bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ukrainian experience in implementation of the flexible provisions of the TRIPS Agreement in the context of European integration and the pandemic
Authors: Kashyntseva Oksana , Iolkin Yaroslav 
Published: November 2021

Keywords: intellectual property, human rights, patients' rights, pharmaceutical nationalism,protectionism, vaccines, generics, COVID-19
The article concerns the analysis of global trends in theparadigm of intellectual property rights on the objects used in the diagnosis, preventionand treatment of COVID-19. The experience of the implementation of pharmaceuticalnationalism policies provided by the EU, Canada and Israel are presented in the article.The authors provide the legal backgrounds of the need for Ukraine to be a co-sponsor ofthe IP waivers proposals, which are submitted to the TRIPS Council by some membersof the WTO. The authors stress the need for Ukraine to use the historic opportunity forthe development of the national pharmaceutical industry, which would contribute tothe interests of the domestic patient, and make proposals for the necessary changes tonational legislation.The authors also stressed the position of the governments of Germany and France.Thus, in Germany there is the Law on Governmental Use of Patented Inventions duringa Pandemic. The law provides, inter alia, for amendments to the Patent Law, accordingto which the Federal Ministry of Health has the right to authorize the use of relevantpatents to ensure the production and supply of pharmaceuticals or medical devices.In 2020, France adopted the Emergency Law № 2020-290 to combat theCOVID-19 epidemic, which introduced Article 3131 15 of the French Public HealthCode. This rule authorizes the Prime Minister to issue orders to recover or seize allgoods and services necessary to combat the disaster, to temporarily control the price ofproducts and, if necessary, to take any measures to ensure that patients are providedwith appropriate drugs to deal with the disaster, related to health. It is useful forUkraine to use the experience of Canada in terms of facilitating negotiations with majorvaccine manufacturers to establish national drug production and in terms of developinglegislation in the field of compulsory licensing.It is obviously, voluntary licences from patent owners, which provide for the fulltransfer of technology, and not just patent disclosure, are the most effective tool for thenational production of biosimilars. However, international experience shows that pharmaceuticalcompanies are holding back the issuance of compulsory licences. Therefore,our government's biosecurity portfolio should include an effective tool for compulsory licensingor emergency use of biosimilars and generic drugs by the Government.
Legal education on intellectual property
Authors: Chomakhashvili Olena 
Published: November 2021

Keywords: legal education, legal values, intellectual property law, invention
The article focuseson a comprehensive study of the concept and importance of legal education on intellectualproperty. Particular attention is paid to the social importance and significanceof the entire sphere of intellectual property and is considered as a legal value. Theauthor attempts to determine the relationship between the level and popularity of inventionand general culture in the field of intellectual property. The stages and methodsof obtaining knowledge on the basics of the intellectual property are considered.The problematic issues concerning the necessary measures in the field of educationon intellectual property issues are analysed. The concept of educational measuresis described in detail, which is aimed at intensifying the understanding of Ukrainiansociety of the need for legal application of intellectual property rights. Proposals weremade to increase educational activities on intellectual property issues and awarenessof their value to society.
The purpose of the article is to study the general structure of legal education and tooutline the place of intellectual property law in the general system of legal education.Find out the essence and importance of legal education on intellectual property issues.In order to achieve the goal, we formulate the task: to consider the structure of legaleducation; formulate arguments in favour of studying the field of intellectual propertyand propose measures to promote intellectual property and inventive activity.The article is devoted to the study of education in the field of intellectual propertylaw, the essence of which is personal non-property rights of intellectual property andproperty rights of intellectual property.The basis for innovative economic development is the widespread introduction ofintellectual property. For this, highly qualified specialists are needed. The importanceof constant training of specialists in the field of intellectual property and supportof invention is substantiated.A new concept of training specialists in intellectual property is considered, accordingto which the master's program in the complex covers three areas: technical expertise ofintellectual property, the economy of intellectual property and the law of intellectualproperty. This activity is focused on the formation of the necessary level of knowledgeand education of respect for intellectual work and its results, which are embodied in intellectualproperty, as well as informing the public about possible losses and existingthreats to the well-being and health of people that contain counterfeit and pirated goods.The place of education on intellectual property in the system of general and highereducation has been determined. The general characteristics of educational levels inthe field of intellectual property is outlined.
Comprehensive Analysis and Identification of Prognostic Biomarkers and Therapeutic Targets Among FAM83 Family Members for Gastric Cancer
Authors: Zhang Tianhao , Lai Shurong , Cai Yuzhi , Huang Zhixin , Li Ying , Chen Sile , Zhang Zhimei , Ye Zhijun , Lai Xiaoling , Zhai Ertao , Cai Shirong , Chen Jianhui 
Published: November 2021

