bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of MUC5AC by VEGF in human primary bronchial epithelial cells: implications for asthma
Authors: Kim Sung-Ho , Pei Qing-Mei , Jiang Ping , Liu Juan , Sun Rong-Fei , Qian Xue-Jiao , Liu Jiang-Bo 
Published: December 2019

Abstract
Background
Airway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Therefore, we sought to investigate the effect of VEGF on MUC5AC expression and study the underlying mechanisms.

Methods
In order to elucidate the precise mechanism underlying the effect of VEGF on MUC5AC expression, we tested the effects of VEGF on RhoA activation and the association of caveolin-1 and VEGFR2 in Primary Bronchial Epithelial Cells.

Results
VEGF up-regulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and activated RhoA. Additionally, VEGF-induced MUC5AC expression and RhoA activation were enhanced by disrupting caveolae with cholesterol depletion and reversed by cholesterol repletion, and inhibited by a selective VEGF receptor 2 (VEGFR2) inhibitor SU1498. Furthermore, phospho-VEGFR2 expression was decreased via overexpression of caveolin-1. VEGF treatment reduced the association of caveolin-1 and VEGFR2.

Conclusion
Collectively, our findings suggest that VEGF up-regulates MUC5AC expression and RhoA activation by interaction with VEGFR2, and this phenomenon was related with the association of caveolin-1 and VEGFR2. Further studies on these mechanisms are needed to facilitate the development of treatments for asthma.
Use of gene expression studies to investigate the human immunological response to malaria infection
Authors: Hodgson Susanne H. , Muller Julius , Lockstone Helen E. , Hill Adrian V. S. , Marsh Kevin , Draper Simon J. , Knight Julian C. 
Published: December 2019

AbstractBackgroundTranscriptional profiling of the human immune response to malaria has been used to identify diagnostic markers, understand the pathogenicity of severe disease and dissect the mechanisms of naturally acquired immunity (NAI). However, interpreting this body of work is difficult given considerable variation in study design, definition of disease, patient selection and methodology employed. This work details a comprehensive review of gene expression profiling (GEP) of the human immune response to malaria to determine how this technology has been applied to date, instances where this has advanced understanding of NAI and the extent of variability in methodology between studies to allow informed comparison of data and interpretation of results.MethodsDatasets from the gene expression omnibus (GEO) including the search terms; ‘plasmodium’ or ‘malaria’ or ‘sporozoite’ or ‘merozoite’ or ‘gametocyte’ and ‘Homo sapiens’ were identified and publications analysed. Datasets of gene expression changes in relation to malaria vaccines were excluded.ResultsTwenty-three GEO datasets and 25 related publications were included in the final review. All datasets related toPlasmodium falciparuminfection, except two that related toPlasmodium vivaxinfection. The majority of datasets included samples from individuals infected with malaria ‘naturally’ in the field (n = 13, 57%), however some related to controlled human malaria infection (CHMI) studies (n = 6, 26%), or cells stimulated withPlasmodiumin vitro (n = 6, 26%). The majority of studies examined gene expression changes relating to the blood stage of the parasite. Significant heterogeneity between datasets was identified in terms of study design, sample type, platform used and method of analysis. Seven datasets specifically investigated transcriptional changes associated with NAI to malaria, with evidence supporting suppression of the innate pro-inflammatory response as an important mechanism for this in the majority of these studies. However, further interpretation of this body of work was limited by heterogeneity between studies and small sample sizes.ConclusionsGEP in malaria is a potentially powerful tool, but to date studies have been hypothesis generating with small sample sizes and widely varying methodology. As CHMI studies are increasingly performed in endemic settings, there will be growing opportunity to use GEP to understand detailed time-course changes in host response and understand in greater detail the mechanisms of NAI.
Understanding the gap between access and use: a qualitative study on barriers and facilitators to insecticide-treated net use in Ghana
Authors: Ahorlu Collins Stephen , Adongo Philip , Koenker Hannah , Zigirumugabe Sixte , Sika-Bright Solomon , Koka Eric , Tabong Philip Teg-Nefaah , Piccinini Danielle , Segbaya Sylvester , Olapeju Bolanle , Monroe April 
Published: December 2019

Abstract
Background
Mass and continuous distribution channels have significantly increased access to insecticide-treated nets (ITNs) in Ghana since 2000. Despite these gains, a large gap remains between ITN access and use.

