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Prevalence and risk factors of nutritional anaemia among adolescents in India: a systematic review with meta-analysis of prevalence.

BACKGROUND: Nutritional anaemia is a major public health concern among adolescents in India, threatening physical growth, cognitive development, and future maternal health. This systematic review with meta-analysis of prevalence aimed to estimate the pooled prevalence of nutritional anaemia among Indian adolescents aged 10-19 years and identify key associated risk factors. METHODS: A systematic search was conducted across PubMed, Embase, Web of Science, and Scopus up to February 2025. Data were extracted on study design, setting, diagnostic methods, prevalence, and risk factors. Quality was assessed with a modified Newcastle-Ottawa Scale. A random-effects meta-analysis estimated pooled prevalence, with subgroup analyses by state and gender, and pooled odds ratios for risk factors. RESULTS: Forty-five studies encompassing diverse Indian regions and 159,979 adolescents were included. The pooled prevalence of nutritional anaemia was 56% (95% CI: 49%-63%), with higher rates among girls (62%) than boys (39%). Iron deficiency (OR 2.38-4.68), other micronutrient deficiencies, low socioeconomic status, poor dietary diversity, female gender, and inadequate supplementation were consistently associated with higher anaemia risk. CONCLUSION: Nutritional anaemia impacts more than half of Indian adolescents, with notable regional and gender differences. Its complex nutritional, socioeconomic, and behavioural causes demand targeted, context-specific interventions to enhance adolescent health nationwide.

Humans

Extended Reality Interventions for Osteoarthritis of the Knee and Recovery After Total Knee Arthroplasty: Systematic Review and Meta-Analyses.

BACKGROUND: Nonpharmacologic interventions are important for treating knee pain due to osteoarthritis or after total knee arthroplasty (TKA), and extended reality (XR) technology may enhance treatments for these indications. OBJECTIVE: This systematic review aimed to evaluate XR interventions for pain due to knee osteoarthritis (KOA) or for recovery after TKA. METHODS: Databases were searched through May 2023 and updated in December 2025. Eligible trials evaluated XR interventions to treat KOA pain or after TKA. We classified interventions by depth of immersion and clinical mechanism. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria to determine the certainty of evidence for prioritized outcomes. Meta-analyses were performed when ≥3 studies evaluated similar comparisons, outcomes, and time points. RESULTS: Eligible trials addressed KOA (k=12) or recovery after TKA (k=9). Sample sizes ranged from 36 to 306 participants, and most studies had a follow-up of ≤3 months. Nineteen studies assessed pain-related functioning and pain intensity, and 5 assessed adverse events (AEs). For KOA, 10 studies examined interactive digital rehabilitation (IDR), and 2 examined virtual reality (VR)-digitally augmented exercise (DAE). IDR for KOA may result in better pain-related functioning (low certainty of evidence [COE]; pooled standardized mean difference [SMD] -0.59, 95% CI -1.11 to -0.06; prediction interval [PI] -1.72 to 0.55; k=5) and lower pain intensity at 6-8 weeks (low COE; pooled SMD -0.46, 95% CI -0.92 to 0.00; PI -1.39 to 0.47; k=4). VR-DAE for KOA (k=2) produced inconsistent results (very low COE). For post-TKA studies, 5 examined IDR, 2 examined VR-DAE, 1 examined VR-distraction, and 1 examined VR-psychoeducation. Post-TKA IDR may result in better pain-related functioning (low [k=4] and moderate COE [k=1]) but little to no difference in pain intensity (low-moderate COE; pooled SMD at 3-4 months -0.12, 95% CI -0.75 to 0.52; PI -1.63 to 1.27; k=3). VR-psychoeducation probably results in lower pain at 4 weeks (moderate COE; k=1), and VR-distraction may result in 6 months (low COE; k=1), whereas VR-DAE produced mixed findings (k=2; very low COE). IDR was not associated with AEs, and VR may not be associated with AEs for KOA (high and low COE), though AE reporting was uncommon (k=5) and evidence was very uncertain for post-TKA. CONCLUSIONS: IDR may augment treatment for KOA and post-TKA recovery, and VR may benefit post-TKA rehabilitation. This review is the first to stratify by level of immersion, clinical mechanism, and follow-up duration and to systematically evaluate AEs. IDR may be ready for integration into KOA care, while use after TKA needs more evidence. Randomized controlled trials with implementation outcomes could determine how XR interventions can be used for KOA, whereas trials evaluating efficacy and AEs are needed before their use for post-TKA.

