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Statement of problem Strontium has been validated for potent bone-seeking and antiosteoporotic properties and elicits a potentially beneficial impact on implant osseointegration in patients with osteoporosis. However, the efficacy of strontium supplementation on improving new bone formation and implant osseointegration in the presence of osteoporotic bone is still unclear. Purpose The purpose of this systematic review was to comprehensively assess the efficacy of strontium supplementation, encompassing oral intake and local delivery of strontium, on implant osseointegration in patients with osteoporosis. Material and methods Searches on electronic databases (MEDLINE or PubMed, Web of Science, EBSCO, Embase, and Clinicaltrials.gov ) and manual searches were conducted to identify relevant preclinical animal trials up to June 2020. The primary outcomes were the percentage of bone-implant contact and bone area; the secondary outcomes were quantitative parameters of biomechanical tests and microcomputed tomography (μCT). Results Fourteen preclinical trials (1 rabbit, 1 sheep, and 12 rat), with a total of 404 ovariectomized animals and 798 implants, were eligible for analysis. The results revealed a significant 17.1% increase in bone-implant contact and 13.5% increase in bone area, favoring strontium supplementation despite considerable heterogeneity. Subgroup analyses of both bone-implant contact and bone area exhibited similar outcomes with low to moderate heterogeneity. Results of biomechanical and μCT tests showed that strontium-enriched implantation tended to optimize the mechanical strength and microarchitecture of newly formed bone despite moderate to generally high heterogeneity. Conclusions Based on the available preclinical evidence, strontium supplementation, including local and systemic delivery, showed promising results for enhancing implant osseointegration in the presence of osteoporosis during 4 to 12 weeks of healing. Future well-designed standardized studies are necessary to validate the efficacy and safety of strontium supplementation and to establish a standard methodology for incorporating Sr into implant surfaces in a clinical setting.

Unmanned aerial vehicles (UAVs) serve as aerial base stations to provide controlled wireless connections for ground users. Due to their constraints on both mobility and energy consumption, a key problem is how to deploy UAVs adaptively in a geographic area with changing traffic demand of mobile users, while meeting the aforementioned constraints. In this paper, we propose a QoE-driven and energy-efficient adaptive deployment strategy for multi-UAV networks based on hybrid deep reinforcement learning to solve the problem of incomplete information game, where the UAVs can adjust their moving directions and distance to serve users who move randomly in the target area. Through the hybrid deep reinforcement learning with centralized training and distributed testing, UAVs can be trained offline to obtain the global state information and learn a completely distributed control strategy, with which each UAV only needs to take actions based on its observed state in the real deployment to be fully adaptive. Moreover, in order to improve the speed and effect of learning, we improve hybrid reinforcement learning, by adding genetic algorithms and TD-error-based resampling optimization mechanism. Simulation results show that the hybrid deep reinforcement learning algorithm has better efficiency and robustness in multi-UAV control, and has better performance in terms of QoE, energy consumption and average throughput, by which average throughput can be increased by 20% to 60%.

Purpose: Triple-negative breast cancer (TNBC) is a highly heterogeneous disease. Patients with early-stage TNBCs have distinct likelihood of distant recurrence. Current therapeutic guidance is still limited.Methods: We extracted transcriptome data for 189 pathologically confirmed pT1-2N0M0 TNBC patients at Fudan University Shanghai Cancer Center. Candidate mRNAs were filtered, which was followed by differential expressed mRNAs analysis, survival analysis, and LASSO Cox regression model. All-subsets regression program was used for constructing a multi-mRNA signature in the training set (n=159); the accuracy and prognostic value were then validated using an independent validation set (n=158). Results: Here, we profiled the transcriptome data from 189 early-stage TNBC patients along with 50 paired normal tissues. Early-stage TNBCs are featured of basal-like and immune-suppressed subtype and homologous recombination ability deficiency. We developed a prognostic signature contained seven mRNAs from transcriptome data (ACAN, KRT5, TMEM101, LCA5, RPP40, LAGE3, CDKL2). In both the training (n=159) and validation cohorts (n=158), the signature could identify patients with relatively high recurrence risks and serve as an independent prognostic factor. The signature had better prognostic value than traditional clinicopathological features in both sets. Among the seven mRNAs, TMEM101 is highly expressed in TNBC and represents a potential therapeutic target. Inhibition of TMEM101 impaired tumor progression.Conclusions: Our 7-mRNA signature could accurately predict recurrence risks of early-stage TNBCs. Clinical and genomic low risk TNBC patients may have the opportunity to avoid adjuvant chemotherapy

As customers take virtual machines (VMs) as their demands, high-efficient placement of VMs is required to reduce the energy consumption in data centers. Existing Virtual Machine placement (VMP) strategies can minimize energy consumption of data centers by optimizing resource allocation in terms of multiple physical resources (e.g., memory, bandwidth, CPU, etc.). However, these strategies ignore the role of heat recirculation in the data center, which can cause a huge energy waste in cooling. To address this problem, we propose a heat-recirculation-aware VMP strategy for reducing the energy consumption of data centers. This novel VMP strategy takes into account heat recirculation coupled with multiple physical resource allocation to reduce the energy consumption of data centers. We design a simulated annealing based algorithm called SABA to lower the energy consumption of data centers where multiple VMs are deployed. SABA remarkably cuts down the energy consumption of physical resources through two salient features. First, it obtains an approximation of the optimum with much fewer iterations than simulated annealing algorithm (SA). Second, it reduces the number of activated servers required for VM tasks. We quantitatively evaluate the performance of SABA in terms of algorithm efficiency, the number of activated servers and the energy-saving. We compare the performance of SABA with state-of-art XINT-GA, PPVMP, TSTD and SA algorithms. Moreover, we evaluate the efficiency of SABA by leveraging a real-world 50 hours trace from practical IBM cloud data centers. Experimental results indicate that our heat-recirculation-aware VM placement strategy provides a powerful solution for improving the energy efficiency of data centers (SABA improves energy efficiency of cooling by up to 13.2% over TSTD, 13.8% over XINT-GA and 45% over PPVMP algorithm).

