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This paper proposes a generalized deep continual learning-based cybertwin (GDC) modeling framework for developing one wind turbine (WT) cybertwin serving multiple modeling tasks in the wind farm operations and maintenance (O&M). A generalized WT cybertwin modeling problem is first formulated. Fully connected deep neural networks (DNNs) are adopted as the backbone for developing the GDC. The online elastic weight consolidation (OEWC) method is incorporated to mitigate the catastrophic forgetting phenomenon among different modeling tasks. Computational experiments are conducted to validate the effectiveness of the proposed GDC framework based on the supervisory control and data acquisition (SCADA) data. Three classical tasks, the WT gearbox failure detection, WT blade breakage detection, and wind power prediction, studied in the wind farm O&M are considered in the experiment. Compared with considered benchmarking models, the proposed GDC can achieve high accuracies on new tasks while maintain high accuracies on previous tasks.

Based on the core developmental demands of smart steel manufacturing plants, this review analyzes the essential characteristics of the steel manufacturing process and its implications for production and operation decision optimization (PODO). A discussion on the potential application of technologies, including the Industrial Internet, big data, cloud computing, and 5G, in the PODO of smart steel plants based on the Industry 4.0 intelligent manufacturing and human-cyber-physical system (HCPS) is also presented. An adaptive update conception for a new dual-level cyber system (for management control and unit operation) of a flat-structured HCPS for steel plants is proposed to eliminate issues such as the hierarchical structure of the cyber system, the occurrence of data islands, and weak intelligence in PODO ability. Additionally, the review provided an in-depth analysis of the closed-loop decision logic of a dual-level HCPS. The critical technologies required for developing the HCPS model include data platforms and their associated application technologies, intelligent modeling, human-machine collaboration, and platform-based integration. Finally, suggestions are proposed to develop smart steel plants, including concept renewal, technological integration, and talent training.

Intra-arterial infusion chemotherapy (IAIC), using immunomodulatory cisplatin, is a novel treatment for bladder cancer (BC) that allows the delivery of specific drugs to the local malignant lesion. To explore the immunomodulatory effect of cisplatin during IAIC, we detected the proportion of immunosuppressed cells in BC tissue from eight BC patients, with the reduction of myeloid-derived suppressor cells (MDSCs), more specifically fibrocytic-MDSCs (f-MDSCs). Further, we demonstrated that cisplatin inhibits their proliferation and immunosuppressive activity. f-MDSCs promote tumor proliferation and metastasis in the BC immune environment. Then, we analyzed the genetic differences detected in samples before and after chemotherapy and found that granulocyte colony-stimulating factors (G-CSF) decreased after IAIC. Furthermore, G-CSF methylation decreased following treatment with cisplatin. Specifically, treatment with cisplatin decreased the methylase (METTL3) levels in BC cells, which is important for G-CSF production. Collectively, cisplatin decreased the number of f-MDSCs during IAIC, by blocking G-CSF methylation via targeting METTL3.

This is a retrospective case–control study to ascertain the factors influencing nosocomial infection (NI) in elderly patients with hip fractures. A total of 80,174 patients (≥ 60 years) who suffered hip fractures between 2006 and 2017 were identified through a national inquiry of 94 hospitals. The patients were divided into an NI group and control group according to the occurrence or lack of occurrence of NI within 48 hours after surgery, respectively. Age, gender, hip fracture pattern, whether to operate, surgical treatments, and comorbidities were recorded as variables. A total of 9806 elderly hip fracture patients (60 years) were included, 1977 of whom were patients diagnosed with NI. The control group consisted of randomly drawn cases from the 9806 patients from different hospitals with a rate of one NI patient: four patients without NI. Patient gender, age, and in particular the number of comorbidities were associated with occurrence of NI. Using regression models to predict infection outcomes based on the number of comorbidities had an area under the curve (AUC) of 0.714, while using the Charlson comorbidity index (CCI) yielded a smaller value of 0.694. The most common comorbidities of this elderly cohort were chronic respiratory disease, hypertension, diabetes mellitus, cerebrovascular disease, and coronary heart disease. Older age, male gender, and greater number of comorbidities were found to be associated with the occurrence of NI. In particular, the number of comorbidities was the most accurate predictor of NI occurrence, and when used to build a regression model, it had greater predictive capability than CCI to predict NI in elderly hip fracture patients. Additionally, the common diseases of the elderly should be primarily considered when investigating the relationship between comorbidities and NI in older patients.

Piezochromic luminescent materials have shown great potential in advanced optoelectronic applications. However, most of luminescent materials usually undergo emission quenching under external stimuli. Herein, we demonstrate for the first time that the photoluminescence of carbon dots (CDs) confined within sodium hydroxide can be enhanced when high pressure is applied. They exhibit a 1.6-fold fluorescence enhancement compared with pristine CDs. Importantly, the enhanced fluorescence intensity can be retained after the release of pressure to ambient conditions. A combination of experimental analysis and theoretical simulations indicates that such an enhanced emission is mainly attributed to the strong confinement resulting from the sodium hydroxide matrix, which can separate the CDs spatially and restrict the nonradiative pathway. These results provide a rational strategy for manipulating the optical properties of CDs with enhanced and retainable photoluminescence (PL) performance, thus opening up a venue for designing luminescent CDs-based materials.

Acne inversa/hidradenitis suppurativa is a chronic, recurrent, inflammatory skin disease that affects the pilosebaceous units, causinfollicular occlusion. The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility, inflammation and immunity, microorganisms, obesity, and smoking. acne inversa/hidradenitis suppurativa is difficult to treat, and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life. Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade. Medical treatments include antibiotics, retinoids, biologics, immunosuppressive agents, and antiandrogen agents. Adjuvant treatments include surgery and laser/light therapies. This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment.

To explore the effect of low-frequency magnetic stimulation at Shenmen (HT 7) acupoint on blood oxygen levels in the prefrontal cortex of healthy subjects. Functional near-infrared spectroscopy (fNIRS) technology was used to collect real-time data of oxygenated hemoglobin (oxy-Hb) in the prefrontal cortex of 16 healthy subjects at resting state and low-frequency magnetic stimulation of Shenmen. The mean and integral values of blood oxygen concentration were analyzed. Compared with the resting state, the mean and integral values of blood oxygen concentration were decreased during the task period, recovery period, and the whole process in the magnetic stimulation of Shenmen acupoint (P

BACKGROUND Acute pancreatitis is the leading cause of hospitalization for acute gastrointestinal disease worldwide. The effects of probiotics in mild acute pancreatitis have not been studied. We hypothesized that the administration of probiotics may accelerate the recovery of intestinal function and shorten the length of hospital stay (LOS) in patients with mild pancreatitis. AIM To investigate the value of probiotics in reducing the LOS in patients with mild acute pancreatitis. METHODS We conducted a double-blind randomized clinical trial to evaluate the effects of probiotics administered to patients with mild acute pancreatitis at a tertiary medical center. The patients were given probiotics capsules (a mixed preparation of Bacillus subtilis and Enterococcus faecium) or placebo. The primary study endpoint was the LOS. The secondary endpoints included time to abdominal pain relief, recurrent abdominal pain, and time to successful oral feeding. RESULTS A total of 128 patients were included, with 64 patients in each arm. The severity of illness and the etiological distribution of disease were similar in the two groups. There was a significant reduction in the LOS in the probiotics treatment group vs the placebo group (5.36 ± 0.15 vs 6.02 ± 0.17 d, P < 0.05). The probiotics group was associated with a shorter time to abdominal pain relief and time to successful oral feeding (P < 0.01 for both) than the placebo group. No statistical difference was found in recurrent abdominal pain between the two groups. CONCLUSION The study results showed that the administration of probiotics capsules is associated with a shorter duration of hospitalization in patients with mild acute pancreatitis.

