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1,4-Dioxane is a widespread groundwater contaminant frequently co-occurring with chlorinated solvents. The group-6 propane monooxygenase (PRM) from Mycobacterium dioxanotrophicus PH-06 degrades dioxane efficiently, yet the molecular determinants underlying its broad substrate spectrum and inhibition behavior remain unresolved. Here, we combined AlphaFold2-based structure prediction, molecular docking, and alchemical free energy calculations to systematically characterize ligand binding in PH-06 PRM. The catalytic center (residues 87-265), coordinated by two histidines and four glutamates, exhibited calculated binding free energies for five substrates (C2-C4 alkanes and cyclic ethers) that significantly correlated with experimentally determined degradation rates (p < 0.05), supporting the ability of ligand binding thermodynamics to capture major substrate-recognition trends in PH-06 PRM. In addition, we identified a remote binding site (residues 329-446) approximately 30 &#xc5; from the catalytic center. Thermodynamic analysis indicates that this remote site can attract methane and ethane, potentially limiting their access to the catalytic center. Comparative binding analyses of three common chlorinated solvent inhibitors (i.e., trichloroethylene [TCE], 1,1-dichloroethylene [DCE], and 1,1,1-trichloroethane [TCA]) revealed distinct site preferences consistent with their experimentally observed inhibition modes. Noncompetitive inhibitors (DCE and TCA) displayed stronger affinity for the remote site, whereas the competitive inhibitor TCE exhibited comparable affinity for both binding regions. Sequence conservation, contact probability analysis, and Gene Ontology enrichment further suggest the structural relevance of the remote site and its possible role in ligand recognition and inhibitor selectivity. These findings demonstrate that the AlphaFold-guided free energy calculations can capture experimentally observed substrate and inhibitor trends in PH-06 PRM, while identifying a remote ligand-binding pocket that warrants further mechanistic investigation.

This study aimed to describe rural data from the Australian National Study of Mental Health and Wellbeing survey (2020-2022) to assess strengths-based questions, differences by rurality, and factors associated with excellent social connectedness. Survey questions were mapped to the Rural Strengths Socioecological Framework. Descriptive and logistic analyses assessed rural adults' use of strengths by remoteness and presence of affective/anxiety disorders in the past 12&#x2009;months. Logistic regression explored factors associated with social connectedness. Survey questions reflected some strengths within the Framework including self-management techniques, family and friend support, social connectedness, and health care personnel. However, questions were primarily framed using a deficit perspective and many strengths from the Framework (i.e. nature, rural norms, culture, and lay personnel) were absent. Most strengths did not differ significantly between levels of rurality, though making healthy diet choices (as a self-management technique) was significantly lower in remote areas. Adults without affective/anxiety disorders more often reported good social support and self-efficacy. Conversely, those with affective/anxiety disorders were more likely to self-manage and access consultations for mental health. Excellent social connectedness was associated with better mental health. The survey questions reflected limited strengths. Future surveys should include a broader range of strengths-based questions spanning the extent of the Rural Strengths Socioecological Framework. Healthy diet choices as a self-management tool in remote areas may need to be prioritised. Findings also suggest the need for targeted approaches to protect, improve, or leverage social connectedness for those with more severe illness in rural areas.

