The Supreme Court (SC) of India's judgment on March 11, 2026, in Harish Rana vs Union of India brought greater clarity on the complex issue of end-of-life decisions; specifically on withdrawal of care from persons in a "permanent vegetative state" [1]. In an earlier landmark judgment in Aruna Shanbaug vs Union of India in 2011, the Court had allowed petitions in favour of "withholding or withdrawal of life support" to allow "a dignified death", in very rare cases, following specific procedures outlined in that judgment [2]. In 2018, in Common Cause vs Union of India, the SC recognised the "right to die with dignity" as an extension of the fundamental "right to live with dignity" under Article 21 of the Indian Constitution. Patients who were terminally ill could refuse futile or burdensome treatment and could register Advance Directives, against unnecessary suffering caused by such treatment [3]. That judgment detailed the decision-making process to be followed for withdrawal of treatment, in order to protect vulnerable patients and prevent misuse. These procedural steps were later simplified by the SC in 2023 into what is termed "Common Cause Guidelines 2023" [4].
Reconstruction of distal radius defects following oncological resection remains technically challenging. Free fibula flap (FFF) arthrodesis offers a biological and durable reconstructive option; however, reports remain limited. We retrospectively reviewed 8 patients who underwent en bloc resection of Campanacci grade III giant cell tumors (2017-2024) of the distal radius, followed by reconstruction with FFF arthrodesis. Clinical, radiological, and functional outcomes were analyzed, including union, recurrence, complications, donor-site morbidity, and Musculoskeletal Tumor Society, Disabilities of the Arm, Shoulder, and Hand (DASH), and visual analog scale scores. All patients achieved radiographic union (mean 7 mo proximally, 11 mo distally). Median follow-up was 36 months. Seven (87.5%) patients remained disease-free; 1 patient developed multicentric soft-tissue local recurrence with pulmonary metastases, which was managed surgically along with radiotherapy and medical treatment. The patient remained disease-free at last follow-up. Mean Musculoskeletal Tumor Society score was 24.5, DASH score was 20.3, and visual analog scale score was 2.3, indicating satisfactory limb function and minimal pain. Donor-site morbidity was minimal. FFF arthrodesis maintained viability even after postoperative fractures, soft-tissue recurrences, and adjuvant therapy, underscoring its robustness. It represents a valuable microsurgical option when long-term stability and biological incorporation are prioritized.
Shigella is a leading cause of childhood diarrhea in low- and middle-income countries and is increasingly resistant to first-line antibiotics. We conducted a surveillance study to determine the incidence, genomic characteristics, and AMR profiles of Shigella infections in children under five with moderate to severe diarrhea (MSD) in Lusaka, Zambia. Between 15 September 2020 and 30 November 2021, a prospective cohort study of 1,400 children under five was enrolled during a community census in a peri-urban setting and passively followed for 9.5 months for MSD. During enrollment, socio-demographic data were collected using electronic questionnaires, while clinical data were collected through the DHIS platform. The main outcome, Shigella in diarrheal stool in under 5 children, was detected using culture and Loop-mediated Isothermal Amplification (LAMP) targeting the ipaH gene. Cox proportional hazards models were used to assess the incidence and risk factors of Shigella (ipaH) infections. Whole-genome sequencing (WGS) was used to characterize the genomic diversity and antimicrobial resistance genes, complemented by phenotypic antibiotic susceptibility testing. There were 230 first