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BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of

We aimed to determine the surface locations of the nerve fascicles that innervate the lumbricals and interossei, re-examine the branching pattern of the deep branch of the ulnar nerve (dUN), and provide a clear description of their course. Eleven fresh-frozen adult cadaver hands were investigated. Nerve fascicles that innervate the lumbricals, interossei, and surface landmarks including the distal wrist crease and 2-5 proximal finger creases were marked by radio opaque fibers and subjected to X-ray. We analyzed the images and set a quadrant-linked hand surface. Subsequently, we measured the lengths of both axes and the coordinates of the branch locations in the quadrant. The surface locations of branches that innervated the lumbricals and interossei were clearly quantified. The branches of dUN exhibited a 4-group distribution pattern. Novel methods for quantitatively locating the surface anatomy of these branches and demonstration of a 4-group branching pattern of the dUN were established.

Objectives Our study aims to investigate whether PI3K/mTOR dual inhibitor LY3023414 has synergistic effects with carboplatin in suppressing endometrial cancer (EC), and explore the mechanisms and toxicity of combined therapy. Methods The effects of combined therapy of LY3023414 and carboplatin on cell viability, long-term survival and cell apoptosis were studied in vitro, and on subcutaneous xenograft model of HEC-1A cells and patient derived xenograft (PDX) models with different PI3K pathway mutational patterns in vivo. The synergistic mechanisms were explored on ATM/Chk2 and PI3K signaling pathway. The toxicity of combined therapy was also observed. Results Combined treatment of LY3023414 and carboplatin synergistically inhibited proliferation, colony formation, promoted apoptosis of EC cells, and significantly activated ATM/Chk2 signaling pathway. LY3023414 had synergistic anti-tumor effects with carboplatin in HEC-1A subcutaneous xenograft which harbors PIK3CA mutation. The sensitivity to LY3023414 and carboplatin differed in PDX of EC cases with different mutational patterns of PI3K pathway, and combined therapy exhibited distinct synergistic anti-tumor effects in those harboring different PI3K pathway mutations. No increased drug toxicity in nude mice was seen in combined groups. Conclusions Combined therapy of PI3K/mTOR dual inhibitor LY3023414 and carboplatin had synergistic anti-tumor effects in EC cell line and some of the PDX EC models, without increasing the toxicity of single drug. Enhanced carboplatin-induced DNA damage response (DDR) and cell apoptosis may be the mechanisms of synergistic effects. The anti-tumor effects may correlate with the mutational pattern of PI3K pathway, which provides experimental basis of individual treatments of ECs in the future.

Background Cryptococcal meningitis (CM) remains a leading cause of death in HIV-infected patients, despite advances in CM diagnostic and therapeutic strategies. This study was performed with the aim to develop and validate a novel scoring model to predict mortality risk in HIV-infected patients with CM (HIV/CM). Methods Data on HIV/CM inpatients were obtained from a Multicenter Cohort study in China. Independent risk factors associated with mortality were identified based on data from 2013 to 2017, and a novel scoring model for mortality risk prediction was established. The bootstrapping statistical method was used for internal validation. External validation was performed using data from 2018 to 2020. Results We found that six predictors, including age, stiff neck, impaired consciousness, intracranial pressure, CD4+ T-cell count, and urea levels, were associated with poor prognosis in HIV/CM patients. The novel scoring model could effectively identify HIV/CM patients at high risk of death on admission (area under curve 0.876; p Conclusions Our developed scoring model of six variables is simple, convenient, and accurate for screening high-risk patients with HIV/CM, which may be a useful tool for physicians to assess prognosis in HIV/CM inpatients.

Purpose: Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic. Experimental Design: MYOCD is a clinically relevant TSG in lung cancer patients. Our in vitro and in vivo data confirm its tumor suppressive function. Further analysis reveals that MYOCD potently inhibits stemness of lung cancer stem cells. Mechanistically, MYOCD localizes to TGFBR2 promoter region and thereby recruits PRMT5/MEP50 complex to epigenetically silence its transcription. Conclusions: NSCLC cells deficient of MYOCD are particularly sensitive to TGFBR kinase inhibitor (TGFBRi). TGFBRi and stemness inhibitor synergize with existing drugs to treat MYOCD deficient lung cancers. Our current work shows that loss of function of MYOCD creates Achilles' heels in lung cancer cells, which might be exploited in clinic.

This study aims to evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) alone or combined with transcatheter arterial chemoembolization (TACE) for patients with hepatocellular carcinoma (HCC) but were contraindicated for hepatectomy and radiofrequency ablation (RFA). Patients between 20 and 80 years of age with 1–3 foci of HCC were selected. Included patients have had primary or recurrent liver lesions with no evidence of extra-hepatic metastasis prior to the study. Patients were treated with ultrasound-guided HIFU alone or HIFU combined with TACE (treated with TACE once within 4 weeks prior to receiving HIFU). Thirty-seven patients were enrolled, for a total of 45 lesions. The 2-year local control (LC) rate was 73.0% and the median LC time was 22 months. The 2-year progression-free survival (PFS) was 29.7% and the median PFS time was 9 months. Finally, the 2-year overall survival (OS) was 70.3%, and the median OS time was 24 months. The most common adverse events (AEs) were elevated liver enzymes, followed by fatigue, and pain, no grade 4 AEs or death occurred. Multivariate analysis showed that age, Child–Pugh class, and the number of tumors were independent prognostic factors for PFS and that the AFP levels and the number of tumors were significantly correlated with the OS. This study indicates that the HIFU/HIFU combined with TACE treatment is safe, and is capable of achieving both a good LC rate and a considerably good prognosis. The procedure should be considered for patients who were deemed unsuitable for other local treatments.

There has been a lot of controversies about the correlation between vitamin D and colorectal cancer (CRC). In this meta-analysis, we purposed to explore the relationship between vitamin D and the incidence of CRC/the prognosis of CRC. A systematic search for articles in databases (Pubmed, Web of Science, EBSCO and Cochrane Library) was terminated in April 2020. The primary outcomes were the incidence rate of CRC and the long-term survival of patients with CRC. According to the estimated pooled OR from 21 eligible studies, covering 904,152 people, the use of vitamin D was inversely associated with the incidence of CRC [OR = 0.87, (0.82–0.92)]. Among the four studies included in this meta-analysis, covering 7486 patients, compared the overall survival (OS) of CRC between the vitamin D users and the non-users. Based on the estimated pooled HR, vitamin D potentially improved the long-term survival of CRC patients [HR = 0.91, (0.83–0.98)]. This meta-analysis demonstrates that vitamin D not only has a positive impact on the incidence of CRC from either the dietary or supplemental sources but also benefits clinical outcomes and improves the long-term survival of CRC patients. However, further studies are recommended to clarify the above phenomena.

