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Primary intracranial malignant peripheral nerve sheath tumors (MPNSTs) not associated with cranial nerves are rare and aggressive neoplasms. The rarity of presentation has precluded rigorous analysis of diagnosis, risk factors, treatment, and survival. We analyzed every reported case through exhaustive literature review. In addition, we present our own experience managed with resection, radiotherapy, and first use of targeted therapy in a tumor of this type for a BRAF mutation identified during next-generation sequencing.Two databases, PubMed and Embase, and crossed references were queried for intracranial MPNSTs not associated with a cranial nerve. Extracted variables included demographics, risk factors, tumor characteristics, interventions, and outcomes. Univariate and multivariate analysis was performed to identify factors with survival benefit.A total of 56 patients (including the present case) were included from 743 literature results. There was a male/female ratio of 1.5:1 and mean diagnosis age of 29.7 ± 21.8 years. Seventy-one percent of cases were sporadic and 23% neurofibromatosis type 1 related. Median survival was 29 ± 22.1 months with 1-year survival of 60%. Factors associated on univariate analysis with reduced survival were subtotal resection (P = 0.05), older age (P = 0.023), triton histology (P0.001), and early recurrence (≤6 months) (P = 0.018). On multivariate analysis, gross total resection reduced mortality risk (P = 0.011), whereas triton histology (P = 0.017) and infratentorial tumor location (P = 0.037) increased mortality.We present a systematic review of intracranial MPNSTs not associated with a cranial nerve. These tumors have poor prognosis and benefit from aggressive resection, multimodal treatment, and close follow-up. Next-generation sequencing can show molecular alterations for potential targeted therapy.

Biorepositories provide a critical resource for gaining knowledge of emerging infectious diseases and offer a mechanism to rapidly respond to outbreaks; the emergence of the novel coronavirus, SARS-CoV-2, has proved their importance. During the COVID-19 pandemic, the absence of centralized, national biorepository efforts meant that the onus fell on individual institutions to establish sample repositories. As a safety-net hospital, Boston Medical Center (BMC) recognized the importance of creating a COVID-19 biorepository to both support critical science at BMC and ensure representation in research for its urban patient population, most of whom are from underserved communities. This article offers a realistic overview of the authors' experience in establishing this biorepository at the onset of the COVID-19 pandemic during the height of the first surge of cases in Boston, Massachusetts, with the hope that the challenges and solutions described are useful to other institutions. Going forward, funders, policymakers, and infectious disease and public health communities must support biorepository implementation as an essential element of future pandemic preparedness.

Background Chronic jet lag (CJL)-induced circadian rhythm disruption (CRD) is positively correlated with an increased risk of allergic diseases. However, little is known about the mechanism involved in allergic rhinitis (AR). Methods Aberrant light/dark cycles-induced CRD mice were randomly divided into negative control (NC) group, AR group, CRD+NC group, and CRD+AR group (n = 8/group). After ovalbumin (OVA) challenge, nasal symptom scores were recorded. The expression of Occludin and ZO-1 in both nasal mucosa and lung tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-PCR) and immunohistochemical staining. The level of OVA-specific immunoglobulin E (sIgE) and T-helper (Th)-related cytokines in the plasma was measured by enzyme-linked immunosorbent assay (ELISA), and the proportion of Th1, Th2, Th17, and regulatory T cell (Treg) in splenocytes was evaluated by flow cytometry. Results The nasal symptom score in the CRD+AR group was significantly higher than those in the AR group with respect to eosinophil infiltration, mast cell degranulation, and goblet cell hyperplasia. The expression of ZO-1 and Occludin in the nasal mucosa and lung tissues in the CRD+AR group were significantly lower than those in the AR group. Furthermore, Th2 and Th17 cell counts from splenocytes and OVA-sIgE, interleukin 4 (IL-4), IL-6, IL-13, and IL-17A levels in plasma were significantly increased in the CRD+AR group than in the AR group, whereas Th1 and Treg cell count and interferon γ (IFN-γ) level were significantly decreased in the CRD+AR group. Conclusion CRD experimentally mimicked CJL in human activities, could exacerbate local and systemic allergic reactions in AR mice, partially through decreasing Occludin and ZO-1 level in the respiratory mucosa and increasing Th2-like immune response in splenocytes.

The gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) has recently been recognized as one of the novel marker for adverse cardiovascular events and risk of death. However, data on the relationship between TMAO and atrial fibrillation (AF) is limited. The current study was performed to quantify and evaluate the relationship between circulating TMAO levels and AF occurrence.The electronic databases PubMed, Cochrane Library, and Embase were systematically searched to March 20, 2021. Research studies were considered that recorded or analyzed the prevalence of AF in individuals in specific populations as well as their circulating TMAO levels. A meta-analysis of two-class variables was used to obtain pooled effects. A dose-response meta-analysis was used to investigate the dose-response relationship between TMAO levels and the risk of AF.Six studies with a total of 8,837 individuals and 1,668 AF cases were included in the present meta-analysis. Compared with a lower circulating TMAO level, a higher TMAO level was associated with a higher prevalence of AF [odds ratio (OR): 1.40; 95% confidence interval (CI): 1.23, 1.59; I2=19.8%]. The dose-response analysis revealed the risk of AF increased by 6% per 1-µmol/L increment (OR: 1.06; 95% CI: 1.00, 1.11), 32% per 5-µmol/L increment (OR: 1.32; 95% CI: 1.03, 1.70), and 73% per 10-µmol/L increment (OR: 1.73; 95% CI: 1.05, 2.86) of the circulating TMAO level.This is the first systematic literature review and meta-analysis to demonstrate a significant dose-dependent relationship between increased AF risk and circulating TMAO levels.

Purpose To determine the safety and efficacy of microsphere embolization plus transarterial infusion chemotherapy for the treatment of gastroesophageal junction cancer with hepatic metastasis. Methods Sixty patients with gastroesophageal junction cancer and hepatic metastasis were randomly divided into two groups: group A (treatment group), which was treated with transarterial infusion chemotherapy plus microsphere embolization for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis; and group B (control group), which was treated with transarterial infusion chemotherapy for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis. The chemotherapy regimen used consisted of oxaliplatin plus FUDR. The embolization agent used for gastroesophageal cancer and the hepatic metastasis were Embosphere and ultra-liquefied lipiodol, respectively. Results The median survival time of patients in group A was 19 months, with survival rates at 12, 18, and 24 months of 93.3%, 60.0%, and 23.3%, respectively. The median survival time of patients in group B was 13 months, with survival rates at 12, 18, and 24 months of 60.0%, 30.0%, and 3.3%, respectively. There was a significant difference in survival between the two groups (P = 0.00). One month after treatment, the severity of dysphagia was significantly less in group A, as compared to that in group B (p Conclusion Treatment of gastroesophageal junction cancer with hepatic metastasis by transarterial infusion chemotherapy plus microsphere embolization can rapidly reduce tumor size near the gastroesophageal junction. This treatment is an effective therapeutic option for these patients as it can relieve dysphagia and improve long-term survival rate.

