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A simple statistical technique to improve seasonal predictions of northeast monsoon rainfall over India using selective ensemble mean
The journey to diagnosis and care of functional neurological disorder (FND)
Purpose Functional neurological disorder (FND) is a common condition, associated with high disability and healthcare costs, and poor treatment access. This qualitative study aimed to explore participants’ experiences of being diagnosed with functional neurological disorder (FND), accessing treatment, and navigating life after diagnosis. Participants were drawn from a randomised feasibility study of eye movement desensitisation and reprocessing therapy for people with FND (MODIFI, Trial Registration: NCT05455450 ( www.clinicaltrials.gov )). Methods Reflexive thematic analysis was used to analyse the data from eighteen semi-structured interviews with participants diagnosed with FND. Results Six main themes were identified: (1) the process of seeking a diagnosis and initial relief from the physical struggles, (2) receiving a diagnosis of FND, (3) treatment for FND, (4) the burden of FND in day-to-day life, (5) the need to assert agency and return to normal, and (6) hopes for the future. Conclusion The findings emphasize the need for personalised and compassionate care for individuals suffering from FND, underpinned by increased service provision within the healthcare system.
Resilience assessment of EMU train control onboard system considering degraded operation modes
Cryptic diversity in Astroblepus (Siluriformes: Astroblepidae): Integrative taxonomy reveals evolutionary complexity in the Esmeraldas River Basin, Ecuador
Astroblepus is a genus of endemic Andean catfishes with problematic taxonomy because of cryptic diversity, ambiguous historical descriptions, and morphological plasticity. This study applied an integrative taxonomy approach—combining DNA barcoding (COI gene), geometric morphometrics, and traditional morphological characters—to assess the species diversity within the genus Astroblepus in the Esmeraldas River basin (Ecuador), where five species are currently recognized. A total of 395 specimens were analyzed (386 for morphometrics, 33 for genetics), integrating both new and publicly available sequences. The molecular analysis delimited seven evolutionary lineages, exceeding previously known diversity. The validity of A. eigenmanni and A. fissidens was confirmed; a possible synonym between A. mindoensis and A. theresiae was suggested, and A. aff. mindoensis was recovered as their sister group. Within A. cyclopus we identified two cryptic lineages (5.6% divergence), and two new lineages ( Astroblepus sp. and A. aff. mindoensis ) were discovered, characterized by distinct morphometric autapomorphies. Geometric morphometrics revealed four morphological clusters, with significant segregation between A. cyclopus and Astroblepus sp., but overlap within more complex groups. Altitudinal distribution and isolation among sub-basins may be drivers of divergence. These results reveal an underestimated diversity in the basin, highlighting the need for formal taxonomic revisions, sampling in unexplored areas, and urgent conservation strategies considering habitat fragmentation.
CuAgent provides a RAG-assisted intelligent framework to investigate cuproptosis
Abstract Cuproptosis is a novel form of regulated cell death driven by intracellular copper accumulation, leading to lipoylated protein aggregation and Fe-S cluster destabilization. Dysregulation of this process has been implicated in various pathological conditions, including cancers, neurodegenerative diseases and metabolic diseases. Despite rapidly growing interest in cuproptosis, a systematically curated intelligent agent dedicated to cuproptosis-related genes (CRGs) and their disease associations remains lacking. To address this, we constructed a cuproptosis-related artificial intelligence (AI) knowledge base, named CuAgent, by manually curating 465 experimentally validated CRGs and 163 associated diseases. CuAgent introduces an innovative intelligent agent that enables users to perform natural language queries and receive data-driven responses. In addition, agent offers gene queries and analytical tools (expression profiling, survival analysis, protein interaction network visualization and correlation analysis). This study provides critical insights into cuproptosis progression, presenting a comprehensive and interactive resource to advance the understanding of cuproptosis. URL: https://bioinfor.nefu.edu.cn/CuAgent/home/ .
