bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dose everolimus promotes a pro-inflammatory phenotype and facilitates the epithelial to mesenchymal transition of primary bronchial epithelial cells isolated from cystic fibrosis patients.
Authors: Granata Simona , Santoro Gloria , Masola Valentina , Pontrelli Paola , Sallustio Fabio , Lombardi Gianmarco , Verlato Alberto , Zaza Gianluigi 
Published: August 2020

Abstract
Background: Lung transplantation is still the best therapeutic option for cystic fibrosis (CF) patients, but, unfortunately, immunosuppressive therapies, often employed at high dosages to avoid acute rejection, may induce severe complications. In particular, patients treated with high dose of mammalian target of rapamycin inhibitors (mTOR-Is) may experience lung fibrosis (including bronchiolitis obliterans-organizing pneumonia). Although epithelial to mesenchymal transition (EMT) of airway cells has a central role in this process, the complete biological machinery is not completely clarified.Methods: In order to improve our knowledge on this process, primary bronchial epithelial cells carrying F508del mutation were treated with 5 and 100 nM everolimus (EVE) for 24 hours. Subsequently, RNA was hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Real-Time PCR was, then, used to validate microarray results and to measure major EMT biomarkers. Trans-epithelial resistance was measured by Millicell-ERS ohmmeter.Results: High dosage EVE induced a significant up-regulation of 42 genes and a down-regulation of 12 genes. After pathway analysis by Gene Set Enrichment Analysis and Ingenuity Pathway Analysis, we found that most of them were implicated in the pro-inflammatory pathway. Real-Time PCR validated these results and revealed that, in addition to pro-inflammatory genes (IL-1α, IL-8, Pim-1 Oncogene), EVE at high dosage was able to up-regulate major EMT biomarkers (such as: alpha-smooth muscle actin, connective tissue growth factor and metalloproteinase 12). In lung, EMT is the convergence point between inflammation and the progression of fibrotic damage. Additionally, EVE at this dosage reduced the trans-epithelial resistance (altering tight junction strength). In contrast, lower EVE did not trigger similar effects.Conclusions: We demonstrated that high dose EVE may trigger a pro-inflammatory/fibrotic biological machinery in bronchial epithelial cells from CF patients. Our results, although obtained in vitro, suggest that solid organ transplant recipients affected by CF should be treated with the lowest possible dose of mTOR inhibitors to minimize/avoid the onset and development of lung complications. In vivo studies might be useful to confirm our hypothesis.
Assessment of the validity of parameters describing temporal and spatial characteristics of spontaneous infant activity in the period of fidgety movements
Authors: Doroniewicz Iwona , Ledwoń Daniel , Bugdol Monika , Kieszczyńska Katarzyna , Affanasowicz Alicja , Matyja Małgorzata , Michnik Robert , Mitas Andrzej W. , Myśliwiec Andrzej 
Published: August 2020

Abstract
Background: The assessment of spontaneous activity of infants is of fundamental importance to the diagnosis and prediction of abnormal psychomotor development in children. Comprehensive and early diagnosis allows for quick and effective treatment and therapy. Subjective methods are based on the knowledge and experience of the diagnostician. The lack of objective methods to assess the motor development of infants makes it necessary to search for solutions for reliable, credible, and reproducible assessment expressed in numerical or pictorial terms. This study discusses the possibilities of pictorial standardization and optimization of measurable infant behavior based on video recordings. Methods: The authors attempt to perform computer analysis of spontaneous movements depending on the left, right, and front head position. The study was based on data of 26 healthy infants aged 7 to 15 weeks, with three infants included in an in-depth analysis. The selected films represented the input data for the parameters used as the author's temporal and spatial characteristics describing the global movements of the upper and lower limbs. The obtained videos were used as the input data for the algorithm of automatic detection of characteristic points using the OpenPose library. Results: The following movement characteristics were analysed: Factor of Movement's Area (FMA) ("amount of movement in the movement"), Factor of Movement's Shape (FMS) ("circularity” or "ellipticity" of the movement), Center of Movement's Area (CMA) ("inward and outward" and "up and down" movements). Preliminary analysis of the videos showed that the activity of the limbs, especially the upper limbs, may depend on the position of the head.Conclusions: The movement behavior of the infants varies in terms of the range and quality of movement, depending on age and head position.
Development and Launch of the First Obstetrics and Gynaecology Master of Medicine Residency Training Programme in Botswana
Authors: Luckett Rebecca , Nassali Mercy , Melese Tadele , Moreri-Ntshabele Badani , Moloi Thabo , Hofmeyr Justus , Chobanga Kudrra , Masunge Japhter , Makhema Joe , Pollard Maisie , Ricciotti Hope , Ramogola-Masire Doreeen , Bazzett-Matabele Lisa 
Published: August 2020

