共找到 20 条结果
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviours. Diagnosing ASD early is difficult for healthcare professionals due to its diverse and intricate presentation. However, early detection is vital for enhancing outcomes and enabling the children to access targeted therapies that support the development of social and communication skills. Moreover, Classical models were time-consuming and resource-intensive, and they required lengthy assessments and specialized training. To bridge these complications, this research proposes a Sales Training-Based Optimization enabled Deep High-Order Principal Component Network (STBO_DHPCNet) for ASD classification using resting-state fMRI (rs-fMRI) brain images from 1114 subjects in the ABIDE dataset. First, gamma correction is applied to enhance the quality of the autism brain image. Next, the Region of Interest (ROI) extraction is performed. Afterwards, the nub region extraction is performed based on Sales Training Based Optimization (STBO). On the other hand, feature extraction is done based on an enhanced brain image. Finally, the classification of ASD is done by using DHPCNet, and it is trained using STBO. Here, DHPCNet is developed by incorporating the Deep High-Order Attention Neural Network (DHA-Net) and Principal Component Analysis Network (PCA-Net). Moreover, the evaluation results show that the DHPCNet gained an increased range of accuracy, sensitivity and specificity as 95.62%, 94.79%, and 95.86%.
In France, methylphenidate, mainly used in the treatment of ADHD, has been subject to prescription restrictions that were relaxed at the end of 2021. This study analyses trends in methylphenidate consumption in France and examines changes following the modification to prescribing rules in 2021. This ecological study was based on data from the Medic'AM database, which records reimbursed outpatient drug dispensation in France from January 2016 to December 2023. Methylphenidate sales were expressed as defined daily dose per thousand inhabitants per day (DDD/TID) and expenditure as euros per thousand inhabitants. Time-series analyses were conducted to assess changes in methylphenidate sales and associated expenditure following modifications to prescribing arrangements in September and November 2021. Methylphenidate consumption rose from 0.607 DDD/TID per month in 2016 to 1.457 DDD/TID in 2023, an increase of 84%. Associated expenditure followed a similar upward trend. A more pronounced increase in methylphenidate sales was observed after the end of 2021. The study shows a clear increase in methylphenidate sales after 2021, coinciding with changes in prescribing regulations. Given the ecological design, this temporal association cannot be interpreted as causal. The observed trends likely reflect multiple factors, including regulatory changes, increased recognition of ADHD, and evolving clinical practices. These findings highlight how changes in prescribing policies may be associated with variation in healthcare utilization and expenditure. In France, methylphenidate, a medication mainly used to treat attention‐deficit/hyperactivity disorder (ADHD), has been subject to strict prescribing rules, which were relaxed at the end of 2021. These changes allowed community‐based specialists to initiate treatment and extended access to adults. Using national health insurance data on outpatient drug dispensations from 2016 to 2023, this study examined trends in methylphenidate sales over time. Use increased by 84% during this period, along with a rise in related healthcare expenditure. A more marked increase was observed after the changes in prescribing rules in 2021. Because this study was based on aggregated data, it cannot determine whether these policy changes directly caused the increase. However, the findings suggest that regulatory changes, along with other factors such as improved recognition of ADHD, may have contributed to increased use of methylphenidate. Overall, this study shows that changes in prescribing rules may be associated with changes in medication use and healthcare spending.
The goal of this study was to describe characteristics of warnings from state cannabis programs in the United States. From September 2024 to February 2025, we compiled regulations related to cannabis warnings on product packages in states with legalized cannabis sales (medical and adult-use), verifying regulations with regulators from each state. Two coders independently coded warning regulations for different characteristics. We identified 60 state cannabis programs across the United States with legalized cannabis sales, of which 56 (93%) required cannabis warnings. Of the programs requiring warnings, 55% included warning content about a specific health risk, most often addiction (41%). Few programs had warnings about cannabis' effects on mental health (16%), respiratory health (5%), or cardiovascular health (4%). Few programs required warnings to contrast with backgrounds (23%), rotating warnings (7%), or front-of-package warnings (4%). The mean number of words in warnings was 57 (Standard Deviation: 30), and the mean reading level was 9th grade. Although 93% of cannabis programs with legalized sales require warnings, only half mention specific health risks; less than 10% require rotating or front-of-package warnings; and warnings may be difficult to read and understand. Further research is vital to strengthen cannabis warning labels.
Background Recreational cannabis legalization has expanded rapidly in the United States; however, population-level analyses examining its association with traffic fatalities yield mixed results. These heterogeneous findings arise from methodological limitations, including short follow-up windows, a focus on early-adopting states, and methods that do not adequately account for staggered policy adoption. Methods We analyzed a 50-state panel (2005-2024) using an imputation-based difference-in-differences estimator designed for staggered policy adoption. The outcome was the log traffic fatality rate per one billion vehicle miles traveled. We estimated effects from the year of legalization through year four, with four pre-treatment years to assess parallel trends. The primary model included state- and year-fixed effects and controlled for demographic composition, weather (precipitation and annual average temperature), unemployment, traffic safety laws, and COVID-19 mortality. Sensitivity analyses estimated robustness by varying the sample composition (excluding early adopters, pandemic years, and Florida), modifying the treatment definition (legalization effective date vs. retail sales start), and including Poisson count-model replication. Results The panel included 1,000 state-year observations; the primary difference-in-differences analysis used 951 observations meeting all inclusion criteria. Post-legalization, traffic fatality rates increased by approximately 4.2% in the legalization year (τ=0: 0.041; 95% confidence interval (CI): 0.006, 0.077; p=0.022) and 6.1% by year four (τ=4: 0.060; 95% CI: 0.007, 0.112; p=0.027). Pre-treatment trends were parallel between treatment and control groups (joint test: χ²(4)=4.93; p=0.295), and the post-legalization increase was statistically significant overall (joint test: χ²(5)=11.56; p=0.041). Findings remained consistent when excluding early-adopting states, pandemic years, or Florida, and a Poisson count-model replication produced the same direction and magnitude. When treatment was instead indexed to the start of retail sales, no increase was observed in the first year (τ = 0: 0.011; 95% CI: -0.027, 0.050), and the overall post-retail joint test did not reach conventional significance (p = 0.067). Conclusion Legalizing recreational cannabis was followed by a rise in traffic deaths during the first four years after the law took effect. The increase began at legalization rather than at the start of retail sales. This suggests that the change in law and shifting public attitudes had a greater impact on traffic safety than the availability of cannabis in stores. States considering legalization should prepare traffic safety measures in advance, while those that have already legalized should reinforce existing efforts to address ongoing risks.