All 17 of Nevada's counties carry a federal Health Professional Shortage Area (HPSA) designation, straining the state's capacity to deliver care remotely. This narrative review examines four dimensions of that capacity. It asks how telehealth is regulated and used, how far health information exchange and electronic health records have spread, whether broadband can support remote care, and what role artificial intelligence (AI) and remote patient monitoring (RPM) now play. Throughout, it considers how the state's workforce shortages, geography, and demographic diversity shape both demand for digital health and the barriers to it, with attention to equity. Four databases (PubMed/MEDLINE, CINAHL, Scopus, Google Scholar) were searched alongside federal, state, and policy grey literature for English-language sources from January 2015 to March 2026, yielding 88 sources, 40 peer-reviewed. Nevada has enacted comparatively expansive telehealth legislation, including conditional payment parity made permanent under Senate Bill 119 (2023); however, the limited utilization evidence shows uptake varying by race, ethnicity, and language. The sole statewide HIE operates under an opt-in consent model that constrains data availability, and roughly 100,000 Nevadans lack wireline broadband at the federal benchmark speed, concentrated in rural areas. AI and RPM are being deployed in rural settings without published evaluation, and nearly all peer-reviewed evidence on Nevada's digital health derives from a single study. Nevada's policy framework has outpaced its infrastructure and equity conditions; closing that gap requires coordinated action across HIE consent reform, broadband-telehealth alignment, Medicaid RPM reimbursement, and community-level investment in digital literacy and language access.

This study presents a comprehensive 15-year (2009-2023) assessment of persistent organic pollutants (POPs) in the Spanish atmosphere to evaluate the Stockholm Convention's effectiveness. Polyurethane foam passive samplers were deployed across 23 sites to monitor legacy pesticides and industrial chemicals. Results reveal a concentration hierarchy dominated by hexachlorobenzene (HCB), which accounted for a median of 41% of the &#x2211;POP concentrations and displayed a remote-enriched spatial pattern characteristic of global distillation. In contrast, legacy pesticides and indicator polychlorinated biphenyls (iPCBs) were influenced by temperature-dependent secondary volatilization from historically contaminated soils, as indicated by Clausius-Clapeyron analyses. These compounds frequently exhibited an unexpected urban enrichment likely associated with heat island effects, while polybrominated diphenyl ethers (PBDEs) displayed a pronounced urban gradient (a 35-fold increase from remote baselines) driven by the late-regulated BDE-209. Long-term temporal analyses underscore a sharp regulatory dichotomy. Early-banned compounds, such as endosulfan, HCB and dichlorodiphenyltrichloroethane (DDT), and lighter PBDEs, are experiencing rapid environmental depletion, with significant annual declines of up to -33%. Conversely, pentachlorobenzene (PeCB), iPCBs, and BDE-209 show stalled or locally increasing trends (up to +20%), sustained by unintentional combustion, active consumer goods, and regulatory lag times. Altitudinal profiling across Tenerife sites highlights this divergence: coastal areas reflect local secondary emissions, whereas high-altitude observations confirm the progressive clearance of the global free troposphere. Overall, these findings provide new insights into the spatial and temporal dynamics of atmospheric POPs, reaffirming the role of long-term monitoring in guiding international abatement strategies.

Health-related quality of life (HRQoL) is frequently impaired in cirrhosis. Among the most critical components of reduced HRQoL in cirrhosis is disturbed sleep. Despite the importance of sleep in cirrhosis and overall health, sleep is rarely clinically assessed and the specific aspects of sleep which drive reduced wellbeing are understudied. Remote monitoring with wearable technology may facilitate sleep assessment and targeted intervention. We enrolled 119 participants with cirrhosis across two academic medical centers and collected baseline clinical, cognitive and laboratory assessment and 6 months of longitudinal wearable tracking with an Oura Ring. HRQoL was assessed with the Chronic Liver Disease Questionnaire (CLDQ) and subjective sleep quality with the Pittsburgh Sleep Quality Index. Association of sleep metrics with HRQoL and subjective sleep was assessed in multivariable mixed effects model, with mediation analysis further analyzing the relationship. Across analysis of 12516 sleep episodes in 88 participants who completed all assessments and &#x2265;14 valid sleep nights, there was a strong association between measured sleep and reported sleep quality as well as HRQoL, with reduction in sleep efficiency, overall sleep time, and sleep regularity index (SRI). In adjusted mediation analyses, SRI was the strongest mediator (49.9% total mediation effect, ACME = - 0.093, p<0.001) of the relationship between liver disease severity (as measured by Child-Turcotte-Pugh Score) and CLDQ. In a large prospective study of remote sleep monitoring in liver disease, we found that sleep regularity had a strong association with patient-reported sleep quality and wellbeing, and was the strongest sleep metric mediating the relationship between progressive liver disease and overall HRQoL. These findings suggest the potential for circadian-targeted interventions in patients with cirrhosis. Sleep impairment is a major contributor to reduced wellbeing in cirrhosis, but existing sleep assessments often are too cumbersome to be used clinically and fail to capture long-term sleep patterns and circadian disruption. Using six months of wearable-derived sleep data, this study identifies sleep irregularity, as captured by the Sleep Regularity Index, as the sleep metric most strongly associated with patient reported sleep and overall wellbeing impairment. These findings suggest that sleep regularity, a marker of circadian rhythm dysfunction, may be an important digital biomarker for progressive worsening in cirrhosis and highlight a possible target for future interventions. If validated in future studies, wearable monitoring of sleep could provide clinicians and researchers a scalable approach for identifying patients with cirrhosis at increased risk for impaired wellbeing through sleep disturbance and monitor response to treatment.

