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Indigenous body image amid rapid social and economic change: A reflexive thematic analysis of Wayuu narratives.

The Wayuu, Colombia's largest Indigenous group, are experiencing rapid social, economic, and technological change, including expanding internet access, educational opportunities, and increasing exposure to globalised media. Though the harmful effects of appearance-idealised media imagery on body image are well documented, indigenous body image research remains unevenly distributed across global contexts, with Latin American Indigenous communities particularly underrepresented. This study explored how Wayuu people understand and experience appearance ideals and body image in the context of expanding digital media exposure and rapid sociocultural and economic change. Five focus groups of up to 9 participants were conducted with 29 Wayuu participants (18-68 years; 23 women, 6 men). Using reflexive thematic analysis, three overarching themes were identified: (1) Intersecting sources of appearance pressure: encompassing influences from social media, Wayuu family expectations, and discrimination from non-Indigenous peers; (2) Negotiating and resisting appearance ideals: from body dissatisfaction and restrictive eating to affirmation of cultural identity as protection; and (3) The changing role of appearance in today's Wayuu culture: participants linked globalised appearance ideals to expanding educational opportunities, migration, digital connectivity, and broader socioeconomic transformations occurring within Wayuu territories. While exposure to global ideals fostered comparison and dissatisfaction, cultural pride and collective belonging appeared to buffer against internalised colonial values. Culturally grounded media literacy and education initiatives co-developed with Wayuu communities could foster critical reflection while strengthening heritage. These results highlight the need for decolonial, community-based approaches to body image research and intervention in Indigenous contexts.

Adolescent

Morphological changes and transcriptomic insights into skeletal development of embryos and larvae of the sea urchin Strongylocentrotus intermedius.

To explore morphological features and molecular dynamics underlying skeletogenesis in the sea urchin Strongylocentrotus intermedius, we conducted combined morphological observation and comparative transcriptome analyses across representative embryonic and larval developmental stages. Morphological results showed that triradiate spicules first emerged at the gastrula stage. The 8-arm pluteus stage was identified as a key phase for skeletal remodeling, during which new three-radiate crystals transformed into complex stereoscopic ossicles including tube feet, spines and test plates. Transcriptomic data indicated that most differentially expressed genes (DEGs) were downregulated from the blastula to gastrula. The altered expression of basal metabolic genes and extracellular matrix genes including Colp2α and calm may be correlated with the linear mineralization of early spicules, which potentially reflects an energy adjustment pattern in developing larvae. During the transition from 6-arm to 8-arm pluteus, expression changes of calmodulin-like, Colp2α and SISin18G001660 suggest potential associations with regional calcium deposition and modifications of skeletal matrix properties. This work systematically characterizes morphological traits and transcriptional dynamics of skeletogenesis in S. intermedius. Its early spiculogenesis follows the conserved developmental pattern of echinoderms, while massive formation of stereoscopic ossicles occurs at the 8-arm pluteus stage. Stage-specific transcriptional changes across key larval skeletogenic stages are uncovered, offering transcriptomic resources for functional verification of skeletal regulatory genes.

Animals

Identifying stakeholder behaviors for competency-based pharmacy education: A stage 1 behavior change wheel analysis.

INTRODUCTION/OBJECTIVES: Competency-Based Pharmacy Education (CBPE) is a strategic priority for preparing graduates to meet evolving healthcare needs. However, efforts to implement CBPE can stall due to behavioral challenges among faculty, administrators, preceptors, and learners. This study aimed to apply Stage 1 of the Behavior Change Wheel (BCW) to identify stakeholder-specific behaviors and associated determinants needed to implement the five core components of CBPE. METHODS: A multi-method approach grounded in the BCW, the Capability, Opportunity, Motivation - Behavior (COM-B) model, and the Theoretical Domains Framework (TDF) was used. Data were gathered through (1) targeted literature review; (2) structured focus groups with competency-based education experts and pharmacy education stakeholders; and (3) an iterative consensus process. Behaviors were mapped to the five CBPE components: (1) defined competencies, (2) developmental progression, (3) tailored instruction, (4) authentic experiential learning, and (5) programmatic assessment, and then mapped to COM-B and TDF constructs. RESULTS: Over fifty stakeholder-specific behaviors were identified and specified across the CBPE framework. This revealed shared barriers such as limited instructional design knowledge (psychological capability), insufficient assessment of infrastructure (physical opportunity), and misaligned professional identity (reflective motivation). Key TDF domains included knowledge, environmental context, beliefs about capabilities, and professional roles. The behavioral problem statements, specifications, and determinants were identified to support future intervention planning. CONCLUSION: This Stage 1 analysis provides a behaviorally grounded foundation for CBPE implementation by identifying stakeholder behaviors and conditions that enable change. These findings will inform the development of readiness-to-change assessments and targeted interventions (BCW Stages 2 and 3), supporting scalable and sustainable CBPE transformation in pharmacy education.

