bluuebunny/crossref_metadata_2025 huggingface dataset:
On work-for-hire intellectual property assets created under employment agreements for conducting scientific research, development and engineering
Authors: Denysenko Roman
Published: June 2021

Keywords: subjects of contractual relationships, work-for-hire intellectual propertyassets, author, employer, property rights for work-for-hire intellectual property assets,consideration

The article analyzes the legal regime of official works createdduring the performance of the contract for the performance of research or researchand development and technological work. It is proved that the subjects of contractualrelations in addition to the executor and the customer should also include the creator(author, inventor) — an employee working in a scientific institution or enterprise,whose creative work created an official object of intellectual property. At the sametime, a scientific institution (enterprise) that has hired an employee under an employmentagreement (contract) acts as an employer. Based on the analysis of the legislationin the field of intellectual property and scientific sources, the author identifiesthe features of intellectual property. The meaning of the terms «duties» and «employer's order» is investigated. It is stated that there is no definition in the legislation ofUkraine of the term «official task» and requirements for registration of official taskfor the creation of a work. The grounds for recognizing the objects of intellectual propertyrights as official are determined and analyzed. The peculiarities of the distributionof property rights to official objects between the customer, the executor and theemployee-author in the context of the legal relations that arise and accompany theperformance of contracts are considered. Various contractual constructions used inthe mechanism of division of property rights into official objects are analyzed. Proposalsare formulated aimed at improving the local regulation of the distribution of propertyrights to service facilities. Particular attention in the article is paid to the issue ofpayment of remuneration to the author of the official object. The structure of such remunerationis analyzed, sources of its payment are offered, terms of payment of suchremuneration and their legal definition. It is proposed that the contracts provide forobligations (guarantees) of the parties to «finance» the customer and pay the contractorremuneration to the author for the creation and use of the official object.
Doctrinal approaches to the definition of civil procedural law
Authors: Shtefan Olena
Published: June 2021

Keywords: civil procedural law, civil process, civil proceedings, subject of civil procedurallaw

The process of reforming procedural legislation, its harmonization, harmonization with theprinciples and standards of international law, as well as other processes taking place insociety and the state are the factors that affect the need to revise the doctrinal definitions of civil procedural law. One of the most developed issues in the theory of civil procedurallaw is its definition. In turn, the development of science is impossible without reviewingeven established doctrinal approaches and provisions.An analysis of the special literature, mostly educational, led to the conclusion thatscholars use approaches to the definition of the term "civil procedural law", which weredeveloped and included in the theory of civil procedural law in the 50s-60s of the twentiethcentury. Modern definitions of civil procedural law are based on the provisions of theold invalid legislation, or on the provisions of the legislation of other countries (for example,the Russian Federation). Therefore, the purpose of this study was to review the existingdefinitions in the theory of civil procedural law and their harmonization with theprovisions of current legislation of Ukraine.In the process of researching doctrinal approaches to the definition of civil procedurallaw, it was found that researchers invest in the definition of the subject, purpose of thisbranch of law, as well as additional characteristics of civil procedural law (participants,sectoral affiliation, stage, etc.).The lack of a single doctrinal approach to the definition of the subject of civil procedurallaw, which is part of the definition of civil procedural law, prompted to study thesubject of civil procedural law and propose its author's definition.Based on the provisions of current legislation, the article presents the author's definitionof civil procedural law as a branch of law, set and system of legal norms, the subjectof which are public relations arising in civil proceedings on the basis of fair, impartialand timely consideration and resolution of civil cases in order to effectively protect violated,unrecognized or disputed rights, freedoms or interests of individuals, rights and interestsof legal entities, the interests of the state.
THEORETICAL AND METHODICAL PROBLEMS OF THE DEVELOPMENT OF THE VALUATION OF INTELLECTUAL PROPERTY RIGHTS
Authors: Олександр Бутнік-Сіверський
Published: June 2021

The article summarizes theoretical and methodical problems related to the need to create a logical valuation theory and methodology of intellectual property, identification and valuation of intellectual property rights and its relation to accounting; the problem of methods of valuation of intellectual property rights within their subject characteris considered, as well as identification of the majority of intellectual resources that take part in production and contribute to the improvement of product quality, technological update, innovative orientation of economic processes; the need to strengthen the state policy of carrying out the valuation of intellectual property rights in relation to intangible assets within the objects of intellectual propertyrights (OIPRs) has been considered. The author analyzes the relationship to the value appraisal of OIPRs, which is most often done by using a narrow range of methods (approaches) within the generally recognized: income, cost and market (comparative) approaches, that affects the limitation of the selected methods of valuation, leads to a template use of valuation methodic without a variety of  OIPRs that have specific features of their use. Also it is disclosed the meaningful meaning of the development of a single terminology and value classification, whichcan be carried out on the basis of synthesis of foreign experience in the field of valuation and value management, as well as the analysis of valuation standards.The problem became due to the OIPRs conducting of value appraisal of the advanced intellectual capital, that is complicated by the fact that by economic essence it does not belong to the traditional assets of the enterprise and has its own peculiarities. It is urgent to rethink existing standards on valuation and supplement them with new ones in the direction of minimizing fundamental contradictions between the traditional accounting methodology and the valuation of OIPRs, taking into account the peculiarities of the development of the information and intellectual economy. It is methodically detailed by the economic content the techniques used to determine the value of OIPRs, which are divided into three groups: approaches, methods and methodologies, from the point of view of economic content, conditions of application and valuation procedure, as well as requirements for the appraisal of the value of OIPRs in the privatization of state enterprises and  organizations. The author considers the problems of organization of training of professional ppraisers in Ukraine taking into account the requirements of State Property Fund of Ukraine and their legal support.
THE RIGHTS TO SURROGATE MOTHERHOOD FOR SAME-SEX PARTNERSHIPS
Authors: Оксана Покальчук
Published: June 2021