Plastic pollution is an ever-growing concern around the globe, with current research portraying the presence of contaminants even in previously pristine regions. Especially small particles, micro- and nanoplastics, can be dispersed over long stretches by atmospheric transport, reaching even the most remote areas of the planet. This study aims to portray current levels of nanoplastic contamination (<&#x2009;1&#xa0;&#x3bc;m) by analyzing snow samples from high-altitude glaciers in the European Alps (2300-3800&#xa0;m) via TD-PTR-MS. We were able to detect six common plastic pollutants, with PE and PP contributing over 60% of the total mass concentration measured across all sites. On average, nanoplastic concentrations of 85 ng mL-&#x2009;1 (range: 3.6&#x2009;&#xb1;&#x2009;12 ng mL-&#x2009;1 - 470&#x2009;&#xb1;&#x2009;76 ng mL-&#x2009;1) were detected at sampled glacier surfaces. Access to these remote regions was enabled through a citizen-science initiative, involving trained mountaineers for sample collection. The results were applied to atmospheric modelling, highlighting possible point sources of contamination. While agriculture and local plastic factories were revealed as potential sources of nanoplastics, spatial and temporal limitations complicated comparison inside the sample cluster.

ObjectiveThis study examined perspectives of rehabilitation professionals and environmental designers to identify benefits, challenges, and design considerations for outdoor therapy spaces.BackgroundThe therapeutic potential of nature-based environments has gained recognition among researchers, healthcare practitioners, and designers, highlighting an opportunity to leverage outdoor environments in physical and occupational therapy. However, our understanding of the benefits, challenges, and considerations for implementation remains limited.MethodsThis exploratory qualitative study used thematic analysis of in-depth semistructured interviews following Braun and Clarke's six-phase framework. Interviews were conducted remotely with a purposive sample of 23 rehabilitation professionals (physical therapists, occupational therapists, horticultural therapists, and medical staff) and design practitioners (landscape architects, architects, and planners) involved in outdoor rehabilitation.ResultsFive primary themes were identified related to benefits, challenges, and design considerations: holistic health impact, real-world activities as therapy, the control-choice paradox, hazards and discomforts, and logistical and management barriers. Two distinct spatial typologies emerged: publicly owned, dispersed sites and privately owned, centralized sites. Nineteen environmental features were identified as high priority, with terrain variety (91%), environmental variety and choice (87%), and graduated challenge (70%) most frequently cited. Rehabilitation professionals emphasized practical concerns and therapeutic functionality, while designers prioritized sensory diversity and spatial arrangement.ConclusionOutdoor rehabilitation environments offer holistic health benefits and real-world therapeutic opportunities but require careful planning to address logistical barriers and environmental challenges. Successful implementation depends on early engagement of therapists and the establishment of supportive organizational cultures. Cross-disciplinary collaboration between therapists and designers is essential.