Methods
A qualitative research study was carried out to explore the individual and contextual factors influencing ITN use among those with access in three sites in Ghana. Eighteen focus group discussions, and free listing and ranking activities were carried out with 174 participants; seven of those participants were selected for in-depth case study. Focus group discussions and case study interviews were audio-recorded, transcribed verbatim, and analysed thematically.

Results
ITN use, as described by study participants, was not binary; it varied throughout the night, across seasons, and over time. Heat was the most commonly cited barrier to consistent ITN use and contributed to low reported ITN use during the dry season. Barriers to ITN use throughout the year included skin irritation; lack of airflow in the sleeping space; and, in some cases, a lack of information on the connection between the use of ITNs and malaria prevention. Falling ill or losing a loved one to malaria was the most powerful motivator for consistent ITN use. Participants also discussed developing a habit of ITN use and the economic benefit of prevention over treatment as facilitating factors. Participants reported gender differences in ITN use, noting that men were more likely than women and children to stay outdoors late at night and more likely to sleep outdoors without an ITN.

Conclusion
The study results suggest the greatest gains in ITN use among those with access could be made by promoting consistent use throughout the year among occasional and seasonal users. Opportunities for improving communication messages, such as increasing the time ITNs are aired before first use, as well as structural approaches to enhance the usability of ITNs in challenging contexts, such as promoting solutions for outdoor ITN use, were identified from this work. The information from this study can be used to inform social and behaviour change messaging and innovative approaches to closing the ITN use gap in Ghana.
Associations between twelve common gene polymorphisms and susceptibility to hepatocellular carcinoma: evidence from a meta-analysis
Authors: Quan Yi , Yang Jun , Qin Tao , Hu Yufang 
Published: December 2019

Abstract
Background
Associations between polymorphisms in vitamin D receptor (VDR)/vascular endothelial growth factor (VEGF)/interleukin-18 (IL-18)/mannose-binding lectin (MBL) and susceptibility to hepatocellular carcinoma (HCC) were already explored by many studies, yet the results of these studies were inconsistent. The aim of this meta-analysis was to better clarify associations between polymorphisms in VDR/VEGF/IL-18/MBL and HCC by combing the results of all relevant studies.

Methods
Eligible publications were searched from PubMed, Embase, WOS, and CNKI. We used Review Manager to combine the results of individual studies.

Results
Thirty studies were included in this study. Combined results revealed that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms were all significantly associated with HCC in the overall pooled population. We also obtained similar significant associations for VDR rs7975232, VDR rs2228570, IL-18 rs1946518, and MBL rs7096206 polymorphisms in Asians.

Conclusions
Collectively, this meta-analysis proved that VDR rs7975232, VDR rs2228570, VEGF rs699947, VEGF rs3025039, IL-18 rs1946518, and MBL rs7096206 polymorphisms may confer susceptibility to HCC in certain populations.
Repeated lumbar punctures within 3 days may affect CSF biomarker levels
Authors: Olsson Martin , Ärlig Johan , Hedner Jan , Blennow Kaj , Zetterberg Henrik 
Published: December 2019

AbstractLumbar puncture (LP) is a common way of collecting cerebrospinal fluid (CSF) both in the clinic and in research. In this extension of a study on the relationship between sleep deprivation and CSF biomarkers for Alzheimer’s disease, we investigated CSF biomarker dynamics in relation to rebound sleep after sleep deprivation. Two LPs were performed within 3 days in 13 healthy volunteers. We noticed an unexpected sharp rise in biomarker concentrations in the second sample and therefore repeated the experiment, but without sleep intervention, in four additional individuals. The findings were similar in these subjects, suggesting an inherent methodological problem with repeated LPs. The result corroborates findings in studies with repeated CSF collection via indwelling lumbar catheters, and needs to be addressed in, for instance, pharmacodynamic studies employing these techniques.
Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma
Authors: Lewitzki Victor , Klement Rainer J. , Kosmala Rebekka , Lisowski Dominik , Flentje Michael , Polat Bülent 
Published: December 2019

Abstract
Background
Current standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ.

