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IMPACT OF ARTIFICIAL INTELLIGENCE ASSISTANCE ON CLINICIAN PERFORMANCE IN DIAGNOSING DEVELOPMENTAL DYSPLASIA OF THE HIP
IntroductionArtificial intelligence (AI) models have shown reasonable ability in identifying developmental dysplasia of the hip. This study evaluates the impact of AI-assisted image interpretation on the diagnostic performance of ‘expert’ and ‘non-expert’ clinicians.MethodsA multi-reader, multi-case study was conducted with 10 readers (5 consultants and 5 registrars). The study included 70 static 2D hip ultrasound scans from 70 patients (age range 0.86-19.86 weeks, mean age 8.6 weeks, 55.7% female and 65.7% left). There were 35 normal (Graf 1) and 35 abnormal (Graf 2 n=25; Graf 3/4 n=10) images. The reference standards were the Graf alpha angle and femoral head coverage (FHC) derived from anatomical points (landmarks) checked by two senior experts. The clinicians placed landmarks without (Phase1) and with AI assistance (Phase2). Their diagnostic performance (sensitivity/specificity), confidence rating (1-5) and time taken were reported.ResultsFor the Graf method, the mean sensitivity/specificity values for ‘experts’ without vs with AI were 0.75/0.93 vs 0.71/0.96, respectively. For ‘non-experts’, this was 0.75/0.90 vs 0.70/0.95. For FHC%, the sensitivity/specificity values for ‘experts’ (0.97/0.92) and ‘non-experts’ (0.98/0.93) were unchanged between phases. AI assistance significantly increased the rate that all clinicians reported the highest level of confidence in their annotations. The mean time taken (hh:mm) by ‘experts’ without vs with AI was 04:49 vs 05:07, for ‘non-experts’ it was 05:04 vs 04:52.ConclusionsThe FHC demonstrated better overall sensitivity as a screening method. AI assistance improved the diagnostic confidence of all clinicians without reducing their performance and made ‘non-experts’ faster.
TESTING THE USABILITY AND ACCEPTABILITY OF THE NON-STOP APP, A DIGITAL SELF-MANAGEMENT INTERVENTION FOR CHILDREN WITH PERTHES’ DISEASE
Perthes’ Disease is a rare paediatric hip condition that affects the blood supply to the femoral head, leading to bone death and regeneration. This process causes pain, mobility issues, and prolonged recovery periods, impacting a child's quality of life. Effective self-management interventions, particularly digital tools, have been identified by key stakeholders as acceptable methods of helping children and families cope with the disease. This study assessed the usability and acceptability of the NON-STOP app, a digital self-management intervention for children with Perthes’ Disease.A mixed-methods approach was employed, involving a single-arm trial and nested focus groups. Thirty-one children with Perthes’ Disease were recruited from three NHS hospitals to use the NON-STOP app over six weeks. App usage data were collected, and participants completed baseline and post-trial assessments, including PROMIS Mobility, CPAQ, and Health ITUES, to evaluate the app's usability. Following the trial, a subset of participants took part in focus groups to explore their experiences and gather qualitative feedback on the app's strengths and areas for improvement.Quantitative findings showed that app engagement was moderate. Usage metrics were useful when considering optimum intervention dosage. The average pain score, measured using the Wong-Baker FACES scale, remained low, suggesting the app's exercises were well-tolerated. Qualitative feedback from the focus groups indicated that the app was generally well-received. Users appreciated the instructional videos to help with exercise completion. A key strength to the intervention was the inclusion of rewards, and avatar customisation features, which motivated children to engage with the NON-STOP appThe NON-STOP app was found to be an acceptable and usable tool for children with Perthes’ Disease. The app's ability to promote self-management and independence in children was highlighted as a key benefit. These findings support the continued development and refinement of the NON-STOP app, with potential for broader implementation in future clinical trials targeting the management of Perthes’ Disease. By promoting self-management and engagement through innovative, child-friendly features, the NON-STOP app addresses a critical need for accessible, scalable tools in paediatric care.
CONSORT 2025 statement: updated guideline for reporting randomised trials.
Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.
A computational pipeline for spatial mechano-transcriptomics.
