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Prostate cancer (PCa) is characterized as a “cold tumor” with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.

Abstract Background Patients with idiopathic scoliosis commonly present with an imbalance of the paraspinal muscles. However, it is unclear whether this muscle imbalance is an underlying cause or a result of idiopathic scoliosis. This study aimed to investigate the role of paraspinal muscles in the development of idiopathic scoliosis based on surface electromyography (sEMG) and radiographic analyses. Methods This was a single-center prospective study of 27 patients with single-curve idiopathic scoliosis. Posteroanterior whole-spine radiographs and sEMG activity of the erector spinae muscles were obtained for all patients in the habitual standing position (HSP), relaxed prone position (RPP), and prone extension position (PEP). The Cobb angle, symmetrical index (SI) of the sEMG activity (convex/concave), and correlation between the two factors were analyzed. Results In the total cohort, the mean Cobb angle in the HSP was significantly greater than the mean Cobb angle in the RPP (RPP-Cobb) (p

Abstract Abnormal lipid metabolism and lipid accumulation are characteristic hallmarks of renal cell carcinoma (RCC). While there is prior evidence closely linking such lipid accumulation within RCC cells and consequent tumorigenesis, the mechanisms underlying this process remain incompletely understood. In this study, a series of bioinformatics analyses were initially performed by screening RCC databases and gene sets, ultimately leading to the identification of TRIB3 as an oncogene that functions as a central regulator of lipid metabolism. TRIB3 overexpression was observed in both RCC patient tumor tissues and cell lines, and this upregulation was correlated with a worse RCC patient prognosis. When TRIB3 was knocked down, this resulted in a reduction in lipid accumulation and the consequent induction of endoplasmic reticulum (ER) stress-related apoptotic cell death. At the molecular level, interactions between TRIB3 and PLIN2 were found to abrogate TEB4-mediated PLIN2 ubiquitination and consequent degradation, thus maintaining higher PLIN2 expression levels. This simultaneously helps facilitate the accumulation of lipids while preserving ER homeostasis, thus driving accelerated RCC tumor progression. This TRIB3-PLIN2 axis thus represents a promising new target for efforts to treat RCC.

Agricultural non-point source pollution (ANP) had become an important source of water pollution, which seriously restricted the coordinated development of Beijing, Tianjin and Hebei. As the primary agricultural production base in the region of Beijing-Tianjin-Hebei, Hebei had serious ANP. In order to clarify the current status of ANP in Hebei and figure out the main pollution source and areas, ANP load of Hebei from 2000 to 2021 were evaluated by the export coefficient modeling (ECM) and spatial-temporal characteristics were carried out using geographic information system (GIS). In addition, ANP severity and emission characteristics of Hebei in 2021 were evaluated. The results showed that the environmental impact of ANP in southwest area was obviously more serious than that in northeast area of Hebei. Especially, ANP emissions in Hebei showed significant decreasing inflection points in 2007 and 2017, respectively, reaching a minimum by 2021. The TN and TP emissions of ANP in Hebei were 315,026.1 t and 50,323.76 t in 2021, respectively. The contribution of agricultural land, livestock and poultry breeding and rural life to TN and TP emissions were 37%, 34%, 29% and 20%, 61% and 18%, respectively. The ANP pollution mainly came from livestock and poultry breeding in Hebei Province. Based on cluster analysis, cities in Hebei were divided into four types, and the control strategies for ANP environment management were put forward.

Abstract Background Tooth extraction is a common procedure performed by oral and maxillofacial surgeons or dentists, often resulting in dental fear and anxiety. The use of relaxing music, audiovisuals, and virtual reality (VR) technologies has been employed to reduce dental anxiety. This network meta-analysis (NMA) aimed to assess the comparative effectiveness of relaxing music, audiovisuals, and VR in reducing dental anxiety associated with tooth extraction. Methods Four electronic databases were searched up to March 8, 2023, to identify randomized controlled trials (RCTs) evaluating different multimedia interventions, including the application of using relaxing music, audiovisuals, and VR technologies for dental anxiety. Studies utilizing various anxiety scales for tooth extraction were considered eligible. The pooled standard mean difference (SMD) and 95% confidence interval (CI) of anxiety scale scores were analyzed using Bayesian NMA. Results A total of 11 RCTs were included in this NMA. The Bayesian NMA results demonstrated that relaxing music (SMD = -0.64, 95% CI: -1.04, -0.25) and VR (SMD = -0.54, 95% CI: -1.08, -0.02) were associated with a reduction in dental anxiety, while audiovisuals (SMD = -0.34, 95% CI: -0.97, 0.33) required further consideration. Ranking probabilities indicated that relaxing music might be the most acceptable method for individuals with dental anxiety. The frequentist NMA yielded consistent rankings in a sensitivity analysis. Conclusions Relaxing music shows the greatest potential for reducing dental anxiety related to tooth extraction when compared to other multimedia interventions.

Abstract Background Association of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the association between cigarette smoking and prostate cancer risk. Methods We conducted a systematic search on PubMed, Embase, Cochrane Library, and Web of Science without language or time restrictions on June 11, 2022. Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective cohort studies that assessed the association between cigarette smoking habits and the risk of prostate cancer were included. Quality assessment was conducted using the Newcastle–Ottawa Scale. We used random-effects models to obtain pooled estimates and the corresponding 95% confidence intervals. Results A total of 7296 publications were screened, of which 44 cohort studies were identified for qualitative analysis; 39 articles comprising 3 296 398 participants and 130 924 cases were selected for further meta-analysis. Current smoking had a significantly reduced risk of prostate cancer (RR, 0.74; 95% CI, 0.68–0.80; P

Abstract Background Bladder cancer is the tenth most common cancer worldwide. For patients with T1 high-grade or T2 bladder cancer, radical cystectomy is recommended. However, radical cystectomy is associated with various complications and has a detrimental impact on the quality of life. Bladder-sparing therapy has been widely explored in patients with muscle-invasive bladder cancer, and whether a combination of transurethral resection of bladder tumour (TURBT) with chemotherapy and immunotherapy shows definite superiority over TURBT plus chemotherapy is still a matter of debate. The aim of this study is to investigate the efficacy and safety of TURBT combined with chemotherapy and immunotherapy in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer who are unwilling or unsuitable to undergo radical cystectomy. Methods An open-label, multi-institutional, two-armed randomized controlled study will be performed with 86 patients with T1 high-grade or T2 bladder cancer meeting the eligibility criteria. Participants in the experimental group (n = 43) will receive TURBT combined with chemotherapy (GC: gemcitabine 1000 mg/m2 on the 1st day and the 8th day, cisplatin 70 mg/m2 on the 2nd day, repeated every 21 days) and immunotherapy (toripalimab 240 mg on the 5th day, repeated every 21 days), and those in the control group (n = 43) will receive TURBT plus chemotherapy (GC). The primary outcome is pathological response, and the secondary outcomes include progression-free survival, overall survival, toxicities, and quality of life. Discussion To the best of our knowledge, this is the first study to evaluate the efficacy and safety of TURBT combined with GC regimen and toripalimab in bladder-sparing therapy in patients with T1 high-grade or T2 bladder cancer. The expected benefit is that the combination of TURBT with chemotherapy and immunotherapy would be more effective than TURBT plus chemotherapy without compromising the quality of life and increasing the toxicity. Trial registration ChiCTR2200060546, chictr.org.cn, registered on June 14, 2022.