Education, Pharmacy

Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial.

BACKGROUND: Artificial intelligence (AI)-based computer-aided detection (CADe) systems improve adenoma detection in average-risk colorectal cancer screening. Meanwhile, evidence in Lynch syndrome surveillance is sparse and inconsistent. We assessed the effect of CADe on adenoma detection during Lynch syndrome surveillance. Computer-aided optical diagnosis (CADx) performance for optical differentiation of colorectal lesions was evaluated as a secondary aim. METHODS: CADLY2 was an international, multicentre, open-label, randomised controlled superiority trial at nine specialised hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome scheduled for surveillance colonoscopy were randomly assigned (1:1) to high-definition white-light (HD-WL) colonoscopy alone or to HD-WL colonoscopy with computer-aided assistance from CAD EYE (Fujifilm, Tokyo, Japan). CAD EYE was used for CADe during withdrawal and for CADx after lesion detection. Randomisation was done centrally through a secure web-based system using Pocock's minimisation algorithm with a stochastic component and was stratified by centre, sex, previous colorectal cancer, underlying pathogenic variant, and interval since previous colonoscopy. Allocation concealment was ensured through the centralised web-based system. Patients were masked to group allocation until the start of withdrawal in procedures with mild sedation, or until completion of the procedure in procedures with propofol-based sedation. Endoscopists were not masked. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma, analysed in the full analysis set (defined as all randomly allocated patients with available data for the primary outcome). The diagnostic performance of the CADx system was evaluated as a secondary outcome. The safety analysis set comprised all randomly allocated patients who underwent a study colonoscopy. This study is registered with the German Clinical Trials Register, DRKS00030695, and is completed. FINDINGS: Between May 9, 2023, and Oct 30, 2025, 757 patients were randomly allocated to HD-WL colonoscopy (377 patients) or to AI-assisted colonoscopy (380 patients); 733 patients were included in the full analysis set (369 HD-WL and 364 AI-assisted). The median age was 49 years (IQR 38-59) in the HD-WL group and 50 years (38-59) in the AI-assisted group; 213 (58%) were female and 156 (42%) male in the HD-WL group, and 207 (57%) were female and 157 (43%) male in the AI-assisted group. The adenoma detection rate was 30·9% (114 of 369 patients) with HD-WL versus 33·8% (123 of 364 patients) with CADe assistance (odds ratio 1·14 [95% CI 0·83-1·57], p=0·41). For CADx differentiation of neoplastic versus non-neoplastic lesions in the paired lesion-level analysis, with histopathology as the reference standard and sessile serrated lesions and traditional serrated adenomas classified as non-neoplastic, CADx sensitivity was 85·9% (95% CI 82·0-89·1) and specificity was 91·4% (89·4-93·0). Three adverse events occurred in the AI-assisted group: two mild post-polypectomy bleedings and one serious pulmonary embolism or deep venous thrombosis unrelated to the procedure. No adverse events occurred in the HD-WL group. INTERPRETATION: CADe-assisted colonoscopy did not show the absolute improvement in adenoma detection rate that was assumed in the prespecified sample-size calculation. CADx did not clearly improve lesion differentiation beyond expert optical diagnosis in expert Lynch syndrome surveillance settings. FUNDING: Third-party research funding of the National Center for Hereditary Tumor Syndromes, University Hospital Bonn.

Humans

Subacute and long-term changes in cognitive functioning after administration of classic psychedelics, MDMA and ketamine: A systematic review of clinical and preclinical evidence.