Background: Primary biliary cholangitis (PBC) is a complex disease with high heritability. We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and PBC in families and sporadic cases to evaluate the genetic components of the disease. Methods: We performed whole exome sequencing in three PBC families. We genotyped HLA-DRB1 and calculated the association between HLA-DRB1 alleles and the encoding amino acid sequences with the clinical features. Results: Ten variants harboured the HLA-DRB1 gene associated with PBC. DRB1 x07:01, 14:01 and 14:05 were highly increased in PBC. Ten coding region polymorphisms were associated with PBC that encode the amino acid variants of HLA-DR beta 54, beta 59 and beta 66 located in the peptide-binding site of the MHC molecule. Glutamine at position 54 was confirmed as a risk amino acid, verifying the results of familial aggregation analysis of PBC families. Discussion: Familial aggregation analysis indicated that HLA-DRB1 is a candidate gene for the risk of disease course. Considering that amino acid variations are critical to peptide-binding properties, they underlie the major component of MHC association with PBC. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Context Light therapy is a non-pharmacological therapy that is currently being studied in cancer-related symptoms and is certificated as a low-risk intervention by FDA. Cancer-related fatigue (CRF) is the most common symptom reported by cancer patients. Objective To examine the effectiveness of light therapy for CRF in cancer patients through a systematic review and meta-analysis. Methods We conducted a systematic review of four electronic databases targeted randomized clinical trials evaluating light therapy for CRF (CRD42020215446), from inception to May 2021. The primary outcome was changes of CRF scores; secondary outcomes included depression, sleep, and quality of life (QoL). We quantitatively pooled outcomes using meta-analysis with random-effects models and assessed methodological bias. Results We identified thirteen RCTs representing 551 cancer patients, encompassing breast (n = 5), ovarian or endometrial (n = 1), multiple myeloma (n = 1), lung (n = 1), or combined (n = 5) cancers. The comparison groups included dim light (n = 12) and waiting list (n = 1). Duration of intervention ranged from 1 to 12 weeks. Light intensities ranged from 417.9 to 12,000 lux. Light therapy was associated with a significant improvement in CRF (SMD = 0.45, P = 0.007), depression (SMD = -0.26, P = 0.03) and sleep difficulty (SMD = -2.46, P = 0.0006); a statistically non-significant trend was observed for QoL (SMD = 0.33, P = 0.09). Funnel plots for CRF suggest not significant publication bias. Conclusion Light therapy could be a feasible and effective option for improving CRF in cancer patients. Larger sample, rigor trials design and a standard protocol of intervention are needed to draw more conclusive conclusions.

Drusen is considered as the landmark for diagnosis of AMD and important risk factor for the development of AMD. Therefore, accurate segmentation of drusen in retinal OCT images is crucial for early diagnosis of AMD. However, drusen segmentation in retinal OCT images is still very challenging due to the large variations in size and shape of drusen, blurred boundaries, and speckle noise interference. Moreover, the lack of OCT dataset with pixel-level annotation is also a vital factor hindering the improvement of drusen segmentation accuracy. To solve these problems, a novel multi-scale transformer global attention network (MsTGANet) is proposed for drusen segmentation in retinal OCT images. In MsTGANet, which is based on U-Shape architecture, a novel multi-scale transformer non-local (MsTNL) module is designed and inserted into the top of encoder path, aiming at capturing multi-scale non-local features with long-range dependencies from different layers of encoder. Meanwhile, a novel multi-semantic global channel and spatial joint attention module (MsGCS) between encoder and decoder is proposed to guide the model to fuse different semantic features, thereby improving the model's ability to learn multi-semantic global contextual information. Furthermore, to alleviate the shortage of labeled data, we propose a novel semi-supervised version of MsTGANet (Semi-MsTGANet) based on pseudo-labeled data augmentation strategy, which can leverage a large amount of unlabeled data to further improve the segmentation performance. Finally, comprehensive experiments are conducted to evaluate the performance of the proposed MsTGANet and Semi-MsTGANet. The experimental results show that our proposed methods achieve better segmentation accuracy than other state-of-the-art CNN-based methods.

Raw optical coherence tomography (OCT) images typically are of low quality because speckle noise blurs retinal structures, severely compromising visual quality and degrading performances of subsequent image analysis tasks. In our previous study (Ma et al., 2018), we have developed a Conditional Generative Adversarial Network (cGAN) for speckle noise removal in OCT images collected by several commercial OCT scanners, which we collectively refer to as scanner T. In this paper, we improve the cGAN model and apply it to our in-house OCT scanner (scanner B) for speckle noise suppression. The proposed model consists of two steps: 1) We train a Cycle-Consistent GAN (CycleGAN) to learn style transfer between two OCT image datasets collected by different scanners. The purpose of the CycleGAN is to leverage the ground truth dataset created in our previous study. 2) We train a mini-cGAN model based on the PatchGAN mechanism with the ground truth dataset to suppress speckle noise in OCT images. After training, we first apply the CycleGAN model to convert raw images collected by scanner B to match the style of the images from scanner T, and subsequently use the mini-cGAN model to suppress speckle noise in the style transferred images. We evaluate the proposed method on a dataset collected by scanner B. Experimental results show that the improved model outperforms our previous method and other state-of-the-art models in speckle noise removal, retinal structure preservation and contrast enhancement.

Radiotherapy (RT) is a major modality of postoperative treatment in breast cancer. The maximal standardized value (SUVmax) is 18FDG-PET/CT derived parameter that reported to be a valuable prognostic factor in cancer patients. Herein, we aimed to identify a prognostic gene signature associated with glucose uptake for breast cancer patients after RT by leveraging the mRNA expression profiling on public datasets. The glucose uptake signature was constructed using the single sample gene set enrichment analysis (ssGSEA) algorithm and evaluated in GSE21217 where SUVmax value was measured by PET-CT directly. The prognostic value was validated in three post-RT breast cancer cohorts (GSE103744, NKI, and FUSCC databases). The patients were stratified into glucose uptake signature score-high and low groups. Patients with a higher score had worse survival than those with a lower score. Mechanistically, the glucose uptake signature was calculated in each cell type of a single-cell RNA-seq database from five breast cancer patients. Glucose uptake signature score was significantly elevated in the malignant epithelial cells compared with normal ones. The immunosuppression markers including PDCD1, TIGIT, LAG3, and HAVCR2 were significantly upregulated in the T cells bearing a high glucose uptake signature score. Collectively, our results demonstrated the potential prognostic value of a glucose uptake signature in the post-RT breast cancer patients., Graphical abstract, A glucose uptake gene signature was constructed and validated to predict survival in radiotherapy-treated breast cancer patients. The correlation between this gene signature and immunosuppressive markers has been explored.

Metastatic breast cancer is a leading health burden worldwide. Previous studies have shown that metadherin (MTDH) promotes breast cancer initiation, metastasis and therapy resistance; however, the therapeutic potential of targeting MTDH remains largely unexplored. Here, we used genetically modified mice and demonstrate that genetic ablation of Mtdh inhibits breast cancer development through disrupting the interaction with staphylococcal nuclease domain-containing 1 (SND1), which is required to sustain breast cancer progression in established tumors. We performed a small-molecule compound screening to identify a class of specific inhibitors that disrupts the protein–protein interaction (PPI) between MTDH and SND1 and show that our lead candidate compounds C26-A2 and C26-A6 suppressed tumor growth and metastasis and enhanced chemotherapy sensitivity in preclinical models of triple-negative breast cancer (TNBC). Our results demonstrate a significant therapeutic potential in targeting the MTDH–SND1 complex and identify a new class of therapeutic agents for metastatic breast cancer. Kang and colleagues identify a specific compound blocking MTDH1–SND1 interaction, which prevents metastatic breast cancer progression, induces regression of established metastasis in preclinical models and restores chemosensitivity.