Background Neuropathic pain typically refers to the pain caused by somatosensory system injury or diseases, which is usually characterized by ambulatory pain, allodynia, and hyperalgesia. Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal dorsal cord might serve a predominant role in regulating the algesia of neuropathic pain. The high efficacy and safety, as well as the plausible ability in providing comfort, entitle dexmedetomidine (DEX) to an effective anesthetic adjuvant. The aim of this study was to investigate the effect of DEX on the expression of nNOS in spinal dorsal cord in a rat model with chronic neuropathic pain.

Abstract. Increasing evidence indicates that N6-methyladenosine (m6A) methylation modification serves important functions in biological metabolism. Dysregulation of m6A regulators is related to the progression of different malignancies, including renal cell carcinoma (RCC). Recent studies have reported preliminary findings on the influence of m6A regulator dysregulation on RCC tumorigenesis and development. However, no comprehensive review that integrates and analyzes the roles of m6A modification in RCC has been published to date. In this review, we focus on the dysregulation of m6A regulators as it relates to RCC tumorigenesis and development, as well as possible applications of m6A modification in RCC diagnosis and therapeutics.

Patients with early-stage Parkinson’s disease (PD) exhibit various but subtle motor symptoms, especially postural instability and gait disorders (PIGD). Patients show deteriorated gait performance at turns as the complex gait task requires more limb coordination and postural stability control, which may help to discriminate signs of early PIGD. In this study, we firstly proposed an IMU-based gait assessment model for quantifying comprehensive gait variables in both straight walking and turning tasks from five domains: respectively gait spatiotemporal parameters, joint kinematic parameters, variability, asymmetry, and stability. Twenty-one patients with idiopathic Parkinson’s disease at the early stage and nineteen age-matched healthy elderly adults were enrolled in the study. Each participant wore a full-body motion analysis system with 11 inertial sensors and walked along a path consisting of straight walking and 180-degree turns at a self-comfortable speed. A total of one hundred and thirty-nine gait parameters were derived for each gait task. We explored the factor effect of group and gait tasks on gait parameters using a two-way mixed analysis of variance. The discriminating ability of gait parameters between PD and the control group was evaluated using receiver operating characteristic analysis. Sensitive gait features were optimally screened (AUC $>$ 0.7) and categorized into 22 groups to classify PD and healthy controls based on a machine learning method. Results demonstrated that PD patients exhibited more gait abnormalities at turns, especially on the RoM and stability of the neck, shoulder, pelvic, and hip joints compared to the healthy control group. These gait metrics have good discriminating abilities to identify early-stage PD (AUC $>$ 0.65). Moreover, the inclusion of gait features at turns can significantly improve the classification accuracy compared to that only used parameters during straight walking. We show that quantitative gait metrics during turning have great potential to be used for enhancing early-stage PD detection.

Abstract Metabolic dysfunction is seen in cancer cells where increased glycolysis provides energy for growth. Circular RNAs (circRNAs) are thought to assist in glucose metabolism and the switch to glycolysis. Through screening, we found that circVAMP3 was necessary for both glycolytic and proliferative activities in renal cell carcinoma (RCC). Furthermore, circVAMP3 expression was elevated in RCC patients in correspondence with TNM stage. Mechanistically, circVAMP3 was observed to interact directly with lactate dehydrogenase A (LDHA) and modulate its activity. The circVAMP3–LDHA interaction facilitated LDHA phosphorylation at tyrosine 10 (Y10) catalyzed by the upstream kinase fibroblast growth factor receptor type 1 (FGFR1). Therefore, this study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation through regulating the enzymatic activity of glycolytic enzyme, suggesting that circVAMP3 may represent an RCC biomarker and treatment target.

Abstract Background Androgen deprivation therapy (ADT) combined with docetaxel chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, mCRPC patients are mainly frail elderly men, constantly accompanied by comorbidities and showing poor tolerance to standard docetaxel chemotherapy. Some exploratory studies administering modified chemotherapy regimens have reported noninferior oncologic outcomes with fewer adverse events, yet most are retrospective or small studies, and prospective randomized controlled trials have rarely been conducted. Therefore, we designed this modified docetaxel chemotherapy regimen in patients with mCRPC, aiming to evaluate its efficacy and safety compared with the standard docetaxel chemotherapy regimen. Methods This is an open-label, multi-institutional, prospective, randomized non-inferiority trial. A total of 128 patients with mCRPC will be randomized to receive ADT combined with modified docetaxel chemotherapy (experimental group, n=64) or ADT combined with standard docetaxel chemotherapy (control group, n=64). Patients in the experimental group will receive a modified regimen with docetaxel 40 mg/m2 on the 1st day and 35 mg/m2 on the 8th day, repeated every 21 days. The primary endpoint is progression-free survival at 2 years. Secondary endpoints include overall survival, prostate-specific antigen response rate, pain response rate, toxicity and quality of life. Discussion The expected benefit for the patient in the experimental arm is noninferior efficacy with decreased toxicity and improved quality of life compared with that in the control arm. To the best of our knowledge, this will be the first multicentre prospective randomized study to assess the efficacy and safety of modified docetaxel chemotherapy in patients with mCRPC in China. The results of this trial may provide benefit to mCRPC patients, especially those with poor performance. Trial registration chictr.org.cn Identifier: ChiCTR2100046636 (May 24, 2021). Ongoing study.

Abstract Background Cancer cells prefer utilizing aerobic glycolysis in order to exacerbate tumor mass and maintain un-regulated proliferative rates. As a key glycolytic activator, phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) has been implicated in multiple tumor type progression. However, the specific function and clinical significance of PFKFB3 in renal cell carcinoma (RCC) are yet not clarified. This investigation assessed PFKFB3 roles in RCC. Methods PFKFB3 expression levels were analyzed in clear cell renal cell carcinoma (ccRCC) tissues, together with its relationship with clinical characteristics of ccRCC. Real-time PCR and Western blot assays were employed for determining PFKFB3 expression in different RCC cell lines. Furthermore, we determined the glycolytic activity by glucose uptake, lactate secretion assay and ECAR analysis. CCK-8 assay, clone formation, flow cytometry and EdU assessments were performed for monitoring tumor proliferative capacity and cell-cycle distribution. Furthermore, a murine xenograft model was employed for investigating the effect of PFKFB3 on tumor growth in vivo. Results PFKFB3 was significantly up-regulated in RCC specimens and cell lines in comparison to normal control. Overexpression of PFKFB3 was directly correlated to later TNM stages, thus becoming a robust prognostic biomarker for ccRCC cases. Furthermore, PFKFB3 knockdown suppressed cell glycolysis, proliferative rate and cell-cycle G1/S conversion in RCC cells. Importantly, in vivo experiments confirmed that PFKFB3 knockdown delayed tumor growth derived from the ACHN cell line. Conclusions Such results suggest that PFKFB3 is a key molecular player in RCC progression via mediating glycolysis / proliferation and provides a potential therapeutic target against RCC.