Background Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. Methods A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. Results 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. Conclusions Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.

BACKGROUND: In the 6(th) World Symposium on Pulmonary Hypertension (PH), the hemodynamic definition of PH was reduced from a mean pulmonary artery pressure (mPAP) ≥25 to >20 mmHg. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of precapillary PH. METHODS: We retrospectively enrolled patients who underwent right heart catheterization from January 2012 to December 2018. All included patients were reassessed according to the revised hemodynamic definition. RESULTS: A total of 1,251 patients were included for analysis, of whom 1,044 patients had precapillary PH and 182 patients had mPAP

BACKGROUND: Atrial fibrillation (AF) relapse following radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (PeAF) continues to be a concern. This study establishes a connection between left atrial appendage peak flow velocity (LAAV) and recurrence of AF in individuals having PeAF following first RFCA. METHODS: We retrospectively studied 164 successive PeAF patients who had first RFCA between January 2018 and December 2019. Before the ablation, the LAAV was recorded using transesophageal echocardiography (TEE). The demographic and clinical data of the individuals were gathered. Participants were monitored at regular intervals to monitor for recurrence of AF. We employed Cox proportional hazards regression to determine if LAAV, as well as other clinical indicators, were predictive of AF recurrence in follow-up. RESULTS: In this study, AF relapse was seen in 43 patients (26.2%) following a median follow-up of 15 [interquartile range (IQR): 12–18] months. It was shown that the LAAV was decreased in individuals who had recurrences of AF (0.36±0.05 vs. 0.45±0.17 m/s, P=0.004). Using Kaplan-Meier analysis, it was discovered that the low LAAV (0.37 m/s) group had a poorer event-free survival rate compared to the high LAAV (>0.37 m/s) group (17.6 vs. 21.2 months, log-rank P=0.002) group. Based on the results of the multivariate Cox regression analysis, a LAAV of fewer than 0.37 m/s [hazard ratio (HR): 2.32; 95% confidence interval (CI): 1.177–4.227; P=0.014] was shown to be an independent predictor of AF recurrence following RFCA. CONCLUSIONS: A low LAAV is associated with AF relapse, and it is a predictor of AF relapse following the first RFCA for PeAF. This discovery may be useful in the optimization of treatment strategies and the care of patients with PeAF.

OBJECTIVES The purpose of this study was to observe the effect of subcutaneous stimulation of the peripheral nerve on acute or subacute zoster occurring in trigeminal nerve branches, and to evaluate the preventive effect of prior temporary implant of a peripheral stimulation electrode in the acute or subacute phase of herpes zoster (HZ) (from 30 to 90 d after zoster onset) before postherpetic neuralgia (PHN) presents. METHODS AND MATERIALS A total of 26 patients' medical records were analyzed. All of patients had received temporary subcutaneous peripheral nerve stimulation (PNS). The clinical efficacy of treatment was evaluated on a visual analog scale (VAS), and dosages of pain medication were recorded before and at 1 to 6 months after the temporary stimulation. The rate of PHN was reevaluated at a 6 months follow-up. RESULTS There was a significant decrease in VAS values after PNS. Medication doses decreased significantly after TPNS. The rate of clinically meaningful PHN (VAS >3) dropped below 4%. DISCUSSION This study revealed that PNS is an effective treatment for trigeminal herpetic neuralgia following acute or subacute HZ. As a extend neuromodulation method, subcutaneous peripheral nerve-field stimulation might be a useful option to reduce the progression of neuropathic changes caused by persistent transmission of pain signals in the trigeminal nerve branches after the acute or subacute phase of HZ.

Aim: Construct a clinical predictive model based on easily accessible clinical features and imaging data to identify patients 65 years of age and younger with mild cognitive impairment(MCI) who may progress to Alzheimer’s disease(AD). Methods: From the ADNI database, patients with MCI who were less than or equal to 65 years of age and who had been followed for 6–60 months were selected.We collected demographic data, neuropsychological test scale scores, and structural magnetic images of these patients. Clinical characteristics were then screened, and VBM and SBM analyses were performed using structural nuclear magnetic images to obtain imaging histology characteristics. Finally, predictive models were constructed combining the clinical and imaging histology characteristics. Results: The constructed nomogram has a cross-validated AUC of 0.872 in the training set and 0.867 in the verification set, and the calibration curve fits well.We also provide an online model-based forecasting tool. Conclusion: The model has good performance and uses convenience,it should be able to provide assistance in clinical work to screen relatively young MCI patients who may progress to AD.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide, with a high genetic susceptibility. Rs2302685, a functional germline variant of LRP6, has been recently found to associate with NAFLD risk. This study was aimed to clarify the underlying mechanism associated with rs2302685 risk and its impact on pharmacotherapy in treatment of NAFLD. Methods: Venous blood samples were collected from NAFLD and non-NAFLD patients for SNP genotyping by using mass spectrometry. The Lrp6-floxdel mouse (Lrp6 (+/-)) was generated to model the partial function associated with human rs2302685. The liver injury and therapeutic effects of silibinin were compared between Lrp6 (+/-) and Lrp6 (+/+) mice received a methionine-choline deficient (MCD) diet or normal diet. The effect of Lrp6 functional alteration on Wnt/β-catenin-Cyp2e1 signaling activities was evaluated by a series of cellular and molecular assays. Results: The T allele of LRP6 rs2302685 was confirmed to associate with a higher risk of NAFLD in human subjects. The carriers of rs2302685 had reduced level of AST and ALT as compared with the noncarriers. The Lrp6 (+/-) mice exhibited a less severe liver injury induced by MCD but a reduced response to the treatment of silibinin in comparison to the Lrp6 (+/+) mice, suggesting Lrp6 as a target of silibinin. Wnt/β-catenin-Cyp2e1 signaling together with ROS generation could be exacerbated by the overexpression of Lrp6, while decreased in response to Lrp6 siRNA or silibinin treatment under NAFLD modeling. Conclusions: The Lrp6 function affects individual susceptibility to NAFLD and the therapeutic effect of silibinin through the Wnt/β-catenin-Cyp2e1 signaling pathway. The present work has provided an underlying mechanism for human individual susceptibility to NAFLD associated with Lrp6 polymorphisms as well as a rationale for the effective use of silibinin in NAFLD patients.