Despite increased overall survival rates, curative options for metastatic breast cancer remain limited. We have previously shown that metadherin (MTDH) is frequently overexpressed in poor prognosis breast cancer, where it promotes metastasis and therapy resistance through its interaction with staphylococcal nuclease domain-containing 1 (SND1). Through genetic and pharmacological targeting of the MTDH–SND1 interaction, we reveal a key role for this complex in suppressing antitumor T cell responses in breast cancer. The MTDH–SND1 complex reduces tumor antigen presentation and inhibits T cell infiltration and activation by binding to and destabilizing Tap1/2 messenger RNAs, which encode key components of the antigen-presentation machinery. Following small-molecule compound C26-A6 treatment to disrupt the MTDH–SND1 complex, we showed enhanced immune surveillance and sensitivity to anti-programmed cell death protein 1 therapy in preclinical models of metastatic breast cancer, in support of this combination therapy as a viable approach to increase immune-checkpoint blockade therapy responses in metastatic breast cancer. Kang and colleagues demonstrate that pharmacological targeting of the MTDH1–SND1 axis prevents immune evasion during metastatic progression and provides a synergistic combination strategy with immune-checkpoint blockade to treat metastasis.

Immunohistochemical analysis has become an integral component in the diagnostic work up of hematopoietic neoplasms. It is not uncommon that visualization of single protein expression by immunohistochemistry among cells of interest may become a difficult task. Common scenarios of such include extensive colonization of germinal centers in the differential diagnosis of marginal zone lymphoma and follicular lymphoma, low-level bone marrow involvement by lymphoma and paucity of neoplastic lymphocytes in the setting of numerous background reactive lymphocytes, among others. For this reason, we have developed a variety of easy-to-employ dual-color dual-antibody immunohistochemical assays to aid in solving these diagnostic dilemmas. Herein, we share examples of our use of dual immunohistochemistry to illustrate its beneficial and practical objective.

The soil inhabits many microbes, including plant parasitic nematodes. Plant parasitic nematodes are reported to cause substantial damage to crops which results in yield and economic losses. Chemical control is the most widely used method to control plant parasitic nematodes. However, the consequences of synthetic chemicals are detrimental to human health, animals, and the environment and face so many strict regulatory measures. Synthetic chemicals are also not reliable with their inability to provide long-term protection. Many studies have shown that the use of beneficial fungi and bacteria has the potential to prevent and suppress plant parasitic nematodes while keeping the environment safe. Several experiments have demonstrated that bioproducts of microbial origin are cheap, safe, and provide long-lasting biocontrol effects against pathogens both in vitro and field conditions. Therefore, this review aims to discuss mechanisms that beneficial microbes and their products use to successfully suppress plant parasitic nematodes. The review also explains the importance of using commercial bionematicides in the sustainable management of plant parasitic nematodes. The existing challenges that are limiting the full application of beneficial microbes, and what needs to be done to fully utilize biocontrol agents in the management of plant parasitic nematodes have also been discussed. To the best of our knowledge, this review has come at the right time to give researchers and plant growers more options when several synthetic chemical nematicides are being banned by regulatory authorities due to their hazardous effects.

The most serious and common complication of the medication recommended by World Health Organization (WHO) for tuberculosis (TB) is anti-tuberculosis drugs-induced hepatotoxicity (ATDH). Pregnane X receptor (PXR) is a key factor of ATDH, while Hepatocyte nuclear factor 4α (HNF4α) and hepatocyte nuclear factor 4 alpha-antisense-1 (HNF4α-AS1) may have co-regulating relationship with PXR. This study aimed to explore whether the genetic variants of HNF4α and HNF4α-AS1 are associated with the predisposition of ATDH.TB patients diagnosed in West China Hospital between December 2014 and April 2018 were enrolled. TagSNPs in HNF4α and HNF4α-AS1 gene from the samples of the patients were genotyped with a custom-designed 2×48-plex SNP ScanTM Kit. The frequencies of the alleles, genotypes, genetic models and haplotype distribution of the variants were compared between the case and control groups. The association between SNP and ATDH risk was assessed by single factor logistic regression.Logistic regression analysis showed that none of the 15 genetic variants in HNF4α and HNF4α-AS1 genes were significantly associated with susceptibility to ATDH in the Chinese Han population after Bonferroni correction.A challenge has arisen to the promising application of SNPs in the HNF4α and HNF4α-AS1 genes as genetic markers for ATDH, and further study is needed with a larger sample size.

We noticed an unusual increase of aged adults in first-episode schizophrenia in January and February 2020 since the outbreak of COVID-19. This retrospective study aims to statistically validate this observation and find potential risk factors, if applicable. The demographics of schizophrenia in outpatients (both first-episode and follow-up) from January to March 2020 (36,624 records) and similar periods of 2017-2019 (114,141 records) were analyzed and compared to minimize seasonal influence. Limited personal information (age, gender, approximate residence) was investigated to find risk factors. After considering seasonal factors such as the Spring festival, the age of the first-episode schizophrenia was significantly increased in January (46.60 ± 15.14) and February (51.53 ± 14.74) but went back to normal in March 2020 (38.89 ± 14.59), compared with similar periods from 2017 to 2019 (Jan., 40.77 ± 15.26; Feb., 39.69 ± 15.10; Mar., 42.04 ± 15.83). Meanwhile, a slight but not significant change was found in the distribution of gender and approximate residence (urban/suburb). Our data supported that risk of first-episode schizophrenia in aged adults increased during the COVID-19 outbreak, which is consistent with the fact that COVID-19 is more lethal to elders. Public healthcare should prepare in advance for potential risks in public mental health, especially for elders.

Background Severe community-acquired pneumonia (SCAP) is a serious health threat in elderly individuals, and a prospective, observational study was conducted to explore the prognostic factors. Methods Patients (≥65 years old) with SCAP that had an intensive care unit (ICU) stay >24 h were recruited at our center. Clinical and laboratory data were collected and various assessment scores were calculated. The follow-up period was censored at the date of death or at hospital discharge, whichever came first. Results A total of 120 elderly patients with SCAP were included. Among them, 61 were cured (survival group) and 59 died due to SCAP (mortality group). Multivariate logistic regression analysis showed that chronic obstructive pulmonary disorder (COPD, β=2.061, P=0.008) and CD3+CD4+ T cell count (β=-0.019, P=0.017) were independent prognostic factors for death in elderly patients with SCAP. The area under the receiver operating characteristic (ROC) curve (AUROC) for the age- and gender-adjusted model was estimated to be 0.915 [95% confidence interval (CI): 0.858-0.972] for mortality, and the sensitivity and specificity of the model were 91.53% and 86.89%, respectively. Conclusions Our findings suggest that COPD and the CD3+CD4+ T cell count are independent prognostic factors for mortality, and the constructed model was moderately accurate in the prediction of mortality for elderly patients with SCAP.

