bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Two Novel Genes SNX10 and PTGDS with Cervical Squamous Cell Carcinoma Prognosis
Authors: Jiang Pinping , Cao Ying , Gao Feng , Sun Wei , Liu Jinhui , Xie Manxin , Fu Shilong 
Published: August 2020

Abstract
Background: Cervical cancer (CC) is the primary cause of death in women. This study sought to investigate the therapeutic targets of CC. Methods: We downloaded four gene expression profiles from GEO. The RRA method was used to integrate and screen DEGs between CC and normal samples. Functional analysis was performed by clusterprofiler. We built PPI network by STRING and selected hub modules via MCODE. CMap was used to find molecules with therapeutic potential for CC. We also validated hub genes in GEO datasets, GEPIA, immunohistochemistry. Cox regression analysis, TCGA methylation analysis and ONCOMINE were carried out. ROC curve analysis and GSEA were also done to dig out the significance of hub genes. Results: Functional analysis revealed that DEGs were significantly enriched in binding, cell proliferation, transcriptional activity and cell cycle regulation. PPI network screened 30 prominent proteins, with CDK1 having the strongest association with CC. Cmap showed that apigenin, thioguanine and trichostatin A might be used to treat CC. Eight genes were screened out through GEPIA. Of them, only PTGDS and SNX10 have not been reported in CC related articles. The validation in GEO showed that PTGDS showed low expression in tumor tissues while SNX10 showed high expression in tumor tissues. Their expression profiles were consistent with the results in immunohistochemistry. They can distinguish CC and normal tissue and have good diagnostic efficiency. GSEA showed that the two genes were associated with the chemokine signaling pathway. TCGA methylation analysis showed that patients with low-expressed and hyper-methylated PTGDS had a bad prognosis than the patients with high-expressed and hypo-methylated PTGDS. Cox regression analysis showed that SNX10 and PTGDS were independent prognostic indicators for OS among CC patients. Conclusions: In conclusion, PTGDS and SNX10 showed abnormal expression and methylation in CC. Both genes could be used to develop new target treatments for CC.
Age-Related Changes in the Gut Microbiota Promote Atrial Fibrillation
Authors: Zhang Yun , Zhang Song , Li Bolin , Luo Yingchun , Gong Yongtai , Jin Xuexin , Zhang Jiawei , Zhou Yun , Zhuo Xiaozhen , Wang Zixi , Zhao Xinbo , Han Xuejie , Gao Yunlong , Yu Hui , Liang Desen , Zhao Shiqi , Sun Danghui , Wang Dingyu , Xu Wei , Qu Guangjin , Bo Wanlan , Li Dan , Wu Yue , Li Yue 
Published: August 2020

Abstract
Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.
Design of an Optimally-Diagnostic Skin Test With Fewer Samples for Diagnosis of Sensitivity to Eight Allergens: a First-In-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects
Authors: Ning Xiaoyi , Kuang Yun , Zhao Shuwei , Yang Guoping , Hou Wenjing , Guo Chengxian , Xie Jinlian , Gong Liying , Zhu Xuerui , Cui Chang , Yang Shuang , Yang Xiaoyan , Guo Chengjun , Liu Ruiling , Xiang Yuxiang , Huang Jie 
Published: August 2020

Abstract
Background: Skin prick test is usually the preferred test in the diagnostic workup for allergic diseases, while there are few types of standardized allergen extracts available. Besides, standardization and composition give no assurance that the allergen extracts are within the concentration range that give the best chance of a true diagnosis. We designed a first-in-human diagnostic skin test with fewer samples to identify the optimally diagnostic concentration for eight standardized extracts from frequent native allergens, and to assess the safety of the eight allergens extracts’ simultaneous administration for supporting clinical allergen screening.Methods: Patients aged 18-45 years who had a history of allergic diseases were enrolled in this two-part open-label, parallel study: Study 1, each patient was given three concentrations of one allergen extract in turn. Study 2, each patient was given two concentrations of eight allergens extracts. Negative and positive controls were given each time the allergen was given. Both safety and sensitivity were evaluated to determine the optimally diagnostic concentration. Related-Samples Friedman's Two-Way Analysis was used to evaluate the difference of wheal diameter between different concentrations of each allergen. SPSS Statistics 26 was used for statistical analysis, and the significance test level was 0.05.Results: The sensitivity of allergens increased with the increasing of concentration. The eight investigated allergens showed good safety and did not reach the dose limit toxicity whether used alone or in combination. The optimally diagnostic concentration for eight aeroallergens were respectively determined as 33333 DU/mL, 12000 DU/mL, 8667 DU/mL, 50000 DU/mL, 40000 DU/mL, 3333 DU/mL, 7000 DU/mL, and 5000 DU/mL.Conclusions: This study designed a solution to determine the optimally diagnostic concentration with fewer subjects for further clinical trials of the eight investigated allergens and the results of this phase I clinical trial support further clinical research of investigated allergens. Trial registration: The trial was registered on www.chictr.org.cn (ChiCTR1900023952, 06/19/2019, retrospectively registered).
The Protein Tyrosine Kinase Inhibitor Genistein Suppresses Hypoxia-Induced Atrial Natriuretic Peptide Secretion Mediated by the PI3K/Akt-HIF-1α Pathway in Isolated Beating Rat Atria
Authors: Zhang Qiu-li , Bian Chao-chao , Li Ping , Hong Lan , Liu Li-ping , Cui Bai-ri , Cui Xun 
Published: August 2020

