Forecasting influenza epidemics in China using transmission dynamic model with absolute humidity.

Background: An influenza forecasting system is critical to influenza epidemic preparedness. Low temperature has long been recognized as a condition favoring influenza epidemic, yet it fails to justify the summer influenza peak in tropics/subtropics. Recent studies have suggested that absolute humidity (AH) had a U-shape relationship with influenza survival and transmission across climate zones, indicating that a unified influenza forecasting system could be established for China with various climate conditions. Methods: Our study has generated weekly influenza forecasts by season and type/subtype in northern and southern China from 2011 to 2021, using a forecasting system combining an AH-driven susceptible-infected-recovered-susceptible (SIRS) model and the ensemble adjustment Kalman filter (EAKF). Model performance was assessed by sensitivity and specificity in predicting epidemics, and by accuracies in predicting peak timing and magnitude. Results: Our forecast system can generally well predict seasonal influenza epidemics (mean sensitivity>87.5%; mean specificity >80%). The average forecast accuracies were 82% and 60% for peak timing and magnitude at 3-6 weeks ahead for northern China, higher than those of 42% and 20% for southern China. The accuracy was generally better when the forecast was made closer to the actual peak time. Discussion: The established AH-driven forecasting system can generally well predict the occurrence of seasonal influenza epidemics in China.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Impact of hot and cold nights on pneumonia hospitalisations in children under five years: Evidence from low-, middle-, and high-income countries.

BACKGROUND: Studies have shown that abnormal temperature at night is a risk factor for respiratory health. However, there is limited evidence on the impact of hot and cold nights on cause-specific diseases such as pneumonia, which is a leading cause of morbidity and mortality in children. METHODS: We collected daily data on pneumonia hospitalisations in children under five years from 2011 to 2017 in three low-, middle- and high-income countries (Bangladesh, China, and Australia). The intensity of hot and cold nights was measured by excess temperature. A space-time-stratified case-crossover analysis was used to estimate the association between hot and cold nights and childhood pneumonia hospitalisations. We further estimated the fraction of childhood pneumonia hospitalisations attributable to hot and cold nights. RESULTS: Both hot and cold nights were associated with an increased risk of hospitalisations for childhood pneumonia in low-, middle-, and high-income countries, with a greater disease burden from hot nights. Specifically, the fraction of childhood pneumonia attributable to hot nights was the largest in Australia [21.2%, 95% confidence interval (CI): 11.8%-28.1%], followed by Bangladesh (15.2%, 95% CI: 4.1%-23.8%) and China (2.7%, 95% CI: 0.4%-4.7%). Additionally, the fraction of childhood pneumonia attributable to cold nights was 1.3% (95% CI: 0.4%-2.0%) in Bangladesh and 0.4% (95% CI: 0.1%-0.7%) in China. CONCLUSION: This multi-country study suggests that hot and cold nights are not only associated with a higher risk of pneumonia hospitalisations in children but also responsible for substantial fraction of hospitalisations, with a greater impact from hot nights.

Diagnostic Value of Metagenomic next-generation sequencing and X-pert in Bronchoalveolar lavage fluid for pneumonia in HIV-infected and HIV-uninfected patients.

Background: The pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. Methods: Between January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. Results: HIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/µL vs. 31 cells/µL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

Exceptional heatwaves and mortality in Europe: Greater impacts since the coronavirus disease 2019 outbreak.

Record-breaking hot weather (exceptional heatwaves) has been increasingly common worldwide, posing a significant threat to human health. However, little is known about the effect of these exceptional heatwaves on mortality in Europe, especially since the coronavirus disease 2019 (COVID-19) outbreak, which converges with climate change to affect healthcare systems and human lives. We collected mortality data of 967 regions in 30 European countries over the last decade (2014-2023) from the Eurostat. A standard time-series analysis was used to estimate the effect of exceptional heatwaves by quasi-Poisson regression model, including the main effect (effect from heatwave intensity) and the added effect (effect from heatwave duration), on mortality for each region during two periods (before and since the COVID-19 outbreak). We used random effects meta-analysis to pool the mortality risk (i.e., relative risk [RR]) and burden (i.e., attributable fraction [AF]) associated with exceptional heatwaves, at the country level and for Europe as a whole. In Europe, the mortality burden attributable to main and added effects increased from 0.492% (95% CI: 0.488%-0.496%) to 1.276% (95% CI: 1.266%-1.285%) and from 0.307% (95% CI: 0.294%-0.318%) to 0.428% (95% CI: 0.407%-0.448%), respectively. Furthermore, substantial variations across countries were observed, with some countries such as France and Spain experiencing a large increase in the mortality burden attributable to exceptional heatwaves since the COVID-19 outbreak. Our findings underscore the urgent need for heat-health actions to consider the multi-effects of exceptional heatwaves amidst a warming climate.

