bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dissecting the Mechanism of Yuzhi Zhixue Granule on Ovulatory Dysfunctional Uterine Bleeding by Network Pharmacology and Molecular Docking
Authors: Li Jialin , Luo Hua , Liu Xinkui , Zhang Jingyuan , Zhou Wei , Guo Siyu , Chen Xiuping , Liu Yingying , Jia Shanshan , Wang Haojia , Li Bingbing , Cheng Guoliang , Wu Jiarui 
Published: July 2020

Abstract
Background: Yuzhi Zhixue Granule (YZG)is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.Methods: The putative targets of YZG based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Search Tool for Interacting Chemicals (STITCH) databases were collected. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding afﬁnity of the seven putative targets with the corresponding compounds.Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.
Analysis of Y Chromosome Microdeletion and Karyotype in 516 Patients With Azoospermia
Authors: Wu Lihua , Hu Jingjing , He Yiqun , Zhang Yicong , Liang Kailing , Guo Li , Chen Hanbiao , Wang Ting 
Published: July 2020

Abstract
Background: To investigate the correlation between Y chromosome microdeletion and cytogenetic analysis in patients with azoospermia.Methods: A total of 516 patients with azoospermia were enrolled from March 2015 to December 2019. Karyotype analysis(G-banding) was performed with peripheral blood.Y-chromosome azoospermia factor (AZF) were detected by quantitative fluorescent polymerase chain reaction (QF-PCR).Results: Chromosome abnormality was detected in 66 of the 516 azoospermia patients, with an abnormal rate of 12.8% In addition, 7.8% cases(40/516) presented with Y-chromosome AZF microdeletions, in which 27 cases patients with karyotype of 46,XY(67.5%,27/40) and 13 cases of chromosome abnormalities (32.5%,13/40).Conclusion: The incidence of Y chromosome microdeletion was higher in the patients with karyotype of 46,XY. Conventional cytogenetics cannot directly reflect the microdeletions of Y chromosome. Therefore, the combination of this two detection methods can help to clarify the genetic causes of patients with azoospermia and provide a theoretical basis for clinical assisted reproductive technology.
Acceptability and feasibility of S-1 plus cisplatin adjuvant chemotherapy for completely resected non-small cell lung cancer: an open-label, single arm, multicenter, phase 2 trial
Authors: Uematsu Shugo , Sano Atsushi , Isobe Kazutoshi , Usui Kazuhiro , Matsumoto Jun , Kiribayashi Takaharu , Obara Kiyohaya , Kitami Akihiko , Murakami Yoshitaka , Iyoda Akira 
Published: July 2020

Abstract
Background

Although platinum-based chemotherapy is accepted as adjuvant chemotherapy for resectable advanced non-small cell lung cancer (NSCLC), its completion rate is low due to severe adverse events. S-1 plus cisplatin is associated with relatively low toxicity and an unimpaired quality of life, and has been used for unresectable advanced lung cancer. We investigated the acceptability and feasibility of combination therapy with S-1 plus cisplatin as postoperative adjuvant chemotherapy following complete resection of pathological stage II-IIIA NSCLC.
Methods

Enrolled patients received oral S-1 at a dose depending on their body weight twice daily for 21 days with intravenous cisplatin 60 mg/m2 on day 8, with 1 cycle comprising 5 weeks and 4 cycles. Patients received standard precautions against adverse events and received standard treatment when adverse events occurred. The primary endpoint was completion rate; secondary endpoints included safety, status of drug administration, disease-free survival, and overall survival.
Results

A total of 19 patients [14 men, 5 women; mean age, 59.1 years; mean body surface area, 1.688 m2; 17 with an Eastern Cooperative Oncology Group performance status (PS) of 0 and 2 with a PS of 1; 7 (36.8%) with stage II disease and 12 (63.2%) with stage IIIA disease] were enrolled. The rate of completion of 4 cycles was 68.4%. Grade 3 adverse events that occurred in ≥10% of patients included neutropenia (21.1%), nausea (21.1%), and anorexia (15.8%). No grade 4 adverse events, febrile neutropenia, or treatment-related deaths occurred. The mean relative dose intensity was 79% for S-1 and 80% for cisplatin. The 2-year disease-free survival rate was 42.1%, and 2-year overall survival rate was 83.3%.
Conclusion

This study demonstrated the acceptability and feasibility of using S-1 plus cisplatin as adjuvant chemotherapy.
The effect of primary granulocyte-colony stimulating factor prophylaxis on the incidence of febrile neutropenia in patients with testicular germ cell tumors
Authors: Hapakova Nikola , Chovanec Michal , Rejlekova Katarina , Kalavska Katarina , Obertova Jana , Palacka Patrik , De Angelis Valentina , Světlovská Daniela , Sycova-Mila Zuzana , Mardiak Jozef , Mego Michal 
Published: July 2020

