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Climate change has led to an increasing frequency and intensity of extreme climate events such as heat and drought extremes with considerable global public health burden. This systematic review collected 87 domestic and international studies from 2000 to 2023, considering the impacts of heat extremes, drought extremes, and compound hot-dry events on infectious diseases attributable to various transmission pathways such as waterborne, foodborne, insect-borne, airborne, and contact-transmitted diseases. Our results showed that high temperature was associated with increased transmission risks of waterborne and foodborne diseases including infectious diarrheal diseases (cholera, dysentery, typhoid, and paratyphoid) and infectious gastroenteritis; vector-borne diseases including dengue fever, Zika virus (ZIKV) disease, chikungunya fever, malaria, West Nile fever, and Rift Valley fever; airborne diseases including influenza-like diseases, influenza A, measles, and mumps; and contact-transmitted diseases including HIV/AIDS, schistosomiasis, and leptospirosis. Additionally, drought conditions also amplified the transmission risks of waterborne and foodborne diseases including cholera, Escherichia coli infection, rotavirus infection, and hepatitis E; vector-borne diseases such as scrub typhus, schistosomiasis, hemorrhagic fever with renal syndrome, and West Nile fever; airborne diseases including meningococcal meningitis, pertussis, measles, and upper respiratory infections; and contact-transmitted diseases such as HIV/AIDS. Along with global warming, the frequency of compound high temperature and drought events shows a considerably increasing trend, causing more adverse health effects than heat or drought alone. However, there is limited research quantifying their effects on infectious diseases. These associations may be mediated through temperature and precipitation on infectious disease pathogens, transmission vectors, population susceptibility, public health services, and behaviors. In the context of climate change, the increasing occurrence of compound events of high temperatures and droughts raises health concerns, and further studies are needed to enhance our understanding of the impacts of climate change on infectious diseases and improve human adaption to climate change.

Abstract Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.

This paper utilizes data on the records of damage to expressways and main roads caused by precipitation in Liaoning Province from 2017 to 2021. It analyzes the temporal and spatial characteristics of damage accidents, calculates the effective rainfall before the occurrence of accidents, and establishes a probability fitting model for road water damage. The results show that precipitation-induced road damage events in Liaoning Province generally occur from May to October, with a peak in July and August. The occurrence of road water damage follows a pattern of gradually delaying from northwest to southeast, and the number of accidents is highly correlated with precipitation. The eastern and western parts of Liaoning are high-incidence areas, with Dandong, Chaoyang, Huludao, and Benxi being the high-incidence areas within the province. Among various methods compared, the fitting effect of the road water damage probability conforms to the Gaussian distribution probability density function. The critical rainfall threshold for disaster in the eastern and southern parts of Liaoning is higher than that in the central and northern parts. Under the same effective rainfall conditions, the risk of road water damage in plain areas is higher than in mountainous and hilly areas. The road water damage situation during a flooding process in Liaoning in 2022 is used for verification, indicating a strong role in flood control guidance.

Abstract The inference of cell–cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Abstract Accurately imaging seismogenic structures is crucial for seismic hazard assessment. This is especially important around the deformation front (DF) region off SW Taiwan, where seismic potential is high but the fault structure and seismic activity are still poorly understood. Here, we present a comprehensive delineation of seismogenic structures along the onshore and offshore DF of SW Taiwan, utilizing hypocenter relocations and first-motion focal mechanism solutions from January 1991 to March 2019. Five distinctive seismogenic structures are delineated. Particularly, the energetic seismic activity initialled after the 2017 Mw5.3 Tainan earthquake and migrated northeastward along the western side of the DF. The offshore trace of the DF could serve as a boundary delimiting the seismic activity driven by the flexural stress of the subducted Eurasia Plate to the west of the DF. This observation could constrain the magnitude estimation of future earthquakes offshore SW Taiwan. Meanwhile, the areas with higher seismic moment release are located near the DF rather than known faults, indicating that the DF may dominate the seismic moment release. However, further study is warranted into the intricate relationship among seismic strain variation, the structure of DF, and seismic activity to further understand the seismic potential. Our first-motion focal mechanism solutions show that several earthquakes in SW Taiwan were characterized by P-axis orientations parallel to the strike of the Taiwan orogeny. Those events are preferably explained by the lateral compression induced by the ongoing collision between the Eurasia and Philippine Sea plates.