episodes of Shigella over a follow-up time of 9,581.7 child-months, yielding an incidence of 24.0 (95% CI 21.1-27.3) cases per 1,000 child-months, with the highest incidence among 2 to 3-year-olds. The key risk factors identified were the water source (p=0.025) and age group (p=0.014). Genotypic characterization revealed 10 S. flexneri , 9 S. sonnei , and 3 S. boydii . The S. sonnei isolates formed two clusters, differing in virulence factors and plasmid profiles, indicating two possible circulating strains. Shigella isolates exhibited phenotypic and genotypic multidrug resistance, including against trimethoprim, aminoglycosides, and beta-lactams. Plasmid-mediated quinolone resistance (qnrS1) was identified in four S. flexneri isolates, with these genes located on the IncFIB(K) plasmid, highlighting the potential for horizontal transmission and spread of quinolone resistance in this region. No phenotypic and genotypic resistance to macrolides, the first-line treatment for Shigella in Zambia, was observed. We report a high burden of Shigella with multidrug resistance, including resistance to fluoroquinolones. These findings highlight the increasing resistance of Shigella to first-line antibiotics and underscore the importance of developing safe and effective vaccines, improving WASH conditions, and ongoing AMR surveillance. The EDCTP2 program, supported by the European Union, the Faculty for the Future Foundation (FFTF), the Netherlands Organization for Health Research and Development (ZonMw), and Health-Holland AMR-Global, Gloria, and Track-AMR. Evidence before this study: Despite Shigella being a leading cause of bacterial diarrheal mortality globally, there is a critical lack of up-to-date data on its burden and associated antimicrobial resistance (AMR) in high-risk settings, such as sub-Saharan Africa (SSA). We searched PubMed for studies published between 2000 and May 2025, using the terms " Shigella ," "antimicrobial resistance," and "sub-Saharan Africa." Only three studies (GEMS, MAL-ED, VIDA) involving extensive surveillance in SSA countries were identified, all conducted before 2018. None integrated disease burden, genomic characterization of circulating strains, and both phenotypic and genotypic AMR profiling. In Zambia, we found no published surveillance data on Shigella or resistance patterns in children. The added value of the study: We present an up-to-date, integrated assessment of the burden, genomic diversity, and AMR profiles among Shigella isolates in children under five in SSA, specifically in a high-risk peri-urban setting in Lusaka, Zambia. By prospectively following a large cohort of 1,400 children and combining culture with WGS, we provide detailed insights into the disease burden and epidemiology of circulating Shigella strains and the relevance of candidate vaccine antigens. We reveal a high prevalence of multidrug resistance (MDR), including plasmid-mediated and phenotypic resistance to ciprofloxacin, the first-line treatment for Shigella . We further complement genotypic AMR with phenotypic AMR testing to predict potential resistance genes while measuring antibiotic susceptibility in real clinical settings. Implications of all the available evidence: We demonstrate that Shigella is genomically diverse and an important etiology of moderate to severe gastroenteritis in Zambian children. Risk factors include increasing age and poor WASH. We observed plasmid-mediated resistance to ciprofloxacin and MDR, which threatens the efficacy of current Shigella treatment and risks population-level AMR spread. These results highlight the need for improved WASH, antibiotic stewardship, and the development of effective vaccines, supported by ongoing genomic surveillance, to facilitate disease monitoring, inform treatment guidelines, guide vaccine antigen selection, and inform evidence-based antibiotic stewardship.