The growing populist sentiment in society and, as a consequence, the reactive adoption of new restrictive legal acts that discriminate and unjustifiably restrict citizens' rights, is a major challenge for the scientific community and human rights in Ukraine. The issue of reproductive rights is one of the most important elements of common discriminatory and often unscientific narratives both in the EU and in Ukraine. Therefore, the scientific community has to take up this challenge and, by examining and exploring the various aspects of the right to reproduce, uphold the rule of science and the rights of Ukrainans, especially in this domain. Surrogate motherhood is always used in combination with other methods of assisted reproductive technology. Thus, surrogate motherhood, as a method of treatment, is burdened not only with legal uncertainty, but also with additional necessary steps (taking donor material, instrumental insemination, etc.) that precede assisted gestation.It is believed that all assisted reproductive technologies, including surrogacy, are treatment methods; therefore, their use cannot in any way depend on a person's social status, including gender self-identification, the fact of marriage or same-sex partnership.The list of medical grounds for surrogate motherhood is defined in the Order of the Ministry of Health of Ukraine On Approval of the Procedure for the Use of Assisted Reproductive Technologies in Ukraine. However, we emphasize that the list should be expanded to include diagnoses of transsexuality and other gender identity disorders according to the International Classification of Diseases. Thus, according to item 10 ofthe Unified Clinical Protocol of Primary, Secondary (Specialized) and Tertiary (Highly Specialized) Medical Care: Gender Dysphoria, reproduction opportunities for FtM patients may include freezing of oocytes (eggs) or embryos. Frozen gametes and embryos can later be used for delivery by a surrogate mother. The question stands whythis possibility is not considered in the protocol for the MtF transition with the subsequent possibility of delivery by a surrogate mother. Obviously, with the MtF transition, even with gender reassignment surgery, including the operation the genitals, the woman is not capable of independent childbearing. Such a woman can thus exerciseher right to reproduction only by fertilizing a donor egg with her sperm and then having the embryo that is genetically hers carried to term by a surrogate mother. The issue of male identity for the origin of the donor material (sperm) also needs separate legal regulation. However, in our opinion, this social group should not be discriminated against in access to surrogate motherhood as an assisted reproductive technology.
IMPLEMENTATION OF THE OPEN INNOVATION MODEL IN THE CONDITIONS OF DEVELOPMENT OF THE DIGITAL ECONOMY
Authors: Анастасія Ярмолюк
Published: June 2021

The author emphasizes that the model of open innovation involves the search for creative innovative ideas, joint research and creation of innovations with partners and the strategic use of intellectualproperty rights. In this way, the potential of invention is used in solving the problems of innovation. The article notes that the model of open innovation involves increasing the return on their own research and development through the alienation of patents or the issuance of licenses for the use of intellectual property rights. However, the authoridentifies an important problem of information leakage, which is the object of intellectual property rights. Therefore, as noted in the article, an innovative enterprise must have control over intellectual property so that competitors do not profit from the use of innovative ideas of others. It is also necessary to form high-quality intellectual property support systems. In the article, the author details the role of intellectual property in promoting innovation within the concept of open innovation. Innovativetechnologies have been successfully commercialized with the strategic use of intellectual property rights. Intellectual property plays a key role in enhancing the competitiveness of innovative enterprises, preserving their innovative advantages and facilitating the process of bringing innovative technologies to market created within the framework of an open innovation model. Intellectual property also significantly helps external partners make informed decisions about the need to assist with technical knowledge and funding to overcome the innovative ideas of the Death Valley from the time of invention to the launch of a new product. So, the author emphasizes that intellectual property plays a significant role in facilitating access to early stage capital suppliers, including seed capital, business angels, venture capitalists, financial institutions that help the invention to enter the market. In the partnership of innovative businesses, patents become a reliable source of additional income for small and medium-sized businesses.
JUDICIAL CORPS FORMATION AS A FACTOR OF INFLUENCE ON THE GENESIS OF UKRAINIAN STATEHOOD IN THE ANCIET RUSSIAN ERA
Authors: Інна Коваленко
Published: June 2021

