BackgroundClinical guidelines recommend a stepped-care strategy for patients with hip and knee osteoarthritis that begins with nonoperative approaches, including education, pain medication, and self-care. However, the implementation of stepped-care remains limited. Digital self-management interventions have the potential to support patients in applying lifestyle advice and self-care strategies, but current tools often provide generic support without long-term continuity. Artificial intelligence offers new opportunities to deliver personalized, just-in-time self-management interventions for people with osteoarthritis. The development of such artificial intelligence algorithms is limited due to a lack of rich, longitudinal datasets.ObjectiveThe primary objective of this study is to develop and evaluate data-driven models that support personalized recommendations on the optimal timing and optimal advice (physical activity promotion, sleep optimization, weight management, no program) for individuals with hip or knee osteoarthritis.MethodsThis prospective cross-over study aims to include 600 people with hip or knee osteoarthritis, meeting the National Institute for Health and Care Excellence criteria. The study is registered at ClinicalTrials.gov (registered February 2, 2026, NCT07423858). We aim to screen digital health literacy in our sample. Participants will be recruited across the Netherlands and will use the e-cOAch web app, with 3 self-care programs (ie, physical activity promotion, weight management, and sleep optimization). Each participant will complete all three 12-week programs and one 12-week control period in a randomized sequence. Participants will be followed for 12 months, with biweekly assessments conducted via the app. The primary outcome for model development will be deterioration in physical functioning, measured by a decrease in the Hip Disability and Osteoarthritis Outcome Score subscale activities of daily living of 6.7 or the Knee Injury and Osteoarthritis Outcome Score subscale activities of daily living of 8.2. Secondary outcomes will be pain and participation. Additional measures will include patient characteristics (date of birth, sex, height, level of education, comorbidity, ethnicity, use of a walking device, use of pain medication, device for e-cOAch, duration of osteoarthritis complaints, health and digital literacy, smoking, alcohol use), physical activity, sleep quality and insomnia, psychosocial factors, behavioral determinants, and engagement with the app. These data will inform the development of data-driven models using supervised (causal) machine learning.ResultsThe funding for the study was granted in 2023. At the time of manuscript submission, 520 participants had been recruited. Recruitment is expected to be completed in March 2026, with data collection projected to conclude in April 2027. The publication of the results is anticipated in spring 2028.ConclusionsThis study will provide data-driven models that forecast changes in physical functioning over time and support personalized recommendations on the optimal timing of specific self-care programs for people with hip or knee osteoarthritis. These models will be integrated into a new iteration of a self-management app, e-cOAch (version 2), to provide personalized support for people with osteoarthritis across varying levels of digital health literacy.

This study utilized a case-crossover design to assess the acute, transient trigger effect of weather-related factors on acute aortic dissection (AAD) onset, while inherently controlling for all stable individual-level confounders. This retrospective, single-center case-crossover study included 293 consecutive patients with AAD treated at a tertiary care center between January 2019 and December 2021. For each patient, the day of AAD onset (case period) was compared with the seven preceding days (control periods). Daily weather-related data, including mean temperature and day-to-day temperature change, were obtained. Conditional logistic regression analysis was performed to estimate the acute risk of AAD onset associated with weather-related variables, allowing for the matching of patient-specific, time-invariant factors. Multivariate conditional logistic regression analysis identified two weather-related factors independently associated with AAD onset: mean temperature and the change in minimum temperature from the previous day. A decrease in mean temperature significantly increased the risk of AAD; the risk increased by 1.13 times (95% CI: 1.06-1.20) for every 1℃ decrease in mean temperature. Similarly, a larger drop in minimum temperature from the previous day acutely increased the risk; the risk increased by 1.04 times (95% CI: 1.01-1.08) for every 1℃ decrease in minimum temperature from the previous day. The onset of AAD is acutely triggered by low mean temperature and a significant drop in minimum temperature from the previous day, independent of individual patient risk factors.

