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BackgroundCoronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations.MethodsBased on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI.ResultsFive unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments.ConclusionAccording to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Ampelopsin (APL), a major bioactive constituent of Ampelopsis grossedentata, exerts a number of biological effects. Here, we explored the anti-diabetic activity of APL and elucidate the underlying mechanism of this action. In palmitate-induced insulin resistance of L6 myotubes, APL treatment markedly up- regulated phosphorylated insulin receptor substrate-1 and protein kinase B, along with a corresponding increase of glucose uptake capacity. APL treatment also increased expressions of fibroblast growth factor (FGF21) and phosphorylated adenosine 5'-monophosphate -activated protein kinase (p-AMPK), however inhibiting AMPK by Compound C or AMPK siRNA, or blockage of FGF21 by FGF21 siRNA, obviously weakened APL -induced increases of FGF21 and p-AMPK as well as glucose uptake capacity in palmitate -pretreated L6 myotubes. Furthermore, APL could activate PPAR γ resulting in increases of glucose uptake capacity and expressions of FGF21 and p-AMPK in palmitate -pretreated L6 myotubes, whereas all those effects were obviously abolished by addition of GW9662, a specific inhibitor of peroxisome proliferator- activated receptor -γ (PPARγ), and PPARγsiRNA. Using molecular modeling and the luciferase reporter assays, we observed that APL could dock with the catalytic domain of PPARγ and dose-dependently up-regulate PPARγ activity. In summary, APL maybe a potential agonist of PPARγ and promotes insulin sensitization by activating PPARγ and subsequently regulating FGF21- AMPK signaling pathway. These results provide new insights into the protective health effects of APL, especially for the treatment of Type 2 diabetes mellitus.

ObjectiveThe main pathological change of myocarditis is an inflammatory injury of cardiomyocytes. Long noncoding RNAs (lncRNAs) are closely related to inflammation, and our previous study showed that differential expression of lncRNAs is associated with myocarditis. This study aimed to investigate the impact of lncRNAs on the onset of myocarditis.MethodsRNA expression was measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Lipopolysaccharide (LPS) was used to induce inflammation in human cardiomyocytes (HCMs). The expression of inflammatory cytokines and myocardial injury markers was detected by enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Cell viability and apoptosis were measured by the cell counting kit-8 assay and flow cytometry. The binding force between lncRNA NONHSAT122636.2 and microRNA miRNA-2110 was detected using the dual-luciferase assay.ResultsNONHSAT122636.2 was dynamically expressed in patients with myocarditis and negatively correlated with inflammation severity. The overexpression of NONHSAT122636.2 improved inflammatory injury in LPS-stimulated HCMs. The study observed that there was a weak binding force between NONHSAT122636.2 and miR-2110.ConclusionNONHSAT122636.2 attenuates myocardial inflammation and apoptosis in myocarditis. Additionally, its expression decreases in the peripheral blood of children suffering from myocarditis and in patients who are diagnosed for the first time showing higher diagnostic sensitivity and specificity. This decrease is negatively correlated with the degree of inflammation. Overall, the study suggests that NONHSAT122636.2 can be exploited as a potential diagnostic biomarker for pediatric myocarditis.

ObjectiveThe purpose of this study was to evaluate the effect of different teaching methods of geriatric nursing on the mastery of geriatric knowledge among nursing students and their attitude toward the elderly.MethodsRelevant randomized controlled trials (RCTs) and quasi-experimental studies on teaching methods to improve nursing students' knowledge and attitude were systematically retrieved in electronic databases. The time scale of retrieval spans from the database establishment to January 2024, and the database consists of PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure Database (CNKI), China Biological literature database (CBM), Wanfang Database and VIP Database. Network meta-analysis was performed by Stata 16.0 software.ResultsThirty-nine studies involving 5310 nursing students met our inclusion criteria, and a total of 6 teaching methods were analyzed. According to the surface under the cumulative ranking (SUCRA) ranking, problem-based learning (PBL) was most effective in enhancing the knowledge mastery of geriatric nursing, while simulation-based learning (SBL) demonstrated the best application effect in improving nursing students' attitude toward the elderly. When considering both knowledge acquisition and attitude improvement simultaneously, service learning combined with traditional teaching method (SL+TTM) was found to exhibit the most optimal effectiveness.ConclusionEducators in geriatric nursing education should prioritize the adoption of PBL, SBL and SL + TTM to enhance nursing students' knowledge and attitude.Protocol registryPROSPERO (CRD42023442001).

Influenza A viruses (IAVs) continue to pose a huge threat to public health, and their prevention and treatment remain major international issues. Neuraminidase (NA) is the second most abundant surface glycoprotein on influenza viruses, and antibodies to NA have been shown to be effective against influenza infection. In this study, we generated a monoclonal antibody (mAb), named FNA1, directed toward N1 NAs. FNA1 reacted with H1N1 and H5N1 NA, but failed to react with the NA proteins of H3N2 and H7N9. In vitro, FNA1 displayed potent antiviral activity that mediated both NA inhibition (NI) and blocking of pseudovirus release. Moreover, residues 219, 254, 358, and 388 in the NA protein were critical for FNA1 binding to H1N1 NA. However, further validation is necessary to confirm whether FNA1 mAb is indeed a good inhibitor against NA for application against H1N1 and H5N1 viruses.

BackgroundObservational studies have previously shown a potential link between psycho-emotional disorders, such as mood swings, highly strung, anxious feelings, and gastroesophageal reflux disease (GERD). However, the credibility of these associations could be influenced by various confounding factors. Consequently, our study sought to employ a Mendelian randomization (MR) approach to elucidate a potential causal relationship between psycho-emotional disorders and GERD.MethodInformation on independent genetic variants linked to mood swings, highly strung, and anxious feelings was gathered from European populations participating in the IEU Open GWAS research. The FinnGen Consortium provided the genome-wide association study (GWAS) summary statistics for GERD. Our analysis employed the inverse variance weighted (IVW) method under the random effects model as the main analytical method. To further bolster our findings, we employed the weighted median and MR Egger methods. In addition, we conducted a series of sensitivity analyses.ResultsOur study supports the existence of a causal relationship between psycho-emotional disorders and GERD. Mood swings, highly strung, and anxious feelings adversely affected GERD risk (mood swings: OR 2.21, 95% CI 1.19-5.59, p = 3.09 × 10-2; highly strung: OR 5.63, 95% CI 1.77-17.94, p = 3.42 × 10-3; anxious feelings: OR 2.48, 95% CI 1.08-4.33, p = 2.89 × 10-2).ConclusionThis Mendelian randomization study provides robust support for the notion that mood swings, highly strung and anxious feelings, are associated with an increased risk of developing GERD.