The success of deep learning has led to a rising interest in the generalization property of the stochastic gradient descent (SGD) method, and stability is one popular approach to study it. Existing generalization bounds based on stability do not incorporate the interplay between the optimization of SGD and the underlying data distribution, and hence cannot even capture the effect of randomized labels on the generalization performance. In this paper, we establish generalization error bounds for SGD by characterizing the corresponding stability in terms of the on-average variance of the stochastic gradients. Such characterizations lead to improved bounds on the generalization error of SGD and experimentally explain the effect of the random labels on the generalization performance. We also study the regularized risk minimization problem with strongly convex regularizers, and obtain improved generalization error bounds for the proximal SGD.

Background Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disorder worldwide, and there is no established treatment for this disease. We conducted a network meta-analysis (NMA) to compare existing treatments, which include four classes of antidiabetic drugs, and examined the optimum treatments for NAFLD. Aim To compare the effectiveness of different treatments for NAFLD. Methods An NMA was conducted using Stata 14.0 (Corporation LLC, College Station, United States) and R (X64 3.6.3 version) in this study. Eligible randomized controlled trials (RCTs) were searched in the PubMed, Cochrane Library, Embase, Medline and Web of Science databases from database inception to April 2021. Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference, respectively. An inconsistency model and "node-splitting" technique were used to test for inconsistency. Funnel plots were used to evaluate publication bias. Results Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis. Data were pooled using a random-effects model. Our NMA results revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were the most effective treatment, yielding improvements in hepatic fat content (HFC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum γ-glutamyl transferase (GGT) and body weight [surface under the cumulative ranking curve (SUCRA) = 99.6%, 92.6%, 82.8%, 92.3% and 99.6%, respectively], while thiazolidinediones (TZDs) were the best intervention for reducing the NAFLD activity score (NAS; SUCRA = 98.9%). In addition, moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups (SUCRA = 25.1%, 66.2%, 63.5%, 58.2% and 71.9% for HFC, ALT, AST, GGT and body weight, respectively). However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively). Conclusion GLP-1RAs may be the optimum choice for most patients with NAFLD. However, TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.

BackgroundHIV self-testing (HIVST), especially the secondary distribution of HIVST (SD-HIVST) initiated by sexual health influencers (SHIs), has been recognized as an effective strategy in promoting HIV testing, especially among men who have sex with men (MSM). This quasi-experimental study aimed to evaluate whether SHIs identified through the ensemble machine learning approach can distribute more HIVST than those who identified by the empiricalscale.MethodsWe will recruit eligible adults (≥18 years old) who were assigned male gender at birth, and willing to participate in potential SD-HIVST online. Participants will be assigned randomly to two groups (scale group or machine learning group), followed by a separate process of SHI identification based on the group assignment. After identification, all index participants (defined as identified SHIs who are verbally consented to participate in SD-HIVST or who directly order HIVST kits) will follow the same procedure for SD-HIVST acquisition and distribution. Index participants can order HIVST online and distribute them to members within their social networks (defined as alters) in-person or virtually through a personalized peer referral link. Once a unique alter uploads a photographed test result to the platform, both the alter and the corresponding index participant will receive a fixed incentive of 3 USD. The index MSM can order up to five HIVST in the first three months and ten HIVST in the following three months. Each index participant will need to complete a baseline survey at the first-time ordering and one to two follow-upbased on the times of ordering,, three months after ordering. This trial will be comparing 1) the mean number of alters motivated by each index participant in each group and 2) the mean number of newly-tested alters motivated by each index participant in each group.DiscussionIn promoting the efficacy of identifying SHIs for SD-HIVST, our study has the potential to enhance testing coverage, particularly among marginalized individuals and those who are reluctant to for HIV and other sexually transmitted infections.Trial registrationWe registered the study on the Chinese Clinical Trial Registry website on 4th November 2021, with registration numberChiCTR2000039632.

Background There is currently no widely-accepted consensus for the management of hepatocellular carcinoma with portal vein tumor thrombus. We evaluate the safety and efficacy of ultrasound-guided percutaneous brachytherapy with iodine-125 seeds for the treatment of hepatocellular carcinoma with portal vein-branch tumor thrombus (PVBTT). Methods Sixty-nine hepatocellular carcinoma patients with PVBTT were enrolled; 34 received transarterial chemoembolization (TACE) combined with iodine-125 seeds implanted in the PVBTT; 35 were treated with TACE alone. Adverse events, objective response rate, disease control rate, progression-free survival, and overall survival were compared between the two groups. Tumor responses of PVBTT and intrahepatic tumor were correlated. Multivariate and subgroup analyses were conducted for overall survival. Results No grade 3 or 4 adverse events were recorded, and there was no difference in grade 1 or 2 adverse events between the two groups. Objective response rate and disease control rate for PVBTT were 58.9 and 91.2%, respectively, in the combined treatment group, which were significantly greater than the 5.7 and 54.3% rates, respectively, in the TACE-alone group (both p’s ≤ 0.001). Intrahepatic tumor response was positively correlated with the PVBTT response (γ = 0.782, p p p = 0.003). Multivariate analysis revealed that application of brachytherapy and lower grade PVBTT (Vp1 + Vp2 vs. Vp3) were protective predictors of overall survival. In stratified analysis, the benefit of overall survival was more significant in the subgroup of PVBTT Vp1 + Vp2 rather than in Vp3. Conclusions The combination of iodine-125 seed brachytherapy guided by ultrasound and TACE is a convenient, safe, and effective treatment for patients with HCC and PVBTT, conferring a better survival benefit than TACE alone.

BACKGROUND: To investigate whether the interval between adjuvant chemotherapy (CT) completion and postoperative radiation therapy initiation (ICR) after breast-conserving surgery (BCS) affects ipsilateral breast tumor recurrence (IBTR) or survival. METHODS: All women who were diagnosed with invasive breast cancer and underwent BCS between 2005 and 2014 were included. In total, 1,472 patients underwent adjuvant CT followed by postoperative radiation therapy (RT) (CT+), whereas 402 patients received postoperative RT alone (CT−). Analyses were stratified by ICR and the interval between surgery and the initiation of postoperative RT (ISR) in these two cohorts. The cutoff points for treatment delay were 47 days in the CT+ cohort and 69 days in the CT− cohort. IBTR, local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS) were assessed through Kaplan-Meier (K-M) analysis. Univariate and multivariate regression analyses were performed to determine the prognostic factors of survival outcomes. RESULTS: The median follow-up duration was 56 months. There was an association between a delay in ICR and an increase in IBTR in the CT+ group (P=0.014 for intervals ≤47 vs. >47 days). This association was confirmed by multivariate analyses [hazard ratio (HR) of 2.766; P=0.046] in the hormone receptor-negative subgroup. The 5-year cumulative incidence rates of IBTR were 1.3% and 3.3% (≤47 vs. >47 days, respectively) in the CT+ cohort. For patients in the CT− cohort, a longer delay of initiation of postoperative RT (≤69 vs. >69 days) significantly decreased DFS (HR of 6.430; P=0.002). The 5-year cumulative incidence rates of disease recurrence were 3.0% for RT starting ≤69 days after surgery and 12.6% for RT starting >69 days after surgery. CONCLUSIONS: A high IBTR rate was related to an ICR beyond 47 days. Delay of RT after CT or surgery among patients who undergo BCS should be avoided, especially among patients in the hormone receptor-negative subgroup.

