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Integrated care has become a global focus in efforts to improve health system performance and service delivery. China began exploring the construction of integrated care and the formation of county medical communities to improve county-level medical services in 2017. The Fujian-Sanming model has attracted extensive attention during this process. In this study, we used Sanming as the example, and the data envelopment analysis (DEA) model and Malmquist index were used to analyze the effectiveness and summarize the construction experience of advanced areas. We discuss the overall medical and health service efficiency in the county as it relates to the county medical community policy. We referenced previous studies to select three input indicators and two output indicators that represent the medical and health services in the county. We then conducted an efficiency analysis of 10 counties in Sanming from both the static and dynamic perspectives using a combination of the traditional DEA-BCC model and DEA-Malmquist index. In addition, we measured the efficiency of the primary medical institutions in Sanming. The average technical efficiency (TE), pure technical efficiency (PTE), and scale efficiency (SE) improved from 0.814, 0.907, and 0.898 to 0.917, 0.965, and 0.948, respectively, from 2017 to 2022. These improvements reflected a better use of resources, improved management practices, and more appropriate allocations of the service capacity. The DEA-Malmquist index results showed that the total factor productivity (TFP) of the medical and health services in the counties of Sanming was 0.957 from 2017 to 2022, slightly lower than 1. This result indicated that resource allocation had not yet reached an optimal state, possibly due to the COVID-19 pandemic impact. In addition, disparities between counties persisted, and the primary healthcare institutions generally exhibited lower efficiency levels. The results of this study demonstrated that under the county medical community policy, the efficiency of medical and healthcare services in Sanming improved. The study results suggest that future efforts should focus on strengthening county hospitals, enhancing the capacity of primary care institutions, and promoting coordinated development across counties. The Sanming model offers valuable insights, particularly for developing countries, regarding strategies to advance integrated care reform.
Medical image segmentation plays a vital role in computer-assisted diagnosis, yet the heavy reliance on large-scale pixel-level annotations limits its scalability in real-world clinical applications. To alleviate this bottleneck, we propose a framework for annotation-efficient medical segmentation that leverages sparse supervision from scribbles and points. The framework is guided by three key principles. First, an auxiliary reconstruction branch is employed to enhance supervision and enrich feature representations derived from limited annotations. Second, a vector quantization (VQ) memory bank stores texture-specific and global features, which are dynamically refined to generate reliable pseudo labels. Third, a cross-latent graph neural network (GNN) exploits non-local dependencies from reconstruction features and transfers this relational knowledge to segmentation features, enabling context-aware and structurally consistent predictions. Extensive experiments on three benchmark datasets (ACDC, BraTS'19, and Pancreas-CT) demonstrate that our framework achieves competitive or superior performance compared with state-of-the-art weakly supervised methods, while approaching fully supervised accuracy. These results highlight the potential of our approach to substantially reduce annotation costs without compromising segmentation quality.
Background and Objectives: Traumatic brain injury (TBI) affects millions of people worldwide. The Glasgow Coma Scale (GCS) is commonly used to characterize its severity. Head computed tomography (CT) is frequently the diagnostic imaging modality of choice. Recently, blood-based biomarkers such as ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) have emerged as possible adjuncts to head CT in evaluating mild TBI (mTBI). We aim to validate the performance of the Abbott Alinity i TBI test (UCH-L1 and GFAP) compared to head CT in an Asian cohort with mTBI and GCS 15. Materials and Methods: This prospective observational study was conducted at a tertiary academic medical center from 2 December 2024 to 19 March 2025. Patients aged 21 years and above who sustained head injury within 12 h of ED attendance had GCS of 15 and required head CT as per attending physician were eligible. Plasma was separated from whole blood within 10 min of collection and immediately stored at -20 °C. UCH-L1 and GFAP levels were analyzed in batches within 28 days of recruitment at the hospital central laboratory using the Alinity i TBI test. Results: Among 120 patients enrolled, there was predominance of males (55.8%, 67/120) and Chinese ethnicity (75.8%, 91/120). The median age was 73 (interquartile range [IQR] 56 to 79) years. Overall incidence of positive head CT was 9.2% (11/120); all 11 patients had positive Alinity i TBI tests. The sensitivity and negative predictive value of the biomarkers in our cohort were both 100% (95% confidence intervals [CIs] 71.5% to 100% and 78.2% to 100%, respectively), specificity 13.8% (95% CI 7.9% to 21.7%) and positive predictive value 10.5% (95%CI 5.4% to 18%). Exploratory post hoc analysis suggested that GFAP alone, at the prespecified assay threshold, was associated with modestly higher specificity [21.1% (95% CI 13.9% to 30.0%)] in this cohort. Conclusions: The Alinity i TBI test can safely rule out intracranial injury in patients with mTBI and GCS 15 presenting within 12 h of injury. However, specificity was low, limiting its ability to reduce head CT use in its current form. Exploratory post hoc analyses of the individual biomarkers, particularly GFAP alone, should be interpreted cautiously. Future studies should focus on optimizing specificity while maintaining a high degree of sensitivity.
