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The aim of this study was to evaluate the survival benefits of adjuvant chemotherapy in patients with positive lymph nodes after esophagectomy for esophageal squamous cell carcinoma.Patients who underwent esophagectomy for esophageal cancer in the Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital) in Zhengzhou, China from 2013 to 2017 were selected for this retrospective cohort study. Patients with positive lymph nodes were grouped into the surgery alone group or the adjuvant chemotherapy group. Propensity score matching (1:1) was used to minimize baseline differences.Among the 5118 patients who underwent esophagectomy, 792 patients were enrolled in the study. After matching, 253 (of 476) patients (adjuvant chemotherapy group) and 253 (of 316) patients (surgery alone group) were included. The median overall survival was significantly prolonged in the adjuvant chemotherapy group (54.0 months; 95% CI, 41.1-66.9 months) compared with the surgery alone group (28.0 months; 95% CI, 22.4-33.6 months) (P.001). A significant difference was also observed in median disease-free survival between the 2 groups (adjuvant chemotherapy group, 33.0 months [95% CI, 20.8-45.2 months] compared with the surgery alone group, 22.0 months [95% CI, 17.0-27.0 months]; P = .007). In a multivariable analysis, receiving adjuvant chemotherapy (P.001) was significantly associated with a reduced risk of death, and dissection of more than 6 lymph node stations (P = .05) was marginally associated with a reduced risk of death.Postoperative adjuvant chemotherapy improves the overall survival and disease-free survival of patients with resected esophageal squamous cell carcinoma with positive lymph nodes.

For power batteries used in the electric vehicle, accurate state-of-charge estimation is important. However, as one of the most commonly used estimation method, the least square support vector regression is hard to balance the accuracy and efficiency. To solve this problem, the fuzzy information granulation based on asymmetric Gaussian membership function is proposed to improve the utilization efficiency of the effective data and enhance the prediction accuracy of battery states. In addition, the performance of the proposed method is compared with that of other commonly used member -ship functions. In experiments, the dynamic stress test condition and the urban dynamometer driving schedule condition are used to verify the effectiveness. Compared with the most commonly used triangle membership function, the proposed method improves the accuracy of estimation by 6.47% and 2.18% under two current conditions, respectively.

Muscle strength after detraining is still higher than the level before training, which is an important issue for middle-aged and older adults. The purpose of the present study was to examine the effects of detraining duration (DD), resistance training duration (RTD), and intensity on the maintenance of resistance training (RT) benefits after detraining in middle-aged and older adults. A systematic search yielded 15 randomized control trails (n = 383) eligible for inclusion. The results showed that RTD ≥ 24 weeks and DD ≥ RTD, the RT benefits were still significantly maintained even with medium and low intensity (standardized mean difference = 1.16, 95% confidence interval, CI [0.38, 1.94], p = .004). When RTD p = .0002; DD 8–16 weeks: standardized mean difference = 1.35, 95% CI [0.66, 2.04], p = .0001). However, when DD > RTD, the RT benefits were not maintained even with high intensity. In summary, when RTD was less than 24 weeks, RTD > DD was an important factor in maintaining muscle strength.

At present, the crowdsourcing-based indoor navigation system (CINS) has attracted extensive attention from both industry and academia owing to its low-cost and high-accuracy performance. Unfortunately, the system that relies on crowdsourced data is vulnerable to the collusion attack, which leads to severe security issues. To address the security issues in the CINS, we propose to utilize a fully trusted fog server platform to advocate secure transactions between service requesters and responders. First, we propose a novel reputation incentive mechanism based on the behaviors of responders. Then, we employ the offensive and defensive game to model the interactions between the fog server platform and the responders, whereby a social welfare optimization problem is formulated to maximize the social welfare of the system. Next, the game equilibriums are found by using the replicator dynamic equation while the game stability is discussed. Finally, the simulation results show that the proposed mechanism can effectively encourage responders to provide positive navigation services and obtain more social welfare of the system compared with the conventional mechanisms.

Objective Previous clinical studies and meta-analyses have shown controversial results on the association between C3435T polymorphism of the ABCB1 gene and anti-epileptic drug (AED) resistance. Based on the fact that sample size and confounding factors could contribute to the inconsistency, we performed an updated meta-analysis by including the most recent studies, and subgroup analysis was conducted to evaluate the effect of confounding factors on the association. Materials and methods We searched articles in 6 electronic databases including PubMed, Medline, Embase, Web of science, Cochrane Library, CNKI (China National Knowledge Infrastructure) for relevant articles up to June 2020. Results The current analysis showed that the C allele of C3435T variant was a risk factor for drug resistance in the overall populations (C allele vs. T allele, OR: 1.13; 95% CI: 1.02 - 1.25; p = 0.02) and in the Caucasians (C allele vs. T allele, OR: 1.09; 95% CI: 1.09 - 1.43; p = 0.002), while no association was observed in Asians and Indians. Particularly, our study reported for the first time that the 3435T allele was more common in epilepsy patients with drug resistance in the Tunisian population (C allele vs. T allele, OR: 0.31; 95% CI: 0.15 - 0.65; p = 0.002). In addition, our present analysis suggested an association between C3435T and AED resistance in cryptogenic, symptomatic, but not in idiopathic patients. Subgroup studies based on age and gender showed no association. Conclusion AED resistance in Caucasian and Tunisian populations may benefit from ABCB1 C3435T genotyping. We recommend that more details, such as gender and etiology of epilepsy, should be taken into account to draw a reliable conclusion in future studies.

Exploiting high-performance, low-cost, and robust bifunctional catalysts toward electrochemical water splitting is of great importance, but remains challenging.