Background Gastric cancer (GCa) is one of the six major malignancies in the world with low survival rate. Although there are advances in therapeutic approaches, the prognosis of patients with GCa remains not optimistic. Therefore, this study aimed to evaluate the prognostic value of miR-324-5p, as well as its functional role in GCa progression. Methods The expression of miR-324-5p in tumor tissues and cell lines was examined using real-time quantitative PCR. The prognostic value of miR-324-5p in patients with GCa was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Gain- and loss-of-function experiments were performed to evaluate the biological function of miR-324-5p during the progression of GCa, and a target gene of miR-324-5p was proposed. Results The expression of miR-324-5p was up-regulated in GCa tissues and cell lines. Patients with high expression of miR-324-5p had more cases with positive lymph node metastasis, advanced TNM stage, and worse overall survival compared with patients with low expression. The elevated miR-324-5p was an independent prognostic indicator of GCa. In addition, the inhibition of miR-324-5p could suppress GCa cell proliferation, migration and invasion and promote cell apoptosis, and PTEN was demonstrated to serve as a direct target of miR-324-5p in GCa progression. Conclusion The present study indicates that miR-324-5p overexpression predicts poor prognosis in GCa patients, and the reduction of miR-324-5p can inhibit GCa biological processes. PTEN is a target gene of GCa, which may mediate the biological function of miR-324-5p in GCa progression.

Background: There are great interindividual variations in the clinical efficacy of methotrexate (MTX) treatment and patients’ genetic background seems promising in its explanation. Objectives: The study aimed to test whether the polymorphism of annexin A6 (ANxA6) gene, a susceptibility factor for psoriasis, was associated with the clinical response to MTX therapy. Methods: A total of 325 patients enrolled in the study received oral MTX treatment, of whom 310 completed the 1-year study and performed the genotype analysis. They were defined as responders (a reduction of Psoriasis Area and Severity Index [PASI] score ≥75%) and nonresponders (a reduction of PASI Results: We found significant associations for the ANxA6 SNPs of rs11960458, rs960709, and rs13168551 with psoriasis severity. Patients with rs11960458 CC genotype and rs960709 GG genotype showed higher percentages of PASI75 and improvement rates of PASI at 12 weeks. And on 1-year treatment, statistical difference occurred in rs11960458 rather than other SNPs compared between responders and nonresponders that the frequency of CC genotype was higher in responders (p = 0.019). After adjustment for potential confounders, patients with rs11960458 TT/CT genotype (at 12 weeks: OR 0.483, 95% CI 0.245–0.951, p = 0.035; at 1 year: OR 0.483, 95% CI 0.280–0.833, p = 0.009) were significantly more likely to not respond to MTX both on the short-term and long-term treatment, while rs960709 and rs13168551 polymorphisms were only associated with the short-term efficacy of MTX (p = 0.018 and p = 0.036, respectively). Conclusions: The CC ge­notype of ANxA6 (rs11960458) was significantly associated with a better response when compared to those patients with the TT/CT genotype, thus being a potential predictor for the clinical efficacy of MTX.

Objective: The aim of this study was to evaluate the impact of initial surgical treatments and surgical re-exploration on the oncological outcomes of patients with incidentally diagnosed uterine leiomyosarcoma (uLMS). Design: A retrospective analysis of 87 patients who underwent re-exploration for incidentally diagnosed uLMS at the Fudan University Shanghai Cancer Center was performed. Methods: Kaplan-Meier and Cox proportional hazards regression models were used for analyses. Results: The median age (range) at diagnosis was 49 (23–76) years. The median disease-free survival (DFS) and overall survival (OS) were 15.1 and 56.7 months, respectively. The Kaplan-Meier curves and log-rank tests showed the median DFS was longer in patients with restaging operation (N = 30) than without (N = 55) (p = 0.017) but no significant difference in median OS (p = 0.142). In patients who underwent myomectomy/subtotal hysterectomy, 5 patients (28.5%) had remnant sarcoma during re-exploration with complete uterine removal, and re-exploration was associated with longer DFS (p = 0.038) and OS (p = 0.042). Limitations: The limitation of this study is its retrospective observational design with a limited number of patients. Conclusion: Reoperation with total hysterectomy after incomplete surgery may be helpful in patients with incidentally diagnosed uLMS at the first treatment.

Although headgear is rarely used in adult patients, its use in adults is mainly for anchorage control. In the current case report, a 24-year-old patient had a skeletal Class I relationship with a Class II tendency, brachyfacial pattern, significant facial asymmetry, and dental 3/4 cusp Class II molar and canine relationships on both sides. The patient declined surgery, and facial asymmetry was not his concern. The final treatment goal was to achieve a stable Class I dental relationship and normal occlusion without significantly compromising the patient's profile. The patient was compliant with the use of cervical-pull headgear after he refused the options of orthodontic-orthognathic combined treatment, maxillary premolar extraction, or temporary skeletal anchorage mini-implants. A 5-mm maxillary arch distal movement was accomplished without significant distal tipping of the molar crowns. The active treatment duration was 31 months. Proper overbite and overjet, balanced occlusion, and an acceptable facial profile were achieved. The treatment results inspire reconsideration of the possibility of using headgear in dental Class II correction in adult patients.

We aimed to retrospectively analyze the therapeutic outcomes of using glucocorticoid combined with a vasodilator, breviscapine, versus glucocorticoid alone in patients with sudden sensorineural hearing loss (SSNHL) and to explore the impact on different audiometric curves.Data from 154 patients were collected between January 2017 and December 2018. Patients received treatments of either glucocorticoid combined with breviscapine (GC + Bre) or glucocorticoid alone (GC). These two groups were stratified into low frequencies SSNHL (LF-SSNHL), high frequencies SSNHL (HF-SSNHL), all frequencies SSNHL (AF-SSNHL), and total deafness SSNHL (TD-SSNHL) subgroups according to their corresponding audiograms. The hearing level was evaluated by pure tone audiometry, and hearing recovery was calculated by comparing the pure tone average (PTA) at pretreatment and 4 weeks after therapy.Hearing recovery was significantly greater for GC + Bre than GC-only treatment in the AF-SSNHL and TD-SSNHL subgroups (P 0.05) and to a lesser extent in the LF-SSNHL and HF-SSNHL subgroups (P 0.05). Logistic regression analysis also showed a favorable outcome for SSNHL in the GC + Bre group (odds ratio 2.848, P 0.05).Treating SSNHL using glucocorticoid combined with breviscapine could be more beneficial than using glucocorticoid alone, especially for patients with AF-SSNHL and TD-SSNHL.ChiCTR18000170072.