Alcohol is a major preventable risk factor for cancer, causally linked to seven types of cancer. Yet the potential cancer-preventive impact of population-level alcohol control policies remains unquantified; this study provides the first such estimates for the European Union (EU). We conducted a modelling analysis for 27 EU countries to estimate changes in alcohol consumption and alcohol-attributable cancer incidence. Four policy scenarios were examined, based on real-world studies from high-income economies reviewed in the International Agency for Research on Cancer Handbooks of Cancer Prevention Volume 20B: increased alcohol excise taxation, a Sunday alcohol sales ban, a national alcohol marketing ban, and an integrated alcohol policy implemented in Lithuania Relative changes in recorded alcohol consumption were applied to 2012 exposure data to estimate cancer incidence in 2022, assuming a 10-year latency period. Alcohol-attributable fractions were calculated for seven causally related cancers by country, sex, and age, with uncertainty quantified using Monte Carlo-like simulation. In 2022, an estimated 146,194 cancer cases (16.1% across seven causally related sites) in the EU were attributable to alcohol. All policy scenarios would have reduced cancer incidence across the EU. The integrated policy scenario would avert 9220 cases (95% UI: 8568-9833; 6.5% of alcohol-attributable cases). Increased taxation would avert 8387 cases (95% UI: 7954-8 862, 5.9%), a Sunday sales ban 5491 cases (95% UI: 5365-5 618, 3.8%), and a marketing ban 6434 cases (95% UI: 5899-6 973, 4.5%). The largest absolute reductions were for female breast, and oesophageal cancers. Implementation of major alcohol policies could prevent thousands of cancer cases in the EU. Population-level alcohol policies represent an underused tool for cancer prevention and should be integrated within EU and national cancer control frameworks. EU4Health Programme (SANTE/2022/SI2.883729); French National Cancer Institute (INCa_19160).
Riparian buffer zones can reduce pesticide transport from agricultural land to streams but may themselves become contaminated and expose non-target organisms to pesticides. Despite their ecological importance, pesticide occurrence in riparian vegetation and soil remains difficult to predict. Here, we developed a machine learning framework to predict the occurrence of individual pesticides in riparian buffer zones using physicochemical properties, German national pesticide sales data, spatially explicit land use, and topographic predictors. We trained the model on presence-absence data for 93 pesticides measured in vegetation and soil along transects between agricultural fields and streams. The model performance was high for both vegetation and soil. Across 20 cross-validation runs, overall accuracy averaged 0.94 ± 0.01 for vegetation and 0.93 ± 0.01 for soil, with macro average F1-scores of 0.85 ± 0.02 and 0.76 ± 0.02, respectively. Predictor importance analyses showed that national pesticide sales, followed by physicochemical properties, contributed most strongly to model predictions at the individual-predictor level. At the grouped level, physicochemical properties contributed most strongly to model performance in both vegetation and soil. Including adjacent field samples improved soil predictions, whereas stream samples did not improve soil or vegetation predictions. Our results show that pesticide occurrence in riparian buffer zones can be predicted from a combination of usage intensity, compound-specific environmental behavior, and landscape context. Therefore, this approach may support the targeted monitoring and management of non-target habitats in agricultural landscapes.
 INTRODUCTION: The therapeutic role of metamizole (dipyrone) remains controversial because of the risk of metamizole-induced agranulocytosis, a very rare, idiosyncratic, life-threatening adverse reaction. We described utilisation, spontaneous reporting and recent regulatory actions in Switzerland.  We estimated national metamizole utilisation as defined daily doses (DDD; WHO DDD 3 g/day) for 2014-2023, derived from aggregated national sales data; individual case safety reports (ICSR) of metamizole-induced agranulocytosis were retrieved from VigiBase (the WHO global safety database) for 2014-2024. Outputs included annual counts, fatal proportion and utilisation-normalised reporting (metamizole-induced agranulocytosis per million DDD); analyses were primarily descriptive. Utilisation increased by ~79% during the analysed period with a formulation mix of 95.7% oral, 4.2% ampoules, 0.1% suppositories. Metamizole-induced agranulocytosis reports rose from 13 (2014) to 57 (2024), with year-to-year variability; the fatal proportion declined from 13.5% (2014-2018; 17/126) to 5.8% (2019-2023; 13/224) and 1.8% in 2024 (1/57). Utilisation-normalised reporting increased from 1.42 to 3.29 per million DDD (total), while fatal reports remained low and trended downward (mean 0.249 per million DDD, 2014-2023). Among Swiss fatal cases, methotrexate was co-reported as a concomitant drug in 39.5% (15/38) (extended fatal set 2011-2025; fatal ICSRs irrespective of onset year). Switzerland contributes a disproportionately high absolute number of cumulative metamizole-induced agranulocytosis reports.  EMA and Swissmedic implemented strengthened warnings; Swissmedic additionally required a red-framed outer carton statement, clarified indications (second-line severe pain; refractory high fever) and advised avoiding concomitant methotrexate; a Direct Healthcare Professional Communication was issued. Regulatory assessments by EMA and Swissmedic concluded that the benefits of metamizole continue to outweigh the risks, provided the drug is used appropriately, action is taken promptly at first symptoms and concomitant methotrexate is avoided. However, the number of reported cases of agranulocytosis underscores the known risk in the context of widespread use. Spontaneous reports reflect reporting intensity, not incidence; ongoing monitoring of risk-minimisation effectiveness is warranted.