Abstract
Background: Sub-Saharan Africa (SSA) faces a severe shortage of Obstetrician Gynaecologists (OBGYNs). While the Lancet Commission for Global Surgery recommends 20 OBGYNs per 100,000 population, Botswana has only 40 OBGYNs for a population of 2.3 million. We describe the development of the first OBGYN Master of Medicine (MMed) training programme in Botswana to address this human resource shortage.Methods: We developed a curriculum for a 4-year OBGYN MMed at the University of Botswana (UB). We benchmarked curriculum content, learning outcomes, competencies, assessment strategies and research requirements with regional and international programmes. We engaged relevant local stakeholders and developed international collaborations to support in-country subspecialty training. Results: The OBGYN MMed curriculum was completed and approved by all relevant UB bodies within ten months during which time additional staff were recruited and programme financing was assured. The programme was advertised immediately; 26 candidates applied for four positions, and all selected candidates accepted. The programme was launched in January 2020 with government salary support of all residents. The national accreditation process was initiated.Conclusion: Training OBGYNs in-country has many benefits to health systems in SSA. Curricula can be adjusted to local resource context yet achieve international standards through thoughtful design and purposeful collaborations.
The Fluid Management and Hemodynamic Characteristics of PiCCO Employed on Young Children with Severe Hand, Foot, and Mouth Disease—A Retrospective Study
Authors: Wang Feng-yun , Qiang Xin-hua , Jiang Su-hua , Shao Jing-song , Fang Bin , Zhou Lixin 
Published: August 2020

Abstract
Background Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which are particularly common in preschool children. Severe HFMD is prone to pulmonary edema, and successively progresses to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important in the treatment process. Methods We reviewed young patients with severe HFMD, caused by EV71, and who had been successfully treated in our department. A total of 20 patients met the inclusion criteria. Some cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group and the control group. The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve the clinical outcomes. Results After analysis, the findings were that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or reduce the number of cases which needed mechanical ventilation, it did reduce the incidence of fluid overload and shortened the days of mechanical ventilation. After effective treatment, PiCCO monitoring showed that the cardiac index (CI) increased gradually(p<0.0001), whereas the pulse (P, p<0.0001), the extra vascular lung water index (EVLWI, p<0.0001), the global end diastolic volume index (GEDVI, p=0.0043), and the systemic vascular resistance index (SVRI, p<0.0001) all decreased gradually. ConclusionOur study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has potential clinical benefits which can reduce fluid overload(p=0.085) and duration of mechanical ventilation(p=0.028). However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.
The Development of a Surgical Readiness Interview Tool for Patients to Improve Conversation on Modifiable Risk Factors Prior to Total Joint Arthroplasty
Authors: Barton Kristen I , Hewison Christopher E , Kania-Richmond Ania 
Published: August 2020