Grant-free Non-Orthogonal Multiple Access (NOMA) is a promising solution to enable massive wireless access service for 5G systems and beyond. Conventional grant-free NOMA schemes directly apply the spreading signatures optimized for the grant-based scenarios, which, however, ignore the users’ diversified activation probabilities. In addition, the conventional grant-free NOMA schemes are not designed with finite-alphabet signatures, which hinders the encoder/decoder implementation using practical low-cost hardware. Therefore, to overcome these limitations, we propose a finite-alphabet signature design for the grant-free NOMA with random and nonuniform user activations. Herein, the NOMA signatures are optimized by the autoencoder-based transceivers with both transmitter and receiver being in the form of deep neural network. First, the quantized deep learning is employed in the NOMA signature training, which jointly optimizes the sequence generation and quantization. Moreover, in order to improve the training rate, we propose a specific neural network receiver, where the network structure resembles the successive interference cancellation procedures. The experiment results show that the obtained NOMA signatures commendably exploit the users’ activation profiles, and the proposed scheme outperforms the conventional ones especially when the users have unequal activation probabilities.

Cloud radio access networks (C-RANs) is a promising technology for improving the performance of future mobile networks. In this paper, we focus on the joint remote radio head (RRH) activation and user association problem in dense C-RANs. Considering that a certain required minimum data rate may not be satisfied universally for all users in some situation, we aim to first maximize the number of users whose minimum data rate constraints can be guaranteed, and then maximize the system profit, which is a combination of the system throughput and the total power consumption. Due to the NP-hard feature of the problem, the conventional algorithms are impractical when the network size is large due to large computational complexity. Therefore, we adopt the max-sum algorithm to efficiently solve the joint RRH activation and user association problem, which can be implemented efficiently in a distributed manner. The signaling overhead of the max-sum algorithm can be reduced further by simplifying message updating rules and by shortening messages exchanged between nodes. Considering the fact that the high density of RRH deployment may hinder the convergence rate of the max-sum algorithm, we also propose a simplified algorithm by decomposing the original problem into two sub-problems, and each can be solved by the max-sum algorithm individually. Simulation results prove the efficiencies of the proposed algorithms.

Coronavirus disease 2019 (COVID-19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of patients with COVID-19 have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID-19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long-term pulmonary defects, and posttraumatic stress disorder. In this study, we, therefore, queried relevant literature concerning severe acute respiratory syndrome, Middle East respiratory syndrome, and COVID-19 for reference to come to a consensus on follow-up strategies. We found that strategies, such as the implementation of polymerase chain reaction testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long-term follow-up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome.

Fill factor (FF) is a determining parameter for the power conversion efficiency (PCE) of organic solar cells (OSC). So far, nonfullerene (NF) OSCs with state-of-the-art PCEs exhibit FFs

Renal cell carcinoma (RCC) is among the most common cancers of the genitourinary system. Once RCC has progressed to a high tumor stage, surgery is no longer the optimal option, and treatment with drugs is more suitable. However, a proportion of patients with advanced RCC (aRCC) experience accelerated progression following targeted therapy or immunotherapy, a condition known as hyperprogressive disease (HPD). There is a growing body of literature that recognizes the importance of HPD. In the present review, thousands of studies that describe a variety of treatments for aRCC were identified in PubMed, Web of Science, and Cochrane Library and analyzed to establish the severity of clinical outcomes. Therefore, we managed to perform a review related to HPD of aRCC in these databases. It was found that 7~74% of patients advanced into progressive disease, 0~45% of patients died during post-treatment assessment, possibly due to fatal HPD. However, risk factors, mechanisms, and predictive factors are still not entirely clear. It is suggested that combination therapies might play a pivotal role in preventing HPD. Additional light needs to be shed on customization of therapies for aRCC after more data is collected and analyzed for HPD.

Background This study aimed to evaluate the efficacy and safety of apatinib with a low dose of 250 mg/d in the treatment of platinum‐resistant or platinum‐refractory ovarian cancer patients. Methods Patients with platinum‐resistant or platinum‐refractory ovarian carcinoma treated with 250 mg/d apatinib in our institution from November 2016 to December 2017 were retrospectively reviewed. The tumor response and progression were evaluated according to the standard by incorporating the levels of CA125 and Response Evaluation Criteria in Solid Tumors 1.1. CTCAE 4.03 was used to evaluate adverse events (AEs). Results Fifty‐two eligible patients were enrolled in per‐protocol (PP) analysis and 65 patients (including 13 lost to follow‐up) were included in the intention‐to‐treat (ITT) analysis. In PP analysis, 18 patients (34.6%) had partial response (PR), 22 patients (42.3%) had stable disease (SD), and the disease control rate (DCR) was 61.5%. Median progression‐free survival (PFS) was 4.0 months (95% CI, 2.83‐5.17 m), and median overall survival (OS) was 25.33 months (95% CI, 17.74‐32.92 m). The objective response rate and DCR for patients in ITT analysis were 27.7% and 49.2%, respectively. The top three treatment‐related AEs were hypertension, hand‐foot syndrome, and leukopenia. Eight patients (15.4%) in PP population had grade 3 treatment‐related AEs. Previous chemotherapy lines, number of recurrences, and AEs did not affect the efficacy of apatinib. Age older than 60 was associated with higher rates of disease control and prolonged PFS (P, Apatinib 250 mg/day is a feasible treatment in patients with platinum‐resistant or platinum‐refractory EOC.

Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1β, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-β1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1β) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.

As the computing nodes of a fog computing system are located at the network edge, it can provide low-latency and reliable computing services to Internet of Things (IoT) mobile devices (MDs). By wirelessly offloading all/part of the computational tasks from MDs to the infrastructure fog nodes, it addresses the contradiction between the limited battery capacity of MDs and their long-lasting operation requirement. Different from previous works, the uncertainty caused by the channel measurements is taken into account in this paper, which yields a robust offloading strategy against realistic channel estimation errors. For this system, we design an energy-efficient computation offloading strategy, while satisfying the delay constraint. By using the Conditional Value-at-Risk (CVaR) framework, the original offloading problem is transformed into a Mixed Integer Nonlinear Programming (MINLP) problem, which is complicated and very challenging to solve. To overcome this issue, we apply Benders decomposition to find the optimal offloading solution. Numerical results show that proposed offloading strategy efficiently achieves obtain the optimal solution of the MINLP problem, and is robust to channel estimation errors.

