Prediction of overall survival for patients with metastatic castration-resistant prostate cancer : development of a prognostic model through a crowdsourced challenge with open clinical trial data

Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer.Peer reviewe

Water Corrosion of Tungsten Target for Accelerator-Driven Neutron Source

The water corrosion of tungsten as a target material can affect the safe operation of accelerator-driven neutron source. This paper reported the corrosion behaviors of tungsten in ultrapure water and tap water for 7, 14, 21, 30 and 60 days. Moreover, ICP-MS, XRD, XPS, SEM-EDS and LSCM were used to analyze the components in solutions, crystalline structures, chemical compositions and surface morphologies. It was found that the dissolution of tungsten, due to corrosion, reached its maximum between 30 days and 60 days in both solutions. The cube-shape substance, CaWO4, was the main corrosion product after tungsten in tap water. The tungsten oxide was changed from WO3 to WO2 during the corrosion of tungsten in ultrapure water. Compared with tungsten in ultrapure water, tungsten in tap water had its surface completely destroyed, with a dense diamond shape. Therefore, based on the analysis from this study, the corrosion mechanisms of tungsten in ultrapure and tap water were revealed

Study of the Crystallographic Distortion Mechanism during the Annealing of Kaolinite

The distortion process of kaolinite annealed from 25 °C to 550 °C for different holding times can be characterized using a thermogravimetric/differential scanning calorimeter (TG/DSC) for thermal analysis, X-ray diffraction (XRD) for establishing the crystal structure, the Fourier transform infrared spectrum (FTIR) for identifying the functional groups, and a scanning electron microscope (SEM) for establishing the microstructure. Dehydroxylation is the main reaction during annealing from 25 °C to 550 °C and leads to kaolinite crystal distortion. A stable crystal structure during distortion was obtained by optimizing the bulk phase with quantum chemistry. Then, the crystal structure was studied by using ab initio multiple scattering calculations for X-ray absorption of the fine structure (XAFS). The results of X-ray absorption near the edge structures (XANES) determined that peak shifts and intensity phases slightly increased. The crystal structure distortion of kaolinite during annealing can be explained by the experimental and simulation results. This work provides theoretical support for identifying kaolinite with different degrees of distortion and has the potential for further developments in coal gangue separation

System value assessment method of energy storage system for multi‐services of power system considering battery degradation

Abstract The energy storage system (ESS) is a promising technology to address issues caused by the large‐scale deployment of renewable energy. Deploying ESS is a business decision that requires potential revenue assessment. Current value assessment methods focus on the energy storage owner or the electricity utility. The system value of the ESS needs to be fully considered to gain a broad understanding of benefits across the whole power system. Thus, this study proposes a system value assessment method of grid‐integrated ESS to quantify the total system value‐avoided cost based on an improved DC power flow model considering transmission losses. Four typical applications (production cost saving, upgrade deferral, environmental benefit, and transmission loss saving) are chosen to represent the system value of the ESS across the whole power system. In addition, the co‐optimisation model considering the “source‐grid‐storage” coordination operation and battery capacity degradation, is proposed for peak shaving and frequency regulation based on the Chinese power market rule. The proposed method is tested in simulation and experimental studies

DoMYB5 and DobHLH24, Transcription Factors Involved in Regulating Anthocyanin Accumulation in <i>Dendrobium officinale</i>

As a kind of orchid plant with both medicinal and ornamental value, Dendrobium officinale has garnered increasing research attention in recent years. The MYB and bHLH transcription factors play important roles in the synthesis and accumulation of anthocyanin. However, how MYB and bHLH transcription factors work in the synthesis and accumulation of anthocyanin in D. officinale is still unclear. In this study, we cloned and characterized one MYB and one bHLH transcription factor, namely, D. officinale MYB5 (DoMYB5) and D. officinaleb bHLH24 (DobHLH24), respectively. Their expression levels were positively correlated with the anthocyanin content in the flowers, stems, and leaves of D. officinale varieties with different colors. The transient expression of DoMYB5 and DobHLH24 in D. officinale leaf and their stable expression in tobacco significantly promoted the accumulation of anthocyanin. Both DoMYB5 and DobHLH24 could directly bind to the promoters of D. officinale CHS (DoCHS) and D. officinale DFR (DoDFR) and regulate DoCHS and DoDFR expression. The co-transformation of the two transcription factors significantly enhanced the expression levels of DoCHS and DoDFR. DoMYB5 and DobHLH24 may enhance the regulatory effect by forming heterodimers. Drawing on the results of our experiments, we propose that DobHLH24 may function as a regulatory partner by interacting directly with DoMYB5 to stimulate anthocyanin accumulation in D. officinale

The lead time and geographical variations of Baidu Search Index in the early warning of COVID-19

Abstract Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of “COVID-19 epidemic”, “Novel Coronavirus” and “COVID-19” can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0–28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5–8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1–3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70–0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase

DataSheet2_Chinese herbal medicine for the treatment of chronic fatigue syndrome: A systematic review and meta-analysis.pdf

Objectives: This meta-analysis aimed to assess the effectiveness and safety of Chinese herbal medicine (CHM) in treating chronic fatigue syndrome (CFS).Methods: Nine electronic databases were searched from inception to May 2022. Two reviewers screened studies, extracted the data, and assessed the risk of bias independently. The meta-analysis was performed using the Stata 12.0 software.Results: Eighty-four RCTs that explored the efficacy of 69 kinds of Chinese herbal formulas with various dosage forms (decoction, granule, oral liquid, pill, ointment, capsule, and herbal porridge), involving 6,944 participants were identified. This meta-analysis showed that the application of CHM for CFS can decrease Fatigue Scale scores (WMD: –1.77; 95%CI: –1.96 to –1.57; p Conclusion: Our study showed that CHM seems to be effective and safe in the treatment of CFS. However, given the poor quality of reports from these studies, the results should be interpreted cautiously. More international multi-centered, double-blinded, well-designed, randomized controlled trials are needed in future research.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319680], identifier [CRD42022319680].</p