Association between physical activity and mental health (emotional and peer problems) in children and adolescents, a national follow-up study
Background While extensive evidence demonstrates the beneficial effects of physical activity on adult mental health, research examining these relationships in childhood remains limited and inconsistent. This study investigated the prospective associations between objectively measured physical activity and sedentary behavior at age 7 and emotional and peer difficulties at ages 11 and 14 using the UK Millennium Cohort Study. Methods Accelerometer-measured physical activity data from 6,434 participants at age 7 were analyzed. Emotional and peer problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) at ages 7, 11, and 14. Multiple linear regression models examined associations between physical activity levels (sedentary, light, and moderate-to-vigorous [MVPA]) and mental health outcomes, adjusting for baseline SDQ scores and demographic and socioeconomic covariates. Results Greater MVPA at age 7 was significantly associated with fewer emotional problems at ages 11 (β = −0.004, 95% CI [−0.007, −0.002], p = 0.002) and 14 (β = −0.004, 95% CI [−0.007, −0.001], p = 0.007), and fewer peer problems at ages 11 (β = −0.005, 95% CI [−0.007, −0.003], p < 0.001) and 14 (β = −0.005, 95% CI [−0.008, −0.003], p < 0.001). Sedentary time and light physical activity showed no significant associations. Lower socioeconomic status and parental stress were associated with greater emotional and peer difficulties. Conclusions Early childhood MVPA demonstrates protective effects against emotional and peer difficulties that persist into mid-adolescence. These findings provide evidence for the long-term mental health benefits of promoting MVPA in early childhood and highlight the importance of physical activity interventions for supporting healthy psychosocial development.
A dosimetry innovation using hybrid pixel detectors in interventional theatres
Abstract Healthcare professionals using fluoroscopic imaging systems rank among the most highly exposed workers to ionising radiations, yet current radiation protection detectors fail to provide accurate measurements in these scenarios. The pulsed structure of the X-ray beam produced by these medical devices poses significant challenges to conventional instruments in measuring and characterising time-structured radiation fields. Furthermore, radiation protection detectors consistently overestimate staff exposure at these low energies (< 100 keV) due to the inherent limitations of the dosimetric system currently in-use. In this study, we present a new hybrid pixel detector, originally developed for particle tracking and timing measurements in high-energy physics experiments at CERN, to overcome the above-mentioned challenges. By integrating single-photon energy measurement and precise timing capabilities, the detector enables highly accurate dose quantification across a broad range of diagnostic X-ray conditions while simultaneously resolving the spectral structure of radiation fields. Our findings demonstrate the detector’s suitability for advanced dosimetry assessment in clinical environments. It uniquely measures photon fluence and energy spectra in clinical X-ray fields, enabling accurate, pulse-independent determination of any exposure-related quantity. By giving access to fundamental radiation field parameters, this work lays the foundation for next-generation detectors that enhance staff safety and advance radiation epidemiology.
Stomatal responses of differently CO2-acclimated plants to natural and experimental CO2 gradients
Stomata, the microscopic pores in the epidermis of plant leaves, facilitate gas exchange between the leaf interior and the external environment and thus play a pivotal role in the global carbon, water, and energy cycles. Their development and function are influenced by atmospheric CO₂ levels. However, the mechanisms and the extent of this influence remain incompletely understood. Understanding the stomatal responses to variations in atmospheric CO₂ is essential for predicting their impact on future plant productivity or the role of vegetation as a carbon sink. We investigated the stomatal responses – specifically stomatal aperture and stomatal frequency – of C₃ plants acclimated to either ambient (approximately 40 Pa) or reduced (approximately 30 Pa) partial pressure of CO₂ (pCO₂). Stomatal responses were assessed both under natural conditions along an altitudinal gradient and under controlled experimental conditions with defined CO₂ levels (30 vs. 42 Pa). Our results showed that, under experimental conditions, stomatal frequency decreased with increasing CO₂ levels in both plant groups, regardless of their acclimation history. Furthermore, plants exposed to reduced pCO₂ exhibited smaller stomatal apertures compared to those grown at ambient pCO₂. Above-ground fresh biomass was higher at ambient CO₂ levels than at reduced levels. Interestingly, no significant difference in stomatal frequency was observed between plants that were acclimated and grown under reduced pCO₂ (at 2,970 m a.s.l.) and those under ambient pCO₂ (540 m). These results support the hypothesis that the inverse stomatal response to CO₂ – i.e., a reduction in stomatal frequency with increasing CO₂ levels – is a general physiological pattern in C₃ plants in the range of 30–42 Pa. However, this response pattern can be overridden by specific (locally occurring) environmental conditions such as low humidity or elevated temperatures. Furthermore, the findings are consistent with the optimal stomatal theory, which postulates that plants regulate stomatal conductance, including stomatal frequency and aperture, to maximize photosynthesis while minimizing water loss to achieve optimal water-use efficiency.