Occupational exposure to per- and polyfluoroalkyl substances (PFASs) is a growing concern, as workers may experience higher exposures compared to the general population. However, the contribution of occupational exposure to PFAS on overall body burden remains understudied. This study aims to identify occupational groups with high PFAS body burden based on the data from 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) and assess potential health risks using the National Academy of Sciences, Engineering, and Medicine (NASEM) guidelines for clinicians. Serum concentration of 12 PFAS compounds among U.S. residents aged ≥16 yr was obtained from the 2013 to 2014 NHANES (N = 2099), which provides the most recent cycle with detailed information on current and longest jobs. Occupational history was obtained from 2010 U.S. Bureau of the Census Industrial & Occupational Classification coding system reported in the NHANES dataset. Occupations and industries associated with the highest PFAS body burden were determined and categorized into 3 risk groups per NASEM thresholds (<2, 2 to 20, and >20 ng/mL) for the sum of 7 PFAS. Survey-weighted linear regressions were conducted to compare PFAS levels across 23 occupational/industry groups, stratified by gender and age. Higher total PFAS concentrations (sum of all detectable PFAS) were observed for both current and longest jobs (GMs: 12.4 to 14.4 ng/mL) in construction/extraction, installation/maintenance/repair, and arts/design/entertainment/sports/media occupations. PFOA, PFOS, PFHxS, and PFNA accounted for >70% of total PFAS body burden. Over 20% of participants exceeded the NASEM high-risk threshold (≥20 ng/mL) in installation/maintenance/repair, construction, manufacturing, durable goods, and transportation/warehousing, with GMs ranging from 28.6 to 37.6 ng/mL. Elevated PFAS levels were observed in construction and installation/maintenance/repair groups in adjusted models, relative to their respective reference groups. Significantly elevated associations were most pronounced among adults aged 30 to 64 and among females in installation/maintenance/repair compared with sales. The observed differences in PFAS serum levels, including elevated body burdens among workers in construction/extraction, arts/design/entertainment/sports/media, and installation/maintenance/repair, underscore the need for targeted biomonitoring and exposure intervention among these occupational groups.
In April 2024, medical cannabis was removed from the list of narcotic drugs in Germany. This case study explores trends in the supply and demand of medical cannabis over a one-year period. Information on available cannabis flower products (including product names, sales prices, stock quantities and THC and CBD concentrations) was regularly accessed from one online dispensary in Germany. Product demand was ascertained by differences in stock quantity over time. Accounting for the impact of %THC and prices, the supply and demand of medical cannabis were explored. Between December 2024 (n=266) and November 2025 (n=401), the number of cannabis flower products available for purchase increased (total availability across the study period: n=996). Median %THC remained mostly stable, but the price per 10mg THC dropped by -0.003€ every week (95% Confidence Interval[CI]: -0.004 to -0.002€). Products with 20 to 29.9% THC made up more than two-thirds of total demand. Product demand quantities increased with every percentage point higher %THC (Incidence Rate Ratio[IRR]=1.13, 95% CI: 1.08 to 1.17) and decreased with every € higher price (IRR=0.59, 95% CI: 0.55 to 0.63; R2 = 0.38). The price changed at least once for about every second product, with price reductions being associated with demand increases. This case study suggests that a highly dynamic commercial market for medical cannabis is evolving in Germany. The increasing demand for cheap products with high %THC contrasts with the available evidence on the safe use of medical cannabis use. Current regulation of the medical cannabis market may not align with public health principles.
The illicit drug trade generates billions of dollars in revenue per year, much of which comes from wholesale and retail sales late in the supply chain. Yet, the methods retailers and low-level wholesalers use to launder this revenue remain poorly understood. Using in-depth interviews with illicit drug entrepreneurs in the United States and the United Kingdom, this article analyses laundering strategies among such market actors. Our findings indicate that a significant proportion of their illicit proceeds are disposed of through relatively small-scale 'everyday' cash transactions (< $1,000) that are effectively untraceable. For those generating more substantial revenues, a variety of accessible and uncomplicated laundering strategies are employed, such as reporting such revenues as taxable income, using proxies to launder funds, and using revenues as investment capital within small-scale legal enterprise. Ultimately, we identify uncomplicated, yet largely effective, methods of laundering criminal proceeds amongst our sample of low- to medium-level illicit drug sellers. Though the sums at an individual level are relatively trivial, the 'mass of minor offences' of this nature likely accounts for a significant share of laundered drug revenues in Western consumer drug markets.