In this article the effectiveness of the judiciary in the period of ancient statehood was analyzed. A study of society's perception of the word «court» in the considered period, taking into account the philologicaland legal approach to the mentioned phenomenon. The possibility and peculiarities of the existence of a court as an out state institution, as well as the peculiarities of such an institution of the state are analyzed. Thus, the article examines the pre-state (community), state and church stages of the formation of the judiciary.In particular, the pre-state stage outlines the features of certain categories of disputes, such as criminal or civil matters. In addition, the requirements for persons who had the right to administer justice in the East Slavic tribes were grouped and the following main features were identified: generic, psychological, unconditional. The dependenceof the judiciary formation on religious and political factors has also been established.At the same time, a characteristic feature of the period is the proximity ofthe judiciary to the people. A special focus in this article was given to the period of the emergence of the state. This stage radically changed the views on the effectiveness of the management method, which also influenced the change of views on the administration of justice.However, this period is characterized by the weakening of the judiciary as an independent branch of government, due to the concentration of managerial powers in the hands of the feudal lord, respectively, there was no clear list of requirements for the position of judge. The period under study is characterized by the following features of the procedure for the formation of the judiciary: the administration of justice wasstrictly dependent on the power that belonged to the prince; judging has become a privilege and sometimes a lucrative business; the formation of the judiciary depended significantly on the level of administration of justice, because the community courts for a long time operated in parallel with the princes.In addition, in this article the period after the baptism of Russia by St. Vladimir in 998 was analyzed and investigated. After this event in the territory of modern Ukraine, along with the princely court, the ecclesiastical court began to act at the same time.
EXTRAJUDICIAL REMEDIES FOR THE RIGHT TO A DOMAIN NAME
Authors: Ян Коваленко
Published: June 2021

Today, each member of the business industry in one way or another presents his company, his product or services he provides on the World Wide Web. The main purpose of the company in the internet is to create and use its own website to provide information about their product and to find a potential buyer, as well as demonstrate their advantages and how they differ from their competitors. The main purpose of registeringa specific «domain name» is to create favorable (convenient) conditions for the buyer who wanted to get acquainted with the company or its range. After all, if a domain name is associatively similar to the name of an individual company, then it will be much easier for the buyer to find the website of such a company than through a search using search engines.Business representatives do not always succeed, especially if the name (trademark, brand) of the company is widely known, or if such a company has become a «victim» of unfair competition. This creates controversy over which parties are interested in resolving as quickly and cheaply as possible.This is greatly facilitated by the work of the World Intellectual Property Organization and a number of documents, among which the leading are «Principles for Dispute Resolution on Identical Domain Names» and «Principles of Uniform Rules for Dispute Resolution on Domain Names» (UDRP), adopted by ICANN. However, their analysis, as well as the analysis of law enforcement practice, allow us to speak not only about the effectiveness, but also about certain shortcomings of the proposed ICANN procedure for resolving disputes over domain names, which entail ambiguous dispute resolution practices.The analysis of the regulation of protection of rights to the domain name is carried out with the prescriptions of the «Principles for the resolution of disputes about the same domain names» and the «Uniform Domain Name Dispute Resolution Rules» (UDRP) adopted by ICANN. An attempt is made to highlight the advantages and disadvantages of an out-of-court procedure for resolving disputes over domain names and suggested possible ways to improve such a system in Ukraine.
COVID-19 Multi-Targeted Drug Repurposing Using Few-Shot Learning
Authors: Liu Yang , Wu You , Shen Xiaoke , Xie Lei
Published: June 2021

The life-threatening disease COVID-19 has inspired significant efforts to discover novel therapeutic agents through repurposing of existing drugs. Although multi-targeted (polypharmacological) therapies are recognized as the most efficient approach to system diseases such as COVID-19, computational multi-targeted compound screening has been limited by the scarcity of high-quality experimental data and difficulties in extracting information from molecules. This study introducesMolGNN, a new deep learning model for molecular property prediction.MolGNNapplies a graph neural network to computational learning of chemical molecule embedding. Comparing to state-of-the-art approaches heavily relying on labeled experimental data, our method achieves equivalent or superior prediction performance without manual labels in the pretraining stage, and excellent performance on data with only a few labels. Our results indicate thatMolGNNis robust to scarce training data, and hence a powerful few-shot learning tool.MolGNNpredicted several multi-targeted molecules against both human Janus kinases and the SARS-CoV-2 main protease, which are preferential targets for drugs aiming, respectively, at alleviating cytokine storm COVID-19 symptoms and suppressing viral replication. We also predicted molecules potentially inhibiting cell death induced by SARS-CoV-2. Several ofMolGNNtop predictions are supported by existing experimental and clinical evidence, demonstrating the potential value of our method.
Proteomics Investigation of the Time Course Responses of RAW264.7 Macrophages to Infections With the Wild-Type and Twin-Arginine Translocation Mutant Strains of Brucella melitensis
Authors: Yan Xin , Hu Sen , Yang Yan , Xu Da , Liu Wenxing , Li Ganwu , Cai Wentong , Bu Zhigao
Published: June 2021

