Showing papers by "Nanchang University published in 2021"

A deep learning algorithm using CT images to screen for Corona virus disease (COVID-19).

Abstract: The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has caused more than 26 million cases of Corona virus disease (COVID-19) in the world so far. To control the spread of the disease, screening large numbers of suspected cases for appropriate quarantine and treatment are a priority. Pathogenic laboratory testing is typically the gold standard, but it bears the burden of significant false negativity, adding to the urgent need of alternative diagnostic methods to combat the disease. Based on COVID-19 radiographic changes in CT images, this study hypothesized that artificial intelligence methods might be able to extract specific graphical features of COVID-19 and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control. We collected 1065 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the inception transfer-learning model to establish the algorithm, followed by internal and external validation. The internal validation achieved a total accuracy of 89.5% with a specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with a specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images, the first two nucleic acid test results were negative, and 46 were predicted as COVID-19 positive by the algorithm, with an accuracy of 85.2%. These results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis. • The study evaluated the diagnostic performance of a deep learning algorithm using CT images to screen for COVID-19 during the influenza season. • As a screening method, our model achieved a relatively high sensitivity on internal and external CT image datasets. • The model was used to distinguish between COVID-19 and other typical viral pneumonia, both of which have quite similar radiologic characteristics.

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

Abstract: Summary Background China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2–3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. Methods This randomised, open-label, phase 2–3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab–bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov , NCT03794440 . The study is closed to new participants and follow-up is ongoing for long-term outcomes. Findings Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab–bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8–46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5–11·7) in the sintilimab–bevacizumab biosimilar group and 10·0 months (8·4–11·7) in the sorafenib group. Patients in the sintilimab–bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1–5·7]) than did patients in the sorafenib group (2·8 months [2·7–3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46–0·70; p Interpretation Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. Funding Innovent Biologics. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial.

Abstract: Purpose: We assessed the efficacy and safety of camrelizumab [an anti-programmed death (PD-1) mAb] plus apatinib (a VEGFR-2 tyrosine kinase inhibitor) in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods: This nonrandomized, open-label, multicenter, phase II study enrolled patients with advanced HCC who were treatment-naive or refractory/intolerant to first-line targeted therapy. Patients received intravenous camrelizumab 200 mg (for bodyweight ≥50 kg) or 3 mg/kg (for bodyweight Results: Seventy patients in the first-line setting and 120 patients in the second-line setting were enrolled. As of January 10, 2020, the ORR was 34.3% [24/70; 95% confidence interval (CI), 23.3–46.6] in the first-line and 22.5% (27/120; 95% CI, 15.4–31.0) in the second-line cohort per IRC. Median progression-free survival in both cohorts was 5.7 months (95% CI, 5.4–7.4) and 5.5 months (95% CI, 3.7–5.6), respectively. The 12-month survival rate was 74.7% (95% CI, 62.5–83.5) and 68.2% (95% CI, 59.0–75.7), respectively. Grade ≥3 treatment-related adverse events (TRAE) were reported in 147 (77.4%) of 190 patients, with the most common being hypertension (34.2%). Serious TRAEs occurred in 55 (28.9%) patients. Two (1.1%) treatment-related deaths occurred. Conclusions: Camrelizumab combined with apatinib showed promising efficacy and manageable safety in patients with advanced HCC in both the first-line and second-line setting. It might represent a novel treatment option for these patients. See related commentary by Pinato et al., p. 908

Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)-H Bonds.

Abstract: Transition-metal-catalyzed, coordination-assisted C(sp3)-H functionalization has revolutionized synthetic planning over the past few decades as the use of these directing groups has allowed for increased access to many strategic positions in organic molecules. Nonetheless, several challenges remain preeminent, such as the requirement for high temperatures, the difficulty in removing or converting directing groups, and, although many metals provide some reactivity, the difficulty in employing metals outside of palladium. This review aims to give a comprehensive overview of coordination-assisted, transition-metal-catalyzed, direct functionalization of nonactivated C(sp3)-H bonds by covering the literature since 2004 in order to demonstrate the current state-of-the-art methods as well as the current limitations. For clarity, this review has been divided into nine sections by the transition metal catalyst with subdivisions by the type of bond formation. Synthetic applications and reaction mechanism are discussed where appropriate.

A smartphone-read ultrasensitive and quantitative saliva test for COVID-19.

Abstract: Point-of-care COVID-19 assays that are more sensitive than the current RT-PCR (reverse transcription polymerase chain reaction) gold standard assay are needed to improve disease control efforts. We describe the development of a portable, ultrasensitive saliva-based COVID-19 assay with a 15-min sample-to-answer time that does not require RNA isolation or laboratory equipment. This assay uses CRISPR-Cas12a activity to enhance viral amplicon signal, which is stimulated by the laser diode of a smartphone-based fluorescence microscope device. This device robustly quantified viral load over a broad linear range (1 to 105 copies/μl) and exhibited a limit of detection (0.38 copies/μl) below that of the RT-PCR reference assay. CRISPR-read SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) RNA levels were similar in patient saliva and nasal swabs, and viral loads measured by RT-PCR and the smartphone-read CRISPR assay demonstrated good correlation, supporting the potential use of this portable assay for saliva-based point-of-care COVID-19 diagnosis.