The 8th International Society for Respiratory Viruses (ISRV) Antiviral Group Conference, held jointly with the 3rd International Meeting on Respiratory Pathogens in Singapore (17-20 September 2025), examined evolving approaches to prevention and management of respiratory infections. This report summarizes the major themes and perspectives that emerged across the meeting. We reviewed plenary sessions, thematic symposia and panel discussions and synthesized recurring concepts relevant to clinical practice and preparedness. Discussions were organized into key domains, including therapeutics, host response, vaccination, surveillance, diagnostics and research infrastructure. Presentations highlighted the development of long-acting and broadly active antivirals, interest in combination therapy and early treatment, and increasing recognition that inflammatory host responses contribute substantially to disease severity. Advances in vaccines targeting conserved viral components and long-acting monoclonal antibodies were discussed, along with the growing role of adaptive platform trials and harmonized clinical endpoints. A recurring theme was the transition from pathogen-centred management to a broader framework incorporating host responses. Speakers also emphasized integrated surveillance using genomic sequencing, metagenomics and rapid point-of-care diagnostics within a One Health framework addressing zoonotic spillover. The meeting illustrated how clinical care, translational science and public health preparedness are becoming increasingly interconnected. Sustained investment in surveillance systems, clinical trial platforms and access to therapeutics will be necessary to translate scientific progress into routine care and to strengthen readiness for future epidemics and pandemics.
We describe Mycobacterium abscessus infections in immunocompetent children with cervicofacial lymphadenitis and localized soft tissue infections. The presence of multi-nodal disease was significantly associated with refractory infection in cervicofacial lymphadenitis. Almost all children were treated with both antimicrobials and surgery, and close to half required repeat surgery.
Background. Recurrent respiratory papillomatosis (RRP) in children remains a pressing issue in pediatric otolaryngology, characterized by a chronic course, frequent relapses, and the need for repeat surgical interventions. The aim of this study was to evaluate whether the surgical technique used for primary removal of pediatric RRP-CO2 laser, microdebrider, or a combined approach-was associated with clinically documented recurrence and early recurrence within 12 months. Materials and Methods. A retrospective study of 53 medical records of children who underwent their first surgery for RRP between 2019 and 2023 was conducted. Three surgical approaches were used: CO2 laser, microdebrider, and a combined method. Statistical analysis was performed using Pearson's χ2 test, and the strength of association was evaluated with Cramér's V. Results. The most frequently used method was the CO2 laser (n = 25), followed by a microdebrider (n = 16), and a combined method (n = 12). During the observation period, disease recurrence was recorded in 35 of 53 patients (66.0%): in 20 children, within the first 12 months after surgery, and in 15, after more than 12 months. No recurrence was documented in the available medical records for 18 patients during the observation period. No statistically significant effect of the surgical treatment method on the recurrence rate (p = 0.813) or the risk of early recurrence (p = 0.926) was found. Also, no significant association was found between the child's age and either the overall recurrence rate (p = 0.510) or the likelihood of early recurrence (p = 0.217). Conclusions. Within the limitations of this retrospective single-center study, neither the surgical treatment method nor the patient's age was associated with clinically documented recurrence or early recurrence recorded in the available medical records.