Brucella, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane; protein substrates translocated byBrucellainclude ABC transporters, oxidoreductases, and cell envelope biosynthesis proteins. Previously, we showed that a Tat mutant ofBrucella melitensisM28 exhibits reduced survival within murine macrophages. In this study, we compared the host responses elicited by wild-type M28 and its Tat-mutant strains ex vivo. We utilized label-free quantitative proteomics to assess proteomic changes in RAW264.7 macrophages after infection with M28 and its Tat mutants. A total of 6085 macrophage proteins were identified with high confidence, and 79, 50, and 99 proteins were differentially produced upon infection with the Tat mutant at 4, 24, and 48 hpi, respectively, relative to the wild-type infection. Gene ontology and KEGG enrichment analysis indicated that immune response-related proteins were enriched among the upregulated proteins. Compared to the wild-type M28 infection, the most upregulated proteins upon Tat-mutant infection included the cytosolic nucleic acid signaling pathway-related proteins IFIH1, DHX58, IFI202, IFI204, and ISG15 and the NF-κB signaling pathway-related proteins PTGS2, CD40, and TRAF1, suggesting that the host increases the production of these proteins in response to Tat mutant infection. Upregulation of some proteins was further verified by a parallel reaction monitoring (PRM) assay. ELISA and qRT-PCR assays indicated that Tat mutant infection significantly induced proinflammatory cytokine (TNF-α and IL-6) and nitric oxide (NO) production. Finally, we showed that the Tat mutant displays higher sensitivity to nitrosative stress than the wild type and that treatment with the NO synthase inhibitor L-NMMA significantly increases the intracellular survival of the Tat mutant, indicating that NO production contributes to restricting Tat mutant survival within macrophages. Collectively, this work improves our understanding of host immune responses to Tat mutants and provides insights into the mechanisms underlying the attenuated virulence of Tat mutants.
Chromosomal Integration of Huge and Complex blaNDM-Carrying Genetic Elements in Enterobacteriaceae
Authors: Luo Xinhua , Yin Zhe , Zeng Lijun , Hu Lingfei , Jiang Xiaoyuan , Jing Ying , Chen Fangzhou , Wang Dongguo , Song Yajun , Yang Huiying , Zhou Dongsheng
Published: June 2021

In this study, a detailed genetic dissection of the huge and complex blaNDM-carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn6588; two related IMEs Tn6523 (SGI1) and Tn6589; four related ICEs Tn6512 (R391), Tn6575 (ICEPvuChnBC22), Tn6576, and Tn6577; Tn7 and its derivatives Tn6726 and 40.7-kb Tn7-related element; and two related IMEs Tn6591 (GIsul2) and Tn6590. At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn6576 carried another ICE Tn6582. In particular, the six blaNDM-carrying genetic elements Tn6588, Tn6589, Tn6575, Tn6576, Tn6726, and 40.7-kb Tn7-related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core blaNDM genetic environments manifested as four different Tn125 derivatives and, notably, two or more copies of relevant Tn125 derivatives were found in each of Tn6576, Tn6588, Tn6589, and 40.7-kb Tn7-related element. The huge and complex blaNDM-carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn6576, Tn6577, and Tn6582, two IMEs, Tn6588 and Tn6589, two composite transposons Tn6580a and Tn6580b, and one integron In1718.
Change in Postprandial Level of Remnant Cholesterol After a Daily Breakfast in Chinese Patients With Hypertension
Authors: Xu Jin , Qu Peiliu , Du Xiao , Xiang Qunyan , Guo Liling , Zhu Liyuan , Tan Yangrong , Fu Yan , Wen Tie , Liu Ling
Published: June 2021

Background: Hypertension (HBP) is usually accompanied by hypertriglyceridemia that represents the increased triglyceride-rich lipoproteins and cholesterol content in remnant lipoproteins [i.e., remnant cholesterol (RC)]. According to the European Atherosclerosis Society (EAS), high RC (HRC) is defined as fasting RC ≥0.8 mmol/L and/or postprandial RC ≥0.9 mmol/L. However, little is known about postprandial change in RC level after a daily meal in Chinese patients with HBP.

Methods: One hundred thirty-five subjects, including 90 hypertensive patients (HBP group) and 45 non-HBP controls (CON group), were recruited in this study. Serum levels of blood lipids, including calculated RC, were explored at 0, 2, and 4 h after a daily breakfast. Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point of postprandial HRC.

Results: Fasting TG and RC levels were significantly higher in the HBP group (P < 0.05), both of which increased significantly after a daily meal in the two groups (P < 0.05). Moreover, postprandial RC level was significantly higher in the HBP group (P < 0.05). ROC curve analysis showed that the optimal cutoff point for RC after a daily meal to predict HRC corresponding to fasting RC of 0.8 mmol/L was 0.91 mmol/L, which was very close to that recommended by the EAS, i.e., 0.9 mmol/L. Fasting HRC was found in 31.1% of hypertensive patients but not in the controls. According to the postprandial cutoff point, postprandial HRC was found in approximately half of hypertensive patients and ~1-third of the controls.

