We aimed to establish an external quality assessment (EQA) programme for the yaws eradication campaign that would meet the needs of reference and district-level laboratories in low- and middle-income countries. We designed proficiency testing items (PTIs) using a plasmid containing gene target sequences for Treponema pallidum (TP) and Haemophilus ducreyi (HD). The storage stability of the plasmids under different environmental conditions was then tested. A proficiency testing panel of seven swabs loaded with different concentrations of plasmids in different combinations, as well as human HEK293 cells to simulate the sample background, was prepared and sent to participating reference (RL) and district (DL) laboratories in Ghana, Côte d'Ivoire and Cameroon followed by three rounds of blinded proficiency testing. We tested quantitative real-time PCR (qPCR) performance of reference laboratories and loop-mediated isothermal amplification (LAMP) performance of district laboratories and retested 20% of human field samples at the London School of Hygiene & Tropical Medicine laboratories to further assess qPCR quality. PTIs proved to be stable in dry conditions with no significant loss of copy number. Participating laboratories achieved qPCR results with a concordance of 95.0-100.0% (97.7% ± 5.2% (mean±standard deviation ((SD)) with the provider and a concordance of 76.0-100.0% (TP: 90.3 ± 13.7% and HD: 78.5 ± 7.5% (mean±SD)) for LAMP results, with inconsistencies, particularly in the detection of low HD plasmid DNA levels combined with high TP plasmid copies. Retesting of field samples resulted in 100% correct TP and HD sample identification by the African reference laboratories. We have developed a functional plasmid-based EQA programme specifically designed to meet the needs of resource-poor settings in the tropics. The programme is suitable as a blueprint for other disease programmes.
Logging is widely recognized as one of the most hazardous industries. Despite the prominence of this sector in Türkiye's Eastern Black Sea region, comprehensive forensic investigations of logging-related deaths are limited. This retrospective study examined 102 logging-related fatalities identified among 4,878 forensic autopsies performed between 2013 and 2023 by the Recep Tayyip Erdoğan University. Demographic, occupational, environmental, seasonal, and medical response characteristics were extracted from autopsy reports and supplemented with information from police and judicial records. The victims were predominantly male (93.1%) with an average age of 57.4 years. Two-thirds of them were unregistered workers, and 5.9% were foreign nationals. Tree-strike injuries were the leading cause of death (51.0%), followed by falls from trees (30.4%). Fatalities most frequently occurred in the fall (32.4%), with cranial trauma predominating in the summer and thoracic inju-ries in the spring. Autopsy findings revealed extensive polytrauma, including pelvic and extremity fractures (71.6%) and intracranial hemorrhage (53.9%). Most incidents were witnessed (78.4%); however, unwitnessed deaths occurred disproportionately among older informal workers on private lands. Female victims (6.9%) primarily died while performing auxiliary tasks and frequently lacked medical intervention (83%). This study represents the first comprehensive medico-legal evaluation of logging-related fatalities in the Eastern Black Sea region. The findings highlight the pivotal role of unregulated labor, hazardous seasonal working conditions, and limited emergency response capacity in shaping mortality patterns. Targeted interventions, including stricter enforcement of occupational safety regulations, training for informal workers, and improved access to rural emergency services, are urgently needed to reduce preventable deaths in forestry and logging