Robust Transmission Design for Intelligent Reflecting Surface-Aided Secure Communication Systems With Imperfect Cascaded CSI

Abstract: In this paper, we investigate the design of robust and secure transmission in intelligent reflecting surface (IRS) aided wireless communication systems. In particular, a multi-antenna access point (AP) communicates with a single-antenna legitimate receiver in the presence of multiple single-antenna eavesdroppers, where the artificial noise (AN) is transmitted to enhance the security performance. Besides, we assume that the cascaded AP-IRS-user channels are imperfect due to the channel estimation error. To minimize the transmit power, the beamforming vector at the transmitter, the AN covariance matrix, and the IRS phase shifts are jointly optimized subject to the outage rate probability constraints under the statistical cascaded channel state information (CSI) error model. To handle the resulting non-convex optimization problem, we first approximate the outage rate probability constraints by using the Bernstein-type inequality. Then, we develop a suboptimal algorithm based on alternating optimization, the penalty-based and semidefinite relaxation methods. Simulation results reveal that the proposed scheme significantly reduces the transmit power compared to other benchmark schemes.

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.

Abstract: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD.

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial

Abstract: Summary Background The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. Methods In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18–75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT03707509 , and is closed for enrolment but is ongoing. Findings Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3–11·4]) than in the placebo group (median 6·9 months [5·9–7·3]; hazard ratio 0·54 [95% CI 0·39–0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one ( Interpretation Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. Funding Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). Translation For the Chinese translation of the abstract see Supplementary Materials section.

Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic-Synergized Multimodal Therapy.

Abstract: Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective tumor treatment. However, the limited intratumoral Fenton reaction efficiency restricts the therapeutic efficacy of CDT. Recent years have witnessed the impressive development of various strategies to increase the efficiency of intratumoral Fenton reaction. The introduction of these reinforcement strategies can dramatically improve the treatment efficiency of CDT and further promote the development of enhanced CDT (ECDT)-based multimodal anticancer treatments. In this review, the authors systematically introduce these reinforcement strategies, from their basic working principles, reinforcement mechanisms to their representative clinical applications. Then, ECDT-based multimodal anticancer therapy is discussed, including how to integrate these emerging Fenton reinforcement strategies for accelerating the development of multimodal anticancer therapy, as well as the synergistic mechanisms of ECDT and other treatment methods. Eventually, future direction and challenges of ECDT and ECDT-based multimodal synergistic therapies are elaborated, highlighting the key scientific problems and unsolved technical bottlenecks to facilitate clinical translation.

NaNbO3-(Bi0.5Li0.5)TiO3 Lead-Free Relaxor Ferroelectric Capacitors with Superior Energy-Storage Performances via Multiple Synergistic Design

Abstract: Relaxor ferroelectric (FE) ceramic capacitors have attracted increasing attention for their excellent energy-storage performance. However, it is extremely difficult to achieve desirable comprehensive energy-storage features required for industrial applications. In this work, very high recoverable energy density W-rec approximate to 8.73 J cm(-3), high efficiency eta approximate to 80.1%, ultrafast discharge rate of

Correlation Between Relative Nasopharyngeal Virus RNA Load and Lymphocyte Count Disease Severity in Patients with COVID-19.

Abstract: The aim of this study was to analyze the correlation between dynamic changes in the nasopharyngeal viral load of patients infected with the new coronavirus causing pneumonia and lymphocyte count disease severity. Cases newly diagnosed with COVID-19 at the First Affiliated Hospital of Nanchang University from January 2020 to February 2020 were analyzed retrospectively. Quantitative real-time polymerase chain reaction was used to determine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from throat swab sample ΔCT values; lymphocyte and lymphocyte subset counts, coagulation system factor levels, myocardial injury indexes, and laboratory biochemical indicators were compared between the mild group and the severe group. The correlation between the relative load of nasopharyngeal SARS-CoV-2 RNA and severe disease symptoms was analyzed. Of the 76 patients, 49 were male and 27 were female. The lymphocyte, CD4+ T lymphocyte, and CD8+ T lymphocyte counts all differed significantly between the two groups (p < 0.001), as did differences in interleukin (IL)-2R, IL-6, and IL-8 levels (p = 0.022, 0.026, and 0.012, respectively). Moreover, there were significant differences in prothrombin time, D-dimer, and fibrinogen levels between the mild group and the severe group (p = 0.029, 0.006, and <0.001, respectively), and in lactate dehydrogenase and troponin (p < 0.001 and p = 0.007, respectively). SARS-CoV-2 RNA load and lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count were linearly negatively correlated (p < 0.001). SARS-CoV-2 RNA load was positively correlated with IL-2R, prothrombin time, lactate dehydrogenase, and hypersensitive troponin T (p = 0.002, p = 0.009, and p < 0.001, respectively). In addition, the time that it took for the nucleic acid test to turn negative was significantly shorter for patients in the mild group than for those in the severe group (Z = -6.713, p < 0.001). In conclusion, relative SARS-CoV-2 RNA load in the nasopharynx is closely related to COVID-19 severity. If the relative RNA load was higher, the lymphocyte count was lower, organ damage was greater, and the time it took for the nucleic acid test to turn negative was longer.