Objective This study collected randomized controlled trials (RCTs) published in the social sciences in China and assessed their risk of bias and reporting quality. Study Design and Setting Three databases were systematically searched for publications from January 2000 to June 2020 for RCTs in the social sciences published by Chinese researchers. The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool (CCRBT), and reporting quality was assessed using the Consolidated Standards of Reporting Trials for Social and Psychological Interventions (CONSORT-SPI). Results A total of 316 RCTs were identified, including 204 articles in English and 112 articles in Chinese. The most frequently researched interventions focused on education (33.9%), and the most frequently studied population were students (32.9%). Eighty-seven percent of RCTs had intermediate reporting quality. Twenty-four of the 43 CONSORT-SPI sub-items had a compliance rate of less than 50%. Most RCTs had an unclear risk of bias for blinding outcome assessors (84.5%), blinding participants and personnel (82.9%), allocation concealment (73.1%), and random sequence generation (68.0%). A low proportion of CONSORT-SPI items were reported and, high proportion of the papers had unclear risk of bias. Conclusion The quality and reporting of RCTs in the social sciences needs improvement in China, especially for reporting methods and results. Most studies had an unclear risk of bias as they lacked important methodological information.

Background Major depressive disorder (MDD) is the most common mental disorder associated with suicide attempts. When a patient first visits the clinic, clinicians are often expected to make concrete diagnose about acute suicidal risk. However, the timeliness of suicide attempts correlates with patients with MDD has not been tested. Methods We divided 1718 first-episode and untreated MDD outpatients into those who did not have suicide attempts (non-attempts), recent suicide attempters (≤14 days before assessment) and long - dated suicide attempters (> 30 days before assessment). Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, 14 - item Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S) was assessed. Body mass index, some glycolipid metabolism and thyroid hormone parameters were measured. A gradient-boosted decision trees statistical model was used to generate equally weighted classification for distinguishing recent and long - dated suicide attempters from non-attempts. Results The classifier identified higher excitement, hostility, anxiety, depression symptoms and higher free thyroxine (FT4) as risk factors for recent suicide attempters with an estimated accuracy of 87% (sensitivity, 59.1%; specificity, 61.2 %). For long - dated suicide attempters’ risk factors, single status, higher anxiety and hostility symptoms, higher LDLC and lower BMI, the estimated accuracy was 88% (sensitivity, 52.8%; specificity, 49.6%). Conclusions Risk factors for suicide attempt among patients with MDD can be identified by integrating demographic, clinical, and biological variables as early as possible during the first time see a doctor.

Background The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. Methods Real‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor. Results Compared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants. Conclusions ER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production. Level of Evidence NA

Background Doctors can detect symptoms of diabetic retinopathy (DR) early by using retinal ophthalmoscopy, and they can improve diagnostic efficiency with the assistance of deep learning to select treatments and support personnel workflow. Conventionally, most deep learning methods for DR diagnosis categorize retinal ophthalmoscopy images into training and validation data sets according to the 80/20 rule, and they use the synthetic minority oversampling technique (SMOTE) in data processing (e.g., rotating, scaling, and translating training images) to increase the number of training samples. Oversampling training may lead to overfitting of the training model. Therefore, untrained or unverified images can yield erroneous predictions. Although the accuracy of prediction results is 90%–99%, this overfitting of training data may distort training module variables. Results This study uses a 2-stage training method to solve the overfitting problem. In the training phase, to build the model, the Learning module 1 used to identify the DR and no-DR. The Learning module 2 on SMOTE synthetic datasets to identify the mild-NPDR, moderate NPDR, severe NPDR and proliferative DR classification. These two modules also used early stopping and data dividing methods to reduce overfitting by oversampling. In the test phase, we use the DIARETDB0, DIARETDB1, eOphtha, MESSIDOR, and DRIVE datasets to evaluate the performance of the training network. The prediction accuracy achieved to 85.38%, 84.27%, 85.75%, 86.73%, and 92.5%. Conclusions Based on the experiment, a general deep learning model for detecting DR was developed, and it could be used with all DR databases. We provided a simple method of addressing the imbalance of DR databases, and this method can be used with other medical images.

The prosperity of the biotherapeutics market reflects the feasibility and effectiveness of therapeutic antibodies for the treatment of cancers, inflammatory disorders, and refractory infections. As drawbacks emerge in clinical trials and practice, such as impeded binding, reduced effector functions, and frequent adverse reactions, modifications of therapeutic antibodies are unprecedently burgeoning in research and development (R&D). These modifications include: ① modified glycosylation; ② fragment of crystallizable domain (Fc) amino acid alterations; ③ cross-isotype or cross-subclass exchanges; ④ antibody–drug conjugates (ADCs); ⑤ single chain of variable region fragment (scFv) for chimeric antigen receptor T (CAR-T) cells; and ⑥ bispecific antibodies (bsAbs) in order to promote binding affinity, half-life in circulation, effectiveness toward target cells and, ultimately, to achieve overall improved efficacy. While many achievements have been made around the world in the past decades, China has been playing an active role in this realm, with its great demand for biotherapeutics with R&D potential. This review recapitulates the international progress that has been achieved with modified therapeutic antibodies, and then focuses on that of China in an independent section.

Supercapacitors possessing fast-charging characteristics and long lifespan are becoming increasingly important for powering portable and smart energy storage devices, and combining capacitive and battery-type materials into an integrated device is an effective method for increasing the overall performance of capacitors. Silicene is being designed as a cathode for the development of enhanced capacitance and ultra-cycle stable zinc-ion hybrid capacitors. Possessing a maximum areal capacity of 14 mF cm-2, a maximum power density of 9 mW cm-2, capacitance retention of 112% even after 10 000 cycles, and an unexpectedly high energy density of 23 mJ cm-2, this achievement of the zinc-ion hybrid capacitor would be superior to that of previously reported silicon-based supercapacitors. The DFT calculations further reveal that Zn ions dominate the capacitive behavior of the silicene electrode. The support association between silicene and zinc-ion hybrid capacitors so that they can take advantage of each other's strengths, which takes electrochemical energy technology to a stage, offering a straightforward proposal for integration and implementation of silicon-based materials.