Data deficiency is a substantial challenge for extinction risk assessments because incomplete data means we cannot accurately identify priority protected areas for conservation. Here, we use the International Union for Conservation of Nature (IUCN) distributions of amphibians, sharks and rays, fish, mammals, birds, and reptiles to identify hotspots of data deficient species. We found that areas with high numbers of data deficient species were not randomly distributed and did not necessarily overlap with hotspots of biodiversity, particularly in the Amazon and West Africa. Data deficiency hotspots were concentrated around tropical South America, Africa, and Southeast Asia; however, this distribution varied between taxa. Hotspots of data deficient amphibians were concentrated around the tropical Andean forests of Colombia, Peru, and Ecuador; throughout Brazil; and in the New Guinea Highlands. The tropical forests of the Congo River basin, Papua New Guinea, and the Philippines were hotspots for avian data deficiency. Data deficient chondrichthyans were concentrated in the tropical seas, particularly around the western coast of Africa, East Asia, and the tropical Americas. Indochina was identified as the primary hotspot for data deficient freshwater fish, whereas the Indo-Pacific was the primary hotspot for data deficient marine fish. Data deficient marine mammals were broadly distributed around the southern oceans, South America, Southeast Asia, and Northwest Africa. Data deficient herpetofauna were concentrated around tropical Asia, whereas tropical South America, Indonesia, and central Africa were the hotspots for data deficient terrestrial mammals. Although data deficiency reflected drivers of biodiversity more broadly (e.g., latitude), other factors were also influential, including the amount of conservation funding invested by a country and population density. Increasing evidence suggests that data deficient species are disproportionately likely to be threatened with extinction. Scientists urgently need to focus their research efforts on these data deficiency hotspots and ensure protected area networks are suitably representative and include data deficient species. Furthermore, the accuracy of status assessments needs to be ascertained, and data deficient species need to be prioritized for study to ensure they are not lost before they are identified. Identificación de puntos calientes de deficiencia de datos faunísticos para dirigir la investigación y el monitoreo urgentes Resumen La falta de datos es un reto importante para las evaluaciones del riesgo de extinción, ya que la información incompleta nos impide identificar con precisión las áreas protegidas prioritarias para la conservación. En este estudio, utilizamos los datos de distribución de la Unión Internacional para la Conservación de la Naturaleza (UICN) sobre anfibios, tiburones y rayas, peces, mamíferos, aves y reptiles para identificar los puntos críticos de especies con datos insuficientes. Descubrimos que las áreas con un elevado número de especies con datos insuficientes no se distribuían de forma aleatoria y no se solapaban necesariamente con los puntos calientes de biodiversidad, especialmente en la Amazonía y África Occidental. Los puntos calientes de especies con datos insuficientes se concentraban en torno a las zonas tropicales de Sudamérica, África y el sudeste asiático; sin embargo, esta distribución variaba entre los taxones. Los puntos calientes de anfibios con datos insuficientes se concentraban en torno a los bosques tropicales andinos de Colombia, Perú y Ecuador; en todo Brasil; y en las tierras altas de Nueva Guinea. Los bosques tropicales de la cuenca del río Congo, Papúa Nueva Guinea y Filipinas eran puntos calientes para las aves con datos insuficientes. Los condrictios con datos insuficientes se concentraban en los mares tropicales, especialmente en torno a la costa occidental de África, el este de Asia y las zonas tropicales de América. Se identificó Indochina como el principal punto caliente para los peces de agua dulce con datos insuficientes, mientras que el Indo‐Pacífico era el principal punto caliente para los peces marinos con datos insuficientes. Los mamíferos marinos con datos insuficientes se distribuían ampliamente por los océanos del sur, Sudamérica, el sudeste asiático y el noroeste de África. La herpetofauna con datos insuficientes se concentraba en la zona tropical de Asia, mientras que la zona tropical de Sudamérica, Indonesia y África central eran los puntos calientes para los mamíferos terrestres con datos insuficientes. Si bien la falta de datos reflejaba factores que influyen en la biodiversidad de manera más general (por ejemplo, la latitud), también influían otros factores, como la cantidad de fondos destinados a la conservación por parte de un país y la densidad de población. Cada vez hay más indicios de que las especies con datos insuficientes tienen una probabilidad desproporcionadamente mayor de estar en peligro de extinción. Los científicos deben centrar urgentemente sus esfuerzos de investigación en estos puntos calientes de falta de datos y garantizar que las redes de áreas protegidas sean adecuadamente representativas e incluyan a las especies con datos insuficientes. Además, es necesario verificar la precisión de las evaluaciones de estado, y se debe dar prioridad al estudio de las especies con datos insuficientes para garantizar que no se pierdan antes de ser identificadas.