Advances in spatial profiling technologies are providing insights into how molecular programs are influenced by local signaling and environmental cues. However, cell fate specification and tissue patterning involve the interplay of biochemical and mechanical feedback. Here we develop a computational framework that enables the joint statistical analysis of transcriptional and mechanical signals in the context of spatial transcriptomics. To illustrate the application and utility of the approach, we use spatial transcriptomics data from the developing mouse embryo to infer the forces acting on individual cells, and use these results to identify mechanical, morphometric and gene expression signatures that are predictive of tissue compartment boundaries. In addition, we use geoadditive structural equation modeling to identify gene modules that predict the mechanical behavior of cells in an unbiased manner. This computational framework is easily generalized to other spatial profiling contexts, providing a generic scheme for exploring the interplay of biomolecular and mechanical cues in tissues.
Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms.
Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes. JAK-STAT signaling differentially regulates CDC42-dependent HSC polarity, niche interaction and mutant cell expansion. Asymmetric HSC distribution causes differential BM niche remodeling: sinusoidal dilation in polycythemia vera and endosteal niche expansion in essential thrombocythemia. MPN development accelerates in a prematurely aged BM microenvironment, suggesting that the specialized niche can modulate mutant cell expansion. Finally, dissimilar HSC-niche interactions underpin variable clinical response to JAK inhibitor. Therefore, HSC-niche interactions influence the expansion rate and therapy response of cells carrying the same clonal hematopoiesis oncogenic driver.
Tumour heterogeneity promotes collective invasion and cancer metastatic dissemination.
Heterogeneity within tumour cell populations is commonly observed in most cancers. However, its impact on metastatic dissemination, one of the primary determinants of the disease prognosis, remains poorly understood. Working with a simplified numerical model of tumour spheroids, we investigated the impact of mechanical heterogeneity on the onset of tumour invasion into surrounding tissues. Our work establishes a positive link between tumour heterogeneity and metastatic dissemination, and recapitulates a number of invasion patterns identified in vivo, such as multicellular finger-like protrusions. Two complementary mechanisms are at play in heterogeneous tumours. A small proportion of stronger cells are able to initiate and lead the escape of cells, while collective effects in the bulk of the tumour provide the coordination required to sustain the invasive process through multicellular streaming. This suggests that the multicellular dynamics observed during metastasis is a generic feature of mechanically heterogeneous cell populations and might rely on a limited and generic set of attributes.
A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium.
Epithelial cells rapidly adapt their behaviour in response to increasing tissue demands. However, the processes that finely control these cell decisions remain largely unknown. The postnatal period covering the transition between early tissue expansion and the establishment of adult homeostasis provides a convenient model with which to explore this question. Here, we demonstrate that the onset of homeostasis in the epithelium of the mouse oesophagus is guided by the progressive build-up of mechanical strain at the organ level. Single-cell RNA sequencing and whole-organ stretching experiments revealed that the mechanical stress experienced by the growing oesophagus triggers the emergence of a bright Krüppel-like factor 4 (KLF4) committed basal population, which balances cell proliferation and marks the transition towards homeostasis in a yes-associated protein (YAP)-dependent manner. Our results point to a simple mechanism whereby mechanical changes experienced at the whole-tissue level are integrated with those sensed at the cellular level to control epithelial cell fate.
Theory of mechanochemical patterning in biphasic biological tissues.
The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing's reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller-Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis.
On growth and force: mechanical forces in development.
The EMBO/EMBL Symposium 'Mechanical Forces in Development' was held in Heidelberg, Germany, on 3-6 July 2019. This interdisciplinary symposium brought together an impressive and diverse line-up of speakers seeking to address the origin and role of mechanical forces in development. Emphasising the importance of integrative approaches and theoretical simulations to obtain comprehensive mechanistic insights into complex morphogenetic processes, the meeting provided an ideal platform to discuss the concepts and methods of developmental mechanobiology in an era of fast technical and conceptual progress. Here, we summarise the concepts and findings discussed during the meeting, as well as the agenda it sets for the future of developmental mechanobiology.
Deep learning for bioimage analysis in developmental biology.
Deep learning has transformed the way large and complex image datasets can be processed, reshaping what is possible in bioimage analysis. As the complexity and size of bioimage data continues to grow, this new analysis paradigm is becoming increasingly ubiquitous. In this Review, we begin by introducing the concepts needed for beginners to understand deep learning. We then review how deep learning has impacted bioimage analysis and explore the open-source resources available to integrate it into a research project. Finally, we discuss the future of deep learning applied to cell and developmental biology. We analyze how state-of-the-art methodologies have the potential to transform our understanding of biological systems through new image-based analysis and modelling that integrate multimodal inputs in space and time.