At present, there is no uniform standard mean of identifying handgrip strength (HGS) asymmetry based on maximum or average HGS values. Therefore, this study aimed to explore the accuracy of different calculation methods in the evaluation of HGS asymmetry. Using the maximum reading of two trials from both hands (Method A) as the reference standard, the accuracy of the HGS asymmetry identified by the average value of two trials of both hands (Method B) was determined by using various indicators, including specificity, sensitivity, the area under the receiver operating characteristic curve (AUC), positive, and negative predictive values. Overall, 12,163 individuals were included in this study, of whom 47.61% (5791/12,163) were male. The percentages of individuals with HGS asymmetry differed as a function of age and sex when using these two different methods. When employing Method A, 38.52%, 41.57%, and 44.57% of males 45 ≤ age

In recent years, with the development of deep learning technology, deep neural networks have been widely used in the field of medical image segmentation. U-shaped Network(U-Net) is a segmentation network proposed for medical images based on full-convolution and is gradually becoming the most commonly used segmentation architecture in the medical field. The encoder of U-Net is mainly used to capture the context information in the image, which plays an important role in the performance of the semantic segmentation algorithm. However, it is unstable for U-Net with simple skip connection to perform unstably in global multi-scale modelling, and it is prone to semantic gaps in feature fusion. Inspired by this, in this work, we propose a Deep Tensor Low Rank Channel Cross Fusion Neural Network (DTLR-CS) to replace the simple skip connection in U-Net. To avoid space compression and to solve the high rank problem, we designed a tensor low-ranking module to generate a large number of low-rank tensors containing context features. To reduce semantic differences, we introduced a cross-fusion connection module, which consists of a channel cross-fusion sub-module and a feature connection sub-module. Based on the proposed network, experiments have shown that our network has accurate cell segmentation performance.

Quercus wutaishanica is the dominant tree species in the natural ecosystem restoration of temperate forests in China, and it plays an active role in maintaining ecological balance. However, little is known about how ecosystem versatility develops during the restoration of forest ecosystems dominated by Q. wutaishanica. In this study, we investigated the species composition of the Q. wutaishanica community, soil nutrients, and their functional traits at various restoration stages, and comprehensively analyzed the correlations among them. At the early stage of restoration (10 years of restoration), there were Spiraea pubescens and Syringa pubescens in Q. wutaishanica community (87% of the total species), while had a larger niche width. In the middle of restoration (30 years of restoration), shannon and evenness indices were the largest, while soil total carbon, ammonium nitrogen and chlorophyll content of Q. wutaishanica leaves were the highest; among them, soil total carbon was 15.7% higher than that in 10 years of restoration, 32.4% higher than that in 40 years of restoration, ammonium nitrogen was 71.7% higher than that in 40 years of restoration, and chlorophyll content was 217.9% higher than that in 10 years of restoration, and 51.8% higher than that in 40 years of restoration. At the later stage of restoration (40 years of restoration), Lonicera ferdinandii occupied the dominant ecological niche, and soil available nitrogen, available phosphorus content and leaf thickness were the largest; while AN was 10.9% higher than that of 10 years of restoration, 16.5% higher than that of 30 years of restoration, AP was 60.6% higher than that of 10 years of restoration, 21.6% higher than that of 30 years of restoration, leaf thickness was 22.3% higher than that of 10 years of restoration, 84.9% higher than that of 30 years of restoration. However, the restriction of various soil nutrients was reduced. Our study highlighted the effectiveness of soil resource availability in plant communities during restoration, reduced competition for light among plants, and altered species richness. Furthermore, changes in the interrelationship between plant community composition and leaf functional traits of the dominant species responded positively to community restoration. These results further deepen our understanding of forest management and restoration of forest communities. In the future, it is necessary to comprehensively consider the influence of various factors on forest community restoration.

Autism Spectrum Disorder (ASD) is a developmental disorder in which children display repetitive behavior, restricted range of interests, and atypical social interaction and communication. CUL3, coding for a Cullin family scaffold protein mediating assembly of ubiquitin ligase complexes through BTB domain substrate-recruiting adaptors, has been identified as a high-risk gene for autism. Although complete knockout of Cul3 results in embryonic lethality, Cul3 heterozygous mice have reduced CUL3 protein, demonstrate comparable body weight, and display minimal behavioral differences including decreased spatial object recognition memory. In measures of reciprocal social interaction, Cul3 heterozygous mice behaved similarly to their wild-type littermates. In area CA1 of hippocampus, reduction of Cul3 significantly increased mEPSC frequency but not amplitude nor baseline evoked synaptic transmission or paired-pulse ratio. Sholl and spine analysis data suggest there is a small yet significant difference in CA1 pyramidal neuron dendritic branching and stubby spine density. Unbiased proteomic analysis of Cul3 heterozygous brain tissue revealed dysregulation of various cytoskeletal organization proteins, among others. Overall, our results suggest that Cul3 heterozygous deletion impairs spatial object recognition memory, alters cytoskeletal organization proteins, but does not cause major hippocampal neuronal morphology, functional, or behavioral abnormalities in adult global Cul3 heterozygous mice.

A questionnaire survey for parents of children under 5 years of age was conducted to analyze vaccine hesitancy with the 13-valent pneumococcal conjugate vaccine (PCV13) in Shanghai, China. A total of 892 valid questionnaires were collected. Descriptive statistical methods, Chi-square test and effect size of Cohen were used. Among participants, 421 (48.8%) had children who had been vaccinated with PCV13 before the survey while 227 (26.73%) planned vaccination with PCV13 in the future. The main reasons for not receiving vaccination were the fear of adverse reactions (79, 26.7%), beyond vaccination age (69, 23.3%), and no need to vaccinate (44, 14.9%). Reducing vaccine hesitancy and increasing vaccination willingness can be achieved through health interventions, lower vaccine prices, and the adjustment of vaccination strategies.

In recent years, intelligent robots have facilitated intelligent production, and a new type of problem (personnel-robot-position matching (PRPM)) has been encountered in personnel-position matching (PPM). In this study, a dynamic three-sided matching model is proposed to solve the PRPM problem in an intelligent production line based on man-machine collaboration. The first issue considered is setting the dynamic reference point, which is addressed in the information evaluation phase by proposing a method for setting the dynamic reference point based on the prospect theory. Another important issue involves multistage preference information integration, wherein a probability density function and a value function are introduced. Considering the attenuation of preference information in a time series, the attenuation index model is introduced to calculate the satisfaction matrix. Furthermore, a dynamic three-sided matching model is established. Additionally, a multi-objective decision-making model is established to optimize the matching of multiple sides (personnel, intelligent robots, and positions). Subsequently, the model is transformed into a single objective model using the triangular balance principle, which is introduced to obtain the final optimisation results in this modelling process. A case study is presented to illustrate the practicality of the dynamic three-sided matching model in intelligent environments. The results indicate that this model can solve the PRPM problem in an intelligent production line.