Objective: We aim to develop a polymer library consisting of phenylalanine-based poly(ester amide)s (Phe-PEAs) for cancer therapy and investigate the structure–property relationship of these polymers to understand their impact on the drug delivery efficiency of corresponding nanoparticles (NPs). Impact Statement: Our study provides insights into the structure–property relationship of polymers in NP-based drug delivery applications and offers a potential polymer library and NP platform for enhancing cancer therapy. Introduction: Polymer NP-based drug delivery systems have demonstrated substantial potential in cancer therapy by improving drug efficacy and minimizing systemic toxicity. However, successful design and optimization of these systems require a comprehensive understanding of the relationship between polymer structure and physicochemical properties, which directly influence the drug delivery efficiency of the corresponding NPs. Methods: A series of Phe-PEAs with tunable structures was synthesized by varying the length of the methylene group in the diol part of the polymers. Subsequently, Phe-PEAs were formulated into NPs for doxorubicin (DOX) delivery in prostate cancer therapy. Results: Small adjustments in polymer structure induced the changes in the hydrophobicity and thermal properties of the PEAs, consequently NP size, drug loading capacity, cellular uptake efficacy, and cytotoxicity. Additionally, DOX-loaded Phe-PEA NPs demonstrated enhanced tumor suppression and reduced side effects in prostate tumor-bearing mice. Conclusion: Phe-PEAs, with their finely tunable structures, show great promise as effective and customizable nanocarriers for cancer therapy.

The infections and diseases caused by harmful bacteria are regarded as the worldwide health-threatening issue. The most antibiotics-based delivery systems restricted the controlled drug release at specific infection sites due to the stable chemical conjugation, thus largely compromising the treatment effectiveness. Herein, we report the construction of light controlled drug-based supramolecular polymer (LDSP), which is endowed the “switch on” function for realizing the controllable antibiotics released in specific sites. LDSP was first formed based on the host-guest interaction between β-cyclodextrin units grafted hyaluronic acid chain (HA-CD) and azobenzene moiety linked by two enoxacin units (Azo-(Eno)2), and could further self-assemble into light controlled drug-based supramolecular polymer self-assemblies (LDSPSAs). Under the UV light irradiation, the “switch on” function of LDSPSAs could be effectively turned on at the specific infected tissues due to the smartly dissociated host-guest interaction, facilitating the controlled release of the hydrophobic Azo-(Eno)2 to interact with bacteria for efficient antibacterial effect. The biological evaluation demonstrated that LDSPSAs achieved good antibacterial efficiency and well biosafety.

Vaccine hesitancy is considered as one main cause of the stagnant uptake ratio of COVID-19 vaccines in Europe and the US where vaccines are sufficiently supplied. A fast and accurate grasp of public attitudes toward vaccination is critical to addressing vaccine hesitancy, and social media platforms have proved to be an effective source of public opinions. In this paper, we describe the collection and release of a dataset of tweets related to COVID-19 vaccines. This dataset consists of the IDs of 2,198,090 tweets collected from Western Europe, 17,934 of which are annotated with the originators’ vaccination stances. Our annotation will facilitate using and developing data-driven models to extract vaccination attitudes from social media posts and thus further confirm the power of social media in public health surveillance. To lay the groundwork for future research, we not only perform statistical analysis and visualization of our dataset, but also evaluate and compare the performance of established text-based benchmarks in vaccination stance extraction. We demonstrate one potential use of our data in practice in tracking the temporal changes in public COVID-19 vaccination attitudes.

Abstract Androgen receptor (AR) signaling inhibitors provide limited survival benefits to patients with prostate cancer (PCa), and worse, few feasible genomic lesions restrict targeted treatment to PCa. Thus, a better understanding of the critical dependencies of PCa may enable more feasible therapeutic approaches to the dilemma. We performed a kinome-scale CRISPR/Cas9 screen and identified cyclin-dependent kinase 12 (CDK12) as being conservatively required for PCa cell survival. Suppression of CDK12 by the covalent inhibitor THZ531 led to an obvious anti-PCa effect. Mechanistically, THZ531 downregulated AR signaling and preferentially repressed a distinct class of CDK12 inhibition-sensitive transcripts (CDK12-ISTs), including prostate lineage-specific genes, and contributed to cellular survival processes. Integration of the super-enhancer (SE) landscape and CDK12-ISTs indicated a group of potential PCa oncogenes, further conferring the sensitivity of PCa cells to CDK12 inhibition. Importantly, THZ531 strikingly synergized with multiple AR antagonists. The synergistic effect may be driven by attenuated H3K27ac signaling on AR targets and an intensive SE-associated apoptosis pathway. In conclusion, we highlight the validity of CDK12 as a druggable target in PCa. The synergy of THZ531 and AR antagonists suggests a potential combination therapy for PCa.

ObjectiveThis study aimed to investigate burnout situation of social workers (SWs) who experienced the COVID-19 pandemic-related community lockdown 1 year before, and to assess the protective value of trait mindfulness (TM) in states of burnout.MethodWe surveyed the burnout, trait mindfulness, negative emotions (NEs) and wellbeing (WB) of 182 social workers provided services to Wuhan lockdowns community by COVID-19 one year before. Burnout were measured using the Maslach Burnout Inventory–Human Services Survey; TM using the Mindful Attention Awareness Scale; NEs using the Depression Anxiety and Stress Scale-21; and WB using the General Wellbeing Schedule. We also performed correlation regression analysis and mediation test for burnout, TM, NEs, and WB.ResultsAmong the 182 respondents, 75 (41.2%) still suffered from severe burnout. TM was negatively correlated with burnout (r = −0.623), negatively correlated with NEs (r = −0.560), and positively correlated with WB (r = 0.617). Burnout had a significantly positive correlation with NEs (r = 0.544) and a significantly negative correlation with WB (r = −0.666). Further, WB had significantly negative correlation with NEs (r = −0.758). After controlling for age, gender, marital status, educational level, and years of employment, burnout had a significantly positive predictive effect on NEs (β = 0.509), whereas TM had a significantly negative predictive effect on NEs (β = −0.334). TM played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of 0.088 and 39.7%, respectively. Burnout had a significantly negative predictive effect on WB (β = −0.598), whereas TM had a significantly positive predictive effect on WB (β = 0.299). TM played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of −0.164 and 30.3%, respectively. WB had a significantly negative predictive effect on NEs (β = −0.711), and it played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of 0.185 and 83.3%, respectively.ConclusionThe current levels of burnout among local SWs remained high 1 year after the community lockdowns. TM played a mediating role in the relationship between burnout, NEs, and WB. Concomitantly, WB played a mediating role in the relationship between burnout and NEs. Therefore, in the context of burnout, TM is a protective factor for reducing emotional stress and risks of developing psychiatric disorders through the enhancement of WB.