Bioelectronics are pivotal to biomedical engineering as they enable seamless communication between electronic devices and living tissues. However, conventional interfaces with static, rigid configurations often suffer from mechanical mismatch, chronic inflammation, and progressive signal degradation. By integrating stimuli-responsive materials with programmable architectures, 4D-printed devices enable in situ shape transformation and modulus adaptation, establishing a new paradigm for adaptive, high-fidelity biointerfaces. This review systematically examines recent advancements in 4D-printed bioelectronics. We first evaluate how smart materials-including hydrogels, liquid crystal elastomers (LCEs), and shape memory polymers (SMPs)-synergize with structural concepts such as auxetic lattices and kirigami/origami geometries to achieve dynamic compliance. Subsequently, we list advanced additive manufacturing strategies, particularly vat photopolymerization and direct ink writing (DIW) as well as hybrid printing strategies, which ensure high-precision fabrication. Furthermore, we highlight transformative biomedical applications, including neural interfaces, wearable devices, soft robotics, and implantable therapeutic devices. Finally, we discuss future directions for 4D-printed bioelectronic devices, focusing on the long-term stability of bioelectronic signal transduction, the integration of multifunctionality, bidirectional bioelectronic modulation, manufacturing scalability and standardization, and artificial intelligence (AI)-driven design and predictive modeling.
Personalized healthcare is crucial for transforming medical practice, offering more precise, efficient, and patient-centerd care. It not only improves individual health outcomes but also enhances the overall efficiency of healthcare systems. Wearable and implantable devices have emerged as key technologies in this transformation, offering unprecedented opportunities for real-time physiological monitoring, early disease detection, and personalized health intervention. In parallel, the rapid advancement of artificial intelligence (AI) has further accelerated the integration of data-driven intelligence into healthcare systems, making interdisciplinary research at the intersection of AI, flexible electronics, and biomedical engineering increasingly important. However, the long-term deployment of intelligent wearable and implantable healthcare systems remains fundamentally constrained by power sustainability, mechanical flexibility, and the energy cost of on-device data processing. This review focuses on self-powered intelligence as an emerging paradigm for personalized healthcare, enabling continuous, long-term, and autonomous health monitoring beyond the limitations of battery-powered systems. By integrating flexible and smart electronics with low-power AI, self-powered intelligence provide a viable pathway toward intelligent, on-body and in-body healthcare platforms capable of real-time analysis and personalized health management.
Staphylococcus aureus is a leading cause of bacterial keratitis and antimicrobial resistance-associated death globally. This study aimed to evaluate the efficacy of CaD23, a human-derived hybrid antimicrobial peptide (AMP), in combination with antibiotics in treating S. aureus infections. The efficacy of CaD23 and six medically important antibiotics (amikacin, cefuroxime, chloramphenicol, fosfomycin, vancomycin and levofloxacin) was examined against six strains of methicillin-sensitive and methicillin-resistant S. aureus using a minimum inhibitory concentration (MIC) assay. CaD23-antibiotic interactions were evaluated using checkerboard and time-kill kinetics assays. 3,3'-dipropylthiadicarbocyanine iodide (DiSC3,5) cytoplasmic membrane depolarisation assay was performed to examine the mechanism of action. Overall, CaD23 exhibited good efficacy against all MSSA and MRSA (MIC = 16-32 μg/mL [6.7-13.3 μM]). Of 20 peptide-antibiotic-organism combinations, 19 (95%) combinations demonstrated positive interactions, with six (31.6%) and 13 (68.4%) exhibiting synergistic (FICI = 0.293-0.412) and additive effects (FICI = 0.521-0.890), respectively. CaD23 was able to achieve complete bacterial eradication significantly faster than cefuroxime and levofloxacin (15 min vs. 8-24 h). When used at a sub-MIC concentration, CaD23 could accelerate the killing of S. aureus of cefuroxime from 8-24 h to within 1 h and enhance the activity of levofloxacin by 90%. CaD23 was shown to rapidly depolarise the inner membrane of S. aureus within seconds of the treatment. In conclusion, CaD23-antibiotic combination therapy serves as a useful strategy for tackling drug-resistant ocular and systemic S. aureus infections.
