With the population of older adults growing, nurses are increasingly likely to care for older patients. Ageist attitudes and behaviors in nurses may affect care quality, patient health, and care willingness. Ageism, referring to prejudice, stereotyping, or discrimination against individuals or groups based on their age, has been widely studied in the literature, primarily in non-East Asian countries, and few studies have been designed to investigate ageism and ageist behaviors among hospital nurses in Taiwan. This study was designed to investigate ageism and ageist behaviors among hospital nurses and identify the factors associated with ageist behaviors. A cross-sectional approach was used, and 359 nurses in Taiwan were enrolled as participants. Data were collected using a structured questionnaire comprising sociodemographic characteristics, the Fraboni Scale of Ageism (FSA), and Relating to Older People Evaluation (ROPE). The mean FSA scale score was 68.77 ± 8.83 and the mean proportion of ROPE was 0.39 ± 0.13, with 0.51 ± 0.16 for positive ageist behaviors and 0.34 ± 0.15 for negative ageist behaviors. Age, working unit, having taken age-related courses at school, and aging anxiety were all shown to relate significantly to ageist behaviors. In addition, a significant association was found between ageism and ageist behaviors. Predictors of ageist behaviors include age, working unit, having taken age-related courses at school, and ageism. The findings of this study indicate discriminatory attitudes and behaviors toward older adults exist among hospital nurses and that nurses who are older, work in operating rooms or critical care units, have not taken age-related courses in school, or have higher levels of ageism are at higher relative risk of exhibiting ageist behaviors. The findings of this study may be used to guide nursing managers in developing tailored interventions for nurses across different age groups and work units to effectively prevent or mitigate ageist behaviors. Furthermore, nursing educators may use this information to design age-related courses to enhance student awareness of ageist behaviors.
Tetrathiatriarylmethyl (trityl) radicals are key spin probes for electron paramagnetic resonance (EPR) spectroscopy and crucial building blocks for high-performance dynamic nuclear polarization (DNP) agents. However, their applications have been limited by complex synthesis and structural modifications. In this study, we address this limitation by developing an oxidative radical-polar crossover (ORPC) strategy for trityl derivatization. This approach utilizes oxidization of trityl radicals by nitrosyl tetrafluoroborate (NOBF4) to the corresponding trityl carbocations, which subsequently undergo aromatic nucleophilic substitution (SNAr) with a diverse range of nucleophiles to afford various trityl derivatives. This method exhibits several notable advantages: (1) wide substrate scope, compatible with N-, S-, P-, and C-centered nucleophiles, including water-sensitive organozinc reagents; (2) high regioselectivity for monofunctionalization of a single aryl ring, avoiding statistical reaction mixtures; (3) iterative ORPC reaction which enables the synthesis of both symmetric trityls with three identical substituents and asymmetric trityls with three distinct substituents; (4) significantly improved yields which are 1.5-2 fold higher than those reported in the literature. This straightforward approach provides a powerful tool for tailoring trityl radicals to advance their applications in the fields of EPR and DNP.