Objectives(1) To assess the methodological quality and risk of bias of radiomics studies investigating the diagnostic performance in adrenal masses and (2) to determine the potential diagnostic value of radiomics in adrenal tumors by quantitative analysis.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched for eligible literature. Methodological quality and risk of bias in the included studies were assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS). The diagnostic performance was evaluated by pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Spearman’s correlation coefficient and subgroup analysis were used to investigate the cause of heterogeneity. Publication bias was examined using the Deeks’ funnel plot.ResultsTwenty-eight studies investigating the diagnostic performance of radiomics in adrenal tumors were identified, with a total of 3579 samples. The average RQS was 5.11 (14.2% of total) with an acceptable inter-rater agreement (ICC 0.94, 95% CI 0.93–0.95). The risk of bias was moderate according to the result of QUADAS-2. Nine studies investigating the use of CT-based radiomics in differentiating malignant from benign adrenal tumors were included in the quantitative analysis. The pooled sensitivity, specificity, DOR and AUC with 95% confidence intervals were 0.80 (0.68-0.88), 0.83 (0.73-0.90), 19.06 (7.87-46.19) and 0.88 (0.85–0.91), respectively. There was significant heterogeneity among the included studies but no threshold effect in the meta-analysis. The result of subgroup analysis demonstrated that radiomics based on unenhanced and contrast-enhanced CT possessed higher diagnostic performance, and second-order or higher-order features could enhance the diagnostic sensitivity but also increase the false positive rate. No significant difference in diagnostic ability was observed between studies with machine learning and those without.ConclusionsThe methodological quality and risk of bias of studies investigating the diagnostic performance of radiomics in adrenal tumors should be further improved in the future. CT-based radiomics has the potential benefits in differentiating malignant from benign adrenal tumors. The heterogeneity between the included studies was a major limitation to obtaining more accurate conclusions.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/ CRD 42022331999 .

This work investigated the removal of cadmium ions (Cd2+) by using biochar derived from Barracuda Grass. The biochars derived from the pyrolysis of roots (BGR), stems (BGS) and leaves (BGL) were characterized and their performance for cadmium adsorption was studied at varying parameters of temperature, time, and alkali (earth) metal concentrations. The maximum adsorption amount at equilibrium of BGR, BGS and BGL was determined experimentally as 8.38 mg/g, 42.12 mg/g, and 30.39 mg/g. Adsorption fitting results revealed that Cd2+ adsorbed on BGR and BGS preferred to be multilayer-covered, and BGL was more likely to have monolayer-covered functions. The kinetic data fitted well to the pseudo-second-order model (R2 > 0.99), revealing the adsorption process was a spontaneous monolayer chemisorption process. The results of alkaline (earth) metals leaching of biochar revealed that the inherent alkaline (earth) metals in biochar made inhibitory functions on the Cd2+ adsorption behavior by occupying the active sites. And in the process of wastewater treatment, the leaching of alkaline earth metals might enhance the complexation reaction between surface groups and Cd2+. This study provides a feasible strategy for the resource utilization of abundant hydrophytic plants in waste management.

Network embedding has shown its effectiveness in many tasks, such as link prediction, node classification, and community detection. Most attributed network embedding methods consider topological features and attribute features to obtain a node embedding but ignore its implicit information behavior features, including information inquiry, interaction, and sharing. These can potentially lead to ineffective performance for downstream applications. In this article, we propose a novel network embedding framework, named information behavior extraction (IBE), that incorporates nodes’ topological features, attribute features, and information behavior features within a joint embedding framework. To design IBE, we use an existing embedding method (e.g., SDNE, CANE, or CENE) to extract a node’s topological features and attribute features into a basic vector. Then, we propose a topic-sensitive network embedding (TNE) model to extract a node’s information behavior features and eventually generate information behavior feature vectors. In our TNE model, we design an importance score rating algorithm (ISR), which considers both effects of the topic-based community of a node and its interaction with adjacent nodes to capture the node’s information behavior features. Eventually, we concatenate a node’s information behavior feature vector with its basic vector to get its ultimate joint embedding vector. Extensive experiments demonstrate that our method achieves significant and consistent improvements compared to several state-of-the-art embedding methods on link prediction.

The iron and steel industry is a large emitter of CO2 globally. This is especially true for the iron and steel industries in China, Japan, and Korea due to their production volumes and the prevalence of carbon-based steel production. With few low-carbon and commercially available alternatives, the iron and steel industry is truly a hard-to-abate sector. Each of the countries of interest have committed to a net-zero future involving the mitigation of emissions from steel production. However, few studies have investigated the means by which to achieve decarbonization beyond the inclusion of price signalling policies (e.g., carbon tax or emission trading schemes). Here, we use E3ME-FTT:Steel to simulate technology diffusion in the ISI under several policy environments and we investigate the likely impacts on the wider economy. The results show that penalizing carbon intensive processes can incentivize a transition towards scrap recycling, but it is relatively unsuccessful in aiding the uptake of low carbon primary steelmaking. A combination of support and penalizing policies can achieve deep decarbonisation (>80% emission reduction compared with the baseline). Mitigating the emissions in the iron and steel industry can lead to economic benefits in terms of GDP (China: +0.8%; Japan: +1.3%; Korea: +0.1%), and employment (Japan: +0.7%; Korea: +0.3%) with China, where job losses in the coal sector would negate job gains elsewhere, as the exception.

Abstract Objective With the development of interventional therapy and precise radiotherapy, such as 3‐D conformal intensity‐modulated radiation therapy and stereotactic body radiotherapy (SBRT), transarterial chemoembolization (TACE) combined with radiotherapy has become an important method of comprehensive treatment for advanced liver cancer. However, few studies focus on the treatment of massive hepatocellular carcinoma (HCC) with SBRT. In this study, we investigated the effects and prognostic factors of whole‐body gamma‐knife SBRT combined with TACE in the treatment of massive HCC. Methods A retrospective analysis was carried out in 81 patients with massive, who received super gamma‐knife (type SGS‐I) SBRT after TACE treatment between 2 January 2011 and 30 June 2016. The curative effects were evaluated using the Modified Response Evaluation Criteria in Solid Tumors criteria. The alpha‐fetoprotein and alanine aminotransferase levels were measured before and after treatment. Patients were followed up for overall survival and 1‐, 3‐, and 5‐year survival rates. Adverse reactions were evaluated using the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer criteria. Results A total of 81 patients were evaluated, including 29 patients with complete response, 48 patients with partial response, two patients with stable disease, and two patients with progressive disease; the total response rate was 95.06%. The 1‐year local control rate was 71.60%. The overall survival rates at 1, 3, and 5 years were 81.48%, 40.74%, and 16.67%, respectively. The median survival time was 15.0 months (95% CI 10.1–19.8 months). Progression‐free time was 11.0 months (95% CI 9.5–14.4 months). The alpha‐fetoprotein level after treatment was (85.53 ± 21.36) μg/L and was significantly lower than that before treatment (635.62 ± 125.83 μg/L; t = 8.189, P = 0.002). The alanine aminotransferase levels were 70.34 ± 16.60 and (54.95 ± 12.02) U/L before and after treatment, respectively, and were not significantly different (t = 1.348, P = 0.624). Multivariate analysis showed that a portal vein tumor thrombus (χ2 = 4.727, P = 0.016) and the Child–Pugh grade of liver function (χ2 = 4.893, P = 0.013) were adverse prognostic factors of overall survival. The 1‐year local control rates and the median survival times were 72.03% and 71.17%, and 16 and14 months, respectively, for the clinical target volumes ≥120 cm3 and

MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor β, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.