Introduction Histopathological characteristics of cytomegalovirus (CMV) lymphadenitis have been well described. Rare studies have reported the immune status and clinical features. Clinically, experts believed that CMV lymphadenitis develops in immunocompromised and immunocompetent patients. Infectious mononucleosis (IM)-like syndrome is the most well-known clinical presentation. Methods We reviewed archived CMV immunohistochemical stains on lymphoid tissues. The clinicopathological features of CMV-positive cases were studied. Results For lymph nodes, we detected CMV in 29% (5/17) allogeneic peripheral blood hematopoietic stem cell transplantation (PBSCT) recipients, 29% (4/14) post-autologous PBSCT patients, 13% (6/47) patients treated with intravenous chemotherapy, and 9% (9/96) immunocompetent patients. We detected CMV in 7% (2/24) of tonsils but not in the nasopharynx, tongue base, or spleen specimens. The patients with iatrogenic immunodeficiency ranged from 37 to 76 years old. CMV infections developed a few years after lymphoma treatment (median duration after allogeneic PBSCT, 932 days; after autologous PBSCT, 370 days; and after chemotherapy, 626 days). The most common clinical presentation was neck mass (13/25, 42%), followed by asymptomatic image finding (10/25, 40%). Positron emission tomography/computed tomography (PET/CT) scan showed increased uptake compared to the liver in all patients (11/11, 100%). Of 10 lymphoma patients, 8 (80%) had a Deauville score of 4–5; they accounted for 30% (8/27) of lymphoma patients with false-positive PET/CT scan results. All cases were self-limiting. 96% (23/25) cases had Epstein–Barr virus coinfection, and EBER-positive cells were predominantly in a few germinal centers. Conclusions Cytomegalovirus (CMV) lymphadenitis and tonsillitis were subclinical infections, not primary CMV infection with IM-like syndrome. The lymphadenopathy typically developed a few years after lymphoma treatments in the middle-aged and the elderly. The lesions mimicked lymphoma relapse in PET scans. Therefore, recognizing CMV infection in lymphoid tissues is of clinical importance. Graphic abstract

This prospective non-randomized, multicenter clinical trial was performed to investigate efficacy and safety of 131I-labeled metuximab in adjuvant treatment of unresectable hepatocellular carcinoma. Methods: Patients were assigned to treatment with transcatheter arterial chemoembolization (TACE) combined with 131I-metuximab or TACE alone. The primary outcome was overall tumor recurrence. The secondary outcomes were safety and overall survival. Results: The median time to tumor recurrence was 6 months in the TACE+131I-metuximab group (n = 160) and 3 months in the TACE group (n = 160) (hazard ratio, 0.55; 95% confidence interval, 0.43 to 0.70; P < 0.001). The median overall survival was 28 months in the TACE+131I-metuximab group and 19 months in the TACE group (hazard ratio, 0.62; 95% confidence interval, 0.47 to 0.82; P = 0.001). Conclusion: TACE+131I-metuximab showed a greater anti-recurrence benefit, significantly improved the 5-year survival of patients with advanced hepatocellular carcinoma, and was well tolerated by patients.

Background This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. Methods In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. Results In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14–1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p

IgA nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and end-stage renal disease worldwide. Currently, clinical interventions for IgAN are limited, and many patients seek out alternative therapies such as traditional Chinese medicine (TCM). In the last several years, TCM has accumulated ample application experiences and achieved favorable clinical effects. This article summarizes high-quality research from basic science to clinical applications aimed to provide more evidence-based medicine proof for the clinical treatment of IgAN. In summary, qi and yin deficiency accounted for the largest proportion in IgAN patients, and the treatment of IgAN should be based on supplementing qi and nourishing yin. Further, for patients with severe IgAN, the treatment combination of Chinese and Western medicines is better than pure Chinese medicine or hormone therapy. In addition, the pharmacological mechanism of Chinese herbal medicines is mostly based on restoring the immune function, relieving the inflammation damage, and inhibiting proliferation of the glomerular mesangial cells.

Gastric cancer (GC) is the third leading cause of cancer-associated mortality globally. Although the diagnosis and therapeutic strategies for GC have improved, the prognosis for advanced gastric cancer (AGC) remains poor. Hence, the present study sought to design a zebrafish model established by microinjecting human MGC-803 GC cell line for studying personalized molecular-targeted cancer therapy. Apatinib, a novel molecular-targeted agent, was evaluated for its in vivo efficacy through a comparison among the control groups (no treatment) and subject groups (treatment). Newly formed vessel length and tumor volume were measured in all of the groups for further study. The length of newly formed vessels was obviously shortened after apatinib treatment in the zebrafish model established in this study. Meanwhile, apatinib exhibited the best antitumor growth effect with dose and time dependence by suppressing AKT/GSK3α/β signaling, which may be the mechanism underlying the profound antitumor clinical effect of apatinib. The data indicated that apatinib therapy exerts an anti-angiogenesis effect and it can be recommended as a proper antitumor growth therapy for GC patients. Additionally, zebrafish models could be designed as a potential practical tool to explore new anti-GC cancer drugs.

Previous studies have demonstrated that patients with schizophrenia (SZ) have greater rate of metabolic disorder as compared with the control population, which likely be the consequence of use of atypical antipsychotics. Olanzapine is a widely used antipsychotic, which increases the weight of SZ patients. However, the underlying mechanism remains poorly understood. Here we report the metabolomics-based understanding of the weight gain induced by olanzapine. 57 first-episode drug-naïve patients (FEDN) were recruited, of whom 27 patients completed a 4-week clinical trial. We then profiled the metabolomes of their plasma with the LC-MS-based nontargeted metabolomics approach at the baseline and after olanzapine monotherapy for 4 weeks. We observed that the plasma of the olanzapine-treated patient had significantly higher lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE) and lower carnitine as compared with that of the baseline plasma samples. Moreover, regression analyses indicated that the change of LysoPC(14:0) level was an independent contributor to the olanzapine-induced weight gain. Our study suggests that the metabolomics-based approach may facilitate the identification of biomarkers associated with the metabolic disorder causing by antipsychotic in schizophrenia patients.