activities. Ormancılık, dünyanın en tehlikeli iş sektörlerinden biri olarak kabul edilmektedir. Türkiye’nin Doğu Karadeniz Bölgesinde bu sektörün yaygınlığına rağmen, literatürde ormancılıkla ilişkili ölümlere yönelik kapsamlı adli incelemeler sınırlıdır. Bu retrospektif çalışmada, 2013–2023 yılları arasında Recep Tayyip Erdoğan Üniversitesi tarafından gerçekleştirilen 4.878 otopsi arasından seçilen 102 ormancılıkla ilişkili ölüm olgusu incelenmiştir. Demografik, mesleki, çevresel, mevsimsel ve tıbbi müdahale ile ilgili veriler otopsi raporlarından elde edilerek polis ve adli kayıtlarla desteklenmiştir. Olguların büyük çoğunluğu erkekti (%93.1) ve ortalama yaş 57.4 idi. Vakaların üçte ikisi kayıt dışı işçilerden oluşmakta olup, %5.9’u yabancı uyrukluydu. En sık ölüm nedeni kesilen ağacın işçiye yüksek enerjili teması (%51.0) olup bunu ağaçtan düşmeler (%30.4) izlemekteydi. Ölümler çoğunlukla sonbahar mevsiminde (%32.4) görülürken, yazın kraniyal travmalar, ilkbaharda ise torasik yaralanmalar baskın bulunmuştur. Otopsi bulguları geniş yayılımlı multitravmaları ortaya koymuştur; pelvis ve ekstremite kırıkları (%71.6) ile kafa içi kanamalar (%53.9) en sık bulgulardı. Olayların çoğu en az bir tanık huzurunda gerçekleşmiştir (%78.4); ancak tanıksız ölümler, genellikle özel arazilerde çalışan yaşlı ve kayıt dışı işçiler arasında daha sık gözlenmiştir. Kadın olgular (%6.9) çoğunlukla odunculuk ile ilişkili olan yardımcı işlerde çalışırken ölmüştür ve bu olgulara yapılan tıbbi müdahale oranı düşük bulunmuştur (%83). Bu çalışma, Doğu Karadeniz Bölgesinde ormancılıkla ilişkili ölümlerin kapsamlı adli-tıbbi değerlendirmesini sunmaktadır. Bulgular, düzensiz iş gücü, tehlikeli mevsimsel çalışma koşulları ve sınırlı acil sağlık hizmetlerinin ölüm örüntülerini belirlemedeki kritik rolünü ortaya koymaktadır. Kayıt dışı çalışanların eğitim almasının sağlanması, iş güvenliği mevzuatının daha sıkı uygulanması ve kırsal acil sağlık hizmetlerinin güçlendirilmesi, bölge insanına ilköğretim düzeyinde bazı temel eğitimlerin verilmesi gibi hedefe yönelik önlemler, ormancılık faaliyetlerine bağlı önlenebilir ölümleri azaltmak için acilen gerekli olduğu düşüncesindeyiz.
Regional integrated energy systems (RIES) represent a promising approach for the energy transition and sustainable development, leveraging the flexible, coordinated operation of a multienergy system. With the growing penetration of renewable energy sources and the increasing complexity of energy management, the optimization of RIES necessitates the integration of demand response (DR) mechanisms. The optimization problems are increasingly characterized by multiobjective optimization. This study proposes a novel bilevel multiobjective optimization model for RIES, designed to minimize operational costs, reduce carbon emissions, and enhance load stability simultaneously. The model utilizes dynamic carbon emission factors, derived from the carbon emission flow (CEF) calculation, and time-of-use (TOU) energy pricing as DR signals. The Pareto front for demand-side strategies is obtained using the NSGA-II algorithm, coordinated with an upper-level economic dispatch solved by GUROBI, thereby balancing system and user benefits and identifying the optimal trade-offs among these conflicting objectives. Validation through integrated case studies with a 30-bus power, 20-node gas, and 8-node heat system demonstrates that multiobjective optimization with DR significantly improves economic and environmental performance: achieving a 10.29% cost reduction and a 1.42% carbon decrease, load variation was effectively managed, with electric and thermal load reductions of 3.50% and 6.50%, respectively. However, maintaining system load stability comes at the expense of fully achieving economic and low-carbon objectives, highlighting the critical trade-offs inherent in multiobjective optimization.
