bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experience of EU countries on ethical aspects of patenting biotechnologies in the field of medicine and pharmacy
Authors: Ponomarova Olena 
Published: July 2021

Keywords: patenting, ethics, biotechnological inventions, medicine, pharmaceuticals,health
The progress ofmodern biotechnological achievements poses new ethical and social challenges to society.Research using biotechnology in medicine and pharmacy leads to more in-depthknowledge of diseases. With the help of biotechnology, it becomes possible to treatpreviously incurable diseases. It is worth noting that today with the possibility ofusing biotechnological developments, the scientific community in a very short timewas able to successfully invent vaccines against COVID-19.During clinical trials, the safety of study subjects should be unneglected for therapid introduction of the product to the market. Ethics and innovation in modern societyalways go hand in hand, especially in the field of health care. The worldwidespread of COVID-19 underscores the importance of maintaining a balance betweenethics and intellectual property rights when human lives are in mortal danger.Society is concerned about the ethics of patenting life, namely, the possibility ofpatenting genes, cell lines and human tissues. The Directive states that the humanbody cannot be invented at certain stages of its formation and development, includinggerm cells, as well as the simple discovery of one of its components, including the sequenceor partial sequence of a gene.Patents that relate to the human gene are particularly critically examined ethically.Ethics, morality, and law are interrelated components and are extremely importantfor society to accept the invention. EU patent law is based on ethical principles. Thus, theadoption of the Directive was envisaged for the development of the EU economy, the abilityto regulate controversial issues regarding the patenting of biotechnological inventionsby criteria of ethics and morality and to harmonize EU legislation.Owners who run biotechnology institutions (organizations) must protect the results ofresearch, and obtaining patents is the most effective way. After all, long-term researchand development of new products or processes require significant financial costs. The intellectualproperty product must be protected by a patent, including biotechnological inventions.
Issues of the protection of intellectual property in process euro-atlantic integration
Authors: Zaikivskyi Oleksandr , Onistrat Oleksandr 
Published: July 2021

Key words: Euro-Atlantic integration, intellectual property, objects of intellectualproperty rights, infringement of intellectual property rights, scientific and technical cooperation,military-technical cooperation
Some issues concerning the protection of intellectualproperty in the process of Euro-Atlantic integration are considered, in particularthe peculiarities of the protection of intellectual property in the implementation of internationalcooperation of Ukraine and the protection of national interests in theprocess of this cooperation. The legislation of Ukraine regulating activities related tointernational scientific and technical and military-technical cooperation is analysed.The importance of intellectual property protection at all stages of international cooperationof Ukraine and the need to improve the legislation on the regulation of intellectualproperty protection in the process of this cooperation is determined. It is suggested totake a number of measures to address issues related to the protection of intellectualproperty in the process of international cooperation of Ukraine and the protection of nationalinterests regarding the use of intellectual property rights in the process of thiscooperation.The protection of intellectual property in international cooperation should be ensuredprimarily by bilateral agreements on this issue, which should be concluded at thebeginning of cooperation in any field, as well as agreements on the protection of classifiedinformation. These agreements should define the basic principles for concludingagreements (contracts) and be aimed at mutual protection of information, prevention ofinfringement of the rights for the results of intellectual activity when using them in thecourse of cooperation.To deal with this issue, it is necessary to systematically and comprehensively approachthe improvement of legislation on intellectual property in the defence sector, especially on the protection of national interests in the implementation of cooperation inthe process of Euro-Atlantic integration. It is necessary to clearly define in the legislationthe obligations of all subjects to ensure the protection of intellectual property at allstages of cooperation, as well as expanding the list of violations and responsibility fortheir implementation, especially for actions that threaten infringement of intellectualproperty rights measures to ensure the protection of intellectual property rights.
Laser coagulation in combination with LIFT for transsphincteric anal fistulas
Authors: Vasiliev S. V. , Nedozimovanyi A. I. , Popov D. E. , Gor I. V. , Moshkova T. A. 
Published: July 2021

Aim: to improve the results of fistula treatment, to evaluate the effectiveness of the combined use of LIFT and FiLaC techniques.Patients and methods: the study included 35 patients with transsphincter fistulas of cryptopglandular etiology involved more than 1/3 of the sphincter. All patients underwent surgery with laser energy (the laser conductor speed is 1 mm per second, the wavelength is 1470 nm, the radiation output is 13 W) after the LIFT procedure.Results: the primary healing rate was 28/35 (80,0%). The patients who failed the combined procedure (cases of prolonged healing more than 3 months) underwent a second procedure ReFiLaC, which led to the closure of fistula in 2 of 3 patients. A median follow-up period was 10,2 months. No incontinence to solid and liquid stools was detected.Conclusion: preliminary results of the study permits to assess the potential of the combined low-invasive approach for anal fistulas as positive.
Age-Dependent Regulation of Notch Family Members in the Neuronal Stem Cell Niches of the Short-Lived Killifish Nothobranchius furzeri
Authors: Bagnoli Sara , Terzibasi Tozzini Eva 
Published: July 2021