Humans

Performance of AI-Based Screening Tools for Obstructive Sleep Apnea Across Apnea-Hypopnea Index Thresholds: Systematic Review and Meta-Analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent but remains substantially underdiagnosed. Polysomnography (PSG) is the reference standard, but its cost and limited availability constrain large-scale case identification. AI-based screening tools may support risk stratification and referral prioritization, but their diagnostic accuracy across apnea-hypopnea index (AHI) thresholds remains uncertain. OBJECTIVE: This review aimed to systematically evaluate the diagnostic accuracy of AI-based OSA screening tools at AHI thresholds of ≥5, ≥15, and ≥30 events/hour, with emphasis on models using non-PSG-derived inputs. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies published from January 1, 2016, to May 3, 2026. Eligible studies included adults evaluated for suspected OSA or recruited from population-based cohorts, assessed AI-based models intended or interpretable for OSA screening, risk prediction, or screening-oriented severity classification, used PSG as the reference standard, and reported sufficient data to construct or reconstruct 2×2 contingency tables. Diagnostic accuracy was synthesized separately by AHI threshold and input source using bivariate random-effects models, with 95% CIs and prediction intervals (PIs). Risk of bias and certainty of evidence were assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grading of Recommendations Assessment, Development, and Evaluation), respectively. RESULTS: A total of 60 studies were included, of which 47 contributed data to the meta-analysis. At AHI thresholds of ≥5, ≥15, and ≥30 events/hour, pooled sensitivities were 0.94 (95% CI 0.92-0.96; 95% PI 0.71-0.99), 0.87 (95% CI 0.84-0.89; 95% PI 0.66-0.96), and 0.83 (95% CI 0.79-0.87; 95% PI 0.61-0.94), respectively; the corresponding specificities were 0.77 (95% CI 0.69-0.84; 95% PI 0.30-0.96), 0.81 (95% CI 0.75-0.85; 95% PI 0.39-0.96), and 0.91 (95% CI 0.87-0.94; 95% PI 0.55-0.99), respectively. The corresponding areas under the summary receiver operating characteristic curves were 0.943, 0.907, and 0.920. For non-PSG-derived tools, sensitivities were 0.92, 0.85, and 0.81, and specificities were 0.70, 0.74, and 0.85 at the 3 thresholds, respectively. For PSG-derived models, sensitivities were 0.96, 0.90, and 0.85, and specificities were 0.82, 0.88, and 0.96, respectively. Exploratory subgroup analyses suggested performance variation across selected study and model characteristics, including region, algorithmic framework, data source, and validation method. CONCLUSIONS: AI-based tools showed generally favorable screening performance for OSA across clinically relevant AHI thresholds, although wide PIs suggest variable performance across future comparable populations and settings. By synthesizing diagnostic accuracy across 3 AHI thresholds and distinguishing non-PSG-derived from PSG-derived models, this review extends previous broad or modality-specific reviews and offers a clinically interpretable, pathway-specific basis for linking model performance to intended use. The findings may clarify potential roles for non-PSG-derived tools in front-end screening and referral prioritization and for PSG-derived models in reduced-channel assessment and sleep-laboratory workflow support. Given substantial heterogeneity, limited external validation, and low or very low certainty of evidence, prospective validation is needed before routine implementation.

Humans

How is goal setting used in interventions for chronic disease prevention and management in sub-Saharan Africa? A systematic review and narrative synthesis.

Non-communicable diseases are increasingly prevalent in sub-Saharan Africa, and goal setting is often used to promote healthy self-management behaviours. In this review, we aimed to synthesise literature around how goal setting is used, for application in future interventions in the region. A systematic search was conducted in six databases and results screened for eligibility. Study characteristics, intervention details, goal setting components, feedback from participants and facilitators were extracted. Data were analysed using narrative synthesis and thematic analysis. The Mixed Methods Appraisal Tool was used to assess study quality. We included 24 publications describing 18 unique interventions. Included studies were of high to moderate methodological quality. Goal setting intervention components were informed by a variety of frameworks and involved a range of tasks. Interventions were often facilitator-led; many were conducted in group settings. Participants reported goal setting as useful for putting self-management into practice but encountered challenges related to language and literacy levels. Adequate detail on goal setting intervention components was not always present. Through this review, we provide a comprehensive picture of the variability of goal setting approaches in chronic disease prevention and management in sub-Saharan Africa and recommend more standardised use and reporting of goal setting intervention components.