Long-term primary culture of mammalian cells has been always difficult due to unavoidable senescence. Conventional methods for generating immortalized cell lines usually require manipulation of genome which leads to change of important biological and genetic characteristics. Recently, conditional reprogramming (CR) emerges as a novel next generation tool for long-term culture of primary epithelium cells derived from almost all origins without alteration of genetic background of primary cells. CR co-cultures primary cells with inactivated mouse 3T3-J2 fibroblasts in the presence of RHO-related protein kinase (ROCK) inhibitor Y-27632, enabling primary cells to acquire stem-like characteristics while retain their ability to fully differentiate. With only a few years’ development, CR shows broad prospects in applications in varied areas including disease modeling, regenerative medicine, drug evaluation, drug discovery as well as precision medicine. This review is thus to comprehensively summarize and assess current progress in understanding mechanism of CR and its wide applications, highlighting the value of CR in both basic and translational researches and discussing the challenges faced with CR.

At present, modern medical data processing systems based on cloud computing, as a very important part of the auxiliary tumor pain treatment program, have played a key role in the soft services of the entire tumor pain treatment program. This article aims at the radiation dose verification problem of tumor patients in tumor treatment. The modern medical data processing system constructed by cloud computing technology is used to solve this kind of problem. The method used in this article is to select 100 tumor patients and use cloud computing-based oncology medical data processing system to analyze patients of different ages and body types, common irradiation sites and irradiation angles, and other irradiation parameters, and calculate using Monte Carlo method. Interventional treatment of the patient's various organs and tissues and the combined results into a large database. The experimental results show that the construction and application of a tumor medical data processing system based on cloud computing can better combine the individual condition and disease characteristics of tumor patients, give an accurate radiation dose for tumor pain treatment, and reduce the incidence of risk events. Compared with the experimental and simulation data of related literature, the results show that the cloud computing-based tumor medical data processing system proposed in this paper has improved the standardization of tumor pain treatment by nearly 15% on average, and the treatment plan satisfaction has increased by nearly 20%.

The relationship between slope and prevention structures under the action of rainfall is complicated. In this paper, a series of model tests were carried out to study the coevolution mechanism of slope and prevention structures under rainfall. It was found that the prestressed grouting steel anchor tube frame beam composite structure has a good reinforcement and protective effect on the slope. Specifically, less damage degree is observed for a slope with prestressed grouting steel anchor tube frame beam, while the slope of without prestressed grouting steel anchor tube frame beam suffers from severe deformation. Under the effect of rainfall, the evolution process of slope and prevention structure cooperative deformation can be divided into three stages: creep stage, extrusion stage, and acceleration stage. The antisliding force provided by the prevention structure is positively correlated with the slope deformation. Moreover, as an initiating factor for changes in various monitoring parameters, rainfall plays a dominant role in the variation of earth pressure reinforcement by steel anchor tube.

Chronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, specialized pro-resolving mediator derived from docosahexaenoic acid, exhibits potent resolution of inflammation in several neurological disorders. This preclinical study evaluates the therapeutic potential and underlying targets of RvD2 in two mouse models of chronic pain, including sciatic nerve ligation-caused neuropathic pain and sarcoma-caused bone cancer pain. Herein, we report that repetitive injections of RvD2 (intrathecal, 500 ng) reduce the initiation of mechanical allodynia and heat hyperalgesia following sciatic nerve damage and bone cancer. Single exposure to RvD2 (intrathecal, 500 ng) attenuates the established neuropathic pain and bone cancer pain. Furthermore, systemic RvD2 (intravenous, 5 μg) therapy is effective in attenuating chronic pain behaviors. Strikingly, RvD2 treatment suppresses spinal IL-17 overexpression, chemokine CXCL1 release and astrocyte activation in mice undergoing sciatic nerve trauma and bone cancer. Pharmacological neutralization of IL-17 ameliorates chronic neuropathic pain and persistent bone cancer pain, as well as reducing spinal CXCL1 release. Recombinant IL-17-evoked acute pain behaviors and spinal CXCL1 release are mitigated after RvD2 administration. In addition, RvD2 treatment dampens exogenous CXCL1-caused transient pain phenotypes. Overall, these current findings identify that RvD2 therapy is effective against the initiation and persistence of long-lasting neuropathic pain and bone cancer pain, which may be through spinal down-modulation of IL-17 secretion, CXCL1 release and astrocyte activation.

Platelets are essential components in the tumor microenvironment. For decades, clinical data have demonstrated that cancer patients have a high risk of thrombosis that is associated with adverse prognosis and decreased survival, indicating the involvement of platelets in cancer progression. Increasing evidence confirms that cancer cells are able to induce production and activation of platelets. Once activated, platelets serve as allies of cancer cells in tumor growth and metastasis. They can protect circulating tumor cells (CTCs) against the immune system and detachment-induced apoptosis while facilitating angiogenesis and tumor cell adhesion and invasion. Therefore, antiplatelet agents and platelet-based therapies should be developed for cancer treatment. Here, we discuss the mechanisms underlying the bidirectional cancer-platelet crosstalk and platelet-based therapeutic approaches.

Abstract Objective Currently, concurrent chemoradiotherapy has become the standard treatment for locally advanced non‐small cell lung cancer, but it is often difficult for elderly patients to tolerate. In this study, we evaluated the curative effect, acute radiation reaction, and clinical application of stereotactic radiotherapy with whole‐body gamma‐knife combined with pemetrexed treatment in elderly patients with locally advanced lung adenocarcinoma. Methods A total of 37 elderly patients with lung adenocarcinoma from Hubei Provincial Armed Police Corps Hospital from 2 January 2013 to 30 December 2015, who were treated with stereotactic radiotherapy with super‐gamma‐knife, were included in the study. The radiotherapy plan was made according to the patient's physical condition, tumor location and size, and therapeutic purpose. A dose of 3.5–5 Gy was administered by 50–70% isodose curve, with a total dose range of peripheral irradiation 35–45 Gy. In the same period, pemetrexed was administered at 500 mg/m2, the first day of chemotherapy (d1), intravenous drip, with 21 days as one cycle, and the number of cycles was more than two. Results The median follow‐up duration was 18 months, and the 1‐, 2‐, and 3‐year follow‐up rates were 86.49% (32/37), 59.46% (33/37), and 21.62% (8/37), respectively. There were no missing cases. After 2–3 months of treatment, computed tomography showed that 13 patients (35.14%) had complete remission, 22 patients (59.46%) had partial remission, one patient (2.70%) achieved a stable status, and one patient (2.70%) still had progression, and the total response rate was 94.59%. The 1‐year local control rate was 67.57%. The 1‐, 2‐, and 3‐year overall survival rates were 86.49%, 45.45%, and 25.00%, respectively. The median overall survival time was 17.0 months (95% CI 14.5–21.3 months); the progression‐free survival time was 12.0 months (95% CI 11.6–12.8 months). Multivariate analysis showed that lymph node stage N ≥2 and radiotherapy biological effective dose 2 acute or late lung and esophagus toxicity was observed. Conclusions In elderly patients with lung adenocarcinoma, stereotactic body radiotherapy with super‐gamma‐knife combined with pemetrexed treatment is safe and definitive, with mild adverse effects.