Background:The annual killifishNothobranchius furzeriis a new experimental model organism in biology, since it represents the vertebrate species with the shortest captive life span and also shows the fastest maturation and senescence recorded in the laboratory. Here, we use this model to investigate the age-dependent decay of neurogenesis in the telencephalon (brain region sharing the same embryonic origin with the mammalian adult niches), focusing on the expression of the Notch pathway genes.Results:We observed that the major ligands/receptors of the pathway showed a negative correlation with age, indicating age-dependent downregulation of the Notch pathway. Moreover, expression ofnotch1awas clearly limited to active neurogenic niches and declined during aging, without changing its regional patterning. Expression ofnotch3is not visibly influenced by aging.Conclusion:Both expression pattern and regulation differ betweennotch1aandnotch3, with the former being limited to mitotically active regions and reduced by aging and the latter being present in all cells with a neurogenic potential, regardless of the level of their actual mitotic activity, and so is less influenced by age. This finally suggests a possible differential role of the two receptors in the regulation of the niche proliferative potential throughout the entire fish life.
Complete Revascularisation in Impella-Supported Infarct-Related Cardiogenic Shock Patients Is Associated With Improved Mortality
Authors: Schäfer Andreas , Westenfeld Ralf , Sieweke Jan-Thorben , Zietzer Andreas , Wiora Julian , Masiero Giulia , Sanchez Martinez Carolina , Tarantini Giuseppe , Werner Nikos 
Published: July 2021

Background: Acute myocardial infarction-related cardiogenic shock (AMI-CS) still has high likelihood of in-hospital mortality. The only trial evidence currently available for the intra-aortic balloon pump showed no benefit of its routine use in AMI-CS. While a potential benefit of complete revascularisation has been suggested in urgent revascularisation, the CULPRIT-SHOCK trial demonstrated no benefit of multivessel compared to culprit-lesion only revascularisation in AMI-CS. However, mechanical circulatory support was only used in a minority of patients.Objectives: We hypothesised that more complete revascularisation facilitated by Impella support is related to lower mortality in AMI-CS patients.Methods: We analysed data from 202 consecutive Impella-treated AMI-CS patients at four European high-volume shock centres (age 66 ± 11 years, 83% male). Forty-seven percentage (n = 94) had cardiac arrest before Impella implantation. Revascularisation was categorised as incomplete if residual SYNTAX-score (rS) was &gt;8.Results: Overall 30-day mortality was 47%. Mortality was higher when Impella was implanted post-PCI (Impella-post-PCI: 57%, Impella-pre-PCI: 38%, p = 0.0053) and if revascularisation was incomplete (rS ≤ 8: 37%, rS &gt; 8: 56%, p = 0.0099). Patients with both pre-PCI Impella implantation and complete revascularisation had significantly lower mortality (33%) than those with incomplete revascularisation and implantation post PCI (72%, p &lt; 0.001).Conclusions: Our retrospective analysis suggests that complete revascularisation supported by an Impella microaxial pump implanted prior to PCI is associated with lower mortality than incomplete revascularisation in patients with AMI-CS.
Long-Term Effects of the Harvesting of Trapa natans on Local Water Quality and Aquatic Macrophyte Community in Lake Erhai, China
Authors: Yuan Changbo , Bai Xiaohu , Zhu Tianshun , Wen Zihao , Cao Te , Zhang Xiaolin , Ni Leyi 
Published: July 2021

Trapanatansis one of the main species causing the swamping in the littoral zones of Erhai Lake. It commonly forms a dense canopy on the water surface in the growing season (June–September), which hampers the local water quality and habitat of submerged macrophytes, and releases nutrients to the water after death in autumn and winter, resulting in the deterioration of local water quality. At present, there are many and positive research studies on the short-term effects of harvesting water chestnut on water quality and aquatic plants, but long-term observation results are lacking. In response to the above problems, we studied responses of water quality and aquatic plant community to the removal ofTrapain littoral zone of a northern bay in Erhai from August 2014 to January 2017. This could be the first attempt to discover the long-term effects of floating-leaved vegetation management in the freshwater ecosystem. The results showed that the artificial removal ofTrapasignificantly improved the local water quality in the growing season, for example, the concentrations of total nitrogen (TN), dissolved nitrogen (DN), total phosphorus (TP), and dissolved phosphorus (DP) in the non-Trapazone (NTZ) were much lower than the concentrations of those in the adjacentTrapazone (TZ). And the biomass of aquatic macrophyte community (BAMC) was significantly increased in the NTZ, up to the maximum value of about 21 kg/m2in fresh weight. However, the diversity indexes of the community in the NTZ declined. Therefore, we suggested that although the removal ofTrapaimproved the water quality and increased the productivity of the submerged aquatic plant community, it reduced the species diversity of the aquatic plant community in the long run. This is another issue that we need to pay attention to in the later management in Erhai Lake.
Forecast of Hemorrhagic Fever With Renal Syndrome and Meteorological Factors of Three Cities in Liaoning Province, China, 2005–2019
Authors: Sun Wanwan , Liu Zhidong , Liu Qiyong , Li Wen , Lu Liang 
Published: July 2021