This study aims to establish an interpretable framework for analyzing root causes of autonomous vehicle (AV) crashes by leveraging unstructured crash narratives. It addresses critical gaps in existing research, including fragmented causal attribution and limited utilization of textual data for mechanistic insights. We propose an integrated framework that combines Large Language Model (LLM) and Chain-of-Thought (CoT) reasoning to analyze the causal mechanisms of AV crashes using original crash narratives. First, this study employs a sentence-level resampling method to oversample the labeled data. Second, the instruction-tuned LLM is used to extract structured Crash Causality Frames (CCFs), quintuple encoding Movement, Impact, Damage, Effect and Location, from 931 California DMV crash reports. Then, a system-theoretic taxonomy maps CCF elements to 64 causal indicators across five domains. Finally, CoT reasoning generates stepwise natural-language explanations to enhance interpretability. The optimized LLaMA-70B + LoRA model achieved 86.64% Accuracy in CCF extraction, while Data_sCR resampling further improved metrics to 97.93%. Analysis revealed five dominant causation patterns: Pattern 1 (30.5%, pure CV anomalies), Pattern 2 (51.9%, AV-CV interaction failures), and Patterns 3-5 (17.7%, integrating human/environment/, and infrastructure factors). Critical cross-domain couplings were identified (A1 and B2), with rear-end collisions (82.06%) predominating in Pattern 2 scenarios. Moreover, the CoT module generates auditable, step-by-step causal chains to enhance interpretability. Under a practical balance between reliability and computational cost, the accuracy of the generated CoT causal chains reaches 91.04%. The framework transforms unstructured crash narratives into interpretable causal models, demonstrating that systemic interactions (particularly AV-CV behavioral mismatches) constitute primary crash catalysts. Practical implications include: (1) Enhancing real-time CV intention prediction via V2X, (2) Developing context-aware sensor fusion for adverse environments, and (3) Implementing standardized tester training protocols for takeover scenarios.
FTO (Fat mass and obesity-associated protein) is an RNA demethylase crucial for epitranscriptomic regulation, catalyzing the removal of N6-methyladenosine (m6A) modifications. We designed a series of carbazole derivatives and identified compound K27 as a promising FTO inhibitor, exhibiting an IC50 value of 35.58 ± 5.23 μM. Spectroscopic analyses confirmed the binding of K27 to FTO and revealed ligand-induced changes in the protein microenvironment. Moreover, molecular docking and 300 ns molecular dynamics simulations demonstrated stable binding of K27 within the FTO active site. Collectively, these results highlight K27 as a promising lead scaffold for developing FTO inhibitors.
Over 90% of nurse practitioners (NPs) are employed in hospitals in Taiwan. The influence of different practice environments and manager leadership styles on NP interprofessional collaboration and quality of care in acute care hospitals has been inadequately studied. This study was designed to investigate the influence of practice environment and leadership style on NP interprofessional collaboration and the quality of care they provide in acute care settings. A cross-sectional design and a national online survey were employed to collect data from 1,198 NPs who are members of the Taiwan Association of Nurse Practitioners (TANP). The measures utilized in this study include the Nurse Practitioner Acute Care Organizational Climate Questionnaire, the Multifactor Leadership Questionnaire-Form 6S, and the Provider-Perceptions of Team Effectiveness Questionnaire (Provider-PTE). A multiple regression model was applied to identify the factors potentially associated with interprofessional collaboration and quality of care. Physician relations and professional visibility were identified as the two most critical factors within the practice environment, enhancing interprofessional collaboration and quality of care, and "management with expectation" was identified as a key leadership strategy for improving both outcomes. These three factors accounted for 44.8% and 30.6% of the respective variances in NP interprofessional collaboration and quality of care. Improving practice-environment factors such as relationship with physicians and professional visibility, as well as managing NPs using an expectations-based leadership style, offer the potential to significantly enhance NP interprofessional collaboration and the quality of care they provide. Health care organizations may consider developing policies that focus on improving the practice environment as well as implementing transactional leadership styles to promote NP interprofessional collaboration and the quality of care they provide.