The 2016 International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS) is a collaborative distillation of available research and consensus recommendations for the management for chronic rhinosinusitis (CRS). However, implementation of the ICAR:RS recommendations in the reality of clinical practice is not clearly defined.An anonymous, web-based survey of the American Rhinologic Society membership was performed in October, 2018. Respondents were asked about the frequency that they recommended the various treatments reviewed in ICAR:RS in the context of medical management for CRS. A 7-point Likert-type scale assessed the frequency of treatment patterns.A total of 140 members completed the survey (response rate 11.9%). Seventy-two (51.4%) were in practice for 0 to 15 years, 61 (43.6%) completed a rhinology fellowship, and 73 (52.1%) worked in private practice. Disparate treatment patterns were reported for each of the therapies assessed for CRS, including those that were "recommended" or "recommended against" in ICAR:RS. Members with15 years of experience were more likely to use nasal saline irrigation. Fellowship-trained respondents reported a greater likelihood of using nasal saline irrigation and aspirin desensitization (for patients with aspirin-exacerbated respiratory disease). Practitioners in academic medicine were more likely to utilize aspirin desensitization than those in private practice. Surgeons performing100 sinus surgeries per year were more likely to use topical antibiotics.The range of reported treatment patterns identified in this study despite the availability of the ICAR:RS recommendations may suggest the need for improved standardization of CRS management.

Software Defined Networking (SDN) presents a tremendous opportunity for developing abstract management of network updates. However, network updates introduce challenges in terms of consistency. Many consistent update algorithms are proposed for Ethernet, but there is seldom update algorithm for distributed time-triggered system to satisfy requirements of strict real-time and mixed-critical. The contribution of this paper is to present a distributed update mechanism and a mixed-critical update algorithm for the time-triggered (TT) and rate-constrained (RC) traffics to reduce the memory space complexity, computational time complexity, update time, and keep per-packet consistent strictly. More specifically, consistent update is defined and some basic update algorithms are described. And then a packet-based network model is built to describe network resources. Subsequently, the update mechanism is changed for the TT and RC traffics. Meanwhile, a mixed-critical update algorithm, which contains a time window-based update and a rate-constrained update for TT and RC traffics respectively, is proposed. Whether the mixed-critical update algorithm is consistent updates or not is proved logically. Finally, experiments analyzed the performance of the mixed-critical update algorithm, compared with four conventional updates. The results show that there is no black hole, loop and inconsistent path for the mixed-critical update algorithm. The most important thing is that the memory space complexity is reduced by 19.93% at least, compared with two-phase update. Meanwhile, the computational time complexity and update time are reduced by 17.14% and 7.96% respectively, compared with time-based update. The mixed-critical update algorithm provides a method to optimize policy update tasks for distributed time-triggered system, so as to improve the ability of system reconfiguration.

Content: Urban residential greenspace is considerably contributing to sustainable cities and residents’ well-being. An increasing number of studies have examined the greenspace inequalities and species biodiversity in relation to social theories in private gardens of US and European cities; however, much less studied is landscape configurations, especially in rapidly urbanizing cities like Beijing, China.Objectives: To demonstrate the fine-scale landscape variations of residential greenspace in Beijing urban area, and also to examine the main predictors of neighborhood characteristics on greenspace landscapes.Methods: A greenmap of Beijing urban area was first derived from Pleiades-1A images, then residential greenspace landscapes were examined using six landscape metrics, finally correlation and multiple regression analysis were performed to explore the relationships of greenspace landscape metrics and neighborhood characteristics.Results: The neighborhood characteristics are affecting residential greenspace of Beijing city. The neighborhoods with more and fragmented green coverage, complex patch shape and higher patch size variations are generally more aged, more distant to the city center and have lower plot-ratios. A distance of one additional kilometer to city center increases the vegetation coverage by 0.16% and the mean patch size by 10.17 m2. A neighborhood of one year older increases the patch density by 8.69. Moreover, one unit higher plot-ratio reduces the edge density by 5.66, and the patch size coefficient of variation by 7.03.Conclusions: Urban structure affects residential landscapes, and greenspace management approaches applied to optimize urban human well-being should integrate urban/landscape ecology with residential architecture.

In the last five years, the tremendous progress achieved in the field of polymer solar cells (PSCs) has attracted extensive attention to this emerging technology for exploiting renewable energy. Owing to their excellent optoelectronic features and outstanding manufacturability for film deposition, wide bandgap (WBG) polymer donors have become a leading component in bulk heterojunction layers and thus, a correlative review focusing on their molecular design, aggregation behavior and photovoltaic properties is necessary. In this feature article, we summarize our recent efforts in developing WBG polymer donors and understanding the charge separation and non-radiative recombination energy loss in high-performance non-fullerene (NF) PSCs. We also discuss the opportunities and challenges towards the realization of the commercialization of NF PSCs based on WBG polymer donors.

We consider a supply chain consisting of a supplier and a buyer. The buyer faces demand as a function of the selling price. There is risk of supply disruption, but the supplier can rebuild his capacity if he has invested for the capacity restoration before a disruption. To motivate the supplier to invest, the buyer can use one of two incentive contracts, namely direct and indirect . With a direct contract, the buyer provides a financial subsidy to share the supplier's capacity restoration cost when disruption occurs. With an indirect contract, the buyer adjusts the wholesale price in the case of disruption to stimulate the capacity restoration. Both contracts allow the buyer to adjust the order quantity in the case of disruption. We analyze decisions of each supply chain member under the two contracts with different commitment strategies (the ex ante commitment (EA) strategy under which the contract is signed before disruption and the ex post commitment (EP) strategy under which the contract is signed after disruption), and study how the supply disruption affects the buyer's selling price to end customers. We show that, from the perspective of either the supplier or the buyer, the incentive contract under the EA strategy is preferred by leading to a greater profit. Further, through numerical experiments, we recognize conditions for the fixed investment cost, probability of disruption, and regular wholesale price, under which each incentive contract encourages the supplier to invest for the capacity restoration, and brings greater profit to each supply chain member.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4+CD25+/CD4+ and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan–Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

Current scar surveys have included many questions to evaluate the physical characteristics of scars, with some expanding to include physical implications and patient opinions. This review provides an analysis of frequently used scar assessment methods to date and highlights potential areas for improvement. We build the case that a new assessment tool is necessary, specifically one that centers on psychosocial consequences of scars that influence patient decision making for treatment, allowing physicians to individualize treatment conversations with patients. We postulate that survey techniques used in consumer product marketing, such as choice-based conjoint analysis, may be effective in determining the factors strongly influencing patient decision making and spending in scar treatment; therefore, more research in this area is warranted. By incorporating these psychosocial and economic considerations driving scar treatment decisions, future scar assessment tools may accomplish much more than characterizing/documenting the clinical aspects of scars. Rather, these patient-centered, holistic tools may be implemented by plastic surgeons and other clinicians specifically to provide patients with personalized treatment options that maximize long-term patient satisfaction.

