bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of the international protection of technical means of protection
Authors: Drobiazko Volodymyr 
Published: October 2021

Drobyazko V. Formation of the international protection of technical means of protection. The statute considers the establishment of international protection of technical means of protection in the field of copyright and related rights, analyzes the relevant WIPO documents, the provisions of articles 11 of the WIPO Copyright Treaty (WCT) and 18 of the WIPO Performances and Phonograms Treaty (WPPT), their innovative character is justified, The analysis of the provisions of the Law of Ukraine «On Copyright and Related Rights» on the protection of technical means of protection of works and objects of related rights is carried out.
Technical means are effective when the use of a protected work or an object of related rights is controlled by the owner of the rights by applying access control or aprotection method, such as encoding, or such as a copy control mechanism for the purpose of protection.According to Article 11 of the WCT and Article 18 of the WPPT, the Contracting Parties shall offer for proper legal protection and effective remedies against circumventing existing technical means used by holders of rights in connection with the exercise of their rights under these agreements and restricting actions with regard to their works, performances or phonograms, which are not permitted by them or are not permitted by law.In the process of enforcing these treaties, it became clear that it was impossible to offer legal protection and effective legal remedies against circumvention if the protection and legal remedies did not extend to preparatory actions. That is, legal protection and effective legal remedies should also be provided for protection against the manufacture, import, distribution, sale, rental, advertising for sale or rental, or for the commercial use of devices, products or components, or from providing services that: promote, advertise, or sell in rounds; or have only a limited commercial business a significant purpose, or use, other than to get around; or are primarily designed, manufactured, remade, or implemented to offer a workaround or to aid in bypassing any effective technical means.Keywords: copyright, related rights, technical remedies, circumvention, effectiveactions against violation of rights
A Novel Plant Leaf Patch Absorbed With IL-33 Antibody Decreases Venous Neointimal hyperplasia
Authors: Xie Boao , Bai Xiche , Sun Peng , Zhang Liwei , Wei Shunbo , Bai Hualong 
Published: October 2021

Introduction: We recently showed that a decellularized leaf scaffold can be loaded with polylactic-co-glycolic acid (PLGA)-based rapamycin nanoparticles, this leaf patch can then inhibit venous neointimal hyperplasia in a rat inferior vena cava (IVC) venoplasty model. IL-33 plays a role in the neointimal formation after vascular injury. We hypothesized that plant leaves can absorb therapeutic drug solution and can be used as a patch with drug delivery capability, and plant leaves absorbed with IL-33 antibody can decrease venous neointimal hyperplasia in the rat IVC venoplasty model.Method: A human spiral saphenous vein (SVG) graft implanted in the popliteal vein was harvested from a patient with trauma and analyzed by immunofluorescence. Male Sprague-Dawley rats (aged 6–8 weeks) were used to create the IVC patch venoplasty model. Plant leaves absorbed with rhodamine, distilled water (control), rapamycin, IL-33, and IL-33 antibody were cut into patches (3 × 1.5 mm2) and implanted into the rat IVC. Patches were explanted at day 14 for analysis.Result: At day 14, in the patch absorbed with rhodamine group, immunofluorescence showed rhodamine fluorescence in the neointima, inside the patch, and in the adventitia. There was a significantly thinner neointima in the plant patch absorbed with rapamycin (p = 0.0231) compared to the patch absorbed with distilled water. There was a significantly large number of IL-33 (p = 0.006) and IL-1β (p = 0.012) positive cells in the human SVG neointima compared to the human great saphenous vein. In rats, there was a significantly thinner neointima, a smaller number of IL-33 (p = 0.0006) and IL-1β (p = 0.0008) positive cells in the IL-33 antibody-absorbed patch group compared to the IL-33-absorbed patch group.Conclusion: We found that the natural absorption capability of plant leaves means they can absorb drug solution efficiently and can also be used as a novel drug delivery system and venous patch. IL-33 plays a role in venous neointimal hyperplasia both in humans and rats; neutralization of IL-33 by IL-33 antibody can be a therapeutic method to decrease venous neointimal hyperplasia.
Plasma Metabolomics Reveals Metabolic Profiling For Diabetic Retinopathy and Disease Progression
Authors: Sun Yu , Zou Huiling , Li Xingjia , Xu Shuhang , Liu Chao 
Published: October 2021