Background: Gastric cancer (GC) is one of the most common and poor prognosis malignancy in the world. The Family with sequence similarity 83 (FAM83) comprises of eight members of A–H. Accumulating evidence confirmed important roles for FAM83 family in tumorigenesis and progression. However, the prognostic values of FAM83 family in GC still have not been clarified.Methods: ONCOMINE, UALCAN, GEPIA, THE HUMAN PROTEIN ATLAS, Kaplan–Meier Plotter, cBioPortal, DAVID, STRING and TIMER databases and R software were adopted in this study.Results: In this study, we demonstrated that the mRNA levels of FAM83 B/C/D/H were significantly up-regulated in stomach adenocarcinoma (STAD), but the protein level of FAM83G/H were remarkable lowly in STAD. Next, FAM83C/D/G/H were significantly associated with tumor stages in STAD patients. Then, the mutation rate of FAM83 family members in STAD patients was 46%, and the highest mutation rate was FAM83H (23%). Furthermore, the functions of FAM83 family and their 259 co-expression genes were primarily related to Shigellosis, RNA degradation and Ribosome biogenesis in eukaryotes pathway. Besides, we have established the prognostic model of FAM83 family in STAD, including the prognostic model of STAD patients (FAM83C/D/G), STAD with lymph node metastasis (FAM83C/D/G/H) and STAD with ERBB2 high expression (FAM83G/H). FAM83C/D high expression with a poor prognosis, while FAM83G/H high expression with a favorable prognosis of STAD. Additionally, we found that the expression of FAM83C/D/G/H were significantly correlated with the infiltration of six types of immune cells [B cells, CD8+T cells, CD4+T cells, macrophages and Myeloid dendritic cells (DC)], whereas CD4+T cells and Macrophage cells have higher risk scores (HR &gt; 1) when FAM83C lowly expression and FAM83D highly expression. The risk score of NK cells was significantly reduced when FAM83G lowly expression and FAM83H highly expression (HR &lt; 1).Conclusion: These findings suggested that FAM83C/D/G/H might play key roles in STAD tumorigenesis and progression, and FAM83C/D might be risk factors but FAM83G/H might be favorable prognostic factors for STAD patients. In addition, CD4+T cells and Macrophage cells may be the promoters of FAM83D in progression of STAD, while NK cells may promote the protective effect of FAM83H on STAD patients.
Diaportones A–C: Three New Metabolites From Endophytic Fungus Diaporthe foeniculina BZM-15
Authors: Kang Fenghua , Lu Xiuxiang , Zhang Sha , Chen Dekun , Kuang Min , Peng Weiwei , Tan Jianbing , Xu Kangping , Zou Zhenxing , Tan Haibo 
Published: November 2021

Phytochemical investigation of Diaporthe foeniculina BZM-15 led to one new γ-butyrolactone derivative, diaportone A (1), one cyclopentenone derivative, diaportone B (3), and one monoterpene derivative, diaportone C (5), along with six known compounds (2, 4, and 6–9). Their structures as well as the absolute configurations were characterized by means of NMR, HRESIMS, and ECD spectroscopy and quantum chemistry calculation, respectively. Furthermore, all compounds were evaluated for their cytotoxic activity and antibacterial activity, and compounds 7 and 8 displayed significant antiproliferative effects on three human cancer cell lines (SF-268, MCF-7, and HepG2) with IC50 values ranging from 3.6 to 15.8 μM.
Angiogenesis, Anti-Tumor, and Anti-Metastatic Activity of Novel α-Substituted Hetero-Aromatic Chalcone Hybrids as Inhibitors of Microtubule Polymerization
Authors: Sun Moran , Wang Yuyang , Yuan Minghua , Zhao Qing , Zhang Yixin , Yao Yongfang , Duan Yongtao 
Published: November 2021