To determine the prevalence and associated factors of ophthalmic self-medication (OSM) and explore the lived experiences of adult patients with ophthalmic problems attending the University of Gondar Comprehensive Specialized Hospital Tertiary Eye Care and Training Center, Northwest Ethiopia. An institution-based mixed-methods study comprising a cross-sectional quantitative component and a phenomenological qualitative component. This study was conducted at the University of Gondar Comprehensive Specialized Hospital Tertiary Eye Care and Training Center, Northwest Ethiopia, between 28 May and 6 August 2025. For the quantitative component, 463 adult patients with ophthalmic problems were included via systematic random sampling. Data were collected using a semi-structured questionnaire and analysed with SPSS V.27. Multivariable logistic regression identified factors associated with OSM. For the qualitative component, eight participants with a history of OSM were purposively selected for in-depth interviews, and data were thematically analysed using OpenCode V.4.0. Prevalence of OSM, factors associated with OSM and themes from the qualitative analysis. The prevalence of OSM was 43.4% (95% CI 38.8 to 48.1). Significant predictors included long travel distance to health facilities (adjusted OR (AOR) = 4.49; 95% CI 2.48 to 8.16), drug availability at home (AOR=3.33; 95% CI 1.97 to 5.62), chronic systemic illness (AOR=2.96; 95% CI 1.51 to 5.80), poor knowledge about risks (AOR=3.19; 95% CI 1.95 to 5.21) and lack of health insurance (AOR=2.29; 95% CI 1.25 to 4.20). Older age was a protective factor (AOR=0.22; 95% CI 0.07 to 0.71). Qualitative findings revealed that accessibility, perceived knowledge, socio-cultural influences, symptom severity and health system barriers were key reasons for OSM. OSM is common in Northwest Ethiopia, driven by both individual and systemic factors. Interventions should focus on awareness creation, expanding insurance coverage, regulating over-the-counter sales and improving access to eye care services.
Understanding adolescents' perspectives on how alcohol policies and the normalization of alcohol consumption affect their behavior remains crucial. This study explores how microsocial systems (peers and family) shape adolescent alcohol consumption within the macrosocial systems (social norms and public policies) in which they are embedded. We conducted 25 group interviews with 197 students in Years 8 to 10 (55.3% girls) enrolled in nine schools. Interviews were analyzed using Reflexive Thematic Analysis. Despite recent restrictions on alcohol sales to adolescents, participants perceived alcohol as still easily accessible. Young people employ various strategies to obtain it, and small neighborhood retailers often fail to comply with regulations despite being aware of them. These macrosocial dynamics also contribute to the normalization of alcohol use during celebrations and in private settings such as the home. In addition, social norms help explain parental attitudes that legitimize adolescents' early experiences with alcohol in the home, while these attitudes-together with parents' own drinking behaviors-further reinforce the normalization of alcohol use. Prevention strategies for adolescents should address the normalization of alcohol use in Chile and its embedding in social contexts, such as families. The enforcement of alcohol policies must be assessed, considering adolescents' reports of access to alcohol.
This study presents a pure multi-criteria decision-making framework to select circular packaging alternatives for an e-commerce shipping pack that includes the outer box, void filler, sealing tape, and return handling. Packaging decisions in e-commerce are inherently multi-objective: they must protect products and reduce damage, keep total cost low, avoid dimensional-weight penalties, fit recovery infrastructure, and lower life-cycle emissions. These choices are often made with linguistic assessments, uncertain return rates, and heterogeneous customer behaviors across markets. To address this setting, we integrate Spherical Fuzzy Step-wise Weight Assessment Ratio Analysis (SF-SWARA) for criteria weighting and Spherical Fuzzy Combined Compromise Solution (SF-CoCoSo) for alternative ranking. A criteria system is defined to reflect operational and circularity priorities, including protective performance, total cost of ownership, compatibility with local collection and recycling systems, consumer acceptance and convenience, hygiene and contamination risk in returns, feasibility of implementing reverse logistics, and carbon footprint. An expert panel expresses relative importance and alternative performance using spherical fuzzy linguistic terms, and SF-SWARA yields a normalized weight vector. Five alternatives are assessed under the same spherical fuzzy environment: a single-use recyclable pack, a reusable pack, a compostable pack, a deposit-return pack, and a minimal-pack design. SF-CoCoSo generates compromise scores by combining additive and multiplicative principles, enabling balanced choices under conflicting objectives. Robustness is examined through sensitivity analysis that perturbs key weights and by benchmarking rankings against an alternative spherical fuzzy method. The framework provides a transparent, replicable decision aid for e-retailers, third-party logistics providers, and packaging designers, supporting context-specific adoption of circular packaging while safeguarding fulfillment performance and customer experience.
The taekwondo roundhouse kick is a fundamental and performance-critical technique that requires precise lower-limb muscle coordination. However, previous studies have mainly focused on discrete electromyographic variables, providing limited insight into waveform-level variations across the kicking cycle, particularly between athletes of different age and training levels. Therefore, this study aimed to investigate lower-limb surface electromyographic (sEMG) waveform differences during the roundhouse kick between elite and youth taekwondo athletes using functional principal component analysis (FPCA). Thirty-eight male taekwondo athletes were included (19 elite, 19 youth). Surface electromyography was recorded bilaterally from seven trunk and lower-limb muscles, including the rectus abdominis, gluteus maximus, rectus femoris, biceps femoris, semitendinosus, lateral gastrocnemius, and tibialis anterior, and three-dimensional kinematic data were collected synchronously during standardized roundhouse kicks. Time-normalized sEMG waveforms were analyzed using FPCA to identify dominant and secondary modes of variation. Group differences in principal component scores were tested using independent-samples comparisons, with Benjamini-Hochberg false discovery rate correction applied across muscle × component tests. After FDR correction, significant between-group differences were identified in four muscle-component combinations. In the support leg, significant differences were observed in PC1 of the left tibialis anterior (p_FDR = 0.001, Cohen's d = 1.726) and left rectus femoris (p_FDR = 0.029, Cohen's d = 1.058), whereas the left lateral gastrocnemius differed in PC2 (p_FDR = 0.040, Cohen's d = 0.943). In the swing leg, the right biceps femoris differed in PC1 (p_FDR = 0.015, Cohen's d = 1.206). Elite and youth taekwondo athletes showed distinct muscle-specific and phase-dependent neuromuscular organization during the roundhouse kick, particularly in support-leg control and swing-leg posterior-chain regulation. FPCA revealed whole-waveform differences that were not captured by conventional discrete measures, providing useful evidence for technique analysis, youth athlete development, and more targeted taekwondo training.