Current cancer therapies have encountered adverse response due to poor therapeutic efficiency, severe side effects and acquired resistance to multiple drugs. Thus, there are urgent needs for finding new cancer-targeted pharmacological strategies. In this review, we summarized the current understanding with THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), which demonstrated promising anti-tumor activity against different cancer types. By introducing the anti-tumor behaviors and the potential targets for different cancers, this review aims to provide more effective approaches to CDK7 inhibitor-based therapeutic agents and deeper insight into the diverse tumor proliferation mechanisms. Keywords: THZ1, Cyclin-dependent kinase 7, Cancer therapy, Transcription, Super-enhancer

Brain disorders represent 32% of the global disease burden, with 169 million Europeans affected. Constraint-based metabolic modelling and other approaches have been applied to predict new treatments for these and other diseases. Many recent studies focused on enhancing, among others, drug predictions by generating generic metabolic models of brain cells and on the contextualisation of the genome-scale metabolic models with expression data. Experimental flux rates were primarily used to constrain or validate the model inputs. Bi-cellular models were reconstructed to study the interaction between different cell types. This review highlights the evolution of genome-scale models for neurodegenerative diseases and glioma. We discuss the advantages and drawbacks of each approach and propose improvements, such as building bi-cellular models, tailoring the biomass formulations for glioma and refinement of the cerebrospinal fluid composition.

BackgroundRecent research of clear cell renal cell carcinoma (ccRCC) is focused on the tumor immune microenvironment (TIME). Chromatin accessibility is critical for regulation of gene expression. However, its role in different immunological subtypes of ccRCC based on immune cell infiltration has not been systematically studied.MethodsFive hundred thirty patient data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) were adopted to estimate immune cell infiltration. Twenty-four types of immune cells were evaluated with single-sample Gene Set Enrichment Analysis (ssGSEA). Patients were divided into two clusters based on immune cell infiltration. Systematic chromatin accessibility analysis was conducted based on the two clusters.ResultsWe compared the relative expression of the immune gene signatures among 530 patients of TCGA-KIRC using ssGSEA. Overall survival (OS) analysis revealed 10 types of immune cells were significantly associated with prognosis. Patients were divided into two clusters based on 24 types of immune cell infiltration. Immune cell signals as well as PD-1/PD-L1 signal were higher in cluster 1. Among the two clusters, 2,400 differential peaks were found in TCGA-KIRC Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) data. The distribution of differential peaks and prognosis-related immune cells in 23 chromosomes are essentially the same. There is no peak distribution downstream. The proportion of peaks upstream of the 5’ transcription start site decreases, and both sides of binding regions of the TSS 0.1-1 kb becomes smaller. Enrichment analysis of GO and KEGG of these differential peaks showed that they are remarkably related to the immune regulation in tumor microenvironment. Known motifs and de novo motifs were found by linking motif annotations to different peaks. Survival analysis of related motif transcription factors were prognostic. The GSEA enrichment analysis showed that high SP1 expression positively correlates with TGF-beta signaling and inflammatory response, while negatively correlates with TNF-alpha signaling via NFKB. High KLF12 expression negatively correlates with interferon gamma response, IL2-STAT5 signaling, TNF-alpha signaling via NFKB, IL6-JAK-STAT3 signaling.ConclusionThe abnormality of chromatin accessibility may play an important regulatory role in ccRCC immunity.

BackgroundProstate cancer (PCa) is the second most common cancer among males in the world and the majority of patients will eventually progress to the metastatic phase. How to choose an effective way for the treatment of metastatic PCa, especially in the later stage of the disease is still confusing. Herein we reported the case of a patient diagnosed with metastatic PCa and conducted a literature review on this issue.Case PresentationA 57-year-old man with metastatic PCa had been managed by Dr. J.P. since April 2012 when the patient was admitted to the Third Affiliated Hospital of Sun Yat-sen University by aggravating frequent urination and dysuria. The prostate-specific antigen (PSA) concentration was 140 ng/ml, and the diagnosis of PCa was confirmed by prostate biopsy, with Gleason score 4 + 5 = 9. Chest CT and bone scan indicated multiple metastases in the lungs and bones. Triptorelin, bicalutamide, zoledronic acid, and docetaxel were then administered, six cycles later, the metastatic tumors in the lungs disappeared and those in the bones lessened significantly, along with a remarkable reduction in PSA level (< 2 ng/ml). Intermittent androgen deprivation was subsequently conducted until August 2018, when the serum PSA level was found to be 250 ng/ml, again docetaxel 75 mg/m2 was administered immediately but the patient was intolerant this time. Instead, abiraterone was administered until March 2019 because of intolerable gastrointestinal side-effects and increasing PSA level. In October 2019, the patient came to our center, a modified approach of docetaxel (day 1 40 mg/m2 + day 8 35 mg/m2) was administered. Luckily, the PSA level decreased rapidly, the bone pain was greatly relieved, and no obvious side effects occurred. However, four cycles later, docetaxel failed to work anymore, the metastatic tumor in the liver progressed. We proposed several regimens as alternatives, but they were soon denied due to the high prices or unavailability or uncertain effect of the drugs. In addition, the patient’s condition deteriorated speedily and can no longer bear any aggressive treatment. Finally, the patient died of multiple organ failure in August 2020.ConclusionThe experiences of this case provide valuable evidence and reference for the treatment choices of metastatic PCa, in some circumstances modified and advanced regimens may produce unexpected effects.

This paper proposes a framework for a layout evaluation of urban public sports facilities. First, the buffer analysis method is used to measure the service level of public sports facilities. The study findings indicate that the overall service level of public sports facilities presents the spatial characteristics of a central agglomeration, and the value of the service level diffuses outward from high to low. There is evident spatial heterogeneity in the layout of public sports facilities in Hangzhou. Second, the Gini coefficient, Lorenz curve, and location entropy are employed to measure the equity of the distribution among spatial units and the intradistrict disparity. The results show a mismatch between the spatial distribution of the facilities and the distribution of the permanent population. The patterns of distribution of the location entropy classes of Hangzhou can be divided into three types: balanced, alternating, and divergent districts. The method in this paper is effective in measuring spatial equity and visualizing it. it has a certain degree of systemicity, universality and operability. At the same time, this method can compare the diachronic characteristics of the same city and the synchronic characteristics of different cities, which has universal application value.

Recent research regards the electroencephalogram (EEG) as a promising method to study real-time brain dynamic changes in patients with Parkinson's disease (PD), but a deeper understanding is needed to discern coincident pathophysiology, patterns of changes, and diagnosis. This review summarized recent research on EEG characterization related to the cognitive and motor functions in PD patients and discussed its potential to be used as diagnostic biomarkers. Thirty papers out of 220 published from 2010 to 2020 were reviewed. Movement abnormalities and cognitive decline are related to changes in EEG spectrum and event-related potentials (ERPs) during typical oddball paradigms and/or combined motor tasks. Abnormalities in β and δ frequency bands are, respectively the main manifestation of dyskinesia and cognitive decline in PD. The review showed that PD patients have noteworthy changes in specific EEG characterizations, however, the underlying mechanism of the interrelation between gait and cognitive is still unclear. Understanding the specific nature of the relationship is essential for development of novel invasive clinical diagnostic and therapeutic methods.

