bluuebunny/crossref_metadata_2025_split huggingface dataset:
The legal and organizational principles of attestation of candidates to patent attorneys
Authors: Kulinich Olha , Pototskyi Mykola 
Published: March 2023

Keywords: intellectual property, attestation, representation, legal status, patent attorneys
The article is devoted to the study of the organizational and legal principles of attestation of candidates to patent attorneys in Ukraine. The article analyses formation and development of the institute of patent attorneys in the context of obtaining the legal status of a patent attorney and adducesperiodization of the stages of development of the attestation procedure from 1994 to2022. The possibility is substantiated of conditional distinguishing of four stages. The first stage of formation of legal bases of the institute of patent attorneys in Ukraine (1994−1996) is connected with creation of legal bases of functioning of the institute, definition of standard and requirements for obtaining the legal status of a patent attorney, introduction of procedure of attestation of candidates to patent attorneys, formation of community of patent attorneys. The second stage of the development of the institute of patent attorneys conditionallylasted from 1996 to 2016 and is conditionally characterized as a period of strong development of the patent attorneys community, in particular by regular attestation, the creation of the first professional association of patent attorneys and their active assistance in the development of intellectual property protection.
The third stage, which has been ongoing from 2017 to the present, is actually characterized by the suspension of attestation and the block of the possibility of obtaining the legal status of a patent attorney. It has been established that the result of the reform of the system of legal protection of intellectual property, in particular the liquidation of the State Intellectual Property Service and the subordination of the relevant sphere of intellectual property to the competence of the Ministry of Economy, was the suspension of the attestation procedure. The exclusion from participation in the attestation procedure of the educationalinstitution, based on which attestation and transfer of the relevant functions to the subordinate enterprise took place, partially complicated the continuation of the attestation procedure. The expulsion from participation of the educational institution in the attestation procedure, because of which the attestation took place and transfer of the relevant functions to the subordinate enterprise, partially complicated the continuation of the attestation procedure. The attention has been drawn to the absence of the corresponding order of the Ministry of Economy on the approval of composition of the Attestation and the Appeal Commission. The authors have described the prospects for the development of the attestation procedure at the fourth stage, which can tentatively begin in 2022.
Hyaluronic acid-based bioink improves the differentiation and network formation of neural progenitor cells
Authors: Pereira Inês , Lopez-Martinez Maria J. , Villasante Aranzazu , Introna Clelia , Tornero Daniel , Canals Josep M. , Samitier Josep 
Published: March 2023

Introduction: Three-dimensional (3D) bioprinting is a promising technique for the development of neuronal in vitro models because it controls the deposition of materials and cells. Finding a biomaterial that supports neural differentiation in vitro while ensuring compatibility with the technique of 3D bioprinting of a self-standing construct is a challenge.Methods: In this study, gelatin methacryloyl (GelMA), methacrylated alginate (AlgMA), and hyaluronic acid (HA) were examined by exploiting their biocompatibility and tunable mechanical properties to resemble the extracellular matrix (ECM) and to create a suitable material for printing neural progenitor cells (NPCs), supporting their long-term differentiation. NPCs were printed and differentiated for up to 15 days, and cell viability and neuronal differentiation markers were assessed throughout the culture.Results and Discussion: This composite biomaterial presented the desired physical properties to mimic the ECM of the brain with high water intake, low stiffness, and slow degradation while allowing the printing of defined structures. The viability rates were maintained at approximately 80% at all time points. However, the levels of β-III tubulin marker increased over time, demonstrating the compatibility of this biomaterial with neuronal cell culture and differentiation. Furthermore, these cells showed increased maturation with corresponding functional properties, which was also demonstrated by the formation of a neuronal network that was observed by recording spontaneous activity via Ca2+ imaging.
Biomechanical study of internal fixation methods for femoral neck fractures based on Pauwels angle
Authors: Wang Fuyang , Liu Yuchen , Huo Yi , Wang Ziming , Zhang Jinge , Xu Minghao , Ma Kaiming , Wang Linbao , Lu Yongtao , Cheng Liangliang , Zhao Dewei 
Published: March 2023

