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Analyzing the vast amount of omics data generated comprehensively by high-throughput sequencing technology is of utmost importance for scientists. In this context, we propose HiOmics, a cloud-based platform equipped with nearly 300 plugins designed for the comprehensive analysis and visualization of omics data. HiOmics utilizes the Element Plus framework to craft a user-friendly interface and harnesses Docker container technology to ensure the reliability and reproducibility of data analysis results. Furthermore, HiOmics employs the Workflow Description Language and Cromwell engine to construct workflows, ensuring the portability of data analysis and simplifying the examination of intricate data. Additionally, HiOmics has developed DataCheck, a tool based on Golang, which verifies and converts data formats. Finally, by leveraging the object storage technology and batch computing capabilities of public cloud platforms, HiOmics enables the storage and processing of large-scale data while maintaining resource independence among users.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Abstract Background Immune checkpoint inhibitors (ICI) have dramatically improved the life expectancy of patients with metastatic melanoma. However, about half of the patient population still present resistance to these treatments. We have previously shown Notch1 contributes to a non-inflamed TME in melanoma that reduces the response to ICI. Here, we addressed the therapeutic effects of a novel anti-Notch1 neutralizing antibody we produced, alone and in combination with immune checkpoint inhibition in melanoma models. Methods Anti-Notch1 was designed to interfere with ligand binding. Mice were immunized with a peptide encompassing EGF-like repeats 11–15 of human Notch1, the minimal required region that allows ligand binding and Notch1 activation. Positive clones were expanded and tested for neutralizing capabilities. Anti-Notch1-NIC was used to determine whether anti-Notch1 was able to reduce Notch1 cleavage; while anti-SNAP23 and BCAT2 were used as downstream Notch1 and Notch2 targets, respectively. K457 human melanoma cells and the YUMM2.1 and 1.7 syngeneic mouse melanoma cells were used. Cell death after anti-Notch1 treatment was determined by trypan blue staining and compared to the effects of the gamma-secretase inhibitor DBZ. 10 mg/kg anti-Notch1 was used for in vivo tumor growth of YUMM2.1 and 1.7 cells. Tumors were measured and processed for flow cytometry using antibodies against major immune cell populations. Results Anti-Notch1 selectively inhibited Notch1 but not Notch2; caused significant melanoma cell death in vitro but did not affect normal melanocytes. In vivo, it delayed tumor growth without evident signs of gastro-intestinal toxicities; and importantly promoted an inflamed TME by increasing the cytotoxic CD8+ T cells while reducing the tolerogenic Tregs and MDSCs, resulting in enhanced efficacy of anti-PD-1. Conclusions Anti-Notch1 safely exerts anti-melanoma effects and improves immune checkpoint inhibitor efficacy. Thus, anti-Notch1 could represent a novel addition to the immunotherapy repertoire for melanoma.

Abstract Sponge city stormwater management (SCSM) strategy in China aims for sustainable stormwater handling. While many studies have examined the technical aspects of sponge city green infrastructure (SCGI), few have explored public perspectives. This study sought to understand public perceptions, the perceived value of SCGI’s ecosystem service benefits, and the potential for diverse financial compensation methods in sponge city construction. A survey conducted in five Northeastern Chinese cities, involving 1,534 participants, was analyzed using descriptive statistics and logistic regression. The findings reveal no significant correlation between socio-demographic factors and understanding of stormwater management, indicating the concept’s broad accessibility. Public valuation of ecosystem services showed clear priorities, and factors like homeownership and flood experiences significantly impacted the valuation of specific services. Moreover, the study identified a generally positive public attitude towards investing in SCSM, particularly through stormwater fees, underscoring the viability of diverse funding mechanisms. These insights are pivotal for policymakers and urban planners in formulating sustainable and resilient urban water management strategies.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

Global population aging trends are intensifying, presenting multifaceted economic and social challenges for countries worldwide. As the world’s largest developing country, China has entered a phase of extreme demographic aging, posing significant questions about its impact on the ongoing upgrading of industrial structures. How does this demographic shift influence the upgrading of industrial structures, and does technological innovation mitigate or exacerbate this impact? The empirical results indicate that population aging impedes upgrading the industrial structure, while technological innovation positively affects the relationship between the two. Moreover, using technological innovation as a threshold variable, the impact of population aging on industrial structure upgrading evolves in a “gradient” manner from “impediment” to “insignificant” to “promotion” as the technological innovation levels increase. These findings offer practical guidance for tailoring industrial policies to different stages of technological advancement.