Background Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition associated with aging, insulin resistance, metabolic syndrome, genetic factors and more. Although genetic traits are among the most important risks factors for NAFLD, the understanding of their influence is still quite limited. The present study aimed at identifying novel single nucleotide polymorphisms (SNPs) that may confer a risk for NAFLD in the Han Chinese population. Methods Based on the “two-hit hypothesis”, candidate SNPs, including Sirtuin3 rs28365927, were genotyped by MassARRAY in B-type ultrasonography-proven NAFLD patients (n = 292) and healthy controls (n = 387). Results In a model analysis of individuals matched based on gender and age that compared 223 NAFLD and 223 non-NAFLD patients, the rs28365927 GA + AA genotype was a significant risk factor for the development of NAFLD in a dominant model. Rs28365927 was significantly associated with a higher NAFLD risk in both an additive model (A vs G) and genotypic model (GA vs GG). Among the NAFLD patients, serum levels of total bilirubin (TBIL), DBIL direct bilirubin (DBIL) and glutamic-pyruvic transaminase (ALT) in rs28365927 A allele carriers (GA + AA) were 11.1, 14.7 and 41.5% higher, respectively, than in non-carriers (GG). Furthermore, among the NAFLD patients, the carriers of Rs28365927 allele A were positively correlated with higher ALT levels. Conclusion Sirtuin3 rs28365927 functional variant confers to the high risk of non-alcoholic fatty liver disease in Chinese Han population. The rs28365927 A allele significantly increased the ALT levels of NAFLD patients.

Background To evaluate the safety and efficacy of arsenic trioxide (ATO) combined with VNP20009 in treating the advanced hepatocellular carcinoma (HCC). Methods The proliferation assay, migration assay and real-time PCR analyses were performed to assess the impact of ATO combined with VNP20009 on the McA-RH7777 cells. Forty Buffalo rats were orthotopically implanted with HCC in the livers and randomly divided into four groups: (A) ATO plus VNP20009; (B) ATO; (C) VNP20009; and (D) control. ATO (2 mg/kg) was administered by peritoneal injection once a day and continued for five days. VNP20009 (about 1×107 CFU) was directly injected into the tail vein. MRI examinations were performed to access the tumor responses one and 2 weeks later, respectively. Micro CT scans of chest were performed to assess the lung metastases. Hematoxylin-eosin (HE) staining and immunohistochemical analyses were performed to analyze the tumor tissues. Results In the in vitro experiments, VNP20009 suppressed the proliferation of McA-RH7777 cells, attenuated their migration ability, and weakened the potential of metastases. MRI examinations showed that the mean residual tumor volumes of ATO plus VNP20009 group on the 7th day and 14th day after the administration of ATO combined with VNP20009 were significantly smaller than those of other groups. Micro CT scans revealed that the lung metastases rates of ATO plus VNP20009 group and VNP20009 group were significantly lower than those of other groups. Immunohistochemical analyses displayed that the levels of VEGF and Vimentin in the tumors of ATO plus VNP20009 group were obviously lower than those of other groups. The median survival of rats in the ATO plus VNP20009 group was longer than those of other groups. Conclusions The strategy of ATO combined with VNP20009 was safe and had a potential to inhibit tumor growth, decrease the lung metastases, and prolong the overall survival in treating the advanced HCC. The two complementary interventions may have synergistic effects.

Objectives This study aims to evaluate the association between polymorphisms of methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity in Chinese patients with primary central nervous system lymphoma. Methods Sixty-five patients in 411 treatment courses were enrolled and their toxicities were evaluated. The association between 30 candidate SNPs from 20 methotrexate pathway genes and high-dose methotrexate-related hepatotoxicity was analysed by PLINK and logistic regression. Key findings TYMS 6 bp DI + II (rs151264360; OR, 0.41; 95% CI, 0.25–0.66; P = 0.00029), MTHFD1 1958 GA + AA (rs2236225; OR, 0.55; 95% CI, 0.33–0.91; P = 0.020) and CCND1 870 GA + GG (rs9344; OR, 0.42; 95% CI, 0.24–0.73; P = 0.0024) had less risk of hepatotoxicity compared with their homozygotes (DD, GG and AA, respectively), while ABCC2 intron 29 GA + GG (rs3740065; OR, 3.14; 95% CI, 1.89–5.20; P = 0.00001) was more prevalent in patients with hepatotoxicity than TT. Conclusions TYMS 6 bp DI + II, MTHFD1 1958 GA + AA, CCND1 870 GA + GG genotypes were associated with a lower probability of hepatotoxicity in patients with primary central nervous system lymphoma on high-dose methotrexate therapy, and ABCC2 intron 29 GA + GG was correlated with increased risk of hepatotoxicity.

Intestinal dysfunction is frequently driven by abnormalities of specific genes, microbiota, or microenvironmental factors, which usually differ across individuals, as do intestinal physiology and pathology. Therefore, it's necessary to develop personalized therapeutic strategies, which are currently limited by the lack of a simulated intestine model. The mature human intestinal mucosa is covered by a single layer of columnar epithelial cells that are derived from intestinal stem cells (ISCs). The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments. However, a simulated intestine model will serve as an indispensable foundation for personalized drug screening. In this article, we review the advantages and disadvantages of conventional 2-dimensional models, intestinal organoid models, and current microfluidic intestine-on-a-chip (IOAC) models. The main technological strategies are summarized, and an advanced microfluidic primary IOAC model is proposed for personalized intestinal medicine. In this model, primary ISCs and the microbiome are isolated from individuals and co-cultured in a multi-channel microfluidic chip to establish a microengineered intestine device. The device can faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions. Moreover, the ISCs can be genetically edited before seeding, and monitoring sensors and post-analysis abilities can also be incorporated into the device to achieve high-throughput and rapid pharmaceutical studies. We also discuss the potential future applications and challenges of the microfluidic platform. The development of cell biology, biomaterials, and tissue engineering will drive the advancement of the simulated intestine, making a significant contribution to personalized medicine in the future. Graphical abstract The intestine is a primary organ for digestion, absorption, and metabolism, as well as a major site for the host-commensal microbiota interaction and mucosal immunity. The complexity of the organ dramatically increases the difficulty of faithfully mimicking in vivo microenvironments, though physiological 3-dimensional of the native small intestinal epithelial tissue has been well documented. An intestinal stem cells-based microfluidic intestine-on-a-chip model that faithfully simulate in vivo fluidic flow, peristalsis-like motions, host-microbe crosstalk, and multi-cell type interactions will make a significant contribution.