Delirium is a serious acute neurocognitive condition that is common and debilitating in older people who undergo major surgery or are acutely ill. The nature of delirium, baseline comorbidity of older adults and related contextual factors present unique ethical challenges in delirium prevention and treatment trials; yet there is limited literature on how these challenges should be best addressed. The objective of this rapid review was to examine the reporting of key ethical processes for older adults (approval, recruitment, consent, retention) in delirium intervention trials. A rapid search in December 2023 with restricted key terms ("Delirium," "Randomized Controlled Trial"), databases (PubMed, CINAHL), older adult participants and English language, and a final publication date range of 2020 to 2023, resulted in 411 articles screened, 153 full-text reviews, and 51 randomized controlled trial (RCTs) reports (with 11 published protocols) included. Data extraction and synthesis aligned with general guidance for ethical approval, processes and reporting of clinical studies, including for people with key vulnerabilities for research participation. Trials were categorized by degree of ethical reporting and statistical tests explored associated trial characteristics. The 51 RCTs were conducted in diverse countries, with the most sizeable proportion in China (51%). Most trials evaluated a delirium prevention (96%) and/or pharmacological intervention (69%) and were individually randomized (88%), phase 3 (84%), and perioperative (75%). No trial fully reported all ethical processes. Most of the 51 trials fully reported who provided consent (88%), the consent approach (88%), and ethical approval details (63%); around half fully reported safety assessments (59%) and how, where and when participants were recruited (49%). However, few trials fully reported who recruited participants (31%), who obtained consent (22%); how trial information was provided (27%), whether capacity was assessed prior to consent (10%), how participants were supported though the trial design or processes (18%) or in-trial communications (8%). Compared to the 19 trials (37%) with little to no reporting of ethical processes, the 16 (31%) trials with fuller reporting more often had a separately published protocol (56% vs 0%, P < .001), were conducted outside of China (87.5% vs 11%, P < .001) and had lower median consent (56% vs 96%, P < .01) and retention rates (89% vs 96%, P < .05). These results will help inform future efforts focused on improving the conduct and reporting of ethical processes in delirium trials.
Ending the abuse of older people in Australia is a national policy priority. Harmonisation of financial enduring power of attorney (FEPOA) legislation is regularly called for to protect against financial elder abuse. A FEPOA is a legal instrument by which an adult appoints one or more people to manage their legal obligations, money and property, particularly during periods of incapacity. Although older Australians are urged to make FEPOAs, and a majority of those over age 65 report having one, these instruments are implicated in an estimated 50%-85% of cases of financial elder abuse. This commentary offers a critical perspective on legislative harmonisation as a policy intervention to prevent financial abuse committed via FEPOA arrangements. We address three main issues. First, we explain several approaches to harmonisation, illustrated with examples from different areas of law-making, noting that harmonisation is often a slow process that does not achieve uniformity. Second, we argue that deficiencies in knowledge and practices that create risks of financial abuse via FEPOAs will not be cured by harmonisation alone. Third, we highlight that the legislative variation across states and territories provides opportunities for innovation in research. Further investment in high-quality research is essential to guide effective legislative and compliance strategies to prevent the financial abuse of older people.
An increasing number of individuals who suffer from hip osteoarthritis (OA) undergoing total hip arthroplasty (THA) have metabolic comorbidities. Among these, metabolic syndrome (MetS) has been identified as a potential key contributor to OA pathogenesis. Although MetS is also known to increase perioperative risks, its impact on treatment outcomes remains poorly understood. We conducted a prospective cohort study aimed at evaluating whether the presence of MetS and its individual components influences postoperative hip function, health-related quality of life, and mental health outcomes following THA. This prospective cohort study included 514 patients who underwent primary THA for hip OA at our university hospital. Patients were stratified into two groups based on the absence (n = 455) or presence (n = 59) of MetS. Patient-reported outcome measures were assessed preoperatively and at one month and one year postoperatively, including hip function, pain , quality of life, and mental health. At one year postoperatively, patients who were diagnosed with MetS exhibited worse scores regarding hip function in several subcategories. Differential effects of the individual MetS components regarding hip function were observed. Dyslipidemia was associated with poorer outcomes, whereas the effects of obesity, T2DM, and hypertension were limited. Importantly, while the proportion of patients reporting yellow flags for depression and anxiety did not differ preoperatively between patients who did and did not have MetS, a higher prevalence was observed in the MetS group at one year postoperatively (MetS: 13.6% versus No MetS: 4.0%, P = 0.006). We demonstrated that MetS is associated with impaired functional and psychological outcomes after THA, with dyslipidemia as a particularly relevant contributing component. Our findings highlight the importance of an integrated preoperative assessment that combines metabolic risk profiling with mental health screening and optimization to enhance patient outcomes.