Humans

Driven toward care, avoiding the end: A systematic review and meta-analysis of the relationship between death anxiety and healthcare utilisation.

Both overuse and underuse of the healthcare system have been recognised as significant problems. Relatedly, growing research has recognised the key role of death anxiety in driving various health-relevant behaviours. However, the relationship between death anxiety and healthcare utilisation has not yet been systematically explored. The current systematic review and meta-analysis addressed this gap. In total, 987 papers were screened for inclusion, of which 63 were included in the final review (Ntotal = 21,271). This included 33 quantitative studies, 27 qualitative studies and 3 mixed-methods designs. In total, 17 studies contained sufficient data to be meta-analysed. Overall, the included studies highlighted a significant relationship between death anxiety and healthcare utilisation; in particular, positive associations with desire for life-prolonging treatments and contact with hospitals and medical professionals. By contrast, a negative association was found with other aspects of healthcare utilisation, including hospice use and end-of-life communication. The sample type emerged as a significant moderator, suggesting that the relationship between death anxiety and healthcare usage was strongest in non-medical samples. The current findings suggest that death anxiety plays a key role in utilisation of the healthcare system. The fear of death may need to be targeted in psychological interventions, in order to ensure maximal effectiveness of health services, and improve outcomes for healthcare users.

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Comparative safety of lipid-lowering drugs alone or in combination: insights from a systematic review and network meta-analysis.

BACKGROUND AND AIMS: Although the safety profile of lipid-lowering therapies (LLTs) is known, there are no comprehensive comparative assessments. We aimed to compare the risk of muscle-related events, diabetes, liver dysfunction, and cognitive disorders among LLTs through a network meta-analysis. METHODS AND RESULTS: Databases were searched from inception to May 2025. Eligible studies included adult patients, using statins, ezetimibe, PCSK9 monoclonal antibodies (PCSK9mAbs), inclisiran, bempedoic acid, or their combinations as intervention, reporting the information about any of the selected adverse events, a total sample size of ≥200 subjects, and had ≥1 month of intervention. Pooled estimates were assessed by fixed effects model within a frequentist setting. Pooled relative risks (RR) and their 95% confidence interval were estimated. A total of 303,397 subjects from 153 RCTs were included. Bempedoic acid ranked the lowest risk of myalgia (vs PCSK9mAbs, RR 0.80 [0.69, 0.93]). PCSK9mAbs were associated with lower incidence of creatine kinase (CK) elevation, diabetes, and liver dysfunction comparing to statins (statins vs PCSK9mAbs, RR 1.44 [1.14, 1.81], RR 1.13 [1.05, 1.22], and RR 1.38 [1.17, 1.62], respectively). In terms of muscle-related events and cognitive disorders, no significant risk differences were found among treatments and their combinations. CONCLUSIONS: PCSK9mAbs appear to have a more favourable safety profile regarding the risk of CK elevation, diabetes, and liver dysfunction. Bempedoic acid seem to be a better choice for subjects with high risk of myalgia. This information can be valuable when selecting therapy for specific patient subgroups at higher risk of certain adverse events.

Humans

Teacher- Versus Video-Delivered Classroom Activity Breaks and Student Physical Activity: The PAAC-3 Trial.