Evidence as to whether COVID-19-mitigating measures affected the metabolic status of pregnant women is lacking. This is the first study to analyze changes in pre-pregnancy weight, body mass index (BMI), gestational weight gain (GWG), the prevalence of overweight and obese women conceiving, and delivery-associated complications during the COVID-19 pandemic compared to pre-pandemic times. This nationwide cohort study analyzed birth registry data from all obstetric departments in Austria. The period from 05 to 12/2020 was defined as the pandemic period (N = 30,806), whereas the period from 05-12/2015-2019 was defined as the pre-pandemic period (N = 162,463). The pre-pregnancy weight and BMI were 64 (57-73) kg and 23.03 (20.70-26.37) kg/m2 during the COVID-19 pandemic versus 63 (56-72) kg and 22.7 (20.57-22.77) kg/m2 during the pre-pandemic period (p < 0.001). The GWG remained constant at 13kg and 4.8kg/m2 between the exposure and control periods (p = 0.69; p = 0.65). A multivariate analysis revealed that the COVID-19 pandemic had a significant impact on pre-pregnancy weight (OR 1.01; 95% CI 1.00-1.02; p < 0.001) after adjusting for covariates (age, height, parity). During the COVID-19 pandemic period, a significantly higher percentage of women with overweight and obesity class I-III were reported compared to pre-pandemic times (p = 0.003, p < 0.001, p< 0.001). Finally, both more macrosomic infants (p = 0.003) and vacuum-assisted deliveries (p = 0.020) occurred during the COVID-19 pandemic. COVID-19-mitigating measures worsened the metabolic status of pregnant women. To counteract this, targeted intervention programs must be implemented immediately as an integral part of the pandemic recovery plan.

Effective management of prenatal nutrient concentrations, such as those associated with folate, is critical for the health of the prospective mother and child, but quantifying them currently requires frequent blood tests and specialized laboratories. Human sweat is a non-invasive alternative to blood that is well suited for point-of-care biosensing. Here we present a skin-interfaced microcapsule that enables collection and storage of pristine, microlitre volumes of sweat and supports an efficient interface to a portable lab-on-a-disc platform for folate quantification. This platform automates an entire enzyme-linked immunoassay sequence for measuring folate in sweat, including incubation, washing, mixing and detection, and facilitates wireless data transmission. A series of tests in human participants reveal a dose-response relationship between oral intake of folate supplements and sweat folate levels, with a strong correlation in levels between sweat and serum. In addition, daily tracking of sweat folate concentrations shows clear differences between control periods without supplementation and daily intake periods. This technology creates possibilities for the routine use of sweat for precise point-of-care assessment of prenatal nutrient bioavailability.

Regression of Left Main Coronary Stenosis During Long-Term Tocilizumab Therapy in Takayasu Arteritis.

Brachycaudus helichrysi (Kaltenbach) (Hemiptera: Aphididae) is a destructive pests of Prunus domestica (L.) (Rosaceae), in India. Life tablestudies are essential tools for understanding population dynamics and predicting the control period of B. helichrysi on plum cultivation. Age-stage, two-sex life tablesof B. helichrysi reared on six plum cultivars under controlled laboratory conditions were constructed. The total phenolic content in the leaves of each cultivar was quantified. Compared with the Red Beaut cultivar of plum, the fecundity, net reproductive rate, intrinsic rate of increase, finite rate of increase, and total longevity of B. helichrysi were significantly lower, and the mean generation time was significantly longer on the Fortune cultivar, followed by Angeleno, Friar, Black Amber, and Santa Rosa. The total phenolic compounds in the leaves of the different cultivars were as follows: Fortune>Angeleno>Friar>Black Amber>Santa Rosa and Red Beaut. The seasonal incidence of aphid was also studied under the field condition, which showed that the highest mean aphid population was recorded during March (113.17/10 leaves), followed by April (74.00/10 leaves), and declined in May (17.30/10 leaves). These findings suggest that the B. helichrysi resistance of cultivars, mainly Fortune and Angeleno, is influenced by the total phenolic compounds in their leaves. The negative correlation observed between phenolic compounds and aphid incidence suggested a potential role of phenolic compounds in mediating plant resistance to aphids. The findings will inform integrated pest management strategies for plum cultivation, promoting crop resilience and ensuring food security.