Abstract
Background: Testicular germ cell tumors (GCTs) are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Patients and methods: This study was conducted from medical records database of GCTs patients treated with first line/adjuvant chemotherapy from January 2000 to December 2017. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 patients suffered FN, while only 29 patients with primary prophylaxis suffered FN (32.8% vs 10.9%, P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009).Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence in patients treated with first line chemotherapy for metastatic disease. Patients receiving G-CSF prophylaxis had significantly longer overall survival. We suggest, that primary G-CSF prophylaxis should be considered in GCT patients receiving first line chemotherapy.
Active Commuting to School Among 36, 781 Spanish Children and Adolescents: A Temporal Trend Study
Authors: Gálvez-Fernández Patricia , Herrador-Colmenero Manuel , Esteban-Cornejo Irene , Castro-Piñero José , Molina-García Javier , Queralt Ana , Aznar Susana , Abarca-Sos Alberto , González-Cutre David , Vidal-Conti Josep , Fernández-Muñoz Santiago , Vida Jerónimo , Ruiz-Ariza Alberto , Rodríguez-Rodríguez Fernando , Moliner-Urdiales Diego , Villa-González Emilio , Barranco-Ruíz Yahira , Huertas-Delgado Francisco Javier , Mandic Sandra , Chillón Palma 
Published: July 2020

Abstract
Background

Active commuting to school (ACS) is an important source to increase the total daily physical activity in youth and improve their health. How the ACS rates change along the time is of interest. The objective of this study was to examine trends in the rates of ACS in a large sample of Spanish children and adolescents aged 6–18 years from 2010 to 2017. The study period included the economic crisis in Spain (2008 to 2013) and secondary analysis was conducted to compare ACS rates during and after the economic crisis.
Methods

To investigate trends in ACS among Spanish children and adolescents, data were obtained from 28 studies conducted across Spain. The study sample comprised 18,343 children (6 to 11.9 years old; 50.5% girls) and 18,438 adolescents (12 to 18 years old; 49.5% girls). The overall trends in ACS were evaluated using multilevel logistic regression analysis.
Results

The rates of ACS in Spanish children and adolescents did not change significantly during the 2010–2017 period, except a sporadic increase in the rate of ACS in adolescents in 2012–2013. No significant association between the ACS and the economic crisis time period in either children or adolescents were found. These findings are in contrast to recently reported declines in ACS rates in other countries.
Conclusions

Strong partnerships between researchers, public health practitioners, policy-makers and communities, as well as long-term commitment and evaluations of interventions aiming to increase ACS are necessary to ensure positive results in the long term.
Patient preferences on rheumatoid arthritis second-line treatment: A discrete choice experiment of Swedish patients
Authors: Bywall Karin Schölin , Kihlbom Ulrik , Hansson Mats , Falahee Marie , Baecklund Eva , Veldwijk Jorien 
Published: July 2020

Abstract
Background
Preference assessments of patients with rheumatoid arthritis (RA) help inform clinical therapeutic decisions for including biologic and targeted synthetic drugs to use. This study assesses patient preferences for biologics or Janus kinases (JAK) inhibitors and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects.
Methods
Between November 2018 to August 2019, patients were recruited to participate in a survey containing demographic and disease-related questions as well as a Discrete Choice Experiment to measure their preferences for second-line therapies using biologics or JAK inhibitors. Treatment characteristics (attributes) included in the DCE were mode of administration, frequency of use, probability of mild short-term side effects, probability of side effects affecting appearance, probability of psychological side effects, probability of severe side effects, and effectiveness of treatment.
Results
A total of 358 patients were included in the analysis. Latent class analysis revealed three preference patterns. When choosing treatment, the respondents found either effectiveness of treatment, mode of administration, or probability of severe side effects as most important. In addition, disease duration and mild side effects influenced the patients’ choices.
Conclusion
Respondents found either effectiveness, severe side effects, or mode of administration as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.
Mir-125a rs12976445 is Associated with Susceptibility to Thyroid Cancer: A Case-control Study
Authors: Montazeri-Najafabady Nima Nima , Dabbaghmanesh Mohammad Hossein , Ghaderi Abbas , Chatrabnous Nazanin , Arabnezhad Mohammad Reza , Amiri Rajeeh Mohammadian 
Published: July 2020