Early detection of tumors has great significance for formative detection and determination of treatment plans. However, cancer detection remains a challenging task due to the interference of diseased tissue, the diversity of mass scales, and the ambiguity of tumor boundaries. It is difficult to extract the features of small-sized tumors and tumor boundaries, so semantic information of high-level feature maps is needed to enrich the regional features and local attention features of tumors. To solve the problems of small tumor objects and lack of contextual features, this paper proposes a novel Semantic Pyramid Network with a Transformer Self-attention, named SPN-TS, for tumor detection. Specifically, the paper first designs a new Feature Pyramid Network in the feature extraction stage. It changes the traditional cross-layer connection scheme and focuses on enriching the features of small-sized tumor regions. Then, we introduce the transformer attention mechanism into the framework to learn the local feature of tumor boundaries. Extensive experimental evaluations were performed on the publicly available CBIS-DDSM dataset, which is a Curated Breast Imaging Subset of the Digital Database for Screening Mammography. The proposed method achieved better performance in these models, achieving 93.26% sensitivity, 95.26% specificity, 96.78% accuracy, and 87.27% Matthews Correlation Coefficient (MCC) value, respectively. The method can achieve the best detection performance by effectively solving the difficulties of small objects and boundaries ambiguity. The algorithm can further promote the detection of other diseases in the future, and also provide algorithmic references for the general object detection field.

C-C motif chemokine receptor-like 2 (CCRL2) is a non-signaling 7 transmembrane receptor that binds chemotactic ligands to shape leukocyte recruitment to sites of inflammation. However, there is a lack of consensus on the ligands that directly bind CCRL2 or their functional impact. Studies with CCRL2 knockout mice have demonstrated that neutrophils have impaired degranulation and migration in response to CXCL8, where the underlying molecular mechanism is proposed to be due to the formation of CCRL2 heterodimers with the chemokine receptor CXCR2. Herein, we characterized the ligands that bind directly to CCRL2 and interrogated the impact of CCRL2 neutralization on CXCL8 signaling in neutrophils using pharmacological antibody tools. Using flow cytometry and Surface Plasmon Resonance microscopy (SPRm) cell binding experiments, we confirmed that chemerin, but not previously reported C-C chemokines, binds CCRL2. Furthermore, we identified human and mouse CCRL2 antibodies that neutralized chemerin binding to CCRL2. Unexpectedly, we found that neutralization of CCRL2 with these antibodies did not attenuate CXCL8-induced human neutrophil degranulation nor CXCL8-induced murine neutrophil recruitment to the peritoneum. Based on the observed differences in modulating CCRL2 function with neutralizing antibodies compared to the reported CCRL2 deficient murine models, we hypothesize that the ligand binding function of CCRL2 is dispensable for CXCL8 signaling in neutrophils. Finally, extensive profiling of CCRL2 expression on peripheral blood leukocytes revealed monocytes, dendritic cells (DC), and subpopulations of natural killer T (NKT) cells as additional targets, highlighting potential roles for CCRL2 in human cell types beyond neutrophils that warrants future investigation.

IntroductionThe study examined the association of usual source of care (USC) and healthcare access using a series of access indicators including both positive and negative measures for the US population in 2005 and 2015 while controlling for individual sociodemographic and socioeconomic characteristics. Results of the study would help advance the knowledge of the relationship between USC and access to care and assist decisionmakers in targeted interventions to enhance USC as a strategy to enhance access.MethodsThe household component of the US Medical Expenditure Panel Survey (MEPS-HC) in 2005 and 2015 were used for the study. To estimate the relative risk of having USC on access to care, odds ratios (ORs) and their 95% confidence intervals (CIs) were used with unconditional logistic regression and adjusted for socioeconomic and demographic characteristics.ResultsThose with USC were significantly more likely to have better access to care compared to those without USC. The USC-access connection remains significant and strong even after controlling for socioeconomic and demographic characteristics. Regarding subpopulations likely to lack USC, two notable findings are that racial/ethnic minorities (Black, Asian, and Hispanic) are more likely than White to lack USC and that those uninsured are more likely to lack USC.ConclusionThe study contributes to the literature on USC and access to care and has significant policy and practical implications. For example, having a USC is critical to accessing the health system and is particularly important as a tool to addressing racial disparities in access.

Carbon emissions from civil buildings refer to the carbon emissions generated during the operation of civil buildings. With the continuous development of the urban economy and the improvement of people’s living standards, this part of carbon emission puts tremendous pressure on China to achieve the goal of carbon peaking and carbon neutral. In the context of rapid urbanization, studying the spatiotemporal characteristics and influencing factors of the carbon emissions from civil buildings have strong practical significance for China to achieve the "dual carbon" goal. Based on the emission data from 104 prefecture-level cities in China, we examine the spatiotemporal characteristics of the civil building carbon emissions from the perspectives of temporal evolution trend, spatial distribution and its dynamic evolution, spatial difference and its decomposition, and spatial autocorrelation characteristics. Finally, we reveal the influencing factors of the carbon emissions from civil buildings using static panel data models and spatial dynamic panel data models. The results of the study show that: (1) During the sample period, the carbon emissions from civil buildings have increased year by year. The civil building carbon emissions have become an important source of China’s overall carbon emissions. Realizing energy saving and emission reduction in the operational stage of civil buildings is crucial to realizing China’s "dual carbon" goal. (2) According to the estimated results, there is a significant inverted U-shaped non-linear relationship between urbanization and civil building carbon emissions. Most Chinese cities are located in the upward part of the inverted U-shaped curve at present. Thus, the traditional economic growth model characterized by high energy consumption and high emission during rapid urbanization should be abandoned to reduce the carbon emissions from civil buildings. (3) Technological progress and fixed asset investment can effectively reduce the carbon emissions from civil buildings. At the same time, the level of marketization and social consumption expenditure positively affect the carbon emissions from civil buildings. It is necessary to improve the relevant market mechanisms, policy subsidies, and other means to encourage the application of green energy-saving technologies in civil buildings. Also, it is needed to guide the urban residents’ consumption structure and lifestyle in a low-carbon direction, to reduce the energy consumption and carbon emissions during the operation of civil buildings.

BackgroundVaricella is a contagious disease caused by varicella-zoster virus and varicella vaccine (VarV) is the most effective way to prevent and control varicella. Despite high VarV coverage there were still varicella outbreaks in schools and kindergartens. We aim to analyze the epidemiological characteristics of varicella outbreaks in Huangpu District, Shanghai, China from 2011 to 2020.MethodsFor varicella outbreaks, case information and vaccination history were collected. Mann-Kendall test and descriptive methods were used to analyzed the trend and epidemiological catachrestic of varicella outbreaks.ResultsA total of 57 varicella outbreaks were reported from 2011 to 2020, including 30 outbreaks (52.6%) in primary schools. The results of the Mann-Kendall trend test (z = 1.97, p = 0.049) showed an upward trend in the number of cases during the study period, but the trend change was not statistically significant. Emergency vaccination was carried out in 42 (73.7%) outbreaks which influenced the duration of the epidemic (F = 4.53, p = 0.0379). A total of 573 varicella cases were reported, including 357 cases (62.3%) who had received at least one dose of varicella vaccine.ConclusionsThe number of varicella outbreaks has not changed significantly in the decade from 2011 to 2020. The strategy of varicella vaccination, the development and application of varicella vaccine, and the control measures after the occurrence of varicella outbreaks need to be optimized. In addition to vaccination, as a disease transmitted by contact, quarantine measures, good personal hygiene, environmental disinfection, and ventilation are also important.