This study meticulously discusses spillover effects among agricultural futures (AGF), crude oil prices (CRO), and the U.S. dollar (USD) during the volatile phase of China's economic policy (CEPU), utilizing the quantile connectedness approach. The empirical findings show that, in the face of economic instabilities and tail incidents, AGF, CRO, USD, and CEPU exhibit significantly higher return spillover at extreme quantiles in comparison to mean one. Furthermore, the dynamic properties of AGF, CRO, USD, and CEPU are empirically substantiated, and certain crises obviously enhance these spillover effects. The primary innovation involves the integration of CEPU into the analytical framework of the agriculture-energy-financial system. This integration illustrates the interdependencies of the system across a variety of market conditions through dynamic quantile shifts, thereby expanding the theoretical scope. This study recommends actions for different market participants, such as an cross-nation economic cooperation and financial market tracking mechanism.
To investigate the impacts of high-intensity interval training (HIIT) on body morphology along with mental health in obese female college students. One hundred and twenty obese female college students admitted to our university from October 2022 to October 2025 were included and randomly divided into control group and study group. The former implemented routine health education without any structured exercise intervention, while the latter underwent a 12-week HIIT intervention (three sessions per week, 30 min per session). Comparisons included Body morphology indicators, mental health indicators, biochemical indicators, sleep quality along with quality of life. Following the intervention, compared to the control group, the study group demonstrated significant improvements across multiple metrics. Specifically, the study group exhibited a lower body mass index, reduced body fat percentage, decreased waist circumference, and a lower waist-to-hip ratio (P < 0.05). In terms of mental health, the study group had lower scores on the PHQ-9 for depression and the GAD-7 for anxiety, while showing higher scores on the SES for self-esteem (P < 0.05). Physical fitness improvements were also notable, with the study group displaying higher VO2max and vital capacity (P < 0.05). Additionally, the study group showed better lipid profiles, lower fasting blood glucose levels, and improved sleep quality as indicated by lower PSQI scores (P < 0.05). Finally, the study group scored higher on all dimensions of the SF-36 quality of life scale (P < 0.05). HIIT intervention can effectively improve body morphology, mental health, physical fitness, biochemical indicators, sleep quality, and quality of life in obese female college students.
To determine tuberculosis prevalence among health-care facility patients and to assess the effectiveness of chest radiography in facility-based tuberculosis screening. Our cross-sectional analysis used individual-level data collected during 2020-2023 from adults presenting at 796 health-care facilities participating in a public-private partnership in 15 provinces of Viet Nam. We constructed tuberculosis care cascades stratified by symptomatic presentation according to the World Health Organization (WHO) four-symptom screening and chest radiography. We reported diagnostic yield, number needed to screen and positivity. Among 1 423 818 participants, 22 598 had bacteriologically confirmed tuberculosis. Diagnostic yields were 2.2% (19 289/892 894) among symptomatic individuals with cough, 1.0% (1869/191 677) among symptomatic individuals without cough and 0.4% (1440/339 247) among asymptomatic individuals. Tuberculosis-suggestive chest radiograph results compared with normal results increased bacteriologically confirmed positivity by 9.4 percentage points in symptomatic individuals with cough (17.3%; 18 746/108 650 versus 7.9%; 543/6851), by 4.6 percentage points in symptomatic individuals without cough (12.6%; 1748/13 831 versus 8.0%; 121/1515) and by 7.6 percentage points in asymptomatic individuals (15.0%; 1328/8862 versus 7.4%; 112/1511). Without chest radiography, the number of individuals requiring testing to detect tuberculosis among symptomatic individuals with cough and without a cough would have been 6.5 (1 084 571/165 679) and 5.4 (892 894/165 679) times higher, respectively. Chest radiograph screening can reduce the number of expensive molecular tests used in symptomatic patients and enable tuberculosis diagnosis in asymptomatic patients. Future research should analyse cost and cost-effectiveness of using chest radiography in