Abstract
Background

Genistein, an isoflavonoid that can inhibit protein tyrosine kinase (PTK) phosphorylation, was proved to play pivotal roles in the signal transduction pathways of hypoxic disorders.
Aim of the stud

y: In this study, we established a rat model of isolated beating atrium and investigated the regulator role of genistein and its downstream signaling pathways in acute hypoxia-induced ANP secretion.
Methods

Radio-immunoassay was used to detect the ANP content in the atrial perfusates. Western blot analysis was used to determine the protein level of hypoxia-inducible factor-1α (HIF-1α), and GATA4 in the atrial tissue.
Results

The results showed that acute hypoxia substantially promoted ANP secretion, whereas this effect was partly attenuated by the PTKs inhibitor genistein (3 µM). By western blotting analysis, we found that hypoxia-induced the increase in phosphorylation of Akt and transcriptional factors, including HIF-1α, were also reversed by genistein. The perfused HIF-1α inhibitors rotenone (0.5 µM) or CAY10585 (10 µM) plus genistein significantly abolished the enhanced ANP section induced by hypoxia. Additionally, the perfused PI3K/Akt agonist IGF-1 (30 µM) also abolished ANP secretion induced by genistein as well as inhibited expression of HIF-1α.
Conclusions

In summary, our data suggested that acute hypoxia markedly increased ANP secretion by PTKs through the PI3K/HIF-1α depended pathway.
Which factors may influence the implementation of drug dispensing in community pharmacies? A qualitative study
Authors: Cerqueira-Santos Sabrina , Rocha Kérlin Stancine Santos , Araújo Dyego Carlos Souza Anacleto , Júnior Genival Araujo Santos , Menezes Pedro Wlisses dos Santos , Sanchez Júlia Mirão , Mesquita Alessandra Rezende , Lyra Divaldo 
Published: August 2020

Abstract
Background: Implementation of clinical pharmacy services, such as drug dispensing, is a complex process. It is necessary to understand the challenges associated with this practice from the perspective of the actors involved to help ensure optimal service provision. Thus, this study aimed to understand the factors that may influence the implementation of drug dispensing in community pharmacies, according to the perceptions of pharmacists. Methods: This qualitative study was based on semi-structured, face-to-face interviews. The participants were pharmacists who worked in a chain of community pharmacies in Brazil, selected based on their direct participation in the implementation process. The interview recordings were transcribed full verbatim and were independently analyzed using thematic analysis, followed by consensus meetings between researchers. The factors identified by the participants were classified according to the Apoteca framework. This study was approved by the Committee of Ethics in Research and all participants signed an informed consent form. Results: We conducted 18 interviews, with 47 factors that may influence the implementation of drug dispensing in community pharmacies being identified. These factors were allocated to seven categories: support from community pharmacy chain (4), pharmacy infrastructure (11), characteristics of the pharmacy, medicines and other health products (4), pharmacist (16), dispensing work process (2), pharmacy team (2), and patient (8). The classification of factors according to the Apoteca framework allocated most of them to administrative (14) and technical (14) domains, followed by attitudinal (13) and political (5) domains. Conclusions: This study identified several factors that can influence the implementation of drug dispensing and classified them according to the domains of the Apoteca framework, highlighting the multifactorial nature of the implementation process. The results of this study can guide the planning of strategies aimed at providing efficient drug dispensing in community pharmacies.
A continuous data driven translational model to evaluate effectiveness of population-level health interventions: case study, smoking ban in public places on hospital admissions for acute coronary events.
Authors: Bonakdari Hossein , Pelletier Jean-Pierre , Martel-Pelletier Johanne 
Published: August 2020