Anti-amyloid immunotherapies in Alzheimer's disease (AD) are newly authorized for use in the European Union (AD). In a national online survey in 2024, we aimed to assess French practitioners' opinion and knowledge regarding indications and risk management plan. Answers were based on clinical trial criteria. On 303 practitioners, most knew general indications except 19.1% who considered prescribing without AD biomarkers. Side effects were correctly identified, but specific knowledge on amyloid-related imaging abnormalities was lacking. Tertiary memory clinic practitioners had better knowledge on indications (p < 0.001) and side effects (p = 0.033).
Background Attention deficit hyperactivity disorder (ADHD) affects 5% of children and adolescents. Diagnostic criteria rely on behavioural observations. YouTube offers easily accessible health information, including that on ADHD. We analyzed ADHD-related YouTube videos covering causes, treatment, medication, patient presentation, and ADHD deficit hyperkinetic disorder to assess the quality of information. Methods YouTube videos related to ADHD were evaluated in a cross-sectional study. Seven different search terms was used by seven authors to review the top 10 videos each. The videos were scored using the modified video power index (VPI), Global Quality Scale (GQS) and DISCERN scores to evaluate the quality and reliability of the information. The quality of videos was compared based on the nature of the source of the videos. The Statistical Package for the Social Sciences software was used to perform statistical analysis. Results This study included 67 videos, mostly by doctors (n = 21, 31.3%), most often describing ADHD symptoms (n = 58, 86.57%). The median GQS for the videos was 4, and the reliability score was also 4. The quality of videos was similar among the source of videos with p values for VPI, GQS, and global reliability being 0.073, 0.922, and 0.617, respectively. Conclusion The quality of videos on ADHD on YouTube are similar irrespective of the source such as doctors, patients, healthcare providers etc.
Glochidion puberum (L.) Hutch., a member of the family Phyllanthaceae, is widely distributed in China and possesses both medicinal and ornamental value. Despite its ecological and economic significance, the complete chloroplast genome of G. puberum had not been reported, and its phylogenetic placement within the genus Glochidion has remained unresolved. In this study, we assembled and annotated the complete chloroplast genome of G. puberum for the first time. The chloroplast genome is 157,133 bp in length, exhibiting an overall GC content of 37% and containing 129 genes. The result of phylogenetic analysis revealed a close evolutionary relationship among G. puberum, G. hirsutum, and G. chodoense based on complete chloroplast genome. These findings provide comprehensive genomic data for G. puberum and offer new perspectives on the phylogenetic relationships and evolutionary position in the broader Phyllanthaceae family.
Effective clinical communication is essential for medical practice, with standardized patients (SPs) being a reliable standard training method despite resource limitations. While large language models (LLMs) show strong role-playing abilities, current virtual patients (VPs) based on single LLMs face fidelity and interaction challenges. Recent advances in multiagent frameworks, which have demonstrated considerable potential in handling complex tasks, offer a new perspective for creating VPs in medical education. This study aimed to develop and evaluate a novel multiagent VP framework that simulates SPs through a collaborative agent design, thereby enhancing human-like fidelity and interaction performance in clinical communication training-oriented VP simulation. Our multiagent framework constructed 5 specialized subagents by simulating the functional partitioning of brain regions, collaboratively simulating the entire process, from case reception to interactive consultation scenarios, designed for medical students. To enhance the interaction performance of VPs, we incorporated retrieval-augmented technology, while deep character reasoning was used to improve response richness and realism. We evaluated the proposed framework through a 2-phase experiment in which the metrics of response quality, role-playing performance, interaction efficiency, information accumulation, and perceived educational utility were applied consistently: first, to compare different base models, and second, to benchmark the complete framework against a single-LLM baseline. The multiagent framework outperformed single-LLM baselines across multiple evaluation settings, achieving high information accuracy and role-playing scores under standardized dialogue conditions. Specifically, the GPT-4o-based implementation achieved peak factual consistency of 0.769 (SD 0.04), while all configurations maintained >94% clinical accuracy. The Qwen3-32B-based framework achieved the lowest misleading rate of 1.28% (SD 1.20), compared to 4.72% (SD 1.53%) for single-LLM scoring. In assessments using standard dialogue scripts, the Qwen3-32B-based framework attained the highest role-playing competency score of 39.67 (SD 0.71) and received high expert praise. However, limited discriminative power against specific leading questions on low-quality inquiries indicated that while these findings specifically establish high fidelity under structured conditions, further adaptation is required for authentic student interactions. Interaction efficiency remained practical with acceptable latency (~3 s) based on Qwen3-32B while maintaining a stable information pace during multiturn dialogues. Furthermore, a preliminary exploration of factual consistency and role-playing ability across 5 clinical departments demonstrated potential scalability. The multiagent framework offers a viable simulation of SPs through the coordinated interaction of multiple LLM-based agents. This approach enhances the performance of VP simulation, providing a customizable and scalable solution for medical communication training, without compromising patient confidentiality. The framework holds substantial potential for advancing medical education approaches.