To evaluate the baseline MRI characteristics for predicting survival outcomes and construct survival models for risk stratification to facilitate personalized treatment and follow-up strategies in patients with MRI-defined T3 (mrT3) locally advanced rectal cancer (LARC). We retrospectively reviewed 256 mrT3 LARC patients evaluated between 2008 and 2012 in our institution, with an average follow-up period of 6.8 ± 1.2 years. The baseline MRI characteristics, clinical data, and follow-up information were evaluated. The patients were randomized into a training cohort (TC, 186 patients) and validation cohort (VC, 70 patients). The TC dataset was used to develop multivariate nomograms for disease-free survival (DFS) and overall survival (OS), while the VC dataset was used for independent validation of the models. Harrell concordance (C) indices and Hosmer-Lemeshow calibration were used to evaluate the performances of the models. Baseline mrT3 substage, extramural venous invasion (EMVI) grading, mucinous adenocarcinoma, mesorectal fascia involvement, elevated pretreatment carcinoembryonic antigen level, and neoadjuvant chemoradiotherapy (NCRT) were independent predictors of DFS. T3 substage, EMVI grading, and NCRT were also independent predictors of OS. The nomograms constructed permitted the individualized prediction of 3-year and 5-year DFS and 5-year OS with high discrimination (C-index range, 0.833–0.892) and good calibration in the TC and VC. We have identified baseline MRI characteristics that help independently predict survival outcomes in patients with mrT3 LARC. The survival models based on these characteristics allow for the individualized pretreatment risk stratification in patients with mrT3 LARC. • Baseline MRI characteristics can independently stratify risk and predict survival outcomes in patients with mrT3 LARC. • The nomograms built using selected baseline MRI characteristics facilitate the individualized pretreatment risk stratification and help with clinical decision-making in patients with mrT3 LARC. • MR-defined risk factors should, therefore, be carefully reported in the baseline MRI evaluation.

Objective: Cognitive impairment is prevalent in schizophrenia. Macrophage migration inhibitory factor which is released into the circulation under stress or inflammation, is associated with cognition and also plays an important role in immunity. However, no study has investigated the relationship between macrophage migration inhibitory factor and cognitive function in first-episode schizophrenia patients at baseline or after treatment. This study investigated the pre- and post-risperidone treatment correlations between serum macrophage migration inhibitory factor levels and cognitive function in first-episode schizophrenia patients. Methods: A total of 83 first-episode schizophrenia patients who received risperidone monotherapy and 57 healthy controls – matched for sex, age, smoking status, education (years), marital status and waist-to-hip ratio – were included. Macrophage migration inhibitory factor levels were measured before and 10 weeks after treatment in the patient group and at baseline in the controls. Pre- and post-treatment cognitive functions in patients were assessed using the MATRICS Consensus Cognitive Battery. Results: At baseline, macrophage migration inhibitory factor levels were significantly higher in first-episode schizophrenia patients than those in healthy controls ( p Conclusion: Macrophage migration inhibitory factor may be involved in the process of cognitive impairment in first-episode schizophrenia and repair mechanisms following risperidone treatment.

Objective To discern the symptomatic features of coronavirus disease 2019 (COVID‐19) and to evaluate the severity and prognosis of the disease. Methods In this retrospective cohort study, 932 hospitalized patients with COVID‐19 in Wuhan were enrolled, including 52 severe and 880 non‐severe cases. All patients were followed up for 3 months after discharge. The symptomatic features and follow‐up data of the patients in both groups were analyzed and compared. Results Of the 932 patients, fever (60.0%), cough (50.8%) and fatigue (36.4%) were the most common symptoms. In total, 32.7% of the severe cases presented with gastrointestinal symptoms at disease onset, including anorexia, nausea, vomiting or diarrhea, which was significantly higher than that of the non‐severe group (P = 0.0015). The incidence of olfactory disturbance and dysgeusia was only 3.1% and 6.2%, respectively. After adjusting for age and sex, multivariate regression analysis showed that fever lasting for over 5 days (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.00‐3.62, P = 0.0498), anorexia at onset (OR 2.61, 95% CI 1.26‐5.40, P = 0.0096), and modified Medical Research Council level above grade 2 when dyspnea occurred (OR 14.19, 95% CI 7.01‐28.71, P, Clinical courses of major symptoms and duration of viral shedding from illness onset in patients hospitalized with coronavirus disease 2019.

Cloud computing provides a cost-effective deploying environment for hosting and executing workflows as its elasticity, scalability and pay-per-use model. Scientific applications are normally compute- or resource-intensive, and how to run them in the cloud while both meeting QoS of users and guaranteeing the benefits of cloud service providers (CSPs) is still a challenge and depends mainly on workflow scheduling. In this article, we propose a hybrid optimization approach, PSO+LOA, i.e., a combination of particle swarm optimization (PSO) and lion optimization algorithm (LOA) for scheduling workflows in the cloud to minimize the total execution time under budget constraints. The main contributions of our work are: (1) A Euclidean distance (ED) aware particle reposition strategy is defined for two close particles, so as to separate them away from each other, hence enhancing the capability of escaping from local optima. (2) To improve the search and convergence efficiency of original PSO, we modify the velocity update equation by introducing adaptive parameters. (3) Inspired by the multiple-swarm co-evolutionary mechanism of LOA, we integrate PSO with LOA to make a good balance between exploration and exploitation during the whole optimization process. Extensive experiments are conducted over well-known scientific workflows with different sizes and types through WorkflowSim. The experimental results demonstrate that in most cases, PSO+LOA outperforms the existing algorithms in the extent of budget constraint satisfiability, solution quality, i.e., it can generate much better solutions which meet the needs of different budget constraints, especially for large-scale applications, such as the average relative deviation index for PSO+LOA and genetic algorithm (GA) are 0.03% and 0.20%, respectively.

Atherosclerotic cardiovascular disease remains the leading cause of death among patients with diabetes. Early identification of subclinical atherosclerosis is essential for the management of diabetic patients. This study aimed to characterize serum metabolic signatures associated with carotid intima-media thickness (C-IMT), a proxy of subclinical atherosclerosis, in patients with type 2 diabetes mellitus (T2DM). After 1:1 matching by sex, age, body mass index, glycated haemoglobin A1c, and other clinical parameters, a total of 462 T2DM patients were enrolled, consisting of 231 patients with C-IMT of ≥ 1 mm (abnormal C-IMT) and 231 patients with C-IMT of

Background : : Radiographic guided percutaneous gastrostomy has become a safe and effective enteral nutrition method for patients who can not eat by mouth. Fluoroscopy, computed tomography (CT) and cone-beam CT have been routinely used clinically. The aim of this study was to compare the advantages and disadvantages of percutaneous gastrostomy using different radiographic guided methods. Methods : : We retrospectively analyzed the clinical data of 538 patients undergoing percutaneous gastrostomy in our department. According to the image guidance method used in gastrostomy, the patients were divided into groups A by fluoroscopy guidance, group B by fluoroscopy combined with C-arm CT guidance, and group C with the whole process CT guidance. The gastrostomy success rate, complication rate, procedure time, and patient radiation dose were analyzed in the three groups. Results : : Among 538 patients, 534 were successful and the success rates are 94.3%, 99.3%, and 100% in group A, B, and C, respectively (P > 0.05). There were 3 cases occurred postoperative bleeding as serious adverse events and transferred to surgical gastrostomy. The minor complications include local infection, hyperplasia of granulation tissue, tube obstruction or prolapse, and local pain of the ostomy. The minor complication rates were 10.5%, 10.4%, and 7.7% in group A, B, and C, respectively (P > 0.05). The average procedure time was 25.57 ± 5.99 minutes, 29.01 ± 6.63 minutes, and 45.47 ± 8.98 minutes, respectively (χ2 = 87.98, P < 0.001). The average radiation dosage was 27.30 ± 19.27 mGy, 145.07 ± 106.08 mGy, and 2,590.26 ± 1,088.22 mGy, respectively (χ2 = 204.44, P < 0.001). Conclusion : : There were no significant differences in the success rates and complication rates of gastrostomy under the three guiding methods. For difficult cases, CT-guided gastrostomy may be a very useful supplemental method.

