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African swine fever virus is highly contagious, and mortality rates reach up to 100% depending on the host, virus dose, and the transmission routes. The main objective of this study was to develop a network-based simulation model for the farm-level transmission of ASF virus to evaluate the impact of changes in farm connectivity on ASF spread in Vietnam. A hypothetical population of 1,000 pig farms was created and used for the network-based simulation, where each farm represented a node, and the connection between farms represented an edge. The three scenarios modelled in this way (baseline, low, and high) evaluated the impact of connectivity on disease transmission. The median number of infected farms was higher as the connectivity increased (low: 659, baseline: 968 and high: 993). In addition, we evaluated the impact of the culling strategy on the number of infected farms. A total of four scenarios were simulated depending on the timing of culling after a farm was infected. We found that the timing of culling at 16, 12, 8, and 6 weeks had resulted in a reduction of the number of median infected farms by 81.92%, 91.63%, 100%, and 100%, respectively. Finally, our evaluation of the implication of stability of ties between farms indicated that if the farms were to have the same trading partners for at least six months could significantly reduce the median number of infected farms to two (95th percentile: 413) than in the basic model. Our study showed that pig movements among farms had a significant influence on the transmission dynamics of ASF virus. In addition, we found that the either timing of culling, reduction in the number of trading partners each farm had, or decreased mean contact rate during the outbreaks were essential to prevent or stop further outbreaks.

PurposeA considerable number of diabetic foot ulcer (DFU) patients require amputation every year, which worsens their quality of life, aggravates the social burden, and shortens their life expectancy. Considering these negative effects, it is important to explore the relative risk factors affecting amputation in DFU patients.MethodsThe PubMed, SCIE and Embase databases were comprehensively searched for prospective or retrospective studies published before October 31, 2019. All English language studies involving DFU patients were included, and RevMan 5.3 software was used to analyse the data.ResultsThis meta-analysis includes 21 studies involving 6505 participants, including 2006 patients who required a lower limb amputation. The following variables were associated with an increased risk of amputation: male sex (odds ratios (OR) = 1.30, 95% confidence interval (CI) = 1.16~1.46, PConclusionsOur meta-analysis identified several risk factors for amputation in DFU patients, including the male sex, a smoking history, a history of foot ulcers, osteomyelitis, gangrene, a lower body mass index, and a higher white blood cell count. Once gangrene occurs, the risk of amputation rapidly increases.

Starvation is a common stress in fish. The underlying molecular mechanisms associated with growth depression caused by feeding restriction and compensatory growth are not well understood. We investigated the effect of fasting and refeeding on the transcriptome profiles of brain in juvenile S. hollandi using RNA-seq. A total of 4.73 × 108 raw reads were obtained from nine brain samples. De novo transcriptome assembly identified 387,085 unigenes with 2.1×109 nucleotides. A total of 936 annotated unigenes showed significantly differential expression among the control, fasting, and fasting-refeeding groups. The down-regulated differentially expressed genes (DEGs) during fasting were mainly associated with cell cycle, DNA replication, and mitosis. The up-regulated DEGs were mainly related to glucose and lipid metabolism, material transportation, and transcription factors. Most decreased DEGs during fasting were restored to normal levels after refeeding. Comparing with the control group, genes associated with protein synthesis, stimulus response, and carbohydrate metabolism were significantly over-expressed and pro-opio melanocortin (POMC) was down-regulated during the refeeding period. In conclusion, fish mobilized stored energetic materials and reduced energy consumption to prolong survival during fasting. After refeeding, the down-regulation of DEGs, e.g., POMC may be associated with compensatory growth. Up-regulation of DEGs related to ribosomal protein, stimulus response, and carbohydrate metabolism may contribute to eliminate negative effect of starvation on brain. This study provided the first transcriptome data related with impact of short-time starvation and refeeding in S. hollandi brains.

BACKGROUND:Dengue fever is the most widespread infectious disease of humans transmitted by Aedes mosquitoes. It is the leading cause of hospitalization and death in children in the Southeast Asia and western Pacific regions. We analyzed surveillance records from health centers in Vietnam collected between 2001-2012 to determine seasonal trends, develop risk maps and an incidence forecasting model. METHODS:The data were analyzed using a hierarchical spatial Bayesian model that approximates its posterior parameter distributions using the integrated Laplace approximation algorithm (INLA). Meteorological, altitude and land cover (LC) data were used as predictors. The data were grouped by province (n = 63) and month (n = 144) and divided into training (2001-2009) and validation (2010-2012) sets. Thirteen meteorological variables, 7 land cover data and altitude were considered as predictors. Only significant predictors were kept in the final multivariable model. Eleven dummy variables representing month were also fitted to account for seasonal effects. Spatial and temporal effects were accounted for using Besag-York-Mollie (BYM) and autoregressive (1) models. Their levels of significance were analyzed using deviance information criterion (DIC). The model was validated based on the Theil's coefficient which compared predicted and observed incidence estimated using the validation data. Dengue incidence predictions for 2010-2012 were also used to generate risk maps. RESULTS:The mean monthly dengue incidence during the period was 6.94 cases (SD 14.49) per 100,000 people. Analyses on the temporal trends of the disease showed regular seasonal epidemics that were interrupted every 3 years (specifically in July 2004, July 2007 and September 2010) by major fluctuations in incidence. Monthly mean minimum temperature, rainfall, area under urban settlement/build-up areas and altitude were significant in the final model. Minimum temperature and rainfall had non-linear effects and lagging them by two months provided a better fitting model compared to using unlagged variables. Forecasts for the validation period closely mirrored the observed data and accurately captured the troughs and peaks of dengue incidence trajectories. A favorable Theil's coefficient of inequality of 0.22 was generated. CONCLUSIONS:The study identified temperature, rainfall, altitude and area under urban settlement as being significant predictors of dengue incidence. The statistical model fitted the data well based on Theil's coefficient of inequality, and risk maps generated from its predictions identified most of the high-risk provinces throughout the country.

BackgroundLeptospirosis is an important zoonotic disease with a global distribution, affecting a wide range of mammalian animals and humans. Japanese encephalitis (JE) virus is the major vector-borne zoonotic disease in the Asia-Pacific region. The main objective of this study was to evaluate the seroprevalence of serovar-specific Leptospira and JE in swine from 10 provinces in Vietnam.MethodsSamples were initially collected for swine influenza surveillance from March to April 2017 at large-scale farms (with at least 50 sows and/or 250 fattening pigs) with pigs that tested positive for influenza in the previous surveillance period (2015-16).FindingsA total of 2,000 sera samples were analyzed from 10 provinces. Overall, the seroprevalence of leptospirosis was 21.05% (95% CI: 19.28-22.90) using a cut-off titer of ≥ 1:100. The apparent prevalence of JE was 73.45% (95% CI: 71.46-75.37) while the true prevalence was slightly higher (74.46%, 95% credible interval: 73.73-86.41). We found a relatively high presence of leptospirosis and JE in pigs kept on large farms. Prevalence was comparable with other studies suggesting opportunistic testing of samples collected for other surveillance purposes can be a valuable tool to better understand and prevent the potential transmission of these zoonotic diseases from pigs to people in Vietnam.ConclusionOur study provides evidence to veterinarians and animal health professionals for evidence-based practice such as diagnosis, vaccination and zoonotic control. Further investigation into the possible role of different domestic animals, wildlife species or environmental factors is needed to identify the potential risk factors and transmission routes in Vietnam.