Background: The association of ambient temperature with the length of hospital stays and healthcare costs has not been well-explored. We aimed to examine the association of temperature with emergency hospital admission (EHA) count and length of stay (LOS) for total and cause-specific circulatory diseases and evaluate the temperature-related attributable risk and healthcare costs. Methods: This ecologic time series analysis linked the daily circulatory EHA count and LOS from the Hong Kong Hospital Authority with the environmental exposures from the fixed monitoring stations from 2004 to 2019. The generalized linear quasi-Poisson model integrated with a distributed lag nonlinear model was applied to examine ambient temperatures' relative and attributable risks on EHA counts and LOS while adjusting the time-varying confounders. Temperature-related healthcare costs were evaluated based on the estimated attributable number (AN) and charges per attendance or bed day. Results: Among 1276,632 EHAs and 7621,232 bed days of LOS, significant associations of cold temperatures with both EHA counts and LOS for total and cause-specific circulatory diseases were found. The temperature-related attributable fraction (AF) was estimated as 7.98 % (95 % CI: 5.24–10.58 %) for EHA count and 13.09 % (6.80–18.28 %) for LOS for total circulatory diseases. The cold temperature defined as the lower quartile of the ambient temperature range explained more than half of the temperature-related attributable risk and healthcare costs. Conclusion: Cold weather can lead to adverse health outcomes, with considerable pressure on the healthcare system. Longer LOS-associated higher healthcare costs in colder weather may have implications for developing targeted preventions and hospital service planning.

Background: The adverse health impacts of ambient temperature have been well-documented, encompassing not only the mortality and morbidity burden but also mood and mental health disorders. However, the relationship between temperature and social isolation remains unexplored. The objective of the current study was to investigate the potential associations between ambient temperature and social isolation among the aging population. Methods: We took advantage of a cross-sectional survey conducted between January 2017 and November 2018 from a community service program special for older adults aged ≥60 who lived in a central community of Hong Kong. The personal social isolation was assessed by the validated Lubben Social Network Scale-6 (LSNS-6), with a score ranging from 0 to 30 and score of less than 12 indicating social isolation. The environmental exposures, including ambient temperature, sunshine hours, rainfalls, and air pollution, were obtained from the nearby monitoring stations. The association of ambient temperature with LSNS-6 score or social isolation was examined by the generalized linear models while adjusting the potential confounding from other environmental exposures and personal sociodemographic factors. Results: Among the 1616 participants, the distribution of LSNS-6 score was approximately normal and the mean score was a bit higher on cool days than on hot days (13.0 vs. 12.2). Compared with cool temperatures (14.4–19.5oC), the independent effect estimates of hot ambient temperatures (24.5–28.7oC) was associated with a 2.38 (95%CI: 1.63–3.13) decrease in LSNS-6 score. Meanwhile, we observed statistically significant associations of sunshine exposure, gender, health status, marital status, living alone, religion, and housing type with LSNS-6 score or social isolation. Conclusions: Our study revealed a clear association between ambient cool temperatures and reduced social isolation, as well as association between hot temperatures and social isolation among older Chinese adults residing in the urban community of Hong Kong.