BACKGROUND: Classroom activity breaks may increase moderate-to-vigorous physical activity (MVPA); however, few studies have compared teacher and video-delivered approaches under real-world conditions. METHODS: In this cluster randomized trial, 11 elementary schools were assigned to teacher-delivered (PAAC-T; 5 schools, 192 students) or video-delivered (PAAC-V; 6 schools, 276 students) classroom activity breaks across one academic year. Teachers were trained to deliver two 10-min breaks daily. Intervention delivery was tracked via a web-based platform, and classroom MVPA was assessed using accelerometers at baseline and follow-up. RESULTS: Implementation fidelity was low and highly variable, but comparable between PAAC-T (42.3&#x2009;&#xb1;&#x2009;57.1 activity breaks/teacher/year) and PAAC-V (39.2&#x2009;&#xb1;&#x2009;33.9; p&#x2009;=&#x2009;0.96), with teachers delivering &#x223c;50% of the intended daily activity. Classroom MVPA increased significantly in both groups (PAAC-T: 9.8&#x2009;&#xb1;&#x2009;15.9; PAAC-V: 9.1&#x2009;&#xb1;&#x2009;15.3&#x2009;min/day; p&#x2009;<&#x2009;0.001), with no intervention arm-by-time interaction (p&#x2009;=&#x2009;0.43). IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: Classroom physical activity breaks may increase student MVPA, but effectiveness in elementary schools appears to depend on implementation fidelity, administrative support, and equitable system-level infrastructure. CONCLUSIONS: Modest increases in classroom MVPA were observed across both delivery formats, although low and variable implementation fidelity limited conclusions regarding effectiveness and highlighted the need for stronger implementation supports. TRIAL REGISTRATION: NCT03493139.

Humans

From fear to empowerment: the&#xa0;impact of employees AI awareness on workplace well-being - a new insight from the JD-R model.

PURPOSE: The primary purpose of the study was to explore the impact of health workers' awareness of artificial intelligence (AI) on their workplace well-being, addressing a critical gap in the literature. By examining this relationship through the lens of the Job demands-resources (JD-R) model, the study aimed to provide insights into how health workers' perceptions of AI integration in their jobs and careers could influence their informal learning behaviour and, consequently, their overall well-being in the workplace. The study's findings could inform strategies for supporting healthcare workers during technological transformations. DESIGN/METHODOLOGY/APPROACH: The study employed a quantitative research design using a survey methodology to collect data from 420 health workers across 10 hospitals in Ghana that have adopted AI technologies. The study was analysed using OLS and structural equation modelling. FINDINGS: The study findings revealed that health workers' AI awareness positively impacts their informal learning behaviour at the workplace. Again, informal learning behaviour positively impacts health workers' workplace well-being. Moreover, informal learning behaviour mediates the relationship between health workers' AI awareness and workplace wellbeing. Furthermore, employee learning orientation was found to strengthen the effect of AI awareness on informal learning behaviour. RESEARCH LIMITATIONS/IMPLICATIONS: While the study provides valuable insights, it is important to acknowledge its limitations. The study was conducted in a specific context (Ghanaian hospitals adopting AI), which may limit the generalizability of the findings to other healthcare settings or industries. Self-reported data from the questionnaires may be subject to response biases, and the study did not account for potential confounding factors that could influence the relationships between the variables. PRACTICAL IMPLICATIONS: The study offers practical implications for healthcare organizations navigating the digital transformation era. By understanding the positive impact of health workers' AI awareness on their informal learning behaviour and well-being, organizations can prioritize initiatives that foster a learning-oriented culture and provide opportunities for informal learning. This could include implementing mentorship programs, encouraging knowledge-sharing among employees and offering training and development resources to help workers adapt to AI-driven changes. Additionally, the findings highlight the importance of promoting employee learning orientation, which can enhance the effectiveness of such initiatives. ORIGINALITY/VALUE: The study contributes to the existing literature by addressing a relatively unexplored area - the impact of AI awareness on healthcare workers' well-being. While previous research has focused on the potential job displacement effects of AI, this study takes a unique perspective by examining how health workers' perceptions of AI integration can shape their informal learning behaviour and, subsequently, their workplace well-being. By drawing on the JD-R model and incorporating employee learning orientation as a moderator, the study offers a novel theoretical framework for understanding the implications of AI adoption in healthcare organizations.

Humans

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

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Self-reported physical activity in a randomized study from Norwegian Healthy Life Centres.

AIM: This study examines firstly if participation in a three-month intervention at Norwegian Healthy Life Centres (HLCs) improved self-reported physical activity (SR-PA), and secondly to what extent physical activity (PA) status at six months and changes from baseline were associated with demographic and motivational predictors. BACKGROUND: Regular PA is promoted as a central component of public health initiatives aimed at preventing noncommunicable diseases. METHODS: This randomized controlled trial included 118 participants (57 in the intervention group) recruited from HLCs in South-western Norway. The intervention effect was assessed by comparing the intervention group with the waiting-list control group after six months. We examined sociodemographic and motivational predictors of change combining both groups into a single cohort. This trial was registered at ClinicalTrials.gov (ID: NCT02247219). FINDINGS: At six-month follow-up, participants in the intervention group reported higher levels of SR-PA compared with the control group. The estimated effect was modest (B = 0.26, 95% CI -0.01 to 0.53), equivalent to &#x2248;0.37 SD. Although the confidence interval included zero, the estimate remained compatible with a modest positive effect. Autonomous motivation and social support were positively associated with SR-PA after 6 months, while psychological defiance showed a negative association. Autonomous motivation and psychological defiance impacted PA change during the 6-month period in opposite directions.