BackgroundsDiabetic retinopathy (DR), the main retinal vascular complication of DM, is the leading cause of visual impairment and blindness among working-age people worldwide. The aim of this study was to investigate the difference of plasma metabolic profiles in patients with DR to better understand the mechanism of this disease and disease progression.MethodsWe used ultrahigh-performance liquid Q-Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of plasma metabolites in a population with DR and proliferative DR (PDR). A risk score based on the level of the selected metabolite was established and evaluated using the least absolute shrinkage and selection operator regularization logistic regression (LASSO-LR) based machine learning model.Results22 differentially expressed metabolites which belonged to different metabolic pathway were identified and confirmed to be associated with the occurrence of DR. A risk score based on the level of the selected metabolite pseudouridine was established and evaluated to strongly associated with the occurrence of DR. Four circulating plasma metabolites (pseudouridine, glutamate, leucylleucine and N-acetyltryptophan) were identified to be differentially expressed between patients with PDR and other patients, and a risk score formula based on these plasma metabolites was developed and assessed to be significantly related to PDR.ConclusionsOur work highlights the possible use of the risk score assessment based on the plasma metabolites not only reveal in the early diagnosis of DR and PDR but also assist in enhancing current therapeutic strategies in the clinic.
Metallic Iron for Environmental Remediation: The Fallacy of the Electron Efficiency Concept
Authors: Hu Rui , Ndé-Tchoupé Arnaud Igor , Cao Viet , Gwenzi Willis , Noubactep Chicgoua 
Published: October 2021

The suitability of remediation systems using metallic iron (Fe0) has been extensively discussed during the past 3 decades. It has been established that aqueous Fe0 oxidative dissolution is not caused by the presence of any contaminant. Instead, the reductive transformation of contaminants is a consequence of Fe0 oxidation. Yet researchers are still maintaining that electrons from the metal body are involved in the process of contaminant reduction. According to the electron efficiency concept, electrons from Fe0 should be redistributed to: i) contaminants of concern (COCs), ii) natural reducing agents (e.g., H2O, O2), and/or iii) reducible co-contaminants (e.g. NO3-). The electron efficiency is defined as the fraction of electrons from Fe0 oxidation which is utilized for the reductive transformations of COCs. This concept is in frontal contradiction with the view that Fe0 is not directly involved in the process of contaminant reduction. This communication recalls the universality of the concept that reductive processes observed in remediation Fe0/H2O systems are mediated by primary (e.g., FeII, H/H2) and secondary (e.g., Fe3O4, green rusts) products of aqueous iron corrosion. The critical evaluation of the electron efficiency concept suggests that it should be abandoned. Instead, research efforts should be directed towards tackling the real challenges for the design of sustainable Fe0-based water treatment systems based on fundamental mechanisms of iron corrosion.
Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis
Authors: Lin Tong , Zhang Yingzhao , Lin Zhimei , Peng Lisheng 
Published: October 2021

Background: High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear.Methods: Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms.Results: HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for HMGB1 in ACC; HMGB2 in ACC, LGG, LIHC, and SKCM; and HMGB3 in ESCA. Prognostic values were also found for HMGB2 in KIRP and MESO and HMGB3 in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events.Conclusion: This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.
Automated Identification of Skull Fractures With Deep Learning: A Comparison Between Object Detection and Segmentation Approach
Authors: Shan Wei , Guo Jianwei , Mao Xuewei , Zhang Yulei , Huang Yikun , Wang Shuai , Li Zixiao , Meng Xia , Zhang Pingye , Wu Zhenzhou , Wang Qun , Liu Yaou , He Kunlun , Wang Yongjun 
Published: October 2021

Objective: Skull fractures caused by head trauma can lead to life-threatening complications. Hence, timely and accurate identification of fractures is of great importance. Therefore, this study aims to develop a deep learning system for automated identification of skull fractures from cranial computed tomography (CT) scans.Method: This study retrospectively analyzed CT scans of 4,782 patients (median age, 54 years; 2,583 males, 2,199 females; development set: n = 4,168, test set: n = 614) diagnosed with skull fractures between September 2016 and September 2020. Additional data of 7,856 healthy people were included in the analysis to reduce the probability of false detection. Skull fractures in all the scans were manually labeled by seven experienced neurologists. Two deep learning approaches were developed and tested for the identification of skull fractures. In the first approach, the fracture identification task was treated as an object detected problem, and a YOLOv3 network was trained to identify all the instances of skull fracture. In the second approach, the task was treated as a segmentation problem and a modified attention U-net was trained to segment all the voxels representing skull fracture. The developed models were tested using an external test set of 235 patients (93 with, and 142 without skull fracture).Results: On the test set, the YOLOv3 achieved average fracture detection sensitivity and specificity of 80.64, and 85.92%, respectively. On the same dataset, the modified attention U-Net achieved a fracture detection sensitivity and specificity of 82.80, and 88.73%, respectively.Conclusion: Deep learning methods can identify skull fractures with good sensitivity. The segmentation approach to fracture identification may achieve better results.
Discrete-Event Simulation to Model the Thrombolysis Process for Acute Ischemic Stroke Patients at Urban and Rural Hospitals
Authors: Bulmer Tessa , Volders David , Blake John , Kamal Noreen 
Published: October 2021