3D printed concrete (3DPC) is an essential technology for achieving efficient, precise, and sustainable construction. Nevertheless, due to limitations in materials and processes, 3DPC is prone to insufficient green strength and weakness in the interlayer area, which can result in print collapse and diminish its interlayer adhesion strength. Therefore, understanding green strength and interlayer adhesion strength of 3DPC is crucial for ensuring its structural safety. Superabsorbent polymer (SAP) serves as a novel type of concrete admixture, demonstrating the potential to promote green strength development and augment interlayer adhesion properties by facilitating the hydration process through water absorption and release. This study presents the first investigation into the effects of two commercially available SAPs on green strength and interlayer adhesion of 3D printed concrete. The role of SAP in improving interlayer adhesion performance in 3DPC is further elucidated through X-ray diffraction (XRD), Scanning electron microscopy (SEM). The results indicate that, compared to the control group, in the absence of added compensated water to SA1, the compressive strength at 15 min and splitting tensile strength of the printed specimen at 28 d increased by 282 % and 24.9 %, respectively, whereas SA2 demonstrates a relatively weaker enhancement effect. This study demonstrates that SAP promotes structural accumulation during the 3DPC printing stage, thereby presenting itself as a favorable material choice for applications involving 3DPC.

Abstract Background Older adult patients are particularly vulnerable to medication-related issues during the discharge process. To enhance medication discharge education and patient experience, a written medication reminder, incorporating crucial medication side effects and warning signs, was implemented in medicine wards. This study aimed to examine the influence of this reminder on patient experience and medication-taking behaviors among older adults in public healthcare settings. Methods Two separate rounds of cross-sectional surveys were conducted before and after the program implementation among different discharged patients in each round. The study enrolled older adult patients aged ≥ 65 or their caregivers discharged from the medical wards of four pilot public hospitals in Hong Kong. A structured questionnaire was administered via telephone within 14 days of the patient’s discharge. The survey assessed patients' experience with the provided medication information during discharge, including the clarity, adequacy, and usefulness of the information, as well as their overall experience with inpatient services. The self-reported medication-taken behaviors, including adherence and side-effect encounters, were also measured. Results A total of 1,265 responses were collected before the implementation of the medication reminder, and 1,426 responses were obtained after the implementation. Pre/post-implementation survey comparison showed significant improvement in patient experience regarding the clarity of the provided medication information (7.93 ± 1.84 vs. 8.18 ± 1.69, P = 0.002), adequacy (7.92 ± 1.93 vs. 8.15 ± 1.76, P = 0.014), and usefulness (8.06 ± 1.80 vs. 8.26 ± 1.70, P = 0.017), significantly positive experience on the overall discharge information (β coefficient, 0.43 [95%CI, 0.30 to 0.56]) and inpatient service (β coefficient, 0.47 [95%CI, 0.32 to 0.61]). In addition, the side effects encounters were significantly lower in the post-implementation survey group (11.6% vs. 9.0%, P = 0.04) and no statistical difference was found in self-reported medication adherence between the two groups. Conclusions The provision of written medication reminders on key medication risks effectively improved older adult patients’ experience and reduced side effects without any unintended negative consequences. The findings can serve as a reference for similar settings seeking to enhance post-discharge care among older adult patients. Future studies could investigate the influence in other specialties and age groups and include clinical outcomes to test the program’s effectiveness.

Abstract We conducted a retrospective population-based, matched cohort study using the National Health Insurance Research Database to estimate healthcare resource utilisation (HRU) and costs in patients with newly diagnosed AL amyloidosis in Taiwan. Cases were matched 10:1 by age, sex, and area of residence to patients without AL amyloidosis (comparators) randomly selected from the database during the same time period. Annual all-cause HRU and costs for 3 years were quantified. AL amyloidosis-attributable costs were obtained by subtracting all-cause HRU costs incurred by comparators from cases. The mean age of all patients was 60.78 years and 59.07% were male. Co-morbidities were more frequent in cases than comparators. By 6 months after diagnosis, 12.1% of cases had died versus 0.9% of comparators. In the first year, cases had 103% more outpatient visits, 177% more emergency room visits, were hospitalised 4-times more frequently, and spent 5.5-times more days in hospital than comparators, and total healthcare costs were > sixfold higher. Costs incurred during the first year after diagnosis accounted for 55% of the 3-year cumulative cost. High HRU costs associated with delayed diagnosis and end-organ damage indicate a need for earlier diagnosis and more effective treatments for AL amyloidosis.