active and intensified case finding. Déterminer la prévalence de la tuberculose chez les patients des établissements de santé et évaluer l’efficacité des radiographies thoraciques dans le dépistage de la tuberculose en milieu hospitalier. Notre analyse transversale a utilisé des données individuelles recueillies entre 2020 et 2023 auprès d’adultes s’étant présentés dans 796 établissements de santé participant à un partenariat public-privé dans 15 provinces du Vietnam. Nous avons élaboré des cascades de prise en charge de la tuberculose stratifiées en fonction du tableau clinique, selon le dépistage axé sur quatre symptômes de l’Organisation mondiale de la Santé (OMS) et la radiographie thoracique. Nous avons fait état du rendement diagnostique, du nombre de personnes à dépister et du taux de positivité. Sur 1 423 818 participants, 22 598 présentaient une tuberculose confirmée par examen bactériologique. Les rendements diagnostiques étaient de 2,2% (19 289 sur 892 894) chez les personnes symptomatiques présentant une toux, de 1,0% (1 869 sur 191 677) chez les personnes symptomatiques ne présentant pas de toux et de 0,4% (1 440 sur 339 247) chez les personnes asymptomatiques. Les résultats d’une radiographie thoracique évocatrice d’une tuberculose, comparés à des résultats normaux, ont augmenté le taux de positivité confirmée par examen bactériologique de 9,4 points de pourcentage chez les personnes symptomatiques présentant une toux (17,3%; 18 746 sur 108 650 contre 7,9%; 543 sur 6 851), de 4,6 points de pourcentage chez les personnes symptomatiques sans toux (12,6%; 1 748 sur 13 831 contre 8,0%; 121 sur 1 515) et de 7,6 points de pourcentage chez les personnes asymptomatiques (15,0%; 1 328 sur 8 862 contre 7,4%; 112 sur 1 511). Sans radiographie thoracique, le nombre de personnes nécessitant un dépistage de la tuberculose parmi les personnes symptomatiques avec toux et sans toux aurait été respectivement 6,5 fois (1 084 571 sur 165 679) et 5,4 fois (892 894 sur 165 679) plus élevé. Le dépistage par radiographie thoracique permet de réduire le nombre de tests moléculaires coûteux employés chez les patients symptomatiques et de procéder au diagnostic de la tuberculose chez les patients asymptomatiques. Les recherches futures devraient analyser le coût et la rentabilité de l’application de la radiographie thoracique dans la recherche active et intensifiée des cas. Determinar la prevalencia de tuberculosis entre pacientes atendidos en centros sanitarios y evaluar la eficacia de la radiografía de tórax en el cribado de tuberculosis en estos centros. El análisis transversal utilizó datos a nivel individual recopilados entre 2020 y 2023 de personas adultas atendidas en 796 centros sanitarios participantes en una asociación público-privada en 15 provincias de Vietnam. Se construyeron cascadas de atención de la tuberculosis estratificadas según la presentación sintomática, de acuerdo con el cribado de cuatro síntomas de la Organización Mundial de la Salud (OMS) y la radiografía de tórax. Se informaron el rendimiento diagnóstico, el número necesario de personas a examinar y la positividad. De los 1 423 818 participantes, 22 598 presentaron tuberculosis confirmada bacteriológicamente. Los rendimientos diagnósticos fueron del 2,2% (19 289/892 894) en personas sintomáticas con tos, del 1,0% (1869/191 677) en personas sintomáticas sin tos y del 0,4% (1440/339 247) en personas asintomáticas. Los resultados de radiografía de tórax sugestivos de tuberculosis, en comparación con resultados normales, aumentaron la positividad confirmada bacteriológicamente en 9,4 puntos porcentuales en personas sintomáticas con tos (17,3%; 18 746/108 650 frente a 7,9%; 543/6851), en 4,6 puntos porcentuales en personas sintomáticas sin tos (12,6%; 1748/13 831 frente a 8,0%; 121/1515) y en 7,6 puntos porcentuales en personas asintomáticas (15,0%; 1328/8862 frente a 7,4%; 112/1511). Sin radiografía de tórax, el número de personas que habrían requerido pruebas para detectar tuberculosis entre personas sintomáticas con tos y sin tos habría sido 6,5 (1 084 571/165 679) y 5,4 (892 894/165 679) veces mayor, respectivamente. El cribado mediante radiografía de tórax puede reducir el número de pruebas moleculares costosas utilizadas en pacientes sintomáticos y permitir el diagnóstico de tuberculosis en pacientes asintomáticos. Las futuras investigaciones deberían analizar el coste y la eficiencia según los recursos del uso de la radiografía de tórax en la búsqueda activa e intensificada de casos. تحديد مدى انتشار السل بين المرضى المترددين على المرافق الصحية، وتقييم فعالية تصوير الصدر بالأشعة أثناء الكشف عن السل في هذه المرافق. قمنا في