Background To develop a clinical prediction model and web-based survival rate calculator to predict the overall survival (OS) and cancer-specific survival (CSS) of sarcomatoid renal cell carcinoma (SRCC) for clinical diagnosis and treatment. Methods SRCC patient data were retrieved from Surveillance, Epidemiology, and End Results (SEER) database. Factors independently associated with survival were identified by a Cox regression analysis. Nomograms of the prediction model were constructed using a SEER training cohort and validated with a SEER validation cohort. At the same time, the decision analysis curve, receiver operating characteristic curve, and calibration curve were also used to examine and evaluate the model. A web-based survival rate calculator was constructed to help assist in the assessment of the disease condition and clinical prognosis. Results The records of 2,742 SRCC cases were retrieved from SEER, while 1,921 cases with a median OS of 14 and CSS of 32 months were used as the training cohort. The developed nomograms were more accurate than that of the American Joint Committee on Cancer staging (C-indexes of 0.767 versus 0.725 for OS and 0.775 versus 0.715 for CSS), with better discrimination than that of the American Joint Committee on Cancer (AJCC) stage model and the calibration was validated in the SEER validation cohort. The model's 3- and 5-year OS and CSS were superior to AJCC and T staging on the analysis decision curve. The prognosis prediction of SRCC established by the prediction model could be evaluated through the web-based survival rate calculator, which plays a guiding role in clinical treatment. Conclusions Nomograms and a web-based survival rate calculator predicting the OS and CSS of SRCC patients with better discrimination and calibration were developed.

AIM: To report the effectiveness of intravitreal implantation of dexamethasone implant (Ozurdex) after phacoemulsification and intraocular lens implantation in refractory uveitis patients. METHODS: This single-center retrospective study conducted for refractory pan-uveitis patients who underwent cataract surgery combined with intravitreal Ozurdex implantation. The main outcome measurements were best-corrected visual acuity (BCVA), central retinal thickness (CRT), grade of anterior chamber cell (AAC), intraocular pressure (IOP), and systemic/ocular adverse events. RESULTS: Ten eyes of 7 patients were included. BCVA showed significant improvement at 1mo (P=0.004), 3mo (P=0.0004), and 6mo (P=0.001) post operation. There were no statistically significant differences in the postoperative CRT among follow-up groups (P>0.05). No significant differences were observed in the baseline IOP when compared to 1, 3, and 6mo (all P>0.05) post operation. One patient developed a transient elevated IOP post injection. Two eyes (20%) developed posterior capsular opacifications and underwent neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy. In six patients (8 eyes, 71.4%), the systemic steroid usage was reduced to below 10 mg/d. The patients experienced a mean of 1.4±0.52 recurrences of inflammation in the 6mo before operation and 0.7±0.48 in the 6mon post operation. The mean recurrence time was 13±0.58wk (range 12-14wk) post operation. In five of seven patients (7 out of 10 eyes), inflammation relapse was developed postoperatively. Only one patient (2 eyes) needed increased amounts of oral corticosteroids. Intraocular inflammation recurrence in the remaining patients was controlled by topical steroids. CONCLUSION: Ozurdex is considered a safe and effective approach to control postoperative inflammation in cataract surgery for patients with refractory uveitis in our study. After the disappearance of Ozurdex’s anti-inflammatory effects over time, in most cases the recurrent inflammation can be controlled by topical steroids.

Lieb lattice, a two-dimensional edge-centered square lattice, has attracted considerable interest due to its exotic electronic and topological properties. Although various optical and photonic Lieb lattices have been experimentally demonstrated, it remains challenging for an electronic Lieb lattice to be realized in real material systems. Here, based on first-principles calculations and tight-binding modeling, a silver sulfide (Ag2S) monolayer is reported as a long-sought-after inorganic electronic Lieb lattice. This Lieb-lattice Ag2S is further found to be ultrasoft, which enables its electronic properties and topological states near the Fermi level to be finely tuned, as evidenced by the strain-induced topologically non-trivial edge states near the valence band edge. These results not only provide an ideal platform to further explore and harvest interesting quantum properties but also pave a way to pursue other inorganic electronic Lieb lattices in a broader material domain.

Background: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). Methods: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Results: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients’ OS (HR, 0.49; 95% CI: 0.37–0.61) and PFS (HR, 0.52; 95% CI: 0.36–0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27–0.88) and DFS (HR, 0.49; 95% CI: 0.31–0.68). Conclusion: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies.

Line structured light vision sensor (LSLVS) with given movement is widely used in many fields of industry for simple structure, fast scanning speed, and low power consumption. One of the applications is rotating LSLVS as a 3-D LiDAR, which is applicable to tasks with limited power consumption, such as the planetary exploration task. Accurate calibration between the LSLVS and the rotating platform is essential to such system, which is difficult for the characteristics of the movement and the problem of time synchronization. In this work, we aim to perform the spatial and the temporal calibration for the rotating LSLVS in two stages. In the first stage, the extrinsic parameters are calculated based on the image data captured in different orientations, during which the LSLVS remains static to avoid errors caused by time offset. Also, multiple constraints are added in this stage in order to have the high accuracy and robustness of calibration. Then, in the second stage, with the extrinsic parameters being precisely calibrated, the temporal calibration is performed by minimizing the reprojection errors of visual feature points, which indicates the asynchronization between the trajectory profile of the LSLVS recorded by the rotating platform and retrieved from images. The observability of the extrinsic parameters and the time delay are analyzed in detail. Simulated and realistic experiments show the competitive accuracy and robustness of the proposed method.

Background: Cognitive decline in older adults is a serious public health problem today. Association between vitamin D supplementation and cognition remains controversial. Objective: To determine whether a 12-month vitamin D supplementation improves cognitive function in elderly subjects with mild cognitive impairment (MCI), and whether it is mediated through the mechanism in which telomere length (TL) regulate oxidative stress. Methods: This was a double-blind, randomized, placebo-controlled trial in Tianjin, China. Participants were all native Chinese speakers aged 65 years and older with MCI. 183 subjects were randomized to an intervention group (vitamin D 800 IU/day, n = 93) or a placebo group (the matching starch granules, n = 90), and followed up for 12 months. Tests of cognitive function and mechanism-related biomarkers were evaluated at baseline, 6 months, and 12 months. Results: Repeated-measures ANOVA showed substantial improvements in the full scale intelligence quotient (FSIQ), information, digit span, vocabulary, block design, and picture arrangement scores in the vitamin D group over the placebo group (p

Background This study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them. Methods This is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing. Results In this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of ‘9’ was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p Conclusions The developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.