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels (±0.05 mmol/L), forming the LDL-C-matched cohort. Associations between preceding statin treatment, in-hospital mortality, and stroke severity (National Institutes of Health Stroke Scale score ≥16) were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort, respectively. The overall statin effects reduced in-hospital mortality (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.65–0.79, p

Background Although many studies have examined the influence of individual preexisting heart conditions on stroke outcomes, the combined effects of these conditions remain understudied. Methods The data supporting this study's findings are available from the corresponding author upon reasonable request. Data on patients with acute ischemic stroke from the Third China National Stroke Registry were analyzed. Preexisting heart disease spectrum was defined based on the combination pattern of coronary heart disease, atrial fibrillation, and heart failure. In‐hospital stroke outcomes included moderate or severe stroke at admission (the National Institutes of Health Stroke Scale score ≥16), ambulation by day 2, and in‐hospital death. Results Among the 14 019 analyzed patients, 1856 (13.2%) had preexisting heart diseases, of which the most common single heart disease was coronary heart disease (1313 [70.7%]), and the most common combination was coronary heart disease and atrial fibrillation (116 [6.3%]). Patients with preexisting heart diseases had higherprevalence of moderate or severe stroke at admission (4.7% versus 1.9%; adjusted odds ratio [aOR], 2.25 [95% CI, 1.73–2.93]), in‐hospital mortality (0.5% versus 0.2%; aOR, 2.41 [95% CI, 1.11–5.25]), and a lower rate of ambulation by day 2 (73.9% versus 78.6%; aOR, 0.84 [95% CI, 0.75–0.95]). Atrial fibrillation alone (moderate or severe stroke: aOR, 4.82 [95% CI, 3.29–7.06]; in‐hospital mortality: aOR, 4.76 [95% CI, 1.58–14.36]; ambulation by day 2: aOR, 0.58 [95% CI, 0.46–0.72]) or in combination with coronary heart disease and heart failure (moderate or severe stroke: aOR, 11.47 [95% CI, 3.66–35.89]; ambulation by day 2: aOR, 0.41 [95% CI, 0.16–1.05]) had the strongest association with unfavorable outcomes. Conclusion Preexisting heart diseases, particularly atrial fibrillation combined with other heart diseases, are associated with unfavorable in‐hospital stroke outcomes.

Summary: Background: Recent studies showed increased mortality risks after hot nights, but their effect on hospitalizations, especially in vulnerable populations, remains under-studied. Methods: Daily hospitalization, meteorological (including hourly), and air pollution data were collected for the hot seasons (May–October) of 2000–19 in Hong Kong. We derived three hot-night metrics: HNday28 °C, daily minimum temperature ≥28 °C, the governmental definition of hot nights; HNe, hot night excess calculated by summing heat excess of hourly temperatures above 28 °C at night; and HNday90th, hot nights classified using the 90th percentile HNe (17.7 °C⋅h) as a cutoff. We fitted time-series regression with distributed lag nonlinear models to examine the associations of hot-night metrics with various hospitalizations. Findings: During the 3680 study days, 5,002,114 non-cancer non-external (NCNE) hospitalizations were recorded. Half (1874) of the days experienced excess nighttime heat (HNe>0) with a mean (SD) of 8.0 (6.8) °C⋅h; 499 and 187 hot nights were identified by HNday28 °C and HNday90th, respectively. Extreme HNe (99th percentile vs 0 °C⋅h) was significantly associated with increased NCNE hospitalizations over lag 0–4 days by 3.1% [95% confidence interval: 1.5%, 4.8%] overall, with enhanced effects in elderly (5.3% [3.2%, 7.4%]), low-SES individuals (5.3% [2.8%, 8.0%]), and circulatory admissions (3.4% [0.2%, 6.8%]). HNday90th, reflecting extreme HNe, better identified hazardous hot nights than the official HNday28 °C. Interpretation: Excessive nighttime heat is significantly associated with increased hospitalizations, particularly affecting the elderly and socioeconomically disadvantaged individuals. Nighttime heat intensity should be incorporated in defining hot nights with public health relevance. Funding: British Heart Foundation.