Psychedelic agents induce a window of heightened neuroplasticity that extends beyond acute intoxication, during which neural circuits are more amenable to change. This period may facilitate changes in cognition relevant to the treatment of psychiatric disorders. This systematic review synthesised clinical and preclinical evidence of subacute and long-term (≥1 day) effects of classic and non-classic psychedelics on cognition. MEDLINE, EMBASE, APA PsycInfo and Web of Science were searched to identify human and animal studies investigating psychedelics and cognition (executive function, attention, decision-making). Sixty-seven (47 clinical, 20 preclinical) articles met inclusion criteria. Psilocybin demonstrated the most consistent evidence of subacute and longer-term cognitive improvement, particularly in cognitive flexibility and attention. Ketamine showed enhancement across cognitive domains, although findings were heterogeneous. LSD and DMT showed no consistent subacute changes, while MDMA was associated with transient cognitive impairments that resolved within days. Risk of bias assessments revealed selective outcome reporting, poor reporting of missing data and inadequate methodological detail, limiting the confidence of findings. Current evidence provides preliminary support for subacute changes in cognition following administration of select psychedelic agents. Cognitive improvements were more frequently seen in psychiatric populations than healthy subjects, which may reflect a remediation of existing cognitive deficit rather than enhancement above normal functioning. Adequately powered, controlled studies with standardised reporting of cognitive outcomes are required to determine the magnitude, durability and clinical relevance of psychedelic-associated cognitive change.

Hallucinogens

Predictive evolutionary genomics: principles, validation, and practice.

Climate change and habitat loss are driving rapid evolutionary responses in populations world-wide, which creates an urgent need for evolutionary forecasting in conservation and agriculture. Such forecasting can be categorized into three time scales: trait-based models that use multivariate quantitative genetic equations to project correlated phenotypic responses up to c. 20 generations, allele-based analyses that model allele frequency dynamics up to 100 generations, and composite adaptation scores that aggregate many small effects to yield predictions across longer horizons. However, these approaches have remained largely disconnected. Here, we present a Bayesian framework that integrates these three complementary approaches for evolutionary prediction. Our framework combines genomic, phenotypic, and environmental data to yield probabilistic predictions with explicit uncertainty. We show how predictive evolutionary forecasts can be validated with experimental evolution, field experimentation, historical specimens, and reciprocal transplants. These validated forecasts can help advance conservation and agricultural programmes by helping predict which populations are at risk of future extinction, optimizing breeding programmes for future climates, and planning ecosystem management under environmental change. By supporting a shift towards more predictive approaches in evolutionary biology, this framework may help improve our ability to manage biodiversity and food security in a changing world.

Genomics

Changes in hemoglobin levels and cardiometabolic health in adults with metabolic syndrome - a secondary outcome analysis of a six-month randomized controlled trial.

BACKGROUND: Lower hemoglobin (Hb) levels within the normal range have been associated with favorable metabolic traits in cross-sectional studies. This study investigated whether changes in Hb levels correlated with changes in physiological and cardiometabolic parameters during a six-month behavioral intervention in individuals with metabolic syndrome. METHODS: The&#xa0;six-month randomized controlled trial aimed to reduce sedentary behavior in adults with metabolic syndrome (n&#x2009;=&#x2009;64). Key measurements included fasting blood samples, insulin sensitivity during a hyperinsulinemic-euglycemic clamp, insulin-stimulated liver glucose uptake, liver fat content (LFC), indirect calorimetry, cardiorespiratory fitness, and cardiac function. Correlations&#xa0;between changes in these variables and changes in Hb levels at baseline, three, and six months were examined. RESULTS: Cross-sectionally, higher Hb levels correlated with&#xa0;lower insulin sensitivity (r=-0.35, p&#x2009;=&#x2009;0.005), higher resting O2 consumption (r&#x2009;=&#x2009;0.41, p&#x2009;<&#x2009;0.001), higher resting energy expenditure (r&#x2009;=&#x2009;0.49, p&#x2009;<&#x2009;0.001), higher LFC (r&#x2009;=&#x2009;0.40, p&#x2009;=&#x2009;0.011), and greater&#xa0;left ventricular wall thickness (r&#x2009;=&#x2009;0.42, p&#x2009;=&#x2009;0.001). The intervention did not significantly impact Hb levels, and changes in Hb levels did not correlate with most cardiometabolic changes. However, reduced Hb levels correlated with reduced fasting blood glucose (r&#x2009;=&#x2009;0.29, p&#x2009;=&#x2009;0.032), improved insulin sensitivity (r = -0.26, p&#x2009;=&#x2009;0.045), and increased cardiorespiratory fitness (r = -0.29, p&#x2009;=&#x2009;0.033). CONCLUSIONS: Changes in Hb levels did not consistently correlate with changes in cardiometabolic markers during&#xa0;the intervention. However, reductions in Hb levels may relate to improved insulin sensitivity and fitness. Along&#xa0;cross-sectional correlations, this may be clinically relevant for individuals with metabolic syndrome. Further studies are merited to clarify&#xa0;the role of Hb levels in this high-risk group.

