bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration on redox status in saliva of microcephaly children
Authors: Alves Thayane Miranda , Barbieri Cintia Megid , Gomes Marco Aurelio , Araujo Heitor Ceolin , Visquette Nathália de Oliveira , Louzada Liliane Passanezi de Almeida , Silva Cristina Antoniali , Chaves-Neto Antonio Hernandes , Nakamune Ana Claudia de Melo Stevanato 
Published: June 2021

Microcephaly is described as a reduction of the head circumference, due to the premature fusion of the bones of the skull, preventing the brain from growing normally and reaching its maximum development. This condition may result in neurological disorders, phonation and chewing dysfunction, dysphagia and risk of malnutrition. This alteration contributes to oral hygiene impairment, and continuous uses of the antipsychotic and anticonvulsant medication. Thus, the purpose of this study was to evaluate if microcephaly modified redox balance in saliva. Our hypothesis is that in the microcephalic patient's salivary oxidative stress is lower because of the increase in antioxidant defenses. The study included 13 patients with microcephaly (microcephalic group – MC) and 12 patients without neurological disorders (normocephalic group – NC), from zero to ten years old, no edentulous. Saliva was collected using a cotton wool swab, placing it on the child's mouth floor. After centrifugation, supernatants were fractionated and stored at -80 °C for analyses. Lipid oxidative was evaluated by TBARS methods, total antioxidant capacity by the ferric reducing ability (FRAP) assay, uric acid (UA) was quantified by modified Trinder reaction, and superoxide dismutase activity (SOD) by inhibition of the pyrogallol auto-oxidation. Total protein was measured using the method of Lowry. Compared to NC group, TBARS was significantly lower in MC group, while FRAP, UA and SOD were higher. Our hypothesis was confirmed. MC patients have lower salivary oxidative stress, due to increased oxidant defenses.
The series of trademarks: theory, legislation, law enforcement
Authors: Myronenko Nataliia 
Published: June 2021

Key words: trademark, series of signs, dominant element, originality, resolution
The article, based on the analysis of the doctrine of intellectual property law,legislation of Ukraine, law enforcement practice, examines the state and prospects ofproviding legal protection of a series of trademarks. To overcome the existing gap inthe legislation of Ukraine, the need to amend the Law of Ukraine «On Protection ofRights to Marks for Goods and Services» is justified. It is proposed to define «a seriesof marks as a set of trademarks belonging to one owner of interdependent rights, interconnected by the presence of the same dominant verbal, figurative or combined element,having phonetic and semantic similarity, and may also bear minor graphic differencesthat do not change the essence of the trademarks. The lack of definition ofthe term «dominant element» in the legislation is emphasized. Based on the provisionsof the philosophy and doctrine of intellectual property law, the dominant elementmeans the smallest indivisible component of the trademark, which is originaland not descriptive. Based on this, its main features are distinguished: originalityand indivisibility.It is proved that the same position of the dominant element in the structure of allsigns is necessary to create a stable image of consumers in relation to a particularproduct and its manufacturer. Examples of court decisions on recognition or refusal toprovide legal protection to trademarks are given.In the context of reforming the legislation of Ukraine in terms of its approximation toEU legislation and the development of relevant case law, which must meet Europeanstandards, the expediency of using the legal positions of such a leading democratic courtas the European Court of Justice is justified. Attention is drawn to the fact that the decisionof the ECJ is not a source of law for resolving disputes of this category by the courtsof Ukraine. At the same time, they are a source of harmonious interpretation of the nationallegislation of Ukraine in accordance with the established standards of the legalsystem of the European Union. It is proved that this conclusion is consistent with thepurpose and objectives to be solved in the country in the process of implementing the provisionsof the Association Agreement in the legislation of Ukraine. Proposals are formulatedto improve the quality of legislation in the field of IP law.
Assisted reproductive technologies as a legal category
Authors: Pokalchuk Oksana 
Published: June 2021