BackgroundOsteoarthritis (OA) of the knee is one of the most common chronic degenerative joint conditions affecting aging population.AimTo investigate the effectiveness of a combination of home-based exercise and pulsed electromagnetic field (PEMF) therapy to improve muscle strength, physical function, and pain.MethodsSixty patients were randomly assigned to either home-based exercise alone (control group; n = 30) or combined with PEMF therapy (treatment group; n = 30) twice a week for eight weeks. Knee extension, flexion muscle strength, gait speed (GS), 5 time sit-to-stand test (5STS), Visual Analogue Scale (VAS) pain and Knee Injury and Osteoarthritis Outcome Score (KOOS) were recorded at baseline and 4 and 8 weeks.ResultsSignificant improvements in symptomatic knee extension muscle strength (SKE, p = 0.001), flexion strength (SKF, p = 0.011), contralateral knee extension muscle strength (CKE, p = 0.002), and flexion strength (CKF, p = 0.009) were observed for the PEMF treatment group at 8 weeks. Significant reductions in VAS pain scores were observed in both the treatment (p

Objectives: Plasma bile acid (BA) has been widely studied as pathophysiological factors in chronic liver disease. But the changes of plasma BA level in lean metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Here, we clarified the BA metabolic characteristics of lean MAFLD and explored its significance and mechanism as a marker. Methods: We employed ultra-performance liquid chromatography tandem mass spectrometry based on BA metabonomics to characterize circulating bile acid in lean MAFLD patients. Explore its significance as serum biomarkers by further cluster analysis, functional enrichment analysis, and serum concentration change analysis of differential BAs. Evaluation of diagnostic value of differential BAs by ROC analysis. Results: A total of 65 BAs were detected and 17 BAs were identified which showed different expression in the lean-MAFLD group compared with the normal group. Functional annotation and enrichment analysis of KEGG and HMDB showed that differential BAs were mainly related to bile acid biosynthesis, bile secretion, cholesterol metabolism, and familial hypercholangitis, involving diseases including but not limited to cirrhosis, hepatocellular carcinoma, chronic active hepatitis, colorectal cancer, acute liver failure, and portal vein obstruction. ROC analysis displayed that the 6 BA metabolites (GCDCA-3S, GUDCA-3S, CDCA-3S, NCA, TCDCA, and HDCA) exhibited well differential diagnostic ability in discriminating between lean MAFLD patients and normal individuals with an area under the curve (AUC) ⩾0.85. Conclusions: We delineated the characteristics of BA level in patients with lean MAFLD, and identified 6 potential plasma BA biomarkers of lean MAFLD.

BackgroundStroke is the leading cause of mortality in China, with limited evidence of in-hospital burden obtained from nationwide surveys. We aimed to monitor and track the temporal trends and rural-urban disparities in cerebrovascular risk factors, management and outcomes from 2005 to 2015.MethodsWe used a two-stage random sampling survey to create a nationally representative sample of patients admitted for ischaemic stroke in 2005, 2010 and 2015. We sampled participating hospitals with an economic-geographical region-stratified random-sampling approach first and then obtained patients with a systematic sampling approach. We weighed our survey data to estimate the national-level results and assess changes from 2005 to 2015.ResultsWe analysed 28 277 ischaemic stroke admissions from 189 participating hospitals. From 2005 to 2015, the estimated national hospital admission rate for ischaemic stroke per 100 000 people increased (from 75.9 to 402.7, Ptrend