Advanced gravitational decision-making method inspired by newton’s law of universal gravitation
Healthcare resource utilization and cost burden of COVID-19 according to vaccination status in adults in Ontario, Canada, 2021–2023
Aims This study aims to describe healthcare resource utilization (HCRU) and cost burden associated with COVID-19 cases in Ontario, Canada, and assess variations by vaccination status. Methods We conducted a population-based retrospective cohort study using administrative health data from Ontario, focusing on COVID-19 cases from January 1, 2021, to May 31, 2023. Cases were identified by their first positive PCR test, and their healthcare interactions were followed for up to 12 months post-infection. All-cause HCRU and direct healthcare cost were compared before and after infection using generalized linear models. Results Data from a total of 1,321,174 COVID-19 cases were analyzed, with 87% having at least one healthcare interaction in the year preceding their infection. All-cause HCRU increased post-infection, with the greatest rise observed in the first month, largely attributable to hospitalizations (Mean [SD] hospitalizations per person per month [PPPM] at Month 1 vs. Look-back: 1.1 [0.3] vs. 0.1 [0.1], p < .0001) and ICU admissions (mean [SD] admissions PPPM at Month 1 vs. Look-back: 1.0 [0.1] vs. 0.1 [0.0], p < .0001). The healthcare cost per person rose in both the six and twelve months pre- versus post-infection. This increase is primarily attributable to ICU admission, hospitalization, and mechanical ventilation costs. On average, vaccinated individuals exhibited smaller increases in ICU costs (vaccinated: + CAD 5,838 to CAD 18,730 vs. unvaccinated: + CAD 24,597) and hospitalization costs (vaccinated: + CAD 623 to CAD 5,201 vs. unvaccinated: + CAD 9,072) six months post-infection compared to unvaccinated cases. Conclusions Data from this study cohort suggests that COVID-19 strains healthcare resources, namely as a result of hospitalization and mechanical ventilation. Vaccinated individuals demonstrated a reduced burden compared to their unvaccinated counterparts. These findings underscore the importance of vaccination in reducing severe outcomes and healthcare costs, providing insights for public health strategies and individual patient counseling.
Latent profile analysis and influencing factors of compassion fatigue in intensive care unit nurses
Selective Biomass Valorization via Cascade Photooxidation and Photothermal Hydride Shift
Unburnable carbon in the rapidly warming Arctic: Mapping spatial relationships among oil and gas development, ecologically sensitive areas and Indigenous Peoples’ lands
As global temperatures rise due to carbon emissions from fossil fuels, it is estimated that around 60% of oil and gas reserves —termed 'unburnable carbon'—must remain underground to meet international climate targets. The Arctic, warming nearly four times faster than the global average, is a frontline for both climate change impacts and oil and gas development, which pose severe risks to its fragile biodiversity and Indigenous communities. This study presents the first comprehensive spatial atlas of Arctic oil and gas infrastructure using open-access data, assessing overlaps with ecologically sensitive areas and Indigenous Peoples’ lands (IPLs) within the Conservation of Arctic Flora and Fauna (CAFF) boundary. The analysis identified 512,306 km 2 of exploited territory (1.82% of the Arctic region), 44,539 wells, 39,535 km of pipelines, and over 1.95 million km of seismic lines. Results show that 73.30% of hydrocarbon areas intersect IPLs and 7.57% overlap protected areas, with developments located in close proximity to key ecologically sensitive areas and culturally significant sites. These findings highlight the spatial overlaps and potential tensions between oil and gas industry interests and those behind the geographies of ecologically sensitive areas and IPLs, especially in zones such as Alaska’s North Slope and Russia’s Yamal Peninsula. The study calls for a paradigm shift in Arctic governance, from resource extraction toward equity, ecological preservation, and Indigenous inclusion. It supports the implementation of Arctic-specific supply-side climate policies, such as establishing an Arctic Fossil Fuel Non-Proliferation zone, to prevent further ecological degradation and to ensure a just transition. By integrating spatial justice criteria into decision-making, this work provides a tool for guiding sustainable and inclusive land-use and energy transition planning across the region.