Abstract
Background: Total joint arthroplasty (TJA) surgery is conducted forsevere hip and knee osteoarthritis (OA). However, a significant numberof patients referred to orthopedic surgeons with hip and knee OA are not appropriate surgical candidates.Further, many are sent back to their primary care physician because they had not yet exhausted non-surgical options, which suggests the importance surgeons place on exhausting conservative management before proceeding with TJA.The objective of this qualitative inquiry was to 1) explore patients’ perspectives of a surgical readiness interview tool and its potential utility in the management process for patients with OA, and 2) gain input from study participants to further refine the tool and ensure that it is reflective of the patients’ needs and perspectives. Methods: We used a diverse convenience sampling strategy to recruit TJA patients from the hip and knee arthroplasty clinics in Calgary, Alberta. Semi-structured qualitative interviews were conducted using a cognitive interviewing approach in order to elicit information regarding clarity and relevance of the interview tool. All interviews were digitally recorded and transcribed verbatim. Through an iterative process, a coding framework was developed and then applied in the analysis of all interviews. Results: Nine interviews were conducted (n=3 males and n=6), all of whom had a TJA within the previous 12 months. Participants found the questions in the interview tool to be clear and relevant, and nothing listed was unexpected. All participants expressed that they felt comfortable discussing the content of the interview tool with their doctors. The main themes that emerged from the interviews include 1) the need for clarifications, 2) patient-oriented changes, and 3) expectation management. While gaining insight from study participants, the qualitative inquiry confirmed utility of the tool improve the conversation about surgical readiness and utilizing conservative management prior to TJA. Conclusions: Overall, participants were positive about the interview tool and felt that it would lead to better care provision. We recommend the use of the interview tool in primary care settings to support the conversation on modifiable risk factors and non-surgical management strategies for OA prior to TJA.
Impact of Urgent and Emergency Care Vanguards on Delayed Transfers of Care in England
Authors: Malisauskaite Gintare , Jones Karen , Allan Stephen , Roland Daniel , Birks Yvonne , Baxter Kate , Gridley Kate 
Published: August 2020

Abstract
Objectives: To assess the relationship between Urgent and Emergency Care (UEC) Vanguards, which include as an aim the integration of healthcare and social care sectors, and Delayed Transfers of Care (DTOC) at Local Authority level in England. Methods: Difference-in-difference and fixed effects panel estimations were used to compare DTOC between UEC partner site Local Authorities with non-UEC Local Authorities employing quarterly data on days of DTOC from Local Authorities in England for the period 2010 to 2017. Robustness checks included employing Ordinary Least Squared (OLS) and synthetic control estimations; differences between the UEC and non-UEC sites were checked prior to the start of the Vanguards. Results: A statistically significant negative relationship was found between UEC Vanguards and DTOC rates that is robust to various specification checks with no indication of UEC participant sites having lower DTOC rates prior to the start of the initiative. Conclusions: UEC Vanguards appear to be associated with 40.5% lower DTOC rates at 1% significance level compared with other English Local Authorities. The empirical evidence indicates a statistically significant impact; however, more research is required to explain the reasons for this relationship.
Diagnostic Accuracy of Plasma Ghrelin Concentrations in Pediatric Sepsis -associated ARDS: A Single-center Cohort Study
Authors: yuan xiu , Li Shaojun , Zhou Liang , LI yanru , tang tian , Cheng Yuwei , Ao Xiaoxiao , Tan Liping 
Published: August 2020

Abstract
Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a (GHSR1a), which can regulate immunity and inflammation. To assess the diagnostic value of plasma ghrelin levels in sepsis-associated pediatric acute respiratory distress syndrome (PARDS).Methods: We recruited patients from the PICU of a third-class teaching hospital who met the diagnostic criteria for sepsis from January 2019 to January 2020. Clinical data, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors of cohort were evaluated in detail, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) was calculated using logistic regression to calculate and positivity cut-offs was tested. Ghrelin's ability to diagnose and differentiate sepsis-associated PARDS were determined. The log-rank test was used to compare the survival curves of different ghrelin level groups.Main results: Sixty-six PICU patients (30 with ARDS, 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the sepsis patients of the ARDS group than in those of the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584–0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (–LR) of plasma ghrelin for diagnosis of sepsis with PARDS were 86.7%, 50.0%, 59.1%, 81.8%,1.734, and 0.266, respectively. The survival rate of sepsis patients was significantly improved when the ghrelin level was >445 pg/mL.Conclusions: Ghrelin plasma was higher in sepsis-associated PARDS, and accompanied by the increase of inflammatory factors. The increased plasma ghrelin may be due to the anti-inflammatory response, which may be a protective factor in children with sepsis. Yet, there is no evidence to prove that elevated ghrelin appears to be a promising diagnostic indicator of sepsis-associated PARDS. In addition, the ghrelin levels may be a positive predictor of sepsis.Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials. gov/ChiCTR1900023254.
WITHDRAWN: Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis
Authors: Sun Zhongzheng , Xue Hao , Wei Yan , Wang Shaobo , Xu Jianye , Qian Mingyu , Wang Chaochao , Zhao Rongrong , Wang Chengwei , Li Gang 
Published: August 2020

