bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of Family Planning Services With HIV Treatment for Women of Reproductive Age Living With HIV Attending ART in Special Zone of Oromia Regional State, Ethiopia
Authors: Demissie Dereje Bayissa , Mmusi-Phetoe Rose 
Published: December 2020

Abstract
Background: In settings where HIV prevalence is high, management of sexual and reproductive health is critical to reducing HIV transmission and maternal mortality. Integration of family planning with HIV services is appropriate model for HIV therapy, HIV prevention and care with family planning services in a resource limiting area like Ethiopia. The aims of the study were to determine the status of integration of family planning services with HIV treatment for women of reproductive age in Oromia, Ethiopia Methods: A Health facility based cross-sectional study design was conducted with quantitative data collection approach was used to collect data from women living with HIV attending ART clinics in special zone of surrounding Finfinne, Oromia Region in five health centres. Simple random sampling computer-generated sample was used to select 654 respondents. The returned questionnaires were checked for completeness, cleaned manually, coded and entered into EPI INFO 7.1.6 version. These were then transferred to statistical Package for Social Sciences 23.0 for further analysis. Bivariate and multivariable logistic regressions analysis was used to identify factors associated with integration family planning with HIV services with the significant association at adjusted odds ratio (AOR) with 95% confidence interval (CI) to controlled effects of possible confounders from final model. Result: After discarded16 spoiled questionnaires, the completed response rate of this study was 97.6% (654/670). There were 654 respondents whose ages ranged between 18 and 49 years. The mean age of the respondents was 31.86 years with a SD of ±6.0 years. Most of the respondents in the sample were in the age group 26-35 (n=374, 57%), and only 96 (14.7%) were in the age group 18-25. This study determined the overall integration FP-HIV services were 55.8% among reproductive age women living with HIV in Oromia regional state of special zone health centres. Almost all respondents (n=635, 97.1%) preferred integrated sexual reproductive health and HIV services at the same facility, from the same providers, and 622 (95%) were very or mostly satisfied with the utilisation of integrated family planning/HIV services.Conclusion: The identified factors that affected the integration of family planning with HIV services were educational and occupational status, residence, discussion of family planning with healthcare providers, fertility desire and CD4 counts. Therefore, Ministry of health should engage women in the planning, implementation and evaluation of the integrated family planning/HIV services.
A Machine Learning Algorithm to Predict Hyperglycemic Cases Induced by PD-1/PD-L1 Inhibitors in the Real World
Authors: Yang Jincheng , Lin Weilong , Shi Liming , Deng Ming , Yang Wenjing 
Published: December 2020

Abstract
Background: Diabetes mellitus and cancer are amongst the leading causes of deaths worldwide; hyperglycemia plays a major contributory role in neoplastic transformation risk. From reported adverse events of PD-1 or PD-L1 (programmed death 1 or ligand 1) inhibitors in post-marketing monitoring, we aimed to construct an effective machine learning algorithm to predict the probability of hyperglycemic adverse reaction from PD-1/PD-L1 inhibitors treated patients efficiently and rapidly. Methods: Raw data was downloaded from US Food and Drug Administration Adverse Event Reporting System (FDA FAERS). Signal of relationship between drug and adverse reaction based on disproportionality analysis and Bayesian analysis. A multivariate pattern classification of Support Vector Machine (SVM) was used to construct classifier to separate adverse hyperglycemic reaction patients. A 10-fold-3-time cross validation for model setup within training data (80% data) output best parameter values in SVM within R software. The model was validated in each testing data (20% data) and two total drug data, with exactly predictor parameter variables: gamma and nu. Results: Total 95918 case files were downloaded from 7 relevant drugs (cemiplimab, avelumab, durvalumab, atezolizumab, pembrolizumab, ipilimumab, nivolumab). The number-type/number-optimization method was selected to optimize model. Both gamma and nu values correlated with case number showed high adjusted r2 in curve regressions (both r2 >0.95). Indexes of accuracy, F1 score, kappa and sensitivity were greatly improved from the prediction model in training data and two total drug data. Conclusions: The SVM prediction model established here can non-invasively and precisely predict occurrence of hyperglycemic adverse drug reaction (ADR) in PD-1/PD-L1 inhibitors treated patients. Such information is vital to overcome ADR and to improve outcomes by distinguish high hyperglycemia-risk patients, and this machine learning algorithm can eventually add value onto clinical decision making.
MiR-190 Promotes Malignant Transformation and Progression of Human Urothelial Cells through CDKN1B Inhibition
Authors: Huang Shirui , Hua Xiaohui , Kuang Mengjiao , Zhu Junlan , Mu Haiqi , Tian Zhongxian , Zheng Xiaoqun , Xie Qipeng 
Published: December 2020