In Vietnam, rabies has been a notifiable disease for more than 40 years. Over the last five years, on average, more than 350,000 people per year have been bitten by dogs and cats while more than 80 human deaths have been reported yearly. No studies have been conducted to evaluate the geographical and temporal patterns of rabies in humans in Vietnam. Therefore, the main objective of this study was to assess the geographical and temporal distributions of rabies post exposure prophylaxis (PEP) incidence in humans in Vietnam from 2005 to 2015.Average incidence rabies (AIR) PEP rates for every 3 or 4 years (2005-2008, 2009-2012 and 2013-2015) were calculated to describe the spatial distribution of rabies PEP. Hotspot analysis was implemented to identify patterns of spatial significance using the Getis-Ord Gi statistic. For temporal pattern analysis, two regions [Mekong River Delta (MRD) and Southeast Central Coast (SCC)], with the highest incidence rates, and the seasonal-decomposition procedure based on loess (STL), were compared to assess their temporal patterns of rabies PEP.We found hotspots in southern Vietnam and coldspots in northern Vietnam during the study period. Rabies cases were limited to specific areas. In addition, the hotspot analysis showed that new risk areas were identified in each period which were not observed in incidence rate maps. The seasonal plots showed seasonal patterns with a strong peak in February/July and a minor peak in October/December in the MRD region. However, in the SCC, a small peak was detected at the early part of each year and a strong peak in the middle of each year.Our findings provide insight into understanding the geographical and seasonal patterns of rabies PEP in Vietnam. This study provides evidence to aid policy makers when making decisions and investing resources. Such information may also be utilized to raise public awareness to prevent rabies exposures and reduce unnecessary PEP.

Salicylic acid (SA) is synthesized via the phenylalanine lyase (PAL) and isochorismate synthase (ICS) pathways and can influence the stress response in plants by regulating certain secondary metabolites. However, the association between SA and particular secondary metabolites in the Chinese medicinal plant Scutellaria baicalensis Georgi is unclear. To elucidate the association between SA and the secondary metabolites baicalin and baicalein, which constitute the primary effective components of S. baicalensis, we subjected seedlings to drought and salt stress and exogenous SA treatment in a laboratory setting and tested the expression of PAL and ICS, as well as the content of free SA (FSA), total SA (TSA), baicalin, and baicalein. We also assessed the correlation of FSA and TSA with PAL and ICS, and with baicalin and baicalein accumulation, respectively. The results indicated that both FSA and TSA were positively correlated with PAL, ICS, and baicalin, but negatively correlated with baicalein. The findings of this study improve our understanding of the manner in which SA regulates secondary metabolites in S. baicalensis.

Renal interstitial fibrosis (IF) is an important pathologic manifestation of disease progression in a variety of chronic kidney diseases (CKD). However, the quantitative and reproducible analysis of IF remains a challenge, especially in experimental animal models of progressive IF. In this study, we compare traditional polarized Sirius Red morphometry (SRM) to novel Second Harmonic Generation (SHG)-based morphometry of unstained tissues for quantitative analysis of IF in the rat 5 day unilateral ureteral obstruction (UUO) model. To validate the specificity of SHG for detecting fibrillar collagen components in IF, co-localization studies for collagens type I, III, and IV were performed using IHC. In addition, we examined the correlation, dynamic range, sensitivity, and ability of polarized SRM and SHG-based morphometry to detect an anti-fibrotic effect of three different treatment regimens. Comparisons were made across three separate studies in which animals were treated with three mechanistically distinct pharmacologic agents: enalapril (ENA, 15, 30, 60 mg/kg), mycophenolate mofetil (MMF, 2, 20 mg/kg) or the connective tissue growth factor (CTGF) neutralizing antibody, EX75606 (1, 3, 10 mg/kg). Our results demonstrate a strong co-localization of the SHG signal with fibrillar collagens I and III but not non-fibrillar collagen IV. Quantitative IF, calculated as percent cortical area of fibrosis, demonstrated similar response profile for both polarized SRM and SHG-based morphometry. The two methodologies exhibited a strong correlation across all three pharmacology studies (r2 = 0.89-0.96). However, compared with polarized SRM, SHG-based morphometry delivered a greater dynamic range and absolute magnitude of reduction of IF after treatment. In summary, we demonstrate that SHG-based morphometry in unstained kidney tissues is comparable to polarized SRM for quantitation of fibrillar collagens, but with an enhanced sensitivity to detect treatment-induced reductions in IF. Thus, performing SHG-based morphometry on unstained kidney tissue is a reliable alternative to traditional polarized SRM for quantitative analysis of IF.

Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells.SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool.LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC.LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589.

Sex plays an important role in the clinical expression and prognosis of various cardiovascular diseases. This study was designed to observe the effects of sex on hypertrophic cardiomyopathy (HCM).A total of 621 unrelated patients with HCM without heart failure (460 males) were enrolled from 1999 to 2011. Compared to male patients, at baseline female patients were older at diagnosis (49.6±17.2 years vs. 46.7±14.4 years, P = 0.033), and had greater frequency of left ventricular outflow tract obstruction (72/161, 44.7% vs. 149/460, 32.4%, P = 0.005). During the average four year follow-up period (range 2-7 years), survival analysis showed that the incidences of mortality from all causes, cardiovascular death and progression to chronic heart failure were greater in women than in men (P = 0.031, 0.040 and 0.012, respectively). After adjustment for multiple factors that may confound survival and cardiac function, female sex remained an independent risk factor for all-cause mortality, cardiovascular death, and chronic heart failure [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.21-3.95, P = 0.010; HR 2.19, 95% CI 1.17-4.09, P = 0.014; HR 1.73, 95% CI 1.12-2.69, P = 0.014, respectively] in HCM patients. Subgroup analysis revealed that female sex as a risk factor was identified only in patients younger than 50 years old (P = 0.011, 0.011 and 0.009, respectively), but not for those 50 years or older.Our results suggest that female sex is associated with worse survival and heart failure in HCM patients. Further studies are required to determine whether female hormones modify the clinical expression and prognosis of HCM.

BACKGROUND: Calreticulin is a Ca(2+)-binding chaperone of the endoplasmic reticulum which regulates the signal transducer and activator of transcription 3 (STAT3). The effects of the calreticulin-STAT3 signaling pathway on cardiac mitochondria and on the progress of dilated cardiomyopathy (DCM) are still unclear. METHODS AND RESULTS: The DCM model was generated in rats by the daily oral administration of furazolidone. Echocardiographic and hemodynamic studies demonstrated enlarged LV dimensions and reduced systolic and diastolic functions at thirty weeks after the first furazolidone administration. Morphometric analysis showed significant myocardial degeneration, interstitial fibrosis, and mitochondrial swelling with fractured or dissolved cristae in the model group. Compared with the control group, the mitochondrial membrane potential (MMP) level of the freshly isolated cardiac mitochondria and the enzyme activities of cytochrome c oxidase and succinate dehydrogenase in the model group were significantly decreased (P

Two experiments were conducted to investigate the automatic processing of emotional facial expressions while performing low or high demand cognitive tasks under unattended conditions. In Experiment 1, 35 subjects performed low (judging the structure of Chinese words) and high (judging the tone of Chinese words) cognitive load tasks while exposed to unattended pictures of fearful, neutral, or happy faces. The results revealed that the reaction time was slower and the performance accuracy was higher while performing the low cognitive load task than while performing the high cognitive load task. Exposure to fearful faces resulted in significantly longer reaction times and lower accuracy than exposure to neutral faces on the low cognitive load task. In Experiment 2, 26 subjects performed the same word judgment tasks and their brain event-related potentials (ERPs) were measured for a period of 800 ms after the onset of the task stimulus. The amplitudes of the early component of ERP around 176 ms (P2) elicited by unattended fearful faces over frontal-central-parietal recording sites was significantly larger than those elicited by unattended neutral faces while performing the word structure judgment task. Together, the findings of the two experiments indicated that unattended fearful faces captured significantly more attention resources than unattended neutral faces on a low cognitive load task, but not on a high cognitive load task. It was concluded that fearful faces could automatically capture attention if residues of attention resources were available under the unattended condition.