Background: Effective treatment with tissue plasminogen activator (tPA) critically relies on rapid treatment. Door-to-needle time (DNT) is a key measure of hospital efficiency linked to patient outcomes. Numerous changes can reduce DNT, but they are difficult to trial and implement. Discrete-event simulation (DES) provides a way to model and determine the impact of process improvements.Methods: A conceptual framework was developed to illustrate the thrombolysis process; allowing for treatment processes to be replicated using a DES model developed in ARENA. Activity time duration distributions from three sites (one urban and two rural) were used. Five scenarios, three process changes, and two reductions in activity durations, were simulated and tested. Scenarios were tested individually and in combinations. The primary outcome measure is median DNT. The study goal is to determine the largest improvement in DNT at each site.Results: Administration of tPA in the imaging area resulted in the largest median DNT reduction for Site 1 and Site 2 for individual test scenarios (12.6%, 95% CI 12.4–12.8%, and 8.2%, 95% CI 7.5–9.0%, respectively). Ensuring that patients arriving via emergency medical services (EMS) remain on the EMS stretcher to imaging resulted in the largest median DNT improvement for Site 3 (9.2%, 95% CI 7.9–10.5%). Reducing both the treatment decision time and tPA preparation time by 35% resulted in a 11.0% (95% CI 10.0–12.0%) maximum reduction in median DNT. The lowest median and 90th percentile DNTs were achieved by combining all test scenarios, with a maximum reduction of 26.7% (95% CI 24.5–28.9%) and 17.1% (95% CI 12.5–21.7%), respectively.Conclusions: The detailed conceptual framework clarifies the intra-hospital logistics of the thrombolysis process. The most significant median DNT improvement at rural hospitals resulted from ensuring patients arriving via EMS remain on the EMS stretcher to imaging, while urban sites benefit more from administering tPA in the imaging area. Reducing the durations of activities on the critical path will provide further DNT improvements. Significant DNT improvements are achievable in urban and rural settings by combining process changes with reducing activity durations.
Molecular Changes in Prader-Willi Syndrome Neurons Reveals Clues About Increased Autism Susceptibility
Authors: Victor A. Kaitlyn , Donaldson Martin , Johnson Daniel , Miller Winston , Reiter Lawrence T. 
Published: October 2021

Background: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hormonal dysregulation, obesity, intellectual disability, and behavioral problems. Most PWS cases are caused by paternal interstitial deletions of 15q11.2-q13.1, while a smaller number of cases are caused by chromosome 15 maternal uniparental disomy (PW-UPD). Children with PW-UPD are at higher risk for developing autism spectrum disorder (ASD) than the neurotypical population. In this study, we used expression analysis of PW-UPD neurons to try to identify the molecular cause for increased autism risk.Methods: Dental pulp stem cells (DPSC) from neurotypical control and PWS subjects were differentiated to neurons for mRNA sequencing. Significantly differentially expressed transcripts among all groups were identified. Downstream protein analysis including immunocytochemistry and immunoblots were performed to confirm the transcript level data and pathway enrichment findings.Results: We identified 9 transcripts outside of the PWS critical region (15q11.2-q13.1) that may contribute to core PWS phenotypes. Moreover, we discovered a global reduction in mitochondrial transcripts in the PW-UPD + ASD group. We also found decreased mitochondrial abundance along with mitochondrial aggregates in the cell body and neural projections of +ASD neurons.Conclusion: The 9 transcripts we identified common to all PWS subtypes may reveal PWS specific defects during neurodevelopment. Importantly, we found a global reduction in mitochondrial transcripts in PW-UPD + ASD neurons versus control and other PWS subtypes. We then confirmed mitochondrial defects in neurons from individuals with PWS at the cellular level. Quantification of this phenotype supports our hypothesis that the increased incidence of ASD in PW-UPD subjects may arise from mitochondrial defects in developing neurons.
The Association of Dietary Energy Density and Body Composition Components in a Sample of Iranian Adults
Authors: Bazshahi Elham , Pourreza Sanaz , Imani Hossein , Azadbakht Leila , Ebaditabar Mojdeh , Davarzani Samira , Babaei Nadia , Naghshi Sina , Djafarian Kurosh , Shab-Bidar Sakineh 
Published: October 2021