When the body speaks during wartime: Clinical presentation of older vs. younger adults in psychiatric emergencies during wartime.

Familial hypercholesterolaemia (FH) is a common but underdiagnosed genetic condition that leads to high low-density lipoprotein cholesterol and premature cardiovascular disease. Cascade genetic testing remains underutilised as a screening approach. Implementation strategies can increase the diffusion of innovations such as genetic medicine into non-genetic specialty settings more rapidly through dissemination networks. This study aimed to evaluate the success of a multifaceted implementation strategy to increase cascade testing for relatives of a person diagnosed with FH using a primary-tertiary shared care model. A multisite effectiveness-implementation hybrid type III pre-post study was conducted between 2022 and 2024 to compare the implementation of a new shared care model for FH cascade testing in NSW, Australia. During the control period, cascade testing of relatives was offered to FH index cases by a genetic counsellor at the lipid clinic. In the implementation strategy period, FH index cases were offered a cascade testing expression of interest form to provide to their relatives. Relatives were contacted by a genetic counsellor and provided with a pre- and post-cascade testing package, which was also provided to their general practitioner. A total of n = 25 index and n = 6 cascade cases were included in the control period and n = 81 index and n = 56 cascade cases in the implementation period. The number of cascade genetic tests per index case increased significantly from 0.24 in the control period to 0.52 in the implementation strategy period (incident rate ratio = 4.62; 95% CI: 0.39, 8.84; p = 0.032). Among relatives tested, there was no difference in the proportion with a confirmed FH gene change per index case (IRR = 2.15; 95% CI: 0.65, 7.01; p = 0.207). There was no difference in the proportion of index cases with at least one cascade test (OR = 1.49; 95% CI: 0.53, 4.19; p = 0.442). Implementation of our model increased FH cascade testing compared to previous standard care. These findings suggest a greater role for cascade testing in primary care settings. This opens new opportunities for integrating genetic screening into routine general practice, particularly for autosomal dominant conditions such as FH.

Safety of remibrutinib in chronic spontaneous urticaria: a pooled analysis of REMIX-1 and REMIX-2 trials.

This pilot study aimed to evaluate whether replacing nighttime ibuprofen with melatonin, vitamin D, and vitamin B12 (chronotherapy) improves postoperative recovery after third molars extraction, and to explore sex-dependent responses. A double-blind, randomized, two-period pilot crossover trial was conducted with 12 healthy adults undergoing bilateral mandibular third molars extraction. In the control period, participants received ibuprofen 400mg three times daily. In the chronotherapy period, the nighttime ibuprofen dose was replaced with melatonin (10mg), vitamin D (1000 IU), and vitamin B12 (1000µg). Outcomes included pain intensity (Visual Analogue Scale [VAS]), facial swelling, trismus, rescue medication use, and inflammatory cytokines. Overall, chronotherapy was associated with higher postoperative pain, increased vertical swelling, and reduced trismus compared with control. Significant treatment-by-sex interactions were observed. Female participants reported statistically higher, although clinically insignificant, postoperative pain scores with chronotherapy (mean VAS increase: +0.94 points, p < 0.001), along with greater swelling but less restriction in mouth opening. In contrast, males showed similar pain levels but a shorter time to pain cessation and reduced swelling with chronotherapy. Exploratory cytokine analyses suggested broader increases in pro- and anti-inflammatory mediators in males receiving chronotherapy (e.g., IL-10, IL-13), whereas females showed limited cytokine changes. Replacing nighttime ibuprofen with the chronotherapy regimen did not appear to improve overall postoperative pain outcomes. However, chronotherapy may produce sex-dependent postoperative responses, with mixed recovery patterns in females and modest benefits in selected outcomes in males. Given the pilot nature of the study and limited sample size, these findings should be considered exploratory and hypothesis-generating. ClinicalTrials.gov (NCT07133360), retrospectively registered on 2025/06/20.

