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Objective: To explore danish adolescents' experiences of Family-Based Treatment (FBT) for anorexia nervosa (AN). Method: Individual semi-structured interviews were conducted with 15 adolescents (13 females, mean age 15.8 years) at the end of treatment and analysed via inductive reflexive thematic analysis. Result: Three overarching themes were generated through analysis: Losing Control - Gaining Freedom captured adolescents' initial distress at relinquishing responsibility for renourishment to parents, later experienced as liberating, as parental oversight countered AN and restored agency. The Difficult Trust reflected how AN itself complicated trust, with adolescents feeling that others did not always believe or trust them. From Conflict to Closeness described evolving parent-child relationships, showing that early conflicts gave way to strengthened bonds, particularly with the parent who assumed primary responsibility, as collaborative engagement fostered improved communication and mutual understanding. Overall, early distress coexisted with long-term gains in autonomy and familial closeness. Conclusion: By the end of treatment, adolescents came to recognize the rationale and value of parental responsibility for renourishment in FBT, reporting that it facilitated recovery while strengthening relationships. The findings emphasize the importance of trust, safe therapeutic spaces, and active involvement from both parents, and highlight a need for targeted adaptations for transitional-age youth.
Research suggests that end-of-life experiences (ELEs) - unusual or unexplained phenomena around the time of death - can positively influence the dying process. Despite this, few studies have examined whether and how ELEs affect the experience of grief for bereaved loved ones. Using a qualitative approach, the study explored how ELEs shaped grief for eight bereaved individuals based in Aotearoa New Zealand. Interpretive phenomenological analysis was used to analyse the content of semi-structured interviews. Findings suggest that ELEs can shape grief in complex ways - often involving conflicting emotions that can alter a bereaved loved one's perceptions of mortality and moderate the intensity of grief. The study also highlights barriers to sharing these experiences, with fear of judgement playing a key role. Future research may wish to further explore the relationship between ELEs and grief, particularly with underrepresented groups.
Despite the fact that Hungarian school healthcare has a history dating back 140 years, no comprehensive study has yet been conducted to analyze the historical development and impact of system, particularly the institutionalization of the role of health visitors in educational institutions and the development of cooperation between school doctors and health visitors. 1) To explore the historical development of school health services and the takes of school doctors, 2) to analyze the involvement and role of public health visitors in school healthcare, 3) to examine the role of cooperating professionals (doctors, public health visitors, and other professionals present today), 4) to explore the challenges that determine current operations. We studied the relevant legislation, professional regulations, and literature through research, and carried out systematic and analytical work. The role of school doctors shifted from monitoring and epidemic control to preventive care and health promotion tasks. The development of school healthcare is linked to the name of József Fodor, who laid the foundations for the regular health monitoring of school-age children by introducing a public health approach. Health visitors gradually became involved in healthcare within the legal framework, and their role became increasingly important in the areas of prevention, care, and health education. Health visitors initially appeared as professionals supporting the work of doctors. Today, this cooperation extends to all areas of health visitors' professional activities and plays a fundamental role in the effective functioning of school healthcare. The cooperation between school doctors and public health visitors is one of the cornerstones of Hungarian school healthcare and plays a key role in maintaining children's health, prevention, and health promotion. Orv Hetil. 