The refractory nature of periodontitis stems from two interrelated factors: the difficulty in eradicating deeply entrenched pathogenic biofilms and the biofilm-induced impairment of mitochondrial autophagy in immune cells, leading to metabolic dysregulation and persistent inflammation. These processes mutually reinforce each other, creating a self-perpetuating vicious cycle. To address this, we developed a spatiotemporally programmable smart hydrogel (GM hydrogel), constructed on a dynamically crosslinked network of oxidized fucoidan and carboxymethyl chitosan, loaded with silver nanoparticles and EGCG-modified MXene nanosheets (MXene@EGCG-Ag). This near-infrared (NIR) light-responsive platform exhibits excellent injectability, enabling it to completely fill narrow, deep, and irregular periodontal pockets, ensuring intimate contact with pathological sites. The GM hydrogel provides programmed control along both temporal and spatial dimensions. In the temporal dimension, NIR irradiation triggers MXene-mediated mild photothermal effects (<45 °C) that disrupt biofilm structure and facilitate Ag+ and EGCG penetration into deeper tissues. In subsequent stages, sustained EGCG release restores mitochondrial autophagy, reprogramming immune cell metabolism to improve the immune microenvironment. Spatially, the hydrogel penetrates mature biofilms and delivers comprehensive treatment from the surface through deep gingiva to the alveolar bone interface. Experimental results demonstrate that GM hydrogel disrupts ionic homeostasis and impairs biofilm functionality in Porphyromonas gingivalis, exhibiting potent antibacterial effects. Sustained EGCG release activates the PINK1/Parkin-mediated FOXO pathway, which restores mitochondrial autophagy and induces metabolic reprogramming, thereby suppressing inflammation and promoting alveolar bone regeneration.
Unaccompanied Refugee Minors (URMs) are an extremely vulnerable refugee group, at heightened risk of adversity and trauma, as well as long-term, severe mental health difficulties. There is a lack of research providing a contextual understanding of difficulties and active resilience processes to inform how to promote URM wellbeing. This qualitative study explored the difficulties and coping responses of former URMs from Afghanistan and perceptions of how and from where coping strategies are developed. Reflexive Thematic Analysis of 12 interviews generated three overarching themes: "Difficulties and coping: a series of cumulative challenges and vicious cycles"; "Roots to coping"; and "Coping is dynamic: the process of change". Participants reported multiple and compounding difficulties, often present in a triad of physical/psychosomatic pain, mental health difficulties and social challenges. Participants described resilience mechanisms and the barriers to coping strategies being used and effective, revealing how the ability to employ strategies may be limited and that strategies may contribute to further challenges. Experiences of early attachment, culture and identity could be observed to influence the ways coping strategies are appraised and developed. The importance of prioritising belonging and providing trauma- and attachment-informed care is discussed.
To develop the clinical prediction rule (CPR) of upper urinary tract deterioration (UUTD) outcome at three years, which is the average diagnostic timepoint, in patients with traumatic spinal cord injury (TSCI). Retrospective cohort study. Department of Rehabilitation Medicine, Maharaj Nakorn Chiang Mai Hospital. TSCI patients with onset of injury in January 2008December 2020. After screening the medical records of 714 TSCI patients, clinical and urodynamic parameter data from 176 patients, collected at 3-18 months after SCI, were retrospectively analyzed. CPR was developed to predict UUTD at three years after SCI by conducting logistic regression analysis. The performance of the model was evaluated in terms of both discrimination and calibration using the AuROC and calibration plot, respectively. The incidence of UUTD was 18.8% (33/176) with a mean duration of 3.72 years after the onset of injury. The developed CPR consists of three predictive factors: completeness of SCI (American Spinal Injury Association - ASIA Impairment Scale [AIS] C), presence of detrusor overactivity, and the occurrence of autonomic dysreflexia during a urodynamic study, to predict UUTD at three years after SCI. The developed CPR had acceptable discriminative (AuROC = 0.711 [95%CI:0.603-0.819]) and calibrating performance (nearly approximate observed and predicted risk graphs and Brier Score = 0.1245). Our developed CPR for prognosing UUTD at three years after TSCI was established and demonstrated acceptable performance in both discrimination and calibration. However, a further external validation study is needed before applying this CPR in other clinical contexts.