Despite the emergency department (ED) being a primary entry point for acutely ill older adults, delirium in this setting remains poorly characterized. This study aimed to determine ED delirium prevalence, identify associated patient characteristics in a diverse population, describe current ED management practices, and examine hospital utilization outcomes in a large, heterogeneous cohort. This multi-site retrospective cohort study analyzed 2,827 older adult patients (≥ 65years) across three diverse EDs within a single integrated health system in the New York metropolitan area, identifying delirium via rigorous, validated in-depth chart review requiring evidence of acute change from baseline. Independent risk factors for ED delirium and hospital admission were identified via modified Poisson regression. Management strategies and 30-day hospital utilization outcomes were characterized. All analyses were stratified by control and intervention periods of a parent delirium screening trial. ED delirium prevalence was 16.0% (95% confidence interval: 14.6-17.4%), consistent across study periods and sites. The prevalence of delirium was 27.3% among hospitalized patients; 7.9% of all discharged patients had delirium. Independent risk factors included advanced age (adjusted relative risk, aRR = 1.01), dementia (aRR = 3.10), higher Charlson Comorbidity Index (aRR = 1.06), facility arrival (aRR = 1.28), and higher ED acuity (aRR = 3.85 for highest). Patients with delirium were more likely to receive physical restraints, psychoactive medications, and constant observation, but also safety precautions, family involvement, and palliative care consults (all p < 0.001). Delirium independently predicted hospital admission (aRR = 1.54) and was associated with higher 30-day readmissions (19% vs. 13%; p = 0.002). Approximately 1 in 6 older ED patients had delirium, including 7.9% who were discharged home. ED management involved both restrictive (restraints, psychoactive medications) and supportive (Goals-of-Care discussions, family involvement, safety precautions) strategies, though the latter remained underutilized. These findings underscore the critical need for standardized delirium screening, enhanced recognition, and supportive strategies.

Adults with attention deficit/hyperactivity disorder (ADHD) often experience difficulties regulating emotions and balancing activity and rest. Impairments such as motor skills challenges and reduced body awareness, including interpretation of sensory signals and attitudes toward the body, often receive little clinical attention despite their potential negative impact on daily functioning and health. The START intervention is a 12-week structured exercise program that combines regular physical exercise with mindful attention to the body during movement. This study aimed to evaluate the effect of the START intervention on body awareness and movement quality in adults with ADHD. In this randomized controlled trial, 63 adults with ADHD were assessed for body awareness and movement quality before and after a 12-week intervention or treatment-as-usual control period using the Body Awareness Scale - Movement Quality and Experience. Thirty-nine participants completed the study (26 intervention/13 control). Participants in the intervention group showed significantly greater improvement in body awareness compared to the control group, both in total score and in subscales for muscular tension and physical activity. Movement quality improved significantly within the intervention group, although no significant between-group differences were observed. Structured physical exercise with mindful attention to the body enhanced body awareness in adults with ADHD compared to standard care. Effects on movement quality were not statistically different between groups and therefore remain uncertain. These findings suggest that such exercise may be a useful complement to conventional treatments and may support a healthier relationship with the body.

Effects of 16-week aerobic exercise and whole-body vibration on myokines and neurocognitive indices in postmenopausal women: A randomized control study.

A retrospective-present-day analysis on acquired premature ejaculation.

The need for long-term support: Five-year outcomes after severe injury in older adults.