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Efficacy of smartphone- and bibliotherapy-delivered multicomponent lifestyle medicine interventions for probable depression: A three-arm randomized controlled trial.

BACKGROUND: This study examined the efficacy of smartphone- (AG) and bibliotherapy-delivered (BG) lifestyle medicine (LM) interventions compared with a waitlist control group (WLG) in reducing depressive symptoms. METHODS: A total of 122 adults with probable depression were randomized to AG (n&#xa0;=&#xa0;41), BG (n&#xa0;=&#xa0;40), or WLG (n&#xa0;=&#xa0;41). AG and BG received the same core 8-week multicomponent LM intervention via a smartphone application or booklets, respectively. The core content included lifestyle psychoeducation, physical activity, diet and nutrition, stress and sleep management, goal-setting, and motivational techniques. Outcomes were assessed at baseline and immediate post-intervention (Week 9) in all groups, with 1-month (Week 13) and 3-month (Week 21) follow-ups conducted in the intervention groups only. RESULTS: At Week 9, AG (d&#xa0;=&#xa0;0.89) and BG (d&#xa0;=&#xa0;0.64) showed significantly greater reductions in depressive symptoms than WLG, with within-group improvements maintained at 1- and 3-month follow-ups (ps&#xa0;<.001, d&#xa0;=&#xa0;0.77-0.96). Clinically significant improvement was achieved by 78% of AG and 55% of BG participants, both significantly higher than WLG (19.5%; ps&#xa0;<.001). Compared with WLG, both interventions yielded greater improvements in overall lifestyle and physical activity (d&#xa0;=&#xa0;0.59-0.91) at Week 9. The AG showed additional benefits for perceived stress, health responsibility, nutrition, spiritual growth, and stress management (d&#xa0;=&#xa0;0.58-0.73), whereas BG uniquely improved insomnia symptoms (d&#xa0;=&#xa0;0.83). CONCLUSION: Smartphone- and bibliotherapy-delivered LM interventions are efficacious for managing probable depression. Further RCTs comparing them with established treatments are warranted.

Humans

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans

What do we know about medical invalidation and related concepts? - A scoping review and thematic analysis about the definitions, measurements, causes, consequences and potential solutions for medical invalidation.

BACKGROUND: Medical invalidation, medical gaslighting, and related constructs have gained visibility in public discourse but remain inconsistently defined in scientific literature. Despite growing research-often focused on specific diseases- to date, no single review has comprehensively synthesized their definitions, causes, consequences, or methods of measurement. This scoping review addresses this gap by examining medical invalidation and related constructs. METHODS: Using a preregistered protocol, we systematically searched PubMed, CINAHL, Web of Science, Google Scholar, and ProQuest (dissertations) without year restrictions. Eligible sources included peer-reviewed empirical, theoretical, and conceptual work in English addressing invalidation, gaslighting, or closely related notions within healthcare. A total of 158 studies were identified through database searches and citation tracking. Data extraction followed a standardized schema, and findings were synthesized descriptively and through thematic analysis to clarify terminology, map determinants and outcomes, and identify existing measurement approaches. RESULTS: The results showed substantial inconsistency in how "invalidation," "not being taken seriously," and "gaslighting" were defined. Medical invalidation emerged as a multifactorial phenomenon driven by diagnostic challenges, structural and societal factors, provider and patient characteristics, stigma, misattribution, interactional dynamics, academic knowledge gaps, and disease-related complexity. Invalidation was associated with wide-ranging behavioural, emotional, cognitive, physical, relational, and systemic harms, while validation had consistently beneficial effects. Proposed solutions in the summarized studies included communication improvements, clinician training, patient support, targeted research, and structural and systemic changes. DISCUSSIONS: Medical invalidation represents a complex, systemic issue with significant implications for patient safety. The discussion highlights its multifactorial origins, its potential to cause both psychological and physical harm, and the need for clearer conceptualisation within the field. Advancing research requires validated instruments and longitudinal designs to examine underlying mechanisms and consequences. Addressing medical invalidation will demand multi-level interventions to improve communication, reduce structural barriers, and promote equitable, patient-centred care. OSF PREREGISTRATION: https://doi.org/10.17605/OSF.IO/MPE6U.