To eliminate or alleviate the water blocking effect (WBE) encountered while hydraulic fracturing of coal seams, the wettability of the coal body was changed, using gas-wetting reversal technology, thus improving gas drainage. After initial measurements of contact angles, surface tension, surface free energies, erosion resistance, self-absorption capacities, and self-absorption rates of coal samples, a hydrophobic and low-surface-tension gas surfactant was selected. After comparing the results of four candidate surfactants, two surfactants were selected, FC117 and FC134, which were both hydrophobic and exhibited low surface tension, to achieve the desired effect. Testing showed that with increased surfactant concentration contact angles increased and surface tension gradually decreased. After surfactant treatment, the coal surface energy decreased, self-absorption capacities and rates of coal samples decreased significantly, and their erosion resistance was good. After determination and verification of several evaluation parameters, the results showed that the two surfactants performed well and achieved the expected effect. By optimizing and evaluating gas-wetting reversal agents, our work has provided a theoretical basis and scientific guidelines for eliminating the WBE from coal seams, thereby facilitating gas drainage.

This paper aims at revealing how tool paths influence the fatigue resistance of high-speed ball-end hard milled surfaces and proposing corresponding tool path selection methods. Three kinds of tool paths (tool paths A, B, and C with angles relative to the length direction of cuboid workpiece 0°, 90°, and 45°, respectively) were utilized during high-speed milling process of hardened AISI D2 steel. The fatigue resistance of samples for different tool paths was evaluated through three-point bending fatigue tests. Results shows that tool paths have significant effect on fatigue resistance, and the maximum discrepancy in fatigue life can reach about 37.6% for different tool paths. Samples for tool path C shows the longest fatigue life when radial depth of cut ae = 0.1 mm. However, with the further increase of ae, samples for tool path A have the best fatigue resistance, followed by tool path C and B. Microscopic stress concentration and effective residual stress are the main ways by which tool paths influence the fatigue resistance. Changing tool paths leads to the difference in surface topography orientation and then in degree of microscopic stress concentration. Moreover, the effective residual stress (residual stress component in direction parallel to cyclic tensile stress) is also directly determined by tool paths. Tool path selection methods are put forward based on the aforementioned influence mechanisms. This study indicates that improving the fatigue resistance of high-speed ball-end hard milled surfaces suffering given cyclic tensile stress is feasible by choosing appropriate tool paths.

High gas mines and outburst mines contribute to more than 30% of the coal production capacity in China. In view of this, coordinating the development and use of coal and gas has become an urgent concern for China's coal industry. After years of efforts, the concept of a co‐mining mode for coal and gas in China has gone through many stages, including theoretical discussion, engineering application, and assumption of concepts. Three modes have been gradually developed: the Huainan mode, based on pressure relief co‐mining of a protective layer; the Jincheng mode, based on directional long borehole co‐mining; and the YangQuan/SongZao mode, based on cross‐layer borehole co‐mining. These modes provide strong direction and the impetus to solve current predicaments and challenges of coal mining in China. Under the concept of “green” extraction and the corresponding urgent needs for environmental protection, high efficiency, and energy‐saving extraction, experts and scholars in the coal industry are also exploring development trends for coal in the future. For example, researchers have suggested idealized mining methods for replacing traditional mining methods, including fluidized mining technology, intelligent unmanned mining technology, precision mining technology, green development of abandoned mines technology, and mining based on other technical means.

Background We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN). Methods The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan–Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots. Results The records of 21,411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age ≥ 76 yr subgroups could not obtain survival benefit from CN. Conclusion CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them.

To investigate the efficacy and safety of preoperative halo-gravity traction and 1-stage posterior surgery for the treatment of scoliosis with intramedullary anomalies.A total of 11 patients with scoliosis with intramedullary anomalies were evaluated. All patients were treated with preoperative halo-gravity traction and 1-stage posterior surgery. The average age was 11.4 years (range, 7-21 years). All patients were followed-up for at least 2 years (mean, 3.5 years; range, 2-5 years). Their radiologic presentations and complications were reviewed.The operating time was 7.9 hours, and the intraoperative bleeding amount was 1890 mL. Both the Cobb angle of scoliosis and kyphosis were significantly improved after halo-gravity traction and the operation (P0.05). Tethered cords were released, and intraspinal masses (neurofibromatosis and lipoma) were excised. Syringomyelia and split spinal cord malformations were left untreated. None of the patients experienced deterioration in their neurologic status after surgery. No severe complications, such as infection, cerebrospinal fluid leakage, failed internal fixation, or fractured pedicle screws or rods occurred after the operation. There was no deterioration of neurologic function, delayed infection, or pseudoarthrosis during the follow-up visits.Preoperative halo-gravity traction and 1-stage posterior surgery provided patients who had scoliosis and intramedullary anomalies an effective and safe treatment option with few complications.

This pedagogical study presents building information modeling (BIM) education in the final semester construction management (CM) program. The case study conducted in Fuzhou University extends BIM education from a single BIM course in earlier undergraduate years to the senior year’s final semester project, which was designed to enable BIM utilization in multiple construction tasks (e.g., 3D site planning). This study consists of two major parts. The first part starts with the newly designed course of the final semester project of CM students. Students’ final semester project work is demonstrated depending on their selected deliverable type, which includes full BIM application group work, two partial BIM application types (i.e., construction planning/scheduling, and take-off estimate), and a research dissertation. The second part starts from the research hypothesis of whether the different deliverable type selected by students would affect their perceptions towards the final project and their professional career. Based on a follow-up questionnaire survey to the whole CM student sample aiming to test the hypotheses with statistical analyses (e.g., analysis of variance and the post-hoc analysis), it was indicated that all the four different deliverable types (i.e., subgroups) could lead to consistent perceptions of the final semester project towards their career development. However, subgroup differences were found. For example, students from the subgroup of full BIM application perceived that they had the highest level of hands-on skill enhancement throughout the project, possibly due to the fact that they linked BIM software tools to virtual reality (VR) hardware. Suggestions were provided to update the future BIM pedagogy in the final semester project, such as proper guide of CM students to opt their project deliverable type depending on their career interests, motivations in BIM utilization, and skill development needs. This current study provides insights in BIM education in terms that: 1) BIM education could be enhanced from a single course level to the senior year project in the CM program level; 2) different options offered in the final stage project within the CM curriculum might affect students’ perceptions towards BIM or their career development; and 3) the experience learned from this case study could be shared in the global community of construction education to update the curriculum incorporating information and communication technologies (e.g., BIM and VR). Future educational work in BIM could continue adopting existing educational theories (e.g., Bloom’s Taxonomy) by addressing the various levels of student learning, and viewing BIM in the bigger picture of digital construction.