Survival benefit of adjuvant TACE for patients with hepatocellular carcinoma and child-pugh B7 or B8 after hepatectomy.

BACKGROUND & AIMS: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. METHODS: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). RESULTS: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. CONCLUSION: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Hierarchical Nanostructures CuBi2O4 Integrated with Polyaniline Nanofibrous for Boosting Hole Extraction in Carbon-Based Perovskite Solar Cells.

Toward commercialization of carbon-based perovskite solar cells (C-PSCs), it is crucial to innovatively design inorganic hole transport layer materials that excel in extracting and transporting charge carriers to promote their photoelectric conversion efficiency (PCE). In this work, a novel and high-connectivity CuBi2O4-polyaniline nanofibrous (CuBi2O4-PN) reticular structure is created by integrating CuBi2O4 hierarchical microspheres (CuBi2O4 MS) with polyaniline nanofibrous. The introduction of CuBi2O4-PN as a hole transport layer (HTL) notably enhances the contact quality of the devices and substantially reduces the surface defects of C-PSCs. In a comparative analysis under identical experimental conditions, MAPbI3 devices incorporating CuBi2O4-PN HTL demonstrated a PCE of 14.79%, achieving a 44.3% increase over the reference device (10.25%). CuBi2O4-treated C-PSCs retained 89.9% of their original PCE after 45 days in storage, and they demonstrated improved stability over a longer time frame. This remarkable improvement in device performance can be attributed to the effective suppression of nonradiative recombination and the enhancement of the carrier transfer process in the device. Additionally, the unique interconnected reticular structure of CuBi2O4-PN provides efficient pathways for hole transfer, significantly contributing to the enhanced efficiency of the device.

Radiation-Emitting metallic stent for unresectable bismuth type III or IV perihilar cholangiocarcinoma: a multicenter randomized trial.

BACKGROUND AIMS: Self-expandable metallic stents (SEMSs) have been recommended for patients with unresectable malignant biliary obstruction while radiation-emitting metallic stents (REMSs) loaded with 125I seeds have recently been approved to provide longer patency and overall survival in malignant biliary tract obstruction. This trial is to evaluate the efficacy and safety of REMS plus hepatic arterial infusion chemotherapy (REMS-HAIC) versus SEMS plus HAIC (SEMS-HAIC) for unresectable perihilar cholangiocarcinoma (pCCA). METHODS: This multicenter randomized controlled trial recruited patients with unresectable Bismuth type III or IV pCCA between March 2021 and January 2023. Patients were randomly assigned (1:1 ratio) to receive either REMS-HAIC or SEMS-HAIC using permuted block randomization, with a block size of six. The primary endpoint was overall survival (OS). The secondary endpoints were time to symptomatic progression (TTSP), stent patency, relief of jaundice, quality of life, and safety. RESULTS: A total of 126 patients were included in the intent-to-treat population, with 63 in each group. The median OS was 10.2 months versus 6.7 months (P=0.002). The median TTSP was 8.6 months versus 5.4 months (P=0.003). The median stent patency was longer in the REMS-HAIC group than in the SEMS-HAIC group (P=0.001). The REMS-HAIC group showed better improvement in physical functioning scale (P<0.05) and fatigue symptoms (P<0.05) when compared to the SEMS-HAIC group. No significant differences were observed in relief of jaundice (85.7% vs. 84.1%; P=0.803) or the incidence of grade 3 or 4 adverse events (9.8% vs. 11.9%; P=0.721). CONCLUSION: REMS plus HAIC showed better OS, TTSP, and stent patency compared with SEMS plus HAIC in patients with unresectable Bismuth type III or IV pCCA with an acceptable safety profile.

Quantifying the historical and future heat-related mortality above the heat alert thresholds of the inaugural Chinese national heat-health action plan.