Ground-level cosmic ray muon detections have various potential applications in the predictions of space and Earth weather variations and muon tomography. However, in order to push its practical applications, a low-power, low-cost, high-accuracy, and portable ground-level cosmic ray muon detection system needs to be developed. In this article, we present a high time-resolution and low-power readout integrated circuit (ROIC) for portable ground-level cosmic ray muon detection. The ROIC comprises preamplifiers, comparators, encoding modules, a delay-locked loop (DLL), and a data transfer module. The preamplifiers amplify the weak signals produced by the muon detector. The comparators convert the amplified signals into digital signals. The encoding modules extract and store the time information of the input pulses produced by the comparator, and the data transfer module transmits them to a microcontroller unit (MCU). A pulse edge detecting method using DLL clocks is employed to improve the time-resolution and limit the power consumption of the ROIC. A 32-channel prototype of the ROIC was designed and fabricated in a 0.18- $\mu \text{m}$ mixed-signal CMOS process. The main chip size is 11.4 mm2. A one-channel double-layer plastic scintillator muon detector was used to test the performance of the ROIC. A time-resolution of 1.0 ns was achieved with a system clock of 50 MHz, and the ROIC power consumption was measured at 1.9 mW/channel. Compared with existing muon readout electronics systems, the system using the proposed ROIC achieves high time-resolution and accuracy, with low power consumption and a smaller size, making it suitable for portable real-time cosmic ray muon detection.

Background/aims Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by recurrent abdominal pain and bowel dysfunction. However, the majority of previous neuroimaging studies focus on brain structure and connections but seldom on the inter-hemispheric connectivity or structural asymmetry. This study uses multi-modal imaging to investigate the abnormal changes across the 2 cerebral hemispheres in patients with IBS. Methods Structural MRI, resting-state functional MRI, and diffusion tensor imaging were acquired from 34 patients with IBS and 33 healthy controls. The voxel-mirrored homotopic connectivity, fractional anisotropy, fiber length, fiber number, and asymmetry index were calculated and assessed for group differences. In addition, we assessed their relevance for the severity of IBS. Results Compared with healthy controls, the inter-hemispheric functional connectivity of patients with IBS showed higher levels in bilateral superior occipital gyrus, middle occipital gyrus, precuneus, posterior cingulate gyrus, and angular gyrus, but lower in supplementary motor area. The statistical results showed no significant difference in inter-hemispheric anatomical connections and structural asymmetry, however negative correlations between inter-hemispheric connectivity and the severity of IBS were found in some regions with significant difference. Conclusion s The functional connections between cerebral hemispheres were more susceptible to IBS than anatomical connections, and brain structure is relatively stable. Besides, the brain areas affected by IBS were concentrated in default mode network and sensorimotor network.

BACKGROUND: Persisting shoulder stiffness adversely affects quality of life by causing pain and motion restrictions especially in patients with diabetes. OBJECTIVE: The aim of this study was to evaluate the outcomes of arthroscopic capsular release in patients with idiopathic shoulder stiffness. METHOD: A literature search was conducted in electronic databases and studies were selected by following precise eligibility criteria. Random-effects meta-analyses were performed to estimate the changes at latest follow-up in scores of the Constant, American Shoulder and Elbow Surgeons (ASES), and University of California at Los Angelis (UCLA) scales, Visual Analogue Scale (VAS), and shoulder range of motion. RESULTS: Nineteen studies were included. The follow-up duration was 42 months [95% confidence interval (CI): 32, 51]. Improvements in scores of the Constant, ASES, UCLA scales, and VAS were 48.3 [95% CI: 38.0, 58.6], 44.6 [95% CI: 24.6, 64.6], 19.3 [95% CI: 16.6, 22.0], and -6.1 [95% CI: -6.9, -5.4] respectively (P< 0.05 all). Improvements in the shoulder range of motion were: abduction 82.0 [95% CI: 65.0, 98.9]; forward flexion 75.9 [95% CI: 59.7, 92.1]; external rotation 43.2 [95% CI: 37.5, 49.0]; and internal rotation 25.4 [95% CI: 15.2, 35.5] degrees; P< 0.05 all). CONCLUSION: Arthroscopic capsular release effectively improves shoulder function in patients with idiopathic shoulder stiffness.

Geotechnical engineering involves various types of uncertainties, as it always deals with highly variable natural materials. Reliability-based design/analysis can play at least a complementary role in the design approach. In this paper, reliability analysis of anti-sliding of retaining wall with the parameters treated as random variables is performed based on the concept of random fields. Both friction angle and cohesion of soils near the interface along the base of retaining wall are treated as Gaussian fields. The spatial correlation and cross correlation of the variables are calculated by a specific covariance function and the seismic loads act on retaining walls are also taken into account. Examples are illustrated to verify the accuracy of the proposed approach. It is found from the numerical results that the spatial correlation of shear strength has an important influence on the probability of the anti-sliding failure of retaining wall. Moreover, the numerical results obtained from the proposed method are in full agreement with those obtained from Monte Carlo simulations. Therefore, the proposed method provides a new view to study the stability of a retaining wall subjected to seismic loads.

The calculation of time-varying meshing stiffness caused by the alternate contacting of the gear tooth is an essential prerequisite to obtain real and effective nonlinear dynamic characteristics of the transmission system, so that the significance of which cannot be overemphasized. Accordingly, this work proposes an improved method to get meshing stiffness with taking fillet-foundation and gear rim deflection into consideration. Compared to the traditional potential energy method, the proposed method has more superior accuracy and performance, and its effectiveness has been further verified by the finite element analytical model. After that, an ideal eight degree of freedoms (DOFs) dynamic model of one stage mass-spring-damper involute spur gear, including lateral and torsional motions, is established to study the dynamic characteristics. Due to the complexity of the gear system operating conditions, we also investigate the influence of various parameters including hub bore radius, transmitting load, and rotation speed on dynamic features, especially in heavy-load and high-speed conditions. From the results, it can be concluded that these parameters will play a prominent role in the spur gear pair dynamic behaviors, providing a certain guidance for gear design.