Nonsmall cell lung cancer (NSCLC) is one of the most prevalent cancers and leading causes of cancer-related mortality worldwide. Despite advancements in medical treatment, current therapeutic strategies are often hindered by late-stage diagnosis, high recurrence rates and resistance to therapies. These challenges highlight the urgent need for novel, less toxic and more effective treatment options. Phytoceuticals, bioactive plant-derived compounds, have gained increasing attention for their potential to complement or enhance conventional cancer therapies. Among these, nobiletin, a polymethoxylated flavonoid found in citrus peels, has promising anti-inflammatory, antioxidant and anticancer properties. This review explores the therapeutic potential of nobiletin in NSCLC, focusing on its ability to modulate key cancer hallmarks such as uncontrolled proliferation, metastasis, immune evasion and multidrug resistance. Preclinical studies suggest that nobiletin inhibits tumour growth, enhances chemosensitivity and suppresses metastasis through multiple pathways. However, its clinical application is currently limited by poor bioavailability, prompting the need for innovative delivery strategies. Therefore, this review also discusses emerging approaches to improve nobiletin's biological activity, supporting further investigations into its role in NSCLC therapy.
Individuals with chronic physical diseases are at elevated risk of developing mental health disorders. Comorbid chronic physical disease and mental health problems (CPDMHP) are associated with substantial societal and healthcare costs. Although enhancing mental healthcare for this population can improve outcomes, efforts to increase service engagement have had limited success. This study evaluates a Solution-Focused Single-Session Consultation (SF-SSC) as a brief, innovative approach to addressing structural and attitudinal barriers to treatment engagement. The study will comprise two phases: Phase 1 will consist of a prospective cross-sectional study of patients in an outpatient community health setting in Singapore. Participants will complete measures of their sociodemographic characteristics, physical and mental health status (e.g., current and past physical and mental health conditions, and service utilization), and psychosocial indicators (e.g., life satisfaction, hope, readiness for change). Phase 2 will involve a two-arm randomized controlled pilot trial that evaluates the feasibility, acceptability, and preliminary effectiveness of the SF-SSC compared with a single session of supportive therapy (SPT). Up to 60 participants from Phase 1 with elevated depression or anxiety symptoms (PHQ-9 or GAD-7 scores ≥ 5) will be randomized to receive the SF-SSC or SPT intervention. Phase 1 analyses will examine the associations among sociodemographic characteristics, physical and mental health factors, and psychological and psychosocial outcomes. The primary outcomes of Phase 2 will be the feasibility and acceptability of the SF-SSC, assessed by the completion of SF-SSC action plans (with a predefined ≥ 70% threshold) and participant-reported usefulness and satisfaction. The primary clinical/process outcome will be treatment engagement, operationalized as the willingness to be referred and attendance at a subsequent appointment. Exploratory secondary outcomes will include psychosocial constructs that are hypothesized to underlie intervention effects, such as hope, perceived agency, readiness to change, and life satisfaction. Given the pilot nature of the trial, clinical and psychosocial findings will be interpreted as preliminary indicators of potential benefit rather than confirmatory evidence of efficacy. Findings from this study will inform future trials examining the large-scale and long-term impact of the intervention. The study will also inform the design of scalable approaches that can be integrated into existing mental healthcare systems to improve mental health service uptake and engagement among individuals with CPDMHP. The trial was retrospectively registered at Clinicaltrials.gov [NCT07116655] on August 11, 2025.