Keywords: moral rights, assisted reproductive technologies, legal category
The author analyzes the legal concept of «assisted reproductive technologies», which is presentedin the works of Ukrainian and foreign scientists. Given the nature and essence of theuse of assisted reproductive technologies as social relations, the author concludes thatthe main part of the researches belongs to the Civil Law branch of scientific knowledge.It is because the right to assisted reproductive technologies is a part of the system ofmoral rights which are the part of the regulation of Civil Law. At the same time, withinthe legal literature the doctrinal understanding of assisted reproductive technologieshave rather multifaceted, but ambiguous nature of its' scope.Thus, the content of the views of scientists which are analysing in the article, reflectsthe provisions on: a) the functional purpose of assisted reproductive technologies; b) thecontent of their application in the determined cases; c) their instrumental understandingas a set of manipulations (methods, techniques, etc.); d) the exceptional importance of these technologies as the main means of overcoming infertility and solving demographicproblems of today; e) innovative nature of use in the medical field.In addition, at the level of modern legal doctrine, the scientific researches of legal aspectsof assisted reproductive technologies is multi-vector, especially in terms of studyingtheir medical and legal nature, content and consequences, accompanied by increasingrelevance of their knowledge under the influence of rapid medical development, inventionand implementation of new medical technologies, including in the field of human reproduction.Generally modern scientific researches on the legal aspects of assisted reproductivetechnologies is represented by a wide range of scientific works, but most of them aremulti-vector in nature, and scientific conclusions are mostly scattered and not systematized.In fact, the «harmony» of the conceptual and categorical apparatus for assisted reproductivetechnologies is important for the formulation of a scientific problem and thedefinition of methods for its further resolving.
Medical research: state and problems
Authors: Ponomarova Olena 
Published: June 2021

Keywords: medical research, ethical aspects of research, patient rights, as the objectof research, informed consent
In the article, the author conducted a study of medical research with human participation, analyzed the legislation of Ukraine and international documents and found that there is no unified conceptof «medical research», but uses different terms, such as biomedical experiment, clinicaltrial, clinical trials, etc. The legal acts of Ukraine provide for a variety of terms, but dothey all mean the same concept. It would be appropriate to enshrine at the level of thelaw the concept of broad meaning «medical research», which would include such types as:«medical and biological experiments», «clinical trials» and so on. Referring to internationalinstruments on the search for the concept of «medical research» also revealed differencesin the conceptual understanding of the concept of «medical research». Instead, itwas found that all the legal acts analyzed in the article stipulate that medical examinationswith human participation, as the object of research, begin only after the person hasgiven voluntary informed consent to conduct research on him.The procedure for conducting medical examinations with the participation of a personas an object of study in all legal documents referred to in the article provides for themandatory voluntary consent of the person who is the object of research. Article 10, paragraph2, of the Convention for the Protection of Human Rights and Dignity of Biologyand Medicine: The Convention on Human Rights and Biomedicine guarantees everyonethe right to access any information collected about their health. However, the desire ofindividuals not to receive such information must also be respected. The rights of patientsduring medical research, as the object of research, including the study of their biologicalmaterial and data, regardless of the country in which they live and where medical researchtakes place, national laws must guarantee ethical standards at the highest levelof medical research and ensure strong legal basis for future medical research. The socialfunction of the state is the vocation to protect the researcher and the subjects.
An Early Diagnostic Clue for COL18A1- and LAMA1-Associated Diseases: High Myopia With Alopecia Areata in the Cranial Midline
Authors: Wang Panfeng , Jia Xiaoyun , Xiao Xueshan , Li Shiqiang , Long Yuxi , Liu Mengchu , Li Yongyu , Li Jun , Xu Yan , Zhang Qingjiong 
Published: June 2021