BackgroundThe skeleton is a preferred site for prostate cancer metastasis, and once metastases occur, the disease becomes incurable. Increasing evidence indicates the prognostic value of skeletal-related parameters, but remains controversial.ObjectiveTo perform a systematic review of the existing literature on assessing the prognostic value of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BSAP), urinary N-telopeptide (uNTx), bone scan index (BSI), and Brief Pain Inventory Short Form (BPI-SF) score in castration-resistant prostate cancer (CRPC) patients with skeleton metastasis.Evidence AcquisitionPubMed, Web of Science, Cochrane Library, Medline, OVID, and Embase between 2010 and 2019 were reviewed. Key terms included randomized trials, prostate cancer, alkaline phosphatase, bone-specific alkaline phosphatase, urinary N-telopeptide, bone scan index, and Brief Pain Inventory Short Form. Data were collected, checked, and analyzed from December 2019 to March 2020. Hazard ratios (HRs) and overall survival (OS) were extracted to estimate the relationship between the above parameters and OS in patients with metastatic prostate cancer (mPCa).Evidence SynthesisA total of 1,055 studies were identified via initial screening, including 1,032 from database research and 23 from other sources. After deduplication, 164 records were further excluded according to titles and abstracts. The remaining 36 potential articles were carefully screened. In the end, 15 eligible studies syntheses, which were published between 2010 and 2019, comprised data for a total of 11,378 patients, whose mean age ranged from 66 to 72 years. The sample size ranged from 82 to 1,901 patients. And the median follow-up time ranged from 24 to 55 months. Based on 15 randomized controlled trials published between 2010 and 2019, higher ALP levels (HR = 1.60, 95% CI: 1.38–1.87 P < 0.001), higher BSAP levels (HR = 1.31, 95% CI: 1.11–1.54 P = 0.001), higher uNTx levels (HR = 1.40, 95% CI: 1.29–1.52 P < 0.001), BSI progression (HR = 1.18, 95% CI: 1.08–1.29 P < 0.001), and higher BPI-SF score (HR = 1.47, 95% CI: 1.35–1.61 P < 0.001) had an association with inferior OS.ConclusionsHigher levels of ALP/BSAP and uNTx, a higher BPI-SF score, and progression of BSI predict inferior OS in patients with mCRPC. More randomized control trials are needed to investigate the promising value of these parameters.

Purpose: Accumulative studies suggest the Glasgow prognostic score (GPS) and modified Glasgow prognostic score (mGPS) to be potential biomarkers; however, their prognostic value remains debatable. Our meta-analysis focused on assessing the accurate prognostic value of GPS and mGPS in patients with renal cell carcinoma (RCC) in addition to their effectiveness.Methods: To investigate the relationship between mGPS/GPS and prognostic value in patients with RCC, we performed a comprehensive retrieval of relevant articles from databases such as PubMed, Embase, Web of Science, and Medline up to February 1, 2020. STATA 15.0 software was used to obtain pooled hazard ratios (HRs) and their 95% confidence intervals for survival outcome, including overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS). A formal meta-analysis of these outcomes was performed.Results: In total, 2,691 patients with RCC were enrolled from 15 cohort studies. Higher GPS/mGPS (GPS/mGPS of 2) indicated poorer OS, CSS, PFS, and RFS in patients with RCC. Similarly, medium GPS/mGPS (GPS/mGPS of 1) also had a significant association with poorer OS, CSS, PFS, and RFS but superior than higher GPS/mGPS in these patients.Conclusion: GPS and mGPS are effective biomarkers for predicting prognosis in patients with RCC, and higher GPS and mGPS are closely related to inferior survival outcomes. More randomized controlled trials are needed to investigate the promising value of GPS/mGPS in the future.

This study set out to investigate the effect of massage on the Toll-like receptor 4 (TLR4) signalling pathway in the dorsal root ganglia of rats that had undergone spinal nerve ligation (SNL), with the hypothesis that massage could be used as an analgesic. Forty female SD rats were randomly divided into 5 groups: the control group, sham-operated group, model group, sham massage group, and massage group. There were 8 rats in each group. SNL rat models were established in the model group, sham massage group, and massage group. Rats in the sham-operated group underwent surgery to expose the vertebral nerves, but no further procedures were performed. The control group consisted of intact animals. The rats in the massage group underwent massage using a massage simulation machine once a day for 14 d in succession; the hind limbs of the rats in the sham massage group were gently touched with a cloth bag once a day for 14 continuous days. The rats in the control group, the sham-operated group, and the model group did not receive any intervention and were observed for 14 d. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) of rats in each group were detected 1 d before modelling and at 1, 3, 7, and 14 d after modelling. Fourteen days after modelling, the expression levels of TLR4, IRAK1, TRAF6, TNF-α, and IL-6 were detected in all rats. The PWTL and PWMT of SNL rats were decreased, while these parameters were elevated after massage. SNL rats showed higher levels of TLR4, IRAK1, TRAF6, IL-6, and TNF-α, and massage effectively lowered the expression levels of these molecules. Inhibiting activation of the TLR4 signalling pathway, which can reduce the release of inflammatory factors, may be one mechanism by which massage treats neuropathic pain.

An information outbreak occurs on social media along with the COVID-19 pandemic and leads to an infodemic. Predicting the popularity of online content, known as cascade prediction, allows for not only catching in advance information that deserves attention, but also identifying false information that will widely spread and require quick response to mitigate its negative impact. Among the various information diffusion patterns leveraged in previous works, the spillover effect of the information exposed to users on their decisions to participate in diffusing certain information has not been studied. In this paper, we focus on the diffusion of information related to COVID-19 preventive measures due to its special role in consolidating public efforts to slow down the spread of the virus. Through our collected Twitter dataset, we validate the existence of the spillover effects. Building on this finding, we propose extensions to three cascade prediction methods based on Graph Neural Networks (GNNs). Experiments conducted on our dataset demonstrated that the use of the identified spillover effects significantly improves the state-of-the-art GNN methods in predicting the popularity of not only preventive measure messages, but also other COVID-19 messages.

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 (CRMP4) methylation levels and the Cancer of the Prostate Risk Assessment (CAPRA-S) Postsurgical score of patients who required adjuvant hormone therapy (AHT) after radical prostatectomy (RP). We retrospectively analyzed 305 patients with prostate cancer (PCa) who received RP and subsequent androgen deprivation therapy (ADT). Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality (CSM) in patients with ≥15% CRMP4 methylation were 6.81 (95% CI: 2.34-19.80) and 12.83 (95% CI: 2.16-26.10), respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels ≥15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ≥6 and CRMP4 methylation levels ≥15% were independent predictors of these outcomes (uni- and multi-variable Cox regression analyses). The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ≥15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.