Conclusion: Postprandial RC level increased significantly after a daily meal, and hypertensive patients had higher percentage of HRC at both fasting and postprandial states. More importantly, the detection of postprandial lipids could be helpful to find HRC.
Comprehensive Data Integration Approach to Assess Immune Responses and Correlates of RTS,S/AS01-Mediated Protection From Malaria Infection in Controlled Human Malaria Infection Trials
Authors: Young William Chad , Carpp Lindsay N. , Chaudhury Sidhartha , Regules Jason A. , Bergmann-Leitner Elke S. , Ockenhouse Christian , Wille-Reece Ulrike , deCamp Allan C. , Hughes Ellis , Mahoney Celia , Pallikkuth Suresh , Pahwa Savita , Dennison S. Moses , Mudrak Sarah V. , Alam S. Munir , Seaton Kelly E. , Spreng Rachel L. , Fallon Jon , Michell Ashlin , Ulloa-Montoya Fernando , Coccia Margherita , Jongert Erik , Alter Galit , Tomaras Georgia D. , Gottardo Raphael
Published: June 2021

RTS,S/AS01 (GSK) is the world’s first malaria vaccine. However, despite initial efficacy of almost 70% over the first 6 months of follow-up, efficacy waned over time. A deeper understanding of the immune features that contribute to RTS,S/AS01-mediated protection could be beneficial for further vaccine development. In two recent controlled human malaria infection (CHMI) trials of the RTS,S/AS01 vaccine in malaria-naïve adults, MAL068 and MAL071, vaccine efficacy against patent parasitemia ranged from 44% to 87% across studies and arms (each study included a standard RTS,S/AS01 arm with three vaccine doses delivered in four-week-intervals, as well as an alternative arm with a modified version of this regimen). In each trial, RTS,S/AS01 immunogenicity was interrogated using a broad range of immunological assays, assessing cellular and humoral immune parameters as well as gene expression. Here, we used a predictive modeling framework to identify immune biomarkers measured at day-of-challenge that could predict sterile protection against malaria infection. Using cross-validation on MAL068 data (either the standard RTS,S/AS01 arm alone, or across both the standard RTS,S/AS01 arm and the alternative arm), top-performing univariate models identified variables related to Fc effector functions and titer of antibodies that bind to the central repeat region (NANP6) of CSP as the most predictive variables; all NANP6-related variables consistently associated with protection. In cross-study prediction analyses of MAL071 outcomes (the standard RTS,S/AS01 arm), top-performing univariate models again identified variables related to Fc effector functions of NANP6-targeting antibodies as highly predictive. We found little benefit–with this dataset–in terms of improved prediction accuracy in bivariate models vs. univariate models. These findings await validation in children living in malaria-endemic regions, and in vaccinees administered a fourth RTS,S/AS01 dose. Our findings support a “quality as well as quantity” hypothesis for RTS,S/AS01-elicited antibodies against NANP6, implying that malaria vaccine clinical trials should assess both titer and Fc effector functions of anti-NANP6 antibodies.
The Spatiotemporal Pattern of Cultural Evolution Response to Agricultural Development and Climate Change From Yangshao Culture to Bronze Age in the Yellow River Basin and Surrounding Regions, North China
Authors: Wang Lin , Cui Yifu
Published: June 2021

The processes and mechanisms of cultural evolution provide helpful insights into the origin and development of civilizations. This study analyses data from the national archaeological survey using kernel density analysis, a geospatial tool provided by ArcGIS10 software, to explore the spatiotemporal pattern of cultural evolution from the beginning of the Yangshao cultural period to the Bronze Age in the Yellow River basin. Agricultural development and the environmental background of this region were reconstructed using published flotation materials and high-resolution paleoclimate records. The results indicate that cultural expansion and differentiation from Yangshao (7000–5000 BP) to Longshan period (4600–4000 BP) are responding to the establishment and strengthening of millet-based agriculture and the appearance of multiple subsistence strategies in the context of environmental deterioration. To the Bronze Age, the center of sites accumulates to the Central Plains and Shandong, in contrast to the continuous cultural expansion and differentiation. The opposite circumstance may result from early urbanization along with the formation of a social system with high centralization of power.
A Multicenter Survey of Type I Diabetes Mellitus in Chinese Children
Authors: Hou Ling , Li Xiuzhen , Liu Li , Wei Hanyang , Xiong Feng , Du Hongwei , Yang Yu , Zhang Huifeng , Zhang Qin , Yao Hui , Fu Junfen , Yan Xiaoli , Cui Lanwei , Liu Geli , Li Tang , Chen Shaoke , Li Pin , Xin Ying , Liang Xiangrong , Yu Baosheng , Dong Zhiya , Chen Ruimin , Ma Huamei , Cheng Xinran , Luo Feihong , Gong Chunxiu , Song Wenhui , Chen Xiaobo , Zhang Zhixin , Peng Xiangyun , Li Guimei , Liang Liyang , Maimaiti Mireguli , Cheung Pik To , Luo Xiaoping
Published: June 2021

Purpose

To investigate the features and treatment status of children with type 1 diabetes mellitus (T1DM) in China.