2026; 167(19): 753-764. Bevezetés: Annak ellenére, hogy a magyar iskola-egészségügyi ellátás 140 éves múltra tekint vissza, mindeddig nem készült átfogó tanulmány, amely a történeti fejlődést és annak hatását elemezve vizsgálta volna a rendszer kialakulásának folyamatát, különösen a védőnői szerep intézményesülését az oktatási intézményekben, valamint az iskolaorvos és a védőnő közötti együttműködés fejlődését. Célkitűzés: Az 1) iskola-egészségügyi szolgáltatás, az iskolaorvosok feladatainak történeti fejlődésének feltárása, 2) a védőnők iskola-egészségügyi ellátásba való bekapcsolódásának és szerepének elemzése, 3) az együttműködő szakemberek (orvos, védőnő, valamint a napjainkban jelen lévő szakemberek) szerepének vizsgálata, 4) a jelenkori működést meghatározó kihívások feltárása. Módszer: Szakirodalmi kutatómunkával tanulmányoztuk a témához kapcsolódó jogszabályokat, szakmai szabályozókat, szakirodalmi közleményeket, rendszerező, elemző munkát végeztünk. Eredmények: Az iskolaorvosok feladatköre az ellenőrző és járványügyi tevékenységektől a megelőző, gondozó és egészségfejlesztő feladatok felé mozdult. Az iskola-egészségügyi ellátás kialakulása Fodor József nevéhez fűződik, aki a közegészségügyi szemlélet meghonosításával megalapozta az iskoláskorú gyermekek rendszeres egészségügyi felügyeletét. A védőnők fokozatosan, jogszabályi keretek között kapcsolódtak be az ellátásba, és szerepük egyre hangsúlyosabbá vált a prevenció, a gondozás és az egészségnevelés területén. Megbeszélés: A védőnő kezdetben az orvos munkáját támogató szakemberként jelent meg. Napjainkban ez az együttműködés kiterjed a védőnő valamennyi szakmai tevékenységi területére, és alapvető szerepet játszik az iskola-egészségügyi ellátás hatékony működésében. Következtetés: Az iskolaorvos és a védőnő közötti együttműködés a magyar iskola-egészségügy egyik meghatározó pillére, és kulcsfontosságú a gyermekek egészségmegőrzésében, prevenciójában és egészségfejlesztésében. Orv Hetil. 2026; 167(19): 753–764.
Tire wear particles (TWP) are produced due to abrasion and, consequently, deposited on the roadside where they are transferred to the surrounding soil and surface waters. Despite the growing interest on TWP and related chemicals' effects on aquatic organisms, their potential interaction with periphytic biofilm communities is not well understood. As these complex assemblages of microorganisms form the base of aquatic food webs, it is critical to assess the potential impact of tire particles to these communities. We used cryogenically milled tire tread (CMTT), as a surrogate for TWP, to (1) expose periphyton to four CMTT concentrations (0, 50, 500, 1000 mg/L) for 14 days, and (2) compare periphyton responses to CMTT particles (1000 mg/L) and associated chemicals in separate 4 day exposures. In both scenarios, about 25-30% of CMTT were found associated with the periphyton assemblage, illustrating its function as a sink. Additionally, photosynthetic efficiency decreased slightly at the highest tested concentration, 1000 mg/L, and/or associated chemicals, while algal biomass (chlorophyll a) at 14 days decreased ∼30% for 500 and 1000 mg/L CMTT. After the 14 days exposure, changes to the community structure and composition were detected for all CMTT concentrations. In particular, the bacteria phylum Bacillota became nearly absent in the presence of CMTT; similarly, diatom abundance decreased by 45, 85 and 70% at 50, 500, and 1000 mg/L CMTT compared to control, respectively. Consequently, other groups, such as Cyanobacteriota and green algae, became more abundant at higher CMTT concentrations. For the 4 days exposure, CMTT-related chemicals alone caused effects comparable to CMTT particles. Overall, this work highlights the importance of investigating periphyton community responses to TWP, as we show they are susceptible to tire-derived toxicity, while also influencing the fate and effects of tire particles and chemicals in aquatic environments.