Abstract Background Remnant cholesterol (RC) and nonhigh-density lipoprotein cholesterol (nonHDL-C) are key risk factors for atherosclerotic cardiovascular disease (ASCVD), with apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] also contributing to its residual risk. However, real-world population-based evidence regarding the impact of current clinical LDL-C-centric lipid-lowering therapy (LLT) on achieving RC and nonHDL-C goals, as well as on modifying residual CVD risk factors is limited. Methods This prospective observational study enrolled 897 CVD patients from September, 2020 to July, 2021. All participants had previously received low-/moderate-intensity LLT and were discharged with either low-/moderate-intensity LLT or high-intensity LLT. After a median follow-up of 3 months, changes in RC, nonHDL-C, and other biomarkers were assessed. Multivariate logistic regression was performed to analyze the impact of the LLT on goal attainment. Results Among all patients, 83.50% transitioned to high-intensity LLT from low or moderate. After follow-up, the high-intensity group saw significantly greater reductions in RC (-20.51% vs. -3.90%, P = 0.025), nonHDL-C (-25.12% vs. 0.00%, P

Abstract Objective This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). Methods Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. Results The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814–0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. Conclusion This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

To assess the viability and effectiveness of bioretention cell in enhancing rainwater resource utilization within sponge cities, this study employs field monitoring, laboratory testing, and statistical analysis to evaluate the water purification capabilities of bioretention cell. Findings indicate a marked purification impact on surface runoff, with removal efficiencies of 59.81% for suspended solids (SS), 39.01% for chemical oxygen demand (COD), 37.53% for ammonia nitrogen (NH3-N), and 30.49% for total phosphorus (TP). The treated water largely complies with rainwater reuse guidelines and tertiary sewage discharge standards. Notably, while previous research in China has emphasized water volume control in sponge city infrastructures, less attention has been given to the qualitative aspects and field-based evaluations. This research not only fills that gap but also offers valuable insights and practical implications for bioretention cell integration into sponge city development. Moreover, the methodology and outcomes of this study serve as a benchmark for future sponge city project assessments, offering guidance to relevant authorities. HIGHLIGHTS Explored the purification of bioretention cells on rainwater.; Under the same conditions, the bioretention cell has the best purification effect on suspended solids.; The bioretention cell's effluent quality complies with standards for urban recycled water, wastewater discharge, and sponge city assessments.;

Abstract Objective This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. Methods The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). Results A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p

Treatment for lung cancer continues to rapidly evolve. Here, we describe trends in the initial treatment of adults with newly diagnosed primary non-small-cell lung cancer in Japan. This retrospective cohort study used data from JMDC Inc. Claims Database from 2015 to 2023. Adults with lung cancer, confirmed using a combination of diagnosis, treatment, or procedure codes, were enrolled. A total of 9373 patients were included, with a mean age of approximately 59 years. The median time from diagnosis to treatment initiation ranged from 38 days in patients treated surgically to 25 days in patients with distant metastases. The observed trends were a decrease in the percentage of newly diagnosed patients with distant metastases, a decline in chemotherapy use in patients with early-stage disease, and in advanced disease, a more than doubling in the use of targeted therapy, including checkpoint inhibitors, while radiotherapy and chemotherapy tended to decrease. The observed changes in treatment were driven mainly by the increased use of targeted therapies including checkpoint inhibitors and are aligned with current treatment guidelines in Japan. The observation of fewer patients with distant metastases over time possibly indicates earlier detection. Additional research is needed to understand if new therapies are being extended to older and frail patients with lung cancer in Japan.

BackgroundOsteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors.Methods135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function.ResultsBMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS (r2 = −0.383, p < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS (r2 = −0.528, p < 0.01). In the stepwise multiple linear regression models, pain intensity (β = 0.712, p < 0.001), knee flexor muscle strength (β = 0.112, p = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: β = −0.428, p < 0.001) and flexor muscle strength (6MGS: β = 0.367, p < 0.001), were the main predictors with performance-based physical function.ConclusionPain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.