BACKGROUND: The safflower, Carthamus tinctorius L., is a worldwide oil crop, and its flowers, which have a high flavonoid content, are an important medicinal resource against cardiovascular disease in traditional medicine. Because the safflower has a large and complex genome, the development of its genomic resources has been delayed. Second-generation Illumina sequencing is now an efficient route for generating an enormous volume of sequences that can represent a large number of genes and their expression levels. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the genes and pathways that might control flavonoids and other secondary metabolites in the safflower, we used Illumina sequencing to perform a de novo assembly of the safflower tubular flower tissue transcriptome. We obtained a total of 4.69 Gb in clean nucleotides comprising 52,119,104 clean sequencing reads, 195,320 contigs, and 120,778 unigenes. Based on similarity searches with known proteins, we annotated 70,342 of the unigenes (about 58% of the identified unigenes) with cut-off E-values of 10(-5). In total, 21,943 of the safflower unigenes were found to have COG classifications, and BLAST2GO assigned 26,332 of the unigenes to 1,754 GO term annotations. In addition, we assigned 30,203 of the unigenes to 121 KEGG pathways. When we focused on genes identified as contributing to flavonoid biosynthesis and the biosynthesis of unsaturated fatty acids, which are important pathways that control flower and seed quality, respectively, we found that these genes were fairly well conserved in the safflower genome compared to those of other plants. CONCLUSIONS/SIGNIFICANCE: Our study provides abundant genomic data for Carthamus tinctorius L. and offers comprehensive sequence resources for studying the safflower. We believe that these transcriptome datasets will serve as an important public information platform to accelerate studies of the safflower genome, and may help us define the mechanisms of flower tissue-specific and secondary metabolism in this non-model plant.

BACKGROUND AND OBJECTIVE: Oesophageal cancer is one of the most common and deadliest cancers worldwide. Our previous population-based study reported a high prevalence of oesophageal cancer in Chaoshan, Guangdong Province, China. Ancestors of the Chaoshan population migrated from the Taihang Mountain region of north-central China, which is another high-incidence area for oesophageal cancer. The purpose of the present study was to obtain evidence of inherited susceptibility to oesophageal cancer in the Chaoshan population, with reference to the Taihang Mountain population, with the eventual goal of molecular identification of the disease genes. METHODS: We conducted familial correlation, commingling, and complex segregation analyses of 224 families from the Chaoshan population and 403 families from the Taihang population using the FPMM program of S.A.G.E. version 5.3.0. A second analysis focused on specific families having large numbers of affected individuals or early onset of the disease. RESULTS: For the general population, moderate sib-sib correlation was noticed for esophageal cancer. Additionally, brother-brother correlation was even higher. Commingling analyses indicated that a three-component distribution model best accounts for the variation in age of onset of oesophageal cancer, and that a multifactorial model provides the best fit to the general population data. An autosomal dominant mode and a dominant or recessive major gene with polygenic inheritance were found to be the best models of inherited susceptibility to oesophageal cancer in some large families. CONCLUSIONS: The current results provide evidence for inherited susceptibility to oesophageal cancer in certain high-risk groups in China, and support efforts to identify the susceptibility genes.