Methods
Data of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method.

Results
Median overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95% CI 1.47–3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95% CI 1.21–3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504).

Conclusions
Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability.
A descriptive survey on the use of resuscitative endovascular balloon occlusion of the aorta (REBOA) for pelvic fractures at US level I trauma centers
Authors: Jarvis Stephanie , Kelly Michael , Mains Charles , Corrigan Chad , Patel Nimesh , Carrick Matthew , Lieser Mark , Banton Kaysie , Bar-Or David 
Published: December 2019

AbstractBackgroundResuscitative endovascular balloon occlusion of the aorta (REBOA) is not widely adopted for pelvic fracture management. Western Trauma Association recommends REBOA for hemodynamically unstable pelvic fractures, whereas Eastern Association for the Surgery of Trauma and Advanced Trauma Life Support do not.MethodUtilizing a prospective cross-sectional survey, all 158 trauma medical directors at American College of Surgeons-verified Level I trauma centers were emailed survey invitations. The study aimed to determine the rate of REBOA use, REBOA indicators, and the treatment sequence of REBOA for hemodynamically unstable pelvic fractures.ResultsOf those invited, 25% (40/158) participated and 90% (36/40) completed the survey. Nearly half of trauma centers [42% (15/36)] use REBOA for pelvic fracture management. All participants included hemodynamic instability as an indicator for REBOA placement in pelvic fractures. In addition to hemodynamic instability, 29% (4/14) stated REBOA is used for patients who are ineligible for angioembolization, 14% (2/14) use REBOA when interventional radiology is unavailable, 7% (1/14) use REBOA for patients with a negative FAST. Fifty percent (7/14) responded that hemodynamically unstable pelvic fractures exclusively indicates REBOA placement. Hemodynamic instability for pelvic fractures was most commonly defined as systolic blood pressure of < 90 [56% (20/36)]. At centers using REBOA, REBOA was the first line of treatment for hemodynamically unstable pelvic fractures 40% (6/15) of the time.ConclusionsThere is little consensus on REBOA use for pelvic fractures at US Level I Trauma Centers, except that hemodynamically unstable pelvic fractures consistently indicated REBOA use.
Vireo: Bayesian demultiplexing of pooled single-cell RNA-seq data without genotype reference
Authors: Huang Yuanhua , McCarthy Davis J. , Stegle Oliver 
Published: December 2019

AbstractMultiplexed single-cell RNA-seq analysis of multiple samples using pooling is a promising experimental design, offering increased throughput while allowing to overcome batch variation. To reconstruct the sample identify of each cell, genetic variants that segregate between the samples in the pool have been proposed as natural barcode for cell demultiplexing. Existing demultiplexing strategies rely on availability of complete genotype data from the pooled samples, which limits the applicability of such methods, in particular when genetic variation is not the primary object of study. To address this, we here present Vireo, a computationally efficient Bayesian model to demultiplex single-cell data from pooled experimental designs. Uniquely, our model can be applied in settings when only partial or no genotype information is available. Using pools based on synthetic mixtures and results on real data, we demonstrate the robustness of Vireo and illustrate the utility of multiplexed experimental designs for common expression analyses.
Retraining automatic action tendencies for smoking using mobile phone-based approach-avoidance bias training: A study protocol for a randomized controlled study
Authors: Machulska Alla , Kleinke Kristian , Eiler Tanja Joan , Grünewald Armin , Brück Rainer , Jahn Katharina , Niehaves Björn , Gethmann Carl Friedrich , Klucken Tim 
Published: December 2019

Abstract
Background
Automatic tendencies to approach drug-related cues have been linked to the development and maintainance of harmful drug-taking behavior. Recent studies have demonstrated that these automatic approach tendencies can be targeted directly by means of cognitive bias modification (CBM). Moreover, changing those approach tendencies may enhance treatment outcomes. However, training and therapy effects tend to be rather small and adherence to the training might be impaired by time-consuming multiple laboratory training sessions. Here, we present a protocol for a randomized controlled design to improve CBM training efficiency and facilitate access to the training by providing mobile-phone-based training sessions at home to current smokers motivated to quit smoking.