Mesomorphous butterfly-like shape molecules based on benzodithiophene, benzodithiophene-4,8-dione and cyclopentadithiophen-4-one core moieties were efficiently synthesized by the Suzuki-Miyaura coupling and Scholl oxidative cyclo-dehydrogenation reactions' tandem. Most of the butterfly molecules spontaneously self-organize into columnar hexagonal mesophase. The electron-deficient systems possess strong solvent-gelling ability but are not luminescent, whereas the electron-rich terms do not form gels but strongly emit light between 400 and 600 nm. The charge carrier mobility was also measured by time-of-flight transient photocurrent technique in the mesophases for some of the compounds. They display hole-transport performances with positive charge mobility in the 10 -3 cm -2 V -1 s -1 range, consistent with the high degree of ordering and stability of the columnar superstructures. One mesogen in particular with benzodithiophen-4,8-dione core shows outstanding ambipolar charge carrier transport with both high electron (μe = 6.6×10 -3 cm -2 V -1 s -1 ) and hole (μh = 4.5×10 -3 cm -2 V -1 s -1 ) mobility values.

Background Stroke is the second leading cause of death worldwide, and 53.4% of stroke survivors suffer from post-stroke cognitive impairment. Post-stroke cognitive impairment can increase hospitalization rate and cost of care and decrease the quality of life of stroke patients. To date, multiple cognitive rehabilitation interventions have been tested in stroke populations with post-stroke cognitive impairment. However, the most efficacious intervention has not been established. This systematic review aims to compare the efficacy of cognitive rehabilitation interventions for patients with post-stroke cognitive impairment. Methods We will search MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, PubMed, and clinical trial registries to identify eligible randomized clinical trials with no restrictions in the date of publication and language. Studies conducted with patients aged 18 or over, with the presence of cognitive impairment after being diagnosed with stroke will be included. Studies will be restricted to randomized controlled trials comparing a cognitive rehabilitation intervention with another intervention. The primary outcome is any clinical changes in the general or specific cognitive domain (e.g., executive function, attention, memory, or perception). The secondary outcomes that will be collected include adverse effects (e.g., stroke, disability, or mortality) and quality of life. Two independent reviewers will assess articles to identify trials eligible for inclusion. Data extraction and risk of bias assessment of the included studies will also be done independently. Any discrepancies will be solved by discussion, or a third reviewer will be consulted if necessary. A meta-analysis will be carried out if appropriate. Discussion This systematic review for patients with post-stroke cognitive impairment will assess the efficacy of cognitive rehabilitation interventions. And our results will help clinical decision-making and support the development of clinical practice guidelines. Trial registration Systematic review registration: PROSPERO CRD42020173988

The last satellite of BeiDou Navigation Satellite System with Global Coverage (BDS-3) constellation was successfully launched on June 23rd, 2020, and the entire system began to provide Positioning, Navigation, and Timing (PNT) services worldwide. We evaluated the performance of location services using BDS with a smartphone that can track the Global Navigation Satellite System (GNSS) satellites in Nottingham, UK. The static and kinematic experiments were conducted in an open meadow and a lakeside route covered by trees, respectively. Experimental results show that BDS has good visibility, and its overall signal carrier-to-noise density ratio (C/N0) is comparable to that of Global Positioning System (GPS). The average C/N0 of BDS-3 satellites with elevation angles above 45° on B1 band is the highest among all systems, reaching 40.0 dB·Hz. The noise level of the BDS pseudorange measurements is within 0.5 m, and it has a good consistency among satellites. In the static experiment, the standard deviations of BDS positioning in the east, north and up directions are 1.09, 1.16, and 3.02 m, respectively, and the R95 value of the horizontal position is 2.88 m. In harsh environments, the number of BDS satellites tracked by the smartphone is susceptible to environmental factors. The bias Root Mean Squares (RMS) in the three directions of the whole kinematic positioning are 6.83, 6.68, 11.67 m, in which the positioning bias RMS values in a semi-open environment are only 2.81, 1.11, 3.29 m. Furthermore, the inclusion of BDS in multiple GNSS systems can significantly improve the positioning precision. This study intends to provide a reference for the further improvements of BDS global PNT services, particularly for Location-Based Services (LBS).

Objectives Convergent evidence has demonstrated that trait impulsivity, a key feature in obsessive-compulsive disorder (OCD), involves dysregulated frontal-striatal circuits. The present study aims to explore relationships between frontal-striatal circuits, trait impulsivity, and obsessive-compulsive symptoms. Methods Thirty-six unmedicated patients with OCD and 50 healthy controls (HCs) matched for age, sex, and years of education underwent a magnetic resonance imaging (MRI) procedure. Voxel-wise statistical parametric analysis was used to investigate the differences in resting-state functional connectivity between brain regions functionally connected to six pairs of a-priori defined striatal seed regions, between patients with OCD and HCs. Associations between frontal-striatal connectivity and both trait impulsivity and symptom severity of OCD were analyzed. Results The results showed altered striatal functional connectivity in OCD group compared to HCs, including increased connectivity of dorsal caudate (DC)-orbitofrontal cortex (OFC), ventral striatum (VS)-OFC, VS-medial prefrontal cortex, and putamen-sensorimotor area, and decreased functional connectivity of DC-anterior cingulate cortex (ACC), putamen-ACC, and putamen-dorsolateral prefrontal cortex (DLPFC). Furthermore, the putamen-DLPFC connectivity was negatively correlated with attentional impulsivity in the OCD group, but showed a positive correlation in HCs. Conclusions The present findings suggested that dorsal cognitive circuits could reflect the level of inhibitory control, which is balanced with the impulsive drive in healthy controls, but breakdown in OCD. Our findings supported that DLPFC-putamen connectivity underlying trait impulsivity, which were involved in the pathophysiology of OCD. The findings have provided new insights into the neurobiological mechanisms of OCD.

Environmental changes significantly affect urban ecological systems that are supported by green infrastructure. Therefore, assessment of the health of green infrastructure is virtually a quality assessment of the residential environment. For the sustainable and healthy management of urban environments, we need an effective system for estimating, diagnosing, and constructing assessment tools for green infrastructure. In this study, remote sensing technology was used to assess the green infrastructure of the Taipei metropolitan area (Taiwan) in a systematic way. To this end, we used the comprehensive index method of vigor, organization, and resilience (VOR) to classify a landscape index and to construct a healthy assessment index. We determined the primary index and weights using the entropy weighting method to establish the assessment model. We show that the core of the metropolitan area lacks green infrastructure with the lowest VOR index, thus indicating that this district requires government-supervised intervention and improvement. We prove that the increase in green infrastructure has a promoting effect on the impact of various health assessment evaluations, and it will gradually slow down and get stabilized after reaching a certain degree. The entropy weighting method can make the data model more stable and reliable, making the results more representative.