For optimal stopping problems with time-inconsistent preference, we measure the inherent level of time-inconsistency by taking the time required to turn the naive strategies into the sophisticated ones. In particular, when in a repeated experiment, the naive agent can observe her actual sequence of actions that is inconsistent with what she has planned at the initial time, and she would then choose her immediate action based on the observations of her later actual behavior. The procedure is repeated until her actual sequence of actions is consistent with her plan at any time. We show that for the preference value of cumulative prospect theory, in which the time-inconsistency is due to the probability distortion, the higher the degree of probability distortion, the more severe the level of time-inconsistency, and the more time required to turn the naive strategies into the sophisticated ones., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hu, Zhou. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To explore the association between radiation after surgery and the 5-year overall survival (OS) and 5-year cancer-specific survival (CSS) in patients with Wilms tumor., Methods: In this cohort study, 1564 participants were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The univariate and multivariable COX proportional risk model as well as competitive risk model were used to explore the covariates associated with 5-year OS and 5-year CSS of patients with Wilms tumor and the correlation between radiation after surgery and 5-year OS or 5-year CSS of patients with Wilms tumor, respectively. The Kaplan-Meier curves of participants were plotted., Results: The median follow-up was 126.00 (84.00, 178.00) months. Patients receiving surgery had higher 5-year survival probability than those not receiving surgery, while participants receiving radiation after surgery showed poor 5-year survival than those not. After adjusting for covariates including age and SEER stage, increased risk of 5-year overall mortality in patients with Wilms tumor [hazard ratio (HR) = 1.62, 95% confidence interval (CI): 1.10-2.41). After the adjustment for confounding factors including age, SEER stage and ethnicity, increased risk of 5-year cancer-specific mortality of patients with Wilms tumor was observed in those receiving radiation after surgery (HR = 1.77, 95%CI: 1.13-2.79)., Conclusion: Radiation after surgery was associated with poor prognosis of patients with Wilms tumor, which indicated that the clinicians should assess whether the patient was suitable for using radiation after surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Surgical aortic valve replacement (SAVR) currently stands as a primary surgical intervention for addressing aortic valve disease in patients. This retrospective study focused on the role of the red blood cell distribution width (RDW) in predicting adverse outcomes among SAVR patients., Methods: The subjects for this study were exclusively derived from the Medical Information Mart for Intensive Care database (MIMIC IV 2.0). Kaplan‒Meier (K-M) curves and Cox proportional hazards regression models were employed to assess the correlation between RDW, one-year mortality, and postoperative atrial fibrillation (POAF). The smooth-fitting curves were used to observe the relative risk (RR) of RDW in one-year mortality and POAF. Furthermore, time-dependent receiver operating characteristic (ROC) curves, the continuous-net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed for comprehensive assessment of the prognostic value of RDW., Results: Analysis of RDW revealed a distinctive inverted U-shaped relationship with one-year mortality, while its association with POAF appeared nearly linear. Cox multiple regression models showed that RDW > 14.35%, along with preoperative potassium concentration and perioperative red blood cell transfusion, were significantly linked to one-year mortality (K-M curves, log-rank P < 0.01). Additionally, RDW was associated with both POAF and prolonged hospital stays (P < 0.05). There was no significant difference in length of stay in ICU. Notably, the inclusion of RDW in the predictive models substantially enhanced its performance. This was evidenced by the time-dependent ROC curve (AUC = 0.829), NRI (P< 0.05), IDI (P< 0.05), and K-M curves (log-rank P< 0.01)., Conclusions: RDW serves as a robust prognostic indicator for SAVR patients, offering a novel means of anticipating adverse postoperative events., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ruan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The main characteristic of cervical cytopathy is reflected in the edge shape of nuclei. Existing computer-aided diagnostic techniques can clearly segment individual nuclei, but cannot clearly segment the rough edges of adherent nucleus. Therefore, we propose an effective method (ASATrans) to accurately segment rough cervical nuclei edges by exploring adaptive spatial aggregation methods. ASATrans creates a Multi-Receptive Embedding Layer that samples patches using diverse-scale kernels. This approach provides cross-scale features to each embedding, preventing semantic corruption that might arise from mapping disparate patches to analogous underlying representations. Furthermore, we design Adaptive Pixel Adjustment Block by introducing a long-range dependency and adaptive spatial aggregation. This is achieved through the stratification of the spatial aggregation process into distinct groups. Each group is given an exclusive sampling volume and modulation scale, fostering a collaborative learning paradigm that combines local features and global dependencies. This collaborative approach to feature extraction achieves adaptability, mitigates interference from unnecessary pixels, and allows for better segmentation of edges in the nucleus. Extensive experiments on two cervical nuclei datasets (HRASPP Dataset, ISBI Dataset), demonstrating that our proposed ASATrans outperforms other state-of-the-art methods by a large margin., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun, Hu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Debris flow risk assessment can provide some reference for debris flow prevention and control projects. In risk assessment, researchers often only focus on the impact of objective or subjective indicators. For this purpose, this paper proposed a weight calculation method based on t-distribution and linear programming optimization algorithm (LPOA). Taking 72 mudslides in Beichuan County as an example, this paper used analytic hierarchy process (AHP), entropy weight method (EWM) and variation coefficient method (VCM) to obtain the initial weights. Based on the initial weights, weight intervals with different confidence levels were obtained by t-distribution. Subsequently, the final weights were obtained by LOPA in the 90% confidence interval. Finally, the final weights were used to calculate the risk score for each debris flow, thus delineating the level of risk for each debris flow. The results showed that this paper's method can avoid overemphasizing the importance of a particular indicator compared to EWM and VCM. In contrast, EWM and VCM ignored the effect of debris flow frequency on debris flow risk. The assessment results showed that the 72 debris flows in Beichuan County were mainly dominated by moderate and light risks. Of these, there were 8 high risk debris flows, 24 medium risk debris flows, and 40 light risk debris flows. The excellent triggering conditions provide favorable conditions for the formation of high-risk debris flows. Slightly and moderate risk debris flows are mainly located on both sides of highways and rivers, still posing a minor threat to Beichuan County. The proposed fusion weighting method effectively avoids the limitations of single weight calculating method. Through comparison and data analysis, the rationality of the proposed method is verified, which can provide some reference for combination weighting method and debris flow risk assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Soccer heading is adversely associated with neurocognitive performance, but whether greater neck strength or anthropometrics mitigates these outcomes is controversial. Here, we examine the effect of neck strength or anthropometrics on associations of soccer heading with neurocognitive outcomes in a large cohort of adult amateur players., Methods: 380 adult amateur league soccer players underwent standardized measurement of neck strength (forward flexion, extension, left lateral flexion, right lateral flexion) and head/neck anthropometric measures (head circumference, neck length, neck circumference and neck volume). Participants were assessed for heading (HeadCount) and cognitive performance (Cogstate) on up to 7 visits over a period of two years. Principal components analysis (PCA) was performed on 8 neck strength and anthropometric measures. We used generalized estimating equations to test the moderation effect of each of the three PCs on 8 previously identified adverse associations of 2-week and 12-month heading estimates with cognitive performance (psychomotor speed, immediate verbal recall, verbal episodic memory, attention, working memory) and of unintentional head impacts on moderate to severe central nervous system symptoms., Results: 3 principal components (PC's) account for 80% of the variance in the PCA. In men, PC1 represents head/neck anthropometric measures, PC2 represents neck strength measures, and PC3 represents the flexor/extensor (F/E) ratio. In women, PC1 represents neck strength, PC2 represents anthropometrics, and PC3 represents the F/E ratio. Of the 48 moderation effects tested, only one showed statistical significance after Bonferroni correction, which was not robust to extensive sensitivity analyses., Conclusion: Neither neck strength nor anthropometrics mitigate adverse associations of soccer heading with cognitive performance in adult amateur players., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