Background Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. Methods We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1–2N−, T1–2N+, T3–4N−, and T3–4N+). Results Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3–4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66–0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P P = 0.11) for T3–4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3–4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64–0.93; P = 0.006), but not in other subgroups. Conclusions NRT might benefit resectable gastric and GEJ cancer patients of T3–4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

Fault diagnosis based on data-driven methods are widely investigated when enough supervised samples of the target machine are available to build a reliable model. However, the labeled samples in practical operated machine are usually scarce and difficult to collect. If the model is built based on the sufficient labeled samples from different source machines, the diagnosis performance will degenerate owing to the domain discrepancy. To solve this issue, in this article, transfer learning (TL) is proposed by leveraging knowledge learned from source domain to target domain. While TL methods for fault diagnosis have been actively studied, most of them focus on learning from a single source. Since the labeled samples can come from multiple domains, more general diagnosis knowledge can be learned, which is beneficial to the prediction for the target domain. Therefore, a new TL approach based on multisource domain adaptation is proposed. A multiadversarial learning strategy is utilized for obtaining feature representations, which are invariant to the multiple domain shifts and discriminative for the learning goal at the same time. Extensive experimental analysis on four different bearing datasets is performed to illustrate the effectiveness and advantage of the proposed method.

We report a new thoracoscopic surgical skill training and assessment system with automatic scoring techniques, the Huaxi Intelligent Thoracoscopic Skill Training and Assessment (HITSTA) system. We also evaluated the discriminative ability of this system compared to our conventional scoring method at our institution. We retrospectively collected training data of thoracic board-certified thoracic surgeons at West China Hospital, Sichuan University from January 1, 2018 to January 1, 2019. Surgeons were assessed by HITSTA system and human examiners simultaneously. Total scores were summed from 3 tasks (grasping with delivery, pattern cutting, and suture with knot). Bland–Altman analysis was used to test agreement of scores made by HITSTA system (automatic scoring) and human examiners (manual scoring). Differentiation ability was also compared between the two scoring methods. Thirty-nine surgeons were recruited. Scores made by HITSTA system and human examiners were not consistent. For suture with knot, automatic scoring method could detect the score differences between different training status (trained: 26.92 ± 12.04, untrained: 19.85 ± 11.12; p = 0.026) and training duration (

Background and study aims The aim of the study was to evaluate short- and long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in China because no study has yet been conducted to confirm its effectiveness in EGC in China. Patients and methods A total of 570 EGC samples from 537 patients were collected for evaluation of en bloc, complete, and curative resection using ESD. Data from 302 patients with at least 3 years of active follow-up were collected for analysis of recurrence of EGC and occurrence of metachronous GC (MGC). Short- and long-outcomes of mixed-type and pure differentiated EGC were also compared. Results En bloc resection rates of 96.0 %, 98.7 %, and 95.2 %, complete resection rates of 91.2 %, 96.6 % and 90.8 %, and curative resection rates of 83.0 %, 96.2 % and 88.2 % were achieved in all EGCs included in the study, those with absolute indication, and those with expanded indication, respectively. As a long-term outcome, recurrence was observed in 1.3 % of patients, 3-year and 5-year recurrence rates being 0.7 % and 1.2 %, respectively. Thirteen patients (4.3 %) exhibited MGCs during follow-up, all of which were resected in a second ESD. Conclusions The effectiveness of ESD for EGC in China was confirmed, with satisfactory short- and long-term outcomes. With scheduled follow-up, the outcomes for mixed-type EGC can be similar to those for pure differentiated EGC after complete resection without development of lymphovascular invasion.

Nan Chen, Jin-Song Zhang, Tian-Xiao Zhang, Yu-Shuang Shao, Fan Zhang Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Ophthalmological Center of China Medical University, Key Laboratory of Ophthalmology, China Medical University, Shenyang, 110005, Liaoning, People’s Republic of ChinaCorrespondence: Fan ZhangDepartment of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Ophthalmological Center of China Medical University, Key Laboratory of Ophthalmology, China Medical University, Shenyang, 110005, Liaoning, People’s Republic of ChinaTel +86 18704088002Email zhangfan66_nn@163.comObjective: The aim of this study is to analyze the effect of the artificial tear drop administration time on the regularity of the corneal surface in patients with dry eye.Methods: Patients with cataract who were admitted to the hospital from January 2018 to December 2018 were divided into four groups (A, B, C, and D) based on their grade of noninvasive tear break-up time (NIBUT) and the concentration of the eye drops used. Groups A and C were classified as NIBUT grade 1 (NIBUTf of 6– 9 s and NIBUTav of 8– 13 s), and groups B and D were classified as NIBUT grade 2 (NIBUTf of < 5 s and NIBUTav of ≤ 7 s). Groups A and B received 0.1% sodium hyaluronate eye drops, and groups C and D received 0.3% sodium hyaluronate eye drops.Results: In group A, there was a significant increase (p < 0.05) in the surface regularity index (SRI) and the surface asymmetry index (SAI) measured 1 s after eye drop administration. In group B, there was a significant decrease (p < 0.05) in the SRI and the SAI measured 1 s and 5 and 10 min after eye drop administration. In group C, there was a significant increase (p < 0.05) in the astigmatism degree, SRI, SAI, and irregular astigmatism index (IAI) measured 1 s after eye drop administration. There was a significant decrease (p < 0.05) in potential visual acuity (PVA). In group D, there was a significant increase in the IAI and Q value (parameters of aspheric characteristics of cornea, corneal Q value) measured 1 s after eye drop administration as well as a significant decrease in PVA (p < 0.05).Conclusion: The use of 0.1% sodium hyaluronate eye drops in patients with dry eye aid the temporary recovery of corneal surface regularity and the stability of tear film. The 0.1% sodium hyaluronate had a significant effect for the first 10 min after treatment.Keywords: dry eye, corneal topography, corneal surface regularity, tear film, sodium hyaluronate