BackgroundHigh myopia with alopecia areata in the occipital region has been observed in patients with Knobloch syndrome caused by COL18A1 mutations. This study investigated other possible genetic causes of high myopia in patients with alopecia areata in the cranial midline.MethodsSix patients with early onset high myopia and alopecia areata in the cranial midline were recruited. Targeted high-throughput sequencing was performed on the proband’s DNA to detect potential pathogenic variants. Cosegregation analysis was performed for available family members. Minigene assay and RNA Sequencing were used to validate the abnormality of possible splicing change and gross deletion. Ophthalmological and neuroimaging examinations were performed.ResultsEight novel and one known loss-of-function mutants were detected in all six patients, including a gross deletion detected by RNA sequencing. Four COL18A1 mutants in three patients with scalp leisure in the occipital region; and five LAMA1 mutations in three patients with scalp leisure in the parietal region. Further assessments indicated that patients with COL18A1 mutations had Knobloch syndrome, and the patients with LAMA1 mutations had Poretti–Boltshauser syndrome.ConclusionOur study found that early onset high myopia with midline alopecia areata could be caused not only by mutations of the COL18A1 gene but also by mutations in the LAMA1 gene. To our knowledge, we are the first to observe scalp defects in patients with LAMA1 mutations. High myopia with alopecia areata in the cranial midline could be treated as an early diagnostic clue for ophthalmologists to consider the two kinds of rare diseases.
Risk Factors for Different Types of Pregnancy Losses: Analysis of 15,210 Pregnancies After Embryo Transfer
Authors: Yang Ai-Min , Xu Xiuhua , Han Yan , Wei Jian-Jun , Hao Gui-Min , Cui Na , Zhao Zhi-Ming , Wang Wei , Huang Xianghua 
Published: June 2021

ObjectiveTo evaluate the risk factors for different types of pregnancy losses after embryo transfer (ET).DesignRetrospective cohort study.SettingReproductive medicine center.ParticipantsA total of 15,210 pregnancies after fresh and frozen-thawed embryo transfer between January 2014 and June 2019.Main Outcome MeasuresThe primary outcome was pregnancy loss (PL) throughout the entire pregnancy. Secondary outcomes were non-visualized PL, early miscarriage, late miscarriage, and stillbirth.MethodsThe effect of patients’ baseline characteristics and IVF/ICSI cycle-specific factors on the risk of PL after fresh and frozen-thawed ET was determined by multivariate logistic regression analysis.ResultsCompared to women under 35 years old, those between 35 and 40 had an increased risk of early miscarriage [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.22-1.83], while those after 40 appeared to have an increased risk of both early miscarriage (OR 3.82, 95% CI 2.65-5.51) and late miscarriage (OR 2.79, 95% CI 1.64-4.77). Overweight patients were observed to have a higher risk of late miscarriage (OR 1.38, 95% CI 1.16-1.65), while obese patients showed a higher risk of both early miscarriage (OR 1.47, 95% CI 1.14-1.91) and late miscarriage (OR 1.80, 95% CI 1.33-2.44). Polycystic ovary syndrome (PCOS) was an independent risk factor for late miscarriage (OR 1.58, 95% CI 1.28-1.96), and the detrimental effect of PCOS was independent of obesity status. Women with uterine factors had a higher risk of early miscarriage (OR 1.77 (95% CI 1.32-2.38) than women without uterine factors. A negative correlation was observed between the thickness of the endometrium and PL (OR 0.95 95% CI 0.92-0.97). There was an increased risk of PL after frozen-thawed ET versus fresh ET (OR 1.12, 95% CI 1.01-1.24). Women who transferred ≥2 embryos showed lower risk of overall PL than women who transferred a single embryo, with adjusted ORs ranged from 0.57~0.94. However, women who transferred three embryos demonstrated a higher risk of late miscarriage than women who transferred a single embryo (OR 2.23, 95% CI 1.36-3.66).ConclusionsPatients with uterine factors demonstrated higher risk of early miscarriage and stillbirth. Being overweight, PCOS, and transferring three embryos was associated with late miscarriage. Being aged 40 and over, obese, and using frozen embryo transfer was associated with early and late miscarriage.
Oral Administration of Lactococcus lactis Producing Interferon Type II, Enhances the Immune Response Against Bacterial Pathogens in Rainbow Trout
Authors: Santibañez Alvaro , Paine Diego , Parra Mick , Muñoz Carlos , Valdes Natalia , Zapata Claudia , Vargas Rodrigo , Gonzalez Alex , Tello Mario 
Published: June 2021