AIM: To summarize the application of deep learning in detecting ophthalmic disease with ultrawide-field fundus images and analyze the advantages, limitations, and possible solutions common to all tasks. METHODS: We searched three academic databases, including PubMed, Web of Science, and Ovid, with the date of August 2022. We matched and screened according to the target keywords and publication year and retrieved a total of 4358 research papers according to the keywords, of which 23 studies were retrieved on applying deep learning in diagnosing ophthalmic disease with ultrawide-field images. RESULTS: Deep learning in ultrawide-field images can detect various ophthalmic diseases and achieve great performance, including diabetic retinopathy, glaucoma, age-related macular degeneration, retinal vein occlusions, retinal detachment, and other peripheral retinal diseases. Compared to fundus images, the ultrawide-field fundus scanning laser ophthalmoscopy enables the capture of the ocular fundus up to 200° in a single exposure, which can observe more areas of the retina. CONCLUSION: The combination of ultrawide-field fundus images and artificial intelligence will achieve great performance in diagnosing multiple ophthalmic diseases in the future.

Abstract The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence‐based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti‐angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)‐positive and deficient DNA mismatch repair (dMMR)/microsatellite instability‐high (MSI‐H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Aiming at the difficulty of feature extraction in complex environments during mulberry detection and the need for embedded devices to lighten the model, this study carries out lightweight improvements on the basis of the YOLOv8n model. First, the CSPPC module incorporates lightweight partial convolution (PConv) within its bottleneck structure, replacing the C2f module to enhance feature extraction efficiency. Secondly, the ADown module is used to replace the traditional downsampling module and the P-Head module is used to replace the traditional convolutional detector head with the partial convolutional detector head. Finally, a knowledge distillation technique is used to compensate for the loss of accuracy due to parameter reduction. Ablation experiments are conducted to evaluate the impact of each module on the model’s performance. The experimental results show that the improved YOLOv8 model has a precision of 88.9%, a recall of 78.1%, and an average precision of 86.8%. The number of parameters is 1.29 × 106, the model size is 2.6 MB, the floating-point computation is 2.6 GFLOPs, and the frame rate reaches 19.84 FPS on the edge end. Therefore, this model provides theoretical and technical support for the deployment and application of mobile detection devices, such as automatic mulberry harvesting in practical scenarios.

Abstract Background The MeltPro TB assay (MeltPro) is a molecular rapid diagnostic test designed for detecting resistance to antituberculosis drugs. However, the performance of MeltPro as an initial diagnostic test for simultaneously detecting the presence of Mycobacterium tuberculosis (MTB) and drug resistance has not been evaluated. This study aims to assess the performance of MeltPro as initial diagnostic test for simultaneous detection of MTB and drug resistance in clinical samples from patients with presumptive pulmonary tuberculosis (PTB). Methods A retrospective analysis was conducted on 1283 patients with presumptive PTB from two clinical centers, out of which 875 were diagnosed with PTB. The diagnostic accuracy of MeltPro, Xpert MTB/RIF (Xpert), and MGIT 960 for PTB detection was evaluated. Rifampicin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and fluoroquinolone (FQ) resistance were detected using MeltPro, with Xpert and/or the broth microdilution plate method (MYCOTB) results as references. Results For the diagnosis of PTB, MeltPro showed a sensitivity of 69.0%, which was similar to Xpert (72.7%; P > 0.05) and higher than MGIT (58.1%; P 0.05). In smear-negative patients, MeltPro's sensitivity was 50.9%, similar to Xpert (56.5%; P > 0.05), and higher than MGIT (33.1%; P

Abstract Background and purpose Nonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event. Methods Data were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes. Results A total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P

Abstract Prostaglandin I2 synthase (PTGIS) is a member of the cytochrome P450 family. Studies have revealed that differential expression of the PTGIS gene is closely related to the pathological and physiological processes of many diseases, including breast cancer, oral squamous cell carcinoma, and head and neck cancer. However, the mechanism of action of the PTGIS gene in colorectal cancer is not fully understood. This study explored the role of PTGIS in colorectal cancer through comprehensive bioinformatics analysis and in vitro experiments, and found that the expression of PTGIS gene in colorectal cancer tissue was significantly lower than that in normal colorectal tissue (P