Abstract In the continental margin of the northeastern South China Sea, the sea level fluctuations since the Last Glacial Maximum have profoundly impacted the sedimentary environment. Our sub-bottom profiler data show a sedimentation process change from deposition to erosion during the Last Glacial Maximum. After the widespread erosion, the sedimentation process returned depositional throughout the Holocene, probably due to the rise of the sea level. This sedimentary process results in a widespread sedimentary unconformity in the continental slope, providing a benchmark for the end of the Last Glacial Maximum. Analyzing the sediment cores, we affirm that the change in current intensity is the primary factor controlling the sedimentary environments. The current intensities strengthened during the eustatic lowstand and weakened during the highstand periods, leading to alternating erosional and depositional processes. The widespread distribution of the erosive surface represents a regional-scale change in the sedimentary environment instead of a local event.

Abstract Introduction Glioblastoma (GBM) poses a significant challenge in oncology, with median survival times barely extending beyond a year due to resistance to standard therapies like temozolomide (TMZ). This study introduces a novel therapeutic strategy combining progesterone (Prog) and abiraterone (Abi) aimed at enhancing GBM treatment efficacy by modulating the tumor microenvironment and augmenting NK cell-mediated immunity. Methods We employed in vitro and in vivo GBM models to assess the effects of Prog and Abi on cell viability, proliferation, apoptosis, and the immune microenvironment. Techniques included cell viability assays, Glo-caspase 3/7 apoptosis assays, RNA-seq and qPCR for gene expression, Seahorse analysis for mitochondrial function, HPLC-MS for metabolomics analysis, and immune analysis by flow cytometry to quantify NK cell infiltration. Results Prog significantly reduced the IC50 of Abi in TMZ-resistant GBM cell, suggesting the enhanced cytotoxicity. Treatment induced greater apoptosis than either agent alone, suppressed tumor growth, and prolonged survival in mouse models. Notably, there was an increase in CD3−/CD19−/CD56+/NK1.1+ NK cell infiltration in treated tumors, indicating a shift towards an anti-tumor immune microenvironment. The combination therapy also resulted in a reduction of MGMT expression and a suppression of mitochondrial respiration and glycolysis in GBM cells. Conclusion The combination of Prog and Abi represents a promising therapeutic approach for GBM, showing potential in suppressing tumor growth, extending survival, and modulating the immune microenvironment. These findings warrant further exploration into the clinical applicability of this strategy to improve outcomes for GBM patients.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract Postoperative acute kidney injury (AKI) is a common complication that is associated with chronic kidney disease, early postsurgical mortality, and prolonged hospital stays. Preterm neonates who undergo surgery are at risk factors for AKI due to underdeveloped kidneys. To date, little is known about the incidence and perioperative risk factors for AKI in preterm neonates undergoing noncardiac surgery. Preterm neonates who underwent noncardiac surgery between January May 1, 2020, and February 28, 2023, were enrolled in the trial according to the inclusion criteria. Both multivariable and logistic regression analyses were used to analyze the associations between characteristic data and AKI. In total, 106 preterm neonates met the inclusion criteria, and 25 preterm neonates (23.6%) developed postoperative AKI. Multivariate analysis revealed that the factors associated with AKI were gestational age

Abstract Background Diabetes mellitus is generally accompanied by dyslipidaemia, but inconsistent relationships between lipid profiles and diabetes are noted. Moreover, genetic variations in insertion/deletion (I/D) polymorphisms at angiotensin-converting enzyme gene (ACE) and T/C polymorphisms in the angiotensin type 1 receptor gene (AGTR1) are related to diabetes and lipid levels, but the associations are controversial. Thus, the current research aimed to explore the effects of ACE I/D, AGTR1 rs5182 and diabetes mellitus on serum lipid profiles in 385 Chinese participants with an average age of 75.01 years. Methods The ACE I/D variant was identified using the polymerase chain reaction (PCR) method, whereas the AGTR1 rs5182 polymorphism was identified using the PCR-based restriction fragment length polymorphism (PCR-RFLP) method and verified with DNA sequencing. Total cholesterol (TC), triglyceride (TG), apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured using routine methods, and the lipid ratios were calculated. Results ACE I/D, but not AGTR1 rs5182, was a predictor of TG/HDL-C for the whole study population. Both ACE I/D and AGTR1 rs5182 were predictors of HDL-C and LDL-C levels in females but not in males. Moreover, in females, diabetes mellitus and ACE I/D were identified as predictors of TG and TG/HDL-C, whereas AGTR1 rs5182 and diabetes mellitus were predictors of TG/HDL-C. Moreover, diabetes mellitus and the combination of ACE I/D and AGTR1 rs5182 variations were predictors of TG and TG/HDL-C exclusively in females. Conclusions The results demonstrated the potential for gender-dependent interactions of ACE I/D, AGTR1 rs5182, and diabetes on lipid profiles. These findings may serve as an additional explanation for the inconsistent changes of blood lipids in individuals with diabetes mellitus, thereby offering a novel perspective for the clinical management of blood lipid levels in diabetic patients.