Boron neutron capture therapy (BNCT) has emerged as a promising therapeutic modality in cancer treatment, demonstrating the ability to selectively eliminate cancer cells through the 10B(n,α)7Li nuclear reaction with minimal side effects on normal tissues. As a binary, target-specific therapeutic modality for malignancies, BNCT critically depends on novel boron delivery carriers that exhibit high tumor affinity and prolonged intratumoral retention. Although several boron carriers have received Food and Drug Administration approval for clinical investigation, leading carriers such as L-p-boronophenylalanine (BPA) and sodium borocaptate (BSH) continue to require high infusion doses and exhibit limited tumor selectivity and affinity, short systemic half-lives, and limited in vivo stability. These challenges have stimulated extensive global research into novel boron-10 carriers and innovative carrier platforms, including amino acids, sugars, porphyrin derivatives, nucleotides, and a variety of nanocarrier systems. This review provides a systematic classification of high-abundance boron-10 carriers, critically examines radio-boron research, and evaluates the potential integration of BNCT into clinical diagnostics and advanced cancer treatment protocols. By detailing the current status of novel boron-10 carriers, this review further aims to elucidate critical challenges and opportunities in BNCT drug development, ultimately providing a theoretical foundation for next-generation BNCT interventions.
Palliative care (PC) integration in pediatric oncology improves outcomes, yet access to PC in the Asia Pacific (AP) region remains limited. This study aimed to understand physician perceptions of PC integration in childhood cancer care across AP. The validated Assessing Doctors' Attitudes on Palliative Treatment survey was modified for use in AP, translated into six languages, and adapted for cultural relevance. The survey was distributed electronically between February 2022 and February 2024 to physicians caring for children with cancer in 18 AP countries. The primary outcome was alignment with WHO PC guidance, calculated as a mean percentage per physician. Secondary analyses explored associations between demographic variables and WHO alignment scores using regression analyses. Open-ended responses were analyzed qualitatively. A total of 621 physicians from 18 countries participated (median country response rate 30%; range, 11%-85% per country). Most (70%; n = 432) had >10 years of clinical experience and no prior PC training (65%; n = 401). Although 57% (n = 352) had access to pediatric PC experts, only 50% (n = 308), 36% (n = 221), 27% (n = 166), and 34% (n = 209) expressed comfort addressing patient/family physical, emotional, spiritual, and grief/bereavement needs, respectively. Additionally, 40% (n = 248) reported feeling burdened addressing end-of-life suffering. The mean alignment with WHO guidance was 76% (range, 48%-92%). Almost all (>90%; n = 570) desired further PC training. Study findings demonstrate that most physicians in AP expressed discomfort with providing core components of PC to patients with cancer and their families. This study signals the urgent need for focused expansion of PC services and training and identifies regional opportunities to improve PC education, research, and advocacy efforts.
In his historical studies of current high-income countries, Angus Deaton demonstrated a correlation between a country's prosperity and the health of its population. His conceptual framework has recently been expanded to include the role of alcohol. In this ecological study, we test the key assumptions of the expanded framework and classify countries with respect to both their levels of alcohol consumption and alcohol control policies to economic development. We explored linear trends from 2000 to 2022 in gross domestic product per capita at purchasing power parity (GDP-PPP per capita), life expectancy, and adult alcohol per capita consumption (APC) in 10 member states of the Association of Southeast Asian Nations (ASEAN), grouping them through cluster analyses based on these three variables. We also scored and ranked the countries based on their alcohol control policies. Lastly, we used generalised least squares models, accounting for temporal autocorrelation, to evaluate the associations between GDP-PPP per capita, life expectancy, and APC. We corroborated Deaton's conclusions that increases in economic wealth were associated with increases in life expectancy, with the largest improvements seen in low-income countries and the smallest in high-income countries. Economic transition was consistently related to increases in the level of alcohol consumption in low-income economies, with the exception of Muslim-majority countries. Following their transition to a lower middle-income status, some ASEAN countries appear to have implemented more effective alcohol control policies that halted further increases in their levels of consumption. In Muslim-majority countries, the level of consumption was low, irrespective of the level of economic development. The implementation of alcohol control policies prevents further increases in alcohol consumption and attributable harm and thus allows countries undergoing economic transition to reap the full health benefits of economic development.
Adoptive TCR-T cell therapy holds great promise for personalised cancer treatment, yet it is limited by poor surface expression, chain mispairing, and suboptimal stability of introduced TCRs. One effective structure-guided approach is to introduce a second interchain disulfide bond between the α and β constant domains. This review summarises the structural and mechanistic basis of this strategy, its impact on TCR folding, CD3 assembly, mechanotransduction, and anti-tumour function, as well as current engineering approaches, persistent challenges, and future perspectives. Preclinical studies demonstrate improved heterodimer stability, reduced mispairing, higher surface expression, and enhanced signalling, positioning the second disulfide bond as a valuable complementary tool in next-generation TCR engineering.