In multi-label learning, feature selection is an essential preprocessing module, which can be exploited a more compact and precise representation of instances. Most of existing multi-label feature selection methods are either converted into multiple single-label feature selection methods or directly utilize half-baked label information, thus it is difficult for them to obtain a discriminative feature subset across multiple labels. To tackle this problem, we propose multi-label feature selection with local discriminant model and label correlations. First, for each instance, a local clique comprising this instance and its neighboring instances is constructed, and a local discriminant model for each local clique is integrated globally to evaluate the clustering performance of all instances. Second, in terms of clustering results, we explore high-order label correlations to reduce the impact of half-baked label information. Finally, we combine l2,1-norm regularization to design the objective function to achieve multi-label feature selection. Comprehensive experiments are conducted on twelve real-world multi-label data sets, and results demonstrate the effectiveness of the proposed method in comparison with several representative methods.

Pediatric lymphoma is a kind of malignant tumor with high mortality. The complexity of pediatric lymphoma shows a great challenge for effective diagnosis and treatment. In order to meet the challenge, the combination of pseudotargeted and targeted metabolomics was used to analyze the serum metabolites in pediatric lymphoma patients and healthy controls for discovering the metabolites related to pediatric lymphoma. The serum samples were obtained from the treatment group ( n = 43 ), the control group ( n = 26 ), and the patients group ( n = 18 ). A total of 17 serum metabolites, including carnitine, leucine, creatine, urea, (6Z,9Z,12Z)-octadecatrienoic acid, linoleate, octadecenoic acid, L-palmitoylcarnitine, hexadecanoic acid, tetradecanoic acid, (9Z)-hexadecenoic acid, uric acid, glucose, 1-methylnicotinamide, hypoxanthine, L-glutamine, and taurine, were found to be related to pediatric lymphoma. They could provide a scientific diagnostic basis and therapeutic target for pediatric lymphoma and elucidate the mechanism of pediatric lymphoma.

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.

Differential morphological profile (DMP) and differential attribute profile (DAP) are effective tools for automated building extraction from very high-resolution (VHR) images. Compared to the DMP, ...

Aims The blood‐brain barrier (BBB) is a specialized and indispensable structure in brain blood vessels that is damaged during Alzheimer's disease (AD). CD147 is expressed on the BBB and deeply engaged in the AD pathological process. In this study, we aimed to provide a better understanding of the roles of CD147 in BBB function in health and neurodegenerative disease. Methods and Results We measured CD147 expression in mouse brains and demonstrated that CD147 is exclusively expressed in brain endothelial cells (BECs), and its expression decreases with age. After constructing endothelial‐specific CD147 knockout mice, we performed RNA‐sequencing on BECs isolated from mice of different ages as well as a range of database analyses. We found that endothelial CD147 is essential for the dual functions of the BBB, including barrier maintenance and transporter regulation. This study also shows that CD147 plays a pivotal role in neurodegenerative diseases, particularly in AD. Conclusions Our findings suggested that targeting CD147 in BECs may represent a novel therapeutic strategy, which promoted the design of future experimental investigations and the mechanistic understanding of neurodegenerative diseases., Mouse primary brain endothelial cells isolated from endothelial‐specific CD147 knockout mice of different ages were performed RNA‐sequencing. CD147 is essential for the dual functions of the blood‐brain barrier, including barrier maintenance and transporter regulation, and neurodegenerative diseases, particularly Alzheimer's disease.

Background Normoalbuminuric diabetic kidney disease (NADKD) is a newly defined DKD, the clinical features and pathogenesis for which are still being understood. This study aimed to investigate the features and risk factors for NADKD in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective cross-sectional study was conducted. The related clinical and laboratory data of patients with T2DM hospitalized between August 2012 and January 2020 were collected for statistical analysis. We classified the patients with T2DM into four groups on the basis of the presence or absence of albuminuria and reduced estimated glomerular filtration rate (eGFR). Analysis of variance, the Kruskal–Wallis test, and the chi-square test were used to compare the groups. Binary logistic regression analyses with a forward stepwise method were performed to explore the risk factors for renal dysfunction in hospitalized patients with normoalbuminuric T2DM. Results Among the 1620 patients evaluated, 500 (30.9%) had DKD, of which 9% had NADKD. The prevalence of stroke, cardiovascular events, carotid plaque, and peripheral arterial disease in NADKD was significantly higher than in a non-DKD control group (normoalbuminuric T2DM patients with eGFR of ≥60 ml/min/1.73 m2). Regression analyses revealed that three significant independent factors were associated with NADKD: age (OR = 1.089, confidence interval [CI] 95% [1.055–1.123], p p = 0.011), and glycated hemoglobin (HbA1c; OR = 0.839, CI 95% [0.716–0.983], p = 0.03). Conclusions NADKD is mainly associated with macrovascular rather than microvascular complications. NADKD is more common in patients with normoalbuminuric T2DM with older age, previous use of RASIs, and good glycemic control.

sRecent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood–pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Zinc ion hybrid capacitors have emerged as promising energy storage devices due to the attributes of high energy density and superb power output. The current electrode materials applied to zinc ion...

Extraordinary optical transmission (EOT) is generated when light transmits through an array of subwavelength holes on a metallic sheet. Most studies have focused on the EOT effect with ideal cylindrical holes. Subsequently, it has been recognized that imperfection in hole fabrication could alter light-matter interaction. Later, adiabatic taper is reported to promote light nano-focusing effect in the optical and near infrared wavelength regime. Due to geometrical and fabrication constraints, it is difficult to fabricate adiabatic taper for mid-infrared responsive nanohole array. In this work, we report the construction of nanohole arrays with varying near-adiabatic taper holes. We demonstrate that when the positive (inverted conic) angle increases from 10° to 20°, the peak full width half maximum (FWHM) improves by 14% from 800 to 700nm, respectively. Furthermore, inverted conical hole is shown to be superior to negative conic angle. Unlike cylindrical hole array, conical hole array maintains high transmission throughput for any given hole dimension while achieving better FWHM. The betterment in performance for conical over cylindrical holes is attributed to a localized plasmonic effect at the terminal exit. Subsequently, the device is demonstrated as a CO2 low flow sensor. The highest sensor sensitivity is determined to be between 1–4sccm.