A library of new heteroaromatic ring-linked chalcone analogs were designed and synthesized of these, compound 7m with α-CH3 substitution and bearing a benzofuran ring, displaying the most potent activity, with IC50 values of 0.07–0.183 µM against three cancer cells. Its low cytotoxicity toward normal human cells and strong potency on drug-resistant cells revealed the possibility for cancer therapy. It also could moderately inhibit in vitro tubulin polymerization with an IC50 value of 12.23 µM, and the disruption of cellular architecture in MCF-7 cells was observed by an immunofluorescence assay. Cellular-based mechanism studies elucidated that 7m arrested the cell cycle at the G2/M phase and induced apoptosis by regulating the expression levels of caspases and PARP protein. Importantly, the compound 7 m was found to inhibit HUVEC tube formation, migration, and invasion in vitro. In vivo assay showed that 7m could effectively destroy angiogenesis of zebrafish embryos. Furthermore, our data suggested that treatment with 7m significantly reduced MCF-7 cell metastasis and proliferation in vitro and in zebrafish xenograft. Collectively, this work showed that chalcone hybrid 7m deserves further investigation as dual potential tubulin polymerization and angiogenesis inhibitor.
The Efficacy of Transcarotid Artery Revascularization With Flow Reversal System Compared to Carotid Endarterectomy: A Systematic Review and Meta-Analysis
Authors: Gao Jianfeng , Chen Zhong , Kou Lei , Zhang Hanfang , Yang Yaoguo 
Published: November 2021

Background: Carotid artery stenosis has long been a critical cause of stroke and death, and it can seriously affect the life quality. Transcarotid artery revascularization (TCAR) and carotid endarterectomy (CEA) are both feasible therapies for this disease. This systematic review and meta-analysis aim to evaluate if the efficacy of the two approaches is comparable.Methods: Clinical studies up to March 2021 were searched through PubMed, Embase, and Scopus from a computer. The screening process was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Newcastle-Ottawa Scale (NOS) was used for methodological quality assessment of works of literature meeting the inclusion criteria, and Review Manager 5.4 was used for data synthesis. The I2 statistic was performed to measure the heterogeneity, and M-H/I-V fixed or random model was utilized depending on the I2 value. The evidence evaluation was accomplished based on grades of recommendation, assessment, development, and evaluation (GRADE) online tool.Results: A total of 14,200 subjects (six comparative studies) were finally included in this pooled study. There is no statistical discrepancy between the two treatments on reducing stroke/death/myocardial infarction (odds ratio [OR] 0.85, 95% CI 0.67–1.07), stroke (OR 1.03, 95% CI 0.77–1.37), or death (OR 1.14, 95% CI 0.67–1.94). Besides, TCAR is associated with a lower incidence of myocardial infarction (P = 0.004), cranial nerve injury (P &lt; 0.00001), and shorter procedure time (P &lt; 0.00001) than CEA among the overall cohort.Conclusions: TCAR is a rapidly developing treatment that reaches a comparable prognosis to CEA and significantly reduces the risk of myocardial infarction under the well-matched condition, which is a dependable choice for patients with carotid stenosis.
Impact of Pre-Revascularization and Post-Revascularization Cardiac Arrest on Survival Prognosis in Patients With Acute Myocardial Infarction and Following Emergency Percutaneous Coronary Intervention
Authors: Zhou Changzuan , Lin Qingcheng , Xiang Guangze , Chen Mengmeng , Cai Mengxing , Zhu Qianli , Zhou Rui , Huang Weijian , Shan Peiren 
Published: November 2021

Objectives: To evaluate the effects of occurrence and timing of sudden cardiac arrest (SCA) on survival in patients with acute myocardial infarction (AMI) who underwent emergency percutaneous coronary intervention (PCI).Methods: We analyzed 1,956 consecutive patients with AMI with emergency PCI from 2014 to 2018. Patients with cardiac arrest events were identified, and their medical records were reviewed.Results: Patients were divided into non-cardiac arrest group (NCA group, n = 1,724), pre-revascularization cardiac arrest (PRCA group, n = 175), and post-revascularization SCA (POCA group, n = 57) according to SCA timing. Compared to NCA group, PRCA group and POCA group presented with higher brain natriuretic polypeptide (BNP), more often Killip class 3/4, atrial fibrillation, and less often completed recovery of coronary artery perfusion (all p &lt; 0.05). Both patients with PRCA and POCA showed increased 30-day all-cause mortality when compared to patients with NCA (8.0 and 70.2% vs. 2.9%, both p &lt; 0.001). However, when compared to patients with NCA, patients with PRCA did not lead to higher mortality during long-term follow-up (median time 917 days) (16.3 vs. 18.6%, p = 0.441), whereas patients with POCA were associated with increased all-cause mortality (36.3 vs. 18.6%, p &lt; 0.001). Multivariate analysis identified Killip class 3/4, atrial fibrillation, high maximum MB isoenzyme of creatine kianse, and high creatinine as predictive factors for POCA. In Cox regression analysis, POCA was found as a strong mortality-increase predictor (HR, 8.87; 95% CI, 2.26–34.72; p = 0.002) for long-term all-cause death.Conclusions: POCA appeared to be a strong life-threatening factor for 30-day and long-term all-cause mortality among patients with AMI who admitted alive and underwent emergency PCI. However, PRCA experience did not lead to a poorer long-term survival in patients with AMI surviving the first 30 days.
Associations of Insomnia With Hypertension and Coronary Artery Disease Among Patients With Type 2 Diabetes Mellitus
Authors: Hu Yonghui , Yan Zhiyue , Fu Zhenrui , Pan Congqing 
Published: November 2021

