bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aspects of the examination of patents relating to medical inventions
Authors: Zhykharev Oleksandr 
Published: March 2023

Keywords: selection invention; medical inventions; examination; patentability criteria
The article contains an analysis of approaches to the examination of selectioninventions for medicines. Selection inventions are inventions created in theprocess of selecting an optimal compound from a group of known compounds or in theprocess of selecting parameters from an interval of known parameters related to thecompounds. Selection inventions must demonstrate an unexpected result that is unknownin the prior art. Selection inventions can potentially be a means of obtaining amonopoly on an already known compound or a medicinal product containing thatcompound, or a method of producing the compound, etc. Therefore, the examination of criteria of patentability for selection inventions is important for maintaining the balanceof interests between the patent holder and the society. The article contains informationabout the difference between the examination of inventions in the patent officeand the forensic examination. The analysis of approaches to examination includesthe law of Ukraine for invention, which provides for the means of combating evergreen(secondary) patents, as well as the opinion of experts of the Patent Office abouta patentability of selection inventions. The article contains the approaches to examinationaccording to the regulations of the European Patent Office and other nationaljurisdictions, as well as the opinion of forensic scientists practising in this field. Apractice example of examination of a selection invention is given. The summary includesrecommendations on approaches to the examination of selection inventions:the subject of the selection invention should not have been specifically disclosed earlier;the subject should exhibit previously unknown and unexpected advantages; thedescription of the selection invention should contain reasonable evidence of non-obviousnessof the selection; the selection invention should meet the condition of inventivestep according to the general requirements as for all the inventions. If unexpected advantagesof existing products were deemed patentable under the applicable law, thepatentability of a selection could be considered when an inventive step is present.
Some aspects of judicial protection of civil legal relations in Estonia
Authors: Shabalin Andrii 
Published: March 2023

Keywords: intellectual property law, codification, EU, civil procedure, civil law,CPC of Estonia
The scientific article examines the peculiarities of the civil proceduralorder for the protection of law in Estonia. Attention is paid to the genesis of modernEstonian civil justice, the peculiarities of some civil legal procedures for considerationand resolution of civil cases are established. It is concluded that all civillegal disputes are resolved according to the rules of civil proceedings, includingdisputes about the protection of intellectual property rights and the protection ofownership rights to immovable property. Instead, there are exceptions — these aredisputes related to European patents, which are resolved in accordance with theAgreement on the Unified European Patent Court. This approach is fully in linewith the pan-European digitalization strategy. Attention is also paid to the implementationof European legal standards in civil justice in Estonia. Thus, it is indicatedthat Estonian courts must follow the relevant practice of the European Courtof Human Rights when deciding civil cases. In Estonia, the Supreme Court canturn to the European Court of Human Rights for an advisory decision on the application,interpretation, and interpretation of the law guaranteed by the Conventionon the Protection of Human Rights and Fundamental Freedoms. Moreover, theparticipants in the legal process, in case of disagreement with the decision of theEstonian courts, including the Supreme Court of Estonia, have the right to appealto the European Court of Human Rights and the Court of Justice of the EU. It is stated that in the Estonian civil process there is a special procedure for the collectionof evidence in accordance with the requests of the EU member states to Estonia.Based on the research, theoretical conclusions and recommendations of relativelyeffective ways of updating (unification, codification) Ukrainian legislationwere formulated, in particular in the aspect of its adaptation to EU legislation.
Ensuring access to treatment for victims of sexual violence as part of the state biosecurity
Authors: Ponomarova Olena 
Published: March 2023