BACKGROUND: China published its inaugural national heat-health action plan (HHAP) in 2023, but the mortality burden associated with temperatures exceeding the heat alert thresholds specified by this HHAP (maximum temperatures >35, 37, or 40 °C) remains unknown. We aimed to estimate the historical and future mortality burden associated with temperatures above the heat alert thresholds of the Chinese national HHAP. METHODS: We conducted time-series analyses to estimate the mortality burden associated with temperatures exceeding the three heat alert thresholds from 2016 to 2019 in Jiangsu Province (including 13 cities, population ∼80.7 million), China. A quasi-Poisson regression in conjunction with a distributed lag non-linear model was used to estimate the dose-response association between maximum temperature and mortality risk from 2016 to 2019, adjusting for potential covariates. We then projected the future mortality burden associated with temperatures exceeding these thresholds under three distinct levels of greenhouse gas (GHG) emission scenarios via scenario shared socioeconomic pathways [SSP] 1-2.6 (low), SSP2-4.5 (intermediate), and SSP5-8.5 (high), respectively, by assuming that there will be no adaptation to heat. Climate scenarios derived from the General Circulation Model (GCM) under the Coupled Model Intercomparison Project Phase 6 (CMIP6) were used. RESULTS: From 2016 to 2019, temperatures above 35 °C were associated with 0.51% of mortality, including 0.40% associated with 35 °C-37 °C and 0.11% associated with >37 °C. Heat-related mortality risk was most prominent in those who were single/divorced/widowed and had <10 years of education. Under SSP2-4.5, compared with the 2020s, the excess mortality associated with >37 °C would increase by 1.4 times in the 2050s and 1.7 times in the 2090s. Under SSP5-8.5, the annual number of days with maximum temperature >37 °C would approximately double every 20 years (67 days annually in the 2090s). Consequently, compared with the 2020s, the excess mortality associated with >37 °C would increase by 2.8 times in the 2050s and 18.4 times in the 2090s. CONCLUSION: Significant mortality risk is associated with temperatures above the lowest heat alert threshold of the Chinese national HHAP (35 °C). If the high GHG emission scenario occurred, the annual number of days and excess mortality associated with maximum temperatures >37 °C would largely increase in the coming decades.

Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population.

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.

Succinate Activates Uncoupling Protein 2 to Suppress Neuroinflammation and Confer Protection Following Intracerebral Hemorrhage.

Aims: Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. Results: We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, the oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxides, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophages, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream 5'-adenosine monophosphate-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I, or AMPK abolished the therapeutic effects of succinate following ICH. Innovation and Conclusion: We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate-mediated intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate.

CT perfusion parameter estimation in stroke using neural network with transformer and physical model priors.

OBJECTIVES: CT perfusion (CTP) imaging is vital in treating acute ischemic stroke by identifying salvageable tissue and the infarcted core. CTP images allow quantitative estimation of CT perfusion parameters, which can provide information on the degree of tissue hypoperfusion and its salvage potential. Traditional methods for estimating perfusion parameters, such as singular value decomposition (SVD) and its variations, are known to be sensitive to noise and inaccuracies in the arterial input function. To our knowledge, there has been no implementation of deep learning methods for CT perfusion parameter estimation. MATERIALS & METHODS: In this work, we propose a deep learning method based on the Transformer model, named CTPerformer-Net, for CT perfusion parameter estimation. In addition, our method incorporates some physical priors. We integrate physical consistency prior, smoothness prior and the physical model prior through the design of the loss function. We also generate a simulation dataset based on physical model prior for training the network model. RESULTS: In the simulation dataset, CTPerformer-Net exhibits a 23.4 % increase in correlation coefficients, a 95.2 % decrease in system error, and a 90.7 % reduction in random error when contrasted with block-circulant SVD. CTPerformer-Net successfully identifies hypoperfused and infarcted lesions in 103 real CTP images from the ISLES 2018 challenge dataset. It achieves a mean dice score of 0.36 for the infarct core segmentation, which is slightly higher than the commercially available software (dice coefficient: 0.34) used as a reference level by the challenge. CONCLUSION: Experimental results on the simulation dataset demonstrate that CTPerformer-Net achieves better performance compared to block-circulant SVD. The real-world patient dataset confirms the validity of CTPerformer-Net.

Study on the anti-HBV activity of matrine alkaloids from Oxytropis ochrocephala by MTT, 3d-QSAR, molecular docking and molecular dynamics simulation.

To elucidate the structure-activity relationship of 17 matrine alkaloids from Oxytropis ochrocephala Bunge, their effect on hepatitis B surface antigen (HBsAg) secretion was studied using the MTT assay. A 3D-QSAR analysis showed a strong correlation between chemical structures and biological activities (q2 = 0.625, r2 = 0.859). Molecular docking and molecular dynamics simulations revealed that hydrogen bonding and hydrophobic interactions with hepatitis B core protein (PDB:5T2P) are key to inhibiting HBsAg secretion, suggesting potential for developing natural anti-hepatitis B drugs.

Ion adsorption-enrichment effect and its driving mechanism for nano-dots lithography with SPM probe on water-soluble crystal surfaces.