Abstract
Background: Ribosomal Protein S27-Like is an evolutionarily conserved ribosomal protein and the role of RPS27L influencing the malignance of several cancers has been reported. However, its effects on glioma were still unknown. This investigation aims to characterize the clinical significance and the biological functions of RPS27L in gliomas.Methods: TCGA databases were explored to analyze the correlation between RPS27L expression and the clinical characteristics of glioma patients. Immunohistochemical staining was performed on glioma cases and normal brain tissues. The function of RPS27L in glioma was further explored using U87MG and A172 cell lines and a orthotopic xenograft model of nude mice.Results: Data obtained from TCGA database showed higher expression of RPS27L in glioma than normal, and the overall survival was lower in the high expression group. Immunohistochemistry showed the expression levels of RPS27L were increased with the tumor grade rising in gliomas. Functional assays showed knockdown of RPS27L inhibited proliferation, cell cycle transition, migration and invasion, while promoted apoptosis. Data of western blot indicated that knockdown of RPS27L increased the level of p21，Bax and Cleaved Caspase-3 while decreased the level of CDK4, cyclinD1, cyclinE1, Bcl-2 and MMP2, MMP9 in glioma cells. In vivo, the growth of orthotopic glioma xenografts was suppressed by expression of RPS27L shRNA, and the tumors with RPS27L shRNA showed less aggressiveness and reduced expression of Ki67, Bcl-2 and MMP2. Conclusions: RPS27L is overexpressed in glioma cells. Knockdown of RPS27L could inhibit the proliferation, migration and invasion while promote apoptosis of glioma cells in vitro and in vivo. RPS27L might be a potential prognostic biomarker and possible target for future therapy in glioma.
Immune‐related Long Noncoding RNA Signature for Patients with Cervical Cancer
Authors: Zheng Jianfeng , Tong Jinyi , Cao Benben , Zhang Xia , Niu Zheng 
Published: August 2020

Abstract
Background: Cervical cancer (CC) is a common gynecological malignancy for which prognostic and therapeutic biomarkers are urgently needed. The signature based on immune‐related lncRNAs(IRLs) of CC has never been reported. This study aimed to establish an IRL signature for patients with CC.Methods: The RNA-seq dataset was obtained from the TCGA, GEO, and GTEx database. The immune scores（IS）based on single-sample gene set enrichment analysis (ssGSEA) were calculated to identify the IRLs, which were then analyzed using univariate Cox regression analysis to identify significant prognostic IRLs. A risk score model was established to divide patients into low-risk and high-risk groups based on the median risk score of these IRLs. This was then validated by splitting TCGA dataset(n=304) into a training-set(n=152) and a valid-set(n=152). The fraction of 22 immune cell subpopulations was evaluated in each sample to identify the differences between low-risk and high-risk groups. Additionally, a ceRNA network associated with the IRLs was constructed.Results: A cohort of 326 CC and 21 normal tissue samples with corresponding clinical information was included in this study. Twenty-eight IRLs were collected according to the Pearson’s correlation analysis between immune score and lncRNA expression (P < 0.01). Four IRLs (BZRAP1-AS1, EMX2OS, ZNF667-AS1, and CTC-429P9.1) with the most significant prognostic values (P < 0.05) were identified which demonstrated an ability to stratify patients into low-risk and high-risk groups by developing a risk score model. It was observed that patients in the low‐risk group showed longer overall survival (OS) than those in the high‐risk group in the training-set, valid-set, and total-set. The area under the curve (AUC) of the receiver operating characteristic curve (ROC curve) for the four IRLs signature in predicting the one-, two-, and three-year survival rates were larger than 0.65. In addition, the low-risk and high-risk groups displayed different immune statuses in GSEA. These IRLs were also significantly correlated with immune cell infiltration. Conclusions: Our results showed that the IRL signature had a prognostic value for CC. Meanwhile, the specific mechanisms of the four-IRLs in the development of CC were ascertained preliminarily.
Gene Biomarker Prediction in Glioma by Integrating scRNA-seq Data and the Gene Regulatory Network
Authors: Qin Guimin , Ma Yuying , Yang Yuhan , Yin Yu , Liu Xiyang , Wang Liming 
Published: August 2020