Investments in health artificial intelligence (AI) are accelerating across European Union member states, yet evidence linking national AI research capacity to population-level health outcomes remains scarce. Most available evaluations focus on the performance of individual-level algorithms rather than system-wide effects. This study examines whether countries with greater health AI research activity achieve better population-level health value, and under what systemic conditions this relationship emerges. We conducted an ecological panel study across all 27 EU member states for the period 2011-2024 (maximum 378 country-year observations). Two novel composite indices were constructed: the Equity-Adjusted Patient Value Index (EAPVI), aggregating self-perceived health, unmet medical needs, income-related equity gaps, and treatable mortality; and the Health AI Capacity Index (HAICI), capturing health AI publication volume, intensity, and international collaboration. Two-way fixed effects panel regressions with Arellano cluster-robust standard errors were estimated. Additional specifications included a HAICI×OOP (out-of-pocket expenditure) interaction, a COVID-19-era structural break model (HAICI×POST2020), Hansen threshold regression, and an event study design to validate parallel pre-trends. Fifteen robustness checks were conducted, including leave-one-country-out analysis, placebo tests, winsorization, and a spatial Durbin model. The Equity-Adjusted Patient Value Index (EAPVI) and the Health AI Capacity Index (HAICI) were not uniformly linked across the 27 European Union member states. Greater national health AI research capacity did not automatically translate into higher equity-adjusted patient value. The relationship between the two indices varied across financial-protection contexts. Marginal-effects analyses showed that higher HAICI was not consistently associated with more favourable EAPVI outcomes: the HAICI-EAPVI association was negative at lower OOP levels and became statistically indistinguishable from zero at higher OOP levels. This pattern is consistent with the multidimensional structure of EAPVI, in which component-level signals may move in opposite directions. For treatable mortality, a marked shift emerged after the onset of the COVID-19 pandemic (P < .001). Countries with greater health AI research capacity experienced substantially fewer treatable deaths after 2020 - approximately 0.925 fewer per 100,000 population per index unit - with effects twice as large in Eastern compared to Western European countries. A Hansen threshold specification identified a HAICI threshold of 37.9, above which the HAICI-treatable mortality association became negative, although this result should be interpreted descriptively rather than as evidence of a causal threshold. The direction of these associations was supported by most robustness checks; however, a first-difference specification that accounts for the non-stationarity of HAICI produced a coefficient of opposite sign, indicating that the reported magnitudes are sensitive to the stationarity assumption. Health AI research capacity does not automatically translate into improved population-level patient value. The observed associations were concentrated in country-years with lower out-of-pocket expenditure and were markedly stronger during the COVID-19 period than before it. This pattern is descriptive; the ecological design does not permit inferences about underlying causal mechanisms such as mobilization of research-side capacity during system stress. Because this is an ecological and correlational analysis, the findings do not identify specific policy levers. They indicate that in this panel the association between health AI research capacity and equity-adjusted population health outcomes was heterogeneous across financial-protection contexts and was most pronounced during the COVID-19 period, a pattern that merits further investigation with study designs capable of supporting causal inference.
Esophageal perforations are associated with high morbidity and mortality and can have iatrogenic or spontaneous causes. Nasogastric tube intubation, while generally considered a safe procedure, can be a very rare iatrogenic cause. A 61-year-old male underwent direct laryngoscopy, total laryngectomy, and esophageal dilation with complex closure for laryngeal obstruction and tracheocutaneous fistula secondary to laryngeal cancer. He experienced an esophageal perforation secondary to nasogastric tube advancement and required emergent surgical exploration via thoracotomy and laparotomy with washout and gastrostomy tube placement. Notably, the tube penetrated the cervical esophageal mucosa, tracked distally within a submucosal plane, and ultimately perforated the stomach at the gastroesophageal junction. He subsequently experienced recurrence of his esophageal strictures and became gastrostomy tube dependent. Signs and symptoms of esophageal perforations can present in a vague and nonspecific manner, mimicking those of other disorders. When a perforation is suspected, a chest X-ray can be used to identify early clues, and a contrast esophagogram and CT scan can be used to confirm the diagnosis. Although uncommon, esophageal perforation should be considered in any patient who develops acute symptoms following nasogastric tube manipulation. Prompt diagnosis and early surgical intervention are essential for optimal outcomes.
Our aim was to explore the reasoning and experiences of women when offered a self-sampling HPV test. This study implemented a qualitative study design and content analysis using an inductive approach. Data consisted of written narratives collected through open-ended questions from a total of 173 women. Women were included if they had been offered a self-sampling device since September 2021 and were southern Sweden residents. To achieve purposive sampling with maximum variation, attenders adhering to the screening programme, nonattenders (absent for at least two screening rounds), and women with cervical dysplasia were recruited. The content analysis generated seven categories: (1) unpleasant experience with a vaginal examination; (2) gratefulness and acceptability of self-sampling; (3) varied perception of one's capacity to perform self-sampling; (4) preference for cervical sampling by healthcare professionals; (5) anxiety and fear concerning a potential or detected HPV infection; (6) different risk assessments for acquiring an HPV infection; and (7) negative impact on mental well-being due to cervical dysplasia. The overarching theme became "the HPV self-sampling reduced practical and emotional barriers to attending the cervical cancer screening programme, but test results may create anxiety." Most women valued HPV self-sampling, although their confidence in performing it varied. Self-sampling can reduce the emotional and practical barriers to participation in cervical cancer screening. However, anxiety about cervical dysplasia or following a positive HPV test was noted, highlighting the need for healthcare professionals to provide personalised information to alleviate negative emotions.