The issue of how the external integration and internal sharing of big data influence organizational innovation has attracted extensive attention worldwide. The existing literature rarely addresses the relationship between big data integration/sharing and organizational innovation from the strategic perspective at a higher level. Consequently, in this study, big data integration and sharing were employed as external and internal influencing factors to explore the origin of organizational innovation from the perspective of the mediating role of strategic learning and the moderating role of market responsiveness. Simultaneously, an online questionnaire survey was conducted to gather data from 237 research staff working in Chinese firms. The empirical analysis indicated that big data integration and sharing promoted organizational innovation. Specifically, strategic learning played a partial mediating role in the correlation between big data integration/sharing and its innovative capability. Moreover, the innovation-promoting degree of big data integration varied among organizations with market response levels. This study has specific theoretical and managerial implications.

An adversarial multi-armed bandit problem with memory constraints is studied where the memory for storing arm statistics is only in a sublinear order of the number of arms. A hierarchical learning framework that offers a sequence of operating points on the tradeoff curve between the regret order and memory complexity is developed. Its sublinear regret orders are established under both weak regret and shifting regret notions. This work appears to be the first on memory-constrained bandit problems in the adversarial setting.

As a fast and nonintrusive measurement and visualization technique, electrical capacitance tomography (ECT) is rapidly expanding its applications in the research on multiphase flow, fluidization, drying, combustion, and so on. However, the marked unevenness of the sensitivity maps sometimes causes unexpected effects in imaging reconstruction, particularly in 3-D cases. To exploit the positive potential of this phenomenon, the authors proposed an image fusion method using the data from two units of ECT sensors in this study. This method is used in image fusion on the reconstructed images for a planar sensor and a cylindrical sensor. In contrast to the conventional fusion models that use fixed weight factors for two sources of data, our model forges weight functions that are set preference the strength of the sensitivity maps. The new algorithm is implemented by first extracting the characteristic information out of the ECT images using the latent low-rank representation and then performing a fusion algorithm with linear weight functions in preference to the significance of the sensitivity maps. The simulation results show that the algorithm effectively retains the advantages of the two units of sensors and mutually compensates the weak points of theirs, and significantly improves the reconstruction quality. The fusion image quality by the new method can response the real situation better in different heights. The results imply that this data fusion method can amend the weakness of ECT cause by the uneven sensitivity maps to a significant extend.

This article reviews the development of Chinese and western translation theories. Firstly, it introduces the three stages of the development of Chinese traditional translation theory, namely, from the initial emphasis on “faithfulness” to the emphasis on “literary grace”, and then to the later debate on the priority on grace or content. Then, it focuses on the development history of western translation theory from ancient Rome to the 20th century, and summarizes two main periods, namely, the period of rhetoric aesthetics and the period of historical comparative linguistics. The former period began with Cicero, who was deeply influenced by Plato, and in turn influenced the later Bible translation and literary translation; the latter period was divided into two stages: before 1950s, it was mainly influenced by structuralist linguistics, and after 1950s, it was profoundly influenced by emerging language schools and modern ideological trends. Through these introductions, it presents the macro framework of the development history of Chinese and western translation theories.

We consider the problem of anomaly detection among a large number of processes, where the probabilistic models of anomalies are unknown. At each time, aggregated noisy observations can be taken from a chosen subset of processes, where the chosen subset conforms to a tree structure. The observation distribution depends on the chosen subset and the absence/presence of anomalies. We develop a sequential search strategy using a hierarchical Kolmogorov-Smirnov (KS) statistics. Referred to as Tree-based Anomaly Search using KS statistics (TASKS), the proposed strategy is order-optimal with respect to the size of the search space and the detection accuracy.

Tomb murals are the special kind of murals that are buried underground. Due to the narrow exit of the tomb passage, the tomb murals were excavated by dividing the whole mural into blocks, which made lots of information missing between the blocks. The digital restoration technology Image inpainting uses the edge information around the missing parts to spread the information inside of the defect area and fills the information from the outside to the inside. But it is not suitable for filling the missing parts between the tomb mural blocks. Because these parts are large for exemplar-based inpainting which may make texture dislocation and for PDE which may make cartoon blur. It is a need to generate the information outwards to complete the information. The generative adversarial network uses deep learning training by the murals remains to generate the information from inside to outside, but the typical GAN doesn‘t have a good nonlinear feature. This paper provided a generating technology based on the deep convolution generative adversarial network to rebuild the missing information between the tomb mural blocks. It built the training data set of the simulation platform with Keras and designed a whole mural generation scheme based on DCGAN. In order to get better generated results to avoid the bad artifacts; it adds the nonlinear layers by choosing 13 layers convolution and 2 deconvolution layers of the generator and contained 5 layers convolution discriminator; it designed a new phased nonlinear loss function by using Pycharm pretreatment for Numpy array file data sets; finally, it completed the generate tomb mural information to obtain the good simulation effect.

Elevated intracranial pressure due to cerebral edema is associated with very poor survival in patients with acute liver failure (ALF). Placing an intracranial pressure monitor (ICPm) aids in management of intracranial hypertension, but is associated with potentially fatal hemorrhagic complications related to the severe coagulopathy associated with ALF. An institutional Acute Liver Failure Clinical Protocol (ALF-CP) was created to correct ALF coagulopathy prior to placing parenchymal ICP monitoring bolts. We aimed to investigate the frequency, severity, and clinical significance of hemorrhagic complications associated with ICPm bolt placement in the setting of an ALF-CP. All assessed patients were managed with the ALF-CP and had rigorous radiologic follow-up allowing assessment of the occurrence and chronology of hemorrhagic complications. We also aimed to compare our outcomes to other studies that were identified through a comprehensive review of the literature. Fourteen ALF patients were included in our analysis. There was no symptomatic hemorrhage after ICP monitor placement though four patients were found to have minor intraparenchymal asymptomatic hemorrhages after liver transplant when the ICP monitor had been removed, making the rate of radiographically identified clinically asymptomatic hemorrhage 28.6%. These results compare favorably to those found in a comprehensive review of the literature which revealed rates as high as 17.5% for symptomatic hemorrhages and 30.4% for asymptomatic hemorrhage. This study suggests that an intraparenchymal ICPm can be placed safely in tertiary referral centers which utilize a protocol such as the ALF-CP that aggressively corrects coagulopathy. The ALF-CP led to advantageous outcomes for ICPm placement with a 0% rate of symptomatic and low rate of asymptomatic hemorrhagic complications, which compares well to results reported in other series. A strict ICPm placement protocol in this setting facilitates management of ALF patients with cerebral edema during the wait time to transplantation or spontaneous recovery.