Abstract Background The fruit ripening period is an important target trait in fruit tree crop breeding programs. Thus, citrus tree breeders seek to develop extreme early ripening cultivars that allow optimization of citrus maturation periods. In this study, we explored the regulatory network involved in fruit ripening in Citrus sinensis using the ‘Newhall’ navel orange variety and its early-ripening mutant, ‘Gannanzao’. This research will provide a basis for further research on important signaling pathways, gene functions and variety breeding of Citrus sinensis related to fruit ripening period. Results Physiological analyses suggested that early fruit ripening in ‘Gannanzao’ is regulated by early accumulation of abscisic acid (ABA), persistently high levels of jasmonic acid (JA), and higher sucrose content in the pericarp. Pericarp samples from ‘Gannanzao’ and ‘Newhall’ navel oranges were sampled for RNA sequencing analysis at 180, 200, and 220 days after flowering; 1430 differentially expressed genes (DEGs) were identified. Functional enrichment analysis indicated that these DEGs were mainly enriched in the plant hormone signal transduction and sugar metabolism pathways, as well as other pathways related to fruit ripening. Important DEGs associated with fruit ripening in ‘Gannanzao’ included genes involved in ABA and JA metabolism and signal transduction, as well as sugar metabolism. Weighted gene co-expression network analysis showed that the deep pink module had the strongest correlations with ABA content, JA content, and early ripening. Based on gene functionality and gene expression analyses of 37 genes in this module, two candidate hub genes and two ethylene response factor 13 (ERF13) genes (Cs_ont_5g000690 and Cs_ont_5g000700) were identified as key genes regulated by ABA and JA signaling. These findings will help to clarify the mechanisms that underlie early citrus fruit ripening and will lead to the development of excellent genetic resources for further breeding of extreme early-ripening varieties. Conclusions Through analyses of the ‘Newhall’ navel orange cultivar and its early-ripening mutant ‘Gannanzao’, we identified genes involved in ABA and JA metabolism, signal transduction, and sugar metabolism that were related to fruit ripening. Among these, two ERF13 genes were inferred to be key genes in the regulation of fruit ripening. These findings provide insights into the genetic architecture related to early fruit ripening in C. sinensis.

Abstract The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

Abstract Three classes of BCMA-directed therapy (BDT) exist: antibody drug-conjugates (ADCs), CAR-T, and T-cell engagers (TCEs), each with distinct strengths and weaknesses. To aid clinicians in selecting between BDTs, we reviewed myeloma patients treated at Mayo Clinic with commercial or investigational BDT between 2018-2023. We identified 339 individuals (1-exposure = 297, 2-exposures = 38, 3-exposures = 4) who received 385 BDTs (ADC = 59, TCE = 134, CAR-T = 192), with median follow-up of 21-months. ADC recipients were older, with more lines of therapy (LOT), and penta-refractory disease. Compared to ADCs, CAR-T (aHR = 0.29, 95%CI = 0.20–0.43) and TCEs (aHR = 0.62, 95%CI = 0.43–0.91) had better progression-free survival (PFS) on analysis adjusted for age, the presence of extramedullary (EMD), penta-refractory disease, multi-hit high-risk cytogenetics, prior BDT, and the number of LOT in the preceding 1-year. Likewise, compared to ADCs, CAR-T (aHR = 0.28, 95%CI = 0.18–0.44) and TCEs (aHR = 0.60, 95%CI = 0.39–0.93) had superior overall survival. Prior BDT exposure negatively impacted all classes but was most striking in CAR-T, ORR 86% vs. 50% and median PFS 13-months vs. 3-months. Of relapses, 54% were extramedullary in nature, and a quarter of these cases had no history of EMD. CAR-T demonstrates superior efficacy and where feasible, should be the initial BDT. However, for patients with prior BDT or rapidly progressive disease, an alternative approach may be preferable.