The oleaginous yeast Yarrowia lipolytica is an attractive chassis for sustainable production of long‑chain ω‑3 polyunsaturated fatty acids (PUFAs). Polyketide synthase (PKS)-like PUFA synthases bypass the canonical oxygen‑dependent desaturase/elongase route, yet the influence of precursor availability on PKS product selectivity in Y. lipolytica remains unclear. Here, we explored a panel of Y. lipolytica strains comprising single‑origin (Aetherobacter fasciculatus, Minicystis rosea) and hybrid PKS clusters. A domain‑shuffled producer, Hyb6, broadened the product spectrum to penta‑unsaturated ω‑3 species, yielding EPA (18.3 mg L-1), DPA (38.8 mg L-1) and trace DHA (1.5 mg L-1) in shake flasks. Time-resolved metabolomics revealed that ω-3 accumulation began in the stationary phase, when acetyl-CoA and malonyl-CoA pools were strongly reduced. l-lysine supplementation upon glycerol depletion was associated with elevated malonyl-CoA levels, accelerated EPA formation (4.6-fold vs. control), and maintenance of an EPA/DPA ratio > 1.9. In contrast, a ketogenic amino-acid mix increased native lipids but reduced EPA selectivity. Transcriptomics revealed l-lysine‑dependent upregulation of acetyl‑CoA supply nodes (ACL1/ACL2, ACS, ACC1) and l-lysine catabolism (KAT1, GCDH, UGA2), together with induction of amino‑acid transporters and protein‑folding machinery. In fed‑batch processes, pulsed l-lysine selectively increased EPA to 405.5 mg L-1 (11.8% selectivity), with DPA at 321.5 mg L-1 and DHA at 14.0 mg L-1. Changes in acetyl-CoA and malonyl-CoA availability are strongly associated with EPA selectivity. Coupling modular PKS design with targeted precursor remodeling provides a versatile strategy to fine-tune product spectra in Y. lipolytica and related microbial PUFA cell factories. The online version contains supplementary material available at 10.1186/s12934-026-02950-x.
The blood-brain barrier (BBB) plays a critical role in maintaining brain homeostasis by tightly regulating molecular transport. However, its integrity is often compromised with aging and in neurodegenerative diseases, contributing to disease pathology. Studying the biological consequences of BBB dysfunction independent of concomitant pathology remains challenging, largely due to the absence of reliable and inducible animal models that avoid unintended side effects such as osmotic effects, neuroinflammation, or vascular damage. In this study, we evaluated the use of Power Doppler ultrasound (PDUS) combined with microbubbles to induce widespread, bilateral BBB opening in the mouse brain. Mice received intravenous infusions of SonoMAC microbubbles during transcranial PDUS application. BBB permeability was assessed via Evans Blue dye extravasation and immunofluorescence analysis of extravasated immunoglobulins. Vessel integrity was evaluated at the ultrastructural level using transmission electron microscopy (TEM). PDUS combined with microbubbles successfully induced widespread BBB opening, as evidenced by diffuse Evans Blue staining and immunoglobulin extravasation in coronal sections. Immunoglobulin leakage was detected in all analyzed brain regions, with lower levels in white matter, likely reflecting its lower vascular density. Leakage appeared to primarily originate from capillaries while TEM analysis revealed no overt vascular damage. These findings support PDUS with microbubbles as a non-destructive, reproducible method to model widespread BBB dysfunction. This approach offers an in vivo platform to study BBB-related pathophysiological processes such as impaired clearance, protein aggregation, and neurotoxicity, as well as for investigation of therapeutic delivery to the brain parenchyma.