Objective: To select the most appropriate internal fixation method based on the Pauwels angle, in order to provide a new concept for clinical accurate treatment of femoral neck fractures (FNFs).Methods: FNFs models of Pauwels 30°; 40°; 50°; 60° were created respectively. For Pauwels ≤ 50°, 1, 2 and 3 Cannulated Compression Screws (CCS) and Porous Tantalum Screws (PTS) were used to fix the fracture for the models. For Pauwels 60°, 3CCS and Medial Buttress Plate (MBP) combined with 1, 2 and 3CCS were used to fix the fracture. Based on the results of the finite element (FE) analysis, the biomechanical properties of each model were compared by analyzing and evaluating the following four parameters: maximal stress of the bone (MBS), maximal stress of the implants (MIS), maximal displacement of bone (MBD), interfragmentary motion (IFM).Results: At Pauwels 30°, the larger parameters were found in 1CCS, which was 94.8 MPa (MBS), 307.7 MPa (MIS), 0.86 mm (MBD) and 0.36 mm (IFM). In 2CCS group, the parameters were 86.1 MPa (MBS), 254.4 MPa (MIS), 0.73 mm (MBD) and 0.27 mm (IFM), which were similar to those of PTS. At Pauwels 40°; 50°, with the increase of the number of used CCS, accordingly, the parameters decreased. Particularly, the MIS (Pauwels 50°) of 1CCS was 1,195.3 MPa, but the other were less than the yield range of the materials. At Pauwels 60°, the MBS of 3CCS group was 128.6 Mpa, which had the risk of failure. In 2CCS + MBP group, the parameters were 124.2 MPa (MBS), 602.5 MPa (MIS), 0.75 mm (MBD) and 0.48 mm (IFM), The model stability was significantly enhanced after adding MBP.Conclusion: Pauwels type Ⅰ (&lt;30°) fractures can reduce the number of CCS, and PTS is an appropriate alternative treatment. For Pauwels type Ⅱ fractures (30°∼50°), the 3CCS fixation method is still recommended. For Pauwels type Ⅲ fractures (&gt;50°), it is recommended to add MBP to the medial femoral neck and combine with 2CCS to establish a satisfactory fracture healing environment.
Chemical, biological and in silico assessment of date (P. dactylifera L.) fruits grown in Ha’il region
Authors: Alsukaibi Abdulmohsen Khalaf Dhahi , Alenezi Khalaf M. , Haque Ashanul , Ahmad Irfan , Saeed Mohd , Verma Mahima , Ansari Irfan Ahmad , Hsieh Ming-Fa 
Published: March 2023

Background: Dates palm (Phoenix dactylifera L.) fruits are among the most widely used fruits in the Middle East and African nations. Numerous researchers confirmed the presence of phytochemicals in P. dactylifera L. fruit and its by-products with broad-ranging biological activities.Objectives: In the present work, phytochemical and biological assessments of two different cultivars of date fruit (ShishiM1 and MajdoolM2 grown in the Ha’il region of Saudi Arabia) have been carried out.Methods: Date fruits were extracted and analyzed by gas chromatography-mass spectrometry (GS-MS),liquid chromatography-mass spectrometry (LC-MS) and Fourier-transform infrared spectroscopy (FT-IR)techniques. The lyophilized methanolic extracts were analyzed for their in-vitro antiproliferative andcytotoxicity against colon cancer (HCT116) cell line. To identify the possible constituents responsible for the bioactivity, in-silico molecular docking and molecular dynamics (MD) simulation studies were carried out.Results: Both cultivars exhibited in-vitro anticancer activity (IC50 = 591.3 μg/mL and 449.9 μg/mL for M1 and M2, respectively) against colon cancer HCT-116 cells. The computational analysis results indicated procyanidin B2 and luteolin-7-O-rutinoside as the active constituents.Conclusion: Based on these results, we conclude that these cultivars could be a valuable source for developing health promoter phytochemicals, leading to the development of the Ha’il region, Saudi Arabia.
Computed tomography–based COVID–19 triage through a deep neural network using mask–weighted global average pooling
Authors: Zhang Hong-Tao , Sun Ze-Yu , Zhou Juan , Gao Shen , Dong Jing-Hui , Liu Yuan , Bai Xu , Ma Jin-Lin , Li Ming , Li Guang , Cai Jian-Ming , Sheng Fu-Geng 
Published: March 2023