It has been confirmed that cholesterol-lowering therapy, particularly the reduction of low-density lipoprotein cholesterol (LDL-C) levels, represents the most effective measure for decreasing the incidence of atherosclerotic cardiovascular disease and related cardiovascular events. Previous studies have shown that active reduction of cholesterol levels significantly increases the goal attainment rate of LDL-C and improves clinical outcomes. Although many cholesterol-lowering medications are currently available in clinical practice and the cholesterol lowering treatment status has improved, the real-world cholesterol management in China, especially the goal attainment rate of LDL-C, is not satisfactory. This issue is closely related to the selection of initial cholesterol-lowering treatment strategies. Furthermore, clinical research has demonstrated that the safety and adherence of cholesterol-lowering therapy are also critical factors influencing treatment effectiveness. In response, the National Cardiovascular Disease Expert Committee Cardiovascular Metabolic Medicine Professional Committee has organized domestic experts to systematically and comprehensively review methods and scientific choices for initiating cholesterol-lowering therapy in the Chinese population and developed a Chinese expert consensus on the selection of initial cholesterol-lowering strategies based on current evidence. It aims to propose optimized initial treatment regimens tailored to individual characteristics, thereby further improving the prevention and management of dyslipidemia in Chinese population.
Multiple sclerosis (MS) is a chronic neuroinflammatory disorder, and approximately 50% of MS patients develop depression, making it one of the most common comorbidities of the disease. MS-related depression significantly reduces quality of life, worsens neurological disability, and increases suicide risk. Despite its high prevalence, the underlying mechanisms remain unclear. While neuroinflammation and neurotransmitter dysregulation have been implicated, recent evidence suggests that ferroptosis, an iron-dependent form of cell death, may contribute to both neuronal death and mood disturbances in MS patients. Ferroptosis is driven by iron accumulation, lipid peroxidation (LPO), and oxidative stress, all of which are elevated in MS lesions. The inflammatory environment in MS may exacerbate ferroptosis-related processes, potentially contributing to demyelination, neuronal dysfunction, and altered neurotransmitter metabolism-factors strongly linked to depressive symptoms. This review examines the potential role of ferroptosis in MS progression and MS-related depressive symptoms, with a particular focus on oxidative damage and inflammatory signaling related to iron metabolism in the central nervous system (CNS). Understanding these mechanisms may inform future therapeutic hypotheses for MS patients suffering from depression.
Immune escape remains a major barrier to durable cancer immunotherapy. Although checkpoint blockade has transformed cancer treatment, resistance commonly reflects broader tumor-intrinsic and microenvironmental programs that sustain immune dysfunction. At this interface, STAT3 emerges as a central organizing node. Beyond its canonical role in inflammatory and oncogenic signaling, STAT3 links tumor cell plasticity, immune suppression, and metabolic adaptation across the tumor ecosystem. In tumor cells, STAT3 promotes stemness, survival, checkpoint ligand expression, impaired antigen presentation, and immunosuppressive secretomes. In immune compartments, it drives regulatory T cell expansion, myeloid-derived suppressor cell accumulation, tumor-associated macrophage polarization, and dendritic cell dysfunction, thereby stabilizing an immune-resistant niche. STAT3 also reinforces immune escape through metabolic rewiring and multicellular feed-forward circuits. These features make STAT3 an attractive but challenging therapeutic target. Here, we discuss how STAT3 functions at the tumor-immune interface to coordinate immune escape and highlight therapeutic opportunities for targeting this axis in cancer.