How to evaluate the resilience level and change trend of supply chain is an important research direction in current supply chain management practice. This paper proposes a new method of supply chain resilience assessment based on hesitant fuzzy linguistic term set (HFLTS) and matter element extension theory. Firstly, based on the research status quo at home and abroad, a low-carbon enterprise supply chain resilience assessment index system is established, which includes six first-level indicators and corresponding 21 second-level indicators of product supply resilience, resource resilience, partner resilience, information response resilience, financial resilience and knowledge resilience. Secondly, HFLTS was used to collect expert opinions and Ordered Weighted Arithmetic (OWA) to calculate the expert composite language, by which the fuzzy evaluation matrix of supply chain resilience assessment indicators was obtained. Once again, the resilience indicator weights are determined based on a game-theoretic portfolio assignment method combining the best-worst method (BWM) and the CRITIC method. Finally, the nearness degree function is combined with the extension comprehensive evaluation method to improve the matter element extension model, and the supply chain resilience assessment model of low-carbon enterprises based on the game theory combination assignment-improved matter element extension is established. Taking X low-carbon enterprise as an example, the evaluation results show that the supply chain resilience level of this enterprise is II, and the eigenvalue of the grade variable is 2.69, and the supply chain resilience is shifting to III, and the supply chain resilience is shifting to III, which indicates that the supply chain resilience of this enterprise is being enhanced. Therefore, the improved matter element extension not only ensures the accuracy of the evaluation results, but also has higher prediction accuracy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The essential role of protein degradation by ubiquitin-proteasome system is exerted primarily for maintaining cellular protein homeostasis. The transcriptional activation of proteasomal genes by mTORC1 signaling depends on Nrf1, but whether this process is directly via SREBP1 remains elusive. In this study, our experiment evidence revealed that Nrf1 is not a direct target of SREBP1, although both are involved in the rapamycin-responsive regulatory networks. Closely scrutinizing two distinct transcriptomic datasets unraveled no significant changes in transcriptional expression of Nrf1 and almost all proteasomal subunits in either siSREBP2-silencing cells or SREBP1-∕-MEFs, when compared to equivalent controls. However, distinct upstream signaling to Nrf1 dislocation by p97 and its processing by DDI1/2, along with downstream proteasomal expression, may be monitored by mTOR signaling, to various certain extents, depending on distinct experimental settings in different types of cells. Our further evidence has been obtained from DDI1-∕-(DDI2insC) cells, demonstrating that putative effects of mTOR on the rapamycin-responsive signaling to Nrf1 and proteasomes may also be executed partially through a DDI1/2-independent mechanism, albeit the detailed regulatory events remain to be determined., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Prostate cancer is the second most frequent cancer diagnosed in men in the world today. Almost all prostate cancers are adenocarcinomas and develop from gland cells. We used the PC3 prostate cancer cell line, which is well studied and derived from a bone metastasis of a grade IV prostatic adenocarcinoma. Cannabidiol (CBD), a major non-psychoactive constituent of cannabis, is a cannabinoid with anti-tumor properties but its effects on prostate cancer cells are not studied in detail. Here, we found cannabidiol decreased prostate cancer cell (PC3) viability up to 37.25% and induced apoptotic cell death in a time and dose-dependent manner. We found that CBD activated the caspases 3/7 pathways and increased DNA fragmentation. Furthermore, we observed an increase of pro-apoptotic genes Bax, an increased level of reactive oxygen species, lower reduced glutathione level, and altered mitochondrial potential in response to CBD treatment leading to lower cellular ATP. Overall, our results suggest that CBD may be effective against prostate cancer cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Considering economic, environmental, and social issues, the sustainability of the supply chain has drawn considerable attention due to societal and environmental changes within the supply chain network. The strategic study of the entire supply chain process and maximizing an organization's competitive advantage depend heavily on supplier selection based on sustainable indicators. Selecting sustainable suppliers for the supply chain is challenging since it is a multi-criteria decision-making (MCDM) problem with significant uncertainty in the decision-making process. This study uses the VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) technique and single-valued neutrosophic sets (SVNS) to deal with the challenge of choosing a sustainable supplier with insufficient information. This method reduces the influence of personal experience and preference on the final evaluation results and the problem of excessive individual regret caused by factor correlation and improves the consistency of evaluation results. Finally, the method's success and adaptability are demonstrated by sensitivity analysis and additional comparison analysis, and the benefits and drawbacks of the suggested framework are examined. Compared to other approaches, it can assist decision-makers in communicating fuzzy and uncertain information, offering a perspective and approach for MCDM in the face of such situations, and helping them select suppliers of high caliber and who practice sustainable business practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tissue slicing-assisted digestion (TSAD) of adult cardiomyocytes has shown significant improvements over conventional chunk methods. However, it remains unclear how this method compares to Langendorff perfusion, the current standard of adult cardiomyocyte isolation. Using adult Bama minipigs, we performed cardiomyocyte isolation via these two distinct methods, and compared the resulting cellular quality, including viability, cellular structure, gene expression, and electrophysiological properties, of cardiomyocytes from 3 distinct anatomical regions, namely the left ventricle, right ventricle, and left atrial appendage. Our results revealed largely indistinguishable cell quality in all of the measured parameters. These findings suggest that that TSAD can be reliably used to isolate adult mammalian cardiomyocytes as a reliable alternative to perfusion in cardiomyocyte isolation from larger mammals, particularly when Langendorff perfusion is not feasible., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cerebral blood flow (CBF) acutely reduces in neonatal hypoxic-ischemic encephalopathy (HIE). Clinic studies have reported that severe CBF impairment can predict HIE outcomes in neonates. Herein, the present study uses a non-invasive 3D ultrasound imaging approach to evaluate the changes of CBF after HI insult, and explores the correlation between CBF alterations and HI-induced brain infarct in mouse pups. The neonatal HI brain injury was induced in postnatal day 7 mouse pups using the Rice-Vannucci model. Non-invasive 3D ultrasound imaging was conducted to image CBF changes with multiple frequencies on mouse pups before common carotid artery (CCA) ligation, immediately after ligation, and 0 or 24 hours after HI. Vascularity ratio of the ipsilateral hemisphere was acutely reduced after unilateral ligation of the CCA alone or in combination with hypoxia, and partially restored at 24 hours after HI. Moreover, regression analysis showed that the vascularity ratio of ipsilateral hemisphere was moderately correlated with brain infarct size 24 hours after HI, indicating that CBF reduction contributes to of HI brain injury. To further verify the association between CBF and HI-induced brain injury, a neuropeptide C-type natriuretic peptide (CNP) or PBS was intranasally administrated to the brain of mouse pups one hour after HI insult. Brain infarction, CBF imaging and long-term neurobehavioral tests were conducted. The result showed that intranasal administration of CNP preserved ipsilateral CBF, reduced the infarct size, and improved neurological function after HI brain injury. Our findings suggest that CBF alteration is an indicator for neonatal HI brain injury, and 3D ultrasound imaging is a useful non-invasive approach for assessment of HI brain injury in mouse model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Urban infrastructure resilience is an important perspective for measuring the development quality of resilient cities and an important way to measure the level of infrastructure development. This paper uses the kernel density estimation, exploratory spatial data analysis, and spatial econometric models to analyze the characteristics of dynamic evolution and the spillover effects of the infrastructure resilience levels in 283 prefecture-level and above cities in China from 2010 to 2019. Our results are as follows. (1) The overall level of urban infrastructure resilience increased. The eastern region had a higher level than the national average. In contrast, the central, western and north-eastern regions had a slightly lower level than the national average. (2) The areas with high and higher resilience levels were mostly cities with more developed economic and social conditions in Eastern China. The areas below moderate resilience levels show a certain degree of clustering and mainly include some cities in Central, Western, and Northeast China. (3) The national level of urban infrastructure resilience shows significant spatial clustering characteristics, and the spatial pattern from coastal to inland regions presents a hotspot-subhotspot-subcoldspot-coldspot distribution. (4) There is a differential spatial spillover effect of national urban infrastructure resilience, which is gradually strengthened under the role of the economy, financial development, population agglomeration and government funding and weakened under the role of urbanization, market consumption and infrastructure investment. By exploring the dynamic evolution of infrastructure resilience in cities at the prefecture level and above and its spatial spillover effects, we provide a scientific basis for avoiding the siphoning effect among cities, improving the level of infrastructure resilience, and guiding the construction and development of resilient cities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Serum lactate dehydrogenase levels reflect disease status in a variety of organs, but its role in indicating pulmonary function is not yet clear. Therefore, this study explored the correlation between pulmonary function and serum lactate dehydrogenase, and investigated thresholds for changes in pulmonary function indicators in the total population as well as in different strata of the population., Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 (n = 3453), univariate and stratified analyses were performed to investigate factors associated with pulmonary function, and multiple regression analysis was used to further investigate the specific relationship with serum lactate dehydrogenase. Smoothed curve fitting, threshold effect and saturation effect analysis were used to explore the threshold level of serum lactate dehydrogenase at the onset of changes in pulmonary function indicators., Results: Adjusted smoothed curve fit plots showed a linear relationship between serum lactate dehydrogenase levels and forced vital capacity and forced expiratory volume in one second: for each 1 U/L increase in serum lactate dehydrogenase levels, forced vital capacity decreased by 1.24 mL (95% CI = -2.05, -0.42, P = 0.0030) and forced expiratory volume in one second by 1.11 mL (95% CI = -1.82, -0.39, P = 0.0025)., Conclusions: Serum lactate dehydrogenase was negatively and linearly correlated with pulmonary function indices in the total population analyzed. Based on the total population and different population stratifications, this study determined the threshold values of serum lactate dehydrogenase at the onset of decline of pulmonary function in different populations. This provides a new serological monitoring indicator for patients suffering from respiratory diseases and has implications for patients with possible clinical impairment of pulmonary function. However, our cross-sectional study was not able to determine a causal relationship between these two factors, and further research is needed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Under the dual background of global industrial value chain and low-carbon emission reduction, the green transformation and upgrading of the manufacturing industry is an important way to promote production and promote sustainable economic development. Considering that the green transformation of the manufacturing industry is a typical complex adaptation system, based on the intrinsic relationship between the dynamic theory and the green transformation of the manufacturing industry, this paper takes the endogenous variable of the transformation of manufacturing enterprises as the entry point, simulates the transformation of new and old dynamic energy of green transformation, and explores the mechanism of green transformation and upgrading of manufacturing industry and the conversion process. According to the model, it is concluded that the green transformation of manufacturing enterprises is the result of the multi-stage transformation of enterprises. In this process, the change inertia overcomes old dynamic inertia and promotes the new dynamic to gradually replace the old dynamic. At the end of the article, specific suggestions are given to promote the green transformation of manufacturing enterprises from the aspects of ideology, policy support, digital empowerment, financial service guarantee system and communication and cooperation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study explored changes in the microbial community structure during straw degradation by a microbial decomposer, M44. The microbial community succession at different degradation periods was analyzed using MiSeq high-throughput sequencing. The results showed that 14 days after inoculation, the filter paper enzyme and endoglucanase activities increased to 2.55 U·mL-1 and 2.34 U·mL-1. The xylanase, laccase, and lignin peroxidase activities rose to 9.86 U·mL-1, 132.16 U·L-1, and 85.43 U·L-1 after 28 d, which was consistent with changes in the straw degradation rate. The degradation rates of straw, lignin, cellulose, and hemicellulose were 31.43%, 13.67%, 25.04%, and 21.69%, respectively, after 28 d of fermentation at 15°C. Proteobacteria, Firmicutes, and Bacteroidetes were the main bacterial species in samples at different degradation stages. The dominant genera included Pseudomonas, Delftia, and Paenibacillus during the initial stage (1 d, 7 d) and the mid-term stage (14 d). The key functional microbes during the late stage (21 d, 28 d) were Rhizobium, Chryseobacterium, Sphingobacterium, Brevundimonas, and Devosia. Changes in the bacterial consortium structure and straw degradation characteristics during different degradation periods were clarified to provide a theoretical basis for the rational utilization of microbial decomposer M44., Competing Interests: The authors have declared that no competing interests exist.