BackgroundThere is an urgent need to find an effective and accurate method for triaging coronavirus disease 2019 (COVID-19) patients from millions or billions of people. Therefore, this study aimed to develop a novel deep-learning approach for COVID-19 triage based on chest computed tomography (CT) images, including normal, pneumonia, and COVID-19 cases.MethodsA total of 2,809 chest CT scans (1,105 COVID-19, 854 normal, and 850 non-3COVID-19 pneumonia cases) were acquired for this study and classified into the training set (n = 2,329) and test set (n = 480). A U-net-based convolutional neural network was used for lung segmentation, and a mask-weighted global average pooling (GAP) method was proposed for the deep neural network to improve the performance of COVID-19 classification between COVID-19 and normal or common pneumonia cases.ResultsThe results for lung segmentation reached a dice value of 96.5% on 30 independent CT scans. The performance of the mask-weighted GAP method achieved the COVID-19 triage with a sensitivity of 96.5% and specificity of 87.8% using the testing dataset. The mask-weighted GAP method demonstrated 0.9% and 2% improvements in sensitivity and specificity, respectively, compared with the normal GAP. In addition, fusion images between the CT images and the highlighted area from the deep learning model using the Grad-CAM method, indicating the lesion region detected using the deep learning method, were drawn and could also be confirmed by radiologists.ConclusionsThis study proposed a mask-weighted GAP-based deep learning method and obtained promising results for COVID-19 triage based on chest CT images. Furthermore, it can be considered a convenient tool to assist doctors in diagnosing COVID-19.
Enhancing urinary tract infection diagnosis for negative culture patients with metagenomic next-generation sequencing (mNGS)
Authors: Jia Kaipeng , Huang Shiwang , Shen Chong , Li Hongjun , Zhang Zhe , Wang Lei , Zhao Gangjian , Wu Zhouliang , Lin Yuda , Xia Han , Tang Mingze , Yang Huifen , Hu Hailong 
Published: March 2023

BackgroundMetagenomic next-generation sequencing (mNGS) is a promising technology that allows unbiased pathogen detection and is increasingly being used for clinical diagnoses. However, its application in urinary tract infection (UTI) is still scarce.MethodsThe medical records of 33 patients with suspected UTI who were admitted to the Second Hospital of Tianjin Medical University from March 2021 to July 2022 and received urine mNGS were retrospectively analyzed. The performance of mNGS and conventional urine culture in diagnosing infection and identifying causative organisms was compared, and the treatment effects were evaluated in terms of changes in urinalyses and urinary symptoms.ResultsIn the detection of bacteria and fungi, mNGS detected at least one pathogen in 29 (87.9%) cases, including 19 (57.6%) with positive mNGS but negative culture results and 10 (30.3%) with both mNGS and culture positive results. The remaining 4 (12.1%) patients were negative by both tests. Overall, mNGS performed better than culture (87.9% vs. 30.3%, P &lt; 0.001). Within the 10 double-positive patients, mNGS matched culture results exactly in 5 cases, partially in 4 cases, and not at all in 1 case. In addition, mNGS detected a broader pathogen spectrum, detecting 26 species compared to only 5 species found in culture. The most abundant bacteria detected by mNGS was Escherichia coli, detected in 9 (27.2%) patients. All anaerobic bacteria, Mycobacterium Tuberculosis and all mixed pathogens were detected by mNGS. The final clinical diagnosis of UTI was made in 25 cases, and the sensitivity of mNGS was significantly higher than culture (100.0% vs 40.0%; P &lt; 0.001) when using the diagnosis as a reference standard; the positive predictive value, negative predictive value and specificity were 86.2%, 100% and 50.0%, respectively. Importantly, targeted antibiotic therapy based on mNGS resulted in significant improvement in urinalyses and urinary symptoms in patients.ConclusionsmNGS is a technology that has shown clear advantages over culture, particularly in the context of mixed infections and UTIs that are difficult to diagnose and treat. It helps to improve the detection of pathogens, guide changes in treatment strategies, and is an effective complement to urine culture.
The role of red blood cell distribution width in predicting coronary artery lesions in pediatric patients with kawasaki disease
Authors: Cai Jianghui , Tang Mi , Shuai Shuping , Zhang Rui , Zhang Hongxi , Yang Yanfeng , Wu MengJun , Liang Hua , Xing Shasha 
Published: March 2023