Abstract
Background: Although great efforts have been made to study the occurrence and development of glioma, the molecular mechanisms of glioma are still unclear. Single-cell sequencing technology provides a new perspective for researchers to explore the pathogens of tumors to further help make treatment and prognosis decisions for patients with tumors.Methods: In this study, we proposed an algorithm framework to explore the molecular mechanisms of glioma by integrating single-cell gene expression profiles and gene regulatory relations. First, since there were great differences among malignant cells from different glioma samples, we analyzed the expression status of malignant cells for each sample, and then tumor consensus genes were identified by constructing and analyzing cell-specific networks. Second, to comprehensively analyze the characteristics of glioma, we integrated transcriptional regulatory relationships and consensus genes to construct a tumor-specific regulatory network. Third, we performed a hybrid clustering analysis to identify glioma cell types. Finally, candidate tumor marker genes were identified based on cell types and known glioma-related genes.Results: We got six identified cell types using the method we proposed and for these cell types, we performed functional and biological pathway enrichment analyses. The candidate tumor marker genes were analyzed through survival analysis and verified using literature from PubMed.Conclusions: The results showed that these candidate tumor marker genes were closely related to glioma and could provide clues for the diagnosis and prognosis of patients with glioma. In addition, we found that four of the candidate tumor marker genes (NDUFS5, NDUFA1, NDUFA13, and NDUFB8) belong to the NADH ubiquinone oxidoreductase subunit gene family, so we inferred that this gene family may be strongly related to glioma.
Up-regulated lncRNA-PVT1 Expression in Peripheral Blood Mononuclear Cells of Patients with Coronary Artery Disease is Correlated with Decreased Interleukin-10 Production
Authors: Miladpour Behnoosh , Seghatoleslam Atefeh , kalani mehdi , Erfani Mehran , Nowrouzi-Sohrabi peyman 
Published: August 2020

Abstract
Background: Plasmacytoma variant translocation 1 (PVT1) is a newly discovered long non-coding RNA (lncRNA), and it has not been previously studied in the inflammatory responses of peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD). Methods: This cross-sectional study was conducted in 15 CAD patients and 15 non-CAD (NCAD) individuals. PVT1 expression in PBMCs of the participants was measured, using real-time PCR. Interleukin (IL)-10, IL-22 and MMP-9 in the plasma and supernatant of the cultured PBMCs in the presence or absence of lipopolysaccharide (LPS) was assessed, using flowcytometry and ELISA.Results: An increased expression of PVT1 was observed in untreated PBMCs of CAD patients compared to the NCAD group. There was a significant up-regulation of PVT1 after LPS treatment in PBMCs of both groups. Plasma matrix metalloproteinase-9 (MMP-9) levels were found to be higher in CAD patients compared to the controls. The level of IL-10 and IL-22 production from the non-treated PBMCs of CAD was significantly lower compared to the NCAD group. In the total examined population, PVT1 expression was negatively correlated with IL-10 secretion. The results also showed a significant negative correlation between PVT1 expression and IL-10 produced by untreated cells. Conclusions: PVT1 expression is increased in PBMCs of CAD patients and this increased expression could be associated with decreased IL-10 production from PBMCs of these patients.