Long-term survival in metastatic colorectal cancer (mCRC) can be achieved by curative-intent metastasectomy. Patients ineligible for upfront (primary) metastasectomy (PM) may become candidates for secondary metastasectomy (SM) following response to primary chemotherapy (PCT), still with curative intent. Most studies focus either on resectable or unresectable mCRC, limiting insights into differential subgroup benefits. Here, real-world data offer a comprehensive evaluation of PM, SM, and PCT. We analyzed real-world data from mCRC patients treated at the certified Comprehensive Cancer Center of the LMU Hospital (CCC MunichLMU) from 2007 to 2021, following ESMO's guidance for real-world evidence (GROW). Overall survival (OS) data were matched with the Bavarian Cancer Registry. OS was assessed using Kaplan-Meier estimates and Cox regression analysis, adjusting for prognostic factors, including primary tumor sidedness and number of metastatic sites. Of 840 evaluable patients, 166 (20%) underwent PM, 520 (62%) received PCT, and 109 (13%) became eligible for SM after response to systemic treatment. OS was significantly longer for PM versus PCT (82.3 vs. 41.6 months, HR = 0.47, p < 0.0001). Multivariate analysis confirmed PM benefit across all subgroups, including high-risk patients (e.g., right-sided and multisite mCRC). OS was comparable between PM and SM (82.3 vs. 80.9 months), whereas patients ineligible for local treatments had the worst OS (25 months). Both PM and SM were associated with excellent OS, also for patients with high-risk mCRC. Our findings underscore the importance of initial evaluation and continuous reassessment of resectability throughout the course of treatment against mCRC, as implemented at the CCC MunichLMU.
A 76-year-old man with angina pectoris underwent percutaneous coronary intervention (PCI) of the left anterior descending artery. While attempting to withdraw the balloon catheter, it fractured and became irretrievable, and he was transferred to our hospital. The ascending aorta was incised under cardiopulmonary bypass to remove the retained catheter, which was entangled with a coronary stent, requiring partial excision of the stent to achieve removal. Intraoperative coronary angiography revealed intimal injury of the left coronary artery. Due to the high risk of subsequent dissection and occlusion, coronary artery bypass grafting (CABG) was performed. The postoperative course was uneventful, and the patient was discharged. This case illustrates a rare complication of PCI in which catheter retention with stent entanglement necessitated surgical removal and concomitant CABG. Prompt surgical intervention is necessary in such cases to prevent life-threatening complications.
Peer workers have become increasingly incorporated into addiction services worldwide, yet mainstream frameworks continue to approach their work in terms of individual roles, clinical outcomes, or organizational barriers and facilitators to implementation. These approaches often overlook the relational and ethical dimensions through which peer support is practiced and experienced, particularly under conditions of stigma, social exclusion, and structural constraint. This study draws on 18 months of ethnographic fieldwork (February 2021-July 2022) in a nonpeer-led nonprofit organization in eastern urban China. Data include participant observation, organizational documents, and in-depth interviews with peer workers and staff. Analysis followed an abductive, interpretive approach informed by anthropological theories of relationality and ordinary ethics. Participants described peer involvement not as a set of individual roles but as ongoing processes of relational restoration and moral navigation. Becoming and remaining a "peer" entailed rebuilding trust with family, sustaining mutual obligations among peers, demonstrating loyalty toward the organization, and negotiating stigma and surveillance in everyday life. While these commitments enabled solidarity and opened limited spaces for agency, they also translated tensions rooted in systemic inequalities into moral evaluations of relationships. In this process, the organization itself became incorporated into participants' relational worlds as a moral partner, while the peer leader worked to mediate competing moral expectations between peers and the institution. This relational-ethical framework complements existing peer scholarship by foregrounding how care, personhood, and accountability are negotiated in everyday practice, offering insights relevant to contexts where peer services are expanding and becoming institutionalized within addiction service systems.