Methods

We recruited patients <14 years of age with T1DM from 33 medical centers in 25 major cities of China between January 2012 and March 2015. All patients completed a questionnaire that was conducted by their pediatric endocrinologists at all centers.

Results

A total of 1,603 children (755 males and 848 females) with T1DM participated in this survey. Of these, 834 (52.03%) of the patients exhibited diabetic ketoacidosis (DKA) at onset, while 769 patients (47.97%) did not exhibit DKA (non-DKA) at onset. There was a higher proportion of females (55.71%) in the cohort of patients exhibiting DKA at onset than in the non-DKA cohort (49.33%). The mean age of patients exhibiting DKA at presentation was 7.12 ± 0.14 years; this was significantly younger than that in non-DKA group (7.79 ± 0.15 years; P < 0.005). The frequency of DKA in 3 years old, 3-7 years old, and 7 years old or more was 77.21%, 26.17%, and 37.62%, respectively. Upon initial diagnosis, 29.4%, 15.2% and 11.8% of patients showed positivity for glutamic acid decarboxylase antibody (GADA), Insulin autoantibodies (IAA), or islet cell antibody (ICA), respectively. During six months follow-up, 244 patients (15.21%) reported receiving insulin pump therapy, and more than 60% of patients monitored their blood glucose levels less than 35 times per week. Although the majority of patients had no problems with obtaining insulin, 4.74% of the children surveyed were not able to receive insulin due to financial reasons, a shortage of insulin preparations, or the failure of the parents or guardians to acquire the appropriate medicine.

Conclusion

DKA is more common in very young children. Treatment and follow-up of T1DM in China still face very serious challenges.
Surgical Extent of Central Lymph Node Dissection for Papillary Thyroid Carcinoma Located in the Isthmus: A Propensity Scoring Matched Study
Authors: Shuai Yanjie , Yue Kai , Duan Yuansheng , Zhou Mengqian , Fang Yan , Liu Jin , Liu Dandan , Jing Chao , Wu Yansheng , Wang Xudong
Published: June 2021

Introduction

To assess the risk factor for the central lymph node (CLN) metastasis and investigated the surgery extent of lymph node dissection for patients with isthmic PTC (papillary thyroid carcinoma).

Materials and Methods

A total of 669 patients with a single nodule of isthmic PTC were retrospectively reviewed. The propensity score matching was performed twice separately. 176 patients respectively from patients who underwent thyroidectomy plus bilateral central lymph node dissection (BCLND) and who underwent thyroidectomy plus unilateral central lymph node dissection (UCLND) were matched. 77 patients were respectively selected from patients who underwent thyroidectomy plus BCLND and who underwent thyroidectomy with no central lymph node dissection (NCLND) were matched.

Results

Among all the patients who underwent BCLND, 81/177 (45.76%) was confirmed with histologically positive CLN metastasis, and the occult lymph node metastasis is 25.42%. A tumor size of 1.05 cm was calculated as the cutoff point for predicting CLN metastasis by ROC curve analysis with 177 patients who underwent BCLND. The 5-year recurrence-free survival (RFS) rates were 92.9% in the NCLND group and 100% in the BCLND group with P<0.05, while there was no statistical difference in 5-year RFS between the BCLND group and UCLND group (P=0.11). The multivariate logistic regression analysis identified that age<55, tumor size>1cm, capsule invasion and lymphovascular invasion were significantly associated with CLN metastasis, while only age and lymphovascular invasion were proved to be independent risk factors related to contralateral CLN metastasis.

Conclusions

The thyroidectomy with NCLND could be insufficient for patients with isthmic PTC especially for those patients with high risk of central lymph node metastasis, considering that the rate of occult lymph node metastasis could not be ignored.
Geographic Pattern of Bryophyte Species Richness in China: The Influence of Environment and Evolutionary History
Authors: Song Xiaotong , Fang Wenzhuo , Chi Xiulian , Shao Xiaoming , Wang Qinggang
Published: June 2021

How contemporary environment interacts with macroevolutionary processes to generate the geographic pattern of bryophyte species is still unresolved. China is very rich in bryophytes, with more than 3,000 bryophytes covering 70% of the families in the world. In this study, we assessed the effects of the contemporary environment (average temperature of the coldest season TCQ, precipitation of the warmest season PWQ, and elevational range) and the recent diversification rates (estimated as mean species number per genus, MSG) on the geographical pattern of species richness for bryophytes and two groups (i.e., liverworts and mosses) in China. We compiled the provincial level distribution of bryophyte species and estimated the geographic pattern of the recent diversification rate by MSG for species in China. Univariate, multivariate regressions and path model analyses were used to assess the relationships between species richness, MSG, and their potential environmental drivers. Species richness of all bryophytes and liverworts significantly increased with the increase of MSG, either in regressions or path analyses, indicating that provinces with high bryophyte richness were mainly inhabited by species (especially liverworts) from lineages with particularly high MSG. In contrast, the species richness of mosses was insignificantly decreased with MSG in univariate regression or insignificantly increased with MSG in path analysis. Both species richness and MSG of all bryophytes and liverworts increased with the increase in energy and water availability. In contrast, for mosses, the species richness significantly increased with the increase of energy and water availability, while MSG decreased with the increase of energy and water availability. The MSG of liverworts increase with the increase of elevational range but the MSG of mosses decrease with the increase of elevational range. Our study suggests that the humid tropical and subtropical mountains in China are not only diversity hotspots for bryophytes, but also cradles for high recent diversification of liverworts, and refuges for mosses to hold many monotypic and oligotypic genera.
Revisiting an Expression Dataset of Discordant Inflammatory Bowel Disease Twin Pairs Using a Mutation Burden Test Reveals CYP2C18 as a Novel Marker
Authors: Du Juan , Yin Jie , Du Haojie , Zhang Jiawei
Published: June 2021