Background: We aimed to investigate the association between the energy density (ED) of diet and body composition components in Iranian adults.Methods: We conducted a cross-sectional study on 267 adults in Tehran. We obtained ED (kcal/g) using the two most common methods: ED1, ED from foods only with the exclusion of all beverages and ED2, from foods and all beverages. Body composition was measured using a multifrequency bio-impedance analysis. To find a strong association, we used both the linear and binary regression analysis in the three adjusted models.Results: The mean of ED1 and ED2 was 1.34 ± 0.23 and 0.89 ± 0.20 kcal/g, respectively. Increasing the ED of diet in both methods was associated with a high intake of dietary fat, of saturated fatty acid (SFA), of monounsaturated fatty acid (MUFA), of polyunsaturated fatty acid (PUFA), of oleic and linoleic acids, accompanied by a low intake of fruits, vegetables, and some vitamins and minerals. There was a significant positive relationship between fat-free mass index (FFMI) and ED1 (β = 4.44, p = 0.02). However, we found no significant association between the consumption of ED1 and fat mass index (FMI) (0.28; 95% CI 0.08, 0.98; p = 0.07), and abdominal obesity (0.91; 95% CI 0.43, 1.94; p = 0.82). Also, ED2 had no association with FMI (0.86; 95% CI 0.26, 2.80; p = 0.81) and abdominal obesity (0.78; 95% CI 0.35, 1.72; p = 0.54). No significant associations were found between ED and other anthropometric indices and body composition components after considering the confounders.Conclusion: This study supports the positive association between ED and poor dietary quality. However, our findings did not show significant associations of dietary energy density (DED) with anthropometric indices and body composition components. Further well-designed studies are required to investigate the exact link between DED and body composition.
Hyponatremia During Induction Therapy in Distinct Pediatric Oncological Cohorts: A Retrospective Study
Authors: Salvador Christina , Salvador Robert , Willeit Peter , Kuntner Christine , Haid Alexandra , Müller Thomas , Kropshofer Gabriele , Crazzolara Roman 
Published: October 2021

BackgroundHyponatremia is a well-known adverse event of repeated therapy with vincristine in oncological patients. However, to date, data in pediatric patients with malignant diseases other than acute lymphoblastic leukemia (ALL) are sparse or lacking.Materials and MethodsA retrospective study of 98 pediatric patients was conducted to analyze the incidence of hyponatremia in a Caucasian cohort of newly diagnosed ALL. For comparison, we further examined five other pediatric oncological cohorts (Hodgkin’s disease, Ewing sarcoma, Wilms tumor, benign glioma of the CNS, Langerhans cell histiocytosis) that receive alkaloids in their induction regimes.ResultsWe found a high incidence of hyponatremia (14.7%) in our ALL cohort with a trend toward male patients of elementary school age. None of the affected patients showed neurological symptoms. By comparison, patients from other malignancy groups did not show significant hyponatremia, regardless of their comparable therapy with alkaloids. We here show a noticeable coincidence of hyponatremia and hypertriglyceridemia in ALL patients, indicating a possible role of L-asparaginase-related hypertriglyceridemia in the development of severe hyponatremia in such patients.ConclusionWe report a higher incidence of hyponatremia following vincristine therapy in Caucasian children with ALL than published before. This hyponatremia could not be demonstrated in other oncologic cohorts treated with alkaloids. L-Asparaginase-induced hypertriglyceridemia may play a role in the certainly multifactorial development of hyponatremia in childhood leukemia.
Encouraging Early Outcomes of Treatment With Arsenic Trioxide Combined With Chemotherapy for Alveolar Rhabdomyosarcoma in Children: 4 Case Reports
Authors: Peng Xiaomin , Xiong Xilin , Li Yang , Feng Chuchu , Liu Hongyan , Wu Pingping , Li Chunmou , Weng Wenjun 
Published: October 2021

BackgroundAlveolar rhabdomyosarcoma (ARMS) is a subtype of rhabdomyosarcoma characterized by its aggressive behavior and poor prognosis, highlighting the need for novel treatment options. Arsenic trioxide (ATO) has been shown to specifically inhibit tumor growth and the metastasis of ARMS in vitro by acting on the hedgehog pathway. Here we report on a pilot clinical study to evaluate the activity of an ATO-combined chemotherapy approach for the treatment of ARMS patients.MethodsWe designed a therapeutic schedule of an ATO-combined chemotherapy, incorporating comprehensive management according to the Intergroup Rhabdomyosarcoma Study Group protocol. ATO was administered at 0.16 mg/kg per day over 8 h via an IV for 10 days combined with a chemotherapeutic regimen of vincristine, actinomycin, and cyclophosphamide (VAC regimen) on the third day, which was repeated every 21 days. A total of eight cycles of ATO-combined chemotherapy were applied throughout the entire scheme.ResultsA total of three refractory/recurrent and one untreated ARMS patient, three male and one female, with a median age of 5.8 years (range, 5.1 to 12.5 years), were enrolled in the present study. All patients were sensitive to combined chemotherapy with ATO and achieved partial or complete remission during treatment. Except for reversible gastrointestinal reaction and myelosuppression, no other adverse events were observed during the process of treatment.ConclusionsThe combined chemotherapy of ATO and the VAC regimen exhibited beneficial activities against ARMS in pediatrics and was well tolerated, but prospective large-scale clinical trials are warranted to determine the long-term efficacy, optimal courses, and late toxicity in this population.