Overexpression of M3 subtype muscarinic receptors (M3R) hastens colon cancer progression. As microRNA (miRNA) expression is commonly dysregulated in cancer, we used microarrays to examine miRNA profiles in muscarinic receptor agonist-treated human colon cancer cells. We used quantitative RT-PCR (qPCR) to validate microarray results and examine miRNA expression in colon cancers and adjacent normal colon. These assays revealed that acetylcholine (ACh) treatment robustly induced miR-222 expression; miR-222 levels were three-fold higher in cancer compared to normal colon. In kinetic studies, ACh induced a 4.6-fold increase in pri-miR-222 levels within 1 h, while mature miR-222 increased gradually to 1.8-fold within 4 h. To identify post-M3R signaling mediating these actions, we used chemical inhibitors and agonists. ACh-induced increases in pri-miR-222 were attenuated by pre-incubating cells with atropine and inhibitors of protein kinase C (PKC) and p38 MAPK. Treatment with a PKC agonist, phorbol 12-myristate 13-acetate, increased pri-miR-222 levels, an effect blocked by PKC and p38 MAPK inhibitors, but not by atropine. Notably, treatment with ACh or transfection with miR-222 mimics increased cell proliferation; atropine blocked the effects of ACh but not miR-222. These findings identify a novel mechanism whereby post-M3R PKC/p38 MAPK signaling stimulates miR-222 expression and colon cancer cell proliferation., Competing Interests: The authors have declared that no competing interests exist.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. A growing number of studies have shown that competitive endogenous RNA (ceRNA) regulatory networks might play important roles during HCC process. The present study aimed to identify a regulatory axis of the ceRNA network associated with the development of HCC. The roles of SNX16 and PAPOLG in HCC were comprehensively analyzed using bioinformatics tools. Subsequently, the "mRNA-miRNA-lncRNA" model was then used to predict the upstream miRNAs and lncRNAs of SNX16 and PAPOLG using the miRNet database, and the miRNAs with low expression and good prognosis in HCC and the lncRNAs with high expression and poor prognosis in HCC were screened by differential expression and survival analysis. Finally, the risk-prognosis models of ceRNA network axes were constructed by univariate and multifactorial Cox proportional risk analysis, and the immune correlations of ceRNA network axes were analyzed using the TIMER and GEPIA database. In this study, the relevant ceRNA network axis GSEC/miR-101-3p/SNX16/PAPOLG with HCC prognosis was constructed, in which GSEC, SNX16, and PAPOLG were highly expressed in HCC with poor prognosis, while miR-101-3p was lowly expressed in HCC with good prognosis. The risk-prognosis model predicted AUC of 0.691, 0.623, and 0.626 for patient survival at 1, 3, and 5 years, respectively. Immuno-infiltration analysis suggested that the GSEC/miR-101-3p/SNX16/PAPOLG axis might affect macrophage polarization. The GSEC/miR-101-3p/SNX16/PAPOLG axis of the ceRNA network axis might be an important factor associated with HCC prognosis and immune infiltration., Competing Interests: The authors have declared that no competing interests exist.

MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via gene silencing. Here, we demonstrated that HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and in the serum of HIV-1-infected individuals. Luciferase reporter assays and western blotting confirmed that a target protein of miR-210-5p, TGIF2, is regulated by HIV-1 infection. Furthermore, HIV-1 Vpr protein induced miR-210-5p expression. The use of a miR-210-5p inhibitor and TGIF2 overexpression showed that Vpr upregulated miR-210-5p and thereby downregulated TGIF2, which might be one of the mechanisms used by Vpr to induce G2 arrest. Moreover, we identified a transcription factor, NF-κB p50, which upregulated miR-210-5p in response to Vpr protein. In conclusion, we identified a mechanism whereby miR-210-5p, which is induced upon HIV-1 infection, targets TGIF2. This pathway was initiated by Vpr protein activating NF-κB p50, which promoted G2 arrest. These alterations orchestrated by miRNA provide new evidence on how HIV-1 interacts with its host during infection and increase our understanding of the mechanism by which Vpr regulates the cell cycle., Competing Interests: The authors have declared that no competing interests exist.

Racial/ethnic disparities are among the top-selective underlying determinants associated with the disproportional impact of the COVID-19 pandemic on human mobility and health outcomes. This study jointly examined county-level racial/ethnic differences in compliance with stay-at-home orders and COVID-19 health outcomes during 2020, leveraging two-year geo-tracking data of mobile devices across ~4.4 million point-of-interests (POIs) in the contiguous United States. Through a set of structural equation modeling, this study quantified how racial/ethnic differences in following stay-at-home orders could mediate COVID-19 health outcomes, controlling for state effects, socioeconomics, demographics, occupation, and partisanship. Results showed that counties with higher Asian populations decreased most in their travel, both in terms of reducing their overall POIs' visiting and increasing their staying home percentage. Moreover, counties with higher White populations experienced the lowest infection rate, while counties with higher African American populations presented the highest case-fatality ratio. Additionally, control variables, particularly partisanship, median household income, percentage of elders, and urbanization, significantly accounted for the county differences in human mobility and COVID-19 health outcomes. Mediation analyses further revealed that human mobility only statistically influenced infection rate but not case-fatality ratio, and such mediation effects varied substantially among racial/ethnic compositions. Last, robustness check of racial gradient at census block group level documented consistent associations but greater magnitude. Taken together, these findings suggest that US residents' responses to COVID-19 are subject to an entrenched and consequential racial/ethnic divide., Competing Interests: The authors have declared that no competing interests exist.

During the outbreak of the COVID-19 pandemic, Non-Pharmaceutical and Pharmaceutical treatments were alternative strategies for governments to intervene. Though many of these intervention methods proved to be effective to stop the spread of COVID-19, i.e., lockdown and curfew, they also posed risk to the economy; in such a scenario, an analysis on how to strike a balance becomes urgent. Our research leverages the mobility big data from the University of Maryland COVID-19 Impact Analysis Platform and employs the Generalized Additive Model (GAM), to understand how the social demographic variables, NPTs (Non-Pharmaceutical Treatments) and PTs (Pharmaceutical Treatments) affect the New Death Rate (NDR) at county-level. We also portray the mutual and interactive effects of NPTs and PTs on NDR. Our results show that there exists a specific usage rate of PTs where its marginal effect starts to suppress the NDR growth, and this specific rate can be reduced through implementing the NPTs., Competing Interests: The authors have declared that no competing interests exist.