Targeted therapy with epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs) is the standard first-line treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Third-generation EGFR-TKIs, represented by osimertinib, have been approved to overcome the EGFR T790M mutation in patients who are resistant to first- or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. However, resistance to the third generation of EGFR-TKIs is still inevitable. Acquired drug resistance is the main reason for limiting the long-term effectiveness of targeted therapy in EGFR-mutated NSCLC patients. The mechanism of EGFR-TKI resistance of the third generation has become a focus of research in the field of targeted therapy. In this review, we summarize the research progress in resistance mechanisms of advanced NSCLC to osimertinib and the potential overcoming strategies and hope to provide a clinical basis and ideas for precision treatment of NSCLC.

Multiple-stage interband cascade infrared photodetector (ICIP) is a new class of semiconductor infrared photodetector that exhibits improved device performance in terms of responsivity and detectivity. The design of the device structure and the electronic structure on superlattices and quantum wells assume abrupt interfaces. However, the emergence of possible interface segregation and atom exchange can only be determined experimentally, impacting the device performance. In this work, the interface atom intermixing and their effects on the energy band structure in a molecular beam epitaxy grown ICIP are studied. Scanning transmission electron microscopy (STEM) reveals atom diffusion and intermixing between the constituent layers of the cascade structure, causing a shift in the quantum state energy levels of the layers and the consequent misalignment of the cascade structures. Combining the STEM observation with high-resolution X-ray diffraction, the alloy composition profiles of the layers are determined. Using the "real" graded composition profiles, the effective band gap of the superlattice absorber and the energy levels of the relaxation region and the tunneling region are recalculated showing a cutoff wavelength of the superlattice absorber 4.93 μm, which is 0.78 μm smaller than that calculated using the nominal step composition profile. However, its agreement is greatly improved with the measured cutoff wavelength of 5.03 μm. The energy level of the narrowest quantum well in the relaxation region is 0.091 eV higher than the conduction miniband of the absorber, which is also consistent with the experiments that the pho-response exits a "turn on" voltage of 0.1 V. The results reported here will help optimize the energy structure design of future ICIP with improved device performance.

This paper presents an experimental investigation on a novel prefabricated concrete wall system with horizontally placed hollow core panels. Compared with traditional clay bricks, prefabricated concrete hollow core panels have the advantages of convenient quality control, reduced self-weight, fast installation, low labour cost, and high load-bearing capacity. In this study, nine full-scale wall specimens (i.e., two under compression, five under compressive and lateral loads, and two under compressive and cyclic lateral loads), which were extracted from an apartment project, were prepared and tested. As evidenced by the experiments, the load-bearing capacities of the walls could satisfy the design requirement. In general, the failure occurred in the panel-to-panel connections, panel-to-frame connections, and corners of openings. The openings (i.e. windows and doors) substantially reduced the compressive and shear capacities and resulted in a more ductile failure. The pinching effect was apparent for wall specimens under cyclic loads, and the energy dissipation capability of the wall was reduced when a door opening was set. The design standard for masonry walls was adopted to estimate the axial compressive and shear strength owing to the unavailability of a design standard specifically for the new type of hollow-core walls. The predicted strength was generally significantly lower than the experimental strength, revealing a large safety margin for engineering applications.

Introduction In order to gain exposure to hospital practice earlier in the education of doctor of pharmacy students, a recent curricular change by the faculty of pharmacy prioritized institutional sites for year two early practice experiences (EPE2s). The goal of this study was to assess whether year two student pharmacists were adequately equipped by the faculty to apply clinical concepts when providing direct patient care in an institutional setting. Methods At the study institution, four students rated the relevancy of clinical concepts covered in five pharmacotherapy courses to their EPE2 practice using a relevance score tool. Students self-evaluated their ability-to-practice (AP) these concepts at the start and end of the rotation using an AP score tool. Results The students determined that all pharmacotherapy courses covered at least one clinical concept that was occasionally seen and applied to practice at the study institution, except for dermatology/ears, eyes, nose, and throat. All AP scores for relevant clinical concepts improved post-rotation except for dyslipidemia, which remained unchanged. Conclusions The year two students who participated in the pilot study had sufficient knowledge to apply pharmacotherapy concepts when performing supervised direct patient care at the study institution.

BackgroundCoronavirus disease 2019 (COVID-19) has spread around the world. This retrospective study aims to analyze the clinical features of COVID-19 patients with cancer and identify death outcome related risk factors.MethodsFrom February 10th to April 15th, 2020, 103 COVID-19 patients with cancer were enrolled. Difference analyses were performed between severe and non-severe patients. A propensity score matching (PSM) analysis was performed, including 103 COVID-19 patients with cancer and 206 matched non-cancer COVID-19 patients. Next, we identified death related risk factors and developed a nomogram for predicting the probability.ResultsIn 103 COVID-19 patients with cancer, the main cancer categories were breast cancer, lung cancer and bladder cancer. Compared to non-severe patients, severe patients had a higher median age, and a higher proportion of smokers, diabetes, heart disease and dyspnea. In addition, most of the laboratory results between two groups were significantly different. PSM analysis found that the proportion of dyspnea was much higher in COVID-19 patients with cancer. The severity incidence in two groups were similar, while a much higher mortality was found in COVID-19 patients with cancer compared to that in COVID-19 patients without cancer (11.7% vs. 4.4%, P = 0.028). Furthermore, we found that neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) were related to death outcome. And a nomogram based on the factors was developed.ConclusionIn COVID-19 patients with cancer, the clinical features and laboratory results between severe group and non-severe group were significantly different. NLR and CRP were the risk factors that could predict death outcome.

Background Tuberculosis (TB) is one of the leading causes of morbidity and mortality in Western China. Preclinical studies have suggested the protective effect of the C-type lectin receptor of family 4 member E (CLEC4E) from TB. Herein, we investigated the association between CLEC4E gene variants and TB susceptibility in a western Chinese Han population. Methods We genotyped four single nucleotide polymorphisms (SNPs) rs10841856, rs10770847, rs10770855 and rs4480590 in the CLEC4E gene using the improved multiplex ligation detection reaction (iMLDR) assay in 900 TB cases and 1534 healthy controls. Results After stratifying the whole data by sex, it was found that males exhibited mutant allele G of rs10841856 was more strongly associated with increased TB risk after Bonferroni correction (OR = 1.334, 95% CI: 1.142–1.560; P p = 0.001 after Bonferroni correction). The genetic model analysis found that rs10841856 was associated with the increased risk of TB among males under the dominant model (OR = 1.557, 95% CI = 1.228–1.984, P P Conclusions Our study revealed that rs10841856 in the CLEC4E gene might be related to increased TB risk, especially the dominant genetic model among male Han individuals from Western China