Abstract
Background: Thyroid cancer is the fifth communal cancer type in females and its occurrence rate continues to rise rapidly worldwide. Latest data demonstrated mir-125 is down-regulated in various cancer types. Methods: a case-control (179 cases, 165 controls) study in order to explore the association of mir-125 rs12976445 with the risk of thyroid cancer in the Iranian population was performed. In order to investigate rs12976445 C/T polymorphisms, polymerase chain reaction restriction–fragment length polymorphism (PCR–RFLP) was done. Logistic regression analyses were done to find the association of mir-125 rs12976445 C/T polymorphisms with thyroid cancer and its stages. Results: The genotype frequencies for patients was [(CC: 81(45.2%), CT: 75(41.9%), TT: 23 (12.9%)], and for controls was [(CC: 100 (60.1%), CT: 53(32.2%), TT: 12 (6.7%)]. The T allele distribution was significantly altered between patients and controls (P=0.002) with the odds ratio of 1.68. In the co-dominant model CC genotype was set as reference and compared with CT, and TT genotypes. In the dominant model, there was a significant difference between CC vs CT genotypes (adjusted OR = 1.69, 95% CI= 1-2.8, P = 0.026), and slightly significant differences between CC vs TT genotypes (adjusted OR = 2.18, 95% CI= 1-4.7, P = 0.047). we compared CT/TT genotype to the reference genotype (CC) and found a highly significant difference (adjusted OR = 1.78, 95% CI= 1.15-2.74, P = 0. 0.009).Conclusion: as the first study, our findings suggest that miR-125a rs12976445 is a possible prognostic biomarker for thyroid cancer patients.
Identification of Key Genes in Hepatitis B Associated Hepatocellular Carcinoma Based on WGCNA
Authors: Liu Chang , Dai Qinghai , Ding Qian , Wei Min , Kong Xiaohong 
Published: July 2020

Abstract
Hepatitis B virus (HBV) chronic infection is one risk factor of hepatocellular carcinoma (HCC). Lots of efforts have been made to illuminate the process of HBV-associated HCC, but its molecular mechanisms of carcinogenesis remain vague. Here, weighted gene co-expression network analysis (WGCNA) was employed to explore the co-expressed modules and hub/key genes correlated to HBV-associated HCC. We found that genes of the most significant module related to HBV-associated HCC were enriched in DNA replication, p53 signaling pathway, cell cycle, and HTLV-1 infection associated pathway; these cellular pathways played critical roles in the initiation and development of HCC or viral infections. Furthermore, seven hub/key genes were identified based on the topological network analysis and verified by expression and Kaplan-Meier survival analysis. This study provides new perspectives to the knowledge of the key pathways and genes in the carcinogenesis process of HBV-associated HCC. Our findings provided potential therapeutic targets and clues of the carcinogenesis of HBV-associated HCC.
The Experience of Parents of Children with Autism Spectrum Disorder During the COVID-19 Pandemic: A Qualitative Analysis
Authors: Parenteau China , Bent Stephen , Hossain Bushra , Chen Yingtong , Widjaja Felicia , Breard Michael , Hendren Robert 
Published: July 2020

Abstract
Families with children with autism spectrum disorder (ASD) face a unique set of challenges with the rise of the COVID-19 pandemic and shelter-in-place related to a diverse set of issues, including explaining COVID-19 and safety precautions in a comprehensible way, building structure in home for e-learning to take place, and guiding children back into social situations and the community. We sought to obtain direct feedback through semi-structured interviews from fifteen parents of children and adolescents from a non-public school for children with level 2 and 3 ASD to both develop an initial guide for families, teachers and clinicians caring for children with ASD and to create awareness in the community about the challenges presented by COVID-19 and shelter-in-place.
The miR-19b-3p/MAP2K3/STAT3 Feedback Loop Regulates Cell Proliferation and Invasion in Esophageal Squamous Cell Carcinoma
Authors: Zhang Ying , Liu Zhaoyong , Lu Weiqing , Yang Xia , Chen Yelong , Wang Hu 
Published: July 2020