Purpose: This study aimed to determine whether insomnia is associated with hypertension (HBP) and coronary artery disease (CAD) in a hospital-based sample of patients with type 2 diabetes mellitus (T2DM).Methods: Our present study included 354 patients with T2DM. According to the diagnostic criteria of insomnia, the participants were assigned to three groups based on the duration of T2DM and insomnia diagnosis. Patients with T2DM alone were placed in group A; patients with T2DM longer than insomnia were placed in group B; and patients with insomnia longer than T2DM were placed in group C. Medical history was collected from all the patients in detail. Besides, the participants underwent thorough physical examinations and laboratory measurements. Propensity score matching (PSM) was applied to evaluate the associations of insomnia with HBP and CAD. The univariate and multivariate logistic regression analysis was used to explore whether insomnia was a risk factor for HBP and CAD in patients with T2DM.Results: Of 354 patients, 225 patients were included in group A, 62 patients were included in group B, and 67 patients were included in group C. Compared with groups B and C, group A showed a lower prevalence of HBP and CAD (p &lt; 0.05). In addition, compared with group B, group C showed no difference in the prevalence of HBP and CAD (p &gt; 0.05). After PSM was performed, groups B and C had a higher prevalence of HBP and CAD (p &lt; 0.05) than group A with no significant difference between groups B and C (p &gt; 0.05). In the univariate and multivariate logistic regression analysis, insomnia was a risk factor for HBP [univariate: odds ratio (OR) = 3.376, 95% CI 2.290–6.093, p &lt; 0.001; multivariate: OR = 2.832, 95% CI 1.373–5.841, p = 0.005] and CAD (univariate: OR = 5.019, 95% CI 3.148–8.001, p &lt; 0.001; multivariate: OR = 5.289, 95% CI 2.579–10.850, p &lt; 0.001).Conclusion: T2DM combined with insomnia was related to HBP and CAD and insomnia was a risk factor for HBP and CAD in patients with T2DM. However, larger, prospective studies are required to confirm our findings.
Prediction of Masked Hypertension and Masked Uncontrolled Hypertension Using Machine Learning
Authors: Hung Ming-Hui , Shih Ling-Chieh , Wang Yu-Ching , Leu Hsin-Bang , Huang Po-Hsun , Wu Tao-Cheng , Lin Shing-Jong , Pan Wen-Harn , Chen Jaw-Wen , Huang Chin-Chou 
Published: November 2021

Objective: This study aimed to develop machine learning-based prediction models to predict masked hypertension and masked uncontrolled hypertension using the clinical characteristics of patients at a single outpatient visit.Methods: Data were derived from two cohorts in Taiwan. The first cohort included 970 hypertensive patients recruited from six medical centers between 2004 and 2005, which were split into a training set (n = 679), a validation set (n = 146), and a test set (n = 145) for model development and internal validation. The second cohort included 416 hypertensive patients recruited from a single medical center between 2012 and 2020, which was used for external validation. We used 33 clinical characteristics as candidate variables to develop models based on logistic regression (LR), random forest (RF), eXtreme Gradient Boosting (XGboost), and artificial neural network (ANN).Results: The four models featured high sensitivity and high negative predictive value (NPV) in internal validation (sensitivity = 0.914–1.000; NPV = 0.853–1.000) and external validation (sensitivity = 0.950–1.000; NPV = 0.875–1.000). The RF, XGboost, and ANN models showed much higher area under the receiver operating characteristic curve (AUC) (0.799–0.851 in internal validation, 0.672–0.837 in external validation) than the LR model. Among the models, the RF model, composed of 6 predictor variables, had the best overall performance in both internal and external validation (AUC = 0.851 and 0.837; sensitivity = 1.000 and 1.000; specificity = 0.609 and 0.580; NPV = 1.000 and 1.000; accuracy = 0.766 and 0.721, respectively).Conclusion: An effective machine learning-based predictive model that requires data from a single clinic visit may help to identify masked hypertension and masked uncontrolled hypertension.
Syn-Eruptive Conditions of the AD 1530 Sub-Plinian Eruption of La Soufrière of Guadeloupe (Lesser Antilles)
Authors: Martel Caroline , Pichavant Michel , Balcone-Boissard Hélène , Boudon Georges 
Published: November 2021