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Using the OPTIMAL Theory to Optimize Aerodynamics in Respiratory Training for Healthy Adults and Individuals With Parkinson's Disease.

BACKGROUND: The OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory is a motor learning framework proposing that optimizing intrinsic motivation enhances motor performance and learning. The theory identifies three key components-Enhanced Expectancies (EE), Autonomy Support (AS) and External Focus of Attention (EF)-which facilitate more efficient, goal-directed movement. These components have been shown to improve motor outcomes in limb-based tasks; however, their application to respiratory training, particularly in clinical contexts such as voice and swallowing therapy in patients with Parkinson's disease (pwPD), has not yet been systematically explored. AIMS: This study aimed to investigate whether implementing OPTIMAL theory strategies during a respiratory muscle strength training (RMST) task improves immediate respiratory motor performance in healthy adults and pwPD. Additionally, we aimed to examine the effects of these strategies on motivation and cognitive engagement. METHODS: This quasi-randomized, single-session trial included 47 participants: Healthy CONTROL (n = 17), Healthy OPTIMAL (n = 16) and PD OPTIMAL (n = 14). Healthy participants were quasi-randomly assigned to either intervention or control conditions, whereas pwPD completed the intervention only. All participants completed a single respiratory session that included baseline, practice and retention phases. Outcome measures included peak expiratory flow, cough peak expiratory flow, cognitive engagement (EEG-based Cognitive Engagement Index) and self-administered motivation questionnaire. OUTCOMES AND RESULTS: Exhalation force improved from baseline to retention in the Healthy OPTIMAL group (baseline: M = 296 L/min; retention: M = 338 L/min; p < 0.001) and the PD OPTIMAL group (baseline: M = 315 L/min; retention: M = 370 L/min; p < 0.0001), but not in the Healthy CONTROL group (p > 0.05). No significant changes in cough strength were observed in any group. No correlations were found between cognitive engagement and exhalation force or motivation scores. However, motivation increased more in the Healthy OPTIMAL group (Questionnaire 1: M = 57.2; Questionnaire 2: M = 60.7) and the PD OPTIMAL group (Questionnaire 1: M = 60.1; Questionnaire 2: M = 62.8) than in the Healthy CONTROL group (Questionnaire 1: M = 61.1; Questionnaire 2: M = 62.5). CONCLUSIONS AND IMPLICATIONS: Implementing the OPTIMAL theory enhances immediate respiratory motor performance in both healthy participants and pwPD. OPTIMAL theory has clinical value in voice and swallowing therapy, although further research is needed to establish long-term efficacy and clinical impact. WHAT THIS PAPER ADDS: What is already known on the subject Motivation is a critical factor in rehabilitation. The OPTIMAL theory has been shown to improve both motivation and motor performance in limb-based tasks. Its impact on respiratory training, however, has not been previously examined. What this paper adds to the existing knowledge This study shows that applying OPTIMAL strategies during a respiratory muscle strength training task significantly improved peak expiratory flow in both healthy adults and people with Parkinson's disease. What are the potential or clinical implications of this work? Integrating the OPTIMAL theory principles into respiratory therapy may enhance motor outcomes, supporting voice, swallowing and cough rehabilitation.

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Comparison between the thoracoabdominal rebalancing (TAR) method and the slow expiratory flow acceleration (SEFA) technique in preterm newborns: protocol for a randomised controlled clinical trial.