Skin photoaging, primarily driven by ultraviolet B (UVB) radiation, is a complex process involving oxidative stress and autophagic dysfunction, for which effective therapeutic options remain limited. Here, we identified a novel peptide, OA-AL14 (ALFWPMKKPWPESC), from the skin secretions of the frog Odorrana andersonii Boulenger, 1882, and investigated its protective effects against UVB-induced photoaging. OA-AL14 exhibited excellent biocompatibility and potent antioxidant activity in vitro. In a UVB-irradiated mouse model, topical application of OA-AL14 significantly ameliorated key features of photoaging, including erythema, pigmentation, epidermal hyperplasia, and barrier disruption. Mechanistically, OA-AL14 activated the Nrf2 antioxidant pathway and restored cellular redox balance. Furthermore, transcriptomic and biochemical analyses revealed that OA-AL14 induced protective autophagy via the AMPK/mTOR signaling pathway. Inhibition of autophagy partially abrogated its protective effects, confirming the functional relevance of this mechanism. These findings establish OA-AL14 as a promising multifunctional candidate for treating skin photoaging by integrating antioxidant defense and autophagy activation.
Urbanization-driven, large-scale rural-to-urban migration in China has substantially modernized household energy use and reshaped air pollution exposure pathways. However, the magnitude, underlying drivers, and temporal evolution of the resulting health outcomes from combined indoor and outdoor air pollution remain insufficiently resolved. Here, by coupling a reconstruction of seven decades of migration (1949-2021) with nationwide household energy surveys, we quantify migration-attributable changes in integrated (indoor + outdoor) PM2.5 exposure and mortality. Relative to a no-migration counterfactual from 1949 onward, migration reduced integrated PM2.5 exposure by 27.6 μg·m-3 (15.7-39.4 as the 95% confidence interval) in 2019 and cumulatively avoided 2.3 (1.9-2.6) million deaths since 1949, with reductions in indoor exposure providing the dominant contribution. Arising from rural-urban disparities in household energy use, these health gains were pronounced even during intermediate stages of societal development and are likely to occur in other transitioning economies worldwide. Our study thus challenges the conventional view that rapid urbanization in developing economies is strictly detrimental to environmental health.
Perilla frutescens (L.) Britton is a highly valuable medicinal plant known for a wide variety of chemotypes based on the components of its essential oils. The appropriate and secure medicinal use of P. frutescens has been severely limited due to the lack of chemotype classification standards and pharmacological studies. In this paper, a classification standard for essential oils in P. frutescens was proposed. The pharmacological activities of different chemotypes or their main components were summarized. Genetic and molecular studies related to the formation of different chemotypes were also reviewed. The molecular mechanism underlying the formation of P. frutescens chemotypes is also discussed to pave the way for the innovation of P. frutescens germplasms for medicinal use.