The aim of this study was to investigate the expression features of discordant inflammatory bowel disease (IBD) twin pairs to identify novel molecular features and markers. We collected an expression dataset of discordant twin pairs with ulcerative colitis and performed integrative analysis to identify the genetic-independent expression features. Through deconvolution of the immune cell populations and tissue expression specificity, we refined the candidate genes for susceptibility to ulcerative colitis. We found that dysregulated immune systems and NOD-related pathways were enriched in the expression network of the discordant IBD twin pairs. Among the identified factors were significantly increased proportions of immune cells, including megakaryocytes, neutrophils, natural killer T cells, and lymphatic endothelial cells. The differentially expressed genes were significantly enriched in a gene set associated with cortical and medullary thymocytes. Finally, by combining these expression features with genetic resources, we identified some candidate genes with potential to serve as novel markers of ulcerative colitis, such as CYP2C18. Ulcerative colitis is a subtype of inflammatory bowel disease and a polygenic disorder. Through integrative analysis, we identified some genes, such as CYP2C18, that are involved in the pathogenesis of IBD as well as some candidate therapeutic targets, such as LOXL2.
COVID-19 and SARS-CoV-2 Variants: Current Challenges and Health Concern
Authors: Zeyaullah Md. , AlShahrani Abdullah M. , Muzammil Khursheed , Ahmad Irfan , Alam Shane , Khan Wajihul Hasan , Ahmad Razi
Published: June 2021

The ongoing coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, was triggered and unfolded quickly throughout the globe by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new virus, transmitted primarily through inhalation or contact with infected droplets, seems very contagious and pathogenic, with an incubation period varying from 2 to 14 days. The epidemic is an ongoing public health problem that challenges the present global health system. A worldwide social and economic stress has been observed. The transitional source of origin and its transport to humans is unknown, but speedy human transportation has been accepted extensively. The typical clinical symptoms of COVID-19 are almost like colds. With case fatality rates varying from 2 to 3 percent, a small number of patients may experience serious health problems or even die. To date, there is a limited number of antiviral agents or vaccines for the treatment of COVID-19. The occurrence and pathogenicity of COVID-19 infection are outlined and comparatively analyzed, given the outbreak’s urgency. The recent developments in diagnostics, treatment, and marketed vaccine are discussed to deal with this viral outbreak. Now the scientist is concerned about the appearance of several variants over the globe and the efficacy of the vaccine against these variants. There is a need for consistent monitoring of the virus epidemiology and surveillance of the ongoing variant and related disease severity.
Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
Authors: Nguyen Nhan , Souza Terezinha , Verheijen Marcha C. T. , Gmuender Hans , Selevsek Nathalie , Schlapbach Ralph , Kleinjans Jos , Jennen Danyel
Published: June 2021

Anthracyclines, including doxorubicin, idarubicin, and epirubicin, are common antitumor drugs as well as well-known cardiotoxic agents. This study analyzed the proteomics alteration in cardiac tissues caused by these 3 anthracyclines analogs. The in vitro human cardiac microtissues were exposed to drugs in 2 weeks; the proteomic data were measured at 7 time points. The heart biopsy data were collected from heart failure patients, in which some patients underwent anthracycline treatment. The anthracyclines-affected proteins were separately identified in the in vitro and in vivo dataset using the WGCNA method. These proteins engage in different cellular pathways including translation, metabolism, mitochondrial function, muscle contraction, and signaling pathways. From proteins detected in 2 datasets, a protein-protein network was established with 4 hub proteins, and 7 weighted proteins from both cardiac microtissue and human biopsies data. These 11 proteins, which involve in mitochondrial functions and the NF-κB signaling pathway, could provide insights into the anthracycline toxic mechanism. Some of them, such as HSPA5, BAG3, and SH3BGRL, are cardiac therapy targets or cardiotoxicity biomarkers. Other proteins, such as ATP5F1B and EEF1D, showed similar responses in both the in vitro and in vivo data. This suggests that the in vitro outcomes could link to clinical phenomena in proteomic analysis.
Prospective Artificial Intelligence to Dissect the Dengue Immune Response and Discover Therapeutics
Authors: Natali Eriberto N. , Babrak Lmar M. , Miho Enkelejda
Published: June 2021