Humans

Lower androgen sulfate metabolites in women with hypermobile Ehlers-Danlos syndrome may be associated with changed metabolism and disposition.

Hypermobile Ehlers-Danlos Syndrome (hEDS), characterized by joint hypermobility and multisystem involvement, is the most common type of EDS. Its comorbidities are wide-ranging, reflecting the involvement of connective tissue and its role in a multitude of processes. hEDS has been hypothesized to have hormonal aspects since the disorder is diagnosed more often in women and symptom changes closely correlate with hormonal shifts. To better understand the etiology and biochemical changes in hEDS and its comorbidities, a multiple-omics study was performed in women, controls (n&#x202f;=&#x202f;45) and those with hEDS (n&#x202f;=&#x202f;45), alongside the collection of questionnaires related to symptom severity. Metabolomic evaluation was performed on serum samples and RNA isolated from fibroblasts cultured from skin punches was analyzed for transcriptomics. Samples from hEDS patients had statistically significantly lower levels of multiple androgen sulfate metabolites, compared with controls, driven largely by participants aged 30-49. Changes to other classes of steroid hormones (corticosteroids, progestogens, and estrogens) were largely not significant between hEDS and control groups. Transcriptomics of skin fibroblasts from hEDS patients revealed downregulation of multiple enzymes involved in biosynthesis, metabolism, and disposition of androgens, compared with controls. Multiple steroid hormones correlated with symptoms surveyed in 18-29 year old participants with hEDS. Shifts in steroid hormone metabolites in hEDS compared with controls may be due to changes to metabolism and disposition, but more validation is necessary to be conclusive. This data provides insights into the unclear links between steroid hormones and hEDS and its comorbidities.

Humans

Proteomic and phosphoproteomic profiles of time-dependent dynamic changes in LPS-induced macrophage polarization.

The temporal proteomic and phosphoproteomic reprogramming during early M1 macrophage polarization (0-6&#xa0;h) remains poorly understood. We performed time-resolved proteomic and phosphoproteomic analyses of LPS-stimulated RAW264.7 macrophages at seven time points within 6&#xa0;h. Time-clustering of differentially expressed molecules revealed two patterns: initial change with partial recovery, and sustained dysregulation. Upregulated proteins and phosphorylation sites were enriched in the Rho GTPase signaling pathway, T-cell receptor signaling pathway, NF-&#x3ba;B cascade, osteoclast differentiation pathway, and antiviral immune pathway. Downregulated pathways were associated with cell cycle regulation, chromatin remodeling, RNA metabolism, and mRNA processing, indicating resource reallocation to prioritize acute inflammatory responses. Kinase-substrate network analysis confirmed the mitogen-activated protein kinase (MAPK), cyclin-dependent kinase (CDK), protein kinase B (AKT), and ribosomal S6 kinase (RSK) families as core upstream phosphorylation regulators. Integrated analysis revealed synergistic and antagonistic relationships between proteomic and phosphoproteomic changes. This study provides a temporal molecular atlas of M1 polarization, delineating inflammatory signaling dynamics and offering a basis for therapeutic target discovery in inflammatory diseases. SIGNIFICANCE: Macrophage M1 polarization is a central event in innate immune defense against pathogenic invasion, yet its dysregulation is a pivotal driver of the onset and progression of a broad spectrum of inflammation-associated disorders, spanning autoimmune diseases, infectious conditions and inflammatory bone diseases, making the dissection of its molecular regulatory mechanisms an urgent research priority in immunology and translational medicine. Dynamic molecular events within 0-6&#xa0;h after LPS stimulation are critical for initiating and shaping M1 inflammatory activation, yet systematic time-resolved proteomic and phosphoproteomic profiling remains insufficient.In this study, we comprehensively characterized temporal proteome and phosphoproteome changes at seven consecutive time points during macrophage polarization, clarified two distinct dynamic molecular patterns, identified core signaling pathways and key kinase regulators involved in inflammatory reprogramming, and uncovered the leading role of post-translational phosphorylation modifications in initiating polarization. This work delineates the time-series molecular atlas of early macrophage activation, provides novel insights into the temporal regulatory mechanism of inflammatory signaling networks, and lays a solid experimental foundation for exploring new intervention targets and regulatory nodes in clinical translational research.