BackgroundRecent studies have shown that red blood cell distribution width (RDW) has emerged as a novel predictor of cardiovascular diseases. We aim to investigate the association between RDW and the risk of coronary artery lesions (CALs) in pediatric patients with Kawasaki disease (KD).MethodsKD patients were classified as the CALs group (patients with CALs) and non-CALs group (patients without CALs). Differences among the groups were analyzed by Mann-Whitney U-test and Chi-square analysis. The independent risk factors of CALs were identified by multivariate logistic regression analysis, followed by receiver operating characteristic (ROC) curve analysis to calculate the optimal cut-off value.ResultsThe red blood cell distribution width (RDW) and C-reactive protein were significantly higher in the CALs group than those in the non-CALs group (p &lt; 0.01). Multivariate logistic regression analysis revealed that RDW (OR = 5.2, 95% CI, 4.064 to 6.654) was independent risk factors of CALs in KD patients (p &lt; 0.01). The subgroup analysis also confirmed that the high level of RDW was an independent risk factor for the development of CALs in patients with complete and incomplete KD. The ROC analysis showed the optimal cut-off value of RDW for predicting CALs was &gt;13.86%, with a sensitivity of 75.79% and specificity of 92.81% (AUC = 0.869, 95% CI = 0.844–0.892; p &lt; 0.0001).ConclusionsRDW is an independent predictor with high sensitivity and specificity to predict CALs in KD patients. The elevation in RDW level (&gt;13.86%) may be used as novel biomarkers for early predicting CALs in KD patients during the acute phase.
Causal association between sleep traits and the risk of coronary artery disease in patients with diabetes
Authors: Tian Mengyun , Ma Hongchuang , Shen Jiaxi , Hu Teng , Cui Hanbin , Huangfu Ning 
Published: March 2023

Background and aimsThe association between sleep traits and coronary artery disease (CAD) in patients with diabetes has been reported in previous observational studies. However, whether these potential relationships are causal remains unclear. We aim to assess the causal relationship between sleep traits and CAD in diabetic.MethodsGenetic instrumental variables associated with five sleep-related traits (insomnia, sleep duration, ease of getting up, morningness and snoring) were extracted from corresponding genome-wide association studies (GWAS). The associations of genetic variants with CAD were based on 15,666 individuals with diabetes (3,968 CAD cases and 11,696 controls). The primary analysis was derived using the inverse variance weighting method. Further sensitivity analysis was conducted to confirm the robustness and consistency of the main results.ResultsGenetic liability to insomnia was significantly related to the increased risk of CAD in individuals with diabetes [odds ratio (OR): 1.163; 95% CI: 1.072–1.254; p = 0.001]. Suggestive evidence was found for the borderline associations between both sleep duration (OR: 0.629; 95% CI: 0.380–1.042, p = 0.072) and snoring (OR: 1.010, 95% CI: 1.000–1.020, p = 0.050) with CAD risk. However, no consistent evidence was found for the association between ease of getting up and morningness with the risk of CAD in diabetic. Similar results can be verified in most sensitivity analyses.ConclusionsWe provide consistent evidence for the causal effect of insomnia on the increased risk of CAD in individuals with diabetes. The management of sleep health should be emphasized to prevent CAD in diabetic patients.
Circulating insulin-like growth factor-1 and risk of lung diseases: A Mendelian randomization analysis
Authors: Jiang Sujing , Xu Zhiyong , Shi Yueli , Liang Sibei , Jiang Xinyuan , Xiao Mingshu , Wang Kai , Ding Liren 
Published: March 2023