Pine wilt disease (PWD), caused by the pine wood nematode (Bursaphelenchus xylophilus), continues to threaten forest ecological security. Unmanned aerial vehicle (UAV) remote sensing makes large-scale screening feasible, but accurate canopy segmentation remains difficult in practice. The main obstacles are threefold: (i) canopy appearance changes noticeably from early to late infection stages, which can cause model representations to drift toward later-stage symptoms and weaken subtle early-stage cues; (ii) dense pixel-wise annotation is costly, making semi-supervised learning dependent on imperfect pseudo-labels; and (iii) forest backgrounds are cluttered and often visually similar to diseased regions, limiting the discriminative ability of RGB appearance alone. To address these three practical difficulties, we build a standardized UAV canopy dataset for PWD and develop a lightweight multimodal segmentation framework. The method combines three components. First, Nested-Tempo Memory Consolidation (NTMC) is designed as a stage-aware extension of EMA-based teacher-student learning. It maintains nested fast/medium/slow temporal trajectories to retain stage-specific knowledge while improving cross-stage stability during Early-Middle-Late sequential training. Second, Drift-Compensated Consistency Regularization (DCCR) integrates reliability calibration into semi-supervised consistency learning, so that unlabeled samples contribute training signals mainly when they are sufficiently reliable, reducing error accumulation from noisy pseudo-supervision. Third, Vegetation-index-conditioned Cross-Modal Attention (VCCA) uses vegetation indices-Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI)-as physiological cues to modulate visual features, thereby reducing the dependence on RGB appearance and improving feature discrimination under texture-similar forest backgrounds. Experiments on one in-house dataset and three external datasets show consistent improvements in mean intersection over union (mIoU), F1-score, and Matthews correlation coefficient (MCC). With all components enabled, the framework improves mIoU from 0.6015 to 0.6829 over the baseline and produces cleaner disease boundaries with fewer background false alarms, demonstrating its potential for practical UAV-based forest disease monitoring.

South Asian summer monsoon (SASM) delivers substantial rains to the Indian subcontinent and drives strong upwelling in the Arabian Sea, making marine upwelling records and terrestrial rainfall records two primary proxies for reconstructing past SASM variability. However, on orbital timescales, these two sets of records vary largely in opposite directions: the upwelling records are in-phase with Southern Hemisphere (SH) summer insolation, whereas the rainfall records are in-phase with Northern Hemisphere (NH) summer insolation. This leaves a long-standing debate on whether SASM is driven by NH or SH insolation. Here, combining paleoclimate records with transient climate simulations that explicitly separate the effects of the NH and SH insolation forcing, we show that the SASM rainfall is dominated by the NH insolation, whereas the Arabian Sea upwelling is forced predominantly by the SH insolation. When boreal summer occurs at perihelion, insolation is strongly enhanced not only in the NH but also in the tropical-subtropical SH. The former enhances the SASM rainfall through Eurasian warming, while the latter weakens the Arabian Sea upwelling by inducing South African warming and subsequent atmospheric teleconnections over the Indian Ocean. Our study reconciles the long-standing debate, and more broadly, reveals that warming in South Africa could exert a significant and previously overlooked remote forcing on the SASM system in past and future climate changes.

Hamstring flexibility can potentially affect the mobility and function of remote musculoskeletal areas, including the cervical spine and temporomandibular joint (TMJ), thereby increasing tension along the myofascial chain and potentially reducing mouth opening, contributing to orofacial discomfort. This review aims to inform clinical practice by exploring the integrated impact of these interventions within the framework of neuro-myofascial connectivity. A comprehensive search was performed across PubMed, Scopus, Web of Science, and PEDro databases spanning the period from the year 2006-2025, restricted to studies published in the English language. Keywords and MeSH terms corresponding to hamstring stretching, mouth opening and Temporomandibular Joint (TMJ) mobility were used incorporating Boolean operators. Randomized control trials and experimental studies investigating acute or short term effects of hamstring stretching on Temporomandibular Joint (TMJ) pain and mouth opening were included. The preliminary results indicate that hamstring stretching can result in temporary improvements in pressure pain threshold and mouth opening; however, the results should be interpreted with caution and the number of the RCTs is small and heterogeneous. The findings support the possibility of myofascial and neural interconnections between the posterior chain and masticatory system; however, the current evidence is insufficient to establish definitive mechanistic conclusions. PROSPERO number: CRD420251173297.