Plasmacytoid dendritic cells (pDCs) are a specialized subset of innate immune cells capable of sensing viral nucleic acids and rapidly producing large amounts of type I interferons (IFN-I). However, excessive IFN-I production can cause various immunopathogenic conditions. The capacity for IFN-I production by pDCs is tightly regulated, yet the underlying mechanisms remain incompletely understood. Here, we describe two levels of negative regulatory mechanisms controlling IFN-I production by pDCs. First, we identified SLC44A2 as a negative regulator of IFN-I production. Slc44a2 was highly expressed in resting pDCs but significantly downregulated upon activation. Deficiency of Slc44a2 led to excessive IFN-I production. Mechanistically, SLC44A2 may restrict IFN-I production by exporting threonine, asparagine, and glutamine, amino acids that we found to be essential for IFN-I production in pDCs. Second, we uncovered an IFN-I-dependent negative feedback mechanism controlling pDC egress. Excessive IFN-I restrained pDC migration by downregulating CCR2 and CCR5. This feedback was generally observed during viral infections, autoimmune diseases, and in Slc44a2-deficient mice. Taken together, these two regulatory mechanisms are essential for maintaining pDC homeostasis and preventing systemic overactivation of IFN-I responses.
Current guidelines recommend routine assessment of serum carbohydrate antigen 19.9 (CA19.9) at diagnosis and during follow-up of patients with intraductal papillary mucinous neoplasm (IPMN) to detect high-grade dysplasia (HGD) and invasive carcinoma (IC). Guidelines consider an elevated serum CA19.9 level (≥37 U/mL) a worrisome feature and a relative indication for surgery. To evaluate the diagnostic accuracy of CA19.9 for identifying patients with IPMN at high risk of HGD and IC. PubMed, Embase (Ovid), and Web of Science databases (inception to March 1, 2025). Studies reporting on diagnostic accuracy of CA19.9 (cut-off 37 U/mL) in patients with resected IPMN. Data extraction was completed by 3 reviewers (March to December 2025). Risk of bias was assessed using the QUADAS-2 tool and evidence certainty with Grading of Recommendations Assessment, Development and Evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies reporting guidelines and the Cochrane Diagnostic Test Accuracy protocol were applied for overall conduct. A random-effects meta-analysis was conducted in December 2025 to obtain a pooled estimate of diagnostic accuracy. Main pancreatic duct involvement and rate of HGD or IC were assessed using meta-regression. Summary receiver operating characteristics curves were generated. The area under the curve (AUC) was calculated as overall test performance. Diagnostic accuracy of serum CA19.9 (≥37 U/mL), reported as pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and AUC and their 95% CIs. Pathology was considered as reference standard. Overall, 24 studies assessing 5281 patients with IPMN were included. Mean age was 64.7 (95% CI, 62.24-67.10) years, and 2919 patients (55%) were male. Serum CA19.9 data were available for 4653 patients (88.1%), with 966 patients (20.8%) showing elevated levels. Pooled estimates of diagnostic accuracy for HGD or IC (present in 1939 patients [41.7%]) demonstrated sensitivity of 0.35 (95% CI, 0.29-0.43), specificity of 0.90 (95% CI, 0.87-0.92), PLR of 3.37 (95% CI, 2.56-4.44), NLR of 0.72 (95% CI, 0.65-0.80), DOR of 4.67 (95% CI, 3.26-6.70), and AUC of 0.78 (95% CI, 0.74-0.82). In this systematic review and meta-analysis, CA19.9 with the current cutoff (37 U/mL) demonstrated poor performance in excluding HGD or IC and only modest value for ruling in IC. These findings suggest CA19.9 should not be used as a standalone or screening test, while its limited rule-in value may aid decision-making in patients with moderate pretest probability. Future studies should investigate whether different cutoffs and dynamic trends could improve diagnostic accuracy.
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