Fusion of gametes possessing meiotically reduced (haploid) chromosome complements is the main pathway of propagation among eukaryotes. However, duckweeds, the smallest angiosperms, propagate mainly vegetatively, and meiosis has not yet been documented in detail for this plant family. The more surprising was the recent evidence of rather frequent interspecific hybrids and triploid clonal accessions, which became obvious by genome size measurements, genomic in situ hybridization (GISH), and combined plastid and nuclear DNA markers. These observations indicated sexual propagation involving reduced as well as unreduced male and female gametes in Lemna minor and L. turionifera, leading to allodiploid and allotriploid hybrids (MT, MMT, MTT) and autotriploid L. minor (MMM) accessions. Here, we i) documented the meiotic stages of Lemna species for the first time photographically; ii) provided evidence of unreduced male gametes through fluorescent in situ hybridization (FISH) with single locus probes; iii) determined their abundance in different individuals and iv) discussed possible reasons for unreduced male gamete formation. These findings open new insights into the modes of sexual reproduction and evolution of duckweeds, which may be useful for future breeding efforts in this emerging crop.
IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory condition characterized by tumefactive lesions in multiple organs. Although glucocorticoids remain the cornerstone of therapy, high relapse rates and treatment-related toxicity have prompted the development of steroid-sparing strategies and targeted therapies. This review summarizes current evidence on pharmacological and non-pharmacological management of IgG4-RD and proposes a practical treatment approach based on available data and clinical experience. Glucocorticoids continue to be the first-line therapy for remission induction, achieving high initial response rates; however, relapses are common, particularly after tapering or withdrawal. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as mycophenolate mofetil, leflunomide, azathioprine, and methotrexate, are frequently used as steroid-sparing agents, although comparative evidence remains limited. B-cell targeted therapies have emerged as key treatment options. Rituximab has demonstrated high efficacy as first-line therapy and in refractory or relapsing disease, and is widely used despite remaining off-label in most regions. More recently, the anti-CD19 monoclonal antibody inebilizumab became the first therapy approved for IgG4-RD following the MITIGATE trial, which showed reduced disease flares and increased rates of glucocorticoid-free remission. Additional emerging therapies include obinutuzumab, obexelimab, CAR-T cell therapy, and cytokine-targeted agents such as dupilumab and tocilizumab, although evidence for most remains limited. Management of IgG4-RD requires an individualized approach based on disease severity, organ involvement, relapse risk, patient's comorbidities and preferences, and access to therapies. B-cell-directed therapies and other targeted agents are emerging as key components of treatment and may enable more effective and steroid-sparing disease control.
The patient is a 66-year-old man. He came to our hospital with fever for two weeks. Based on blood sampling and abdominal computed tomography (CT) scan, a diagnosis of liver abscess was made, and antibiotic treatment was started, but symptoms did not improve, so percutaneous drainage was performed. One week later, he became dyspnea and chest CT scan revealed right pyothorax, so video-assisted thoracoscopic curettage was performed. It has been reported that liver abscesses are complicated by pyothorax in a few percent of cases. There are two hypotheses as to the mechanism. The one is the spread of inflammation from the liver abscess through the diaphragm into the pleural space, and the other is iatrogenic complication of percutaneous liver drainage.
In November 2020, olaparib became the first approved poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) for metastatic castration-resistant prostate cancer (mCRPC) with BRCA1/2 mutations (BRCAm) in the Netherlands. As randomized clinical trials include fitter patients, their findings may not fully reflect real-world outcomes. The aim was to evaluate genomic testing practice and subsequent use and outcomes of olaparib monotherapy in a real-world BRCAm mCRPC population. Data were derived from ten hospitals in the Dutch CAPRI-3 registry, including mCRPC patients diagnosed between 2016 and 2021. Those receiving olaparib in standard-of-care treatment after its national approval (from November 2020) were analyzed and grouped as taxane-naïve (TN) or post-taxane (PT). The primary endpoint was overall survival (OS). Among 1996 mCRPC patients, genomic analysis (somatic and/or germline) was performed in 23.4% (range 3.8-63.2% across hospitals), identifying BRCAm in 11.3% of patients. Tested patients differed significantly in age, comorbidities, and prior treatment. Among 35 eligible BRCAm patients, 27 (77.1%) received olaparib. TN patients (8/27) were significantly older and initiated olaparib at an earlier line of therapy. Median OS was 28.7 months (95% confidence interval (CI) not reached) in TN versus 10.5 months (95% CI 9.6-11.5) in PT patients (p = 0.003). Limitations include the retrospective design and small subgroups. Genomic testing application remained limited and uneven across centers. Most eligible patients received olaparib; TN patients seemed to benefit most.