Abstract Dermatomyositis and polymyositis are rare, idiopathic inflammatory myopathies. Interstitial lung disease is one of the most common and potentially severe extra-muscular manifestations of dermatomyositis and polymyositis and is strongly linked to poor prognosis and early mortality. We aimed to characterise the demographic and clinical characteristics, incidence, and treatment of interstitial lung disease in patients with dermatomyositis or polymyositis. We conducted a retrospective cohort study using the Japan Medical Data Center healthcare claims database. Patients in the database with dermatomyositis (International Classification of Disease version 10 M33.0, M33.1, M33.9) or polymyositis (M33.2) from 01-Jan-2011 until 31-Dec-2019 were identified and followed-up for interstitial lung disease (J84.x) until death, dis-enrolment, or study end (31 December 2020). Cumulative risk curves compared interstitial lung disease risk in dermatomyositis versus polymyositis. Risk factors were evaluated by Cox proportional hazard models. There were 886 patients with dermatomyositis and 745 patients with polymyositis included in the cohort analysis. Mean (standard deviation) age at dermatomyositis/polymyositis diagnosis was 46.0 (16.0)/49.7 (13.3) years and 300 (34%)/104 (14%) developed interstitial lung disease during follow-up. The incidence rate of interstitial lung disease per 100 person-years was 18.42 (95% CI 16.42–20.59) for dermatomyositis and 5.39 (95% CI 4.43–6.50) for polymyositis. In the analysis adjusted for sex, age, and comorbidity score, the risk of interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis (hazard ratio 2.72, 95% CI 2.18–3.41). The rate diverged markedly between the groups in the first year after diagnosis. Risk factors for interstitial lung disease were older age in dermatomyositis, female sex and rheumatoid arthritis in polymyositis. Glucocorticoids with/without tacrolimus were the most common newly prescribed drugs after the interstitial lung disease diagnosis. In conclusion, the risk of developing interstitial lung disease was significantly higher in patients with dermatomyositis than with polymyositis, and risk factors were different in the 2 patient groups.

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.

Introduction: Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor β1(TGF-β1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulfate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-β1/) signalling pathway is still unclear. Methods: In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a and α-SMA by quantitative real-time PCR (qRT‒PCR) and western blotting after siRNA-mediated TGF-β1 silencing, TGF-β1 overexpression and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, SRGAP2a in the Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. Results: The results indicated that nephrin, synaptopodin, CD2AP and SRGAP2a expressions were significantly upregulated and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-β1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-β1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7 and NOX4; and increased ROS production in podocytes. Conclusions: This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP and SRGAP2a by regulating the ROS and TGF-β1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.

Summary: Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists’ optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410–0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists’ proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p

ObjectivesTo compare the prevalence of anxiety/depression, resilience, and social support among nurses, foreign domestic helpers (FDHs), and residents living in subdivided units (SDUs), and to examine their associations in these high-risk groups in Hong Kong during Omicron waves.MethodsWe recruited 1,014 nurses, 621 FDHs, and 651 SDU residents from December 2021 to May 2022 in this cross-sectional survey. The depression, anxiety, social support, and resilience levels were measured by the validated scales. The multivariate binary logistic regression and causal mediation analysis were applied to examine the associations.ResultsWe observed a prevalence of 17.7% in anxiety and 21.6% in depression which were the highest in SDU residents, followed by FDHs, and lowest in nurses. Social support was associated with increased resilience levels and decreased risks of anxiety/depression. The association of social support with mental disorders was partly mediated by resilience, accounting for 30.9% and 20.9% of the total effect of social support on anxiety and depression, respectively.ConclusionPublic health strategies should target improving social support and providing resilience-promoting interventions to help reduce mental disorders in vulnerable groups.