Lipopolysaccharides

Assessment of temporomandibular joint space changes after orthognathic surgery in skeletal malocclusion patients: a systematic review.

PURPOSE: To interpret postoperative changes in temporomandibular joint (TMJ) joint space dimensions and condylar position following orthognathic surgery in patients with skeletal malocclusions, and to determine whether reported alterations represent clinically meaningful displacement or physiological adaptive remodeling. MATERIALS AND METHODS: A comprehensive search of PubMed, SCOPUS, Web of Science, EBSCOhost, and Cochrane Library was performed to assess pre- and postoperative TMJ changes using three-dimensional imaging. Joint spaces including anterior (AJS), superior (SJS), and posterior (PJS) and condylar morphology were evaluated. Methodological quality was appraised using the Joanna Briggs Institute (JBI) checklist. Due to methodological and clinical heterogeneity, findings were synthesized narratively with attention to malocclusion type and surgical movement. RESULTS: A total of 16 studies consisting 628 patients undergoing BSSO, Le Fort I osteotomy, vertical ramus osteotomy, or bimaxillary surgery were included. Most studies reported minor, adaptive postoperative changes in AJS, SJS, and PJS. Class II patients showed more consistent increases in AJS/SJS, whereas Class III patients demonstrated variable posterior or anterior remodelling depending on surgical movement. Volumetric analyses revealed region-specific adaptations without significant condylar displacement. Postoperative temporomandibular disorder symptoms were infrequent, and no consistent evidence supported detrimental TMJ effects attributable to surgery. CONCLUSION: Postoperative TMJ joint space changes after orthognathic surgery primarily represent physiological adaptive remodeling rather than pathological condylar displacement, with reported variability driven by malocclusion type, surgical movement, fixation method, and imaging protocol. Recognizing these predictable patterns is essential to prevent overinterpretation of postoperative imaging and to improve clinical assessment through standardized three-dimensional and long-term evaluation strategies.

Humans

Effects of different training modalities on lower-limb explosive power, acceleration, 20-m sprint performance, and change-of-direction ability in youth soccer players: a systematic review and network meta-analysis.

BACKGROUND: Youth soccer players repeatedly perform explosive actions, short accelerations, linear sprints, decelerations, and multidirectional movements. However, the comparative effects of different structured physical-conditioning programmes remain uncertain. METHODS: Seven databases were searched from inception to 3 July 2026 using a final expanded search strategy encompassing plyometric, strength or resistance, sprint, acceleration, speed, change-of-direction, neuromuscular, multicomponent, and combined training. Randomised controlled trials involving healthy youth soccer players were eligible. Intervention arms were classified using operational, content-based node definitions. Construct-restricted primary networks and expanded sensitivity networks were analysed using frequentist random-effects network meta-analysis. Hedges' adjusted g was preferentially calculated from post-intervention or final-follow-up means, standard deviations, and sample sizes. Estimates were presented so that positive values indicated better performance. P-scores were treated as descriptive ranking summaries. Risk of bias was assessed using an adapted study-level application of the five-domain RoB 2 framework, and confidence in the evidence was assessed using CINeMA. A post hoc strict-age sensitivity analysis excluded two age-boundary studies. RESULTS: Eighty-nine studies were included in the expanded quantitative analysis, of which 74 contributed to at least one construct-restricted primary network. The primary lower-limb explosive-power, acceleration, 20-m sprint, and planned change-of-direction networks included 55, 20, 25, and 38 studies, respectively. Compared with usual soccer training, plyometric training combined with sprint and/or change-of-direction training showed favourable estimates for lower-limb explosive power (SMD 0.79, 95% CI 0.55 to 1.03), acceleration (1.19, 0.90 to 1.49), 20-m sprint performance (0.80, 0.33 to 1.28), and planned change-of-direction ability (1.46, 1.13 to 1.80). Corresponding I&#xb2; values were 34.6%, 21.8%, 65.0%, and 41.0%. Between-design inconsistency was detected in the 20-m sprint (P&#x2009;=&#x2009;0.0036) and change-of-direction (P&#x2009;=&#x2009;0.0007) networks. CINeMA confidence for these four comparisons was low, low, very low, and low, respectively. Expanded sensitivity networks showed substantially greater heterogeneity. The highest-ranked intervention differed across outcome domains but remained consistent within each outcome across the three analysis sets. Excluding the two age-boundary studies did not materially alter the principal estimates. CONCLUSIONS: Plyometric training combined with sprint and/or planned change-of-direction training produced favourable comparative estimates across the four performance outcomes. However, evidence for several nodes and active-versus-active comparisons was sparse, heterogeneity in programmes and outcomes was present, inconsistency was detected in some networks, and confidence in the evidence was low or very low. These limitations do not support a conclusion that any training category is universally superior. The findings should be interpreted as provisional category-level signals rather than definitive training prescriptions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261347297, registered on 21 March 2026, https://www.crd.york.ac.uk/PROSPERO/view/CRD420261347297 .