Regular physical activity reduces the progression of several cancers and offers physical and mental health benefits for cancer survivors. However, many cancer survivors are not sufficiently active to achieve these health benefits. Possible biological mechanisms through which physical activity could affect cancer progression include reduced systemic inflammation and positive changes in metabolic markers. Chronic and acute hyperglycemia could have downstream effects on cell proliferation and tumorigenesis. One novel strategy to motivate cancer survivors to be more active is to provide personalized biological-based feedback that demonstrates the immediate positive impact of physical activity. Continuous glucose monitors (CGMs) have been used to demonstrate the acute beneficial effects of physical activity on insulin sensitivity and glucose metabolisms in controlled lab settings. Using personal data from CGMs to illustrate the immediate impact of physical activity on glucose patterns could be particularly relevant for cancer survivors because they are at a higher risk for developing type 2 diabetes (T2D). As a pilot project, this study aims to (1) test the preliminary effect of a remotely delivered physical activity intervention that incorporates personalized biological-based feedback on daily physical activity levels, and (2) explore the association between daily glucose patterns and cancer-related insulin pathway and inflammatory biomarkers in cancer survivors who are at high risk for T2D. We will recruit 50 insufficiently active, post-treatment cancer survivors who are at elevated risk for T2D. Participants will be randomly assigned into (1) a group that receives personalized biological feedback related to physical activity behaviors; and (2) a control group that receives standard educational material. The feasibility and preliminary efficacy of this wearable sensor-based, biofeedback-enhanced 12-week physical activity intervention will be evaluated. Data from this study will support the further refinement and enhancement of a more comprehensive remotely delivered physical activity intervention that targets cancer survivors. Trial registration: ClinicalTrials.gov Identifier: NCT05490641.

The association between methionine synthase (MTR) A2756G (rs1805087) polymorphism and the susceptibility to congenital heart disease (CHD) has not been fully determined. A meta-analysis of case-control studies was performed to systematically evaluate the above association. Studies were identified by searching the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and WanFang databases from inception to June 20, 2021. Two authors independently performed literature search, data extraction, and quality assessment. Predefined subgroup analyses were carried out to evaluate the impact of the population ethnicity, source of healthy controls (community or hospital-based), and methods used for genotyping on the outcomes. A random-effects model was used to combine the results, and 12 studies were included. Results showed that MTR A2756G polymorphism was not associated with CHD susceptibility under the allele model (odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.86 to 1.07, P = 0.43, I2 = 4%), heterozygote model (OR: 0.95, 95% CI: 0.84 to 1.07, P = 0.41, I2 = 0%), homozygote model (OR: 1.00, 95% CI: 0.64 to 1.55, P = 0.99, I2 = 17%), dominant genetic model (OR: 0.95, 95% CI: 0.84 to 1.07, P = 0.41, I2 = 0%), or recessive genetic model (OR: 0.94, 95% CI: 0.62 to 1.43, P = 0.32, I2 = 13%). Consistent results were found in subgroup analyses between Asian and Caucasian populations in studies with community and hospital-derived controls as well as in studies with PCR-RFLP and direct sequencing (all P values for subgroup differences > 0.05). In conclusion, current evidence does not support an association between MTR A2756G polymorphism and CHD susceptibility.

With the spread of Coronavirus Disease 2019 globally, more than 40,000 healthcare staff rushed to Wuhan, Hubei Province to fight against this threatening disease. All staff had to wear personal protective equipment (PPE) for several hours when caring for patients, which resulted in adverse skin reactions and injuries. In this study, we used an online questionnaire to collect the self-reported skin damages among the first-line medical staff in the epidemic. The questionnaire was designed by four front-line wound care nurses and then revised through Delphi consultants. Items mainly focused on the adverse skin reactions and preventive strategies. The survey was distributed through phone application from March 15th to March 20th and received 275 responses in total. The prevalence of skin reactions (212, 77.09%) was high in both head and hands. The common clinical symptoms of skin reactions were redness, device-like mark, and burning pain in face; and dryness, dermatitis, and itch/irritation in hands. Three risk factors included gender, level of protection, and daily wearing time of PPE were identified that caused skin reactions among medical staff. 150 of 275 (54.55%) participants took preventive strategies like prophylactic dressings, however, more than 75% users had little knowledge about dressings. We suggest the frontline staff strengthened the protection of skin integrity and reduced the prevalence of adverse skin reactions after professional education.

Background & aimThe coronavirus disease 2019 (COVID-19) pandemic has affected the life and work of people worldwide. The present study aimed to evaluate the rhythm disruptions of life, work, and entertainment, and their associations with the psychological impacts during the initial phase of the COVID-19 pandemic.MethodA cross-sectional study was conducted from the 10th to 17th March 2020 in China. A structured e-questionnaire containing general information, the Chinese version of Brief Social Rhythm Scale, and Zung's self-rating scales of depression and anxiety (SDS and SAS) was posted and collected online through a public media (i.e. EQxiu online questionnaire platform). Scores in sleeping, getting up, and socializing (SGS) rhythm and eating, physical practice, and entertainment (EPE) rhythm were compared among and between participants with different sociodemographic backgrounds including gender, age, education, current occupation, annual income, health status, and chronic disease status. Correlations of SDS and SAS with SGS-scale and EPE-scale were also analyzed.ResultsOverall, 5854 participants were included. There were significant differences in the scores of SGS-scale and EPE-scale among people with different sociodemographic backgrounds. The scores were significantly higher in the groups with female gender, low education level, lower or higher than average income, poor health status, ages of 26-30 years or older than 61 years, nurses and subjects with divorce or widow status. There were also significant differences in SAS and SDS scores among people with different sociodemographic backgrounds (all P< 0.05). The overall prevalence of depression and anxiety was 24.3% and 12.6%, respectively, with nurses having the highest rates of depression (32.94%) and anxiety (18.98%) among the different occupational groups. SGS-scale was moderately correlated with SDS and SAS, and disruption of SGS rhythm was an independent risk factor for depression and anxiety.ConclusionSocial rhythm disruption was independently associated with depression and anxiety. Interventions should be applied to people vulnerable to the rhythm disruption during the COVID-19 pandemic.

A recent flood of publications has documented serious problems in scientific reproducibility, power, and reporting of biomedical articles, yet scientists persist in their usual practices. Why? We examined a popular and important preclinical assay, the Forced Swim Test (FST) in mice used to test putative antidepressants. Whether the mice were assayed in a naïve state vs. in a model of depression or stress, and whether the mice were given test agents vs. known antidepressants regarded as positive controls, the mean effect sizes seen in the experiments were indeed extremely large (1.5-2.5 in Cohen's d units); most of the experiments utilized 7-10 animals per group which did have adequate power to reliably detect effects of this magnitude. We propose that this may at least partially explain why investigators using the FST do not perceive intuitively that their experimental designs fall short-even though proper prospective design would require ~21-26 animals per group to detect, at a minimum, large effects (0.8 in Cohen's d units) when the true effect of a test agent is unknown. Our data provide explicit parameters and guidance for investigators seeking to carry out prospective power estimation for the FST. More generally, altering the real-life behavior of scientists in planning their experiments may require developing educational tools that allow them to actively visualize the inter-relationships among effect size, sample size, statistical power, and replicability in a direct and intuitive manner.