Glycosylated hemoglobin A1c (HbA1c) level has strong relevance to microvascular disorders, which are also thought to be the current main aspect of sudden sensorineural hearing loss (SSNHL), so we aim to elucidate the association of the HbA1c level with the severity, types, and prognosis of SSNHL. In this study, comparative analyses based on propensity score matching of the severity, types, and prognosis of SSNHL with the HbA1c level in 116 patients diagnosed as SSNHL were conducted, where they were divided into diabetes mellitus (DM) group and non-DM group. We finally found that, among patients with SSNHL, diabetic patients had a higher HbA1c level, more severe hearing loss, and poorer prognosis than non-diabetic patients. The HbA1c level was found to be significantly correlated with the severity and types of SSNHL, while no strong relevance was found between the higher HbA1c level and the poorer prognosis of SSNHL.

Background and Objective: Acupuncture is used as an alternative treatment for patients with major depressive disorder (MDD). The associated therapeutic effect of acupuncture is often attributed to its modulatory effect on the activity of the pre-frontal cortex (PFC), although the mechanism is not well-studied. We employed a repeated measures design to investigate the brain modulatory effect of acupuncture on the PFC in a group of patients with MDD and investigated whether the modulatory effect is influenced by the severity of the disease.Methods: A total of 47 patients diagnosed with MDD were enrolled in this functional near-infrared spectroscopy experiment. The severity of depressive symptoms was measured at baseline using the Hamilton Depression Rating Scale-24 (HAMD). The cortical activation in the bilateral PFC areas during a verbal fluency task (VFT) was measured before and after a single session of acupuncture in the Baihui acupoint. We further explored the potential correlation between the severity of MDD and task-related activation before and after acupuncture.Results: A single session of acupuncture significantly tended to enhance the activation level of the left frontopolar cortex in patients with severe depression during VFT, but a null effect was found in those with mild to moderate depression. Among patients with severe depression, a strong correlation was observed between HAMD scores and the change in VFT-related activation after acupuncture in the left dorsolateral PFC (DLPFC).Conclusion: A single session of acupuncture did not significantly modulate the activation of the left PFC in patients with mild to moderate depression; however, it demonstrated a tendency to enhance the activation of the frontopolar area in patients with severe depression. Among patients with severe depression, there is a correlation between the activation by acupuncture of left DLPFC during executive functioning and the severity of depressive symptoms, suggesting that the brain activity induced by acupuncture is likely to be influenced by the baseline disease severity in patients with MDD.

ObjectiveThis phase II, single-arm, prospective study aimed to evaluate the efficacy and safety of anlotinib in Chinese patients with recurrent or metastatic cervical cancer (CC).MethodsPatients with histologically proven recurrent or metastatic advanced CC were enrolled at Fudan University Shanghai Cancer Center. Patients received 12 mg of oral anlotinib daily before breakfast for 2 weeks of each 3-week (21 days) cycle separated by a 1-week interval. Anlotinib was administered orally until disease progression, patient withdrawal, intolerant toxicity, or death. The primary endpoint was the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsBetween September 2018 and November 2019, 41 patients were recruited. The median age was 53 years old. The histological results revealed that 82.9% of the recruited patients had squamous cell carcinoma, 14.6% had adenocarcinoma, and 2.4% had other types. At the data cutoff date, six patients were still being treated, and 35 patients had discontinued treatment. Forty (40/41, 97.5%) patients were evaluated for treatment response. The median PFS and OS was 3.2 and 9.9 months, respectively, in patients who received anlotinib treatment. The ORR was 24.4%. In addition, 34.2% (14/41) of patients were confirmed to have stable disease, and 39.0% (16/41) of patients were confirmed to have progressive disease. The DCR was 58.5%. Ten patients (10/41) had a confirmed response during the follow-up period. Most adverse events (AEs) were grade 1 or 2. High-grade AEs (grade 3) included urinary leukocyte positivity (9.8%), hematuria (4.9%), and hypertension (2.4%).ConclusionThis is the first study to evaluate the efficacy and safety of anlotinib in Chinese patients with recurrent or metastatic CC. Anlotinib produced durable clinical responses with manageable safety in these patients.

ObjectiveAiming to investigate diabetic retinopathy (DR) risk factors and predictive models by machine learning using a large sample dataset.DesignRetrospective study based on a large sample and a high dimensional database.SettingA Chinese central tertiary hospital in Beijing.ParticipantsInformation on 32 452 inpatients with type-2 diabetes mellitus (T2DM) were retrieved from the electronic medical record system from 1 January 2013 to 31 December 2017.MethodsSixty variables (including demography information, physical and laboratory measurements, system diseases and insulin treatments) were retained for baseline analysis. The optimal 17 variables were selected by recursive feature elimination. The prediction model was built based on XGBoost algorithm, and it was compared with three other popular machine learning techniques: logistic regression, random forest and support vector machine. In order to explain the results of XGBoost model more visually, the Shapley Additive exPlanation (SHAP) method was used.ResultsDR occurred in 2038 (6.28%) T2DM patients. The XGBoost model was identified as the best prediction model with the highest AUC (area under the curve value, 0.90) and showed that an HbA1c value greater than 8%, nephropathy, a serum creatinine value greater than 100 µmol/L, insulin treatment and diabetic lower extremity arterial disease were associated with an increased risk of DR. A patient’s age over 65 was associated with a decreased risk of DR.ConclusionsWith better comprehensive performance, XGBoost model had high reliability to assess risk indicators of DR. The most critical risk factors of DR and the cut-off of risk factors can be found by SHAP method to render the output of the XGBoost model clinically interpretable.

Industrial Internet of Things (IIoT) has been envisioned as a killer application of 5G and beyond. However, due to the shortness of computation ablility and batery capacity, it is challenging for IIoT devices to process latency-sensitive and resource-sensitive tasks. Moblie Edge Computing (MEC), as a promising paradigm for handling tasks with high quality of service (QoS) requirement and for energy-constrained IIoT devices, allows IIoT devices to offload their tasks to MEC servers, which can significantly reduce the task process delay and energy consumptions. However, the deployment of the MEC servers rely heavily on communication infrastructure, which greatly reduce the flexibility. Toward this end, in this paper, we consider multiple Unmanned Aerial Vehicles (UAV) eqqipped with transceivers as aerial MEC servers to provide IIoT devices computation offloading opportunities due to their high controbility. IIoT devices can choose to offload the tasks to UAVs through air-ground links, or to offload the tasks to the remote cloud center through ground cellular network, or to process the tasks locally. We formulate the multi-UAV-Enabled computation offloading problem as a mixed integer non-linear programming (MINLP) problem and prove its NP-hardness. To obtain the energy-efficient and low complexity solution, we propose an intelligent computation offloading algorithm called multi-agent deep Q-learning with stochastic prioritized replay (MDSPR). Numerical results show that the proposed MDSPR converges fast and outperforms the benchmark algorithms, including random method, deep Q-learning method and double deep Q-learning method in terms of energy efficiency and task successful rate.