This descriptive correlational study aimed to examine the relationships between intensive care nurses' individual and professional characteristics, decision-making styles, and attitudes toward evidence-based nursing practice. Cross-sectional study. The study was conducted with 279 intensive care nurses working in the intensive care units of two university hospitals in Istanbul between October and December 2022. Data were collected using a survey comprising a Descriptive Information Form, the Nurse Decision Making Scale, and the Evidence-Based Nursing Attitude Questionnaire. A structural equation model was developed to analyse the relationships among variables. Examination of path coefficients revealed that nurses' decision-making levels were significantly predicted by the beliefs and expectations toward the EBNP subscale of evidence-based nursing practice (β2 = 0.48, p < 0.001, t = 9.67), duration of intensive care professional experience (β2 = 0.13, p = 0.008, t = 2.66), and engagement with current professional publications (β2 = 0.22, p < 0.001, t = 4.33). The regression model accounted for 35% of the variance in nurses' decision-making levels. Despite generally positive attitudes toward evidence-based nursing among intensive care nurses, the majority demonstrated a strong tendency toward intuitive decision-making approaches. No patient or public involvement.
The 2026 Conference on Retroviruses and Opportunistic Infections (CROI) furthered our understanding of acute COVID-19, long COVID, postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), viral immunity, and SARS-CoV-2 therapeutics. Results of a first-in-human validation study of DNA-encoded monoclonal antibody (DMAb) technology demonstrated safety and robust and durable monoclonal antibody (mAb) production, giving the green light to further develop the DMAb platform. Pemivibart administration to people with advanced HIV was well tolerated and associated with good levels of neutralizing antibodies. A new pan-coronavirus 3C-like protease inhibitor was shown to have similar pharmacokinetics and a similar safety profile in people with renal impairment and people with hepatic impairment. A study of SARS-CoV-2 infections in 2023 demonstrated continued risk for new incident diagnoses and worsening of prior comorbidities in the year after infection. SARS-CoV-2 infection in people with HIV is associated with discernible decline in estimated glomerular filtration rate in the 2 years after infection. A blinded study of circulating SARS-CoV-2 antigen found no association between the presence of antigen and the likelihood of having long COVID. Most people with long COVID in a cohort study have experienced stigma or feeling dismissed in interactions with their clinicians.
Xenotransplantation (XT) has recently been promoted as a potential solution to the organ shortage. While public attitudes toward XT have received increasing attention, little is known about people's XT attitudes when contextualized within the existing human organ supply (deceased, living, and research), and whether XT influences preferences regarding human organ donation. This study examines (i) how donation context shapes XT attitudes, (ii) whether framing XT as an alternative acts as a decoy to increase support for human organ donation, and (iii) ethnic differences in XT attitudes in the UK. An online experiment (N = 3142: 1633 White, 600 Asian, 555 Black, 354 Mixed) employed a 3 (donation focus: deceased organ donation, living organ donation, or donating tissue for research) by 2 (XT decoy nudge: present, absent) between-subjects design. Those exposed to the living donation condition and the XT-decoy were more likely to find XT morally justifiable and say that their trust in the NHS would not decline if pig organs were used as transplants. The XT-decoy did not influence support for human organ donation. UK Ethnic minorities strongly oppose XT but showed support for the NHS doing more to encourage human organ donation, particularly the Black community. These findings show, for the first time, that presenting XT with living donation increased support for XT and reduced concerns that NHS trust would fall if XT were introduced. This has implications for future XT communications and underscores the need for public consultations tailored to ethnic minorities in the UK.
Recombinant adeno-associated virus (AAV) vectors are predominantly nonintegrating, but rare genomic integration events have been associated with oncogenesis in neonatal murine models. Here we report a case of a neuroepithelial tumor that developed in a 5-year-old boy with severe mucopolysaccharidosis type I (MPSI, Hurler subtype) 4 years after intracisternal magna administration of AAV serotype 9 gene therapy. The patient underwent successful resection of the primary tumor. Postoperatively, he has continued to have advanced cognitive function for his age, a finding that indicates mitigation of MPSI. Molecular analysis of the tumor showed clonal integration of rearranged AAV vector elements into the gene PLAG1 and expression of a chimeric AAV-PLAG1 transcript.