Abstract
Background Esophageal squamous cell carcinoma (ESCC) remains one of the most refractory malignancies worldwide. MAP2K3 has been reported to play an important role in tumor progression. However, whether MAP2K3 also affects ESCC remains to be determined. Method We used a CRISPR/Cas9 kinome screen to identify the genes related to ESCC cell survival. The MAP2K3 expression was detected in ESCC tissues by immunohistochemistry and westernblot. The function of MAP2K3 in ESCC was investigated using colony formation assay and Transwell assay in vivo and in vitro. RNA sequence was performed to verify its downstream signaling pathways. DNA binding of the gene promoter region was detected by chromatin immunoprecipitation.Result Downregulation of MAP2K3 was found in ESCC and correlated with clinically poor survival. MAP2K3 inhibited cell proliferation and invasion via the EGFR/STAT3 signaling pathway in ESCC cells. MAP2K3 suppressed STAT3 expression and activation by interacting with MDM2 to promote the ubiquitin proteasome degradation of STAT3. Furthermore, MAP2K3 was a downstream target of miR-19b-3p, which promoted ESCC tumorigenesis. STAT3 binds to the MIR19B promoter region to increase the expression of miR-19b-3p in ESCC cells. Conclusion In summary, our results demonstrated that the miR-19b-3p/MAP2K3/STAT3 feedback loop regulates tumorigenesis in ESCC and elucidate the potential of therapeutically targeting this pathway in ESCC.
A nomogram for predicting the severity of COVID-19 using laboratory examination and CT findings
Authors: Kuang Yani , He Susu , Lin Shuangxiang , Zhu Rui , Zhou Rongzhen , Wang Jian , Li Renzhan , Lin Haiyong , Zhang Zhibang , Pang Peipei , Ji Wenbin 
Published: July 2020

Abstract
Background: The outbreak of COVID-19 has a significant impact on the health of people around the world. In the clinical condition of COVID-19, the condition of critical cases changes rapidly with a high mortality rate. Therefore, early prediction of disease severity and active intervention play an important role in the prognosis of severe patients.Methods: All the patients with COVID-19 in Taizhou city were retrospectively included and segregated into the non-severe and severe group according to the severity of the disease. The clinical manifestations, laboratory examination results, and imaging findings of the 2 groups were analysed for comparing the differences between the 2 groups. Univariate and multivariate logistic regression were used for screening the factors that could predict the disease, and the nomogram was constructed.Results: A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 years (range, 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. By using the method of multivariate logistic regression, the variables to construct nomogram include age (OR: 1.052, 95% CI: 1.020–1.086, P = 0.001), body temperature (OR: 2.252, 95% CI: 1.139–4.450, P = 0.020), lymphocyte count (OR: 1.128, 95% CI: 1.000–1.272, P = 0.049), ADA (OR: 1.163, 95% CI: 1.023–1.323, P = 0.021), PaO2 (OR: 0.972, 95% CI: 0.953–0.992, P = 0.007), IL-10 (OR: 1.184, 95% CI: 1.037–1.351, P = 0.012), and bronchiectasis (OR: 3.818, 95% CI: 1.694–8.605, P = 0.001). The AUC of the established nomogram was 0.877.Conclusions: This study established a stable nomogram for predicting the severity of COVID-19, and the clinicians can use the established nomogram for predicting the severity of newly diagnosed COVID-19 patients and to conduct active intervention for minimising the mortality rate and improving the prognosis of severe patients.
Ixekizumab, With Or Without Concomitant Methotrexate, Improves Signs And Symptoms Of Psa: Week 52 Results From Spirit-P1 And Spirit-P2 Studies
Authors: Combe Bernard , Tsai Tsen-Fang , Huffstutter J. Eugene , Sprabery Aubrey Trevelin , Lin Chen-Yen , Park So Young , Kronbergs Andris , Hufford Matthew M. , Nash Peter 
Published: July 2020

Abstract
BackgroundThe efficacy and safety of ixekizumab (IXE) with and without continuous concomitant methotrexate (MTX), for up to 52 weeks of treatment, was evaluated in patients with active psoriatic arthritis (PsA).MethodsPatients with active PsA who were biologic-naive (SPIRIT-P1) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2), were randomized to 80 mg IXE every 4 (IXE Q4W) or 2 weeks (IXE Q2W), after a 160-mg initial dose. In this post-hoc analysis, efficacy and safety were assessed up to Week 52 in the subgroups of patients who received: (i) IXE as monotherapy and (ii) IXE along with a stable dose of MTX (no dose tapering or increase). Efficacy outcomes included, but were not limited to, the percentage of patients achieving American College of Rheumatology (ACR) responses.ResultsOut of 455 patients initially randomized to IXE, 177 (38.9%) received monotherapy, 230 (50.5%) had concomitant MTX use, and 48 (10.5%) had other concomitant medication. Overall, 183 (40.2%) received IXE with a stable dose of concomitant MTX for 1 year. At Week 52, the percentage of patients achieving ACR20/50/70 responses in IXE Q4W monotherapy versus concomitant MTX groups were 66.3% versus 55.3%, 48.4% versus 38.8%, and 35.8% versus 27.1%, respectively; these responses were generally similar with IXE Q2W. The safety profiles were similar between patients receiving IXE with or without concomitant MTX.ConclusionsIn this post-hoc analysis, treatment with IXE demonstrated sustained efficacy in patients with PsA up to 1 year of treatment, with or without concomitant MTX therapy.Trial registrationClinicalTrials.gov NCT01695239 and NCT02349295