Keywords: intellectual property rights, access to treatment, medicines, sexual violence,humanitarian disaster, war, biosafety
The article focuses on solving the problems of accessto medicines, medical devices in the realities of wartime by the mechanisms of intellectualproperty rights to ensure the biosecurity of the state. As of today, part of the south andeast of Ukraine is under temporary occupation, where war crimes, in particular (sexualviolence/rape) are committed. A victim of sexual violence may need emergency medicalcare for fractures, soft tissue injuries and other injuries, but also needs means of preventingsexually transmitted infections. Committed war crimes: sexual violence, poses agreat danger to the biological security of the country. The provision of medical care andaccess to prevention methods for sexually transmitted infections, hepatitis B and HIV,pregnancy prevention, are all threats to biosecurity, which will lead to the spread of infectiousdiseases and HIV. Ukraine, as a member of the TRIPS Agreement, aiming to treat or provide preventionto a larger number of victims of sexual violence, in accordance with Article 39(3) of theTRIPS Agreement, has legal opportunities to ensure the right to life and health of victims,and therefore to provide access to treatment for post-exposure prophylaxis of HIV,prevention of pregnancy, prevention of sexually transmitted diseases through the mechanismof intellectual property rights, namely to increase the availability of generic antiretroviraldrugs in accordance with the requirements of the TRIPS Agreement. Intellectual property rights play an important role in times of war in expanding accessto medicines and medical devices. It is significant to emphasize the importance andtimeliness of applying the mechanisms of limitation of intellectual property rights tosave people's health, as war is one of the factors that allows a TRIPS Agreement Memberto use Article 73. Article 73 of the TRIPS Agreement provides for security exceptions thatMember States may invoke to defend their non-compliance with the TRIPS Agreement.This provision is unique in the context of international intellectual property law. The applicationof such mechanisms will allow the state to treat more people who need immediateprevention and treatment. In our opinion, the application of this provision means theapplication of the security exception to suspend the rights of patent holders to facilitateeither the import or local production of essential medicines and medical devices.
Bio-inspired aptamers decorated gold nanoparticles enable visualized detection of malathion
Authors: Li Peng , Zhan Haonan , Tao Sijian , Xie Zhuohao , Huang Jiahao 
Published: March 2023

Biosensors always respond to the targets of interest in a specific manner, employing biological or bio-mimic recognition elements such as antibodies and aptamers. Inspired by target recognition in nature, an aptamer-mediated, gold nanoparticle-based sensing approach is developed in this work for effective determination of malathion. The sensing system consists of negatively charged aptamer probes, and polycationic proteins, protamine, as well as exceptional colorimetric nanoprobes, barely gold nanoparticles (AuNPs). Protamine molecules bound to aptamer probes hinder the aggregation of AuNPs, while no such inhibition is maintained when aptamer-specific malathion is introduced into the solution, thus leading to the solution colour change from red to blue observable by the naked eye. The assay is accomplished via a mix-and-measure step within 40 min with a detection limit as low as 1.48 μg/L (3σ/s rule). The assay method also exhibits high selectivity and good applicability for the quantification of malathion in tap water with recovery rates of 98.9%–109.4%. Additionally, the good detection accuracy is also confirmed by the high-performance liquid chromatography method. Therefore, the non-enzymatic, label- and device-free characteristics make it a robust tool for malathion assay in agricultural, environmental, and medical fields.
Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors
Authors: Zhang Yifan , Cheng Siyuan , Zou Hua , Han Zihan , Xie Tong , Zhang Bohan , Dai Die , Yin Xiaochen , Liang Yong , Kou Yan , Tan Yan , Shen Lin , Peng Zhi 
Published: March 2023

IntroductionThe wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.MethodsIn this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.ResultsIn summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.
Inhibition of signal peptidase complex expression affects the development and survival of Schistosoma japonicum
Authors: Yang Wen-Bin , Luo Fang , Zhang Wei , Sun Cheng-Song , Tan Cong , Zhou An , Hu Wei 
Published: March 2023