Background: We investigated the combined effect of white blood cell (WBC) and platelet count on in-hospital mortality and pneumonia in acute ischemic stroke (AIS) patients. Methods: A total of 3,265 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of WBC and platelet count: LWHP (low WBC and high platelet), LWLP (low WBC and low platelet), HWHP (high WBC and high platelet), and HWLP (high WBC and low platelet). A logistic regression model was used to estimate the combined effect of WBC and platelet counts on all-cause in-hospital mortality and pneumonia in AIS patients. Results: HWLP was associated with a 2.07-fold increase in the risk of in-hospital mortality in comparison to LWHP (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI), 1.02-4.18; P-trend =0.020). The risk of pneumonia was significantly higher in patients with HWLP than those with LWHP (adjusted OR 2.29; 95% CI, 1.57-3.35; P-trend Conclusion: High WBC count combined with a low platelet count level at admission was independently associated with in-hospital mortality and pneumonia in AIS patients. Moreover, the combination of WBC count and platelet count level appeared to be a better predictor than WBC count or platelet count alone.

Background In 2020, primary care practices adopted telemedicine as an alternative to in-person visits. Little is known about whether access to telemedicine was equitable, especially among older patients. Our objectives were to (1) examine older adults' use of telemedicine versus in-person primary care visits and (2) compare hospitalization for ambulatory care sensitive conditions (ACSCs) between the groups. Methods In this retrospective cross-sectional study of 17,103 patients aged ≥65 years seen at 32 clinics in the Mid-Atlantic, primary care patients were classified into two groups-telemedicine versus in person-based on the first visit between March and May 2020 and followed up for 14 days. Using multivariable logistic regression, we measured the odds of being seen via telemedicine versus in person as a function of patient demographics, comorbidities, and week of study period. We then measured the odds of ACSC hospitalization by visit modality. Results Mean age was 75.1 years (SD, 7.5), 60.6% of patients were female, 64.6% white, 28.1% black, and 2.0% Hispanic. Overall, 60.3% of patients accessed primary care via telemedicine. Black (vs. white) patients had higher odds of using telemedicine (adjusted odds ratio [aOR], 1.30; 95% CI, 1.14-1.47) and Hispanic (vs. not Hispanic) patients had lower odds (aOR, 0.63; 95% CI, 0.42-0.92). Compared with the in-person group, patients in the telemedicine group had lower odds of ACSC hospitalization (aOR, 0.78; 95% CI, 0.61-1.00). Among patients who used telemedicine, black patients had 1.43 higher odds of ACSC hospitalization (95% CI, 1.02-2.01) compared with white patients. Patients aged 85 or older seen via telemedicine had higher odds of an ACSC hospitalization (aOR, 1.60; 95% CI, 1.03-2.47) compared with patients aged 65-74. Conclusions These findings support the use of telemedicine for primary care access for older adults. However, the observed disparities highlight the need to improve care quality and equity regardless of visit modality.

This study revisits the association between bilateral relations and trade based on rare-event data from Integrated Data for Event Analysis (IDEA). Our results suggest that a country imports more from another if the two countries are friendlier. We further argue that states face two constraints when attempting to manipulate trade. First, they are constrained by domestic institutions such as elections and congress. Second, they are constrained by international institutions such as the World Trade Organization (WTO). Our results show that the imports of authoritarian countries follow the flag of politics, but democratic countries’ imports are less likely to be affected by bilateral relations. Moreover, WTO membership can gradually restrict democratic states from intervening on imports but has little impact on authoritarian governments.

Background Epilepsy was defined as an abnormal brain network model disease in the latest definition. From a microscopic perspective, it is also particularly important to observe the Mutual Information (MI) of the whole brain network based on different lead positions. Methods In this study, we selected EEG data from representative temporal lobe and frontal lobe epilepsy patients. Based on Phase Space Reconstruction and the calculation of MI indicator, we used Complex Network technology to construct a dynamic brain network function model of epilepsy seizure. At the same time, about the analysis of our network, we described the index changes and propagation paths of epilepsy discharge in different periods, and spatially monitors the seizure change process based on the analysis of the parameter characteristics of the complex network. Results Our model portrayed the functional synergy between the various regions of the brain and the state transition during the seizure process. We also characterized the EEG synchronous propagation path and core nodes during seizures. The results shown the full node change path and the distribution of important indicators during the seizure process, which makes the state change of the seizure process more clearly. Conclusion In this study, we have demonstrated that synchronization-based brain networks change with time and space. The EEG synchronous propagation path and core nodes during epileptic seizures can provide a reference for finding the focus area.

Background Epilepsy is one of the diseases of the nervous system, which has a large population in the world. Traditional diagnosis methods mostly depended on the professional neurologists’ reading of the electroencephalogram (EEG), which was time-consuming, inefficient, and subjective. In recent years, automatic epilepsy diagnosis of EEG by deep learning had attracted more and more attention. But the potential of deep neural networks in seizure detection had not been fully developed. Methods In this article, we used a one-dimensional convolutional neural network (1-D CNN) to replace the residual network architecture’s traditional convolutional neural network (CNN). Moreover, we combined the Independent recurrent neural network (indRNN) and CNN to form a new residual network architecture-independent convolutional recurrent neural network (RCNN). Our model can achieve an automatic diagnosis of epilepsy EEG. Firstly, the important features of EEG were learned by using the residual network architecture of 1-D CNN. Then the relationship between the sequences were learned by using the recurrent neural network. Finally, the model outputted the classification results. Results On the small sample data sets of Bonn University, our method was superior to the baseline methods and achieved 100% classification accuracy, 100% classification specificity. For the noisy real-world data, our method also exhibited powerful performance. Conclusion The model we proposed can quickly and accurately identify the different periods of EEG in an ideal condition and the real-world condition. The model can provide automatic detection capabilities for clinical epilepsy EEG detection. We hoped to provide a positive significance for the prediction of epileptic seizures EEG.

Purpose Radiation-induced gastrointestinal syndrome (RIGS) is currently the main cause of death for people exposed to a high dose of irradiation during nuclear incidents, and there is currently no approved effective therapy. Here, we found that CBP/P300 inhibitors, with high efficacy and low toxicity, might be promising radiation mitigators that can cure RIGS. Methods and Materials Ex vivo 3D organoid cultures derived from mouse jejunum and human ileum and colon were used to examine the radio-mitigative effects of CBP/P300 inhibitors. The radio-mitigative effect was evaluated by quantifying the survival rate and size of organoids after radiation. SGC-CBP30 (50 mg/kg body weight), an inhibitor of CBP/P300, was intraperitoneally injected into C57B/6J mice 24 hours after subtotal-body irradiation or whole-body irradiation. The regenerated crypts and animal survival were determined by microcolony assay and the Kaplan-Meier method, respectively. Lgr5-lacZ mice were used to evaluate the survival of intestinal stem cells after treatments. Results We found that CBP/P300 inhibitors were effective mitigators that could be used to treat RIGS. CBP/P300 inhibition promoted the regeneration of intestinal organoids in vitro and of crypts in vivo. Remarkably, the administration of CBP/P300 inhibitors to mice 24 hours after lethal irradiation promoted Lgr5+ intestinal stem cell and crypt recovery, resulting in improved mouse survival. Moreover, our data show that CBP/P300 inhibitors rescued irradiated mice from RIGS by delaying intestinal epithelial cell cycle progression after radiation. Conclusions These data demonstrate that CBP/P300 inhibitors are effective medical countermeasures to mitigate gastrointestinal toxicity from radiation.