Idiopathic pulmonary fibrosis is a progressive and debilitating lung disease with large unmet medical need and few treatment options. We describe an analysis connecting single cell gene expression with bulk gene expression-based subsetting of patient cohorts to identify IPF patient subsets with different underlying pathogenesis and cellular changes. We reproduced earlier findings indicating the existence of two major subsets in IPF and showed that these subsets display different alterations in cellular composition of the lung. We developed classifiers based on the cellular changes in disease to distinguish subsets. Specifically, we showed that one subset of IPF patients had significant increases in gene signature scores for myeloid cells versus a second subset that had significantly increased gene signature scores for ciliated epithelial cells, suggesting a differential pathogenesis among IPF subsets. Ligand-receptor analyses suggested there was a monocyte-macrophage chemoattractant axis (including potentially CCL2-CCR2 and CCL17-CCR4) among the myeloid-enriched IPF subset and a ciliated epithelium-derived chemokine axis (e.g. CCL15) among the ciliated epithelium-enriched IPF subset. We also found that these IPF subsets had differential expression of pirfenidone-responsive genes suggesting that our findings may provide an approach to identify patients with differential responses to pirfenidone and other drugs. We believe this work is an important step towards targeted therapies and biomarkers of response.

BackgroundThere have been inconsistent results regarding the use of carotid artery endarterectomy (CEA) versus carotid artery stenting (CAS) for contralateral carotid occlusion (CCO). This study aimed to determine the optimal revascularization technique for patients with CCO.MethodsWe systematically searched the PubMed, Embase, and Cochrane Library databases to identify eligible studies published from inception to January 2, 2021. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate pooled effect estimates using a random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed.ResultsSix studies involving 6,953 patients were selected for inclusion in this meta-analysis. Our results showed that while CEA was not associated with an increased risk of stroke compared to CAS (OR: 1.07; 95% CI: 0.75-1.51; P = 0.713), CEA was associated with a reduced risk of death compared to CAS (OR: 0.45; 95% CI: 0.29-0.70; P < 0.001). Furthermore, there were no significant differences between CEA and CAS for the risks of myocardial infarction (OR: 1.38; 95% CI: 0.73-2.62; P = 0.319) or major adverse cardiovascular events (OR: 1.03; 95% CI: 0.56-1.88; P = 0.926). Finally, the risk of myocardial infarction for CEA versus CAS was affected by disease status, while the risk of major adverse cardiovascular events was affected by the proportions of patients with male gender, coronary artery disease, and current or prior smoking.ConclusionThis study found that CEA and CAS resulted in similar outcomes for patients with CCO, while the risk of death was reduced in patients treated with CEA. Further high-level evidence should be collected to verify the results of this study.

BACKGROUND:Handwriting ability is related to many neuronal functions, such as visual-perceptual skills, orthographic coding, motor planning and execution, kinesthetic feedback and visual-motor coordination. To date, there is no specific assessment tool for to assess preschool children's handwriting ability in Mainland China. Our study aimed to develop a tool to assess the handwriting ability of children aged 5-6 years old in Mainland China and to analyze its reliability and validity. METHODS:The investigation comprised three phases: 1) original tool generation, 2) tool revision, 3) reliability analysis (i.e., interrater, test-retest) and validity analysis (i.e., content, criterion). RESULTS:The sample included a total of 482 children. The internal consistency (Cronbach alpha) was 0.74. The test-retest correlation coefficients ranged from 0.38 to 0.80. As expected, our data showed an improving trend in handwriting, and differences in respect to age and gender. When compared with the 'handwriting difficulty' group, each subtest score of children in the 'normal' group showed significant differences (p < 0.05). The correlation validity, compared with the visual-motor integration development test (VMI), was 0.17-0.52. CONCLUSION:The Handwriting Test for Preschool Children (HT-PRE), which is a newly developed handwriting screening tool for preschool children aged 5-6 years old in Mainland China, has displayed a very good internal consistency, acceptable test-retest reproducibility, and good criterion-based validity, and has also shown good application prospects for handwriting difficulty screening in a clinical setting.

DaHuangWan (DHW) is a traditional herbal medicine used by Mongolian to treat liver cancer for many years. Clinical application of the drug has been shown to help control tumor progression, prolong survival and improve quality of life. However, the underlying mechanisms and side effects of this drug remain unclear, which greatly limits the clinical application and further optimization of DHW. In this study, we found that DHW inhibits the proliferation of hepatoma cells by modulating the epithelial growth factor (EGF) signaling pathway. Berberine and Costunolide are the main active ingredients in DHW. Interestingly, the combination of Berberine and Costunolide has a dramatic synergistic effect on inhibiting the proliferation of hepatoma cells. Neither Berberine nor Costunolide directly block EGFR phosphorylation. Berberine promotes endocytosis of activated EGFR, while as Costunolide increases ubiquitination of EGFR and reduces EGFR recycling to cell membrane distribution, thereby inhibiting EGF signaling. Berberine and Costunolide target two different steps in regulating the EGF signaling, which explains the synergistic anti-cancer effect of DHW. Since Berberine and Costunolide do not directly target EGFR phosphorylation, DHW could be a supplementary medicine to tyrosine kinase inhibitors in cancer therapy.

Hundreds of target specific peptides are routinely discovered by peptide display platforms. However, due to the high cost of peptide synthesis only a limited number of peptides are chemically made for further analysis. Here we describe an accurate and cost effective method to bin peptides on-phage based on binding region(s), without any requirement for peptide or protein synthesis. This approach, which integrates phage and yeast display platforms, requires display of target and its alanine variants on yeast. Flow cytometry was used to detect binding of peptides on-phage to the target on yeast. Once hits were identified, they were synthesized to confirm their binding region(s) by HDX (Hydrogen deuterium exchange) and crystallography. Moreover, we have successfully shown that this approach can be implemented as part of a panning process to deplete non-functional peptides. This technique can be applied to any target that can be successfully displayed on yeast; it narrows down the number of peptides requiring synthesis; and its utilization during selection results in enrichment of peptide population against defined binding regions on the target.

ObjectiveThe answer to this article lies in: Does the financial activities of physical enterprises have an adverse impact on their main business? Is it conducive to the sustainable development of the national economy? However, when most scholars study the impact of environmental regulations on companies performance, they have not classified companies performance. This article will study the relationship between environmental regulations and performance levels based on the classification of companies performance, and then divide the nature of industry pollution, companies location and nature of property for in-depth research.MethodsFirst, this article uses a random effect variable-intercept model to measure companies financial performance and non-financial performance. Then, the variables are divided into two variable groups: light pollution and heavy pollution according to the nature of industry pollution. Next, the companies are divided into three variable groups: the eastern region, the central region, and the western region. Finally, the company is divided into two variable groups: state-owned and non-state-owned according to the nature of property.ConclusionsThe study found that: (1) Environmental regulations have inhibited companies financial activities. And the inhibitory effect of environmental regulations on the financial performance of enterprises is more obvious in the heavily polluting industries and enterprises in central and eastern regions. (2) Environmental regulations and companies non-financial performance are also negatively related, environmental regulations have also inhibited the non-financial performance of companies, this effect is more pronounced in heavily polluting industries and enterprises in western regions. (3) Income crowding effect brought by China's environmental regulations is greater than the income compensation effect brought by stimulating technological innovation.