BackgroundInsulin-like growth factor-1 (IGF-1) display a vital role in in the pathogenesis of lung diseases, however, the relationship between circulating IGF-1 and lung disease remains unclear.MethodsSingle nucleotide polymorphisms (SNPs) associated with the serum levels of IGF-1 and the outcomes data of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer and idiopathic pulmonary fibrosis (IPF) were screened from the public genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was then performed to assess the independent impact of IGF-1 exposure on these lung diseases.ResultsTotally, 416 SNPs related to circulating IGF-1 levels among 358,072 participants in UK Biobank. According to a primary casual effects model with MR analyses by the inverse variance weighted (IVW) method, the circulating IGF-1 was demonstrated a significantly related with the risk of asthma (OR, 0.992; 95% CI, 0.985-0.999, P=0.0324), while circulating IGF-1 showed no significant correlation with CODP (OR, 1.000; 95% CI, 0.999-1.001, P=0.758), lung cancer (OR, 0.979, 95% CI, 0.849-1.129, P=0.773), as well as IPIGFF (OR, 1.100, 95% CI, 0.794-1.525, P=0.568).ConclusionThe present study demonstrated that circulating IGF-1 may be causally related to lower risk of asthma.
Quantitative proteomics identified a novel invasion biomarker associated with EMT in pituitary adenomas
Authors: Zhang Yu , Li Lei , Ma Xin , Liu Chenan , Liu Gemingtian , Bie Zhixu , Yang Zhijun , Liu Pinan 
Published: March 2023

BackgroundComplete resection of invasive pituitary adenoma is usually difficult, resulting in a high recurrence rate. Therefore, it is needed to find potential diagnostic markers and therapeutic targets for invasive pituitary adenoma.MethodsWe collected samples from patients with invasive and non-invasive pituitary adenomas from Beijing Tiantan Hospital for protein extraction and quantitative analysis. We identified differential proteins (DEPs) by differential analysis of the two groups. The intersection of differential proteins related to invasion and epithelial-mesenchymal transition (EMT) in the GeneCards database was identified as EMT-DEPs. The protein network of EMT-DEPs was analyzed using the STRING database and Cytoscape software, and the hub EMT-DEPs were obtained by the MCC algorithm of the cytoHubba plugin. Correlation analysis was used to obtain the interpairing proteins among EMT-DEPs, and core EMT-DEPs were identified based on the number of paired proteins. The Venn program was used to identify the intersection of hub EMT-DEPs and core EMT-DEPs as key EMT-DEPs. Finally, a series of analyses plus experiments were used to verify the correlation of the target protein with invasion and EMT in pituitary adenoma.ResultsQuantitative comparison of proteins between invasive and non-invasive pituitary adenomas indicated 833 differential proteins. The overlaps of EMT-related proteins and differential proteins consisted of 46 EMT-DEPs. There were 6 intersections between the hub EMT-DEPs and core EMT-DEPs. Using quantitative protein data and GSE169498 chip, we found that solute carrier family 2 member 1 (SLC2A1) was our target protein. SLC2A1 was significantly correlated with the invasiveness of pituitary adenoma, and the ROC curve was satisfactory. The functions and pathways of SLC2A1 and paired protein enrichment were closely linked to the EMT. Consistently, SLC2A1 expression was significantly and positively correlated with the expression of classical markers of EMT. The final experiment revealed that SLC2A1 was significantly upregulated in invasive pituitary adenoma.ConclusionSLC2A1 is significantly upregulated in invasive pituitary adenoma with satisfactory predictive value. It may regulate EMT. It may be a potential diagnostic marker for invasive pituitary adenoma.
Prognostic biomarker GSTK1 in head and neck squamous cell carcinoma and its correlation with immune infiltration and DNA methylation
Authors: Feng Yao , Zhou Ying-Hui , Zhao Jie , Su Xiao-Lin , Chen Ning-Xin , Zhao Ya-Qiong , Ye Qin , Hu Jing , Ou-Yang Ze-Yue , Zhong Meng-Mei , Yang Yi-Fan , Han Peng-Ju , Guo Yue , Feng Yun-Zhi 
Published: March 2023

Background: Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC.Methods: All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed via survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC).Results: GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC.Conclusion: Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target.