Corporate environmental investment helps improve corporate environmental performance, which, therefore, is an effective micro-level solution to mitigate environmental concerns generated by corporate excessive resource exploitation and energy use. Using Chinese listed firms within environment-related industries over the period 2011–2018 as the research setting, this study applies the panel data model to investigate the impact of corporate innovation on environmental investment, as well as the moderating effects of institutional factors. The results show that corporate innovation significantly improves firms' environmental investment with 1% Research & Development (R&D) investment ratio increase generating 2326 CNY (around 351 USD at 2018 exchange rate) increase in environmental investment; the moderating effect of environment policy is positive and significant while the moderating effect of internationalisation level is not significant, indicating that current environment policy implementation helps to strengthen the positive impact of corporate innovation on environmental investment while the role of internationalisation level in this nexus is not observed. From a micro-level perspective, the findings of this study shed light on mitigating environmental concerns through enhancing corporate innovation, and provide evidence that China's corporate internationalisation process awaits more regulatory controls.

Performing fine-grained and real-time network monitoring is the core logic of various data center operation applications, such as traffic engineering, network troubleshooting, and anomaly detecting. However, the state-of-the-art network monitoring solutions either fall short of completely detecting all network incidents ( i.e. , congestion), yielding limited monitoring coverage, or introduce large overheads, yielding limited scalability. In this paper, we present HyperSight, a network traffic monitor with both high coverage and low overheads. The key idea of HyperSight is to monitor networks at the behavior level via tracking packet behavior changes. HyperSight proposes three designs for behavior-level monitoring. First, to facilitate expressing various network monitoring tasks, HyperSight presents a declarative query language based on the streaming processing model. Second, HyperSight proposes Bloom Filter Queue (BFQ), a memory-efficient algorithm to empower in-network capability for monitoring packet behavior changes. BFQ can be implemented on commodity programmable switches. Third, to support dynamic deployment and execution of packet behavior change monitoring tasks without interrupting on-service switches, HyperSight proposes virtual BFQ to support dynamic query compilation. We build a prototype of HyperSight and deploy it on commodity programmable switches. Evaluation results show that HyperSight supports a wide range of network event queries and can monitor over 99% packet behavior changes while keeping remarkably low overheads.

The capacity to diagnose cancer with the existing endogenous biomarkers remains limited because biomarkers usually act at the tumor site and are thus challenging to be detected directly from body fluids with high sensitivity and specificity, especially in the early stage of tumorigenesis. Here, we demonstrate an exogenous tumor-penetrating nanomarker composed of fluorescent nanoparticles conjugated with specific fluorescein-labeled peptides. The injectable nanomarkers perform four functions: they penetrate the tumor, target sites of cancer, cleave specific peptides by on-target protease, and drop off the labeled peptide into host urine for fluorescent detection. Sensitive in vivo tracking and monitoring of the cyclic process of the nanomarker was also accomplished. The nanomarker can noninvasively diagnose and monitor tumors with a volume of about 17 mm3 without invasive core biopsies. Enhanced capacity of early point-of-care detection for cancer is accomplished by receptor-dependent specificity of the signal generation in the urine compared with clinically used blood biomarkers.

The goal of this study is to evaluate the safety and efficacy of high intensity focused ultrasound (HIFU) for patients with colorectal liver metastases (CRLM) but were contraindicated for resection and radiofrequency ablation. Patients between 20 and 80 years of age with 1–3 liver metastases from colorectal cancer were selected. Included patients have had their primary lesions removed with no evidence of extrahepatic metastasis prior to the study. Ultrasound-guided HIFU was employed and target regions’ ablation was achieved with repeated sonications from the deep to shallow regions of the tumors section by section. Thirteen patients were enrolled. The most common adverse events (AEs) were pain (n = 8), followed by fatigue (n = 7), increased aspartate aminotransferase (AST) (n = 7), increased alanine aminotransferase (ALT) (n = 5), and skin edema (n = 4). No grade ≥ 3 AEs occurred and while most patients (76.9%) achieved a complete response, three patients achieved a partial response. The objective response rate was 100% after the first HIFU treatment. Nine patients relapsed but the tumors were mostly isolated to the liver (8/9). The median follow-up period was 25 months. The 2-year progression-free survival (PFS) was 16.7%, and the median PFS was 9 months. Notably, the 2-year overall survival (OS) was 77.8%, and the median OS was 25 months. This study indicates that the HIFU treatment is safe, is able to achieve a good tumor response rate and long-term prognosis even when the foci were in high-risk locations, and should be considered for patients who were considered unsuitable for other local treatments.

Background/Aim. Coronary artery disease (CAD) is a major health problem that has high morbidity and mortality around the world. In recent years, long noncoding RNA H19 has been reported to affect the proliferation and apoptosis of vascular cells, which directly or indirectly results in atherosclerosis. We performed a case-control study to explore the relationship between H19 gene polymorphisms (rs2735971, rs2839698, and rs3024270) and the risk of CAD. Methods. We collected 732 samples from Liaoning Province, China, and three polymorphisms in long noncoding RNA H19 were genotyped using the KASP platform. Results. Our data showed that H19 rs2735971 and rs3024270 variant genotypes were associated with a decreased risk of CAD (rs2735971, P=0.003, odds ratio OR=0.6195, 95% confidence interval=0.44−0.84; rs3024270, P=0.030, OR=0.65, 95% confidence interval=0.44−0.96). No significant association with the risk of CAD was found for H19 rs2839698 polymorphism (P>0.05). In haplotype analysis, H19 polymorphisms of rs2735971-rs2839698-rs3024270 A-C-C haplotype reduced the risk of CAD by 0.61-fold (P=0.004, OR=0.61, 95% confidence interval=0.43–0.86). In addition, we found that rs2839698 interacted with smoking (Pinteraction=0.027), and according to multifactor dimensionality reduction analysis, the three-factor model including H19 rs2839698-smoking-drinking was the best model for the risk of CAD (testing balanced accuracy=0.6979). Conclusion. Our study demonstrated that some genotypes of H19 rs2735971 and rs3024270 polymorphisms, as well as rs2735971-rs2839698-rs3024270 A-C-C haplotype, were associated with the risk of CAD in a Chinese population, and these genotypes have the potential to be biomarkers for predicting CAD risk. We also found that rs2735971-rs2839698-rs3024270 A-C-C may have a significantly lower risk of CAD. The recessive genetic model of rs3024270 could predict the severity of CAD.