Joint Resource and Trajectory Optimization for Security in UAV-Assisted MEC Systems

Abstract: Unmanned aerial vehicle (UAV) has been widely applied in internet-of-things (IoT) scenarios while the security for UAV communications remains a challenging problem due to the broadcast nature of the line-of-sight (LoS) wireless channels. This article investigates the security problems for dual UAV-assisted mobile edge computing (MEC) systems, where one UAV is invoked to help the ground terminal devices (TDs) to compute the offloaded tasks and the other one acts as a jammer to suppress the vicious eavesdroppers. In our framework, minimum secure computing capacity maximization problems are proposed for both the time division multiple access (TDMA) scheme and non-orthogonal multiple access (NOMA) scheme by jointly optimizing the communication resources, computation resources, and UAVs’ trajectories. The formulated problems are non-trivial and challenging to be solved due to the highly coupled variables. To tackle these problems, we first transform them into more tractable ones then a block coordinate descent based algorithm and a penalized block coordinate descent based algorithm are proposed to solve the problems for TDMA and NOMA schemes, respectively. Finally, numerical results show that the security computing capacity performance of the systems is enhanced by the proposed algorithms as compared with the benchmarks. Meanwhile, the NOMA scheme is superior to the TDMA scheme for security improvement.

Landslide susceptibility zonation method based on C5.0 decision tree and K-means cluster algorithms to improve the efficiency of risk management

Abstract: Machine learning algorithms are an important measure with which to perform landslide susceptibility assessments, but most studies use GIS-based classification methods to conduct susceptibility zonation. This study presents a machine learning approach based on the C5.0 decision tree (DT) model and the K-means cluster algorithm to produce a regional landslide susceptibility map. Yanchang County, a typical landslide-prone area located in northwestern China, was taken as the area of interest to introduce the proposed application procedure. A landslide inventory containing 82 landslides was prepared and subsequently randomly partitioned into two subsets: training data (70% landslide pixels) and validation data (30% landslide pixels). Fourteen landslide influencing factors were considered in the input dataset and were used to calculate the landslide occurrence probability based on the C5.0 decision tree model. Susceptibility zonation was implemented according to the cut-off values calculated by the K-means cluster algorithm. The validation results of the model performance analysis showed that the AUC (area under the receiver operating characteristic (ROC) curve) of the proposed model was the highest, reaching 0.88, compared with traditional models (support vector machine (SVM) = 0.85, Bayesian network (BN) = 0.81, frequency ratio (FR) = 0.75, weight of evidence (WOE) = 0.76). The landslide frequency ratio and frequency density of the high susceptibility zones were 6.76/km2 and 0.88/km2, respectively, which were much higher than those of the low susceptibility zones. The top 20% interval of landslide occurrence probability contained 89% of the historical landslides but only accounted for 10.3% of the total area. Our results indicate that the distribution of high susceptibility zones was more focused without containing more “stable” pixels. Therefore, the obtained susceptibility map is suitable for application to landslide risk management practices.

The Risks of miRNA Therapeutics: In a Drug Target Perspective

Abstract: RNAi therapeutics have been growing. Patisiran and givosiran, two siRNA-based drugs, were approved by the Food and Drug Administration in 2018 and 2019, respectively. However, there is rare news on the advance of miRNA drugs (another therapeutic similar to siRNA drug). Here we report the existing obstacles of miRNA therapeutics by analyses for resources available in a drug target perspective, despite being appreciated when it began. Only 10 obtainable miRNA drugs have been in clinical trials with none undergoing phase III, while over 60 siRNA drugs are in complete clinical trial progression including two approvals. We mechanically compared the two types of drug and found that their major distinction lay in the huge discrepancy of the target number of two RNA molecules, which was caused by different complementary ratios. One miRNA generally targets tens and even hundreds of genes. We named it "too many targets for miRNA effect" (TMTME). Further, two adverse events from the discontinuation of two miRNA therapeutics were exactly answered by TMTME. In summary, TMTME is inevitable because of the special complementary approach between miRNA and its target. It means that miRNA therapeutics would trigger a series of unknown and unpreventable consequences, which makes it a considerable alternative for application.