Abstract
BackgroundAlthough miR-190 has been reported to be related to human diseases, especially in the development and progression of cancer, its expression in human bladder cancer (BC) and potential contribution to BC remain unexplored.MethodsqRT-PCR was used to verify the expression level of miR-190 and CDKN1B. Flow cytometry (FCM) assays were performed to detect cell cycle. Soft agar assay was used to measure anchorage-independent growth ability. Methylation-Specific PCR, Dual-luciferase reporter assay and Western blotting were used to elucidate the potential mechanisms involved.ResultsOur studies revealed that downregulation of the CDKN1B/p27 protein is an important event related to miR-190, promoting the malignant transformation of bladder epithelial cells. miR-190 binds directly to CDKN1B 3’-UTR and destabilizes CDKN1B mRNA. Moreover, miR-190 downregulates TET1 by binding to the TET1 CDS region, which mediates hypermethylation of the CDKN1B promoter, thereby resulting in the downregulation of CDKN1B mRNA. These two aspects led to miR-190 inhibition of p27 protein expression in human BC cells. However, the increased expression of miR-190 in BC and its upstream regulatory mechanism remain unclear. A more in-depth mechanistic study showed that c-Jun promotes the transcription of Talin2, the host gene of miR-190, thus upregulating the expression of miR-190 in human BC cells.ConclusionIn this study, we found that miR-190 plays an important role in the development of BC. Taken together, these findings indicate that miR-190 may promote the malignant transformation of human urothelial cells by downregulating CDKN1B, which strengthens our understanding of miR-190 in regulating BC cell transformation.
Oleandrin Induces Immunogenic Cell Death Via the PERK/elF2α/ATF4/CHOP Pathway in Breast Cancer
Authors: Li Xiaoxi , Zheng Jian , Chen Shi , Meng Fan-dong , Ning Jing , Sun Shu-lan 
Published: December 2020

Abstract
Background Chemotherapeutic agents have been linked to immunogenic cell death (ICD) induction that is capable of augmenting antitumor immune surveillance. The cardiac glycoside oleandrin, which inhibits Na+/K+-ATPase pump (NKP), has been shown to suppress breast cancer growth via inducing apoptosis. However, the implications of oleandrin in antitumor immune response and potential ICD induction remain unexplored till now, which is investigated in the present study.Methods Calreticulin (CRT) exposure was detected by immunofluorescence and flow cytometry, and high mobility group protein B1 (HMGB1) and Adenosine Triphosphate (ATP) secretion was quantified by ELISA and both the intracellular and extracellular expression of Heat shock protein 70/90 (HSP70/90) was detected by western blotting in breast cancer cells treated with oleandrin. Dendritic cells (DCs) were co-cultured with oleandrin-treated breast cancer cells before the expressions of activation markers and cytokines were examined by quantitative real time polymerase chain reaction (qRT-PCR), ELISA, and flow cytometry. Immune activation effects of oleandrin were determined in murine breast cancer model using BALB/C mice. The differential mRNA expression incurred by oleandrin was investigated by mRNA sequencing and subsequently confirmed by qRT-PCR and Western blotting. Results Oleandrin treatment induced CRT exposure on cell surface and the release of HMGB1, HSP70/90 and ATP. The maturation and activation of DCs were increased by co-culturing with oleandrin-treated cancer cells, which subsequently enhanced CD8+ T cell cytotoxicity. In animal models, oleandrin inhibited tumor growth and increased tumor infiltrating lymphocytes including DCs and T cells. Mechanistically, oleandrin induced endoplasmic reticulum (ER) stress associated caspase independent immunogenic cell death (ICD) mainly through PERK/elF2α/ATF4/CHOP pathway. Activation of IRE1 pathway but not ATF6, the other two canonical sensors of ER stress, was also observed. Conclusion Oleandrin triggered ER stress and induced ICD-mediated immune destruction of breast cancer cells. Oleandrin combined with immune checkpoint inhibitors might improve the efficacy of immunotherapy.
What Are the Survival Factors in Surgically Resected Synchronous Multiple Primary Lung Cancers: A Retrospective Study
Authors: Li Haichao , Wang Kai , Zhang Xingxing , Chen Rong , Zhao Jian 
Published: December 2020

