Citations

Abstract Objective Sleeper stretching (SS) and cross‐body stretching (CS) are common nonsurgical interventions for the management of glenohumeral internal rotation deficit (GIRD) in overhead athletes such as baseball and volleyball players. However, the effectiveness of these stretching interventions in enhancing the range of motion (ROM) of shoulder internal rotation (IR) in overhead athletes with GIRD remains a subject of uncertainty. This systematic review and meta‐analysis aim to critically assess the efficacy of SS and CS in the ROM of the IR among overhead athletes with GIRD, thereby providing evidence‐based recommendations for their use. Literature Survey A comprehensive search of MEDLINE, Embase, and Scopus databases up to November 2024 was conducted to identify randomized controlled trials investigating the influence of SS and CS on the ROM of shoulder IR in overhead athletes with GIRD. Methodology Data including study characteristics and outcomes were extracted. Risk of bias assessment and random‐effects model meta‐analysis were performed. Synthesis Six eligible studies involving 255 athletes with GIRD were included. The meta‐analysis demonstrated statistically significant differences between stretching and control groups in terms of enhancing the ROM of IR (mean difference [MD], 7°; 95% confidence interval [CI], 1°–13°; p = .02) and horizontal adduction (HAD) ([MD], 6°; [CI], 1°–11°; p = .03). Conclusion SS or combination of SS and CS interventions significantly enhanced the ROM of IR compared to the control group in overhead athletes diagnosed with GIRD. Furthermore, the review confirmed that SS alone also markedly enhances the ROM of HAD. These findings highlight the potential benefits of SS and CS in managing GIRD and suggest a need for further research to optimize these interventions for broader application in overhead athletes.

Abstract Artificial intelligence (AI) is poised to transform healthcare through the lens of 6P medicine: personalized, predictive, preventive, participatory, precision, and public health. This review explores how AI technologies contribute to these six crucial dimensions, offering powerful solutions for enhanced early disease detection, tailored treatment protocols, proactive preventive health measures, and significantly improved patient engagement in their care journey.Our findings highlight AI's immense potential in revolutionizing diagnostics by enabling more accurate and rapid analyses, as well as strengthening public health surveillance capabilities. However, successful and responsible implementation hinges on rigorously addressing crucial cross-cutting challenges such as ensuring data quality, safeguarding patient privacy, navigating complex ethical considerations, seamless system integration, and fostering model interpretability. Aligning AI applications with evolving regulatory frameworks, such as the European Health Data Space (EHDS) and the AI Act, is absolutely essential to accelerate the ethical and effective adoption of 6P medicine. Ultimately, interdisciplinary collaboration among clinicians, technologists, and policymakers is key to unlocking AI's full power to improve patient outcomes and overall healthcare operational efficiency.

Abstract Objective: Electronic Health Record (EHR) data are critical for advancing translational research and AI technologies. The ENACT network offers access to structured EHR data across 57 CTSA hubs. However, substantial information is contained in clinical narratives, requiring natural language processing (NLP) for research. The ENACT NLP Working Group was formed to make NLP-derived clinical information accessible and queryable across the network. Methods: We established the ENACT NLP Working Group with 13 sites selected based on criteria including clinical notes access, IT infrastructure, NLP expertise, and institutional support. We divided sites into five focus groups targeting clinical tasks within disease contexts. Each focus group consisted of two development sites and two validation sites. We extended the ENACT ontology to standardize NLP-derived data and conducted multisite evaluations using the Open Health Natural Language Processing (OHNLP) Toolkit. Results: The working group achieved 100% site retention and deployed NLP infrastructure across all sites. We developed and validated NLP algorithms for rare disease phenotyping, social determinants of health, opioid use disorder, sleep phenotyping, and delirium phenotyping. Performance varied across sites (F1 scores 0.53–0.96), highlighting data heterogeneity impacts. We extended the ENACT common data model and ontology to incorporate NLP-derived data while maintaining Shared Health Research Informatics NEtwork (SHRINE) compatibility. Conclusion: This demonstrates feasibility of deploying NLP infrastructure across large, federated networks. The focus group approach proved more practical than general-purpose approaches. Key lessons include the challenge of data heterogeneity and importance of collaborative governance. This work also provides a foundation that other networks can build on to implement NLP capabilities for translational research.

Abstract Background Compared to Parkinson's disease, atypical parkinsonian disorders (APD) are characterized by a more rapidly progressive course, often leading to profound disability. Effective communication between clinicians, patients, and care partners is essential to support patient‐centered care and shared decision‐making. However, most neurologists lack formal training in serious illness conversations (SIC). Objective To develop a practical SIC guide tailored to the needs of individuals with APD. Methods Members of the CurePSP Centers of Care Palliative Care Working Group, in collaboration with a SIC education expert (TC), developed a SIC guide for APD. A literature review was conducted, followed by online consensus‐building rounds. Results Applying core communication principles—such as active listening, pausing, naming and validating emotions, assessing understanding, and reframing—can foster alignment between clinicians, patients, and their care partners. Navigating the balance between maintaining hope and providing realistic, anticipatory guidance remains challenging but best achieved by honest, compassionate dialogue. Four practical guides were developed, addressing common and often challenging scenarios: delivering an APD diagnosis, eliciting patient goals in the context of changing clinical status, addressing safety concerns, and discussing quality of life and end‐of‐life considerations. Conclusions Patients and their care partners living with APD benefit greatly from individualized guidance, and honest, empathic communication is a vital part of patient‐centered care. While existing SIC frameworks offer valuable foundations, further research is needed to optimize their adaptation for APD—identifying best timing, specific frameworks, relevant outcome measures, and education strategies to build team‐wide competency.