Abstract Background The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. Methods This hospital-based, cross-sectional study was conducted at the Third People’s Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. Results The study included participants primarily between the ages of 20–40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. Conclusion Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 ‘don’t eat me’ signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial–mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.

Abstract The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.

Abstract Adaptive information seeking is essential for humans to effectively navigate complex and dynamic environments. Here, we developed a gaze-contingent eye-tracking paradigm to examine the early emergence of adaptive information-seeking. Toddlers (N = 60, 18-36 months) and adults (N = 42) either learnt that an animal was equally likely to be found in any of four available locations, or that it was most likely to be found in one particular location. Afterwards, they were given control of a torchlight, which they could move with their eyes to explore the otherwise pitch-black task environment. Eye-movement data and Markov models show that, from 24 months of age, toddlers become more exploratory than adults, and start adapting their exploratory strategies to the information structure of the task. These results show that toddlers’ search strategies are more sophisticated than previously thought, and identify the unique features that distinguish their information search from adults’.

Abstract Background Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. Methods Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155−/− mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. Results Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated β-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. Conclusions Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

This paper attempts to explore the feasibility of using cholesteric liquid crystals (CLCs) for reflective displays in active matrix (AM) driving. The study focuses on reverse mode polymer-stabilized cholesteric liquid crystals (PSCLCs) to overcome the inherent bistability of CLCs and achieve faster response times for switching between bright and dark states. Key parameters such as cell gap, monomer concentration, polymerization temperature, and different monomer types and liquid crystal hosts are systematically investigated to optimize the electro-optical properties of the liquid crystals for active matrix driving. The research demonstrates that PSCLCs can operate within a 15 V driving voltage range while maintaining a good bright-dark state contrast ratio (>10) and a response time of less than 42 ms. This suggests significant potential for their application in dynamic reflective display technologies.

Physical activity in childhood is essential for healthy development and wellbeing and school grounds can provide neighbourhood access to safe play spaces. This study examines the relationship between school demographics (school size, school decile, ethnicity of students and population density) and whether school grounds are open or closed for community use outside school hours. Data were gathered from 391 primary and intermediate schools across Tāmaki Makaurau (Auckland), Aotearoa New Zealand (84% of Auckland schools) with 250 schools participating in the full survey. The results indicate that higher school decile and lower population density are associated with school grounds being available for community use. This result is concerning. With closed school grounds more likely to be in lower socio-economic and higher population density areas, the children most affected are the same group who have fewer opportunities and less spaces for active play. The main reason schools closed their grounds was ‘vandalism /graffiti/theft concerns’. Low decile schools whose grounds were open outside of school hours shared a similar commitment to involve their communities widely in school activities and found doing so decreased the levels of vandalism. Their approach may offer useful insights to schools that are currently closed.

Abstract Background In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers’ smart device usage and behavioral outcomes, are limited. Understanding the impact of parent–child interactions on this relationship is crucial for enhancing toddlers’ developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers’ behaviors, as well as the positive effects of mother–child interactions on this influence. Methods We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children’s behavior by using the Child Behavior Checklist (for ages 11/2–5 years), (2) assessments of mother–child interactions by using the Brigance Parent–Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression. Results A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aβ) = 2.17, 95% confidence interval (CI) = 0.39–3.95, p-value = 0.01], withdrawal (aβ = 2.42, 95% CI = 0.15–4.69, p-value = 0.04), and aggressive behavior (aβ = 6.53, 95% CI = 0.25–12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother–child interaction. Nevertheless, positive mother–child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother–child interactions. Conclusion Early mother–child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.