Efforts to scale community health worker programs within primary health care systems in 7 countries illustrated that these efforts are best understood as a complex process of institutional reform. Successful scale up depends on a problem-driven political process; requires that models develop solutions that align with resources, capabilities, and commitments of key stakeholders; and emerges from iterative cycles of learning and improvement., Key Findings Despite strong interest and policy commitments from many countries, models for community-based primary health service delivery have been slow to achieve full scale or deliver quality that matches their potential. Reform requires a carefully choreographed effort to enroll key stakeholders to support change by spotlighting a locally relevant gap in the existing health system's performance. Designing and launching community health programs depends heavily on local context and must draw from models that are available within a given health system and that align with the resources, capabilities, and commitments of key stakeholders. Reform should be viewed as an ongoing adaptive and evolutionary process; learning, governance, and management systems must be designed with this trajectory in mind. Key Implications Ministries of health, development partners, and other reform stakeholders can: Use the principles in the reform cycle process to identify gaps and priorities for technical work or investmentExamine community health efforts to identify where technical approaches can be complemented by political, institutional, and reform approachesCritically examine projects that implement term-limited, externally driven interventions and adapt designs to promote sustained, well-integrated community health programs at scale, To develop guidance for governments and partners seeking to scale community health worker programs, we developed a conceptual framework, collected observations from the scale-up efforts of 7 countries, workshopped the framework with technical groups and with country stakeholders, and reviewed literature in the areas of health and policy reform, change management, institutional development, health systems, and advocacy. We observed that successful scale-up is a complex process of institutional reform. Successful scale-up: (1) depends on a carefully choreographed, problem-driven political process; (2) requires that scaled program models are drawn from solutions that are available in a given health system context and aligned with the resources, capabilities, and commitments of key health sector stakeholders; and (3) emerges from iterative cycles of learning and improvement, rather than a single, linear scale-up effort. We identify stages of the reform process associated with each of these 3 findings: problem prioritization, coalition building, solution gathering, design, program readiness, launch, governance, and management and learning. The resulting Community Health Systems Reform Cycle can be used by government, donors, and nongovernmental partners to prioritize and design community health worker scale-up efforts, diagnose challenges or gaps in successful scale-up and integration, and coordinate the contributions of diverse stakeholders.

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high‐fat diet (HFD). Increases in muscle atrophy markers (FOXO‐3, Atrogin‐1, MuRF‐1) were abrogated by FGF19 in palmitic acid (PA)‐treated C2C12 myotubes and in the skeletal muscle of HFD‐fed mice. FGF19 not only reduced HFD‐induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC‐1α, UCP‐1, PPAR‐γ) in brown adipose tissue (BAT). FGF19 treatment restored PA‐ and HFD‐induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS‐1, GLUT‐4) and mitigated the PA‐ and HFD‐induced decrease in FNDC‐5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT‐1 and PGC‐1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT‐1/PGC‐α signalling pathway, which might be a potential therapeutic target for obesity and SO.

We previously showed that donor plasma mitochondrial DNA (dmtDNA) levels were correlated with renal allograft function. The aim of the current study was to determine whether dmtDNA levels are associated with the occurrence of antibody-mediated rejection (ABMR). This is a retrospective open cohort study comprised of 167 donors and 323 recipients enrolled from January 2015 to December 2017. We quantified the mtDNA level present in donor plasma using quantitative real-time polymerase chain reaction. The average plasma dmtDNA level in the acute rejection (AR) group was higher than that of the control group (0.156 versus 0.075, p0.156, the probability of AR was 62.9%. The plasma dmtDNA level in the ABMR group was significantly higher than that of the T cell-mediated rejection group (0.185 versus 0.099, p=0.032). The area under the receiver operating characteristic curve of dmtDNA for prediction of ABMR was as high as 0.910 (95% CI 0.843-0.977). We demonstrated that plasma dmtDNA was an independent risk factor for ABMR, which is valuable in organ evaluation. dmtDNA level is a possible first predictive marker for ABMR.

Background Individuals with complex dyslipidemia, or those with medication intolerance, are often difficult to manage in primary care. They require the additional attention, expertise, and adherence counseling that occurs in multidisciplinary lipid clinics (MDLCs). We conducted a program evaluation of the first year of a newly implemented MDLC utilizing the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to provide empirical data not only on program effectiveness, but also on components important to local sustainability and future generalizability. Methods The purpose of the MDLC is to increase the uptake of guideline-based care for lipid conditions. Established in 2019, the MDLC provides care via a centralized clinic location within the healthcare system. Primary care providers and cardiologists were invited to refer individuals with lipid conditions. Using a pre/post-study design, we evaluated the implementation outcomes from the MDLC using the RE-AIM framework. Results In 2019, 420 referrals were made to the MDLC (reach). Referrals were made by 19% (148) of the 796 active cardiology and primary care providers, with an average of 35 patient referrals per month in 2019 (SD 12) (adoption). The MDLC saw 83 patients in 2019 (reach). Additionally, 50% (41/82) had at least one follow-up MDLC visit, and 12% (10/82) had two or more follow-up visits in 2019 (implementation). In patients seen by the MDLC, we found an improved diagnosis of specific lipid conditions (FH (familial hypercholesterolemia), hypertriglyceridemia, and dyslipidemia), increased prescribing of evidence-based therapies, high rates of medication prior authorization approvals, and significant reductions in lipid levels by lipid condition subgroup (effectiveness). Over time, the operations team decided to transition from in-person follow-up to telehealth appointments to increase capacity and sustain the clinic (maintenance). Conclusions Despite limited reach and adoption of the MDLC, we found a large intervention effect that included improved diagnosis, increased prescribing of guideline-recommended treatments, and clinically significant reduction of lipid levels. Attention to factors including solutions to decrease the large burden of unseen referrals, discussion of the appropriate number and duration of visits, and sustainability of the clinic model could aid in enhancing the success of the MDLC and improving outcomes for more patients throughout the system.