Microplastic fibers (MPFs) have been found to be a major form of microplastics in freshwaters, and washing of synthetic textiles has been identified as one of their main sources. The aim of this work was to use a panel of 12 different textiles of representative fibers and textile types to investigate the source(s) of the MPF during washing. Using standardized washing tests, textile swatches tailored using five different cutting/sewing methods were washed up to 10 times. The MPF quantity and fiber length were determined using image analysis. The 12 textiles demonstrated great variability in MPF release, ranging from 210 to 72,000 MPF/g textile per wash. The median MPF length ranged from 165 to 841 μm. The number of released MPF was influenced by the cutting method, where scissor-cut samples released 3–21 times higher numbers of MPF than the laser-cut samples. The textiles with mechanically processed surfaces (i.e., fleece) released significantly more (p-value < 0.001) than the textiles with unprocessed surfaces. For all textiles, the MPF release decreased with repeated wash cycles, and a small continuous fiber release was observed after 5–6 washings, accompanied by a slight increase in the fiber length. The decrease in the number of MPF released is likely caused by depletion of the production-inherited MPFs trapped within the threads or the textile structure. The comparison of MPF release from laser-cut samples, which had sealed edges, and the other cutting methods allowed us to separate the contributions of the edge- and surface-sourced fibers from the textiles to the total release. On an average, 84% (range 49–95%) of the MPF release originated from the edges, highlighting the importance of the edge-to-surface ratio when comparing different release studies. The large contribution of the edges to the total release offers options for technical solutions which have the possibility to control MPF formation throughout the textile manufacturing chain by using cutting methods which minimize MPF formation. © 2020 American Chemical Society. ISSN:0013-936X ISSN:1520-5851

As a class of underactuated systems, cooperative dual rotary crane systems (DRCSs) are widely used to complete the task of large payload transportation in complex environments, since the working capacity of single cranes is quite limited. However, the control issues of DRCS fail to receive enough attention at present. Compared with single cranes, DRCSs contain more state variables, geometric constraints, and coupling relationships. Therefore, the complex kinematic and dynamic characteristics make controller design/stability analysis very challenging for DRCS. In order to solve these problems, based on the dynamic model of DRCS established by Lagrange’s method, an output feedback control method with consideration for actuator constraints is designed to realize accurate dual boom positioning and rapid elimination of payload swings. The stability of the equilibrium point for the closed-loop system is analyzed by using Lyapunov techniques and LaSalle’s invariance principle. To the best of our knowledge, this article yields the first solution for effective control of DRCS, which needs no velocity feedback, respects the actuator constraints, and is designed and analyzed without linearizing the complicated nonlinear dynamic equations. Finally, a series of hardware experiments on a self-built experimental platform is carried out to illustrate the effectiveness of the proposed controller. Note to Practitioners —This article is motivated by the control problem of dual rotary boom crane systems. In order to meet industrial requirements, the masses and volumes of to-be-hoisted cargoes are larger than before, and consequently, dual-crane systems are more frequently needed to fulfill transportation tasks. For such systems, although they improve the load capacity, greater challenges are caused when eliminating cargo swings in the transportation process. To the best of our knowledge, current control methods are mainly designed based on linearized/reduced models, whose performance may be not satisfactory when swing angles are large. Moreover, most methods use velocity signals with unexpected noises and ignore the constraints of actuators’ amplitudes, which may not be feasible in practical applications. To solve these problems, this article presents an output feedback controller, which can simultaneously solve the problems of saturation constraints and velocity signal unavailability. The proposed controller can guarantee accurate boom positioning and cargo swing elimination with guaranteed theoretical proof. Furthermore, the control performance is verified experimentally on a self-built testbed. In future efforts, we intend to apply the presented control method to industrial applications.

Landsenses ecology emphasizes people’s comprehensive physical senses and holistic psychological perception in ecosystem, as well as their relationships. It elevates the significance of people’s per...

Distributed machine learning (ML) has been extensively studied to meet the explosive growth of training data. A wide range of machine learning models are trained by a family of first-order optimization algorithms, i.e., stochastic gradient descent (SGD). The core operation of SGD is the calculation of gradients. When executing SGD in a distributed environment, the workers need to exchange local gradients through the network. In order to reduce the communication cost, a category of quantification-based compression algorithms are used to transform the gradients to binary format, at the expense of a low precision loss. Although the existing approaches work fine for dense gradients, we find that these methods are ill-suited for many cases where the gradients are sparse and nonuniformly distributed. In this paper, we study is there a compression framework that can efficiently handle sparse and nonuniform gradients? We propose a general compression framework, called SKCompress, to compress both gradient values and gradient keys in sparse gradients. Our first contribution is a sketch-based method that compresses the gradient values. Sketch is a class of algorithm that approximates the distribution of a data stream with a probabilistic data structure. We first use a quantile sketch to generate splits, sort gradient values into buckets, and encode them with the bucket indexes. Our second contribution is a new sketch algorithm, namely MinMaxSketch, which compresses the bucket indexes. MinMaxSketch builds a set of hash tables and solves hash collisions with a MinMax strategy. Since the bucket indexes are nonuniform, we further adopt Huffman coding to compress MinMaxSketch. To compress the keys of sparse gradients, the third contribution of this paper is a delta-binary encoding method that calculates the increment of the gradient keys and encode them with binary format. An adaptive prefix is proposed to assign different sizes to different gradient keys, so that we can save more space. We also theoretically discuss the correctness and the error bound of our proposed methods. To the best of our knowledge, this is the first effort utilizing data sketch to compress gradients in ML. We implement a prototype system in a real cluster of our industrial partner Tencent Inc. and show that our method is up to $$12\times $$ faster than the existing methods.

Background: Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD. Methods: This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0–52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study. Discussion: The tACS applied in this trial may have treatment effects on MDD with minimal side effects. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048. Key words: Major depressive disorder; Transcranial alternating current stimulation; Treatment; Trial

On March 9, 2020, Ochsner Health admitted its first COVID-19 patient. Less than 2 weeks later, Ochsner became the first hospital in Louisiana to insource diagnostic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While Ochsner soon became

Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations. These parameters demand careful analyses for the robust appraisal of newly formulated drugs during preclinical and clinical trials. In this review, we discuss the usage of PET imaging in radiopharmaceutical development; drug development approaches with PET imaging; and PET developments in oncological and cardiac drug discovery. Nanyang Technological University Authors acknowledge support from Lee Kong Chian School of Medicine, NTU Austrian Institute of Technology and Medical University of Vienna internal grant (NAM/15006), the LKC Medicine Imaging Probe Development Platform, Singapore, and the Cognitive Neuroimaging Centre (CONIC) at Nanyang Technological University, Singapore.