BackgroundHeart failure (HF) is a major cause of morbidity and mortality. However, much of the clinical data is unstructured in the form of radiology reports, while the process of data collection and curation is arduous and time-consuming.PurposeWe utilized a machine learning (ML)-based natural language processing (NLP) approach to extract clinical terms from unstructured radiology reports. Additionally, we investigate the prognostic value of the extracted data in predicting all-cause mortality (ACM) in HF patients.Materials and methodsThis observational cohort study utilized 122,025 thoracoabdominal computed tomography (CT) reports from 11,808 HF patients obtained between 2008 and 2018. 1,560 CT reports were manually annotated for the presence or absence of 14 radiographic findings, in addition to age and gender. Thereafter, a Convolutional Neural Network (CNN) was trained, validated and tested to determine the presence or absence of these features. Further, the ability of CNN to predict ACM was evaluated using Cox regression analysis on the extracted features.Results11,808 CT reports were analyzed from 11,808 patients (mean age 72.8 ± 14.8 years; 52.7% (6,217/11,808) male) from whom 3,107 died during the 10.6-year follow-up. The CNN demonstrated excellent accuracy for retrieval of the 14 radiographic findings with area-under-the-curve (AUC) ranging between 0.83-1.00 (F1 score 0.84-0.97). Cox model showed the time-dependent AUC for predicting ACM was 0.747 (95% confidence interval [CI] of 0.704-0.790) at 30 days.ConclusionAn ML-based NLP approach to unstructured CT reports demonstrates excellent accuracy for the extraction of predetermined radiographic findings, and provides prognostic value in HF patients.

Antibody therapeutics are one of the most important classes of drugs. Antibody structures have become an integral part of predicting the behavior of potential therapeutics, either directly or as the basis of modeling. Structures of Fab:antigen complexes have even greater value. While the crystallization and structure determination of Fabs is easy relative to many other protein classes, especially membrane proteins, broad screening and optimization of crystalline hits is still necessary. Through a comprehensive review of rabbit Fab crystal contacts and their incompatibility with human Fabs, we identified a small secondary structural element from the rabbit light chain constant domain potentially responsible for hindering the crystallization of human Fabs. Upon replacing the human kappa constant domain FG loop (HQGLSSP) with the two residue shorter rabbit loop (QGTTS), we dramatically improved the crystallization of human Fabs and Fab:antigen complexes. Our design, which we call "Crystal Kappa", enables rapid crystallization of human fabs and fab complexes in a broad range of conditions, with less material in smaller screens or from dilute solutions.

Mulberry leaf polysaccharide (MLP) was extracted and purified by DEAE-52 cellulose and Sephadex G-100 column chromatography to afford two major purified polysaccharides (MLP-1 and MLP-2). The purified polysaccharides were characterized, and their immune-enhancing properties were investigated. MLP-1 had a molecular weight of 9.31×104 Da and was composed of mannose, rhamnose, glucose, galactose, xylose, and arabinose in a molar ratio of 0.71:1.00:2.76:1.13:3.70:2.81. The molecular weight of MLP-2 was 2.22×106 Da, and its monosaccharide constituents were mannose, rhamnose, glucose, galactose, and arabinose in a molar ratio of 1.31:8.45:6.94:1.00:11.96. Infrared spectroscopy showed that each MLP had a typical absorption peak characteristic of sugars, and ultraviolet (UV) spectroscopy showed that neither MLP contained nucleic acid or protein components. Then, the abilities of these polysaccharides to stimulate spleen lymphocyte proliferation in mice in vitro were compared by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. MLP-2 was more effective than MLP-1; therefore, MLP-2 was chosen for the study of its immune-enhancing effects in vivo. For the in vivo experiments, 14-day-old chickens immunized with Newcastle disease (ND) vaccine were orally administered MLP-2, and Astragalus polysaccharide (APS) was used as the control. Each chicken was orally administered 4 mg or 8 mg of MLP-2 for seven consecutive days starting three days before ND vaccine immunization. MLP-2 significantly improved the ND serum antibody titer and interleukin-2 (IL-2), interferon-γ (IFN-γ) and immunoglobulin A (sIgA) concentrations in tracheal and jejunal wash fluids, and increasing numbers of immune globulin A-positive (IgA+) cells in cecal tonsils and increased body weight. These results indicated that MLP-2 could significantly enhance immune activity and could therefore be utilized as an immunopotentiator drug candidate.

BackgroundPrevious studies have demonstrated that intensive blood pressure (BP) lowering treatment reduces the risk of all-cause mortality and provides greater vascular protection for patients with hypertension. Whether intensive BP lowering treatment is associated with such benefits in patients with type 2 diabetes mellitus remain unknown. We aimed to clarify these benefits by method of meta-analysis.MethodsThe PubMed, EMBASE, Science Citation Index and Cochrane Library databases were searched to identify randomized controlled trials (RCT) that fulfilled study inclusion criteria. Two investigators independently extracted and summarized the relevant data of the included trials. Random-effects model was applied to calculate the estimates of all effect measures.ResultsWe included 16 RCTs and our meta-analysis showed that intensive BP lowering treatment vs less intensive BP lowering treatment resulted in significant reductions in the all-cause mortality risk [relative risk (RR), 0.82; 95% CI, 0.70-0.96], major CV events (RR, 0.82; 95% CI, 0.73-0.92, MI (RR, 0.86; 95% CI, 0.77-0.96), stroke (RR, 0.72; 95% CI, 0.60-0.88, CV death (RR, 0.73; 95% CI, 0.58-0.92) and albuminuria progression (RR, 0.91 95% CI, 0.84-0.98). However, intensive BP lowering treatment had no clear effect on non-CV death (RR, 0.97; 95% CI, 0.79-1.20), heart failure (HF) (RR, 0.88; 95% CI, 0.71-1.08) or end-stage kidney disease (ESKD) (RR, 1.00; 95% CI, 0.75-1.33). Subgroup analysis showed that the reduction in all cause-mortality was consistent across most patient groups, and intensive BP lowering treatment had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. However, the benefit differed in patients with different CV risk (≥10%: RR, 0.77, 95%CI, 0.64-0.91; ConclusionsOur data indicate that intensive BP lowering treatment provides greater benefits than less intensive treatment among patients with type 2 diabetes mellitus. Further studies are required to more clearly evaluate the benefits and harms of BP targets below those currently recommended with intensive BP lowering treatment.