Background: Hemorrhagic fever with renal syndrome (HFRS) is an endemic in China, accounting for 90% of HFRS cases worldwide and growing. Therefore, it is urgent to monitor and predict HFRS cases to make control measures more effective. In this study, we applied generalized additive models (GAMs) in Liaoning Province, an area with many HFRS cases. Our aim was to determine whether GAMs could be used to accurately predict HFRS cases and to explore the association between meteorological factors and the incidence of HFRS.Methods: HFRS data from Liaoning were collected from January 2005 to May 2019 and used to construct GAMs. Generalized cross-validation (GCV) and adjusted R-square (R2) values were used to evaluate the constructed models. The interclass correlation coefficient (ICC) was used as an index to assess the quality of the proposed models.Results: HFRS cases of the previous month and meteorological factors with different lag times were used to construct GAMs for three cities in Liaoning. The three models predicted the number of HFRS cases in the following month. The ICCs of the three models were 0.822, 0.832, and 0.831. Temperature and the number of cases in the previous month had a positive association with HFRS.Conclusion: GAMs applied to HFRS case data are an important tool for HFRS control in China. This study shows that meteorological factors have an effect on the occurrence of HFRS. A mathematical model based on surveillance data could also be used in forecasting. Our study will inform local CDCs and assist them in carrying out more effective measures for HFRS control and prevention through simple modeling and forecasting.
Case Report: Diagnosis of Human Alveolar Echinococcosis via Next-Generation Sequencing Analysis
Authors: Li Ke , Ma Yubao , Ban Rui , Shi Qiang 
Published: July 2021

Introduction: Alveolar echinococcosis (AE) is a rare parasitic disease caused by the infection of Echinococcus multilocularis. AE may mimic malignancy both in clinical presentation and radiological imaging, which is often misdiagnosed as metastatic tumor. Recently, next-generation sequencing (NGS) technologies are increasingly being used to address a diverse range of biological questions. Here, we describe a rare case of alveolar echinococcosis diagnosed by pan-pathogen screening, using next-generation sequencing. To the best of our knowledge, this is the first reported case of AE which was definitely diagnosed relying NGS of cerebrospinal fluid (CSF).Case Presentation: A 33-year-old man presented with repeat seizure and progressive headache for six months. Head magnetic resonance imaging (MRI) showed multiple masses with edema. Lung and abdominal computer tomography (CT) revealed multiple masses in bilateral lung, liver and the right adrenal gland. Bacterial, tuberculosis and fungal infection were excluded by CSF examination. Repeated target biopsy on the masses in the lung and liver showed as fibrous connective tissue without positive findings. NGS of CSF was performed and detected nucleic acid sequences of E. multilocularis. Consequently, the patient has accepted 1-year albendazole therapy. His case was followed up through imaging procedures.Conclusion: The next-generation sequencing of CSF is a reliable and sensitive diagnostic method for the detection of pathogenic microorganisms, and may allow the accurate diagnosis of alveolar echinococcosis. In view of this case, we recommend NGS as a potential tool for diagnosis of cerebral AE, especially if repeated biopsies are negative.
Circulating miRNAs in Serum as Biomarkers for Early Diagnosis of Non-small Cell Lung Cancer
Authors: Duan Xiaotong , Qiao Simiao , Li Dianhe , Li Shangbiao , Zheng Zhihao , Wang Qin , Zhu Xiaoxia 
Published: July 2021