ABSTRACT Background To explore the prevalence of serious adverse events ( SAEs ) associated with retinal viral gene therapy and to examine trends influencing SAE occurrences in human gene therapy surgeries and pre‐clinical animal trials. Methods Literature review was performed to identify peer‐reviewed human and animal studies relevant to viral gene therapy, subretinal injections, and intravitreal injections. For clinical trials and post‐approval LUXTURNA studies, only those that examined SAEs were included. Results Of included clinical trial studies ( n = 31), SAEs were recorded in 51 out of 438 eyes (11.6%) that received subretinal injections and in 11 out of 348 eyes (3.2%) that received intravitreal injections. There were fewer intravitreal‐related SAEs and less vision loss compared to subretinal gene therapy. Inflammation was the predominant SAE following intravitreal injections, whereas unexplained vision loss was the most common for subretinal injections. Clinical trials utilising subretinal injections met primary or secondary efficacy endpoints more than intravitreal trials. Eighteen studies (429 eyes) of post‐approval LUXTURNA were reviewed, and SAEs were reported in 24.7% of eyes, retinal degeneration being most common (20.7%). For 58 animal studies, SAEs were recorded in 17.3% of eyes that received subretinal injections and 8.7% of eyes that received intravitreal injections. Conclusions Subretinal injections show higher efficacy than intravitreal injections but are associated with more serious adverse events. Consistent adverse event patterns in humans and large animals highlight their predictive value for safety. There is a need for optimised delivery methods, refined dosing protocols, and improved post‐treatment monitoring to improve safety and effectiveness in gene therapy.

Abstract Developmental delay and seizures with or without movement abnormalities (OMIM 617836) caused by heterozygous pathogenic variants in the DHDDS gene (DHDDS-CDG) is a rare genetic disease that belongs to the progressive encephalopathy spectrum. It results in cognitive delay in affected children, accompanied by myoclonus, seizures, ataxia and tremor, which worsens over time. DHDDS encodes a subunit of a DHDDS/NUS1 cis-prenyltransferase ( cis- PTase), a branch point enzyme of the mevalonate pathway essential for N-linked glycosylation. We describe the first mouse model of this disease, Dhdds R37H+/- strain, heterozygous for the human recurrent de novo c.110G>A:p.R37H pathogenic variant. Dhdds R37H+/- mice present with seizures, myoclonus and memory deficits associated with reduced density or/and maturity of inhibitory interneurons in the cortex. Multiomics analyses of mouse CNS tissues, together with the enzymatic/structural characterization of the R37H DHDDS mutant protein, reveal that the variant produces a catalytically inactive enzyme and results in a brain dolichol deficit, aberrant glycosylation of brain glycoproteins, including those involved in synaptic transmission and major perturbations in the CNS proteome and lipidome. Acetazolamide, a carbonic anhydrase inhibitor clinically approved for treatment of glaucoma, epilepsy, and intracranial hypertension, and successfully used “off-label” to treat genetic movement disorders, reduces seizure susceptibility to pentylenetetrazol in Dhdds R37H+/- mice, suggesting potential therapeutic value of using this drug in human DHDDS-CDG patients. Together, our results define cis- PTase as a master regulator of CNS development and function and establish that its monoallelic debilitating variants cause a novel congenital disorder of glycosylation associated with aberrant levels of neuronal proteins and lipids.

Key Points BeWell360-PKD shows that integrating certified health and wellness coaches and augmenting patients' personal capacity as part of autosomal dominant polycystic kidney disease care is feasible and acceptable. Embedding BeWell360 coaches reduced care burden, improved caregiver self-efficacy, and enhanced care engagement by patients with autosomal dominant polycystic kidney disease and by their informal caregivers. This aligns with evolving care standards and guidelines promoting sustainable healthy lifestyle changes through tailored, integrative behavior-change centered interventions. Background Autosomal dominant polycystic kidney disease (ADPKD) imposes substantial care burden on patients and their informal caregivers (CGs), often contributing to nonadherence and impaired quality of life. Existing care models insufficiently address the behavioral and psychosocial dimensions of this burden. To evaluate the feasibility and effect of BeWell360-PKD , a person-centered intervention integrating Health and Wellness Coaching and capacity-workload support into ADPKD care, on care burden, adherence, self-efficacy, activation, and resilience. Methods In this 6-month, single-arm, mixed-methods pilot study, seven patient-CG dyads were enrolled from tertiary care polycystic kidney disease clinic. Board-certified Health and Wellness Coachings delivered individualized coaching within routine nephrology care, emphasizing capacity-building, goal setting, and care enactment support. Primary outcomes included changes in treatment burden (treatment burden questionnaire, ADPKD impact scale) and CG burden (burden scale for family CGs short version). Secondary outcomes included patient activation and resilience and CG self-efficacy. Semistructured interviews explored participant experiences. Results Patients experienced reduced treatment burden (treatment burden questionnaire mean change −9.3) and modest, domain-specific improvements in physical and fatigue-related ADPKD symptom burden. CG self-efficacy improved (+2.4), while CG burden increased (+14.8), and patient activation declined (−6.6). Qualitative themes reflected disease burden, emotional adaptation, and the perceived value of coaching in promoting behavior change and relational support. Conclusions BeWell360-PKD was feasible to implement and demonstrated early signals of benefit in reducing patient burden and improving CG self-efficacy. Increased CG burden and declining activation highlight the complexity of dyadic adaptation in ADPKD and the need for larger, controlled studies to refine and tailor coaching interventions.