Lung adenocarcinoma is a common malignancy that requires new treatments. Arsenic trioxide (ATO) exerts antitumor activity in various cancers; however, its mechanisms of action in lung adenocarcinoma remain unclear. The 24-h half-maximal inhibitory concentration (IC50) of ATO on human lung adenocarcinoma A549 cells was determined using the Cell Counting Kit-8 assay. Cells were treated with the IC50 concentration in the experimental group, and untreated cells served as the control group. A comparative assessment of cell proliferation, apoptosis, invasion, and migration was performed. Transcriptome sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted to identify differentially expressed genes and enriched pathways. Candidate pathway proteins were validated by western blot analysis. The 24-h IC50 of ATO was 99.12 μmol/L. The ATO-treated group exhibited reduced proliferation, increased apoptosis, and decreased invasion and migration ( P < 0.05) compared with that in the control group. Transcriptome analysis revealed 4,522 upregulated and 4,045 downregulated genes, with enrichment in the mammalian target of rapamycin (mTOR) signaling pathway, base excision repair (BER), and apoptosis pathways. At the protein level, total mTOR expression did not significantly change, whereas phosphorylated mTOR (p-mTOR), APE-1, Bcl-2, and Bcl-XL were downregulated, and cleaved caspase-8 and cleaved caspase-9 were upregulated ( P < 0.05). These results indicate that ATO suppresses the malignant phenotype of A549 cells by inhibiting mTOR phosphorylation, downregulating key BER components, and activating the extrinsic and intrinsic apoptotic pathways, providing experimental evidence for further studies of ATO in lung adenocarcinoma therapy.
In recent years, videogames have gathered interest in cognitive neuroscience for their potential to study cognition in dynamical and naturalistic contexts. Yet, the complexity of game environments often challenges traditional modeling approaches, and current annotation methods-typically manual or based on modified games-remain labor-intensive and limited in scope. Here, we introduce a flexible and scalable framework using the gym-retro Python library to emulate a classic action-platformer, Shinobi III: Return of the Ninja Master, and automatically annotate gameplay events directly from the game's memory states. This setup enables the identification of both player actions (e.g., jumping, hitting) and feedback events (e.g., killing an enemy, being hit), without modifying the game. Four individuals played the videogame for a combined total of 32 h (>7 h each) while undergoing functional magnetic resonance imaging (fMRI). Resulting activation maps revealed distributed engagement of visual, motor, executive, and limbic systems, consistent with the cognitive demands of gameplay. Within-participant reproducibility of brain responses across sessions was robust across event types (r ≈ .25-.55), with some consistency observed even for rarer events like HealthLoss. Between-participant correlations were notably lower, reflecting participant-specific neural signatures. Multivoxel pattern analysis showed that brain responses to different in-game events were highly discriminable, with classification accuracy typically around or above 90%, though occasionally dropping to ~40% for less frequent events. These findings demonstrate that automated emulator-based annotations enable robust, interpretable, and scalable mapping of naturalistic cognitive processes using commercial videogames.
Glycated albumin (GA) is a valuable biomarker for monitoring glycemic status. However, measurement standardization is challenged by methodological heterogeneity, where different analytical principles and target measurands cause quantification discrepancies. This study systematically compared prevailing methodologies to identify a robust reference measurement procedure for widespread standardization. We compared a targeted bottom-up proteomics method (ID-LC-MS/MS) with an enzymatic assay and the Japan Society of Clinical Chemistry (JSCC) reference method. A cohort of 129 donor serum specimens and certified reference materials (JCCRM-611) were analyzed to assess methodological comparability. Furthermore, GA concentration-dependent glycation kinetics at the Lys-525 site of albumin was examined. The optimized targeted bottom-up proteomics method showed a strong correlation (r = 0.986) with both the enzymatic assay and JSCC reference method. However, a progressively increasing negative systematic bias was observed at higher GA levels, confirming that Lys-525 underestimates GA at higher levels. In addition, with increasing overall GA concentration, the glycation ratio at the Lys-525 site consistently declined compared to the total glycated lysine residues. The standardization of GA measurements requires a precise, universally accepted definition to address analytical discrepancies. The present results indicate that quantification targeting all glycated lysine residues (as in the JSCC method) aligns more closely with biologically relevant GA values than site-specific measurement at Lys-525, which shows greater bias at higher concentrations. Therefore, further GA standardization would focus on adopting total glycated lysine residues on albumin as the preferred measurand definition, to improve detection accuracy and clinical comparability.