The adaptive derivative-assembled pseudotrotter variational quantum eigensolver (ADAPT-VQE) is a promising hybrid quantum-classical algorithm for molecular ground-state energy calculation, yet its practical scalability is hampered by redundant excitation operators and excessive measurement costs. To address these challenges, we propose Param-ADAPT-VQE, a novel improved algorithm that selects excitation operators based on a parameter-based criterion instead of a traditional gradient-based metric. This strategy effectively avoids redundant operators. We further developed a sub-Hamiltonian technique and integrated a hot-starting VQE optimization strategy, achieving a significant reduction in measurement costs. Numerical experiments on typical molecular systems demonstrate that Param-ADAPT-VQE outperforms the original ADAPT-VQE in ansatz size, computational accuracy, and measurement costs. Furthermore, our scheme retains the fundamental framework of ADAPT-VQE and is thus fully compatible with its various modified versions, enabling further performance improvements in specific aspects. This work presents an efficient and scalable enhancement to ADAPT-VQE, mitigating the core obstacles that impede its practical implementation in molecular quantum chemistry.
Ensitrelvir, an oral inhibitor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease, is approved in Japan for the treatment of mild-to-moderate coronavirus disease 2019 (Covid-19). Previously, no antiviral agents were approved for postexposure prophylaxis in household contacts of patients with Covid-19. In this double-blind, randomized, placebo-controlled trial, we randomly assigned persons who were SARS-CoV-2-negative on local diagnostic testing but were household contacts of a patient with Covid-19 (the index patient) to receive either ensitrelvir (375 mg on day 1 and 125 mg daily on days 2 through 5) or placebo within 72 hours after symptom onset in the index patient. The primary end point was Covid-19 (defined by a central laboratory-confirmed positive reverse-transcriptase-polymerase-chain-reaction assay and the presence of ≥1 of 14 prespecified Covid-19 symptoms lasting ≥48 hours) by day 10 in a household contact in the modified intention-to-treat population (all the participants who underwent randomization, had a central laboratory-confirmed negative RT-PCR test for SARS-CoV-2 at baseline, and received at least one dose of the trial drug or placebo). The modified intention-to-treat population included 1030 participants in the ensitrelvir group and 1011 in the placebo group. The mean age of the participants was 42.4 years; 71.1% had undergone randomization within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. The incidence of Covid-19 was lower in the ensitrelvir group than in the placebo group (2.9% vs. 9.0%; risk ratio, 0.33; 95% confidence interval [CI], 0.22 to 0.49; P<0.001). The incidence of adverse events during the trial was similar in the two groups (15.1% in the ensitrelvir group and 15.5% in the placebo group), as was the incidence of serious adverse events (0.2% in each group). No Covid-19-related hospitalizations or deaths were reported. Ensitrelvir administered to household contacts of a patient with Covid-19 within 72 hours after symptom onset in the index patient was effective in preventing Covid-19 in the contacts. (Funded by Shionogi; SCORPIO-PEP Japan Registry for Clinical Trials number, jRCT2031230124; ClinicalTrials.gov number, NCT05897541.).