Limited access to prenatal care, particularly in maternity care deserts and other underserved communities, contributes to maternal and fetal health disparities. Advances in telehealth and wearable fetal monitoring technologies, including fetal electrocardiography, offer opportunities to support remote fetal assessment and supplement traditional prenatal care. Understanding the acceptability of these technologies among potential users is important for informing future device development and implementation. This study aims to evaluate perceptions of acceptability and user preferences regarding a wireless fetal heart monitor among women of reproductive age. A survey was designed to assess the acceptability and user preferences of a wireless fetal monitoring device among women of reproductive age to guide device development. The survey was administered using the Qualtrics XM online survey platform. The survey was distributed using snowball recruitment through community and online postering. Compensation was offered to survey respondents. Data were analyzed using SPSS (version 29). A total of 163 participants completed the survey, with 103 responses to acceptability questions. Older women aged 30 to 49 years showed higher rates of acceptability (40/54, 74.1%) than young women aged 18 to 29 years (26/49, 53.1%). In total, 70.7% (73/103) of the participants preferred a device measuring 2.5 &#xd7; 7.6 cm or smaller. Designing a device that incorporates patient preferences may increase the likelihood of patient adoption and consistent use. This study examined perceived acceptability of a hypothetical monitoring device, providing a preliminary foundation to inform future device development and acceptability assessment.

Little is known about dementia incidence and its risk factors in people older than 90 years, particularly in heterogeneous populations. We evaluated dementia incidence and examined the associations of sex, race and ethnicity, and APOE genotype with dementia risk after age 90 years using data from LifeAfter90, an ongoing prospective cohort study. LifeAfter90 is a prospective cohort study that enrolled Kaiser Permanente Northern California members, who were at least 90 years old, from the San Francisco Bay Area and Sacramento, USA. Participants were clinically evaluated every 6 months from July 17, 2018, to Nov 9, 2024, in person or remotely. Incident all-cause dementia was diagnosed by a combination of physician assessment, Clinical Dementia Rating, and a Functional Activities Questionnaire. Sex, race and ethnicity, and education were captured during in-person assessments; APOE genotyping was performed using salivary DNA. We estimated age-standardised dementia incidence rates and used age-adjusted Cox and Fine-Gray competing-risk models to study the association between sex, race and ethnicity, APOE genotype, and dementia. The Fine-Gray subdistribution hazard ratio (sHR) models treated death as a competing risk. Models were adjusted for age (time-scale) and individuals were followed until dementia diagnosis or end of follow-up. Of 1120 individuals initially available, 96 with prevalent dementia and 219 with only one clinical evaluation were excluded; 805 participants were included. Median age was 92 years (range 90-103), 494 (61%) were female, 209 (26%) Asian, 191 (24%) African American or Black, 157 (20%) Hispanic or Latinx, 228 (28%) White, and 20 (2%) from other racial or ethnic groups; 413 had APOE data. During mean follow-up of 2 years (SD 1&#xb7;7), 138 (17%) developed dementia and 295 (37%) died. The age-standardised incidence rate was 116&#xb7;82 cases per 1000 person-years (95% CI 93&#xb7;69-139&#xb7;96). In Fine-Gray models, dementia risk was higher in female than in male participants (subdistribution hazard ratio [sHR] 1&#xb7;89, 95% CI 1&#xb7;30-2&#xb7;76) and Black than Asian participants (sHR 1&#xb7;75, 1&#xb7;07-2&#xb7;88), lower in APOE &#x3b5;2 carriers than in non-carriers (sHR 0&#xb7;39, 0&#xb7;17-0&#xb7;88), and not significantly higher in APOE &#x3b5;4 carriers than in non-carriers (sHR 1&#xb7;51, 0&#xb7;92-2&#xb7;47). No significant differences were found by education. Ethnoracial disparities in dementia risk appear to persist after 90 years, and the association between APOE &#x3b5;4 and dementia might differ by sex. These findings reinforce the importance of dementia screening and surveillance, even among people with exceptional longevity. National Institute on Aging.