A magnetically actuated, optically sensed tensile testing method for mechanical characterization of soft biological tissues.
Mechanical properties of soft biological tissues play a critical role in physiology and disease, affecting cell behavior and fate decisions and contributing to tissue development, maintenance, and repair. Limitations of existing tools prevent a comprehensive characterization of soft tissue biomechanics, hindering our understanding of these fundamental processes. Here, we develop an instrument for high-fidelity uniaxial tensile testing of soft biological tissues in controlled environmental conditions, which is based on the closed-loop interaction between an electromagnetic actuator and an optical strain sensor. We first validate the instrument using synthetic elastomers characterized via conventional methods; then, we leverage the proposed device to investigate the mechanical properties of murine esophageal tissue and, individually, of each of its constitutive layers, namely, the epithelial, connective, and muscle tissues. The enhanced reliability of this instrument makes it an ideal platform for future wide-ranging studies of the mechanics of soft biological tissues.
Dynamic regulation of tissue fluidity controls skin repair during wound healing.
During wound healing, different pools of stem cells (SCs) contribute to skin repair. However, how SCs become activated and drive the tissue remodeling essential for skin repair is still poorly understood. Here, by developing a mouse model allowing lineage tracing and basal cell lineage ablation, we monitor SC fate and tissue dynamics during regeneration using confocal and intravital imaging. Analysis of basal cell rearrangements shows dynamic transitions from a solid-like homeostatic state to a fluid-like state allowing tissue remodeling during repair, as predicted by a minimal mathematical modeling of the spatiotemporal dynamics and fate behavior of basal cells. The basal cell layer progressively returns to a solid-like state with re-epithelialization. Bulk, single-cell RNA, and epigenetic profiling of SCs, together with functional experiments, uncover a common regenerative state regulated by the EGFR/AP1 axis activated during tissue fluidization that is essential for skin SC activation and tissue repair.
A qualitative exploration of the barriers to and facilitators of clozapine monitoring in a secure psychiatric setting.
AIMS AND METHOD: To explore the beliefs and understanding of staff and patients at a secure mental health unit regarding clozapine monitoring, and to identify barriers to and facilitators of monitoring. Qualitative semi-structured interviews and focus groups were conducted with 17 staff members and six patients. RESULTS: Six key themes were identified. The key facilitator of effective monitoring was the motivation of staff to help patients to become independent and facilitate recovery. An important barrier was a lack of clarity around the roles of different staff groups in monitoring. Staff and patients widely supported the establishment of an in-patient clozapine clinic and perceived that it would prepare patients for discharge. CLINICAL IMPLICATIONS: An in-patient clozapine clinic is a robust mechanism for clozapine monitoring in secure settings. The barriers and facilitators identified here could be applied to other secure units to guide their systems of clozapine monitoring.
Digital health technologies to strengthen patient-centred outcome assessment in clinical trials in inflammatory arthritis.
Common to all inflammatory arthritides, namely rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and juvenile idiopathic arthritis, is a potential for reduced mobility that manifests through joint pain, swelling, stiffness, and ultimately joint damage. Across these conditions, consensus has been reached on the need to capture outcomes related to mobility, such as functional capacity and physical activity, as core domains in randomised controlled trials. Existing endpoints within these core domains rely wholly on self-reported questionnaires that capture patients' perceptions of their symptoms and activities. These questionnaires are subjective, inherently vulnerable to recall bias, and do not capture the granularity of fluctuations over time. Several early adopters have integrated sensor-based digital health technology (DHT)-derived endpoints to measure physical function and activity in randomised controlled trials for conditions including Parkinson's disease, Duchenne's muscular dystrophy, chronic obstructive pulmonary disease, and heart failure. Despite these applications, there have been no sensor-based DHT-derived endpoints in clinical trials recruiting patients with inflammatory arthritis. Borrowing from case studies across medicine, we outline the opportunities and challenges in developing novel sensor-based DHT-derived endpoints that capture the symptoms and disease manifestations most relevant to patients with inflammatory arthritis.