To clarify the potential anticancer role of celecoxib and its immune-related mechanisms. We confirmed the antitumor effects of celecoxib using Cell Counting Kit-8, wound-healing, colony-formation, and transwell assays. Network pharmacology and enrichment analyses were performed to identify pathways linking celecoxib to cervical cancer. Based on these results, two-sample and two-step Mendelian randomization (MR) analyses using blood expression quantitative trait loci instruments were conducted to evaluate the causal effect of NEU1 inhibition-the key celecoxib target-on cervical cancer risk and to assess immune cell mediation. Celecoxib significantly inhibited cervical cancer cell proliferation, migration, colony formation, and invasion. Network pharmacology and enrichment analyses consistently highlighted T-cell-related immune pathways. MR revealed that genetically proxied NEU1 inhibition reduced cervical cancer risk (OR = 0.736, 95% CI: 0.566-0.958), with CD25 on CD45RA+ CD4+ non-regulatory T cells mediating 28.458% of the total effect. By integrating genetic causal inference, in vitro experiments, and network pharmacology, our study systematically reveals that celecoxib may exert therapeutic effects by targeting against cervical cancer by targeting NEU1 and modulating CD25 on CD45RA+ CD4+ non-regulatory T cell-related immune pathways. This finding highlights both the novelty and the translational potential of this approach.
Precise control over cation distribution is critical for high-performance perovskite solar cells (PSCs). Conventional bulk doping often leads to vertical segregation and lattice strain, while surface passivation dose not ensure bulk homogeneity. We introduce a triple-alkali interlayer (LiOH/KCl/CsI) deposited on the electron transport layer prior to crystallization of the perovskite film. This design spatially decouples crystallization regulation from compositional modulation, i.e., localized Li+ and K+ ions reconstruct the buried contact and passivate defects and interfacial Cs+ acts as a dynamic source for in situ upward diffusion. This bottom-up mechanism facilitates stress-free crystallization, resulting in a dense, preferentially oriented perovskite film with a void-free buried interface and superior compositional homogeneity. Consequently, the resulting champion n-i-p PSC achieves a remarkable power conversion efficiency of 26.13%, with a high open-circuit voltage of 1.184 V and a fill factor of 83.81%. Furthermore, the devices demonstrate robust durability maintaining 93.7% after 1440 h of continuous 1-sun irradiation at 65°C. This work provides a promising pathway for managing cation dynamics to realize efficient and stable perovskite photovoltaics.
Tissue factor pathway inhibitor (TFPI), a key regulator of tissue factor-initiated coagulation through FXa-dependent inhibition of the tissue factor-FVIIa complex, has emerged as a promising target for restoring thrombin generation. This ex vivo pharmacodynamic study aimed to evaluate the KN057, a novel humanized TFPI-neutralizing antibody, in plasma samples from participants with haemophilia or type 3 von Willebrand disease (VWD3). In this ex vivo spiking study, plasmas obtained from haemophilia or VWD3 participants were supplemented with KN057 at the concentration of 0-140.00 nM. The thrombin generation assay (TGA) and the dilute prothrombin time (dPT) assay were performed to assess coagulation responses. Between 26, May 2021, and 3, September 2021, a total of 29 participants were enrolled in this study, including 10 haemophilia A (HA) without inhibitors, 6 haemophilia B (HB) without inhibitors, 6 HA with inhibitors, 3 HB with inhibitors, and 4 VWD3. In participant plasmas supplemented with KN057, peak thrombin and endogenous thrombin potential (ETP) increased notably between 1.12-5.60 nM, and reached a maximal level at 28.00 nM. A dose-dependent decrease in dPT was observed in all participants with haemophilia or VWD3. KN057 exhibited a consistent ex vivo pharmacodynamic profile, including both the response trend and effective concentration range, across plasma samples from patients with HA or HB, irrespective of inhibitor status. Furthermore, its pharmacodynamic activity in plasma from patients with VWD3 was comparable to that observed in haemophilia plasma.