Dengue virus (DENV) poses a serious threat to global health as the causative agent of dengue fever. The virus is endemic in more than 128 countries resulting in approximately 390 million infection cases each year. Currently, there is no approved therapeutic for treatment nor a fully efficacious vaccine. The development of therapeutics is confounded and hampered by the complexity of the immune response to DENV, in particular to sequential infection with different DENV serotypes (DENV1–5). Researchers have shown that the DENV envelope (E) antigen is primarily responsible for the interaction and subsequent invasion of host cells for all serotypes and can elicit neutralizing antibodies in humans. The advent of high-throughput sequencing and the rapid advancements in computational analysis of complex data, has provided tools for the deconvolution of the DENV immune response. Several types of complex statistical analyses, machine learning models and complex visualizations can be applied to begin answering questions about the B- and T-cell immune responses to multiple infections, antibody-dependent enhancement, identification of novel therapeutics and advance vaccine research.
Targeted Next-Generation Sequencing Combined With Circulating-Free DNA Deciphers Spatial Heterogeneity of Resected Multifocal Hepatocellular Carcinoma
Authors: Lin Jianzhen , Zhao Songhui , Wang Dongxu , Song Yang , Che Yue , Yang Xu , Mao Jinzhu , Xie Fucun , Long Junyu , Bai Yi , Yang Xiaobo , Zhang Lei , Bian Jin , Lu Xin , Sang Xinting , Pan Jie , Wang Kai , Zhao Haitao
Published: June 2021

Background

Hepatocellular carcinoma (HCC) has a high risk of recurrence after surgical resection, particularly among patients with multifocal HCC. Genomic heterogeneity contributes to the early recurrence. Few studies focus on targeted next-generation sequencing (tNGS) to depict mutational footprints of heterogeneous multifocal HCC.

Methods

We conducted tNGS with an ultra-deep depth on 31 spatially distinct regions from 11 resected multifocal HCC samples. Matched preoperative peripheral circulating-free DNA (cfDNA) were simultaneously collected. Genomic alterations were identified and compared to depict the heterogeneity of multifocal HCC.

Results

Widespread intertumoral heterogeneity of driver mutations was observed in different subfoci of multifocal HCC. The identified somatic mutations were defined as truncal drivers or branchy drivers according to the phylogenetic reconstruction. TP53 and TERT were the most commonly altered truncal drivers in multifocal HCC, while the most frequently mutated branchy driver was TSC2. HCC patients with a higher level of intertumoral heterogeneity, defined by the ratio of truncal drivers less than 50%, had a shorter RFS after surgical resection (HR=0.17, p=0.028). Genome profiling of cfDNA could effectively capture tumor-derived driver mutations, suggesting cfDNA was a non-invasive strategy to gain insights of genomic alterations in patients with resected multifocal HCC.

Conclusions

Truncal mutations and the level of genomic heterogeneity could be identified by tNGS panel in patients with resected multifocal HCC. cfDNA could serve as a non-invasive and real-time auxiliary method to decipher the intertumoral heterogeneity and identify oncodrivers of multifocal HCC.
From Plant Survival Under Severe Stress to Anti-Viral Human Defense – A Perspective That Calls for Common Efforts
Authors: Arnholdt-Schmitt Birgit , Mohanapriya Gunasekaran , Bharadwaj Revuru , Noceda Carlos , Macedo Elisete Santos , Sathishkumar Ramalingam , Gupta Kapuganti Jagadis , Sircar Debabrata , Kumar Sarma Rajeev , Srivastava Shivani , Adholeya Alok , Thiers KarineLeitão Lima , Aziz Shahid , Velada Isabel , Oliveira Manuela , Quaresma Paulo , Achra Arvind , Gupta Nidhi , Kumar Ashwani , Costa José Hélio
Published: June 2021

Reprogramming of primary virus-infected cells is the critical step that turns viral attacks harmful to humans by initiating super-spreading at cell, organism and population levels. To develop early anti-viral therapies and proactive administration, it is important to understand the very first steps of this process. Plant somatic embryogenesis (SE) is the earliest and most studied model for de novo programming upon severe stress that, in contrast to virus attacks, promotes individual cell and organism survival. We argued that transcript level profiles of target genes established from in vitro SE induction as reference compared to virus-induced profiles can identify differential virus traits that link to harmful reprogramming. To validate this hypothesis, we selected a standard set of genes named ‘ReprogVirus’. This approach was recently applied and published. It resulted in identifying ‘CoV-MAC-TED’, a complex trait that is promising to support combating SARS-CoV-2-induced cell reprogramming in primary infected nose and mouth cells. In this perspective, we aim to explain the rationale of our scientific approach. We are highlighting relevant background knowledge on SE, emphasize the role of alternative oxidase in plant reprogramming and resilience as a learning tool for designing human virus-defense strategies and, present the list of selected genes. As an outlook, we announce wider data collection in a ‘ReprogVirus Platform’ to support anti-viral strategy design through common efforts.