Change-of-direction ability

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans

Weight and metabolic changes in patients with schizophrenia treated with paliperidone palmitate 6-month formulation versus paliperidone palmitate 3-month formulation: a post-hoc analysis.

OBJECTIVE: To determine the effect that paliperidone palmitate 6-month long-acting injectable formulation (PP6M) had on metabolic parameters including body weight (BW), and blood lipid profiles, a post-hoc analysis was conducted to assess changes in BW from baseline to the end of study based on age, body mass index (BMI), and changes in blood lipid profiles during a 12-month, phase 3, double-blind (DB) clinical study. Long term effects of PP6M on BW and BMI were further explored during a 24-month extension study in which participants were treated exclusively with PP6M. METHOD: In the 12-month DB phase, participants were randomized to receive PP6M or paliperidone palmitate 3-month long-acting injectable formulation (PP3M). The mean change in BW and abnormal weight percent change from baseline were calculated at endpoint by age, gender, and BMI. Additionally, treatment-emergent shifts from baseline for the four key lipid parameters (fasting low density lipoprotein [LDL], fasting triglycerides [TG], fasting total cholesterol [TC], and fasting high density lipoprotein [HDL]) during DB were assessed. Following this study, participants were given the opportunity to transition to a 24-month extension study and be treated with PP6M. The mean change and percent change in BW, and the mean change in BMI from DB baseline to the end of the extension study (36&#xa0;months total) were calculated. RESULTS: Participants who were treated with PP6M showed numerically less weight gain, BMI, waist circumference, and more weight decrease compared to PP3M group during 12-month DB phase, though the proportion of participants reporting an abnormal change (&#x2265;7% change) in BW did not significantly differ between PP3M and PP6M. The weight differences were more pronounced in the younger age group (18-25&#xa0;years) and those who were overweight (BMI: 25 to <30&#xa0;kg/m2. Numerical differences in favor of PP6M were found in fasting blood lipids (HDL, LDL, TG, and TC). The changes in BW and BMI over time remained consistent throughout the 24-month extension, favoring PP6M in each instance. CONCLUSIONS: This post-hoc analysis demonstrated that PP6M was comparable to PP3M in terms of metabolic parameters; however, it may have a beneficial effect on weight gain, especially in young patients. TRIAL REGISTRATION: Post-Hoc Analysis of Studies NCT03345342 and NCT04072575 (ClinicalTrials.gov). Significant outcomes The findings from this study have highlighted that participants who were treated with the 6-month long-acting injectable formulation of paliperidone exhibited less weight gain during treatment overall, and significantly less weight gain in adolescents and young adults. Importantly, this trend continued over the course of long-term treatment, regardless of age. Participants treated with the 6-month formulation also had fewer shifts in blood lipids outside of the normal range and had more favorable changes in body mass index and waist circumference. These results suggest that when considering metabolic dysregulation as a factor in choosing a long-acting injectable antipsychotic, the 6-month formulation is a viable alternative to the 3-month formulation, particularly in younger patients with schizophrenia. Limitations Because this is a post hoc analysis and the study was not powered to test weight and metabolic changes, most endpoints were summarized descriptively and the statistical test was limited to the main endpoint (abnormal percent weight gain and loss).