BackgroundSchistosomiasis, the second most neglected tropical disease defined by the WHO, is a significant zoonotic parasitic disease infecting approximately 250 million people globally. This debilitating disease has seriously threatened public health, while only one drug, praziquantel, is used to control it. Because of this, it highlights the significance of identifying more satisfactory target genes for drug development. Protein translocation into the endoplasmic reticulum (ER) is vital to the subsequent localization of secretory and transmembrane proteins. The signal peptidase complex (SPC) is an essential component of the translocation machinery and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. Inhibiting the expression of SPC can lead to the abolishment or weaker cleavage of the signal peptide, and the accumulation of uncleaved protein in the ER would affect the survival of organisms. Despite the evident importance of SPC, in vivo studies exploring its function have yet to be reported in S. japonicum.MethodsThe S. japonicum SPC consists of four proteins: SPC12, SPC18, SPC22 and SPC25. RNA interference was used to investigate the impact of SPC components on schistosome growth and development in vivo. qPCR and in situ hybridization were applied to localize the SPC25 expression. Mayer’s carmalum and Fast Blue B staining were used to observe morphological changes in the reproductive organs of dsRNA-treated worms. The effect of inhibitor treatment on the worm’s viability and pairing was also examined in vitro.ResultsOur results showed that RNAi-SPC delayed the worm's normal development and was even lethal for schistosomula in vivo. Among them, the expression of SPC25 was significantly higher in the developmental stages of the reproductive organs in schistosomes. Moreover, SPC25 possessed high expression in the worm tegument, testes of male worms and the ovaries and vitellarium of female worms. The SPC25 knockdown led to the degeneration of reproductive organs, such as the ovaries and vitellarium of female worms. The SPC25 exhaustion also reduced egg production while reducing the pathological damage of the eggs to the host. Additionally, the SPC-related inhibitor AEBSF or suppressing the expression of SPC25 also impacted cultured worms’ pairing and viability in vitro.ConclusionsThese data demonstrate that SPC is necessary to maintain the development and reproduction of S. japonicum. This research provides a promising anti-schistosomiasis drug target and discovers a new perspective on preventing worm fecundity and maturation.
Association between thyroid cancer and cardiovascular disease: A meta-analysis
Authors: Tsai Wen-Hsuan , Zeng Yi-Hong , Lee Chun-Chuan , Chien Ming-Nan , Liu Sung-Chen , Chien Kuo-Liong , Cheng Shih-Ping , Tseng Po-Jung , Tsai Ming-Chieh 
Published: March 2023

ObjectiveTo determine the association between thyroid cancer and coronary artery disease, atrial fibrillation, cerebrovascular disease, and cardiovascular disease mortality.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to September 22, 2022. Keywords included “thyroid cancer”, “atrial fibrillation”, “coronary artery disease”, “cerebrovascular disease”, and “mortality”. Primary outcomes included the incidence of coronary artery disease, cerebrovascular disease, atrial fibrillation, and cardiovascular disease mortality among patients with thyroid cancer. Secondary outcomes included cardiovascular disease events among those with thyroid cancer that received or did not receive radioactive iodine or lenvatinib. Estimates were pooled using fixed- and random-effects meta-analysis.ResultsA total of 771,220 patients who underwent thyroidectomy in 15 studies were included. Risk for cerebrovascular disease (risk ratio [RR] 1.15 [95% confidence interval (CI) 1.10–1.21]) and atrial fibrillation [RR 1.59 (95% CI: 1.45–1.73)] were significantly increased. Risk for coronary artery disease was significantly increased [RR 1.12 (95% CI: 1.08–1.17)] in the common effect model. Cardiovascular disease mortality associated with thyroid cancer was not significant [RR 0.93 (95% CI: 0.59–1.45)]. Radioactive iodine had a neutral effect on cardiovascular disease [RR 1.00 (95% CI: 0.87–1.16)], and there was no beneficial nor harmful effect among different RAI doses.ConclusionsThyroid cancer was significantly associated with a higher risk for cerebrovascular disease and atrial fibrillation; however, the hazard risk was not different between patients with and without radioactive iodine treatment. Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health.
Use of ablation-season albedo as an indicator of annual mass balance of four glaciers in the Tien Shan
Authors: Yue Xiaoying , Li Zhongqin , Wang Feiteng , Li Huilin 
Published: March 2023