Lactic acid bacteria are a powerful vehicle for releasing of cytokines and immunostimulant peptides at the gastrointestinal level after oral administration. However, its therapeutic application against pathogens that affect rainbow trout and Atlantic salmon has been little explored. Type II interferon in Atlantic salmon activates the antiviral response, protecting against viral infection, but its role against bacterial infection has not been tested in vivo. In this work, through the design of a recombinant lactic acid bacterium capable of producing Interferon gamma from Atlantic salmon, we explore its role against bacterial infection and the ability to stimulate systemic immune response after oral administration of the recombinant probiotic. Recombinant interferon was active in vitro, mainly stimulating IL-6 expression in SHK-1 cells. In vivo, oral administration of the recombinant probiotic produced an increase in IL-6, IFNγ and IL-12 in the spleen and kidney, in addition to stimulating the activity of lysozyme in serum. The challenge trials indicated that the administration of the IFNγ-producing probiotic doubled the survival in fish infected with F. psychrophilum. In conclusion, our results showed that the oral administration of lactic acid bacteria producing IFNγ managed to stimulate the immune response at a systemic level, conferring protection against pathogens, showing a biotechnological potential for its application in aquaculture.
Tight Binding of Plasmid DNA With Self-Assembled Tetramethylguanidinium Conjugated Polyethylenimine Suppresses Transfection Efficiency
Authors: Yadav Santosh , Sharma Ashwani Kumar , Kumar Pradeep 
Published: June 2021

Here, we have demonstrated that on modification of linear polyethylenimine (lPEI, LP) with amphiphilic 3-bromopropyltetramethylguanidinium (PTMG) linker, the transfection efficiency exhibited by the modified polymers decreased while cell viability improved. A series of LP-PTMG polymers was synthesized by the reaction of varying amounts of 3-bromopropyl tetramethylguanidinium linker with lPEI (25 kDa). These modified polymers interacted efficiently with pDNA and formed nanosized complexes as shown by dynamic light scattering analysis. The size of the complexes in the series LP-PTMG/pDNA was observed in the range of ∼178–205 nm. The interaction of modified polymers with plasmid DNA was stronger than linear PEI as evidenced by heparin release assay which showed ∼83% pDNA release from LP-PTMG-3/pDNA complexes in comparison to ∼95% in lPEI/pDNA complexes on treatment with same amount of heparin suggesting the formation of self-assembled structures in modified polymers. The transfection studies in HeLa and Chinese hamster ovary cells showed a decrease in transfection efficiency of LP-PTMG polymers, the reason for this may be strong binding of modified polymers with pDNA due to accumulation of charge on the surface. This finding showed the significance of optimum binding of polymer and DNA to form polyplexes as well as release of DNA from the polyplexes.
LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC
Authors: Yi Tiezhong , Song Yicun , Zuo Lingling , Wang Siyun , Miao Jintian 
Published: June 2021

ObjectivesIncreasing researches emphasize the importance of long non-coding RNAs (lncRNAs) in the development of endometrial cancer (EC). There is wide recognition that LINC00470 is a critical participant in the tumorigenesis of cancers such as gastric cancer and glioblastoma, but its possible effects on EC progression remain to be explored.MethodsWe collected EC tissues and cells, where the expression of LINC00470 was determined, and followed by the Kaplan-Meier analysis of EC patient survival. We next examined the effect of LINC00470 and phosphatase and tensin homolog (PTEN) on EC cell migration, invasion, tube formation in vitro, and angiogenesis in mice xenografted with tumor after gain- or loss-of-function treatments. RNA pull-down, Co-IP, and ChIP experiments were performed to analyze the targeting relationships among LINC00470, MYC and DNMT3a.ResultsLINC00470 was aberrantly upregulated in EC and its high expression correlated to prognosis of EC patients. LINC00470 promoted invasiveness, migration, and angiogenesis of EC cells, and facilitated tumorigenesis and metastasis in vivo, but those effects were reversed by up-regulating PTEN. Functionally, LINC00470 bound to MYC in EC and that LINC00470 stimulated the binding of MYC to DNMT3a, and thus recruited DNMT3a through MYC to promote PTEN methylation.ConclusionsOur findings revealed that LINC00470 stimulated PTEN methylation to inhibit its expression by MYC-induced recruitment of DNMT3a, thus aggravating EC.
Etiology of Severe Pneumonia in Children in Alveolar Lavage Fluid Using a High-Throughput Gene Targeted Amplicon Sequencing Assay
Authors: Li Fei , Wang Yin , Zhang Yuhan , Shi Peng , Cao Linfeng , Su LiYun , Zhu Qiguo , Wang Libo , Lu Roujian , Tan Wenjie , Shen Jun 
Published: June 2021