As the urban populations increase we have to think more deeply about how to make cities less stressful and more creative for people to live in. Liveability and quality of life are key factors while designing and managing energy, water, pollution, and waste systems which are sustainable for the long term. The rapidly developing digital technologies can help to enable these aims to be achieved. New approaches are proposed with recommendations for achieving these goals. As cities grow and change, digital technologies will be at the heart of improvement. This paper considers how observed trends will have implications on the digital cities of the future and how digital technologies will empower citizens and enable their cities to become intelligent, livable, and sustainable.

Building energy management systems (BEMS) are integrated building automation and energy management systems, utilizing IT or ICT, intelligent and interoperable digital communication technologies promoting a holistic approach to controls and providing adaptive operational optimization. The system may have multiple levels from individual sensors and actuators to users’ interface, to facilitate data collection, analysis, diagnose, trend finding, and decision-making. BEMS could provide flexible access to the building automation systems from several different platforms and locations. By using service-oriented abstractions to connect building, systems, and people, BEMS dynamically control indoor climate in a cost-effective manner and ensures the comfort, safety, and wellbeing of the occupants in buildings.

ObjectiveTo determine the effect of gender of reciprocal chromosomal translocation on blastocyst formation and pregnancy outcome in preimplantation genetic testing, including different parental ages.MethodsThis was a retrospective cohort study that enrolled 1034 couples undergoing preimplantation genetic testing-structural rearrangement on account of a carrier of reciprocal chromosomal translocation from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019. Group A represented 528 couples in which the man was the carrier of reciprocal translocation and group B represented 506 couples in which the woman was the carrier of reciprocal translocation. All patients were divided into two groups according to their age: female ageResultsThe blastocyst formation rate of group A (55.3%) is higher than that of group B (50%) and the results were statistically significant (PConclusionWhen the carrier of reciprocal translocation is male, the blastocyst formation rate is higher than that of female carrier. While there is no significant difference between the two in terms of fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate.

Background: The optimal timing for initiation of antiretroviral therapy (ART) in HIV-positive patients with cryptococcal meningitis (CM) has not, as yet, been compellingly elucidated, as research data concerning mortality risk and the occurrence of immune reconstitution inflammatory syndrome (IRIS) in this population remains inconsistent and controversial.Method: The present multicenter randomized clinical trial was conducted in China in patients who presented with confirmed HIV/CM, and who were ART-naïve. Subjects were randomized and stratified into either an early-ART group (ART initiated 2–5 weeks after initiation of antifungal therapy), or a deferred-ART group (ART initiated 5 weeks after initiation of antifungal therapy). Intention-to-treat, and per-protocol analyses of data for these groups were conducted for this study.Result: The probability of survival was found to not be statistically different between patients who started ART between 2–5 weeks of CM therapy initiation (14/47, 29.8%) vs. those initiating ART until 5 weeks after CM therapy initiation (10/55, 18.2%) (p = 0.144). However, initiating ART within 4 weeks after the diagnosis and antifungal treatment of CM resulted in a higher mortality compared with deferring ART initiation until 6 weeks (p = 0.042). The incidence of IRIS did not differ significantly between the early-ART group and the deferred-ART group (6.4 and 7.3%, respectively; p = 0.872). The percentage of patients with severe (grade 3 or 4) adverse events was high in both treatment arms (55.3% in the early-ART group and 41.8% in the deferred-ART group; p=0.183), and there were significantly more grade 4 adverse events in the early-ART group (20 vs. 13; p = 0.042).Conclusion: Although ART initiation from 2 to 5 weeks after initiation of antifungal therapy was not significantly associated with high cumulative mortality or IRIS event rates in HIV/CM patients compared with ART initiation 5 weeks after initiation of antifungal therapy, we found that initiating ART within 4 weeks after CM antifungal treatment resulted in a higher mortality compared with deferring ART initiation until 6 weeks. In addition, we observed that there were significantly more grade 4 adverse events in the early-ART group. Our results support the deferred initiation of ART in HIV-associated CM.Clinical Trials Registration:www.ClinicalTrials.gov, identifier: ChiCTR1900021195.

Deep learning is an important aspect of artificial intelligence and has been applied successfully in many optics-related fields. This paper proposes a generalized framework for generation of starting points for freeform imaging optical design based on deep learning. Compared with our previous work, this framework can be used for highly nonrotationally symmetric freeform refractive, reflective, and catadioptric systems. The system parameters can be advanced and the ranges of these system parameters can be wide. Using a special system evolution method and a K-nearest neighbor method, a full dataset consisting of the primary and secondary parts can be generated automatically. The deep neural network can then be trained in a supervised manner and can be used to generate good starting points directly. The convenience and feasibility of the proposed framework are demonstrated by designing a freeform off-axis three-mirror imaging system, a freeform off-axis four-mirror afocal telescope, and a freeform prism for an augmented reality near-eye display. The design framework reduces the designer’s time and effort significantly and their dependence on advanced design skills. The framework can also be integrated into optical design software and cloud servers for the convenience of more designers.

Background To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. Methods All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. Results Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01–1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. Conclusions In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

In the old days, ‘buildings’ provide a sense of security to safeguard the human life and properties from dangers. The research endeavours focused on structural designs and construction methods to p...

Sketch-based measurement has emerged as a promising alternative to the traditional sampling-based network measurement approaches due to its high accuracy and resource efficiency. While there have been various designs around sketches, they focus on measuring one particular flow key, and it is infeasible to support many keys based on these sketches. In this work, we take a significant step towards supporting arbitrary partial key queries, where we only need to specify a full range of possible flow keys that are of interest before measurement starts, and in query time, we can extract the information of any key in that range. We design CocoSketch, which casts arbitrary partial key queries to the subset sum estimation problem and makes the theoretical tools for subset sum estimation practical. To realize desirable resource-accuracy tradeoffs in software and hardware platforms, we propose two techniques: (1) stochastic variance minimization to significantly reduce per-packet update delay, and (2) removing circular dependencies in the per-packet update logic to make the implementation hardware-friendly. We implement CocoSketch on four popular platforms (CPU, Open vSwitch, P4, and FPGA) and show that compared to baselines that use traditional single-key sketches, CocoSketch improves average packet processing throughput by 27.2x and accuracy by 10.4x when measuring six flow keys.