Glacier mass balance and its sensitivity to climate change depend to a large degree on the albedo and albedo feedback. Although recent increasing studies reconstruct the annual surface mass balance (SMB) based on the relationships between satellite-derived minimum albedo and annual glaciological mass balance (so-called albedo method), a relationship remains conjectural for Tien Shan glaciers. Accumulation and ablation occur simultaneously in summer, causing different surface processes. We examine this relationship using glaciological mass-balance data and the equilibrium-line altitude (ELA) made on the eastern branch of Urumqi Glacier No. 1 (UG1-E), Tuyuksu, Golubin and Glacier No. 354, and ablation-season (May–September) albedo retrieved from Moderate Resolution Imaging Spectroradiometer (MODIS) images from 2000 to 2021. Compared with minimum ablation-season albedo, we find higher coefficients of determination between mean ablation-season albedo and glaciological mass balance at UG1-E and Tuyuksu. In contrast, for Golubin and Glacier No. 354, glaciological mass balance is higher correlated to minimum ablation-season albedo than mean ablation-season albedo. This difference is related to the glaciological mass-balance time period. The relationship between albedo and glaciological mass balance is obtained over a shorter time for Golubin (8 years) and Glacier No. 354 (9 years) than for UG1-E (20 years) and Tuyuksu (20 years). Non-etheless, based on the correlativity between MODIS-derived mean ablation-season albedo and minimum ablation-season albedo and glaciological mass balance of Golubin and Glacier No. 354 over the 2011–2019 period, the annual SMB for these glaciers can be reconstructed using the albedo method over the period 2000–2010. Comparison with previously reconstructed results indicated that the mass balance derived from albedo is robust for Glacier No. 354, while for Golubin, the results derived from the albedo method only captured the relative changes in mass balance. The current study suggested that ablation-season albedo can be regarded as a proxy for annual mass balance, and mean ablation-season albedo may be more reliable than minimum ablation-season albedo for some Tien Shan glaciers.
Genome-wide association study for the primary feather color trait in a native Chinese duck
Authors: Sun Yanfa , Wu Qiong , Lin Rulong , Chen Hongping , Zhang Min , Jiang Bingbing , Wang Yaru , Xue Pengfei , Gan Qiuyun , Shen Yue , Chen Feifan , Liu Jiantao , Zhou Chenxin , Lan Shishi , Pan Haozhe , Deng Fan , Yue Wen , Lu Lizhi , Jiang Xiaobing , Li Yan 
Published: March 2023

Background: To reveal candidate genes and the molecular genetic mechanism underlying primary feather color trait in ducks, a genome-wide association study (GWAS) for the primary feather color trait was performed based on the genotyping-by-sequencing (GBS) technology for a native Chinese female duck, Longyan Shan-ma ducks.Methods: Blood genomic DNA from 314 female Longyan Shan-ma duck were genotyped using GBS technology. A GWAS for the primary feather color trait with genome variations was performed using an univariate linear mixed model based on all SNPs in autosomes.Results: Seven genome-wide significant single nucleotide polymorphisms (SNPs, Bonferroni-adjusted p-value &lt;8.03 × 10−7) within the introns of the genes STARD9, ZNF106, SLC7A5, and BANP genes were associated with the primary feather color trait. Twenty-two genome-wide suggestive SNPs (Bonferroni-adjusted p-value &lt;1.61 × 10−5) of 17 genes (besides ZNF106 and SLC7A5) were also identified. Seven SNPs were located at one 0.22 Mb region (38.65–38.87 Mb) on chromosome 5, and six SNPs were located at one 0.31 Mb region (19.53–19.84 Mb) on chromosome 11. The functions of STARD9, SLC7A5, BANP, LOC101798015, and IPMK were involved pigmentation and follicle development, especially, STARD9 upregulated expression in black feather (haplotype-CCCC) bulb tissue compared with in pockmarked feather (haplotype-TGTT) bulb tissue, implicating these genes as candidate genes for primary feather color trait.Conclusion: The preliminarily findings suggested candidate genes and regions, and the genetic basis of primary feather color trait in a female duck.
Case report: Long-read sequencing identified a novel 14.9-kb deletion of the α-globin gene locus in a family with α-thalassemia in China
Authors: Yuan Yan , Zhou Xia , Deng Jing , Zhu Qun , Peng Zanping , Chen Liya , Zou Ya , Mao Aiping , Meng Wanli , Ma Minhui , Wu Hongliang 
Published: March 2023