ObjectiveTo analyze the relationships between illness uncertainty, social support, and coping mode in hospitalized patients with systematic lupus erythematosus (SLE).MethodsThe General Health Questionnaire, Mishel Uncertainty in Illness Scale, Social Support Rating Scale, and Medical Coping Modes Questionnaire were to the hospitalized patients with SLE (N = 200) in a tertiary hospital in Shaanxi.ResultsThe hospitalized patients with SLE showed a moderate level of illness uncertainty. Furthermore, illness uncertainty was negatively correlated with support availability (r = -0.161, P = 0.023) and facing coping mode (r = -0.231, P = 0.001), and was positively correlated with the yielding coping mode (r = 0.249, P < 0.001).ConclusionThese findings suggest that support availability and coping modes were associated with moderate level of illness uncertainty, indicating that support availability support should be strengthened in hospitalized patients to actively face their disease. This subsequently improves their treatment compliance and quality of life.

The anticariogenic activity of the extract of Glycyrrhiza uralensis (licorice) has been well documented. We recently developed an herbal lollipop containing licorice extracts with Glycyrrhizol A, the compound displaying strong antimicrobial activity against Streptococcus mutans. Preliminary testing showed that the herbal lollipop reduced salivary S. mutans counts in vivo. In this study, we aimed to further test the efficacy of this herbal lollipop for reducing salivary S. mutans levels, and investigate its impact on salivary microbiome. Using a well-established in vitro oral microbiome model, we showed that licorice extract displays targeted killing against S. mutans without affecting the biodiversity of the community. In vivo study corroborated in vitro findings, showing for high caries-risk children aged 3-6 with salivary S. mutans levels >5x105 cells/ml, daily use of 2 licorice-containing lollipops for 3 weeks significantly reduced salivary S. mutans levels compared to the control group. Salivary microbiome analysis showed either no change or even increase in phylogenetic diversity of the oral community following herbal lollipop usage. Although further study with longer term observation is needed, these results suggest that use of licorice extract-containing lollipops can be as a simple and effective way to reduce the risk of dental caries in children.

We examined the impact of statins on Yes-associated Protein (YAP) localization, phosphorylation and transcriptional activity in human and mouse pancreatic ductal adenocarcinoma (PDAC) cells. Exposure of sparse cultures of PANC-1 and MiaPaCa-2 cells to cerivastatin or simvastatin induced a striking re-localization of YAP from the nucleus to the cytoplasm and inhibited the expression of the YAP/TEAD-regulated genes Connective Tissue Growth Factor (CTGF) and Cysteine-rich angiogenic inducer 61 (CYR61). Statins also prevented YAP nuclear import and expression of CTGF and CYR61 stimulated by the mitogenic combination of insulin and neurotensin in dense culture of these PDAC cells. Cerivastatin, simvastatin, atorvastatin and fluvastatin also inhibited colony formation by PANC-1 and MiaPaCa-2 cells in a dose-dependent manner. In contrast, the hydrophilic statin pravastatin did not exert any inhibitory effect even at a high concentration (10 μM). Mechanistically, cerivastatin did not alter the phosphorylation of YAP at Ser127 in either PANC-1 or MiaPaCa-2 cells incubated without or with neurotensin and insulin but blunted the assembly of actin stress fiber in these cells. We extended these findings with human PDAC cells using primary KC and KPC cells, (expressing KrasG12D or both KrasG12D and mutant p53, respectively) isolated from KC or KPC mice. Using cultures of these murine cells, we show that lipophilic statins induced striking YAP translocation from the nucleus to the cytoplasm, inhibited the expression of Ctgf, Cyr61 and Birc5 and profoundly inhibited colony formation of these cells. Administration of simvastatin to KC mice subjected to diet-induced obesity prevented early pancreatic acini depletion and PanIN formation. Collectively, our results show that lipophilic statins restrain YAP activity and proliferation in pancreatic cancer cell models in vitro and attenuates early lesions leading to PDAC in vivo.

Cerebral injury after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) has been implicated in the poor prognosis of CA survivors. This study was designed to evaluate the impact of melatonin on postresuscitation neurological outcomes and to explore the underlying mechanism. Sprague-Dawley rats were randomly assigned to four groups: sham group, CPR group, melatonin pretreatment group (Pre-M) and posttreatment group (Post-M). For the last 2 groups, daily melatonin gavage was performed for 12 consecutive days before or 24 hours after rat survival from CA/CPR. No statistical differences were observed in heart rate (HR), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) at baseline and after restoration of spontaneous circulation (ROSC) among groups. However, melatonin pretreatment or posttreatment significantly improved neurological deficit score and memory and spatial learning ability after CA/CPR. Further studies demonstrated that the complex I- and complex-II supported mitochondrial respiration were greatly increased under melatonin treatment. In addition, melatonin treatment preserved the mitochondrial-binding hexokinase II (HKII) and ATP levels and suppressed the upregulated protein lysine acetylation in hippocampus after CA/CPR. In conclusion, using a rat asphyxial CA model we have demonstrated that treatment with melatonin either before or after CA/CPR provides a promising neuroprotective effect, and this protection was mediated by increasing mitochondrial HKII expression, suppressing protein acetylation and improving mitochondrial function in hippocampus.

Klebsiella pneumoniae (K. pneumoniae) is a frequent pathogen causing nosocomial infections and outbreaks. We developed a multiple cross displacement amplification (MCDA) assay for the detection of K. pneumoniae, which can get the positive results within 40 minutes' isothermal amplification. Gold-nanoparticle lateral flow biosensor (LFB) and colorimetric indicators were used for the rapid readouts of MCDA amplification. The detection limit of this assay was 100 fg per reaction at 65°C, which was confirmed to be the optimal amplification temperature according to the real time turbidimeters. For specificity, all of the 30 clinical-source K. pneumoniae strains were positive for the MCDA, and all of the non-K. pneumoniae strains belonging to 31 different species were negative for this MCDA assay. To evaluate the practical applicability of this method, we assessed its detection limit for K. pneumoniae strains in sputum samples (24 CFU per reaction), and DNA templates of 100 sputum samples further underwent the MCDA-LFB tests. All of the sputum samples being positive for K. pneumoniae (30/100) with the culture method were successfully identified with the MCDA assay, the detection power of which was higher than that of polymerase chain reaction (PCR) (25/100). Thus, the MCDA test for K. pneumoniae combined with the gold nanoparticle LFB as the results readout scheme, are simple, specific, and sensitive methods for the rapid diagnosis of K. pneumoniae in clinical samples.