Soda, N and Shimokochi, Y. Effects of isolated eccentric squat training at different velocities on countermovement jump performance, quadriceps function, and hypertrophy. J Strength Cond Res XX(X): 000-000, 2026-Eccentric training is widely combined with traditional resistance training to improve athletic performance. However, evidence on isolated eccentric training with free weights remains limited. This study investigated the effects of an isolated eccentric squat training at different velocities on quadriceps function, hypertrophy, and the countermovement jump (CMJ) biomechanics. Twenty-four male college students without strength training experience were assigned to 1 of 3 8-week protocols (3 sessions·wk-1): slow eccentric squat (SES), CMJ-specific fast eccentric squat (CMJ-specific-FES), or weighted CMJ (WCMJ) training. The SES group performed 5-second descent squats at back squat 1RM (BSQ1RM); CMJ-specific-FES used rapid descents at 50% BSQ1RM. The WCMJ group trained with loads optimized for maximal power. Quadriceps function, hypertrophy, and 3-dimensional CMJ biomechanics were assessed pre-, mid-, and postintervention. The SES group exhibited the greatest quadriceps hypertrophy (10.7% vs. -0.3-2.5%, p < 0.05-0.1), whereas the CMJ-specific-FES group showed the largest improvement in early phase quadriceps rate of force development, particularly within 25 milliseconds (104.7% vs. -20.1-18.1%, p < 0.01), despite comparable strength gains across groups (9.8-23%, p < 0.05). All groups improved CMJ height and related biomechanical variables; however, the CMJ-specific-FES group demonstrated greater increases in quadriceps activities (38.5-59.6% vs. -16.8-21.2%, p < 0.05-0.1), knee joint positive power (26.4 vs. 7.7%, p < 0.05), and CMJ height (9.6 vs. 0.9%, p < 0.05) than the SES group. These findings suggest eccentric training modes should be tailored to specific goals, such as hypertrophy or explosive power, to achieve optimal training adaptations.
N95 filtering facepiece respirators (FFRs) approved by the National Institute for Occupational Safety and Health are widely used by healthcare workers to prevent the inhalation of hazardous airborne contaminants. Various nose-clip shapes and respirator styles in N95 FFRs are designed to eliminate gaps between the respirator and the wearer's facial skin, ensuring adequate protection for the wearer. However, variations in facial dimensions across sexes and races may affect the fit and, consequently, the performance of these respirators. The primary objective of this study was to assess the effect of N95 FFR design, specifically the nose-clip shape and respirator style, on the fit factor (FF). The second aim was to assess how subject characteristics, specifically sex and race, affect the respirator fit. Additionally, the efficacy of N95 FFRs may degrade over prolonged use. The authors recently developed a portable device called the Exposure Protection Integrated Communicator (EPIC) that uses dual optical sensors to measure particle concentrations inside and outside the workplace and provide real-time monitoring of the workplace protection factor for FFRs. The EPIC's performance was evaluated by comparing its results with the reference PortaCount fit tester. Two cup-shaped FFRs with different noseclip shapes and six N95 FFRs with various styles were tested. Twenty human subjects were recruited to perform the Occupational Safety and Health Administration approved quantitative fit test (QNFT) protocol by running both PortaCount and EPIC devices in triplicate with each respirator. Results indicated that respirator FF was significantly affected by respirator design and subject facial characteristics. Caucasian males generally achieved the best fit, while Hispanic or Latino females had the poorest fit, highlighting the need for design improvements that account for differences in sex and race. Additionally, the comparison between EPIC and PortaCount demonstrated a strong proportional bias, with EPIC tending to report higher fit factor values, particularly under conditions where the respirator achieved higher fit factors. These findings underscore the need for cautious interpretation and potential calibration before EPIC can be reliably used in occupational settings.
Lettuce has developed into several horticultural types, varying dramatically in plant architecture. Stem lettuce, the major type worldwide, has a succulent swollen stem. The genetic and molecular mechanisms underlying the change from small stem in leafy lettuce to large stem in stem lettuce remain largely unknown. In this study, we cloned a major QTL controlling succulent swollen stem in lettuce. The QTL encodes cytokinin oxidase/dehydrogenase 7 (LsCKX7), which degrades cytokinin. The LsCKX7 gene has a nonsense mutation or 2-bp frame-shift insertion in most cultivars of stem lettuce. The non-functional LsCKX7 led to increased concentration of cytokinins in pith and consequently at least 9.6-25.3% increase in stem diameter in different seasons. The two loss-of-function mutations in LsCKX7 occurred only in stem lettuce, suggesting its critical roles in the development of stem lettuce. The mutated LsCKX7 gene can be directly applied in breeding programs of stem lettuce. Our results also shed light on the development of stem pith and provide references for studies on other stem vegetables.