Background The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA). Methods This is a prospective, observational study on GCLM patients with 1–3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS). Results Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group. Conclusion The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA.

Tong Yang,1 Xiangyu Chen,1 Zhigang Mei,1,2 Xiaolu Liu,2 Zhitao Feng,2 Jun Liao,1 Yihui Deng,1 Jinwen Ge1 1Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei, People’s Republic of ChinaCorrespondence: Zhigang Mei; Jinwen GeCollege of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, NO. 300, Xueshi Road, Yuelu District, Changsha, Hunan, 410218, People’s Republic of ChinaEmail meizhigang@hnucm.edu.cn; 001267@hnucm.edu.cnBackground: Cerebral ischemia-reperfusion injury (CIRI) is a crucial factor leading to a poor prognosis for ischemic stroke patients. As a novel Chinese medicine formula, Naotaifang (NTF) was proven to exhibit a neuroprotective effect against ischemic stroke, clinically, and to alleviate CIRI in animals. However, the mechanisms underlying the beneficial effect have not been fully elucidated.Methods: In this study, we combined a network pharmacology approach and an in vivo experiment to explore the specific effects and underlying mechanisms of NTF in the treatment of ischemia-reperfusion injury. A research strategy based on network pharmacology, combining target prediction, network construction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking was used to predict the targets of NTF in treating the ischemic stroke and CIRI. On the other hand, we used HPLC and HRMS to identify biologically active components of NTF. Middle cerebral artery occlusion models in rats were utilized to evaluate the effect and the underlying mechanisms of NTF against CIRI after ischemic stroke.Results: Network pharmacology analysis revealed 43 potential targets and 14 signaling pathways for the treatment of NTF against CIRI after ischemic stroke. Functional enrichment analysis showed that a STAT3/PI3K/AKT signaling pathway serves as the target for in vivo experimental study validation. The results of animal experiments showed that NTF significantly alleviated CIRI by decreasing neurological score, infarct volume, numbers of apoptotic neuronal cells, increasing density of dendritic spines and survival of neurons. Furthermore, NTF could increase the expression of p-STAT3, PI3K, p-AKT. In addition, the detection of apoptosis-related factors showed that the NTF could raise the expression of Bcl-2 and reduce the expression of Bax.Conclusion: This network pharmacological and experimental study indicated that NTF, as a therapeutic candidate for the management of CIRI following ischemic stroke, may exert a protective effect through the STAT3/PI3K/AKT signaling pathway.Keywords: cerebral ischemia-reperfusion injury, stroke, network pharmacology, molecular docking, STAT3/PI3K/AKT signaling pathway

High optical performance systems with wide field-of-view (FOV) have important applications in remote sensing. The radial basis functions, which have a prominent local characteristic in surface description, have attracted much attention in recent years. In this paper, an effective design method for the wide FOV imaging system using Gaussian radial basis function freeform surfaces is proposed. The FOV of the optical system is extended from a relatively small value to a larger one, and the Gaussian radial basis function surfaces are extended stepwise based on certain criteria. A high image quality and small distortion off-axis freeform three-mirror system with a wide FOV ( 60 ∘ × 0.6 ∘ ) is designed as an example. Tolerance analysis considering both surface figure error and assembly error is performed. The design results demonstrate the effectiveness of the proposed method.

Global localization is a fundamental ability for mobile robots. Considering the limitation of single type of sensor, fusing measurements from multiple sensors with complementary properties is a valuable task for study. In this paper, we propose a decoupled optimization-based framework for global–local sensor fusion, which fuses the intermittent 3D global positions and high-frequent 6D odometry poses to infer the 6D global localization results in real-time. The fusion process is formulated as estimating the relative transformation between global and local reference coordinates, translational extrinsic calibration, and the scale of the local pose estimator. We validate the full observability of the system under general movements, and further analyze the degenerated movement patterns where some related system state would be unobservable. A degeneration-aware sensor fusion method is designed which detects the degenerated directions before optimization, and adds constraints specifically along these directions to relieve the effect of the noise. The proposed degeneration-aware global–local sensor fusion method is validated in both simulation and real-world datasets with different sensor configurations, and shows its effectiveness in terms of accuracy and robustness compared with other decoupled sensor fusion methods for global localization.

Background: Currently, the association between sodium-glucose cotransporter 2 inhibitor (SGLT-2i) and malignancy risk has yet to be fully elucidated. This meta-analysis aimed to determine the relationship between SGLT-2i and malignancy risk in type 2 diabetes (T2D) patients.Methods: We searched PubMed, ScienceDirect, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science to identify randomized controlled trials (RCTs) published up to August 2020 related to T2D patients treated with SGLT-2i vs. placebo or other hypoglycemic agents. The meta-analysis's primary outcome was malignancies' incidence, and the results were evaluated using risk ratio (RR) and 95% confidence interval (CI).Results: We reviewed 76 articles (77 RCTs), comprising 45,162 and 43,811 patients in SGLT-2i and control groups, respectively. Compared with the control group, SGLT-2i had no significant association with augmented overall malignancy risk in T2D patients (RR = 1.05, 95% CI = 0.97–1.14, P = 0.20), but ertugliflozin may upsurge the risk (RR = 1.80, 95% CI = 1.02–3.17, P = 0.04). Compared with active hypoglycemic agents, dapagliflozin may increase (RR = 2.71, 95% CI = 1.46–6.43, P = 0.02) and empagliflozin may decrease (RR = 0.67, 95% CI = 0.45–0.98, P = 0.04) the malignancy risk. Compared with placebo, empagliflozin may exhibit risk increase (RR = 1.25, 95% CI = 1.05–1.49, P = 0.01), primarily in digestive system (RR = 1.48, 95% CI = 0.99–2.21, P = 0.05).Conclusions: Our results proposed that in diverse comparisons, ertugliflozin and dapagliflozin seemed to increase the malignancy risk in T2D patients. Empagliflozin may cause malignancy risk reduction compared with active hypoglycemic agents but increase overall risk primarily in the digestive system compared with placebo. In short, the relationship between SGLT-2i and malignancy in T2D patients remains unclear.

We propose a novel point annotated setting for the weakly semi-supervised object detection task, in which the dataset comprises small fully annotated images and large weakly annotated images by points. It achieves a balance between tremendous annotation burden and detection performance. Based on this setting, we analyze existing detectors and find that these detectors have difficulty in fully exploiting the power of the annotated points. To solve this, we introduce a new detector, Point DETR, which extends DETR by adding a point encoder. Extensive experiments conducted on MS-COCO dataset in various data settings show the effectiveness of our method. In particular, when using 20% fully labeled data from COCO, our detector achieves a promising performance, 33.3 AP, which outperforms a strong baseline (FCOS) by 2.0 AP, and we demonstrate the point annotations bring over 10 points in various AR metrics.