Abstract Aims To detect the expression of autophagy components, p38 MAPK (p38) and phosphorylated forkhead box transcription factor O-1 (pFoxO1) in pulmonary vascular endothelial cells of chronic thromboembolic pulmonary hypertension (CTEPH) rats and to investigate the possible mechanism through which tissue factor (TF) regulates autophagy. Methods Pulmonary artery endothelial cells (PAECs) were isolated from CTEPH (CTEPH group) and healthy rats (control group (ctrl group)) which were cocultured with TF at different time points including 12 h, 24 h, 48 h and doses including 0 nM,10 nM, 100 nM, 1µM, 10µM, 100µM and cocultured with TFPI at 48 h including 0 nM, 2.5 nM, 5 nM. The expression of forkhead box transcription factor O-1 (FoxO1), pFoxO1, p38, Beclin-1 and LC3B in PAECs was measured. Coimmunoprecipitation (co-IP) assays were used to detect the interaction between FoxO1 and LC3. Results The protein expression of p-FoxO1/FoxO1 was significantly lower in the CTEPH groups (cocultured with TF from 0 nM to 100 µM) than in the ctrl group at 12 h, 24 h, and 48 h (P

Abstract AI Generated Content Law was extensively promoted in 2023; hence, it is crucial to uncover factors influencing people’s behavioral intentions to comply with the AI Generated Content Law. This study extends the theory of planned behavior to explore the factors influencing people to follow AI Generated Content Law in China. In addition to the factors in TPB model, such as one’s attitudinal factors, normative factors, and perceived behavioral control, we add another factor-moral obligation to extend the theory of planned behavior model. We used convenient sampling and there were 712 effective samples. Using the statistical software Amos17.0, the result shows that attitude, subjective norms, perceived behavioral control and moral obligation all have positive effects on intentions to follow AI Generated Content Law.

Abstract Objectives Acute upper respiratory tract infections (AURTIs) are prevalent in the general population. However, studies on the association of short-term exposure to air pollution with the risk of hospital visits for AURTIs in adults are limited. This study aimed to explore the short-term exposure to air pollutants among Chinese adults living in Ningbo. Methods Quasi-Poisson time serious regressions with distributed lag non-linear models (DLNM) were applied to explore the association between ambient air pollution and AURTIs cases. Patients ≥ 18 years who visit three hospitals, being representative for urban, urban–rural junction and rural were included in this retrospective study. Results In total, 104,441 cases with AURTIs were enrolled in hospital during 2015–2019. The main results showed that particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5), nitrogen dioxide (NO2) and nitrogen dioxide (SO2), were positively associated to hospital visits for AURTIs, except for nitrogen dioxide (O3), which was not statistically significant. The largest single-lag effect for PM2.5 at lag 8 days (RR = 1.02, 95%CI: 1.08–1.40), for NO2 at lag 13 days (RR = 1.03, 95%CI: 1.00–1.06) and for SO2 at lag 5 days (RR = 1.27, 95%CI: 1.08–1.48), respectively. In the stratified analysis, females, and young adults (18–60 years) were more vulnerable to PM2.5 and SO2 and the effect was greater in rural areas and urban–rural junction. Conclusions Exposure to ambient air pollution was significantly associated with hospital visits for AURTIs. This study provides epidemiological evidence for policymakers to control better air quality and establish an enhanced system of air pollution alerts.

Abstract Idecabtagene vicleucel (Ide-cel) has demonstrated excellent efficacy and durable responses in patients with relapsed/refractory multiple myeloma (RRMM). However, the outcomes with ide-cel in patients with extramedullary disease (EMD) remain incompletely characterized. We included patients with RRMM treated with ide-cel between May 2021 and April 2023 across 11 US academic institutions. Visceral or soft tissue lesions non-contiguous from bone was classified as EMD. Time-to-event analyses were performed from date of ide-cel infusion. Among 351 patients, 84 (24%) had EMD prior to infusion. The median follow-up from ide-cel infusion was 18.2 months (95% CI: 17-19.3). The day 90 overall response rates (ORR) were 52% vs. 82% for the EMD and non-EMD cohorts, respectively (p

BackgroundAccess to reliable transportation is fundamental in the management of chronic disease. The purpose of this study was to investigate the association between vehicle ownership at the neighborhood-level and long-term mortality after myocardial infarction (MI).MethodsThis is a retrospective observational study evaluating adult patients admitted for MI between January 1st, 2006, and December 31st, 2016. Neighborhoods were defined by census tract and household vehicle ownership data was obtained from the American Community Survey courtesy of the University of California, Los Angeles Center for Neighborhood Knowledge. Patients were divided into 2 groups: those living in neighborhoods with higher vehicle ownership, and those living in neighborhoods with lower vehicle ownership. The cutoff of 4.34% of households reporting not owning a vehicle was used to define a neighborhood as one with "higher" vs "lower" vehicle ownership as this was the median value for the cohort. The association between vehicle ownership and all-cause mortality after MI was assessed using Cox proportional hazards regression models.ResultsA total of 30,126 patients were included (age 68.1 +/- 13.5 years, 63.2% male). After adjusting for age, sex, race/ethnicity, and medical comorbidities, lower vehicle ownership was associated with increased all-cause mortality after MI (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.06-1.14; p