Cardiac rehabilitation (CR) aims to enhance cardiovascular health and quality of life, as well as survival through structured exercise training, lifestyle education, cardiovascular risk factor management, and psychosocial support. Despite growing evidence linking sleep disorders, poor sleep health, and circadian rhythm disruption to impaired cardiac recovery, reduced exercise adherence, and increased adverse cardiovascular events, systematic assessment and management of sleep and circadian health remain underutilized in CR programs. In this narrative review, we aim to explore and characterize the gap and address the potential benefits of incorporating sleep and circadian rhythm assessment into CR practice. Sleep disorders commonly encountered in patients undergoing CR, including obstructive sleep apnea, central sleep apnea, and insomnia, may adversely affect CR participation, functional recovery, and cardiovascular prognosis. Practical strategies include routine sleep screening with validated assessment tools, selective use of objective sleep assessments, sleep hygiene education, chronotype-informed exercise scheduling, and referral pathways to sleep medicine specialists. Integrating sleep-circadian considerations into CR may enhance cardiac recovery, improve exercise tolerance and adherence, and support more comprehensive, personalized secondary prevention strategies. Artificial intelligence may further support early detection of sleep disturbances, individualized exercise prescription, remote monitoring, and precision CR approaches integrating sleep and circadian health.

Behavioral weight loss interventions (BWL) consisting of remote coaching and self-monitoring have limited effectiveness in breast cancer (BC) survivors. We conducted a single-arm phase II study evaluating addition of Contrave&#xae; for <5% weight loss (%WL) after 2-months of BWL. Women with prior stage 0-III BC and BMI &#x2265;27 kg/m2 were eligible and initiated BWL. We collected weight, patient-reported outcomes, and labs at baseline, 2- and 6-months. At 2-months, participants with &#x2265;5%WL (FAST-BWL) continued BWL; those with <5%WL (SLOW-BWL) received BWL+Contrave&#xae;. The primary endpoint was proportion of SLOW-BWL with &#x2265;5%WL at 6-months, with 30 participants providing 80% power with 5% type I error. Paired t-tests, Kruskal-Wallis tests and mixed-effects models were utilized. Of 55 participants, 2 withdrew prior to 2-months. At 2-months, 15 (28.3%) were FAST-BWL with mean%WL (SD) of 7.2% (1.5); and 38 (71.7%) were SLOW-BWL with mean%WL of 1.2% (2.2). Mean%WL between 2-6 months was similar in SLOW-BWL (3.8%&#xb1;3.6) and FAST-BWL (3.6%&#xb1;2.6). At 6-months, mean%WL was 5.1% (2.9) for SLOW-BWL and 10.8% (3.5) for FAST-BWL; 13/15 (86.7%) FAST-BWL and 16/38 (42%) SLOW-BWL had &#x2265;5%WL. Physical function and pain improved with &#x2265;5%WL (p=0.03 and p=0.02, respectively). SLOW-BWL had improved HbA1c (p=0.003) and triglycerides (p=0.04). Gastrointestinal symptoms were reported in 74% of SLOW-BWL. Of six withdrawals on Contrave&#xae;, one was due to adverse events. Adding Contrave&#xae; for BC survivors with minimal initial benefit from BWL results in clinically meaningful weight loss (&#x2265;5%) in 42% following 6 months of treatment, which also improves selective cardiometabolic risk factors.