We examined the impact that 12-weeks of high-intensity interval training (HIIT) had on aerobic fitness and popliteal artery endothelium-dependent (flow-mediated dilation, FMD) and -independent dilatory function (nitroglycerin-mediated dilation, NMD) in response to an acute bout of prolonged sitting. Twenty-one healthy adults were assigned to HIIT (n = 11, 7♀, 24 ± 8 years) or Control groups (n = 10, 6♀, 22 ± 1 years). Popliteal artery FMD response to 5-min distal cuff occlusion and NMD were assessed via duplex ultrasonography before and after ~ 2-h of uninterrupted sitting. Peak oxygen consumption (relative V̇O2peak) was assessed using a maximal cycle ergometer protocol. All assessments were repeated following the HIIT (2 × 20-min bouts alternating between 15-s intervals at 100% of peak aerobic power and passive recovery) or Control (usual physical activity) periods. The 12-week HIIT intervention improved relative V̇O2peak (35.4 ± 7.8 to 39.5 ± 6.1ml/kg/min, P = 0.005), with no changes observed in the Control group (P = 0.306). Pre-sitting popliteal artery FMD and NMD did not differ from Baseline to Follow-up in either group (all, P ≥ 0.173). In both groups, prolonged sitting attenuated FMD and NMD at Baseline and Follow-up (all, P ≤ 0.076). Sitting-induced changes in popliteal artery FMD (HIIT: -1.4 ± 2.6 to -1.7 ± 1.9%; Control: -2.9 ± 2.2 to -2.0 ± 2.3%) and NMD (HIIT: -3.1 ± 2.9 to -3.2 ± 2.5%; Control: -3.0 ± 2.9 to -3.8 ± 3.7%) were not different between Baseline and Follow-up in either group (all, P ≥ 0.327). A 12-week HIIT intervention improved aerobic fitness but did not provide protection against prolonged sitting-induced impairments in popliteal artery endothelial function or vascular smooth cell function.

Motor imagery (MI) training can enhance maximal strength, making it a promising tool for both athletic performance and clinical rehabilitation. Yet, the mechanisms underlying the increase in maximal strength, usually attributed to neural adaptations, remain to be further elucidated. We therefore aimed at investigating whether four weeks of MI training was likely to affect dorsiflexor strength and tibialis anterior motor units (MU) behavior. Twenty-four healthy adults (12 women; 24.5 ± 3.3 years) were tested at baseline, after a control period (pre-training), and after a 4-week kinesthetic MI training (post-training). Outcomes included maximal voluntary isometric dorsiflexion torque (MVC) as well as MU recruitment and derecruitment thresholds, discharge rates during recruitment, plateau, and derecruitment phases, input-output gain and net discharge-rate changes (ΔDR) recorded from high-density electromyography during submaximal contractions at 35%, 50%, and 70% MVC. At post-training, MVC increased by 7.1 ± 10.7% (p < 0.002) with no baseline to pre-training difference (p = 0.97). Discharge rates at recruitment (p = 0.06), plateau (p = 0.76), and derecruitment (p = 0.88) were not affected by MI training. Recruitment (p < 0.001), but not derecruitment thresholds, rose post-training. Input-output gain was stable (p = 0.36), and ΔDR increased only at 70% MVC between baseline and post-training (p = 0.002). Four weeks of MI training increased force without any change in MU discharge rate and intrinsic MU properties, yet with increased recruitment threshold of MUs.