Background Absolute monocyte count (AMC) is often used to be assessed in cancer follow‐up, which has regained interest as a potential prognostic indicator in many solid tumors, though not consistently or comprehensively. In the present study, we set out to perform a comprehensive meta‐analysis of all available data regarding the prognostic significance of AMC in solid tumors. We also evaluated the association between AMC and clinical features in solid tumors. Methods A hazard ratio (HR) and corresponding 95% confidence interval (CI) or a p value (p) from eligible studies were extracted and subsequently pooled analyzed. Subgroup analyses and meta‐regression analyses were conducted according to the confounders of included studies. In addition, the relationships between AMC and clinical characteristics were also explored in the meta‐analysis. Results Overall, ninety‐three articles comprising 104 studies with 32229 patients were finally included. The results showed that elevated AMC was associated with worse overall survival (OS) (HR = 1.615; 95% CI: 1.475‐1.768; p, Elevated AMC indicates poor long‐term outcomes in solid tumors, which could be applied in the prognosis assessment.

As an innovative way for government affairs disclosure, official microblogs have been widely used in information release, public opinion listening, and public services, which become a model of “Internet + government affairs.” The communication influence of official accounts is mainly related to the account’s attention, activity, and the posted articles. Based on AHP, we design a multi-hierarchy-rank model to filter the factors and determine the most important factors related to the influence of official microblogs. This study explores the communication influence of official microblog from the perspectives of breadth, depth, and intensity; then, a three-dimensional integration of government microblogs influence calculation model for radiation, activity, and interaction is built and a monitoring and analysis system for the communication influence of government microblog is developed; finally, about 2,800 official accounts and more than 1.5 million articles in Zhejiang Province are monitored and analyzed. According to microblog verification, our proposed calculation model not only quantifies the communication influence of official microblogs but also analyzes their dynamics and timeliness. Therefore, it helps government departments to promote the healthy and orderly development of government microblogs.

A functional yogurt was prepared with Ligustrum robustum (Rxob.) Blume extract (LRE), while its antioxidant and hypoglycemic activities were evaluated and its action mechanism was further explored. With the cofermentation of LRE, the yogurt showed the fine quality characteristics, including pH, titratable acidity, texture, syneresis susceptibility, color, microbiological content, and chemical composition. Meanwhile, the yogurt exhibited the remarkable antioxidant capability to enhance the activities of antioxidant enzymes and reduce the malondialdehyde level in animal serums. In addition, the yogurt showed the obvious hypoglycemic activity to inhibit the decrease of glucose tolerance and the increase of postprandial hyperglycemia of diabetes mice. Furthermore, using the analysis of molecular docking, the main compounds of LRE could combine tightly with α-amylase and α-glucosidase by hydrogen bond and hydrophobic interaction, so as to change their spatial structure and inhibit their biocatalytic activity in glucose metabolism. All present results suggested that LRE showed the potential value to be used as supplement to enhance the quality and functions of yogurt in food industry. PRACTICAL APPLICATION: The hypoglycemic and antioxidant activities of a functional yogurt cofermented with LRE were found and its relative action mechanism was also explored. This work provide the experimental and theoretical basis for the application of this yogurt as nutraceuticals to protect human health in food industry.

Causality is crucial to understanding the mechanisms behind complex systems and making decisions that lead to intended outcomes. Event sequence data is widely collected from many real-world processes, such as electronic health records, web clickstreams, and financial transactions, which transmit a great deal of information reflecting the causal relations among event types. Unfortunately, recovering causalities from observational event sequences is challenging, as the heterogeneous and high-dimensional event variables are often connected to rather complex underlying event excitation mechanisms that are hard to infer from limited observations. Many existing automated causal analysis techniques suffer from poor explainability and fail to include an adequate amount of human knowledge. In this paper, we introduce a visual analytics method for recovering causalities in event sequence data. We extend the Granger causality analysis algorithm on Hawkes processes to incorporate user feedback into causal model refinement. The visualization system includes an interactive causal analysis framework that supports bottom-up causal exploration, iterative causal verification and refinement, and causal comparison through a set of novel visualizations and interactions. We report two forms of evaluation: a quantitative evaluation of the model improvements resulting from the user-feedback mechanism, and a qualitative evaluation through case studies in different application domains to demonstrate the usefulness of the system.

Chronic hepatitis B virus (HBV) infection is one of the major global health problems. Although the small protein of hepatitis B virus surface antigen (HBsAg), SHBs, is the most abundant HBV viral protein, its pathogenic role and molecular mechanism in malignant progression of HBV-related hepatocellular carcinoma (HCC) remain largely unknown. Here we reported that SHBs expression induced epithelial-mesenchymal transition (EMT) process in HCC cells and significantly increased their migratory and invasive ability as well as metastatic potential. Mechanistically, SHBs expression in HCC cells induced endoplasmic reticulum (ER) stress that activated the activating transcription factor 4 (ATF4) to increase the expression and secretion of fibroblast growth factor 19 (FGF19). The autocrine released FGF19 in turn activated JAK2/STAT3 signaling for induction of EMT process in HCC. Notably, SHBs was positively correlated with the expression of mesenchymal markers, the phosphorylation status of JAK2 and STAT3 as well as FGF19 levels in human HCC samples. HCC patients with SHBs positive had a more advanced clinical stage and worse prognosis. These results suggest an important role of SHBs in the metastasis and progression of HCC and may highlight a potential target for preventive and therapeutic intervention of HBV-related HCC and its malignant progression.