Wide access to online information favors the search for health content. The aims of the present study were to identify the profile of internet use and degree of difficulty in the search for health information by adults, describing the main contents sought and means used, and to investigate associations with sociodemographic/medical characteristics and degree of health literacy. A household survey was conducted in five municipalities in the South and Central-West regions of Brazil. The questionnaire included demographic and socioeconomic data, internet use, and degree of health literacy. Descriptive analyses and Poisson regression were performed to estimate prevalence ratios. A total of 1,181 individuals were included. Women, age between 18 and 39 years, eight or more years of schooling, high economic class, White race, good self-rated health, and problematic health literacy predominated in the sample. A total of 92.3% had access to the internet and 77.1% of these individuals used the internet to search for health information. The most searched topics were symptoms (89.1%) and medications (84.5%). The search tools most used were Google (94.6%) and YouTube (41.7%). Most participants reported ease in using correct words (68.6%) and finding information (70.2%), but difficulty in assessing reliability (44.8%) and applying information to health-related decisions (25.9%). In the adjusted analysis, a higher education, younger age, and higher levels of health literacy were associated with searching for health information online. The use of the internet was widely reported, despite difficulties in assessing reliability and applying the information. The findings underscore the need for accessible online health content of adequate quality. O amplo acesso a informações online favorece a busca por conteúdos em saúde. Os objetivos foram identificar o perfil de uso da internet e o grau de dificuldade na busca por informações em saúde por adultos, descrevendo os principais conteúdos buscados e meios utilizados, além de avaliar a associação com características sociodemográficas, médicas e com o grau de letramento em saúde. Inquérito domiciliar realizado em cinco municípios das regiões Sul e Centro-oeste do Brasil. O questionário incluiu dados demográficos, socioeconômicos, uso da internet e grau de letramento em saúde. Realizaram-se análises descritivas e regressão de Poisson para estimar razões de prevalência. Foram incluídos 1.181 indivíduos, sobretudo mulheres, entre 18 e 39 anos, 8 anos ou mais de escolaridade, classe econômica elevada, raça branca, boa autoavaliação de saúde e letramento em saúde problemático. Do total, 92,3% tinham acesso à internet; desses, 77,1% a utilizavam para buscar informações em saúde. Os temas mais buscados foram sintomas (89,1%) e medicamentos (84,5%). As ferramentas mais utilizadas foram Google (94,6%) e YouTube (41,7%). A maioria relatou facilidade para usar palavras corretas (68,6%) e encontrar informações (70,2%), mas dificuldade em avaliar a confiabilidade (44,8%) e aplicar as informações em decisões de saúde (25,9%). Na análise ajustada, maior escolaridade, ser jovem e níveis mais elevados de letramento em saúde foram associados à busca por informações em saúde online. O uso da internet foi amplamente relatado, apesar das dificuldades em avaliar a confiabilidade e aplicar as informações, destacando a necessidade de conteúdos em saúde online de qualidade e acessíveis. El amplio acceso a información en línea favorece la búsqueda de contenidos de salud. Los objetivos fueron identificar el perfil de uso de internet y el grado de dificultad en la búsqueda de información de salud entre adultos, describiendo los principales contenidos buscados y los medios utilizados, así como evaluar la asociación con características sociodemográficas, médicas y con el grado de alfabetización en salud. Encuesta domiciliaria realizada en cinco municipios de las regiones Sur y Centro-oeste de Brasil. El cuestionario incluyó datos demográficos y socioeconómicos, uso de internet y nivel de alfabetización en salud. Se realizaron análisis descriptivos y regresión de Poisson para estimar las razones de prevalencia. Se incluyeron en el estudio 1.181 individuos, en su mayoría mujeres, de edades comprendidas entre 18 y 39 años, con 8 o más años de escolaridad, de clase socioeconómica alta, raza blanca, con buena autopercepción de salud y alfabetización en salud problemática. Del total, el 92,3% tenía acceso a internet; de ellos, el 77,1% lo utilizaba para buscar información de salud. Los temas más buscados fueron síntomas (89,1%) y medicamentos (84,5%). Las herramientas más utilizadas fueron Google (94,6%) y YouTube (41,7%). La mayoría indicó facilidad para usar palabras correctas (68,6%) y encontrar información (70,2%), pero dificultad para evaluar la confiabilidad (44,8%) y aplicar la información a decisiones de salud (25,9%). En el análisis ajustado, la mayor escolaridad, ser joven y tener un nivel más alto de alfabetización en salud se asociaron a la búsqueda de información de salud en línea. El uso de internet fue ampliamente reportado, pese a las dificultades para evaluar la confiabilidad y aplicar la información, destacando la necesidad de contenido de salud en línea de calidad y accesible.