Background: The performance of traditional scores is significantly limited to predict mortality in high-risk cardiac surgery. The aim of this study was to compare the performance of STS, ESII and HiriSCORE models in predicting mortality in high-risk patients undergoing CABG., Methods: Cross-sectional analysis in the international prospective database of high-risk patients: HiriSCORE project. We evaluated 248 patients with STS or ESII (5-10%) undergoing CABG in 8 hospitals in Brazil and China. The main outcome was mortality, defined as all deaths occurred during the hospitalization in which the operation was performed, even after 30 days. Five variables were selected as predictors of mortality in this cohort of patients. The model's performance was evaluated through the calibration-in-the-large and the receiver operating curve (ROC) tests., Results: The mean age was 69.90±9.45, with 52.02% being female, 25% of the patients were on New York Heart Association (NYHA) class IV and 49.6% had Canadian Cardiovascular Society (CCS) class 4 angina, and 85.5% had urgency or emergency status. The mortality observed in the sample was 13.31%. The HiriSCORE model showed better calibration (15.0%) compared to ESII (6.6%) and the STS model (2.0%). In the ROC curve, the HiriSCORE model showed better accuracy (ROC = 0.74) than the traditional models STS (ROC = 0.67) and ESII (ROC = 0.50)., Conclusion: Traditional models were inadequate to predict mortality of high-risk patients undergoing CABG. However, the HiriSCORE model was simple and accurate to predict mortality in high-risk patients., Competing Interests: The authors have no conflict of interest to declare in relation to this work.

We aimed to establish and evaluate a standardized emotional situation sentence system (ESSS) relevant to the lives of college students to supplement prior literature and adapt to the needs of emotional research. Two studies were designed for this research; study 1 examined the effect of words in the ESSS and study 2 involved the use of pictures. For Study 1, 778 items were selected by 607 college students and 15 experts. We then tested the scale with 80 undergraduate participants. The ESSS sentences were rated on their degree of valence, arousal, and dominance using a 9-point scale. Cronbach's α (greater than 0.986) of the overall score as well as each sub-score in the three components confirmed the scale's reliability. As seen on a scatter plot, the results suggest that negative emotions (fear, disgust, anger, sadness, anxiety) are convergent and different from the distribution of positive (happiness) and neutral emotions. Study 2 included 30 participants to compare the difference in valence and arousal between the ESSS and emotional pictures. The results indicate that the ESSS is a standardized, situational, and ecological emotional contextual text system, well-suited to invoke emotion in college students. The ESSS has significantly better arousal and potency than pictures; moreover, it can be applied to experimental studies of anxiety-related emotions. However, emotion pictures have shorter response times, and wider application ranges, and they can include more cross-cultural characteristics compared to words., Competing Interests: No authors have competing interests.

Regional innovation is an important research topic in economic geography, the spatio-temporal evolution and mechanism of regional innovation efficiency have recently become a hot for economic geographers. From the perspective of input and output efficiency, this paper constructs evaluation indicator of regional innovation, with the help of Constant Returns to Scale (CRS) and Variable Returns to Scale (VRS) models, and Malmquist indicator method of Data Envelopment Analysis (DEA), to analyze regional innovation performance, evolution trend, spatial differentiation, and evolution mechanism of Yangtze River Delta Urban Agglomeration (YRDUA) of China. The results show that: (i) Innovation efficiency of YRDUA is generally low, most of which is less than 80 percent of optimal efficiency; however, it kept rising from 2000 to 2015. (ii) Spatial inequality of regional innovation in YRDUA is significant, with a spatial pattern in the shape of "Z", composed by Hefei, Nanjing, Shanghai, Hangzhou and Ningbo, innovation efficiency of Shanghai is higher than Zhejiang, Anhui and Jiangsu. (iii) Technology progress is the most important influencing factor, all kinds of changing indicator show a trend of rise, and the total factor productivity is changing significantly. This research can provide theoretical reference for the YRDUA to achieve high-quality integration., Competing Interests: The authors have declared that no competing interests exist.

Learning transfer is widely present in the learning of all kinds of knowledge, skills and social norms, and is one of the important phenomena of learning, and the reasonable use of transfer is conducive to improving the learning effect of students and the quality of teaching. This study starts from the data of college students' academic performance, takes real students' academic performance as a sample, measures the relevance of courses through students' academic performance, constructs various networks of learning transfer, and studies the topology and evolution of the networks to clarify the essential laws of learning transfer and put forward suggestions for the optimization of teaching strategies. Finally, using complex network analysis to analyze and mine the data on college students' academic performance, the article quantifies the overall structure of the courses and their hidden connections in a global and dynamic manner, and discovers the inheritance relationship between the courses, the clustering characteristics and the basic pattern of learning transfer. It also provides a platform for exploring the differences in the course structure of different majors and the learning transfer of male and female students., Competing Interests: The authors have declared that no competing interests exist.

For decades, traditional correlation analysis and regression models have been used in social science research. However, the development of machine learning algorithms makes it possible to apply machine learning techniques for social science research and social issues, which may outperform standard regression methods in some cases. Under the circumstances, this article proposes a methodological workflow for data analysis by machine learning techniques that have the possibility to be widely applied in social issues. Specifically, the workflow tries to uncover the natural mechanisms behind the social issues through a data-driven perspective from feature selection to model building. The advantage of data-driven techniques in feature selection is that the workflow can be built without so much restriction of related knowledge and theory in social science. The advantage of using machine learning techniques in modelling is to uncover non-linear and complex relationships behind social issues. The main purpose of our methodological workflow is to find important fields relevant to the target and provide appropriate predictions. However, to explain the result still needs theory and knowledge from social science. In this paper, we trained a methodological workflow with left-behind children as the social issue case, and all steps and full results are included., Competing Interests: The authors have declared that no competing interests exist.

Intensive management of C. oleifera has produced many pure C. oleifera plantations. The transmission of C. oleifera plantation will potentially affect soil C, N, and P pools as well as their stoichiometric characteristics both in top soil layer and vertical soil profile due to the intensive management. To understand changes in vertical pools and stoichiometric characteristics of soil C, N, and P as affected by intensive management of C. oleifera plantations, both mixed and pure C. oleifera plantations were studied. We conducted studies in five locations in Jiangxi, China with both pure and mixed C. oleifera plantations, to compare changes in vertical pools and stoichiometry of C, N, and P. Both C and N pools were significantly different between mixed and pure plantation types of C. oleifera. However, the ratio of C:N, C:P, and N:P was consistently higher in mixed plantations with C:P and N:P altered but C:N ratio did not change with soil depth. The intensive management significantly impact both C and N pools and the stoichiometry of C, N, and P. Intensive management of C. oleifera plantations decreased both C and N pools, especially at the depth of 30-50 cm soil layer. C. oleifera plantation alteration from mixed to pure should be considered in future forest management practice considering the substantial effects on soil element cycling and distribution along vertical soil profile., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the relationship between food patterns and mild cognitive impairment (MCI) among Chinese elderly to provide evidence for risk prevention and control of MCI among elderly population., Methods: Between February 2017 to October 2018, a stratified multistage cluster sampling method was used to select participants from 760 communities of six districts in Xi'an, China, for 49-item food frequency questionnaire survey. A total of 2311 participants aged 60 to 88 years were included in the study with 444 (19.2%) participants of MCI among Chinese community-dwelling elderly adults. Food patterns associated with risk of dementia were assessed by using a reduced rank regression (RRR) analysis, and the multivariate linear regression was used to test trends of risk factors across scores for the food pattern., Results: Four dietary patterns were extracted which explained 88.65% of the total variation in food intakes. Furthermore, the food pattern 1 (FP1) accounted for 60.25% of the total variation of all responsible variables and as a target dietary pattern in the study, which was related with high intake of legumes, vegetables, fruits, milk and dairy products, nuts and a low intake of noodles and cereals (p<0.05). Multivariate linear regression analysis showed that participants with a high score for FP1 had higher direction, memory and language function and FP1 can improve the ability of cognitive function (p<0.05)., Conclusion: The FP1 of Chinese dietary patterns was significantly correlated with higher cognitive function which can reduce the risk of MCI among Chinese elderly., Competing Interests: The authors have declared that no competing interests exist.