Abstract
BackgroundWith the popularization of high-resolution computed tomography (HRCT), the detection rate of synchronous multiple primary lung cancer (SMPLC) is increasing. We retrospectively analyzed the surgical results of SMPLC patients in our hospital to determine the best treatment, surgical prognosis and survival analysis.MethodsA total of 78 SMPLC patients met the diagnostic criteria underwent complete resection and lymph node dissection or sampling without any preoperative induction therapy in the Department of Thoracic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University. We analyzed the postoperative survival rate, and further studied the relationship between survival rates and sex, age, preoperative symptoms, tumor location, tumor number, tumor size, lymph node metastasis, TNM stage, surgical type, surgical frequency, histopathologic types, vascular infiltration, visceral pleural invasion and postoperative therapy.ResultsAmong 78 patients, the 1-,2-,3-,4- and 5-year disease free survival (DFS) rates were 93.42%, 86.84%, 77.78%, 62.96%, and 60.00%, respectively, while the 1-,2-,3-,4- and 5-year overall survival (OS) rates were 94.73%, 92.11%, 82.22%, 77.78%, and 65.00%, respectively. TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.ConclusionsFirst, SMPLC is different from intrapulmonary metastasis and its clinical stage is also different from the 8th (2015) edition TNM classification for lung cancer. Second, when pulmonary function permits, surgery (complete resection and lymph node dissection) is a significantly beneficial treatment for patients with SMPLC. Third, TNM stage of the largest tumor (II:HR=7.40,III:9.01,p=0.002) was an independent risk factor for DFS. Smoking history (HR=4.34,p=0.039) and TNM stage of the largest tumor (II:HR=9.38,III:9.42,p=0.003) were independent risk factors for overall survival.
Pyrroloquinoline Quinone Regulates the Redox Status in Vitro and Vivo of Weaned Pigs via the Nrf2/HO-1 Pathway
Authors: Huang Caiyun , Fan Zijuan , Han Dandan , Johnston Lee J , Ma Xi , Wang Fenglai 
Published: December 2020

Abstract
BackgroundOxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2.ResultsExperiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: receiving a basal diet (control) and diets supplemented with 0.15, 0.30, and 0.45 % PQQ. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0-28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, occludin and claudin-1; and decrease ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. Conclusions﻿PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.
A Novel Automatic Cough Frequency Monitoring System Combining a Triaxial Accelerometer and a Stretchable Strain Sensor
Authors: Otoshi Takehiro , Nagano Tatsuya , Izumi Shintaro , Hazama Daisuke , Katsurada Naoko , Yamamoto Masatsugu , Tachihara Motoko , Kobayashi Kazuyuki , Nishimura Yoshihiro 
Published: December 2020

Abstract
BackgroundObjective evaluations of cough frequency are considered important for assessing the clinical state of patients with respiratory diseases. While cough monitors with audio recordings are used in research settings, they are rarely used in clinical settings. Issues regarding privacy and background noise (especially the sounds of someone else’s cough) with audio recordings are barriers to the wide use of these monitors in clinical settings; to solve these problems, we developed a novel automatic cough frequency monitoring system combining a triaxial accelerator and a stretchable strain sensor.MethodsEleven healthy adult volunteers and 10 adult patients with cough were enrolled. The participants sat in a chair and wore two devices for 30 minutes for the cough measurements. An accelerator was attached to the epigastric region, and a stretchable strain sensor was worn around their neck. When the subjects coughed, these devices displayed specific waveforms. For the development of the algorithm, the participants’ measurement data from both devices were divided into consecutive small “units” lasting 5 seconds each. Whether each unit corresponded to a “cough unit” was determined by the observer who manually counted the cough records. Then, the data from all the participants were categorized into a training dataset and a test dataset. Using a variational autoencoder, a machine learning algorithm with deep learning, the components of the test dataset were automatically judged as being a “cough unit” or “non-cough unit”.ResultsThe sensitivity and specificity in detecting coughs among 21 participants were 92% and 96%, respectively. The triaxial accelerometer only yielded a sensitivity of 91% and specificity of 95%. Therefore, the diagnostic accuracy improved slightly when the accelerometer was combined with a stretchable strain sensor.Conclusions﻿According to the results of the current study, a cough frequency monitor with good performance can be created by combining an accelerometer and another biometric sensor. Our cough monitor is suitable for ambulatory settings because the devices are small and light. Our cough monitoring system, which does not require audio recordings, has the potential to be widely used in clinical settings without any concerns regarding privacy or background noise.
Up-regulation of nPKC Contributes to Proliferation of Pulmonary Artery Smooth Muscle Cells in Hypoxia-induced Pulmonary Hypertension
Authors: Shi Yiwei , Jiang Rui , Qin Xiaojiang , Gao Anqi , Hou Xiaomin , Chen Liangjing , Xu Xinrong , Chai Lina , Guo Yunting , Zhao Liangyuan , Wu Furong 
Published: December 2020