Background and PurposeSSNHL is a common otology emergency, that may lead to hearing loss and impact quality of life. This study aims to investigate the association of thyroid-related hormone levels with moderately severe-to-profound sudden sensorineural hearing loss (SSNHL) that may contribute to treatment optimization.MethodsThe study included 70 patients with moderately severe-to-profound SSNHL and 100 age- and sex-matched healthy controls. Peripheral venous blood samples were taken from the participants, and their thyroid-related hormone levels were measured at admission and one week after treatment.ResultsThyroid-related hormone levels of total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) (all P

Objectives: As a common otology emergency, sudden sensorineural hearing loss (SSNHL) has a great impact on quality of life. The diagnosis and treatment of SSNHL remain challenging. This study aims to identify and investigate the association of liver functions with SSNHL.Methods: A total of 135 SSNHL patients and 135 sex- and age-matched controls were prospectively enrolled. The baseline and clinical characteristics, along with liver function levels of participators, were collected. Linear correlation, logistic regression, and receiving operator characteristic curve analysis tests were applied to examine the association between liver function levels and SSNHL.Results: There were no differences in baseline characteristics between SSNHL and control groups. The albumin (ALB) level of the SSNHL group was significantly lower than that in the control group (p < 0.001). The logistic regression showed that the low ALB level may be a predictive factor of SSNHL with an adjusted OR of 0.809 (95% CI, 0.742–0.882, p < 0.001). By comparing the indicators of different prognosis groups, we found that the effective group had a significantly lower hearing impair onset and higher ALB (p = 0.001) and AGR (p = 0.003) levels than the ineffective group. Logistic regression revealed that the hearing level onset (OR, 0.976; 95% CI, 0.956–0.997; p = 0.026) and ALB level (OR, 1.181; 95% CI, 1.071–1.301; p = 0.001) showed strong associations with treatment outcome.Conclusions: Lower ALB levels, within the normal ranges, were associated with the occurrence and unfavorable outcome of SSNHL. However, further research on the underlying mechanisms needs to be conducted.

Clinical features and outcomes of FL patients in Chinese population are limited, thus promoting us to perform this analysis on a large cohort of 1845 patients with FL enrolled from nine medical centers nationwide in China. In this cohort, the median age of patients at diagnosis was 53 years, which was comparable to that reported previously for Chinese FL patients (49–51 years) but younger than that for Western FL patients (60–65 years). In contrast with Western patients, Chinese FL patients more likely involved extranodal sites but less frequently infiltrated bone marrow. Other clinical characteristics were comparable between two populations. In this study, 91% of patients were managed with chemotherapy, yielding 72% and 46% of overall-response rate and complete remission. After median 55-month follow-up, 5-year progressive-free and overall survival were 61% and 89%, respectively. Both were analogous to those reported in prior Chinese and Western studies. Consistent with published data, addition of rituximab into both induction (Ri) and maintenance (Rm) treatment led to the most favorable outcomes. Interestingly, Ri only had better outcomes than Rm only. Notably, 7% of patients experienced histologic transformation (HT) and correlated with poor survival. Of the transformed FL cases, 3% and 4% of HT events occurred prior to or post-treatment, respectively. Importantly, the latter displayed worse outcomes than the former. Altogether, this study provides real-world information of the largest cohort of FL patients so far in China, which might lay a foundation for clinical investigation of Chinese FL in future.

To identify semiologic features of automatisms correlating to different seizure onset zones (SOZ).In total, 204 seizures from 74 patients with either oral or manual automatisms were assessed. Patients were divided into four groups depending on the SOZ into frontal, posterior, neocortical temporal, and mesial temporal cortex groups. A k-means analysis was applied on 11 semiologic features on a multi-criteria scale. Then, the resulting clinical patterns were correlated with the SOZs determined by presurgical anatomy-electroclinical data (25 cases with stereo-EEG).Four clinical patterns of automatisms with different accompanying symptoms were identified. The clinical features of clusters 1 and 4 were mostly found in temporal epilepsy whereas clusters 2 and 3 were more frequent in extratemporal epilepsy. Cluster 1 was significantly correlated with mesial temporal lobe epilepsy (p = .017) and was characterised by aura, postictal confusion, short automatisms delay. Cluster 3 included 1/3 patients with frontal lobe epilepsy and was characterised by emotionality. Cluster 4 was related to neocortical temporal lobe epilepsy and characterised by dystonia and short automatism delay (p = .011).The distinct semiologic patterns of automatisms may provide information which may allow clinicians to define the SOZs. These findings could improve diagnostic accuracy and surgical outcome.

Yong-heng Hou,1,&ast; Wen-cheng Shi,2,&ast; Shu Cai,1,&ast; Hong Liu,3 Zhong Zheng,2 Fu-wei Qi,2 Chang Li,4 Xiao-mei Feng,5,6 Ke Peng,1 Fu-hai Ji1 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, Taicang First People’s Hospital, Taicang Affiliated Hospital of Soochow University, Taicang, Jiangsu, People’s Republic of China; 3Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Department of Anesthesiology, University of Utah health, Salt Lake City, UT, USA; 6Transitional Residency Program, Intermountain Medical Center, Salt Lake City, UT, USA&ast;These authors contributed equally to this workCorrespondence: Ke Peng; Fu-hai JiDepartment of Anesthesiology, First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of ChinaTel +86-159-6215-5989; +86-512-6797-2352Email pengke0422@163.com; jifuhaisuda@163.comPurpose: Surgical stress promotes tumor metastasis. Interleukin (IL)-17 plays a pivotal role in cancer progression, and high IL-17 expression predicts poor prognosis of non-small-cell lung cancer (NSCLC). Lidocaine may exert tumor-inhibiting effects. We hypothesize that intravenous lidocaine attenuates surgical stress and reduces serum IL-17 levels during video-assisted thoracic surgery (VATS) for NSCLC.Methods: This randomized, double-blind, placebo-controlled trial included 60 early-stage NSCLC patients undergoing VATS, into a lidocaine group (n = 30; intravenous lidocaine bolus 1.0 mg/kg, and 1.0 mg/kg/h until the end of surgery) or a normal saline control group (n = 30). The primary outcome was serum IL-17 level at 24 hours postoperatively. The secondary outcomes included serum IL-17 level at the time of post-anesthesia care unit (PACU) discharge, serum cortisol level at PACU discharge and postoperative 24 hours, pain scores (0– 10) from PACU discharge to 48 hours postoperatively, incidences of postoperative nausea and vomiting, dizziness, and arrhythmia during 0– 48 hours postoperatively, and 30-day mortality. Long-term outcomes included chemotherapy, cancer recurrence, and mortality.Results: The lidocaine group had lower serum IL-17 at 24 hours postoperatively compared with the control group (23.0 ± 5.8 pg/mL vs 27.3 ± 8.2 pg/mL, difference [95% CI] = − 4.3 [− 8.4 to − 0.2] pg/mL; P = 0.038). The lidocaine group also had reduced serum IL-17 (difference [95% CI] = − 4.6 [− 8.7 to − 0.5] pg/mL), serum cortisol (difference [95% CI] = − 37 [− 73 to − 2] ng/mL), and pain scores (difference [95% CI] = − 0.7 [− 1.3 to − 0.1] points) at PACU discharge. During a median follow-up of 10 (IQR, 9– 13) months, 2 patients in the lidocaine group and 6 patients in the control group received chemotherapy, one patient in the control group had cancer recurrence, and no death event occurred.Conclusion: Intravenous lidocaine was associated with reduced serum IL-17 and cortisol following VATS procedures in early-stage NSCLC patients.Trial Registration: ChiCTR2000030629.Keywords: lidocaine, interleukin-17, non-small-cell lung cancer, video-assisted thoracic surgery, surgical stress