BACKGROUND:South Africa has one of the highest rates of HIV-1 (HIV) infection world-wide, with the highest rates among young women. We analyzed the molecular epidemiology and evolutionary history of HIV in young women attending high school in rural South Africa. METHODS:Samples were obtained from the HPTN 068 randomized controlled trial, which evaluated the effect of cash transfers for school attendance on HIV incidence in women aged 13-20 years (Mpumalanga province, 2011-2015). Plasma samples from HIV-infected participants were analyzed using the ViroSeq HIV-1 Genotyping assay. Phylogenetic analysis was performed using 200 pol gene study sequences and 2,294 subtype C reference sequences from South Africa. Transmission clusters were identified using Cluster Picker and HIV-TRACE, and were characterized using demographic and other epidemiological data. Phylodynamic analyses were performed using the BEAST software. RESULTS:The study enrolled 2,533 young women who were followed through their expected high school graduation date (main study); some participants had a post-study assessment (follow-up study). Two-hundred-twelve of 2,533 enrolled young women had HIV infection. HIV pol sequences were obtained for 94% (n = 201/212) of the HIV-infected participants. All but one of the sequences were HIV-1 subtype C; the non-C subtype sequence was excluded from further analysis. Median pairwise genetic distance between the subtype C sequences was 6.4% (IQR: 5.6-7.2). Overall, 26% of study sequences fell into 21 phylogenetic clusters with 2-6 women per cluster. Thirteen (62%) clusters included women who were HIV-infected at enrollment. Clustering was not associated with study arm, demographic or other epidemiological factors. The estimated date of origin of HIV subtype C in the study population was 1958 (95% highest posterior density [HPD]: 1931-1980), and the median estimated substitution rate among study pol sequences was 1.98x10-3 (95% HPD: 1.15x10-3-2.81x10-3) per site per year. CONCLUSIONS:Phylogenetic analysis suggests that multiple HIV subtype C sublineages circulate among school age girls in South Africa. There were no substantive differences in the molecular epidemiology of HIV between control and intervention arms in the HPTN 068 trial.

Soil rotational tillage is an effective measure to overcome the problems caused by long-term of a single tillage, but the effect of the interval time of rotational tillage practices is not very well understood. Therefore, we conducted a 3-year field study in a wheat-maize cropping system to evaluate the effects of rotary tillage (RT) in rotation with plowing tillage (PT) on soil properties in northern China. Four practices were designed as follows: 3 years of RT to a depth of 10-15 cm (3RT), 3 years of PT to a depth of 30-35 cm (3PT), 1 year of PT followed by 2 years of RT (PT+2RT), and 2 years of PT followed by 1 year of RT (2PT+RT). Within 20 cm of the surface soil, the 3RT treatment significantly increased the soil quality index (SQI) by 6.0%, 8.8% and 13.1%, respectively, relative to the PT+2RT, 2PT+RT and 3PT treatments. The improvement was closely related to the significant increase in the soil organic carbon (SOC) and available nutrients concentrations in the 0-20 cm depths and the improvement of soil invertase, urease, alkaline phosphatase and catalase activities in the topsoil (0-10 cm). However, the opposite effects were observed in the subsoil (20-40 cm). Compared with the 3RT treatment, the 3PT, 2PT+RT and PT+2RT treatments decreased soil bulk density, and significantly enhanced enzyme activities, resulting in an increase in SQI of 32.6%, 24.4% and 0.7%, respectively, especially in the 3PT and 2PT+RT treatments, the difference was significant. When averaged across to all soil depths, the SQI under the 3RT and 2PT+RT treatments was much higher than that under the other treatments. The yields of wheat and maize under the 2PT+RT treatment were 15.0% and 14.3% higher than those under the 3RT treatment, respectively. The 2PT+RT treatment was the most effective tillage practice. These results suggest that RT in rotation with PT could improve soil quality in the soil profile whilst enhancing crop yield after continuous RT, and the benefits were enhanced with an interval time of one year. Therefore, the 2PT+RT treatment could act as an effective method for both soil quality and crop yield improvement in a wheat-maize cropping system under straw incorporation conditions.

[This corrects the article DOI: 10.1371/journal.pone.0173122.].

Deep learning has started to revolutionize several different industries, and the applications of these methods in medicine are now becoming more commonplace. This study focuses on investigating the feasibility of tracking patients and clinical staff wearing Bluetooth Low Energy (BLE) tags in a radiation oncology clinic using artificial neural networks (ANNs) and convolutional neural networks (CNNs). The performance of these networks was compared to relative received signal strength indicator (RSSI) thresholding and triangulation. By utilizing temporal information, a combined CNN+ANN network was capable of correctly identifying the location of the BLE tag with an accuracy of 99.9%. It outperformed a CNN model (accuracy = 94%), a thresholding model employing majority voting (accuracy = 95%), and a triangulation classifier utilizing majority voting (accuracy = 95%). Future studies will seek to deploy this affordable real time location system in hospitals to improve clinical workflow, efficiency, and patient safety.

Pigs have experienced long-term selections, resulting in dramatic phenotypic changes. Structural variants (SVs) are reported to exert extensive impacts on phenotypic changes. We built a high resolution and informative SV map based on high-depth sequencing data from 66 Chinese domestic and wild pigs. We inferred the SV formation mechanisms in the pig genome and used SVs as materials to perform a population-level analysis. We detected the selection signals on chromosome X for northern Chinese domestic pigs, as well as the differentiated loci across the whole genome. Analysis showed that these loci differ between southern and northern Chinese domestic pigs. Our results based on SVs provide new insights into genetic differences in Chinese pigs.

The sigma 1 receptor (S1R) is a unique transmembrane protein that has been shown to regulate neuronal differentiation and cellular survival. It is expressed within several cell types throughout the nervous system and visceral organs, including neurons and glia within the eye. S1R ligands are therapeutic targets for diseases ranging from neurodegenerative conditions to neoplastic disorders. However, effects of S1R activation and inhibition within glia cells are not well characterized. Within the eye, the astrocytes at the optic nerve head are crucial to the health and survival of the neurons that send visual information to the brain. In this study, we used the S1R-specific agonist, (+)-pentazocine, to evaluate S1R activation within optic nerve head-derived astrocytes (ONHAs). Treatment of ONHAs with (+)-pentazocine attenuated the level and duration of stress-induced ERK phosphorylation following oxidative stress exposure and promoted survival of ONHAs. These effects were specific to S1R activation because they were not observed in ONHAs that were depleted of S1R using siRNA-mediated knockdown. Collectively, our results suggest that S1R activation suppresses ERK1/2 phosphorylation and protects ONHAs from oxidative stress-induced death.

Scatter contamination is one of the main sources of decreasing the image quality in cone-beam computed tomography (CBCT). The moving blocker method is economic and effective for scatter correction (SC), which can simultaneously estimate scatter and reconstruct the complete volume within the field of view (FOV) from a single CBCT scan. However, at the regions with large intensity transition in the projection images along the axial blocker moving direction, the estimation of scatter signal from blocked regions in a single projection view can produce large error and cause significant artifacts in reconstructed images and null the usability of these regions. Furthermore, blocker edge detection error can significantly deteriorate both primary signal and scatter signal estimation and lead to unacceptable reconstruction results. In this study, we propose to use the adjacent multi-view projection images to jointly estimate scatter signal more accurately. In return, the more accurately estimated scatter signal can be utilized to detect blocker edges more accurately for greatly improved robustness of moving-blocker based SC. The experimental results using a Catphan phantom and an anthropomorphic pelvis phantom CBCT data show that the new method can effectively suppress the estimation errors of scatter signal in the fast signal transition regions and is able to correct the blocker detection errors. This development will expand the utility of moving-blocker based SC for the target with sharp intensity changes in the projection images and provide the needed robustness for its clinical translation.