تحليلنا المقطعي باستخدام بيانات على مستوى الأفراد، تم جمعها خلال الفترة من 2020 إلى 2023 من أشخاص بالغين يترددون على 796 مرفقًا صحيًا مشاركًا في شراكة بين القطاعين العام والخاص في 15 مقاطعة في فييت نام. وقمنا بتخطيط مسارات لرعاية مرضى السل، مصنفة حسب الأعراض الظاهرة وفقًا لفحص منظمة الصحة العالمية (WHO) للأعراض الأربعة وتصوير الصدر بالأشعة. قمنا بالإبلاغ عن نتيجة التشخيص، وعدد الحالات التي تحتاج إلى فحص، ونسبة النتائج الإيجابية. من بين 1423818 مشاركًا، تم تأكيد إصابة 22598 منهم بالسل عن طريق الفحص الجرثومي. كانت نتيجة التشخيص %2.2 (19289/892894) بين الأفراد الذين يعانون من أعراض السعال، و%1.0 (1869/191677) بين الأفراد الذين يعانون من أعراض دون سعال، و%0.4 (1440/339247) بين الأفراد الذين لا يعانون من أعراض. أما نتائج تصوير الصدر بالأشعة، والتي تشير إلى الإصابة بالسل، فقد أظهرت مقارنةً بالنتائج الطبيعية زيادة في الإيجابية المؤكدة عن طريق الفحص الجرثومي بنسبة 9.4 نقطة مئوية لدى الأفراد الذين يعانون من أعراض السعال (%17.3؛ 18746/108650 مقابل %7.9؛ 543/6851)، وبنسبة 4.6 نقطة مئوية لدى الأفراد الذين يعانون من أعراض دون سعال (%12.6؛ 1748/13831 مقابل %8.0؛ 121/1515)، وبنسبة 7.6 نقطة مئوية لدى الأفراد الذين لا يعانون من أعراض (%15.0؛ 1328/8862 مقابل %7.4؛ 112/1511). لولا تصوير الصدر بالأشعة، لكان عدد الأفراد الذين يحتاجون إلى فحص للكشف عن السل بين المصابين بأعراض السعال، وبين غير المصابين به، أعلى بمقدار 6.5 (1084571/165679)، و5.4 (892894/165679) مرة على التوالي. يمكن لفحص الصدر بالأشعة أن يقلل من عدد الاختبارات الجزيئية باهظة السعر المستخدمة مع المرضى الذين يعانون من أعراض، وأن يسمح بتشخيص السل لدى المرضى الذين لا تظهر عليهم أعراض. يجب أن تتولى الأبحاث المستقبلية تحليل التكلفة وفعالية التكلفة المتعلقة باستخدام تصوير الصدر بالأشعة في الكشف النشط والمكثف عن الحالات. 旨在确定医疗卫生机构患者中的结核病患病率，并评估胸片检查在基于医疗机构的结核病筛查中的有效性。. 我们的横剖分析运用了在 2020 至 2023 年期间从越南 15 个省内参与公私伙伴关系的 796 家医疗卫生机构的成年患者中收集的个体层面数据。我们构建了根据世卫组织 (WHO) 的四症状结核筛查和胸片结果按症状表现分层的结核病护理级联。我们汇报了诊断检出率、需要接受筛查的人数以及阳性率。. 在 1423818 名参与者中，有 22598 名患有细菌学确诊结核病。有咳嗽症状的个体、有其他症状但无咳嗽症状的个体以及无症状个体中的诊断检出率分别为 2.2% (19289/892894)、1.0% (1869/191677) 和 0.4% (1440/339247)。与正常胸片结果相比，提示患有结核病的胸片结果致使有咳嗽症状的个体、有其他症状但无咳嗽症状的个体以及无症状个体中的细菌学确诊阳性率分别提高了 9.4 个百分点【17.3% (18746/108650) 对比 7.9% (543/6851)】、4.6 个百分点【12.6% (1748/13831) 对比 8.0% (121/1515)】和 7.6 个百分点【15.0% (1328/8862) 对比 7.4% (112/1511)】。如未采用胸片检查，则有咳嗽症状的个体和有其他症状但无咳嗽症状的个体中需要接受检测方能发现患有结核病的人数将分别高出 6.5 倍 (1084571/165679) 和 5.4 倍 (892894/165679)。. 胸片筛查可减少针对有症状患者采用昂贵的分子检测的次数，并可实现针对无症状患者的结核病诊断。未来研究应就针对主动发现病例和强化发现病例采用胸片检查的成本和成本效益展开分析。. Определить распространенность туберкулеза среди пациентов медицинских учреждений и оценить эффективность рентгенографии органов грудной клетки при скрининге туберкулеза на базе учреждений. В рамках данного поперечного исследования использовались индивидуальные данные, собранные в 2020–2023 гг. среди взрослых пациентов, обратившихся в 796 медицинских учреждений, участвующих в государственно-частном партнерстве в 15 провинциях Вьетнама. Авторы построили каскады оказания помощи при туберкулезе, стратифицированные по наличию симптомов в соответствии со скринигом на основе четырех симптомов Всемирной организации здравоохранения (ВОЗ) и результатами рентгенографии органов грудной клетки. Были рассчитаны: диагностическая выявляемость, число обследуемых, необходимое для выявления одного случая, и доля положительных результатов. Среди 1 423 818 участников у 22 598 был бактериологически подтвержденный туберкулез. Диагностическая выявляемость составила 2,2% (19 289/892 894) среди лиц с симптомами в виде кашля, 1,0% (1869/191 677) среди лиц с симптомами без кашля и 0,4% (1440/339 247) среди лиц без симптомов. Результаты рентгенографии органов грудной клетки, указывающие на туберкулез, по сравнению с нормальными результатами увеличивали долю бактериологически подтвержденных случаев на 9,4 процентного пункта у лиц с симптомами в виде кашля (17,3%, 18 746/108 650 по сравнению с 7,9%, 543/6851), на 4,6 процентного пункта у лиц с симптомами без кашля (12,6%, 1748/13 831 по сравнению с 8,0%, 121/1515) и на 7,6 процентного пункта у лиц без симптомов (15,0%, 1328/8862 по сравнению с 7,4%, 112/1511). Без использования рентгенографии органов грудной клетки общее число лиц, которых необходимо протестировать для выявления туберкулеза, среди пациентов с симптомами в виде кашля и без него было бы выше в 6,5 раза (1 084 571/165 679) и 5,4 раза (892 894/165 679) соответственно. Скрининг с использованием рентгенографии органов грудной клетки может сократить число дорогостоящих молекулярных тестов у пациентов с симптомами и обеспечить выявление туберкулеза у лиц без симптомов. В дальнейшем необходимо провести анализ затрат и экономической эффективности применения рентгенографии в рамках активного и усиленного выявления случаев заболевания.