Objective: To evaluate the diagnostic value of a high-throughput gene targeted amplicon sequencing (TAS) assay for detecting pathogenic microorganisms in alveolar lavage fluid (ALF) from children with severe community-acquired pneumonia (SCAP).Methods: A retrospective study was performed on 48 frozen ALF samples from 47 severe pneumonia cases admitted to Children's Hospital of Fudan University from January 1, 2019, to March 31, 2019. All samples were tested by a multiplex PCR (Multi-PCR) assay and a TAS assay. The results of the TAS panels were parallel compared with Multi-PCR and Conventional Tests (CT) including culture, direct fluorescent antibody method (DFA), and singleplex polymerase chain reaction (PCR).Results: The proportion of pathogens detection by CT was 81.2% (39/48). The 8 common respiratory viruses including respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (FLUA), influenza B virus (FLUB), parainfluenza virus 1–3 (PIV1-3), and human Metapneumovirus (hMPV) were found in 31.2% (15/48) of the 48 samples by DFA. With the criteria of CT results used as “Golden Standard” for determing of TAS results, the proportion of pathogens detection by TAS was 70.8% (34/48). The difference of proportion of pathogens detection between TAS and CT was not statistically significant (p = 0.232). The sensitivity and specificity of TAS for pathogens detection based on CT were 87.1% (95% CI, 71.77–95.18%) and 100.0% (95% CI, 62.88–100%), the positive predictive value (PPV) and negative predictive value (NPV) were 100.0% (95% CI, 87.35–100%) and 64.2% (95% CI, 35.62–86.02%), respectively. While Multi-PCR results were used as “Golden Standard,” the total pathogens detection rate of TAS was 83.3% (40/48), which had a significant difference with that of Multi-PCR (p = 0.003). The sensitivity and PPV of TAS compared with Multi-PCR were 83.3% (95% CI, 69.23–92.03%) and 100.0% (95% CI, 89.08–100%), respectively. High rates of co-infection were proved by CT, Multi-PCR, and TAS. Mycoplasma pneumoniae (MP) and ADV were the two most frequently detected pathogens in all three assays.Conclusion: Compared with the CT and Multi-PCR methods, this TAS assay had a good performance in detecting bacteriological and viral pathogens from ALF. More research is needed to establish interpretation criteria based on TAS reads or analysis platforms.
Comparative Analysis of Intracellular and in vitro Antioxidant Activities of Essential Oil From White and Black Pepper (Piper nigrum L.)
Authors: Wang Ying , Wang Liang , Tan Jin , Li Rong , Jiang Zi-Tao , Tang Shu-Hua 
Published: June 2021

Ethnopharmacological Relevance: Pepper essential oils have potential immunomodulatory, anti-tumor, and anti-cancer activities. Pepper exhibits the potential to prevent or attenuate carcinogenesis as therapeutic tools. However, the related mechanism remains unelucidated.Aim of the Study: The present study aims to provide reasonable information for the explanation of the dissimilarity of the essential oils from white (WPEO) and black pepper (BPEO).Materials and Methods: WPEO, BPEO, and their single active component, as well as synthetic antioxidants, were compared by the cell model methods and chemical methods, including intracellular antioxidant activity (CAA), total antioxidant activities (TAA), superoxide radical (SR), hydroxyl radical (HR), DPPH radical (DR) scavenging activities and inhibition ability of lipoprotein lipid peroxidation (ILLP).Results: The median effective concentration (EC50) values (mg/mL) of the WPEO and BPEO of SR, HR, DR, and ILLP were 0.437 and 0.327, 0.486 and 0.204, 7.332 and 6.348, 0.688, and 0.624 mg/mL, respectively. The CAA units of WPEO and BPEO were 50.644 and 54.806, respectively. CAA, DR, and TAA of BPEO were significantly higher than those of WPEO (p &lt; 0.05). The BPEO and WPEO can be differentiated as the former have higher correlations with 3-carene, α-pinene, β-pinene, and limonene while the latter has a higher caryophyllene correlation. The WPEO and BPEO show a good intracellular scavenging ability of reactive oxygen species in HeLa cells.Conclusion: Generally, pepper oil has stronger activities than single components, indicating that pepper is a broad-spectrum natural antioxidant.