Objectives: To evaluate the relationship between oral health and geriatric disorders, as well as its role in clinical outcomes among acutely admitted older patients. Design: A retrospective observational study was conducted. Setting: The study was conducted at a medical center in central Taiwan. Participants: A total of 1,141 patients (651 males and 490 females), aged 65 years or older, were admitted due to acute illness with geriatric syndromes from October 1, 2018, to March 31, 2023. Measurements: A comprehensive geriatric assessment (CGA) was conducted, covering the comorbidity index, cognitive status, mood, physical function, nutritional status, mobility, health-related quality of life, frailty, and oral health condition. Oral health was evaluated using a bedside oral examination with scores ranging from 8 to 24, where scores of 8–10 indicated normal oral health, 11–14 indicated moderate impairment, and 15–24 indicated severe impairment. The primary outcome observed was in-hospital mortality. Results: Among the participants, 40.5% experienced cognitive impairment, 24.8% exhibited depressive symptoms, 69.4% had low hand grip strength, 36.5% demonstrated low performance in mobility, and 78.9% were at risk of malnutrition. Severe impairment of oral health was found in 18.8% of the participants, while frailty was observed in 85.1%. Stratification of oral health severity revealed differences in various CGA parameters, including comorbidity, polypharmacy, cognitive impairment, depressive mood, physical activity, mobility, nutritional status, and quality of life, as well as clinical outcomes such as length of stay and in-hospital mortality between the groups. In univariable analysis, age, gender, frailty, oral health impairment, comorbidity index, nutritional status, and cognitive and physical functions were all significantly associated with in-hospital mortality. After adjusting for significant factors, severe oral health impairment remained significantly associated with mortality. Conclusion: In acutely admitted older patients, oral health was associated with geriatric disorders and was linked to in-hospital mortality. Early intervention in oral health may be necessary to improve outcomes.

Castleman disease (CD) is a rare lymphoproliferative disease known as angiofollicular lymph node hyperplasia, firstly reported in 1954. It mainly occurs in adults, presenting with a wide range of clinical manifestations, including paraneoplastic pemphigus (PNP). PNP is a rare and often life-threatening autoimmune disorder characterized by painful blisters and erosions on the skin and mucous membranes. In children, PNP is often linked to Castleman disease, as evidenced in case reports. So far, less than 30 pediatric cases have been reported, with the pathogenesis remaining unclear and treatment approaches varied. Here, we present a pediatric case initially suspected as Behçet's disease due to persistent oral ulcers and conjunctivitis, and undergone a sudden aggravation of clinical features following an allergic reaction. New involvement of skin rashes and imaging findings prompted the final diagnosis as PNP linked to Unicentral Castleman disease (UCD).Through detailing the progression of clinical features and diagnostic work, we aim to arise the awareness of physicians and put emphasize on early recognition and multidisciplinary management, which can improve patient outcomes.

BackgroundParkinson’s disease (PD) is an age-related neurodegenerative disease characterized by the death of dopamine neurons in the substantia nigra. A large number of studies have focused on dopamine neurons themselves, but so far, the pathogenesis of PD has not been fully elucidated.ResultsHere, we explored the significance of oligodendrocyte precursor cells (OPCs)/oligodendrocytes in the pathogenesis of PD using a bioinformatic approach. WGCNA analysis suggested that abnormal development of oligodendrocytes may play a key role in early PD. To verify the transcriptional dynamics of OPCs/oligodendrocytes, we performed differential analysis, cell trajectory construction, cell communication analysis and hdWGCNA analysis using single-cell data from PD patients. Interestingly, the results indicated that there was overlap between hub genes and differentially expressed genes (DEGs) in OPCs not in oligodendrocytes, suggesting that OPCs may be more sensitive to PD drivers. Then, we used ROC binary analysis model to identify five potential biomarkers, including AGPAT4, DNM3, PPP1R12B, PPP2R2B, and LINC00486.ConclusionIn conclusion, our work highlights the potential role of OPCs in driving PD.