A prerequisite in refining volcanic hazard at explosive volcanoes is a better quantification of the timescales of the syn-eruptive processes, such as magma degassing and crystallization prior to eruption. To this aim, new data on the matrices (microlites, residual glasses, and bubbles) of pumice, scoria, and dense clasts erupted during the AD 1530 andesitic eruption of La Soufrière of Guadeloupe are combined with published data from phase-equilibrium and kinetic experiments, in order to estimate pressures of microlite crystallization and magma ascent rates. From the timescale data, we infer that the AD 1530 eruption started with phreatomagmatic explosions tapping magmas that ascended during about 1 month (decompression rate of ∼50 Pa/s) from the coldest parts of the reservoir (∼825°C and a 74 wt% SiO2 melt). These magmas continuously crystallized microlites (∼25 vol% plagioclase, orthopyroxene, clinopyroxene, magnetite, quartz, and apatite), but did not outgas likely due to sealed conduit margins. The flank collapse (preexisting “cold” edifice) that followed the phreatomagmatic phase triggered a sub-Plinian eruption that progressively tapped the hotter main reservoir (∼875°C and 71 wt% SiO2 interstitial melt), emitting banded and homogeneous pumice. The banded pumice did not significantly outgas and mostly lack decompression-induced microlites, suggesting short ascent durations of the order of 0.5–1 day (decompression rates of 1,400–4,000 Pa/s). The following Strombolian phase emitted dark scoria that did not significantly outgas and only crystallized rare microlites, suggesting ascent duration of the order of 2 days (decompression rates of ∼550 Pa/s). The terminal lava dome growth involved fully outgassed magmas ascended during more than 1 month, giving time for microlite crystallization (∼40 vol% plagioclase, orthopyroxene, clinopyroxene, magnetite, and cristobalite). The detection of any shallow new magmatic intrusion is crucial, since it can trigger a sequence of conduit processes leading to an eruption marked by a succession of different and disastrous eruptive styles, following a scenario similar to the AD 1530 eruption. Overall, we provide a combined approach of petrological, geochemical, and experimental data that may be used to infer ascent conditions and rates at other volcanic systems.
Effect of Layer Thickness on the Physical and Mechanical Properties of Sand Powder 3D Printing Specimens
Authors: Xu Qing , Jiang Lishuai , Ma Changqing , Niu Qingjia , Wang Xinzhe 
Published: November 2021

The application of sand powder three-dimensional (3D) printing technology in the field of rock mechanics and mining engineering has tremendous potential, but it is still in the preliminary exploration stage. This study investigated the effect of printing layer thickness on the physical and mechanical properties of rock-like specimens with sand powder 3D printing. Quartz sand powder was used as the printing material, and the specimens were prepared with three different layer thicknesses of 0.2, 0.3, and 0.4 mm. Uniaxial compression tests with a combination of digital image correlation (DIC), acoustic emission (AE) and 3D microscope observations were performed to analyze the mechanical properties and failure patterns of the specimens during loading. Experimental findings showed that increasing the layer thickness from 0.2 to 0.4 mm would result in a decrease in the weight, density, uniaxial compression strength, and elastic modulus of the specimens. The stress-strain curve, deformation and failure patterns, crack growth process, and AE characteristics of the specimens with a layer thickness of 0.2 mm are similar to the AE characteristics of rock-like material, whereas the specimens with layer thicknesses of 0.3 and 0.4 mm deform like a ductile material, which is not appropriate for simulation of coal or rock mass. In future studies, rock-like specimens should be prepared with a small layer thickness.