Abstract
Background It has been indicated that protein kinase C (PKC) plays a vital role in the pathogenesis of hypoxia-induced pulmonary hypertension (PH). The functions or the pathogenic roles of PKCs vary from different types, and their related downstream pathways may also be distinct. Therefore, the specific role of different types of PKC deserves to be elucidated. Discussions regarding conventional PKC (cPKC) have dominated research in recent years, however, the relationship between novel PKC (nPKC) and the development of PH remain unclear. In addition, it is less known whether nPKC has a direct effect on the proliferation of pulmonary artery smooth muscle cells (PASMCs). This study is designed to investigate the role of nPKC in mediating PASMCs proliferation in PH and the underlying mechanisms. Methods Mouse PASMCs was isolated using magnetic separation technology. The PASMCs were divided into 24 h group, 48 h group and 72 h group according to different hypoxia treatment time, then detected cell proliferation rate and nPKC expression level in each group. We treated PASMCs with agonists or inhibitors of PKCδ and PKCε and exposed them to hypoxia or normoxia for 72 h, then measured the proliferation of PASMCs. We also constructed a lentiviral vector containing siRNA fragments for inhibiting PKCδ and PKCε to transfected PASMCs, then examined their proliferation. Results PASMCs isolated successfully by magnetic separation method and were in good condition. Hypoxia promoted the proliferation of PASMCs, and the treatment for 72 h had the most significant effect. Hypoxia upregulated the expression of PKCδ and PKCε in mouse PASMCs, leading to PASMCs proliferation. Moreover, Our study demonstrated that hypoxia induced upregulation of PKCδ and PKCε expression resulting to the proliferation of PASMCs via up-regulating the phosphorylation of AKT and ERK. Conclusions Our study provides clear evidence that increased nPKC expression contributes to PASMCs proliferation and uncovers the correlation between AKT and ERK pathways and nPKC-mediated proliferation of PASMCs. These findings may provide novel targets for molecular therapy of pulmonary hypertension.
Evidence for a Potential Common Gene Network of Smith-Magenis&nbsp;and Potocki-Lupski Syndromes,&nbsp;DAND (DEAF1-Associated Neurodevelopmental Disorder)&nbsp;and&nbsp;ZEB1-Associated Neurodevelopment Disorder
Authors: Chen Li , Jensik Philip J , Yuan Xi , Liu Muyin , Saffen David , Elsea Sarah H 
Published: December 2020

Abstract
Background: Neuropsychiatric disorders are highly heterogeneous and often display overlapping phenotypes, suggesting possible defects in common genetic networks. We previously reported pathogenic variants in deformed epidermal autoregulatory factor-1 (DEAF1) that contribute to DEAF1-associated neurodevelopmental disorder (DAND) and predicted that DEAF1 regulates expression of retinoic acid induced 1 (RAI1), the causative gene of Smith-Magenis syndrome (SMS) and Potocki-Lupski Syndrome (PTLS), through a putative DEAF1 binding sequence (DBS) in RAI1 intron 2, suggesting a common genetic network of these disorders that needs further study. Methods: In this study, we tested the DEAF1 binding and transcriptional regulation of RAI1 using luciferase reporter gene assay, EMSA and ChIP. We explored the upstream regulator of DEAF1 using bioinformatics analysis, qPCR and ChIP, and generated a potential network involving these genes based on patients’ phenotype and bioinformatics analysis.Results: We demonstrated that DEAF1 binds to the RAI1 DBS and regulates RAI1 expression in vitro, and a pathogenic variant in the DEAF1 SAND domain was defective in binding the RAI1 DBS. We also obtained evidence that DEAF1 expression is regulated by the transcription factor ZEB1 via predicted binding sites in DEAF1 intron 1. Microdeletions and variants in ZEB1 have been implicated in brain developmental disorders, including intellectual disability (ID), autism, agenesis of corpus callosum (ACC) and corneal dystrophy. Patients harboring deletions or pathogenic variants of ZEB1, DEAF1 or RAI1 display partially overlapped symptoms, including ID, autistic features, speech impairment, developmental delay and dysmorphologies.Conclusions: Together, these results provide evidence for a common molecular network in ZEB1-associated neurodevelopment disorder, DAND, SMS and PTLS.
Validation of Perceived Physical Fatigability Using the Simplified-Chinese Version of the Pittsburgh Fatigability Scale
Authors: Hu Yixin , Zhang Hangming , Xu Weihao , Zhao Ming , Liu Juan , Wu Linna , Zou Lin , Zuo Jing , Liu Yunxia , Bair Woei-Nan , Qiao Yujia(Suanna) , Glynn Nancy W. 
Published: December 2020

Abstract
Background: The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person’s susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults.Methods: The PFS was translated into the simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach’s alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living).Results: The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach’s alpha=0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36-0.56, p<.001). Age- and sex-adjusted PFS Physical scores had moderate to good overall discrimination for correctly classifying people by their physical performance and daily living performance (AUCs range 0.70-0.87, p<.001)Conclusions: The PFS simplified-Chinese version is a valid instrument to assess perceived physical fatigability in Chinese-speaking older adults with good convergent validity. Thus, the PFS, with low cost and greater feasibility, is a desired tool to measure fatigability in large population studies.