Low-dose radiotherapy (LDRT) is increasingly used for degenerative and inflammatory joint conditions, yet technical guidance for planning shallow-depth periarticular targets remains limited. This study reports our institutional experience with CT-based planning for LDRT to the hands and knees, including immobilization, bolus configuration, beam selection, and quantitative analysis of V100, V95, Dmax, and Dmin for both GTV and PTV. Over a 6-month period, CT simulation and planning workflows were standardized for patients receiving LDRT. For hands, bolus was applied beneath the hand during simulation and again in the TPS; immobilization used individualized or combined masks. Knee simulations used a standard knee sponge. Plans used 6 MV AP-PA or mixed 6 MV (AP) and 10 MV (PA). A total of 56 knees and 30 hands were analyzed. Knee plans achieved strong target coverage (median PTV V95 ≈ 96%) with low hotspot volumes (median Dmax ≈ 107%). Hand plans demonstrated similarly robust coverage (median V95 ≈ 99%), with reproducible hotspot control across all cases. Dmin variability reflected expected dose behavior in shallow-depth regions influenced by anatomic curvature and residual MV buildup. LDRT to hands and knees can be effectively planned using standard 3DCRT techniques with consistent immobilization, bolus placement, and beam energy selection. The workflow produced reproducible dose distributions with V95 > 95% and Dmax < 110%, supporting the technical feasibility and clinical practicality of this approach.
In response to increasing global demand for biobased polymers, this study presents the synthesis and comprehensive thermal characterization of nonisocyanate polyurethanes (NIPUs) derived from soybean oil, focusing on the identification of volatile compounds released during thermal analysis and proposing a degradation mechanism. The materials were obtained via epoxidation, CO2 cycloaddition, and aminolysis using different aminesIPDA, TRIS, and APTESforming poly-(hydroxyurethanes) (PHUs) with variable cross-link densities and hybrid features. Structural analyses via 1H NMR and FTIR confirmed successful conversion at each step, with epoxy group titration indicating ≈91% conversion to cyclic carbonate and efficient catalyst removal, as confirmed by XRF (Br < 0.3% after purification). PHUs achieved high cross-linking, with gel contents up to 91.9%. The presence of APTES significantly modified network architecture, reducing gel content to 33% in some formulations but introducing inorganic siloxane domains. TGA revealed multistage degradation between 250 and 475 °C, with TRIS-based networks demonstrating enhanced thermal resistance. Deconvoluted DTG curves and TG-IR data identified primary volatiles including CO2, amines, ketenes, and silanols, elucidating degradation pathways involving urethane cleavage, retro-aminolysis, and glycerol decomposition. This work advances the understanding of structure-property-degradation relationships in NIPUs and highlights their viability as green engineering alternatives to conventional polyurethanes, aligning with SDGs 9, 12, and 13.
Essential for eukaryotes, multiple copies of the exocyst complex tether each secretory vesicle to the plasma membrane (PM) in constitutive exocytosis. The exocyst higher-order structure (ExHOS) that coordinates the action of these multiple exocysts remains unexplored. We integrated particle tracking, super-resolution microscopy, and cryo-electron tomography to time-resolve the continuum conformational landscape of the ExHOS and to functionally annotate its different conformations. We found that 7 exocysts form a flexible ring-shaped ExHOS that tethers vesicles at <45 nm from the PM. The ExHOS rapidly expands while pulling the vesicle toward the PM in a stepwise mechanism comprising three metastable states at 27, 18, and 5 nm from the PM. After fusion, Sec18 mediates the disassembly of the stationary ExHOS, a function that controls the rate of exocytosis. By resolving biophysical principles in situ, we reconstructed the spatiotemporal dynamics of the multimeric architecture controlling vesicle tethering in exocytosis.