BackgroundNon-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. This study aimed to discover the potential miRNA biomarkers for early detection of NSCLC.MethodsTotal circulating miRNAs were extracted from six patients and six volunteers and run on the miRNA chip. The differentially expressed miRNAs acquired by data mining were intersected with chip results, and qRT-PCR were carried out. Then the differentially miRNAs were validated by using a validation cohort (120 participants). ROC curves were established to evaluate the diagnostic efficacy of the differentially circulating miRNAs. The target genes of the differential miRNAs were identified using the miRTarBase database, and follow-up GO and KEGG enrichment analysis were conducted.ResultsWe identified 577 miRNA which screened according to the criteria (fold change &gt; 2 and p value &lt; 0.05). Among them, seven circulating miRNAs passed additional filtering based on data mining. These miRNAs were further validated in the training and validation cohort. miR-492, miR-590-3p, and miR-631 were differentially expressed in the patients’ serum, and the area under the ROC curve (AUC) values of these miRNAs were 0.789, 0.792, and 0.711, respectively. When using them as a combination to discriminate healthy volunteers from patients, the AUC reached 0.828 (95% CI, 0.750–0.905, p = 0.000) with a sensitivity of 86.7% and specificity of 71.7%. The follow-up enrichment analysis showed that target genes of three miRNA were associated with tumorigenesis and progression, such as cell cycle and P53 signaling pathway.ConclusionsThe combination of miR-492, miR-590-3p, and miR-631 can be utilized to distinguish healthy individuals and early-stage NSCLC patients.ImpactThe combination of miR-492, miR-590-3p, and miR-631 might be a promising serum biomarker in patients for the early diagnosis of NSCLC.
Association Between Lower Extremity Venous Insufficiency and Intrapartum Fetal Compromise: A Nationwide Cross-Sectional Study
Authors: Asúnsolo Ángel , Chaowen Chen , Ortega Miguel A. , Coca Santiago , Borrell Luisa N. , De León-Luis Juan , García-Honduvilla Natalio , Álvarez-Mon Melchor , Buján Julia 
Published: July 2021

Introduction: Chronic venous disorder (CVeD) has a high prevalence, being commonly diagnosed by the presence of varicose veins. In fact, the development of varicose veins in lower extremities and/or pelvic venous insufficiency (LEPVI) is frequent. However, its potential impact on fetal health has not been investigated. This study aimed to examine whether the presence of varicose veins in women's LEPVI is related to an intrapartum fetal compromise event.Materials: A cross-sectional, national study was conducted using medical administrative records (CMBD) of all vaginal births (n = 256,531) recorded in 2015 in Spain. The independent variable was defined as the presence of varicose veins in the legs, vulva, and perineum or hemorrhoids. A logistic regression model was used to assess the association of interest.Results: Among women with vaginal deliveries, those with varicose veins in their LEPVI have a significantly greater odds of intrapartum fetal compromise (OR = 1.30, 99.55%CI = 1.08–1.54) than their counterparts without varicose veins. After adjustment, this association remained significant (OR = 1.25, 99.5%CI = 1.05–1.50).Conclusions: Our findings of an association between varicose veins in women's lower extremities and/or pelvis and intrapartum fetal compromise suggest that varicose veins may be a novel and important clinical risk factor for fetal well-being and health.
Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai
Authors: Bian DongSheng , Jiang Yongmei , Gu Yubei , He Zirui , Chen Qi , Tang Yonghua , Zhong Jie , Shi Yongmei 
Published: July 2021

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited.Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia.Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected.Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09–52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80–9.38).Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.
The Prognostic Accuracy of National Early Warning Score 2 on Predicting Clinical Deterioration for Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Zhang Kai , Zhang Xing , Ding Wenyun , Xuan Nanxia , Tian Baoping , Huang Tiancha , Zhang Zhaocai , Cui Wei , Huang Huaqiong , Zhang Gensheng 
Published: July 2021

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the National Early Warning Score 2 (NEWS2) is recommended for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. Therefore, our purpose is to assess the prognostic accuracy of NEWS2 on predicting clinical deterioration for patients with COVID-19.Methods: We searched PubMed, Embase, Scopus, and the Cochrane Library from December 2019 to March 2021. Clinical deterioration was defined as the need for intensive respiratory support, admission to the intensive care unit, or in-hospital death. Sensitivity, specificity, and likelihood ratios were pooled by using the bivariate random-effects model. Overall prognostic performance was summarized by using the area under the curve (AUC). We performed subgroup analyses to assess the prognostic accuracy of NEWS2 in different conditions.Results: Eighteen studies with 6,922 participants were included. The NEWS2 of five or more was commonly used for predicting clinical deterioration. The pooled sensitivity, specificity, and AUC were 0.82, 0.67, and 0.82, respectively. Benefitting from adding a new SpO2 scoring scale for patients with hypercapnic respiratory failure, the NEWS2 showed better sensitivity (0.82 vs. 0.75) and discrimination (0.82 vs. 0.76) than the original NEWS. In addition, the NEWS2 was a sensitive method (sensitivity: 0.88) for predicting short-term deterioration within 72 h.Conclusions: The NEWS2 had moderate sensitivity and specificity in predicting the deterioration of patients with COVID-19. Our results support the use of NEWS2 monitoring as a sensitive method to initially assess COVID-19 patients at hospital admission, although it has a relatively high false-trigger rate. Our findings indicated that the development of enhanced or modified NEWS may be necessary.