Adult

Differences in circadian rhythm changes between myopic and non-myopic college students over 2&#x2009;years.

This study aimed to characterize and compare the differences in circadian rhythm changes during 2&#x2009;years between college students with myopia and non-myopia based on a longitudinal cohort study. Wake-up time and bedtime were obtained through a self-administered questionnaire. Chronotype was assessed using the reduced Morningness-Eveningness Questionnaire (rMEQ). Circadian rhythm timing was determined by dim-light melatonin onset (DLMO), measured through hourly saliva collection from 21:00 to 01:00. A total of 450 college students (146 [32.4%] males) with a mean age of 18.65&#x2009;&#xb1;&#x2009;1.05&#x2009;years were included, of whom 353 (78.4%) students had myopia. Compared with non-myopic individuals, myopic students slept later, woke up earlier, and exhibited lower rMEQ scores at baseline. Over the 2-year follow-up, both groups showed significantly earlier bedtimes, later wake-up times, and higher rMEQ scores. Only myopic students demonstrated a 45-minute delay in DLMO after the 2-year follow-up. After adjusting for potential confounders, linear mixed-effects models showed that myopic individuals had later bedtimes and earlier wake-up times. These findings indicate significant circadian rhythm changes in individuals with myopia, suggesting the potential of targeted sleep rhythm interventions on preventing myopia.

Myopia

Changes in ACL T2* Metrics Over the Course of the Female Menstrual Cycle: A New Biomarker for the ACL Injury Risk?

BACKGROUND: Sex-based disparities in the anterior cruciate ligament (ACL) injury risk may be partly explained by cyclic variations in sex hormones that drive systemic shifts in tissue osmoregulation. Ultrashort echo time (UTE) T2* magnetic resonance imaging provides a noninvasive, quantitative means of evaluating the water content and collagen orientation in tissue. HYPOTHESIS: Eumenorrheic female participants will exhibit significant ACL T2* changes across the cycle, while anovulatory control participants will demonstrate no significant changes over time. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 25 women with no prior knee injuries were enrolled: 10 premenopausal, eumenorrheic participants and 15 anovulatory control participants (6 postmenopausal and 9 premenopausal using oral contraceptives). Bilateral knee magnetic resonance imaging was performed at 4 time points evenly spaced over 1 month, with the first visit within 24 hours of menses onset. Ovulation status was confirmed using commercially available ovulation predictor kits. Three-dimensional UTE sequences (11 echoes; 0.03-25 ms) were acquired to evaluate bicomponent ACL T2* metrics. Linear mixed-effects models assessed temporal differences in long and short T2* values, and the Cohen d quantified effect size. RESULTS: Eumenorrheic participants demonstrated significantly shorter preovulatory long T2* values compared with postovulatory values (mean difference, 1.0 ms [95% CI, 0.2-1.9 ms]; P = .015; Cohen d = 0.51). No significant temporal differences were observed for any T2* metric in anovulatory controls. CONCLUSION: Eumenorrheic female participants exhibited significant preovulatory to postovulatory changes in ACL T2* metrics, while anovulatory controls demonstrated no significant changes over time. These findings suggest that ACL T2* metrics are sensitive to cyclic fluctuations in female sex hormones across the menstrual cycle.

Humans

From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.

Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.

Journal Article

Effects of dietary interventions on gut microbiota and related cardiometabolic changes in pediatric obesity: a systematic review and meta-analysis.