INTRODUCTION: Preterm newborns (PTNB) present respiratory immaturity and increased susceptibility to muscle fatigue. The thoracoabdominal rebalancing (TAR) method is a physiotherapeutic intervention developed in Brazil that aims to reorganise the synergy of the thoracoabdominal muscles and reduce the effort of the respiratory muscles, a benefit that is particularly important for PTNB; however, the evidence regarding its effectiveness in this population remains inconclusive. Therefore, this study aims to compare the short-term effects of the TAR method and the slow expiratory flow acceleration (SEFA) technique in improving respiratory distress and peripheral oxygen saturation (SpO2) in PTNB admitted to neonatal intensive care unit (NICU). METHODS AND ANALYSIS: The study will be a randomised, controlled, two-arm, parallel-group, single-blind clinical trial. 68 participants will be randomly assigned to one of the two treatment groups. Group 1 will receive four handling techniques of the TAR method for 10&#x2009;min, followed by the rhinopharyngeal retrograde clearance with saline instillation (RRC+I) technique. Group 2 will receive the SEFA technique for 10&#x2009;min, also followed by RRC+I. Primary outcomes are respiratory distress and SpO2. Secondary outcomes are respiratory rate (RR), heart rate (HR), pain, behaviour and diaphragmatic excursion. Assessments will be conducted by a blinded researcher at baseline (T0), immediately after the intervention (T1) and at the 30-minute follow-up (T2). Data will be described using measures of central tendency and dispersion and absolute and relative frequencies. An intention-to-treat analysis will be performed, and intragroup and intergroup comparisons will be assessed using generalised estimating equations (GEE). ETHICS AND DISSEMINATION: The Research Ethics Committee of the Faculty of Health Sciences of Trairi of the Federal University of Rio Grande do Norte approved this study (number 8,055,786). The results will be disseminated through peer-reviewed journal publications, scientific conferences presentations and knowledge translation to the public. TRIAL REGISTRATION NUMBER: This study was registered on Brazilian Registry of Clinical Trials (ReBEC) on 9 January 2026 (RBR-3gbsyc2).

Humans

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated &#x3b2;-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20&#x2009;weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age&#x2009;>&#x2009;=18&#x2009;years, singleton pregnancy, <&#x2009;20&#x2009;weeks' gestation, BMI &#x2265;&#x2009;29&#x2009;kg/m2. Women with GDM <&#x2009;20&#x2009;weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (<&#x2009;30&#x2009;nmol/L, n&#x2009;=&#x2009;102), insufficient (30-50&#x2009;nmol/L, n&#x2009;=&#x2009;222) and sufficient (>&#x2009;50&#x2009;nmol/L, n&#x2009;=&#x2009;638) groups. VitD levels and lipid concentrations were assessed at <&#x2009;20, 24-28 and 35-37&#x2009;weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and &#xdf;-OH-butyrate at 24-28&#x2009;weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher &#xdf;-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20&#x2009;weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype

Effects of a programmed reflexology therapy on sleep quality, insomnia, and fatigue among individuals with poor sleep quality: evidence for autonomic nervous system modulation.

Poor sleep quality is closely associated with autonomic dysregulation and increased risks of cardiovascular, metabolic, and mental disorders. Foot reflexology is a widely used complementary therapy; however, its physiological mechanisms and comparative efficacy remain insufficiently explored. This study aimed to compare the effects of manual reflexology treatment (MRT) and foot massage equipment (FEM) on autonomic nervous system function, sleep quality, insomnia severity, and fatigue in adults with poor sleep quality. Using a randomized crossover design, 32 participants with poor sleep quality received MRT and FEM interventions for 6 weeks each (once weekly, 30-40&#x202f;min/session). Heart rate (HR), blood pressure, and heart rate variability (HRV; time- and frequency-domain indices) were assessed at weeks 1 and 6 before and after each intervention. Subjective outcomes included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Assessment Scale (FAS). Following MRT, participants demonstrated significantly greater reductions in global PSQI scores and all PSQI components compared with FEM. MRT also resulted in larger improvements in insomnia severity and both mental and physical fatigue. In contrast, FEM primarily improved physical fatigue. Physiologically, MRT induced an immediate decrease in HR and significant increases in HRV time-domain indices (SDNN, RMSSD, pNN50), which were sustained after 6 weeks. Frequency-domain analysis further revealed reduced LF, increased HF, and a lower LF/HF ratio, indicating enhanced parasympathetic activity and cumulative autonomic modulation. In conclusion, programmed manual reflexology, delivered according to the TIDieR framework, is more effective than mechanical foot massage in improving autonomic balance, sleep quality, insomnia severity, and fatigue in individuals with poor sleep quality. These findings support MRT as a feasible and evidence-based non-pharmacological complementary intervention for sleep health promotion. TRIAL REGISTRATION: clinicaltrials.gov; NCT Number: NCT07402460; Registered 3 February 2026.

Adult