Using paired-end read orientations to assess technical biases in capture Hi-C.

Hi-C and capture Hi-C (CHi-C) both leverage paired-end sequencing of chimeric fragments to gauge the strength of interactions based on the total number of paired-end reads mapped to a common pair of restriction fragments. Mapped paired-end reads can have four relative orientations, depending on the genomic positions and strands of the two reads. We assigned one paired-end read orientation to each of the four possible re-ligations that can occur between two given restriction fragments.

Valediction.

This issue marks another series of big changes for Community Dental Health. Whilst the cliché tells us that there is nothing permanent except change, Darwin realised that it's "not the strongest of the species that survive, nor the most intelligent, but the one most responsive to change". We're heeding Darwin's words, even though his star never rose as high as publishing in this journal.

Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning.

Integrating diverse types of biological data is essential for a holistic understanding of cancer biology, yet it remains challenging due to data heterogeneity, complexity, and sparsity. Addressing this, our study introduces an unsupervised deep learning model, MOSA (Multi-Omic Synthetic Augmentation), specifically designed to integrate and augment the Cancer Dependency Map (DepMap). Harnessing orthogonal multi-omic information, this model successfully generates molecular and phenotypic profiles, resulting in an increase of 32.

Improving School Mental Health via National Learning Collaboratives With State and Local Teams: Components, Feasibility, and Initial Impacts.

School systems need practical and effective quality improvement strategies to advance school mental health promotion, prevention, and treatment services. Collectively, these efforts can be used to promote child and adolescent mental health, well-being, and academic success. The current study reports on the feasibility, initial impacts of, and recommendations from a national, multi-level learning collaborative conducted by the National Center for School Mental Health, University of Maryland School of Medicine and administered throughout the United States.

Reproductive success and offspring survival decline for female elephant seals past prime age.

Maternal age can influence reproductive success and offspring fitness, but the timing, magnitude and direction of those impacts are not well understood. Evolutionary theory predicts that selection on fertility senescence is stronger than maternal effect senescence, and therefore, the rate of maternal effect senescence will be faster than fertility senescence. We used a 36-year study of northern elephant seals (Mirounga angustirostris) to investigate reproductive senescence.

Making Waves: A justice-centred framework for wastewater-based public health surveillance.

Since 2020 wastewater-based surveillance has quickly been established as an effective and cost-efficient tool for monitoring public health. In this Making Waves article, we argue that these programs must be grounded in principles of justice to achieve global water and health equity. Ethics initiatives to date have focused primarily on privacy, legality, and institutionalised research reviews, often, if not exclusively, in North America and Western Europe.

DeePathNet: A Transformer-Based Deep Learning Model Integrating Multiomic Data with Cancer Pathways.

DeePathNet integrates cancer-specific biological pathways using transformer-based deep learning for enhanced cancer analysis. It outperforms existing models in predicting drug responses, cancer types, and subtypes. By enabling pathway-level biomarker discovery, DeePathNet represents a significant advancement in cancer research and could lead to more effective treatments.