BACKGROUND: Gut microbiota imbalances may contribute to obesity, yet whether dietary interventions can modulate the microbiota and improve metabolic health in pediatrics has not been thoroughly reviewed. This systematic review and meta-analysis explores the impact of dietary interventions on the gut microbiota of children and adolescents with overweight or obesity, and its association with cardiometabolic improvements. METHODS: A systematic search of clinical trials in Pubmed, Cochrane and EMBASE was conducted following PRISMA guidelines (PROSPERO n&#xb0;CRD42024505494). Risk of bias was assessed with RoB2 and ROBINS, for randomized and non-randomized intervention studies. RESULTS: Overall, 60 articles were assessed for full-text eligibility, 8 were included, and 4 provided alpha-diversity data for meta-analysis. A total of 200 participants were included (6-16 years). Six studies implemented calorie-restricted diets, one a low free-sugar diet, and one CHILD-1 diet. The meta-analysis revealed a significant increase in Chao1 (48.76 [95%CI 1.81; 95.70]; I2&#x2009;=&#x2009;86.8%, p&#x2009;<&#x2009;0.001) following a balanced calorie-restricted dietary intervention. Although&#xa0;there was heterogeneity in taxa-level changes, several butyrate-producing genera (Clostridium XVIa, Coprococcus, Roseburia, Faecalibacterium, Blautia, Butyricimonas) increased following dietary intervention. CONCLUSIONS: Balanced dietary interventions with calorie-restriction adequate for pediatric age could increase gut microbiota richness and butyrate-producing bacteria abundance. Future trials should clarify diet-driven gut microbiota changes in childhood obesity and related metabolic changes. IMPACT: Balanced calorie restriction diet may increase gut microbiota richness in childhood obesity Butyrate-producer expansion needs long-term dietary intervention Gaps in linking microbiota-metabolism interplay in pediatric obesity.

Journal Article

Impacts of climate-driven yield changes on the affordability of healthy diets: a modelling study.

BACKGROUND: Food security is central to global nutrition improvement and public health goals, and healthy diets represent a higher-level aspiration beyond merely avoiding hunger. Climate change poses an increasing threat to food systems by affecting crop yields and food prices. Although climate change-driven risks to hunger have been widely studied, the extent to which climate change undermines the affordability of healthy diets while accounting for socioeconomic responses and regional inequalities remains insufficiently understood. This study aimed to quantify the effects of climate change on the future affordability of healthy diets under alternative socioeconomic and climate scenarios. METHODS: We developed an integrated modelling framework that explicitly couples multimodel crop-yield projections with an integrated assessment model (Global Change Analysis Model [GCAM]). Yield responses from six global gridded crop models driven by four climate models were integrated into GCAM, allowing endogenous socioeconomic adjustments such as land-use shifts, production reallocation, and price responses to emerge under shared socioeconomic pathways (SSPs). Diet affordability was then assessed using the Food and Agriculture Organization of the UN's Cost and Affordability of a Healthy Diet framework across three socioeconomic-climate scenarios (SSP1-2.6, SSP2-4.5, and SSP3-6.0). FINDINGS: Under a high-emissions pathway (ie, SSP3-6.0), climate change was projected to render healthy diets unaffordable for a model-mean of 119 million people globally by 2100, even when CO2 fertilisation effects are included, with the upper end of the model ensemble reaching about 1&#xb7;6 billion people. In contrast, climate-induced affordability losses were found to be negligible under both a low-emissions pathway (ie, SSP1-2.6; -0&#xb7;3 million) and a medium-emission pathway (SSP2-4.5; +0&#xb7;2 million). Under a high-emission pathway, model-mean projections indicated that diet costs could increase by up to 12% in the most affected regions by the end of the century. Under medium emissions, cost increases were projected to remain below 4%, whereas under low emissions, affordability changes were projected to be minimum across regions (within approximately 0&#xb7;5%). Substantial regional disparities emerged, with the largest and most consistent affordability losses concentrated in low-income regions that contributed least to historical greenhouse gas emissions. Under SSP3-6.0, these disparities persisted particularly in regions of Africa and Asia despite projected three-to-five-fold increases in income over the century, with climate-induced disruptions to food systems increasing the number of people unable to afford a healthy diet through mid-century. INTERPRETATION: Climate change is likely to exacerbate global nutritional inequalities by disproportionately increasing the affordability risks of healthy diets in regions that have contributed least to historical greenhouse gas emissions. Under high-warming scenarios, socioeconomic development alone is insufficient to fully offset these risks, highlighting the structural vulnerability of low-income food systems to climate-driven price shocks. These findings suggest that in the absence of targeted interventions, climate change could continue to undermine progress towards equitable and health-oriented nutrition outcomes. FUNDING: Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China; National Aeronautics and Space Administration Goddard Institute for Space Studies Climate Impacts Group; Future of Life Institute; and Global Alliance for Improved Nutrition.

Journal Article