Eriochloa villosa is a destructive pernicious weed threatening maize production in Northeast China. While species distribution models (SDMs) identify potential habitats, they often overestimate risk areas, leading to inefficient resource allocation. Bridging the gap between macro-scale prediction and field-level management remains a critical challenge for precision agriculture. We developed an integrated risk navigation framework combining a stacked ensemble SDM (AUC = 0.932) with field-verified economic parameters. Through controlled field experiments, we established a management-oriented economic threshold (ET) of 6.2 plants/m2 and a critical period for weed control (CPWC) of 32 days. Utilizing a novel 'anchor-point calibration' method, we translated ecological probabilities into a three-tiered risk zonation. This approach compressed the priority management area by over 2200-fold compared to traditional statistical thresholds, identifying a High Economic Risk Zone of just 66 km2. The proposed framework concentrates management efforts on high-impact zones, drastically reducing the priority management footprint and optimizing resource allocation compared to conventional strategies. By explicitly incorporating prediction uncertainty, this study provides a highly efficient, scientifically robust decision support tool for pernicious weed management and pesticide reduction in maize systems. © 2026 Society of Chemical Industry.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly recognized chronic liver disorder in children and adolescents, particularly among those with obesity and insulin resistance. Given the emerging role of the gut-liver axis in disease pathogenesis, this study aimed to evaluate the effectiveness of synbiotic supplementation in improving biochemical and ultrasonographic outcomes in pediatric MASLD. This double-blind, randomized, placebo-controlled clinical trial was conducted over 8 weeks. A total of 60 participants aged 10-18 years with MASLD were randomly assigned to receive either synbiotics (n = 30) or placebo (n = 30). The synbiotic formulation contained a combination of nine probiotic strains with a prebiotic component, whereas the placebo consisted of prebiotic-only capsules (fructooligosaccharide with sucrose). The primary outcomes were predefined as changes in liver enzyme activities (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and hepatic steatosis grade assessed by ultrasonography, while secondary outcomes included body mass index (BMI) and lipid profile parameters. Between-group differences were analyzed using appropriate statistical models adjusting for baseline values. After 8 weeks, the synbiotics group showed statistically significant reductions in BMI (- 0.70 ± 0.16 kg/m2), triglycerides (- 10.50 ± 3.10 mg/dL), total cholesterol (- 10.50 ± 2.90 mg/dL), and LDL-cholesterol (- 5.46 ± 1.85 mg/dL) compared with the placebo group (all p < 0.001). Liver enzyme activities decreased significantly in the synbiotics group (ALT - 20.36 ± 7.18 U/L; AST - 16.76 ± 10.67 U/L), with greater reductions than in the placebo group (p < 0.001 for between-group comparisons). Furthermore, improvement in hepatic steatosis grade was observed in 73.3% of participants in the synbiotics group compared to 23.3% in the placebo group (p < 0.001). Synbiotic supplementation over an 8-week period was associated with significant improvements in liver enzyme activities, lipid profile, BMI, and ultrasonographic steatosis grade in children with MASLD. While these findings suggest a beneficial role for synbiotics as an adjunctive strategy, the relatively short intervention period and lack of control for lifestyle factors warrant cautious interpretation. Further studies with longer follow-up, detailed lifestyle assessment, and mechanistic investigations are needed to confirm these results and clarify the underlying pathways.Iranian Registry of Clinical Trials code: IRCT20220314054279N1.

Roots emerging from seeds encounter substantial mechanical resistance during soil entry. A transient root cap cuticle (RCC) forms early in development, yet its contribution to root tip function during this mechanically challenging transition remains unclear. Here, we define an early functional window in which the root tip is transiently optimised for establishment under soil-imposed constraints, and show that this window depends on the RCC. Consistent with a protective role, RCC-deficient seedlings were less efficient at traversing dense substrates and accumulated greater mechanical damage at the tip. Notably, RCC function extended beyond protection: when roots were grown on agar surfaces, RCC deficiency accelerated detachment of the outermost root cap cell layer and disrupted its layer integrity, indicating an additional role in maintaining coordinated root cap turnover. This early window faded with seedling age, preceding RCC loss, and coincided with a developmental reduction in gravitropic responsiveness, thereby defining a restricted period for directional control. RCC-defective mutants exhibited impaired gravitropism across stages, whereas hydrotropic responses were largely unaffected, linking RCC function specifically to gravitropic regulation. Together, these results delineate a transient establishment phase in which the RCC integrates mechanical protection, coordinated turnover, and gravitropic control to promote robust root function during early growth.