To assess the impact of screen time and outdoor activities on myopia progression in Lebanese children and to compare age groups. This prospective study enrolled 100 myopic children aged 3-17 years who presented to the pediatric ophthalmology service at the American University of Beirut Medical Center from February 2023 to January 2025. Behavioral data were obtained using a questionnaire, and clinical data were collected through retrospective chart review dating back to January 2018. Myopia was defined as a spherical equivalent (SE) ≤ -0.50 diopters (D). Annual myopia progression was compared during and after the COVID-19 lockdown and correlated with screen time and outdoor activity. The mean age was 13.2 ± 3.6 years, with a balanced sex distribution. Myopic progression was significantly higher during the COVID-19 lockdown, with the highest progression in 2020-2021 (0.65 ± 0.07 D/year) compared with 2022-2023 and 2023-2024 (both 0.29 ± 0.05 D/year; p < 0.001). Mean SE became more negative over time, reaching -3.43 ± 0.23 D in 2024 (overall p < 0.001). During lockdown, screen time increased significantly (p < 0.001), while outdoor activity decreased significantly (p < 0.001). Twenty-two percent had more than 8 hours of daily screen exposure. Outdoor activity varied: 38% spent 5-10 hours outdoors weekly and 20% exceeded 10 hours. Younger children preferred tablets (p < 0.001) and spent less time on screens (p < 0.001). Nevertheless, questionnaire-derived daily screen time, weekly outdoor time, and screen‑break variables were not statistically significantly associated with myopia progression during or after the lockdown periods in the overall cohort (all p > 0.05). Myopia progression rate was higher during the COVID-19 lockdown than in the post-lockdown period, with significantly higher progression rates in 2020-2021 compared with 2022-2023 and 2023-2024. Screen time increased and outdoor time decreased during lockdown, but were not statistically significantly associated with progression in the overall cohort. These findings add evidence from an underrepresented Middle Eastern population, supporting further longitudinal studies of modifiable environmental factors in myopia progression.
The R. dybowskii oviductal tissue undergoes significant expansion during pre-brumation rather than the pre-spawning period, reflecting a unique physiological adaptation for brumation. While vitamin D is known to support growth and reproductive functions in various organisms, its role in seasonal oviductal hypertrophy remains unclear. In this study, the vitamin D metabolic pathway's role in regulating this process was investigated. Morphometric measurements revealed a significant increase in oviductal weight and luminal diameter during pre-brumation compared to pre-spawning, while histological examination showed marked glandular cell hypertrophy in the ampullary region. Correspondingly, 1,25-(OH)₂D₃ was significantly elevated in the oviduct during pre-brumation. Immunohistochemistry revealed that vitamin D metabolic enzymes Cyp2r1, Cyp27b1, Cyp24a1, the vitamin D receptor (Vdr), and the reductase Dhcr7 were localized in both epithelial cells and glandular cells during pre-spawning, but became predominantly restricted to epithelial cells during pre-brumation. qRT-PCR and western blot analyses confirmed higher expression of Cyp2r1, Cyp27b1, Cyp24a1, and Vdr, but reduced expression of Dhcr7 during pre-brumation. To further evaluate potential functional associations, 25-(OH)D₃ and 1,25-(OH)₂D₃ levels were found to be positively correlated with the mRNA expression of steroidogenic (star, cyp11a1) and proliferative (mki67, and pcna) markers across the two periods. Transcriptome analyses further supported these findings, identifying enrichment of differentially expressed genes within the vitamin and steroid hormone biosynthesis pathways. Collectively, these results suggest vitamin D metabolism is locally upregulated in the oviduct during pre-brumation, potentially via autocrine/paracrine mechanisms, and may contribute to seasonal reproductive adaptation in R. dybowskii.