Facing the scarcity of spectrum resources, the spectrum sharing between radar and communication system has attracted a lot of attention in both industrial and academic communities. In this paper, we consider the co-existence of MIMO radar and MISO secure communication systems. In order to improve the secrecy performance, we jointly design the radar waveform and communication beamformer. Specifically, we aim at maximizing the secrecy capacity under the constraints of transmit power, radar waveform, and interference from BS to radar. To deal with the non-convex problem and the coupled variables, we use semidefinite relaxation (SDR) and successive convex approximation (SCA) techniques to solve the problem. Numerical results show that the proposed joint design algorithm can improve the secrecy performance of communication system signficantly.

Medical image segmentation task has been a hot research topic in the field of computer vision and natural field for many years. With the rapid development and application of convolutional neural networks, more and more medical segmentation models based on deep learning have been proposed, and more successful results and applications have been achieved in many disease segmentation tasks.The effect of medical image segmentation tasks is getting better. However, the computational cost of the medical image segmentation model has not been improved well. In this work, we propose a medical image segmentation model compression scheme that is theoretically applicable to all convolutional neural networks. First, we choose to construct a search space based on the number of convolution kernels at each location where convolution is used in the model, and then use neural network search to find a sub-network in this search space with less computation and high segmentation accuracy. Aiming at the encoding-decoding structure of the segmentation network, we propose Symmetrical-NAS to ensure that the encoding structure and decoding structure of any sub-network in our search space are symmetrical. Since it is too expensive to traverse the entire search space for training to find the most suitable architecture, we use weight sharing for training. During training, a sub-network in the search space is randomly selected for activation each time. Second, we use the method of knowledge distillation for training. We use the basic model as the teacher model and the searched sub-network as the student model to realize the knowledge transfer between the teacher model and the student model. Third, we use separable convolution instead of convolutional layer. Our method can be applied to various medicial image segmentation models regardless of model architectures and learning algorithms. Our method can reduce the computation of medical image segmentation models by 90× regarding FLOPs with little loss of segmentation effect. The code and demo will be publicly available.

Background Systemic mastocytosis is a rare disease and most patients have pigmented urticarial skin lesions. It can be easily missed and misdiagnosed in small biopsies, especially in those patients with nonspecific clinical complaints or untypical skin lesions. Case presentation We report a case of 69-year-old man who have presented with 2-year of diarrhea, progressive weight loss of 20kg and abdominal distention for 3 months. Ultrasound and abdominal CT scan showed massive effusions in abdominal and pelvic cavity. Colonoscopy was performed and showed intensive mucosal proliferations forming polypoid appearances. Microscopically, monotonously uniform, small, round tumor cells with slightly rich cytoplasm were concentrated between the residual glands in the colonoscopic biopsy. The tumor cells showed positive expression of CD117 and S-100, and low Ki-67 proliferation index of 2%, while Trypsin, CK, CD68, CD1a, Langerin, Syn, CgA, CD56, SATB2, CD20, CD3, α-inhibin and SMA were all negative. KIT D816V mutation was detected as well. Liver biopsy showed that CD117 positive cells were more than 15 cells in aggregates around the hepatic portal area and less than 15% mast cells were found in bone marrow smears. No multiple or diffuse pattern of mast cells infiltration was seen by repeated skin biopsies of skin lesions. With all these considered, the diagnosis of aggressive systemic mastocytosis was made. Conclusions The diagnosis of aggressive systemic mastocytosis is challenging for untypical clinical manifestations and subtle or inconspicuous lesions, especially in endoscopic biopsies, which requires awareness and a close teamwork of pathologists and clinicians.

Osteoarthritis (OA) is a major public health challenge that imposes a remarkable burden on the affected individuals and the healthcare system. Based on the clinical observation, males and females have different prevalence rates and severity levels of OA. Thus, sex-based differences may play essential roles in OA’s prognosis and treatment outcomes. To date, the comprehensive understanding of the relationship between sex and OA is still largely lacking. In the current study, we analyzed a published transcriptome dataset of knee articular cartilage (GSE114007) from 18 healthy (five females, 13 males) and 20 OA (11 females, nine males) donors to provide a slight insight into this important but complex issue. First, comparing female healthy cartilage samples with those of males revealed 36 differential expression genes (DEGs), indicating the fundamental sex-related differences at the molecular level. Meanwhile, 923 DEGs were distinguished between OA and healthy female cartilage, which can be enriched to 15 Reactome pathways. On the other hand, when comparing OA and healthy male cartilage, there are only 419 DEGs were identified, and only six pathways were enriched against the Reactome database. The different signaling response to OA in the male and female cartilage was further enforced by recognizing 50 genes with significantly different OA-responsive expression fold changes in males and females. Particularly, 14 Reactome pathways, such as “Extracellular matrix organization”, “Collagen biosynthesis and modifying enzymes”, “Dissolution of fibrin clot”, and “Platelet Aggregation (Plug formation)”, can be noted from these 50 sex-dependent OA-responsive genes. Overall, the current study explores the Sex as a Biological Variable (SABV) at the transcriptomic level in the knee articular cartilage in both healthy status and OA event, which could help predict the differential OA prognosis and treatment outcome of males and female patients.

As a severe progressive degenerative disease, cervical spondylotic myelopathy (CSM) has a poor prognosis and is associated with physical pain, stiffness, motor or sensory dysfunction, and a high risk of spinal cord injury and acroparalysis. Thus, therapeutic strategies that promote efficient spinal cord regeneration in this chronic and progressive disease are urgently needed. Effective and reproducible animal spinal cord compression models are required to understand the complex biological mechanism underlying CSM. Most spinal cord injury models reflect acute and structural destructive conditions, whereas animal models of CSM present a chronic compression in the spinal cord. This paper presents a protocol to generate a rat spinal cord compression model, which was further evaluated by assessing the behavioral score and observing the compressed spinal cord region. The behavioral assessments showed decreased monitor motor disability, including joint movements, stepping ability, coordination, trunk stability, and limb muscle strength. Hematoxylin and eosin (H&E) staining and immunostaining revealed considerable neuronal apoptosis in the compressed region of the spinal cord.