HYPOTHESIS: Water-soluble KDP (KH2PO4) crystals possess excellent optical properties and are employed as frequency converters in clean fusion energy. To improve their performances, there is an immediate necessity to lithograph surface nano-patterns on them. Although the Scanning Probe Microscope (SPM) provides a promising way to achieve this purpose through the water menisci, the driving mechanisms of the lithographic behaviors have not yet been revealed. SIMULATIONS AND EXPERIMENTS: Multi-scale investigations are constructed to explore the underlying driving mechanisms. The SPM probe-induced ion diffusion-transport behaviors are investigated by molecular dynamics. The ion adsorption-enrichment mechanisms are revealed by 18 adsorption models via the ab initio. The SPM probe-induced self-assembly experiments are performed to prove the local heavy concentration. A comprehensive model is developed to describe the lithography mechanisms of the probe-induced self-assembly nano-dots on water-soluble substrates. FINDINGS: It is interestingly found that the KDP growth units (H2PO4-) exhibit obvious adsorption-enrichment effect at 3.16 Å from the probe surface, causing local heavy concentration. The H2PO4- would spontaneously adsorb onto the probe surface, which is dominated by the Si-O bonding reactions. The nano-dots with the height of 27 âˆ¼ 48 nm and diameter of 2.0 âˆ¼ 2.7 µm are lithographed on the KDP substrate. The proposed model further confirms that the lithography processes are driven by the solution supersaturation, solute diffusion, and surface free energy.

Comparison of percutaneous microwave/radiofrequency ablation liver partition and portal vein embolization versus transarterial chemoembolization and portal vein embolization for planned hepatectomy with insufficient future liver remnant.

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.

No value of non-selective beta-blockers after TIPS-insertion.

BACKGROUND AND AIMS: Non-selective beta-blockers (NSBB) are a well-established treatment in patients with clinically significant portal hypertension. However, their potential role after insertion of a transjugular intrahepatic portosystemic shunt (TIPS) still needs to be determined. Of note, recent studies suggested that favourable anti-inflammatory effects of NSBB might be independent from pressure reduction. This study aimed to evaluate whether NSBB-treatment is associated with amelioration of systemic inflammation (SI), hepatic decompensation and survival after TIPS-insertion. METHODS: In a retrospective study comprising 305 consecutive patients, we investigated the impact of NSBB-intake at TIPS-placement on periinterventional cirrhosis-associated complications and continued NSBB-treatment after discharge on complications including hepatic decompensation and mortality during 1-year follow-up, employing multivariable competing-risk-analyses. In a prospective cohort including 45 patients, we performed a comprehensive analysis of SI analysing 48 soluble inflammatory markers (SIMs) at baseline plus 3 and 6 months after TIPS-insertion. RESULTS: Overall, 175 (57.4%) patients received NSBB-therapy prior to TIPS-insertion; upon discharge, this decreased to 131 (22.9%), with 36 (27.5%) discontinuing NSBB within 1-year follow-up. Neither NSBB-therapy at TIPS-insertion nor treatment-continuation after discharge were associated with lower risks for hepatic decompensation, individual cirrhosis-associated complications or mortality neither in the periinterventional period nor during follow-up. Similarly, in the prospective cohort NSBB-intake was not linked to lower levels or a more prominent change of WBC, CRP or any other SIM at any of the investigated time points. CONCLUSION: NSBB-therapy at the time of TIPS-insertion and its (dis-)continuation afterwards seems to have no significant impact on SI, development of hepatic decompensation and survival.

Assessment of early factors for identification or prediction severe acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a rare and serious condition, and severe APIP (SAPIP) can lead to pancreatic necrosis, abscess, multiple organ dysfunction, and other adverse maternal and infant outcomes. Therefore, early identification or prediction of SAPIP is important. AIM: To assess factors for early identification or prediction of SAPIP. METHODS: The clinical data of patients with APIP were retrospectively analyzed. Patients were classified with mild acute pancreatitis or severe acute pancreatitis, and the clinical characteristics and laboratory biochemical indexes were compared between the two groups. Logical regression and receiver operating characteristic curve analyses were performed to assess the efficacy of the factors for identification or prediction of SAPIP. RESULTS: A total of 45 APIP patients were enrolled. Compared with the mild acute pancreatitis group, the severe acute pancreatitis group had significantly increased (P < 0.01) heart rate (HR), hemoglobin, neutrophil ratio (NEUT%), and neutrophil-lymphocyte ratio (NLR), while lymphocytes were significantly decreased (P < 0.01). Logical regression analysis showed that HR, NEUT%, NLR, and lymphocyte count differed significantly (P < 0.01) between the groups. These may be factors for early identification or prediction of SAPIP. The area under the curve of HR, NEUT%, NLR, and lymphocyte count in the receiver operating characteristic curve analysis was 0.748, 0.732, 0.821, and 0.774, respectively. The combined analysis showed that the area under the curve, sensitivity, and specificity were 0.869, 90.5%, and 70.8%, respectively. CONCLUSION: HR, NEUT%, NLR, and lymphocyte count can be used for early identification or prediction of SAPIP, and the combination of the four factors is expected to improve identification or prediction of SAPIP.