Objective: To develop an ultra-low-frequency pressure reactivity index (PRx) (EL-PRx) based on hourly data (0.000 28 Hz) as an alternative to the conventional PRx, which requires high-frequency sampling, and provide a prognostic tool for traumatic brain injury (TBI) in resource-limited settings. Methods: This multicenter retrospective cohort study included 473 participants, including patients with TBI who were identified from the MIMIC-Ⅳ and eICU-CRD databases and those admitted to Fujian Provincial Hospital affiliated with Fuzhou University between April 2018 and April 2025. They were divided into survival (n=360) and non-survival (n=113) groups based on in-hospital all-cause mortality data. EL-PRx was calculated using 9-23 h moving windows. Propensity score matching (1∶1, caliper width 0.1×logit standard deviation) was performed to adjust for confounders, including demographics, vital signs, laboratory findings, comorbidities, supportive therapies, and IMPACT model variables. Restricted cubic spline analysis, univariate logistic regression, and receiver operating characteristic curve analysis were used to evaluate the association between EL-PRx and outcomes and its predictive performance. The optimal clinical threshold was determined using sequential Chi-squared testing. Results: A total of 473 patients were included (360 survivors and 113 non-survivors). EL-PRx was significantly higher for non-survivors than for survivors. The values were 0.14 (0.00, 0.30) and 0.07 (-0.10, 0.16) (P=0.003), respectively, within the 9-h window, and consistent differences were observed across other time windows (all P<0.05). Restricted cubic spline analysis demonstrated a non-linear positive association between EL-PRx and mortality risk. Univariate logistic regression showed that EL-PRx was significantly associated with mortality across different time windows, with odds ratios ranging from 3.825 to 8.073 (all P<0.05); the strongest effect was observed within the 17-h window (OR=8.073, 95%CI 2.053-35.697). Receiver operating characteristic curve analysis indicated that predictive performance was optimal on days 5-6 with a maximum AUC of 0.667. Sequential Chi-squared testing identified 0.15 as the optimal clinical threshold for EL-PRx, which became stable when monitoring duration was≥3-4 days. Conclusion: EL-PRx, which is derived from routinely collected hourly data, can effectively predict in-hospital mortality for patients with TBI. Its threshold is comparable to that of conventional PRx, making it suitable for intensive care settings with limited monitoring resources. 目的： 开发基于极低频数据（0.000 28 Hz，每小时1次）的压力反应性指数（EL-PRx），以替代需高频采样的传统压力反应指数（PRx），为资源有限的医疗中心提供创伤性脑损伤（TBI）预后评估工具。 方法： 本研究为多中心回顾性队列研究。纳入MIMIC-Ⅳ、eICU-CRD及2018年4月—2025年4月收住入福州大学附属省立医院住院患者共473例TBI，根据住院期间全因死亡情况，将患者分为存活组（n=360）和死亡组（n=113），并在9~23 h移动窗口计算EL-PRx。采用倾向评分匹配（1∶1，卡钳宽度0.1×logit标准差）校正包括人口学特征、生命体征、实验室指标、合并症、支持治疗及IMPACT模型指标在内的混杂因素，采用限制性立方样条、单因素logistic回归及受试者工作特征曲线（ROC）分析EL-PRx与预后的关联及预测性能。通过序贯卡方检验确定最佳临床阈值。 结果： 共纳入473例TBI患者，其中存活组360例、死亡组113例。死亡组的EL-PRx均显著高于存活组，其中9 h时间窗EL-PRx的对比结果为0.14（0.00，0.30）比 0.07（-0.10，0.16）（P=0.003），其他时间窗的EL-PRx对比差异亦有统计学意义（均P<0.05）。限制性立方样条分析显示，EL-PRx与死亡风险呈非线性相关。单因素logistic回归分析显示，不同时间窗EL-PRx均为死亡的危险因素，OR值为3.825~8.073（均P<0.05），其中17 h时间窗下EL-PRx预测效应最强（OR=8.073，95%CI 2.053~35.697）。ROC分析显示，第5~6天数据预测性能最佳，AUC最高为0.667。序贯卡方检验确定EL-PRx最佳临床阈值为0.15，且当监测时间≥3~4 d时阈值趋于稳定。 结论： EL-PRx仅需每小时常规监测数据即可有效预测TBI住院病死率，其阈值与传统PRx相当，适用于医疗条件受限的重症监护病房。.