Optimizing allocation of vaccine, a highly scarce resource, is an urgent and critical issue during fighting against on‐going COVID‐19 epidemic. Prior studies suggested that vaccine should be prioritized by age and risk groups, but few of them have considered the spatial prioritization strategy. This study aims to examine the spatial heterogeneity of COVID‐19 transmission in the city naturally, and optimize vaccine distribution strategies considering spatial prioritization. We proposed an integrated spatial model of agent‐based model and SEIR (susceptible‐exposed‐infected‐recovered). It simulated spatiotemporal process of COVID‐19 transmission in a realistic urban context. Individual movements were represented by trajectories of 8,146 randomly sampled mobile phone users on December 28, 2016 in Guangzhou, China, 90% of whom aged 18–60. Simulations were conducted under seven scenarios. Scenarios 1 and 2 examined natural spreading process of COVID‐19 and its final state of herd immunity. Scenarios 3–6 applied four vaccination strategies (random strategy, age strategy, space strategy, and space & age strategy), and identified the optimal vaccine strategy. Scenario 7 assessed the most appropriate vaccine coverage. The results demonstrates herd immunity is heterogeneously distributed in space, thus, vaccine intervention strategies should be spatialized. Among four strategies, space & age strategy is substantially most efficient, with 7.7% fewer in attack rate and 44 days longer than random strategy under 20% vaccine uptake. Space & age strategy requires 30%–40% vaccine coverage to control the epidemic, while the coverage for a random strategy is 60%–70% as a comparison. The application of our research would greatly improves the effectiveness of the vaccine usability., Key Points Spatial heterogeneity in herd immunity rate has been identifiedSpace & age strategy is substantially considered as the most efficient strategy among four vaccination strategies30%–40% vaccine coverage are needed to control the epidemic under space & age strategy, while 60%–70% for a random strategy as a comparison

BACKGROUND: This study aimed to explore the added prognostic value of baseline metabolic volumetric parameters and cell of origin subtypes to the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) in nodal diffuse large B-cell lymphoma (DLBCL) patients. METHODS: A total of 184 consecutive de novo nodal DLBCL patients who underwent baseline positron emission tomography/computed tomography (PET/CT) were included in this study. Kaplan-Meier estimates were generated to evaluate the clinical, biological, and PET/CT parameters’ prognostic value. The Cox proportional hazards model was performed to examine the potential independent predictors for progression-free survival (PFS) and overall survival (OS). RESULTS: With a median follow-up of 35 months, the 3-year PFS and OS were 65.2% and 73.0%, respectively. In univariate analysis, total lesion glycolysis (TLG), cell-of-origin subtypes, and NCCN-IPI were both PFS and OS predictors. High TLG (≥1,852), non-germinal center B (non-GCB), as well as high NCCN-IPI (≥4), were shown to be independently significantly associated with inferior PFS and OS after multivariate analysis. Based on the number of risk factors (high TLG, non-GCB, and high NCCN-IPI), a revised risk model was designed, and the participants were divided into four risk groups with very different outcomes, in which the PFS rates were 89.7%, 66.2%, 51.7%, and 26.7% (χ(2)=30.179, P

Background: Follicular lymphoma (FL) is a malignancy of lymphocytes derived from germinal center (GC). Hepatitis B virus (HBV) infection may increase the incidence of FL. Here, we performed an integrated genomic and transcriptomic analysis to identify molecular characteristics and therapeutic targets for HBV-associated FL.Methods: A total of 253 patients with newly diagnosed FL were enrolled. Whole-genome sequencing (n=13) and whole-exome sequencing (n=87) were performed on tumor samples of 100 patients. Among them, 84 patients were available for transcriptomic sequencing data. Moreover, biological function of immune modulator TNFAIP3 mutation was investigated in vitro using FL cell line SC-1 and in vivo using zebrafish xenograft model.Results: By characterizing altogether 253 FL patients, we showed that patients with HBV infection (surface antigen positive, HBsAg+) were significantly associated with younger age, more frequent spleen involvement, advanced histological grade, higher proliferation index, and poorer progression-free survival. By whole-genome/exome and targeted sequencing, we observed increased mutations in immune modulators (TNFAIP3, CD70, CXCR4, PIM1, KLF2, FAS, CD58, and CD83), decreased mutations in epigenetic modifiers (KMT2D and CREBBP), and low incidence of BCL2 translocation as the core oncogenic program of HBsAg+ FL. By transcriptomic sequencing, we further showed that HBsAg+ FL was enriched by immune-related pathways, antigen processing and presentation and IFN signatures, as well as inflamed signatures and infiltration of CD8+T and Th1 cells, with malignant lymphocytes transiting to post-GC phenotype. In the co-culture system of FL cell line SC-1 with peripheral blood mononuclear cells mimicking in vivo situation, TNFAIP3 mutations induced overexpression of TIGIT on CD8+T cells and VISTA on Th1 cells, both of which were downregulated by lenalidomide, resulting in sensitivity of TNFAIP3-mutant cells to lenalidomide treatment in co-culture system and in zebrafish xenograft model. Of note, negative prognostic impact of HBV infection on patients treated with rituximab-based immunochemotherapy could be overcome by rituximab and lenalidomide.Conclusions: HBV-associated FL may be considered as a specific subtype, based on distinct immune modulator mutations, and CD8+T- and Th1-enriched post-GC phenotype. Moreover, these findings provided new insights into the pathogenetic role of HBV in FL and the potential benefit of immunomodulatory agents in treating HBV-associated FL.

Hyperkinetic seizures (HKS) are characterized by complex movements that commonly occur during seizures arising from diverse cortical structures. A common semiology network may exist and analyzing the anatomo-electrical mechanisms would facilitate presurgical evaluation. Here, quantitative positron emission tomography (PET) and stereoelectroencephalography (SEEG) analysis was used to explore the underlying mechanism of HKS.We retrospectively collected patients with epilepsy with HKS between 2014 and 2019. The interictal PET data of patients with epilepsy with HKS were compared with those of 25 healthy subjects using statistical parametric mapping to identify regions with significant hypometabolism. Then, regions of interest (ROI) for SEEG analysis were identified based on the results of PET analysis. Patients in which the ROIs were covered by intracerebral electrodes were selected for further analysis. Stereoelectroencephalography -clinical correlations with latency measurements were analyzed, and we also performed coherence analysis among ROIs both before and during HKS.Based on the inclusion criteria, 27 patients were analyzed. In the PET analysis, significant hypometabolism was observed in the ipsilateral dorsoanterior insular lobe, bilateral mesial frontal lobes (supplementary motor area/middle cingulate cortex, SMA/MCC), and the bilateral heads of the caudate nuclei in patients with HKS compared with the control group (p 0.001). We selected dorsoanterior insula and SMA/MCC as ROIs for SEEG analysis. Eight patients with 23 HKS events were selected for further analysis. There was a linear correlation between the ictal involvement of both the dorsoanterior insula and SMA/MCC with the onset of HKS. Stereoelectroencephalography analysis indicated alpha range activity seemed more often associated with dorsoanterior insula and SMA/MCC involvement during HKS.The dorsoanterior insular lobe, mesial frontal lobes (SMA/MCC), and the bilateral heads of the caudate nuclei were probably involved in the generation of HKS. The SEEG analysis further indicated that the occurrence of HKS might be partly associated with synchronized rhythmical alpha activity between dorsoanterior insula and SMA/MCC.