Potential Drivers for the Spatiotemporal Patterns of the Global Burden of Chronic Obstructive Pulmonary Disease Attributable to Ambient Ozone, 1990-2019.

Objectives: To identify the long-term spatiotemporal trend of ozone-related chronic obstructive pulmonary disease (COPD) burden by sex and country and to explore potential drivers. Methods: We retrieved data of ozone-related COPD death and disability adjusted life year (DALY) from the Global Burden of Disease 2019. We used a linear regression of natural logarithms of age-standardized rates (ASRs) with calendar year to examine the trends in ASRs and a panel regression to identify country-level factors associated with the trends. Results: Global ozone-attributable COPD deaths increased from 117,114 to 208,342 among men and from 90,265 to 156,880 among women between 1990 and 2019. Although ASRs of ozone-related COPD death and DALY declined globally, they increased in low and low-middle Socio-demographic Index (SDI) regions, with faster rise in women. Elevated average maximum temperature was associated with higher ozone-attributable COPD burden, while more green space was associated with lower burden. Conclusion: More efforts are needed in low and low-middle SDI regions, particularly for women, to diminish inter-country inequality in ozone-attributable COPD. Global warming may exacerbate the burden. Expanding green space may mitigate the burden.

Sex-specific epigenetic signatures of circulating urate and its increase after BCG vaccination.

Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown. Additionally, it is worth investigating if urate changes after perturbations, such as vaccination, are associated with DNA methylation in a sex-specific manner. Methods: We investigated the association between DNA methylation and serum urate concentrations in a Dutch cohort of 325 healthy individuals. Urate concentration and DNA methylation were measured before and after Bacillus Calmette-Guérin (BCG) vaccination, used as a perturbation associated with increased gout flares. The association analysis included united, interaction, and sex-stratified analysis. Validation of the identified CpG sites was conducted using three independent cohorts. Results: 215 CpG sites were associated with serum urate in males, while 5 CpG sites were associated with serum urate in females, indicating sex-specific associations. Circulating urate concentrations significantly increased after BCG vaccination, and baseline DNA methylation was associated with differences in urate concentration before and after vaccination in a sex-specific manner. The CpG sites associated with urate concentration in males were enriched in neuro-protection pathways, whereas in females, the urate change-associated CpG sites were related to lipid and glucose metabolism. Conclusion: Our study enhances the understanding of how epigenetic factors contribute to regulating serum urate levels in a sex-specific manner. These insights have significant implications for the diagnosis, prevention, and treatment of various urate-related diseases and highlight the importance of personalized and sex-specific approaches in medicine.

Ambient temperature and the risk of childhood epilepsy hospitalizations: Potentially neglected risk of temperature extremes and modifying effects of air pollution.

PURPOSE: Extreme temperatures and air pollution are increasingly important risk factors for human health in the background of climate change, with limited evidence available for neurological disorders. This study intended to investigate the short-term effects of extreme temperatures on childhood epilepsy and explore the potential modifying effect of air pollution. METHODS: Daily childhood epilepsy hospitalization, meteorological and air pollution data were collected from 10 cities in Anhui Province of China during 2016-2018. We firstly employed a space-time-stratified case-crossover design and conditional logistic regression model to fit the short-term relationship between temperature and epilepsy. Then, we conducted stratified analyses by the level of air pollution and individual characteristics. RESULTS: Both extreme heat and extreme cold increased the risk of hospitalization for childhood epilepsy. The effect of extreme heat [97.5th vs. minimum hospitalization temperature (MHT)] on hospitalization was acute and emerged at lag0 [OR: 1.229 (95 %CI: 1.035 to 1.459)], while the effect of extreme cold (2.5th vs. MHT) was delayed and appeared at lag5 [OR: 1.098 (95 %CI: 1.043 to 1.156)]. We also found children aged 6-18 years were more susceptible to extreme cold than children aged 0-5 years. Besides, extreme heat and cold effects differed by the level of air pollutants. CONCLUSION: This study suggests that extreme temperatures might be the novel but currently neglected risk factor for childhood epilepsy, and air pollution could further amplify the adverse effect of temperature.