HSN G1 demonstrates multifaceted therapeutic strategy against Alzheimer disease in APP PS1 mouse model
A Monte Carlo simulation study of sample size requirements for the Graded Response Model
Background The graded response model (GRM) is commonly used in psychometrics to analyze ordinal response data. Despite its growing application in scale development and validation, sample size recommendations—such as those provided by the COSMIN guidelines (e.g., n ≥ 1000)—are often based on expert consensus rather than empirical validation. Furthermore, the extent to which the number of items ( J ) and the number of response categories ( K ) contribute to parameter estimation accuracy remains insufficiently explored. Methods We conducted a Monte Carlo simulation to examine how three design conditions—sample size ( n = 500–1500), number of items ( J = 5–50), and a number of response categories ( K = 4–7)—influence the estimation accuracy of the latent trait parameter ( θ ) and the item discrimination parameter ( a ) under the GRM. For each condition, we generated a large population dataset based on predefined distributions for θ , a , and b , and then randomly drew samples ( n ) for estimation. The GRM was fitted using the EM algorithm. Estimation accuracy was evaluated using root mean squared error (RMSE), FPC-corrected RMSE, and Pearson’s correlation coefficient between true and estimated θ values. Results The RMSE of the discrimination parameter a decreased with increasing sample size ( n ) and number of items ( J ), while the effect of K was negligible. In contrast, the RMSE of θ was primarily influenced by J , with only minor effects from n and K . Notably, the Pearson correlation between true and estimated θ values consistently exceeded r = .98 across all conditions, suggesting high ordinal fidelity even with small samples. Increasing J beyond approximately 30 yielded diminishing returns in RMSE reduction. Conclusions Our findings suggest that sample size recommendations for GRM should be flexibly tailored to the measurement goal. For accurate estimation of θ , a sufficiently large number of items (e.g., J ≥ 30) can compensate for smaller sample sizes ( n ≈ 500), whereas precise estimation of a requires larger samples ( n ≥ 1000). The impact of increasing K was limited, indicating that additional response categories may not always enhance parameter recovery. These results provide empirically grounded guidance to support efficient and purpose-specific measurement designs in GRM applications.
Mechanistic insights into the disaggregation of amyloid-β fibrils by EPPS via replica-exchange molecular dynamics simulations
The effects of temperature on nestling growth in a songbird depend on developmental constraints
Climate change can adversely impact animals, especially those that cannot independently thermoregulate or avoid exposure to temperature variation. Altricial bird nestlings may be particularly vulnerable to temperature variation, with cold, hot, and variable temperatures leading to reduced nestling growth. At a broad scale, temperature effects on nestling growth vary across climatic zones, but how temperature effects vary with early-life developmental constraints imposed by the timing of thermoregulatory development, competition with siblings, and the amount of parental care has received less attention. We investigated whether the effects of temperature on the body mass of wild barn swallow ( Hirundo rustica erythrogaster ) nestlings (n = 113 nestlings, 31 nests) in Boulder County, CO depends on timing of exposure during development, relative size within the brood, or level of parental feeding. Lower minimum temperatures were associated with lower nestling mass in early but not late development (before but not after the putative development of thermoregulatory independence). Additionally, we found marginal evidence that the smallest nestling in the brood was more vulnerable to extreme and variable temperatures than other brood mates. Similarly, we found evidence that cold temperatures had stronger negative effects on nestlings in nests receiving low versus high levels of parent feeding. These findings indicate the existence of fine-scale heterogeneity in which the effects of temperature on nestling development are sensitive to metabolic constraints and early-life social environment, providing insight into the factors that may provide resilience to or exacerbate temperature effects on individual birds.
Expert experience-guided virtual datasets for adaptive automatic driving in metro trains
A flow cytometric assay of murine erythrocyte osmotic fragility
Flow cytometric test of erythrocyte osmotic fragility (EOF) is a critical diagnostic tool for evaluating membrane stability in hemolytic disorders and storage lesions of human erythrocytes. However, there is a lack of such protocols tailored for mice, one of the most widely used preclinical animal models. In this work, we developed and optimized a flow cytometric assay of murine EOF, which achieved results comparable to the conventional osmotic fragility test. We also validated the protocol by detecting membrane instability of murine erythrocytes induced by Ca² ⁺ -treatment, long-term storage, and phenylhydrazine (PHZ)-induced acute anemia, respectively. Our results showed that Ca² ⁺ -treatment impaired membrane integrity of mouse erythrocytes, resulting in reduced percentage of residual cells compared to the untreated ones (46.5 ± 9.5% vs 79.6 ± 5.3%, P < 0.0001). We found that murine erythrocytes can be stored in 1 x PBS containing 2% FBS at 4°C for one week with intact membrane stability (81.6 ± 4.6% of residual cells vs 82.1 ± 6.0% for the fresh samples, p > 0.05). In PHZ induced anemia model, significant hemolysis was observed at day 3 post injection. In conclusion, our flow cytometric assay of murine EOF is a powerful high-throughput assay for mouse models of membrane disorders, and holds substantial scientific and translational value for investigating pathoetiological mechanisms and developing therapeutic interventions.