The International Atomic Energy Agency (IAEA) revised the TRS398 Code of Practice in 2024, incorporating dosimetry protocol for pencil beam scanning (PBS) beam delivery system with updated beam quality correction factors (kQ,Qo) for the majority of ionization chambers used in proton beam therapy. This study aims to evaluate the revised TRS398 protocol for dosimetry in an established isochronous cyclotron-based PBS proton therapy system and to quantify its impact on absorbed dose determination. The reference dosimetry measurements were performed using three plane parallel ionization chambers (IBA PPC05, IBA PPC40, PTW Roos) and one cylindrical chamber (IBA FC65-G) in a water phantom on a Proteus Plus PBS proton therapy system. Uniform single-energy scanned fields (10 × 10 cm²) were delivered across 33 clinical proton beam energies ranging from 70.18 MeV to 226.2 MeV. Absorbed dose to water was calculated using kQ,Qo from both the previous and revised TRS398 protocols. Ion recombination (ks) and polarity (kpol) correction factors were determined and evaluated for all chambers for 17 proton energies. The absorbed dose measurements demonstrated good inter-chamber agreement, with a maximum deviation of 2.72% at the lowest energy. Implementation of the revised kQ,Qo values resulted in mean absorbed dose differences of -1.07%, -0.66%, -0.50%, and -1.77% for the PPC05, PPC40, Roos, and FC65-G chambers, respectively, compared to the previous TRS398. The combined relative uncertainty in absorbed dose determination using the revised TRS398 was estimated to be 1.6%. This study assesses the impact of the revised TRS398 dosimetry protocol on absorbed dose determination in PBS proton beams. Experimental measurements using four dosimeters in an isochronous cyclotron-based system show that the revised TRS398 provides a robust framework for PBS reference dosimetry, with the effect of updated kQ,Qo values remaining within the combined measurement uncertainty.
The aim of the present study was to investigate the improvement effect of Ginkgo biloba extract 50 dropping pill (GBE50DP) on vascular cognitive impairment (VCI) induced by cerebral ischemia and its mechanism. The VCI rat model was established by 2-vessel occlusion and randomly divided into the control, model, positive and GBE50DP administration groups. The administration groups were then administered GBE50DP intragastrically for 8 weeks. The social behavior and ability of learning and memory of each group were tested through the Morris water maze and eight-arm maze experiment. The content of oxidative stress and inflammatory factors in the hippocampus of rats were detected using ELISA. Hematoxylin & eosin staining and Terminal-deoxynucleotidyl transferase mediated nick end labeling staining were used to observe the morphological changes of nerve cells in the hippocampal CA1 region of rats. The expression of Caspase-3, Bcl-2, Bax, cytochrome c (Cyto-C), fibroblast-associated antigen (Fas) and poly(ADP-ribose) polymerase-1 (PARP-1) proteins in the hippocampal CA1 region of rats was detected by immunohistochemistry and western blot analysis. The blood components of GBE50DP were analyzed using liquid chromatography-tandem mass spectrometry. The model rats showed significant cognitive impairment; compared with the model group, in the GBE50DP administration groups, the social behavior of rats was markedly improved; the content of superoxide dismutase, glutathione peroxidase and catalase in the hippocampus was markedly increased and that of malondialdehyde, IL-1β, IL-6 and TNF-α was significantly decreased. The pathological changes and expression of Cyto-C, Bax, Bcl-2, Caspase-3, Fas and PARP-1 proteins in brain tissue were markedly improved. The index components of GBE50DP in blood included ginkgolide A, B, C and K and bilobalide, as well as flavonoids such as rutin and quercetin. In conclusion, GBE50DP improved the social behavior, ability of learning and memory in VCI rats, decreased nerve cell damage and protected nerve cells from apoptosis by reducing oxidative stress and inflammation, thereby improving cognitive dysfunction.
Adjuvant pembrolizumab improves disease-free and overall survival among patients with resected clear-cell renal-cell carcinoma. The hypoxia-inducible factor 2α inhibitor belzutifan has activity in advanced disease. Adjuvant pembrolizumab with belzutifan may further improve outcomes in patients with clear-cell renal-cell carcinoma at increased risk for recurrence. In this phase 3, double-blind trial, we randomly assigned participants in a 1:1 ratio to receive intravenous pembrolizumab at a dose of 400 mg every 6 weeks (≤9 doses) and either daily oral belzutifan at a dose of 120 mg (pembrolizumab-belzutifan) or placebo (pembrolizumab-placebo) for up to 1 year. The primary end point was disease-free survival as assessed by the investigator; secondary end points included overall survival and safety. A total of 921 participants were assigned to receive pembrolizumab-belzutifan and 920 were assigned to receive pembrolizumab-placebo. The median time from randomization to the data-cutoff date (August 23, 2025) was 28.4 months (range, 15.0 to 40.1). Disease-free survival was significantly higher with pembrolizumab-belzutifan than with pembrolizumab-placebo (hazard ratio for disease recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87; two-sided P<0.001); the estimated 24-month disease-free survival was 80.7% and 73.7%, respectively. At this interim analysis with 29% of the final-analysis events observed, overall survival did not differ significantly between the groups (hazard ratio for death, 0.78; 95% CI, 0.51 to 1.19; two-sided P = 0.24); the estimated 24-month overall survival was 96.2% with pembrolizumab-belzutifan and 95.7% with pembrolizumab-placebo. Adverse events of grade 3 or higher occurred in 52.1% of the participants who received pembrolizumab-belzutifan and in 30.2% of those who received pembrolizumab-placebo. Treatment with pembrolizumab-belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma at increased risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.).