Mass casualty incidents (MCIs) rapidly exceed routine hospital capacity. Full-scale exercises are essential for preparedness, but systematic, multidimensional evaluations remain scarce. This study aimed to evaluate overall team performance in triage accuracy, workflow, and individual workload throughout a MCI exercise. In a prospective observational study at Heidelberg University Hospital (Germany), healthcare professionals managed 91 simulated casualties using a two-stage triage process. Patients and staff carried location tags enabling continuous spatiotemporal tracking. Objective outcomes included triage accuracy, triage duration, patient flow, and staff–patient contact frequency. Subjective workload and teamwork were assessed using the NASA Task Load Index (NASA-TLX) and the Team Emergency Assessment Measure (TEAM), respectively. Overall triage accuracy was 75.4%. Undertriage occurred in 11.6% of category I and 10.1% of category II cases; overtriage was infrequent (2.9%). Mean triage times differed significantly by category: ‘red’ 59 ± 25 s, ‘yellow’ 173 ± 74 s, ‘green’ 205 ± 100 s (p < 0.0001). Geotracking demonstrated consistent patient flow without detectable bottlenecks and a mean of 7.1 ± 5.7 patient contacts per staff member. NASA-TLX scores indicated high temporal demand but low frustration with an overall workload of 66.7 ± 16; specialists and staff with greater professional experience reported significantly lower perceived workload (p < 0.05). TEAM ratings were homogeneously good across all participants (79.8%). This study provides reproducible benchmark data on simulated hospital MCI response. The integration of geotracking with subjective measures, enables a comprehensive evaluation of hospital disaster preparedness. Moreover, the ability to compare different exercises and collect reliable longitudinal data may further enhance hospital disaster response. The online version contains supplementary material available at 10.1186/s12873-026-01527-6.
Acute myeloid leukemia (AML) is a heterogeneous disease with complex mutational profiles that lead to variable clinical outcomes. NRAS and KRAS are among the most frequently mutated genes in AML, but their clinical impact has not been well-characterized. In this cohort of over 2000 children and young adults with AML, we evaluated the role of mutations in RAS genes and mutation complexity in outcome determination. Given enrichment in KMT2A-rearranged AML (KMT2A-r), we specifically studied the significance of RAS mutations in KMT2A-r AML. Using variant calls from next generation sequencing (NGS) platforms, we identified RAS mutations in 35.1% (N=669) (NRAS, N=518; KRAS, N=216). We demonstrated that NRAS mutations were not associated with outcome in AML or in KMT2A-r AML. In contrast, KRAS mutations demonstrated inferior outcomes in AML, with enrichment of prevalence and enhancement of prognostic implications in KMT2A-r AML, including non-high risk KMT2A fusions. Additionally, we describe a complex RAS mutation cohort (Comp-RAS) characterized by two distinct RAS mutations or high variant allele frequency (VAF) RAS mutations that collectively account for 13.5% (n=90) of patients with RAS mutations. Patients with complex KRAS mutations, and those with complex RAS mutations in the KMT2A-r cohort, had a distinctly adverse outcome, and data demonstrates that Comp-RAS status drives adverse outcomes for those with KRAS mutations in the whole AML cohort.
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Elder abuse affects nearly 15% of older Australians, with those living with dementia at increased risk. This study explored how Australian health care providers identify and respond to different types of elder abuse using six hypothetical vignettes. An online cross-sectional survey (N = 130) evaluated identification and response to instances of elder abuse among geriatricians, general practitioners, and nurse practitioners. Rates of accurate identification were highest for physical (94.3%) and psychological abuse (91.5%), followed by sexual abuse (76.1%), neglect (72.3%), and financial abuse (72%). While most participants provided an appropriate response to psychological abuse, neglect, and financial abuse (100%, 100%, 97.8%), fewer reported an appropriate response to physical (37%) and sexual (67%) abuse. Older age was associated with lower identification accuracy for psychological and physical abuse. General practitioners were more likely to correctly identify neglect. Findings highlight important knowledge and response gaps, underscoring the need for targeted education and training.