Lung cancer is the leading cause of cancer death worldwide. Although diagnostic methods and targeted drugs have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of lung cancer remain enigmatic. The N6-methyladenosine (m6 A) modification is the most common modification of messenger RNA in eukaryotes and plays critical roles in many diseases, especially cancers. Ectopic m6 A modification is associated with human carcinogenesis, including lung cancer. The m6 A modification is mediated by methyltransferases (writers) and demethylases (erasers) and indirectly affects biological processes through the recruitment of specific reader proteins (readers). Many studies have shown that m6 A writers, erasers, and readers serve as specific and sensitive biomarkers for lung cancer diagnosis, prognosis, and therapy. This review summarizes recent studies on the biological functions of the m6 A modification in lung cancer and discusses the potential application of m6 A regulators in lung cancer diagnosis and therapeutics.

Background Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff‐Parkinson‐White (WPW) syndrome and paroxysmal AF, in other patients it can recur. Hypothesis Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. Methods We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P‐wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12‐lead electrocardiography (ECG). Results During the mean follow‐up period of 30.9 ± 9.2 months (range, 3‐36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26‐1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). Conclusions PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12‐lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Compartment syndrome is caused by increased pressure within fascial compartment. We present a unique case of a thigh compartment syndrome that occurred after overnight catheter delivered Tissue plasminogen activator (tPA) thrombolysis of an acutely thrombosis femoral-to above knee popliteal artery Propaten® PTFE (WL Gore & Associates, Flagstaff, AZ) bypass graft. The condition was treated by emergency fasciotomy and the patient recovered uneventfully.

Background Overtreatment and overuse of resources are leading causes of rising health care costs. Identification and elimination process of low value services is important in reducing such costs. At many institutions it is routine to send excised plaque after carotid endarterectomy (CEA) for pathology evaluation. With more than 140,000 CEAs performed annually in the United States, this represents an opportunity for potential cost savings. We set out to examine the cost and clinical use of pathology evaluation of plaque after CEA. Methods We performed a retrospective review of patients undergoing CEA at a single institution from 2016 to 2019. Patients were excluded if they had a prolonged postoperative length of stay or if they had a preoperative stroke. Demographics, perioperative outcomes, and billing costs were recorded. Results We identified 82 total CEAs, of which 42 were excluded according to the aforementioned exclusion criteria. We reviewed 40 CEAs. Mean age of this cohort was 67.2 (±8.3) years. Most (72.5%) were asymptomatic at the time of admission, whereas 27.5% presented with a transient ischemic attack. Mean postoperative length of stay was 1.8 days. The primary insurers were 39.5% private, 39.5% Medicare, and 21.1% Medicaid. Mean total charges for the hospitalization were $83,367 (±$42,874). Of this total, professional fees were $3,512 (±$980) and facility fees were $80,395 (±$42,886). Mean pathology charges were $285 (±$88). The pathology professional fee was $61 (±$27), which represented 1.82% (±0.88) of the professional costs. Reimbursement for the facility pathology charge was $229 (±$57) and for the professional pathology charge was $25 (±$14). All plaque samples were submitted for gross examination and hematoxylin and eosin staining. The correlation rate for the clinical and pathologic diagnosis was 100%. The pathology reports simply read “atherosclerotic plaque” and “calcific plaque” in 32.5% and 45% of samples. For the remaining plaques, 12.5% and 10% of reports also noted fibrosis and degenerative changes, respectively. There were no clinical implications or decisions made based on the pathology reports. Cost of pathology evaluation was on average $285, with an average reimbursement of $235. With 140,000 CEAs done annually, this represents a potential $32.9–$39.9 million saved to the health care system. Conclusions Pathology evaluation of carotid plaque incurs significant costs to the health care system with no clear value for the postoperative care of the patient. Hospital policy regarding mandatory pathologic examination and surgeon preferences regarding plaque analysis should be more closely examined.

Inflammatory bowel disease (IBD) is a group of chronic and recurrent nonspecific inflammatory disorders, including Crohn's disease (CD) and ulcerative colitis (UC). Due to the persistent inflammation of intestinal mucosa caused by immune disorders, barrier dysfunction may be an essential cause of the pathogenesis of IBD. Therefore, exploring the mechanism is very important to clarify the pathogenesis of IBD. In our research, we provided evidence of IL-21 function in IBD. The junction complex protein claudin-5 may be a downstream gene of the IL-21. Anti-IL-21 administrated prevented DSS-simulative colitis via recovering claudin-5 expression in the human colonic epithelial cells. Meanwhile, we described that miR-423-5p could be involved in IL-21/ claudin-5 pathway by regulating NF-κB/MAPKs/JNK signaling pathway, which may provide a new therapeutic target for IBD.

Surface plasmons (SPs) of metals enable the tight focusing and strong absorption of light to realize an efficient utilization of photons at nanoscale. In particular, the SP-generated hot carriers have emerged as a promising way to efficiently drive photochemical and photoelectric processes under moderate conditions. In situ measuring of the transport process and spatial distribution of hot carriers in real space is crucial to efficiently capture the hot carriers. Here, we use electrochemical tip-enhanced Raman spectroscopy (EC-TERS) to in situ monitor an SP-driven decarboxylation and resolve the spatial distribution of hot carriers with a nanometer spatial resolution. The transport distance of about 20 nm for the reactive hot carriers is obtained from the TERS imaging result. The hot carriers with a higher energy have a shorter transport distance. These conclusions can be guides for the design and arrangement of reactants and devices to efficiently make use of plasmonic hot carriers., Revealing the spatial distribution of hot carriers in real space is crucial to their efficient utilization. Here, the authors show that in-situ electrochemical tip-enhanced Raman spectroscopy is able to resolve the spatial distribution of reactive hot carriers with a nanometer spatial resolution.

Face detection has been deployed on edge devices as the basis for face applications, but the devices cannot store large-scale models and have low computing power. The existing anchor-based face detection schemes cannot cover face images over a continuous size range, and their performance is not satisfactory. Obviously, good performances are accompanied by increased storage and lower speed. We find that the feature points in different layers correspond to a specific size range of RFs (receptive fields). According to the survey, the predictable range of RFs with the same size is the face on a continuous scale. Therefore, we argue that RFs are inherent anchors. A Light and Fast Face Detector with an Ommateum Structure (OS-LFFD) is proposed in this paper. By analyzing the correlation between the effective receptive field (ERF) and face sizes, a 4-branch network is designed to cover the objective range of face sizes. Each branch involves an ommateum block with a similar structure and shared parameters. It reduces the number of model parameters (8 M), which makes it much smaller than most face detectors. Experiments on the popular benchmarks WIDER FACE and FDDB using multiple hardware platforms demonstrate that the proposed scheme can considerably balance the accuracy and running speed.