Background:. Chronic obstructive pulmonary disease (COPD) is a common public health problem worldwide. Recent studies have reported that socioeconomic status (SES) is related to the incidence of COPD. This study aimed to investigate the association between SES and COPD among adults in Jiangsu province, China, and to determine the possible direct and indirect effects of SES on the morbidity of COPD. Methods:. A cross-sectional study was conducted among adults aged 40 years and above between May and December of 2015 in Jiangsu province, China. Participants were selected using a multistage sampling approach. COPD, the outcome variable, was diagnosed by physicians based on spirometry, respiratory symptoms, and risk factors. Education, occupation, and monthly family average income (FAI) were used to separately indicate SES as the explanatory variable. Mixed-effects logistic regression models were introduced to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for examining the SES-COPD relationship. A pathway analysis was conducted to further explore the pulmonary function impairment of patients with different SES. Results:. The mean age of the 2421 participants was 56.63 ± 9.62 years. The prevalence of COPD was 11.8% (95% CI: 10.5%–13.1%) among the overall sample population. After adjustment for age, gender, residence, outdoor and indoor air pollution, body weight status, cigarette smoking, and potential study area-level clustering effects, educational attainment was negatively associated with COPD prevalence in men; white collars were at lower risk (OR: 0.60, 95% CI: 0.43–0.83) of experiencing COPD than blue collars; compared with those within the lower FAI subgroup, participants in the upper (OR: 0.68, 95% CI: 0.49–0.97) tertiles were less likely to experience COPD. Such negative associations between all these three SES indicators and COPD were significant among men only. Education, FAI, and occupation had direct or indirect effects on pulmonary function including post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1, FVC, and FEV1 percentage of predicted. Education, FAI, and occupation had indirect effects on pulmonary function indices of all participants mainly through smoking status, indoor air pollution, and outdoor air pollution. We also found that occupation could affect post-bronchodilator FEV1/FVC through body mass index. Conclusions:. Education, occupation, and FAI had an adverse relationship with COPD prevalence in Jiangsu province, China. SES has both direct and indirect associations with pulmonary function impairment. SES is of great significance for COPD morbidity. It is important that population-based COPD prevention strategies should be tailored for people with different SES.

The paper demonstrates a dual-cell smart window based on dichroic-dyed-doped liquid crystal that is switchable among transparent, dark and scattering states. The dual-cell forms the crossed-polaris...

This study aimed to explore the effect of Treatment and Education of Autistic and Communication Handicapped Children (TEACCH) intervention on the rehabilitation of preschool children having autism spectrum disorder (ASD) in China.Sixty children with ASD were randomly assigned to the intervention group (n = 30) or the control group (n = 30). The intervention group received TEACCH training plus Discrete Trial Teaching (DTT) for six months, while the control group received only DTT. The Chinese version of the Psycho-educational Profile (3rd ed.) (CPEP-3) was used to assess participants at baseline, posttest and at six-month follow-up. The results were analyzed using descriptive statistics, t test, χNo significant difference was found between the two groups at baseline (p 0.05). Repeated-measures ANOVA showed that the CPEP-3 subscales had a significant time effect (p 0.001). The two groups significantly differed in expressive language, affective expression, social reciprocity, problem behavior, and personal self-care at posttest and six-month follow-up (p 0.05). They also significantly differed in receptive language, fine motor at posttest (p 0.05), but not at follow-up.This study demonstrated that TEACCH-based group rehabilitation training effectively improved the development of children having ASD. It provided enhanced rehabilitation strategies that assisted children with ASD to learn, function, and reach their goals.

Unipolar barrier structures are used to suppress dark current in photodetectors by blocking majority carriers. Designing unipolar barriers with conventional materials is challenging due to the strict requirements of lattice and band matching. Two-dimensional materials have self-passivated surfaces and tunable band structures, and can thus be used to design unipolar barriers in which lattice mismatch and interface defects are avoided. Here, we show that band-engineered van der Waals heterostructures can be used to build visible and mid-wavelength infrared unipolar barrier photodetectors. Our nBn unipolar barrier photodetectors, which are based on a tungsten disulfide/hexagonal boron nitride/palladium diselenide heterostructure, exhibit a low dark current of 15 pA, a photocurrent of 20 μA and a detectivity of 2.7 × 1012 cm Hz1/2 W−1. Our pBp unipolar barrier photodetectors, which are based on a black phosphorus/molybdenum disulfide/graphene heterostructure, exhibit a room-temperature detectivity of 2.3 × 1010 cm Hz1/2 W−1 in the mid-wavelength infrared region under blackbody radiation. The pBp devices also show a dichroic ratio of 4.9 under blackbody radiation, and a response time of 23 μs under 2 μm laser illumination. Band-engineered van der Waals heterostructures that block dark current without suppressing photocurrent can be used to build detectors with high room-temperature detectivity for visible light and blackbody infrared light.

Flexible and stretchable dry active electrodes for multi bio-potentials sensing based on Ag flakes / polydimethylsiloxane (PDMS) electrically conductive composite (ECC) are developed and characterized. The proposed dry active electrode consists of soft substrate, electrode, and simple circuits with an amplifier and a capacitor. The soft substrate is made of silicone with a molding process, while the electrode is fabricated by bar coating the ECC on the patterned substrate. Furthermore, circuits interconnect, soldering of chip and other components, and connection with flexible PCB (FPC) are all implemented with ECC directly, which simplifies the fabrication process. A portable bio-potential sensing system is also designed and implemented to work with the proposed electrodes. Various experiments were carried out to verify the proposed electrodes as well as the whole sensing system. The connectivity and proper functionality of the electrodes and cables remain stable during the stretching test. The system and the sensors yield good signal quality for multiple bio-potentials. Compared with conventional Ag/AgCl wet passive electrodes in electrocardiogram (ECG) sensing, the proposed dry active electrodes showed comparable noise floor and less sensitivity to power line interferences and motion artifacts. In electroencephalogram (EEG) sensing, the observed alpha rhythm was 12.66 dB higher than the baseline in the eye-close state. The proposed sensors exhibited potential applications in wearable systems in the electromyogram (EMG) grip force measurement and classification test. Overall, the proposed sensors could provide better comforts during long-time wearing according to its better matching modulus with skin and can meet the requirements of high quality multi bio-potential sensing.