Abstract
Background. An important task in developing accurate public health intervention evaluation methods based on historical interrupted time series (ITS) records is to determine the exact lag time between pre- and post-intervention. We propose a novel continuous transitional data-driven hybrid methodology using a non-linear approach based on a combination of stochastic and artificial intelligence methods that facilitate the evaluation of ITS data without knowledge of lag time. Understanding the influence of implemented intervention on outcome(s) is imperative for decision makers in order to manage health systems accurately and in a timely manner. Methods. To validate a developed hybrid model, we used, as an example, a published dataset based on a real health problem on the effects of the Italian smoking ban in public spaces on hospital admissions for acute coronary events. We employed a continuous methodology based on data preprocessing to identify linear and nonlinear components in which autoregressive moving average and generalized structure group method of data handling were combined to model stochastic and nonlinear components of ITS. We analyzed the rate of admission for acute coronary events from January 2002 to November 2006 using this new data-driven hybrid methodology that allowed for long-term outcome prediction. Results. Our results showed the Pearson correlation coefficient of the proposed combined transitional data-driven model exhibited an average of 17.74% enhancement from the single stochastic model and 2.05% from the nonlinear model. In addition, data demonstrated that the developed model improved the mean absolute percentage error and correlation coefficient values for which 2.77% and 0.89 were found compared to 4.02% and 0.76, respectively. Importantly, this model does not use any predefined lag time between pre- and post-intervention.Conclusions. Most of the previous studies employed the linear regression and considered a lag time to interpret the impact of intervention on public health outcome. The proposed hybrid methodology improved ITS prediction from conventional methods and could be used as a reliable alternative in public health intervention evaluation.
Evaluation of the Spanish Population Coverage of a Prospective HLA Haplobank of Induced Pluripotent Stem Cells.
Authors: Alvarez-Palomo Belen , Garcia-Martinez Iris , Gayoso Jorge , Raya Angel , Veiga Anna , Abad María Luisa , Eiras Adolfo , Guzman-Fulgencio Maria , Luis-Hidalgo Mar , Eguizabal Cristina , Santos Silvia , Balas Antonio , Alenda Raquel , Sanchez-Gordo Francisco , Verdugo Laura Ponce , Villa Juliana , Carreras Enric , Vidal Francisco , Madrigal Alejandro , Herrero María José , Rudilla Francesc , Querol Sergi 
Published: August 2020

Abstract
Background iPSC (Induced Pluripotent Stem Cells) banks of iPSC lines with homozygous HLA (Human Leukocyte Antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population. Methods To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, -B and -DRB1 with different stringencies: high resolution, low resolution and beneficial mismatch. Results We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide a HLA-A, HLA-B and HLA-DRB1 matching for 28,23% of the population. Conclusion We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies.
PRDX2 Performs the Oncogenic Functions in Ewing’s Sarcoma
Authors: Xue Ruifeng , Fan Zhengfu , An Yunhe 
Published: August 2020

Abstract
Background: Ewing's sarcoma (ES) is the second most common malignant primary bone tumor in children and adolescents, characterized by malignant proliferation of small round cells. The survival rate of this disease continues to be low. Peroxiredoxin2 (PRDX2) is a multifunctional peroxidase family member with anti-oxidation, involvement in intracellular signaling, chaperones, and tumor. But the function and underlying mechanism of PRDX2 in ES is still unknown. Herein we investigated the role and mechanism of PRDX2 in the development of ES, and tested its potential for the treatment of ES.Methods: We explored the function of PRDX2 on ES through knocking down the expression of NKAP in A673 and RDES cells by siRNA interference (siPRDX2). We examined the effects of siPRDX2 on cell motility and apoptosis using CCK8, colony formation, transwell, gelatin zymography, flow cytometry, PI/Hoechst33342 double dye and western blot assays. In addition, western blot was used to analyze the activation of the AKT/mTOR signaling pathway.Results: Here we showed that downregulation of PRDX2 strongly inhibited the motility of A673 and RDES cells. Interestingly, siPRDX2 induced cell apoptosis. Furthermore, the expression of anti-apoptotic protein Bcl2 in siPRDX2 group was significantly decreased, while the expression of pro-apoptotic protein Bax and cleaved Caspase-9 was strongly increased. Finally to identify the molecular mechanisms involved, we examined related proteins of the AKT/mTOR signaling pathway and found that siPRDX2 significantly inhibited the phosphorylation of AKT and the expression of Cyclin D1.Conclusion: These observations suggest that siPRDX2 inhibited the ES cells motility and induced apoptosis in which the AKT/mTOR signaling pathway involved. The enhanced understanding to this molecular mechanism has provided a strong basis for the development of novel therapeutic strategies for ES.
Usefulness of tissue inhibitor of metalloproteinase 1 as a predictor of sustained remission in patients with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Ishizaki Jun , Takemori Ayako , Horie Kenta , Hiraoka Daisuke , Suemori Koichiro , Matsumoto Takuya , Sada Ken-ei , Amano Koichi , Harigai Masayoshi , Arimura Yoshihiro , Makino Hirofumi , Takenaka Katsuto , Takemori Nobuaki , Hasegawa Hitoshi 
Published: August 2020