Objective: Altered expression of caveolin-1 (CAV1) and autophagy marker ATG4C is observed in various types of human cancers. However, the clinical significance of CAV1 and ATG4C expression in epithelial ovarian cancer (EOC) remains largely unknown. The present study aims to explore the clinicopathological value and prognostic significance of CAV1 and ATG4C expression in EOC., Methods: The expression pattern and prognostic value of CAV1 and ATG4C mRNA in EOC were analyzed using data from the Cancer Genome Atlas (TCGA) database (N = 373). In addition, immunohistochemistry analysis was performed to detect and assay the expression of CAV1 and ATG4C proteins in tissue microarray of EOC., Results: Based on TCGA data, Kaplan-Meier analysis indicated that patients with low CAV1 mRNA (p = 0.021) and high ATG4C mRNA (p = 0.018) expression had a significantly shorter overall survival (OS). Cox regression analysis demonstrated that the expression levels of CAV1 (p = 0.023) and ATG4C mRNA (p = 0.040) were independent prognostic factors for OS in EOC. In addition, the Concordance Index of the nomogram for OS prediction was 0.660. Immunohistochemical analysis showed the expression levels of stromal CAV1 and cancerous ATG4C proteins, and high expression of both CAV1 and ATG4C protein in the stroma were found to significantly correlate with the histologic subtypes of EOC, especially with serous subtype., Conclusions: Decreased expression of CAV1 mRNA and increased expression of ATG4C mRNA in EOC can predict poor overall survival. The expression levels of CAV1 protein in stromal cells and ATG4C protein in cancer cells are significantly associated with histologic subtypes of EOC. These findings suggest that CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC., Competing Interests: he authors have declared that no competing interests exist.

Objectives: To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration., Results: The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60-23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17-26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71-197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24-15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity., Conclusion: Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs., Competing Interests: The authors have declared that no competing interests exist.

This study develops a measure of perceived authenticity in science communication and then explores communication strategies to improve the perceived authenticity of a scientific message. The findings are consistent with literature around trust and credibility, but indicate that authenticity-the perception that the scientist is a unique individual with qualities beyond institutional affiliations or a role in the production of the research-may add a potentially important dimension to accepted categories of integrity and benevolence., Competing Interests: The authors have declared that no competing interests exist.

With the acceleration of global urbanization and climate change, dengue fever is spreading worldwide. Different levels of dengue fever have also occurred in China, especially in southern China, causing enormous economic losses. Unfortunately, there is no effective treatment for dengue, and the most popular dengue vaccine does not exhibit good curative effects. Therefore, we developed a Generalized Additive Mixed Model (GAMM) that gathered climate factors (mean temperature, relative humidity and precipitation) and Baidu search data during 2011-2015 in Guangzhou city to improve the accuracy of dengue fever prediction. Firstly, the time series dengue fever data were decomposed into seasonal, trend and remainder components by the seasonal-trend decomposition procedure based on loess (STL). Secondly, the time lag of variables was determined in cross-correlation analysis and the order of autocorrelation was estimated using autocorrelation (ACF) and partial autocorrelation functions (PACF). Finally, the GAMM was built and evaluated by comparing it with Generalized Additive Mode (GAM). Experimental results indicated that the GAMM (R2: 0.95 and RMSE: 34.1) has a superior prediction capability than GAM (R2: 0.86 and RMSE: 121.9). The study could help the government agencies and hospitals respond early to dengue fever outbreak., Competing Interests: The authors have declared that no competing interests exist.

As the number of known proteins has expanded, how to accurately identify DNA binding proteins has become a significant biological challenge. At present, various computational methods have been proposed to recognize DNA-binding proteins from only amino acid sequences, such as SVM, DNABP and CNN-RNN. However, these methods do not consider the context in amino acid sequences, which makes it difficult for them to adequately capture sequence features. In this study, a new method that coordinates a bidirectional long-term memory recurrent neural network and a convolutional neural network, called CNN-BiLSTM, is proposed to identify DNA binding proteins. The CNN-BiLSTM model can explore the potential contextual relationships of amino acid sequences and obtain more features than can traditional models. The experimental results show that the CNN-BiLSTM achieves a validation set prediction accuracy of 96.5%-7.8% higher than that of SVM, 9.6% higher than that of DNABP and 3.7% higher than that of CNN-RNN. After testing on 20,000 independent samples provided by UniProt that were not involved in model training, the accuracy of CNN-BiLSTM reached 94.5%-12% higher than that of SVM, 4.9% higher than that of DNABP and 4% higher than that of CNN-RNN. We visualized and compared the model training process of CNN-BiLSTM with that of CNN-RNN and found that the former is capable of better generalization from the training dataset, showing that CNN-BiLSTM has a wider range of adaptations to protein sequences. On the test set, CNN-BiLSTM has better credibility because its predicted scores are closer to the sample labels than are those of CNN-RNN. Therefore, the proposed CNN-BiLSTM is a more powerful method for identifying DNA-binding proteins., Competing Interests: The author (SH) is employed by Sichuan Jiuzhou Video Technology Co., Ltd, Mianyang, China. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To assess the availability and affordability of oral anti-diabetic medicines in Shaanxi Province, Western China., Methods: In 2015, the prices and availability of 8 anti-diabetic medicines covering 31 different dosage forms and strengths were collected in six cities of Shaanxi Province. A total of 72 public hospitals and 72 private pharmacies were sampled, using a modified methodology developed by the World Health Organization (WHO) and Health Action International (HAI). Medicine prices were compared with international reference prices to obtain a median price ratio. For urban residents, affordability was assessed as the lowest-paid unskilled government workers to purchase cost of standard treatment in days' wages; for rural residents, days' net income was used., Results: The mean availabilities of originator brands (OBs) and generics were 34.3% and 28.7% in public hospitals, and 44.1% and 64.4% in the private pharmacies. OBs and the lowest priced generics (LPGs) were procured at 12.38 and 4.52 times the international reference price in public hospitals, and 10.26 and 2.81 times the international reference prices in private pharmacies. Treatments with OBs were unaffordable even for urban residents. The affordability of the LPGs was good, except for acarbose, repaglinide and pioglitazone., Conclusions: Most anti-diabetic medicines cannot met the WHO's availability target (80% availability) in Shaanxi Province. The high prices of OBs had severely influenced the affordability of medicines, especially for the rural residents. Effective policies should be initiated to ensure the Chinese people a better access to more affordable anti-diabetic medicines., Competing Interests: The authors have declared that no competing interests exist.