Traditional vaccine development faced significant hurdles, including lengthy timelines and high costs, which hindered rapid responses to pathogens. Although the emergence of AI offered transformative potential, the necessity for a fully integrated workflow was often overlooked in studies focusing on individual tools. This review addressed a critical gap by synthesizing AI technologies across the vaccine design process, focusing on the integrated workflow from antigen discovery to clinical translation. A systematic framework was required to connect disparate tools and ensure seamless transitions. Consequently, this study provided a comprehensive roadmap for pandemic preparedness and vaccine discovery. A systematic analysis based on the PRISMA framework (2015-2024) was conducted, and 19 landmark articles were reviewed.It was demonstrated that the paradigm shift from predictive to generative AI offered unprecedented opportunities for developing novel antigens and adjuvants with superior immunogenicity. Synthesis of the literature revealed rapid progress toward sophisticated deep learning. Transformer models and Protein Language Models emerged as dominant for epitope prediction, while AlphaFold2 became the standard for structural modeling. The advent of generative AI for de novo antigen design represented the leading edge of the discipline. Additionally, AI-enhanced molecular dynamics and digital twin simulations accelerated clinical validation and manufacturing scalability. The "Integrated AI Workflow for Vaccine Design and Development" was emphasized as a comprehensive system and a prerequisite for sustainable innovation. Overall, this analysis served as a strategic roadmap for utilizing AI as a transformative framework for next-generation vaccine discovery and pandemic preparedness.
The first protein kinases and their role in cell regulation were identified in the mid-1950s, but it was not until the 1980s that the first inhibitors of these enzymes were developed. More specific inhibitors that suppressed kinase activity at low nanomolar concentrations were described in the mid-1990s and their potential to treat cancers caused by kinase mutation became clear during the late 1990s. Over 100 protein and lipid kinase inhibitors have now been approved for clinical use during the 21st century with combined annual sales of over US$ 65 billion in 2024. They have not only transformed the clinical care of multiple malignancies but have also been exploited widely to identify physiological substrates and cellular functions of these enzymes. Here, I present some personal reflections on the early days of kinases and their inhibitors, give a few examples of how they were first exploited to dissect signal transduction pathways and explain how the first panels of protein kinases came to be established to facilitate the development of more specific kinase inhibitors.
Since 2021, avian influenza A(H5N1) clade 2.3.4.4b viruses have spread widely among wild birds and domesticated poultry in the United States, with sporadic spillover into mammals. During November 2024-January 2025, 19 domestic cats in Los Angeles County, California, became ill after consumption of commercially purchased raw milk, raw meat, or raw pet food; nine cats tested positive for influenza A(H5N1) virus (clade 2.3.4.4b genotype B3.13). Overall, 139 persons were exposed to the 19 infected cats, and all were monitored for symptoms. Although 30 persons reported influenza-like illness symptoms, none received a positive influenza A(H5) reverse transcription-polymerase chain reaction (RT-PCR) test result. In April 2025, the Los Angeles County Department of Public Health and CDC invited all exposed persons to participate in an influenza A(H5N1) serosurvey to determine whether transmission of influenza A(H5N1) virus occurred, including in those without symptoms. Sera from 25 (18%) of the 139 exposed persons were tested. Among these, antibodies specific to A(H5N1) clade 2.3.4.4.b (antigenically similar to the clade 2.3.4.4.b influenza A[H5N1] virus isolated from the infected cats) were detected in serum from one veterinary professional, who was asymptomatic. This person did not use respiratory or eye protection during the exposure, did not report influenza-like illness after the exposure, and reported no other known risk factors for A(H5N1) infection. These findings represent serologic evidence of possible transmission of influenza A(H5N1) clade 2.3.4.4.b virus from a domestic cat to a human, highlighting concerns about potential cat-to-human transmission of influenza A(H5N1) virus and the importance of infection control practices in veterinary settings.