To investigate the correlation between gingival phenotype and craniofacial profile and to evaluate the morphology of periodontal supporting tissues in the maxillary and mandibular anterior zones. A total of 66 patients with 264 central incisors in good periodontal health were included in this cross-sectional study. CBCT images were used to assess gingiva and alveolar bone thickness of the maxillary and mandibular incisors at four vertical levels. Cephalometric analysis was used to assess the sagittal profile of the craniofacial structures. Gingival thickness was compared in patients with different craniofacial profiles based on ANB value. Linear regression coefficients adjusted by age and gender were used to evaluate the correlation between gingival thickness and the cephalometric parameters. Individuals with a smaller ANB value (ANB

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive joint disease. To date, the etiology and pathogenesis of RA have not been fully elucidated, but a large number of studies have indicated that hypoxia is an important feature of RA. Our study was designed to probe how hypoxia-induced exosome (exo) derived from synovial fibroblasts (SFs) affect RA. In this study, we found that hypoxic environment existed in synovial tissue of RA, and miR-424 expression was increased in RA, and exosome derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation, which Th17 cells increased and Treg cells decreased. Besides, SFs-exo affected the expression of related inflammatory cytokines. And, we also found that FOXP3 was a target gene of miR-424 and exo-miR-424 KD inhibited RA worsening. These results suggested that SFs-exo in hypoxia aggravates rheumatoid arthritis by regulating Treg/Th17 balance and thus may be a potential therapeutic target for RA. Impact statement A comparative study of osteoarthritis (OA) and RA mice was implemented to suggest that miR-424 expression was increased in RA, and exosome-miR-424 derived from synovial fibroblasts (SFs-exo) could significantly induce T cells differentiation in which Th17 cells increased and Treg cells decreased via targeting FOXP3. And thus, miR-424 may be a potential therapeutic target for RA.

Background Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points. Methods Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions. Results In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. Conclusion Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.

Purpose Pancreatic cancer (PC) has poor prognosis despite systemic treatment. Dehydrogenase/reductase member 9 (DHRS9) has been reported to be involved in many events of tumorigenesis, but its prognostic impact in PC remains undetermined. Thus, this study aimed to explore the association between DHRS9 expression and the prognosis of PC and investigate the possible mechanism by which DHRS9 is involved in PC progression. Patients and Methods The study used data: from Gene Expression Omnibus (GEO) and our institution to compare the DHRS9 expression between PC and adjacent normal tissues; from The Cancer Genome Atlas (TCGA) and our institution to assess the clinicopathological characteristics and prognosis of PC patients in high and low DHRS9 expression groups; and from TCGA to predict the potential mechanism of DHRS9 in PC. Western blot assay was used to identify DHRS9 expression in specimens collected from five patients who underwent surgery in our institute. Furthermore, immunohistochemistry (IHC) was then used to identify DHRS9 expression in the specimens of 109 patients who underwent surgery at our institute. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of DHRS9 expression among PC patients. Results All the IHC, Western blot, and GEO datasets indicated that compared to normal tissues, DHRS9 was significantly overexpressed in PC tissues. IHC results demonstrated that the strong intensity of DHRS9 expression was significantly correlated with vascular infiltration (P < 0.05). Further, high DHRS9 expression was identified as a prognostic risk factor for overall survival. Functional analysis of DHRS9 co-expressed genes indicated that DHRS9 was involved in mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Conclusion DHRS9 is upregulated in PC tissue, and high DHRS9 expression is correlated with poor prognosis in PC. DHRS9 may affect the oncological process of PC through MAPK/ERK pathway.

Background and aim Secreted frizzled-related protein 2 (sFRP2) has been reported to be involved in cardiovascular diseases. However, its role in cardiac hypertrophy induced by pressure overload is still elusive. We aimed to examine the role of sFRP2 in the development of cardiac hypertrophy in vivo and in vitro. Methods and results Following cardiac hypertrophy stimulated by aortic banding (AB), the expression of sFRP2 was downregulated in the hypertrophic ventricle. Adeno-associated virus 9 (AAV9) was injected through the tail vein to overexpress sFRP2 in the mouse myocardium. Overexpression of sFRP2 alleviated cardiomyocyte hypertrophy and interstitial fibrosis, as identified by the reduced cardiomyocyte cross-sectional area, heart weight/body weight ratio, and left ventricular (LV) collagen ratio. Additionally, sFRP2 decreased cardiomyocyte apoptosis induced by pressure overload. Western blot showed that sFRP2 prevented the expression of active β-catenin. The Wnt/β-catenin agonist LiCl (1 mmol/kg) abolished the inhibitory effects of sFRP2 on cardiac hypertrophy and apoptosis, as evidenced by the increased cross-sectional area and LV collagen ratio and the deterioration of echocardiographic data. Conclusion Our study indicated that decreased sFRP2 levels were observed in failing mouse hearts. Overexpression of sFRP2 attenuated myocyte hypertrophy and interstitial fibrosis induced by hypertrophic stimuli by inhibiting the Wnt/β-catenin pathway. We revealed that sFRP2 may be a promising therapeutic target for the development of cardiac remodeling. Electronic supplementary material The online version of this article (10.1007/s11010-020-03802-x) contains supplementary material, which is available to authorized users.

The growing demand for the meaningful use of electronic medical records has led to great interest in medical entities and relation extraction technologies. Most existing methods perform relation extraction based on manually labeled documents and rarely consider incorporating knowledge graphs that include rich, valuable structured knowledge, which will cause semantic ambiguities. To address this problem, we propose a knowledge-enhanced relation extraction (KERE) model. First, we extract knowledge information from the knowledge graph to generate a knowledge-guided word embedding. Then, the lexical features are considered supplementary information for semantic understanding. Experiments on real-world datasets show that the KERE model achieves important improvements in a biomedical relation extraction task.

To determine the cause of death, in addition to routine autopsy, some assisted techniques are imperative to achieve a definite diagnosis. Herein, we report a case of 36-year-old man who was found dead in his apartment. Medical drug containers (potassium chloride, zolpidem, and propofol) and medical instruments (syringes and indwelling needles) were also found at the scene. An autopsy revealed large amounts of whitish foamy and brown liquid in the trachea and bronchi, and histopathological findings showed remarkable pulmonary congestion and edema. An injection mark with hemorrhage on the right wrist was found on external examination. Results of forensic pathology excluded the presence of mechanical injuries, mechanical asphyxia, embolism, and other fatal diseases. The data of toxicological analysis showed that concentrations of zolpidem and propofol in blood were appreciably higher than the therapeutic dose but they did not reach the absolute lethal dose. Moreover, the level of potassium in the blood and vitreous humor was higher than the expected concentration after death. A scanning electron microscope (SEM) combined with energy-dispersive X-ray microanalyzer (EDX) was subsequently applied to assess the skin samples collected from bilateral wrists. Ultrastructural observation discovered continuous visible interruption of the skin around the injection mark, and energy spectrum analysis revealed statistically significantly higher potassium content of the skin over the right wrist than the left wrist. Comprehensive analysis concluded that the deceased had died of potassium chloride intravenous injection under the zolpidem and propofol effects.