Introduction Discogenic low back pain is a common form of chronic low back pain. In traditional Chinese medicine, combinations of acupuncture and herbal medicine are frequently used to manage this condition. However, evidence for the efficacy of a combined approach remains scarce. To address this gap, we designed a multicentre, randomised controlled trial to compare the effects of the combined use of acupuncture and Chinese herbal medicine, and their separate applications along with non-steroidal anti-inflammatory drugs, in treating discogenic low back pain.Methods and analysis This is a multicentre, prospective, randomised, four-arm, parallel-controlled trial involving patients with discogenic low back pain. Patients will be randomly divided into four groups (acupuncture combined with herbal medicine, acupuncture, herbal medicine and positive drug control) at a 1:1:1:1 ratio. All patients will undergo a 4-week treatment regimen consisting of acupuncture (active or sham acupuncture) and oral medication (herbal medicine or placebo granules and celecoxib or placebo capsules), as well as a 3-month follow-up assessment. The primary outcome measure will be pain intensity, measured using the Visual Analogue Scale after a 4-week treatment period. Secondary outcome measures will include the lumbar pressure pain threshold, pain-related disability measured using the Oswestry Disability Index, Hospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, 36-Item Short-Form Health Survey and incidence of adverse events. Assuming an SD of 1.8, minimal clinically important difference of 1.5 and a 10% dropout rate, at least 97 participants per group are needed, totalling 388 participants.Ethics and dissemination The study was approved by the Ethics Committee of Dongzhimen Hospital Affiliated with Beijing University of Chinese Medicine (approval number: 2024DZMEC-083-03) and the other seven participating subcentres. All participants will provide written informed consent. This trial will be conducted in accordance with the principles outlined in the Declaration of Helsinki and its amendments. This work will be disseminated through the publication of peer-reviewed manuscripts.Trial registration number ChiCTR2400082428.

Purpose: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users. Methods: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among groups. The Fine and Gray model was utilized to estimate the subdistribution hazard ratio and 95% confidence interval. Results: This study included 701 bevacizumab, 463 ranibizumab, and 984 aflibercept users. After IPTW, all covariates were well-balanced. All three anti-VEGF agents had a low and comparable number per 100 person-years of major adverse cardiac events, heart failure, thromboembolic events, major bleeding, all-cause admission, and all-cause death (all P > 0.05). No significant differences in long-term change of systolic and diastolic blood pressure, low-density lipoprotein, estimated glomerular filtration rate, and alanine transaminase (all P for interaction > 0.05) were observed among groups. Conclusion: Bevacizumab, ranibizumab, and aflibercept had a good systemic safety profile in this study. All groups showed a low and similar SAE risk and no differences in their long-term change of laboratory data. Therefore, these anti-VEGF agents could be prescribed safely to patients with AMD.

Objectives: The World Health Organization’s Integrated Care for Older People (ICOPE) framework launched in 2019 is used to assess the intrinsic capacity of older individuals. Older women may face greater socioeconomic disadvantages, which can impact their physical and mental well-being. Therefore, we examined sex differences in intrinsic capacity and the influence of socioeconomic status. Methods: We conducted a cross-sectional study in Tainan, Taiwan, recruiting 1,268 adults aged 60 or older in 2022. The ICOPE screening assessed cognitive decline, limited mobility, malnutrition, visual impairment, hearing loss, and depressive symptoms. Intrinsic capacity scores ranged from 0 to 6 and were categorized as impairment (1 or higher) or no impairment (0). Binary logistic regression models were used to analyze sex differences in intrinsic capacity, adjusting sequentially for demographics, lifestyle, and socioeconomic factors. Results: The prevalence of intrinsic capacity impairment was 34 %. Women had significantly higher odds of intrinsic capacity impairment (women vs. men, odds ratio [OR] = 1.39, 95 % CI = 1.10–1.75). After sequentially adjusting for demographic characteristics, lifestyle, and socioeconomic factors, the ORs were 1.46 (95 % CI = 1.12–1.90), 1.69 (95 % CI = 1.23–2.31), and 1.24 (95 % CI = 0.88–1.73), respectively. Stratified analyses showed that higher odds of impairment in women than in men was evident only in the financially dependent group (P for interaction = 0.059). Conclusions: Older women in Taiwan have poorer intrinsic capacity than men, a disparity largely attributable to women’s lower socioeconomic status. Strategies to promote healthy aging among women from disadvantaged socioeconomic backgrounds may help mitigate this sex difference in intrinsic capacity.