Abstract
Background: We previously identified tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker of disease activity that distinguished mildly or highly active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) from remission 6 months after the initiation of remission-induction therapy. In the present study, we investigated whether TIMP-1 is clinically useful as a predictor of relapse and sustained remission in AAV patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) during maintenance therapy.Methods: The relationship between serum TIMP-1 levels and clinical outcomes in AAV patients receiving maintenance therapy was assessed using the follow-up data of a Japanese large-cohort study (the RemIT-JAV-RPGN study) and data collected from AAV patients on maintenance therapy in our hospital (the MAAV-EU study).Results: In the RemIT-JAV RPGN study, serum levels of TIMP-1 were significantly higher in mildly active AAV patients with MPA and GPA (median BVAS 5) 6 months after the initiation of remission-induction therapy than in patients in remission. In contrast, no significant differences were observed in C-reactive protein (CRP) or myeloperoxidase-ANCA levels between these groups. Regarding maintenance therapy, elevated levels of TIMP-1 in patients in remission were associated with relapse and/or difficulty reducing the glucocorticoid dosage after 6 to 12 months. In the MAAV-EU study, serum levels of TIMP-1 were elevated in relapsed patients 6 months before relapse, earlier than the increase in serum levels of CRP. Analyses of both studies revealed that approximately 30% of patients in remission with a serum TIMP-1 level ≥ 150 ng/mL relapsed after 6 to 12 months, while the majority of patients with a TIMP-1 level < 150 ng/mL sustained remission for at least 12 months. This result suggests that a serum TIMP-1 level < 150 ng/mL reflects complete remission and ≥ 150 ng/mL indicates subclinical inflammation, even with BVAS 0.Conclusion: We herein demonstrated that TIMP-1 is more useful as a predictive biomarker of sustained remission than as a predictor of relapse in maintenance therapy for AAV. TIMP-1 levels < 150 ng/mL are important for the long-term maintenance of remission and may be an indicator for the tapering or cessation of treatment.
ABS Provides Opportunities for Indigenous and Local Communities in the Limpopo National Park. An ethnobotanical survey of plants used by the Changana community, Limpopo National Park, Mozambique
Authors: Nicosia Enrico , Valenti Roberto , Guillet Alfredo , Malatesta Luca , Tallone Giuliano , Mondlane Telo Da Silva Maximiano , Attorre Fabio 
Published: August 2020

Abstract
Background: Genetic resources are important for the livelihood of the rural population in developing countries and have an economic potential that, through an efficient Access and Benefit Sharing regime, can support sustainable economic development. Considering the wealth of genetic resources in Mozambique, its eligibility for Access and Benefit Sharing projects has been explored. Methods: The socio-economic status of the Changana community of the Limpopo National Park area was studied through a 500 questionnaires socio-economic survey. Considering the livelihood role that plant genetic resources could play for the local rural population, an ethnobotanical survey was conducted, with the support of villagers knowledgeable of wild plant resources and their use. Results: Several criticalities in the living condition of local communities and a generalized lack of adequate economic incomes have emerged from the socio-economic analysis. A list of 101 plant species with important commercial possibilities, mainly related to medical, food and cosmetic sectors, was provided by the ethnobotanical survey. Around 95% of the plant studied which could have effective medical properties showed the greatest potential.Conclusion: A significant potential for Mozambique to be included in Access and Benefit Sharing initiatives was recognized. The present work can contribute to the identification of Access and Benefit Sharing pilot projects, toward the evaluation of the policy efficacy and implementation of the Nagoya Protocol in the Country. The Limpopo National Park area can support Access and Benefit Sharing projects toward the economic development of the indigenous and local communities and the conservation of the Country’s biodiversity.