Methods
Participants (n = 100) are current smokers who smoke at least six cigarettes per day for at least 6 months and are willing to quit smoking. All participants attend a brief behavioral smoking cessation intervention (TAU) and are randomly assigned either to an experimental (TAU + training) or a control group. Participants in the experimental condition are given access to a training application (app) aimed at retraining automatic approach biases for smoking cues. Participants are instructed to perform the app training outside the laboratory context on a daily basis for 14 consecutive days. Participants in the control group do not receive the training. Primary outcome measures are changes in smoking-related approach biases and reductions in daily nicotine consumption as assessed at baseline, post-training and at 6-week follow up. Secondary outcome measures include approach biases for alternative stimuli or smoking stimuli to which participants were not exposed during training, attentional and association biases, biochemical outcomes, and self-reported smoking behavior, also measured at three different time points (baseline, post-training, and follow up). After completion of the study, smokers in the control condition will receive access to the training app.

Discussion
This randomized controlled trial is the first to test the effectiveness of an app-based CBM intervention as an adjunct to a brief smoking cessation intervention in smokers motivated to quit smoking. The results of this study can inform future research in the optimization and advancement of CBM treatment for addiction.

Trial registration
Current Controlled Trials, ISRCTN15690771. Registered on 20 November 2018.
The effect and mechanism of YH0618 granule on chemotherapy- induced hair loss in patients with breast cancer: study protocol for a randomized, double-blind, multi-center clinical trial
Authors: You Jie-shu , Guo Li , Huang Mei , Shi Xin-lei , Lin Man-di , Guo Zhen , Cao Ya-li , Sun You-zhi , Xu Qian , Qu Wei-ling , Liu Huan-lan , Chen Jian-ping 
Published: December 2019

Abstract
Background
Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the “Essence of the kidney is reflected on the hair”. Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction.

Methods/design
Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine.

Discussion
This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development.

Trial registration
Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.
Will savings from biosimilars offset increased costs related to dose escalation? A comparison of infliximab and golimumab for rheumatoid arthritis
Authors: Curtis Jeffrey R. , Xie Fenglong , Kay Jonathan , Kallich Joel D 
Published: December 2019

Abstract
Introduction
Biosimilar infliximab has the potential for appreciable cost savings compared to its reference biologic, but dose escalation is common and increases costs. We compared frequency of dose escalation and associated Medicare-approved amount so as to determine the break-even point at which infliximab dose escalation would offset the cost savings of using a biosimilar, referent to alternatively using golimumab.

Methods
We studied Medicare enrollees with rheumatoid arthritis (RA) initiating infliximab or golimumab. Frequency of dose escalation was summarized descriptively over 18 months, as were Medicare-approved amounts for reimbursement. Analyses were repeated conditioning on high adherence (i.e., non-discontinuation, > 10-week gap). Multivariable-adjusted logistic regression and mixed models evaluated factors associated with infliximab dose escalation.

Results
A total of 5174 infliximab and 2843 golimumab initiators were observed. Dose escalation was rare for golimumab (5%) but common for infliximab (49%), and was even more common (72%) for infliximab among patients who persisted on treatment. Regardless of dose escalation, the adjusted least square mean dollar amounts were appreciably higher for golimumab ($28,146) than for infliximab ($21,216) and greater among persistent patients (cost difference $9269, favoring infliximab). Only when patients escalated infliximab to ≥ 8 mg/kg every 6 weeks was golimumab IV at break-even or less expensive. After controlling for multiple factors, physician ownership of the infusion center was associated with greater likelihood of infliximab dose escalation (odds ratio = 1.25, 95% CI 1.09–1.44).

Conclusion
Despite frequent dose escalation with infliximab that often increase its dose by threefold or more, the savings from the current price of its biosimilar substantially offsets the costs of an alternative infused TNFi biologic for which no biosimilar is available.
Convergence rates to the damped system of compressible adiabatic flow through porous media with boundary effect
Authors: Zhang Lina , Geng Shifeng , Gao Yuling 
Published: December 2019

AbstractIn this paper, we consider convergence rates to solutions for the damped system of compressible adiabatic flow through porous media with boundary effect. Compared with the results obtained by Pan, the better convergence rates are obtained in this paper. Our approach is based on the technical time-weighted energy estimates.