Background: Thalassemia is a hereditary blood disease resulting from globin chain synthesis impairment because of α- and/or β-globin gene variants. α-thalassemia is characterized by non-deletional and deletional variants in the HBA gene locus, of which rare deletional variants are difficult to detect by conventional polymerase chain reaction (PCR)-based methods.Case report: We report the case of a one-month-old boy, who and his mother had abnormal hematological parameters, while his father had normal hematology. Conventional PCR-reverse dot blot (RDB) was performed for all family members to analyze the 23 most common thalassemia variants in China, but did not identify any pathologic variants. Single-molecule real-time (SMRT) long-read sequencing (LRS) technology was then performed and identified an unreported 14.9-kb large deletion (hg38 chr16:168,803-183,737) of the α-globin gene locus, which disrupted both HBA1 and HBA2 genes in the proband and his mother. The exact breakpoints of the deletion were confirmed by gap-PCR and Sanger sequencing.Conclusion: We have detected a novel large deletion in α-globin gene locus in China, which not only enriches the variant spectrum of thalassemia, but also demonstrates the accuracy and efficiency of LRS in detecting rare and novel deletions.
Mechanismbased role of the intestinal microbiota in gestational diabetes mellitus: A systematic review and meta-analysis
Authors: Yan Min , Guo Xiaoying , Ji Guiyuan , Huang Rui , Huang Dongyi , Li Zhifeng , Zhang Dantao , Chen Siyi , Cao Rong , Yang Xingfen , Wu Wei 
Published: March 2023

BackgroundMetabolic disorders caused by intestinal microbial dysregulation are considered to be important causes of gestational diabetes mellitus (GDM). Increasing evidence suggests that the diversity and composition of gut microbes are altered in disease states, yet the critical microbes and mechanisms of disease regulation remain unidentified.MethodsPubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, the Netherlands), the Web of Science™ (Clarivate™, Philadelphia, PA, USA), and the Cochrane Library databases were searched to identify articles published between 7 July 2012 and 7 July 2022 reporting on case–control and controlled studies that analyzed differences in enterobacteria between patients with GDM and healthy individuals. Information on the relative abundance of enterobacteria was collected for comparative diversity comparison, and enterobacterial differences were analyzed using random effects to calculate standardized mean differences at a p-value of 5%.ResultsA total of 22 studies were included in this review, involving a total of 965 GDM patients and 1,508 healthy control participants. Alpha diversity did not differ between the participant groups, but beta diversity was significantly different. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the dominant bacteria, but there was no significant difference between the two groups. Qualitative analysis showed differences between the groups in the Firmicutes/Bacteroidetes ratio, Blautia, and Collinsella, but these differences were not statistically different.ConclusionEnterobacterial profiles were significantly different between the GDM and non-GDM populations. Alpha diversity in patients with GDM is similar to that in healthy people, but beta diversity is significantly different. Firmicutes/Bacteroidetes ratios were significantly increased in GDM, and this, as well as changes in the abundance of species of Blautia and Collinsella, may be responsible for changes in microbiota diversity. Although the results of our meta-analysis are encouraging, more well-conducted studies are needed to clarify the role of the gut microbiome in GDM. The systematic review was registered with PROSPERO (https://www.crd.york.ac.uk/prospero/) as CRD42022357391.