Tipburn is a physiological disorder in lettuce (Lactuca sativa) that causes leaf margin necrosis, reducing marketability, and is exacerbated in hydroponic systems where calcium demand exceeds supply. Although a calcium-mobilizing biostimulant can mitigate tipburn, it is unclear whether its efficacy depends on nutrient solution dissolved oxygen (DO), which is critical for water and nutrient uptake. We evaluated the effects of this calcium-mobilizing biostimulant (0, 0.25, and 0.5 mL⋅L–1) and root-zone DO (achieved without and with varying degrees of moderate active aeration: 2.9, 3.5, and 4.0 mg⋅L–1) on growth and tipburn of hydroponic butterhead lettuce ‘Nancy’ in deep-water culture. At 21 days after transplanting (DAT), increasing DO from 2.9 to 3.5–4.0 mg⋅L–1 increased shoot fresh mass by 98–139%, moisture content by 5–7%, and plant diameter by 31–48%, without affecting dry mass, whereas the biostimulant did not affect growth. At medium DO, the biostimulant reduced percent burnt leaves from 33 to 12%. At 28 DAT, similar DO-dependent growth trends persisted, while high biostimulant concentration reduced tipburn, especially at low DO. These results indicate that active aeration enhances tissue hydration and fresh mass, and that the biostimulant mitigates tipburn primarily under root hypoxia.
By integrating short-read whole-genome sequencing and RNA sequencing (RNA-seq) data with long-read RNA-seq, we dissect the complex genomic architecture of PAX5 intragenic tandem multiplication, revealing that these complex rearrangements result in in-frame transcripts that likely encode proteins with altered domains.
Frailty syndrome (FS) is a critical factor associated with several oxidative stress and age-related diseases. In this work, we investigated the connection between frailty, defined at early stages using a new cut-off value of the Frailty Trait Scale (FTS-5), and plasma biomarkers of oxidative stress. Plasma samples of 76 older women were analyzed to determine free and protein-bounded tryptophan (Trp), kynurenine (Kyn), N-formylKynurenine (N-Kyn), advanced glycation end products, and protein carbonylation. A subgroup of 30 subjects was selected from the entire group to determine malondialdehyde (MDA), free methionine (Met), phenylalanine (Phe), Trp, and Kyn. In the whole group (N = 76), Kyn and the Kyn/Trp ratio were higher in women with a Romberg test altered (p-values = 0.0439, and 0.0472, respectively) and BMI < 25.3 kg/m2 (p-values = 0.0008, and 0.0011, respectively). Increased protein carbonylation was found for subjects with BMI ≥ 25.3 kg/m2. For the subgroup, an increase in the Kyn/Trp ratio was observed in subjects with an altered Romberg test, concomitant with decreased levels of Trp, Met, Phe, and MDA (p-values = 0.0255, 0.0427, 0.0459, and 0.0173, respectively) when data were grouped according to the modified FTS-5. These results highlight the relevance of oxidative biomarkers as a tool for an early diagnosis of FS and its related complications.
Tropical coral reefs face unprecedented threats from ocean acidification and warming, driving alarming declines in reef communities worldwide. Yet environmental history and diverse symbiotic partnerships often shape how corals respond to environmental change. We investigated how the Caribbean coral Siderastrea siderea responds to simulated future ocean conditions by examining holobiont phenotypes, symbiotic communities, and gene expression profiles. After three months of exposure to various acidification and warming scenarios, S. siderea showed only moderate stress responses, with no shifts in algal symbiont or bacterial communities. Remarkably, even under the warmest temperature and lowest pH conditions, coral host gene expression patterns were primarily shaped by which Symbiodiniaceae genus they hosted, rather than experimental treatments. Corals predominantly hosting Durusdinium trenchii exhibited higher lipid content but reduced calcification rates compared to those hosting Cladocopium goreaui, suggesting different metabolic strategies based on which symbiont was predominant in the coral holobiont. While moderate treatment effects were observed, significant changes in holobiont phenotype and gene expression occurred mainly under extreme acidification conditions unlikely to be experienced within the next century. Under these extreme scenarios, we detected reduced growth rates and downregulation of calcification-related genes, indicating potential challenges for skeletal production in future oceans. These findings enhance our understanding of coral acclimatization strategies and emphasize how symbiotic relationships fundamentally shape coral responses to environmental change. As climate change intensifies, these molecular and physiological mechanisms may determine which coral species persist on future reefs.