Background Severe fever with thrombocytopenia syndrome (SFTS), an emerging tickborne infectious disease caused by a novel banyangvirus (SFTS virus, SFTSV), was endemic in several Asian countries with a high mortality up to 30%. Until recently, SFTSV-associated re-infection have not been reported and investigated. Case presentation A 42-year-old female patient was identified as a case of SFTS with re-infection, with two episodes of SFTSV infection on June 2018 and May 2020. The diagnosis of SFTS was confirmed by detection of SFTSV RNA in the blood samples using real-time reverse-transcription polymerase chain reaction and antibodies specific for SFTSV using enzyme linked immunosorbent assay. The changes of viremia and antibody response differed between the two episodes. Phylogenetic analysis showed the two viral genome sequences were in the same clade, but showing 0.6% dissimilarity of the nearly whole nucleotide sequence. Analysis of clinical data revealed that the second episode showed milder illness than that of the first episode. Conclusions Epidemiological and clinical findings, viral whole genomic sequences, and serological evidence, provided evidence for the re-infection of SFTSV rather than prolonged viral shedding or relapse of the original infection. The patients with re-infection of SFTSV may be at high odds of clinically inapparent or mildly symptomatic. More attention should be directed towards the long-term follow up of the recovered patients in the future, to explicitly acquire the decay profile of their immunity response. Graphic abstract

Objective: Abnormal elevation of D-dimer levels is an important indicator of disseminated intravascular clotting. Therefore, we hypothesized that high D-dimer levels were associated with the risk of stroke and adverse clinical outcomes of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).Methods: The present meta-analysis aimed to systematically analyze the associations between D-dimer and the risk of stroke as well as the clinical outcomes of patients with post-stroke or TIA. Meanwhile, dose–response analyses were conducted when there were sufficient data available. Three electronic databases including Pubmed, the Embase database, and the Cochrane Library were searched by two investigators independently. All the pooled results were expressed as risk ratios (RRs).Results: Finally, 22 prospective cohort studies were included into this meta-analysis. The results suggested that high D-dimer levels were associated with increased risks of total stroke (RR 1.4, 95%CI 1.20–1.63), hemorrhagic stroke (RR 1.25, 95%CI 0.69–2.25), and ischemic Stroke (RR 1.55, 95%CI 1.22–1.98), and the dose-dependent relationship was not found upon dose–response analyses. Besides, the high D-dimer levels on admission were correlated with increased risks of all-cause mortality [RR 1.77, 95% confidence interval (CI) 1.26–2.49], 5-day recurrence (RR 2.28, 95%CI 1.32–3.95), and poor functional outcomes (RR 2.01, 95%CI 1.71–2.36) in patients with AIS or TIA.Conclusions: On the whole, high D-dimer levels may be associated with the risks of total stroke and ischemic stroke, but not with hemorrhagic stroke. However, dose–response analyses do not reveal distinct evidence for a dose-dependent association of D-dimer levels with the risk of stroke. Besides, high D-dimer levels on admission may predict adverse clinical outcomes, including all-cause mortality, 5-day recurrence, and 90-day poor functional outcomes, of patients with AIS or TIA. More studies are warranted to quantify the effect of D-dimer levels on the risk of stroke or TIA, so as to verify and substantiate this conclusion in the future.

Background The prognosis of pancreatic cancer (PC) is extremely poor, and most patients with metastatic PC still receive palliative care. Here, we report the efficacy and safety of FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, 5-fluorouracil) in the treatment of metastatic PC. Methods We searched PubMed, Web of Science, EBSCO, and Cochrane library databases for articles that described efficacy and safety of FOLFIRINOX in patients with metastatic PC, from January 1996 to July 2020. The primary outcomes targeted included overall survival (OS) and progression-free survival (PFS). Results We found that FOLFIRINOX could directly improve OS rate of patients with metastatic PC (HR 0.76, 95% Cl 0.67–0.86, pppp>0.05). The main adverse events (AEs) targeted hematological toxicity and the gastrointestinal system, and included febrile neutropenia, a reduction in white blood cells and appetite, as well as diarrhea. Conclusion These findings indicated that FOLFIRINOX has potential benefits for the prognosis of patients with metastatic PC. Furthermore, there is no difference between the regimen of FOLFIRINOX and nab-paclitaxel + gemcitabine in this study. The application of FOLFIRINOX should be according to the actual situation of the patients and the experience of the doctors. Graphical abstract

Aim To compare the prediction error between Barrett Toric calculator and the new online AcrySof Toric calculator which incorporated Barrett astigmatism algorithm in Chinese cataract eyes with normal axial length and anterior chamber depth (ACD). Methods Prospective case-control study. All the cases had axial length (21-26 mm) with ACD no less than 2.4 mm. Keratometric values were measured by LenSTAR 900. The Barrett Toric calculator was used in group 1. In group 2, SRK-T formula was used to determine the spherical power of the Toric lens, and subsequent calculation of the cylinder type was performed using the new online Alcon Toric calculator. At 1 and 3mo after surgery, a comprehensive subjective optometry was performed. The predicted residual astigmatism calculated by the two calculators was compared with that obtained by postoperative refraction, and the difference was defined as the astigmatism correction error [error of refractive astigmatism (ERA)]. The error magnitude (EM) refers to the algebraic deviation of ERA, and the error vector (EV) indicates the vector deviation of ERA. The influence of the two calculation methods on the correction accuracy of toric IOL was quantitatively analyzed. Results The |EM| obtained at 1mo after surgery were 0.21±0.12 D, 0.22±0.18 D in group 1 and group 2 respectively, and correspondingly turned to be 0.19±0.13 D, 0.20±0.19 D at 3mo after surgery, with no statistical difference (P=0.633, P=0.877). The vector analysis showed that |EV| values in two groups at 1mo after surgery were 0.29±0.14@105 (D@angle) and 0.35±0.20@113 (D@angle), respectively, whereas |EV| values 3mo after surgery were 0.27±0.16@86 (D@angle) and 0.32±0.23@102 (D@angle), respectively. The differences between the groups were not statistically significant (P=0.119, P=0.261). Conclusion The clinical effect of Barrett Toric calculator has a much more accurate tendency than that of new online AcrySof Toric calculator, but is not evident in cases with normal axial length and normal anterior posterior ratio.