Early-life gut microbiome development is influenced by host, microbial, environmental, and social factors. Rural infants typically exhibit greater microbial diversity than their urban counterparts, yet microbiome maturation patterns in less industrialized settings remain underexplored. Additionally, though microbial eukaryotes are integral to gut ecology, most studies to date have focused predominantly on bacterial communities. Using shallow shotgun metagenomics and 18S rRNA gene sequencing, we characterized eukaryotic and bacterial gut microbiomes in an intensively sampled longitudinal cohort of ten infants from a rural community in Morelos, Mexico, each followed monthly from the first to the 18th month, providing an unusually detailed view of early-life microbiome development in a low-resource setting. Although both bacterial and eukaryotic alpha diversity increased over time, they showed distinct colonization trajectories. Age, delivery mode, and environmental exposures, such as animal contact and household factors, influenced bacterial and eukaryotic community compositions, as well as bacterial metabolic composition. Inter-kingdom microbial networks varied with age, with a reduction in taxonomic diversity after the first year of life. Age and mode of birth also influenced changes in the overall community structure and connectivity of microbial co-occurrence patterns, but did not impact the associations among specific microbial taxa. Functional profiling revealed that bacterial metabolic potential diversified with age, whereas the mode of birth had a minimal impact on functional variation. These findings highlight the dynamic nature of bacterial and eukaryotic microbiota in early life and underscore the need to explore how rural environmental exposures shape microbial maturation, with potential implications for immune development and long-term health.
Despite three decades of clinical trials, no pharmacological treatment has shown consistent efficacy for the core features of autism spectrum disorder (ASD), and regulatory approvals remain limited to risperidone and aripiprazole for severe irritability. This limited efficacy likely reflects a mismatch between underlying biology and broad trial designs. ASD is a clinically defined neurodevelopmental condition with marked etiologic heterogeneity, shaped by highly polygenic liability and a long tail of rare, often de novo, high-impact variants. Genomic studies implicate synaptic signaling, chromatin regulation, and excitatory-inhibitory processes, but this partial biological convergence does not support a single therapeutic target across the diagnostic spectrum. Debate over environmental risk factors, including prenatal acetaminophen exposure, also shows how weak causal inference can distort research priorities. We propose three priorities for ASD pharmacotherapy: genetically stratified mechanism-linked interventions, pharmacogenomics-informed symptomatic prescribing, and trials using validated or biomarker-informed endpoints that capture outcomes regarded as meaningful by autistic people.
An innovative microdisk array (MDA)-based microextraction technique was developed for the quantification of duloxetine in human urine, followed by HPLC-FLD determination. The MDA system introduces a reusable and miniaturized extraction format, where an array-type configuration enhances mass transfer efficiency while reducing both sample manipulation and solvent requirements. The device was constructed by concentrically positioning two C18 microdisks onto a stainless-steel spinal needle, secured with frit-based supports. The extraction procedure involved immersing the MDA in the aqueous sample for 40 min, followed by a short rinsing step with water and subsequent elution of the analyte using 750 μL of methanol. Experimental variables influencing both adsorption and desorption processes were thoroughly optimized. Under the selected conditions, the method exhibited a linear response within the concentration range of 25-500 ng/mL and a limit of detection of 15 ng/mL. Precision, evaluated as intra- and inter-day variability, remained below 3.1%, while accuracy, expressed as relative recovery, ranged between 102.4% and 118.1%. The greenness of the analytical procedure was evaluated using the MA index, confirming its low environmental impact. Finally, the applicability of the method was verified through successful analysis of human urine samples, demonstrating the potential of the MDA-based approach as an efficient and sustainable sample preparation strategy.