Sepsis is a life‐threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)‐ or caecal ligation and puncture (CLP)‐induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro‐inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti‐oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti‐oxidative enzymes including NQO‐1, GST, HO‐1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin‐induced Nrf2 activation could suppress NF‐κB‐regulated up‐regulation of pro‐inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti‐oxidative enzymes and inhibited NF‐κB‐regulated pro‐inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Background Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors. Methods Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as ‘rapid relapse’ (rrTNBC; distant relapse or death ≤2 years of diagnosis), ‘late relapse’ (lrTNBC; > 2 years) or ‘no relapse’ (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features. Results Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest. Conclusions We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.

Yang Luo,1,* Min-Hao Yu,1,* Yi-Zhou Huang,1 Ran Jing,1 Jun Qin,1 Shao-Lan Qin,1 Jay N Shah,1,2 Ming Zhong1 1Department of Gastrointestinal Surgery, Renji Hospital, Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Department of Surgery, Patan Hospital, Patan Academy of Health Sciences, Lalitpur, Kathmandu, 44700, Nepal*These authors contributed equally to this workCorrespondence: Ming Zhong; Jay N Shah Email drzhongming@hotmail.com; drjaywufei@gmail.comBackground: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers.Methods: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p< 0.05 was considered significant.Results: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT.Conclusion: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.Keywords: anastomotic leakage, Clavien-Dindo complications, laparoscopic anterior resection, left colic artery, low-tie high-tie of the inferior mesenteric artery, rectal cancer

ObjectiveAs elderly parents today will share a longer life with their children than ever before, the spillover effects of children’s human capital on parents’ well-being become increasingly important. This study investigated whether children’s schooling leads parents to give up smoking and whether the effects were moderated by their education or child–parent contact frequency.MethodsUsing data from the China Health and Retirement Longitudinal Study, we conducted an instrumental variable (IV) analysis using China’s compulsory schooling reform in the 1980s as a natural experiment.ResultsThe IV estimates suggest that elderly parents of more highly educated children are more likely to quit smoking. Moreover, the effects are more significant among parents who had not finished primary school and also slightly stronger among parents who live close to their children or meet their children frequently.DiscussionOur findings add to current evidence regarding spillover effects of education on smoking cessation. A child’s education may exert an impact through the spillover of health knowledge.

Context.— The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin lymphoma, accounting for 20% to 40% of all extranodal lymphomas. The majority of these are systemic processes secondarily involving the GI tract. Primary GI lymphomas are less common, accounting for approximately 10% to 15% of all non-Hodgkin lymphomas. Most non-Hodgkin lymphomas involving the GI tract are of B-cell lineage, of which diffuse large B-cell lymphoma is the most common subtype, irrespective of location. Objective.— To review the lymphoproliferative neoplasms of B-cell and T-cell lineage involving the luminal GI tract according to the most prevalent subtypes at each anatomic site. Data Source.— Systematic search of the PubMed database for updated literature on GI lymphoma epidemiology, subtypes, clinical, endoscopic, and genetic findings. Histologic images are derived from our collection of clinical cases. Conclusions.— The GI tract is the most common site of extranodal lymphoproliferative neoplasms. Recognition of the most frequently encountered GI lymphomas is imperative for patient management and treatment.

Magnetic invisible cloaking has been previously demonstrated but only limited to objects with rotational geometries either in spherical or cylindrical shapes, for which the classic analytical bilayer scheme could be strictly applied to design the hiding coat. In this work, we show that a quasi-static cloaking effect could be achieved for irregular objects, e.g., metals with sharp edges, using a numerical optimization scheme. In the quasi-static limit, it is unambiguously proved that the disturbance of the irregular geometries could be well compensated by the inhomogeneous distribution of the soft ferromagnetic (FM) layer either in permeability values or in shapes under the framework of a bilayer cloak. An FM mesh coat with a constant thickness of 0.5 mm was successfully engineered to meet the specific requirements. Experimentally, good cloaking performance with a field disturbance of less than 0.5% has been achieved for a 2 × 2 × 5 cm3 brass bar in a wide frequency range from ∼10 to 250 kHz. A commercial metal scanner was also applied to verify the practical potential. The general strategy to hide almost arbitrary objects was discussed in the end. In principle, the numerical conformal coat engineered by the composite material proposed here could be broadly extended for objects with various geometries.

Background In this study, we sought to assess knowledge, attitudes, and behaviors regarding venous thromboembolism (VTE) prophylaxis among clinicians at a tertiary hospital of China. Methods An electronic questionnaire was sent to clinicians to gather information regarding demographic data (5 items), knowledge about VTE prophylaxis (21 items), behaviors regarding VTE prophylaxis (8 items), and attitudes regarding VTE prophylaxis (7 items). Answers of “strongly agree” and “agree” on the behaviors and attitude items were defined as affirmative responses. Clinicians were also asked to provide suggestions regarding VTE prophylaxis. Results A total of 867 clinicians were included in this study. The overall correct response rate for knowledge items was 60.9%. The median affirmative response rate for behavior items was 48.6% (range 29.5–80.3%), and the median affirmative response rate for attitude items was 98.7% (range 96.9–99.3%). Clinicians were most concerned about the adverse effects triggered by chemical VTE prophylaxis (79.5%) and possibility of a financial penalty when a patient could not be treated with VTE prophylaxis (72.3%). Low patient compliance and low level of clinician knowledge and participation were identified most commonly as difficulties involved in VTE prophylaxis. A total of 78 suggestions were collected; these suggestions generally focused on improving the quality and frequency of staff training (n = 24) and enhancing learning opportunities (n = 22). Conclusions Although the clinicians’ overall attitude toward VTE prophylaxis was positive, the knowledge level was relatively poor, and the rate of affirmative responses regarding behaviors was low. Medical institutions should improve clinician training regarding VTE prophylaxis.

Speckle noise is the main cause of poor optical coherence tomography (OCT) image quality. Convolutional neural networks (CNNs) have shown remarkable performances for speckle noise reduction. However, speckle noise denoising still meets great challenges because the deep learning-based methods need a large amount of labeled data whose acquisition is time-consuming or expensive. Besides, many CNNs-based methods design complex structure based networks with lots of parameters to improve the denoising performance, which consume hardware resources severely and are prone to overfitting. To solve these problems, we propose a novel semi-supervised learning based method for speckle noise denoising in retinal OCT images. First, to improve the model's ability to capture complex and sparse features in OCT images, and avoid the problem of a great increase of parameters, a novel capsule conditional generative adversarial network (Caps-cGAN) with small number of parameters is proposed to construct the semi-supervised learning system. Then, to tackle the problem of retinal structure information loss in OCT images caused by lack of detailed guidance during unsupervised learning, a novel joint semi-supervised loss function composed of unsupervised loss and supervised loss is proposed to train the model. Compared with other state-of-the-art methods, the proposed semi-supervised method is suitable for retinal OCT images collected from different OCT devices and can achieve better performance even only using half of the training data.

This article proposes a deep convolutional neural network with perceptible generalization ability for structural topology optimization. The architecture of the neural network is made up of encoding...