Abstract Background Primary malignant lymphoma of the prostate (PMLP) is prone to occur in the elderly, and it has no significant correlation with lactate dehydrogenase (LDH) and prostate specific antigen (PSA). Clinical symptoms and imaging data of PMLP remain unspecific, and its prognosis is poor. A previous result showed that collapsin response mediator protein 4 (CRMP4) promotor methylation can be used as a predictor for lymph node metastases in prostate biopsies. However, the relationship between CRMP4 promotor methylation and PMLP has not been studied. Methods We investigated the clinicopathological features of PMLP and the significance of CRMP4 methylation in PMLP. The clinical data and diagnosis information of 10 patients with PMLP were retrospectively analyzed. The CRMP4 promotor methylation level in paraffin-embedded tissues of the 10 patients with PMLP were determined and then compared to limited prostate cancer (LPCa) and its negative lymph node tissue [LPCa-LN (−) (10 cases)] and also to metastatic prostate adenocarcinoma (mPCa) and its positive lymph node tissue [mPCa-LN (+) (10 cases)]. Methylation of the CRMP4 promotor in each group was analyzed statistically. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of CRMP4 methylation in PMLP. Results The average methylation value of CRMP4 in 10 PMLP patients, 20 cases of prostate adenocarcinoma tissue, 10 cases LPCa-LN (−) and 10 cases mPCa-LN (+) were 42.3, 30.6, 6.7 and 20.3%, respectively. A Kruskal–Wallis test showed that the difference of CRMP4 methylation was significant (X2 = 38.0, P 40.9% could diagnose PMLP. This method had 90% sensitivity and 95% specificity under conditions of CRMP4 methylation > 40.9%. The area under the curve (AUC) was 0.957. Conclusions Methylation of the CRMP4 gene was significantly increased in PMLP, and it is expected to become a new predictor for PMLP.

Locomotion recognition and prediction is essential for real-time human–machine interactive control. The integration of electromyography (EMG) with mechanical sensors could improve the performance of locomotion recognition. However, the potential of EMG in motion prediction is rarely discussed. This paper firstly investigated the effect of surface EMG on the prediction of locomotion while integrated with inertial data. We collected EMG signals of lower limb muscle groups and linear acceleration data of lower limb segments from ten healthy participants in seven locomotion activities. Classification models were built based on four machine learning methods—support vector machine (SVM), k-nearest neighbor (KNN), artificial neural network (ANN), and linear discriminant analysis (LDA)—where a major vote strategy and a content constraint rule were utilized for improving the online performance of the classification decision. We compared four classifiers and further investigated the effect of data fusion on the online locomotion classification. The results showed that the SVM model with a sliding window size of 80 ms achieved the best recognition performance. The fusion of EMG signals does not only improve the recognition accuracy of steady-state locomotion activity from 90% (using acceleration data only) to 98% (using data fusion) but also enables the prediction of the next steady locomotion (∼370 ms). The study demonstrates that the employment of EMG in locomotion recognition could enhance online prediction performance.

Background: Controversy still exists that whether clopidogrel should add proton pump inhibitors (PPIs) in patients with coronary heart disease after percutaneous coronary intervention (PCI). The aim of this study was to evaluate the efficacy and safety of clopidogrel added proton pump inhibitors (PPIs) vs. clopidogrel for the treatment of patients with coronary heart disease after percutaneous coronary intervention (PCI). Methods and results: We systematically searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library for all clinical trials that were published on this topic through October 2018. We specifically selected the clinical trials that evaluated the efficacy and safety of clopidogrel added proton pump inhibitors vs. clopidogrel in the treatment of patients with coronary heart disease after PCI. RevMan 5.0 software was used for quantitative data analyses.15 randomized controlled trials including 50,366 patients were included. The meta-analysis results showed that compared with the clopidogrel added PPI group, the non-PPI group had significantly less risk of MACE[RR = 0.82,95%CI:0.77–0.88], myocardial infarction recurrence[RR = 0.72,95%CI:0.57–0.90], stent thrombosis[RR = 0.71,95%CI:0.56–0.92], Target vessel revascularization (TVR)[RR = 0.77,95%CI:0.63–0.93] and stroke [RR = 0.72,95%CI:0.67–0.76]. The risks of all cause death [RR = 1.14,95%CI:0.85–1.51], cardiovascular death [RR = 1.14, 95% CI: 0.85–1.52], bleedings events [RR = 1.60,95%CI:0.53–4.81] were similar in the two groups. Conclusions: The patients in the non-PPI group were observed to be associated with less risk of MACE, myocardial infarction recurrence, stent thrombosis, target vessel revascularization (TVR) and stroke. And the two groups had similar all cause death, cardiovascular death, bleedings events. Keywords: Clopidogrel, Proton pump inhibitor (PPI), Cardiovascular outcome, Meta-analysis

The outbreak of the COVID-19 led to a burst of information in major online social networks (OSNs). Facing this constantly changing situation, OSNs have become an essential platform for people expressing opinions and seeking up-to-the-minute information. Thus, discussions on OSNs may become a reflection of reality. This paper aims to figure out how Twitter users in the Greater Region (GR) and related countries react differently over time through conducting a data-driven exploratory study of COVID-19 information using machine learning and representation learning methods. We find that tweet volume and COVID-19 cases in GR and related countries are correlated, but this correlation only exists in a particular period of the pandemic. Moreover, we plot the changing of topics in each country and region from 22 January 2020 to 5 June 2020, figuring out the main differences between GR and related countries.

Based on the experiments of utilization of garlic processing wastewater in a lotus pond, this study demonstrates that lotus pond wetlands have a remarkable ability to remove organic pollutants and decrease chemical oxygen demand (CODCr), biochemical oxygen demand (BOD5), and suspended substances (SS) in garlic processing wastewater. Results also show evident effects of lotus roots on absorption of NH3-N. The pH value in a lotus pond with wastewater discharged was relatively stable. The water quality in the lotus pond reached the class II emission standard, according to the Integrated Wastewater Discharge Standard (GB8978-1996), seven days after pretreated garlic processing wastewater had been discharged into the lotus pond. Garlic processing wastewater irrigation does not produce pollution in the pond sediment and has no negative effect on the growth of lotus roots. Due to utilization of garlic processing wastewater, the output of lotus roots increased by 3.0% to 8.3%, and the quality of lotus roots was improved. Therefore, better purification and utilization results can be achieved.

Based on the MAP-CGE model, this paper simulated the impacts on the output, energy consumption and pollutant emissions of different cement production processes when implementing a low carbon cement standard in China. It also calculated the impacts on the marginal abatement cost and equilibrium price of the cement industry, and analyzed the co-abatement effects of different pollutants. The results showed that implementing the low carbon cement standard will be beneficial in promoting an upgrading of cement production processes, and strengthening the energy conservation and emission reduction in the cement industry. If there is no change in the existing technology, the cement industry will reduce SO2 emissions by 1.17 kg and NOx emissions by 4.44 kg per ton of CO2 emission reduction. Implementing low carbon cement standard can also promote NOx abatement in the cement industry. However, the cement industry will bear the abatement costs, and their equilibrium price will increase slightly. Citation: Pang, J., Y.-C. Shi, X.-Z. Feng, et al., 2014: Analysis on impacts and co-abatement effects of implementing the low carbon cement standard.Adv. Clim. Change Res.,5(1), doi: 10.3724/SP.J.1248.2014.041.