bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro antibiofilm activity of chlorhexidine digluconate on polylactide-based and collagen-based membranes
Authors: Rudolf Jan-Luca , Moser Corina , Sculean Anton , Eick Sigrun 
Published: December 2019

AbstractBackgroundIn Guided Tissue Regeneration (GTR), barrier membranes are used to allow selective cell populations to multiply and to promote periodontal regeneration. A frequent complication is membrane exposure to the oral cavity followed by bacterial colonization. The purpose of this in-vitro-study was to elucidate, if rinsing with a chlorhexidine digluconate solution (CHX) prevents bacterial adhesion, and whether it interferes with attachment of periodontal ligament (PDL) fibroblasts and epithelial cells to membrane surfaces.MethodsFirstly, two bioresorbable membranes (polylactide-based and collagen-based) were dipped into 0.06% CHX and 0.12% CHX, before biofilms (2-species representing periodontal health, 6-species representing a periodontitis) were formed for 2 h and 8 h. Subsequently, colony forming units (cfu) were counted. Secondly, the membranes were treated with CHX and inoculated in bacteria suspension two-time per day for 3 d before cfu were determined. In additional series, the influence of CHX and bacterial lysates on attachment of epithelial cells and PDL fibroblasts was determined. Parameter-free tests were applied for statistical analysis.ResultsCfu in “healthy” biofilms did not differ between the two membranes, more cfu were counted in “periodontitis” biofilm on collagen than on polylactide membranes. One-time dipping of membranes into CHX solutions did not markedly influence the cfu counts of both biofilms on polylactide membrane; those on collagen-based membrane were significantly reduced with being 0.12% CHX more active than 0.06% CHX. More-fold CHX dipping of membranes reduced concentration-dependent the cfu counts of both biofilms on both membranes. In general, the number of attached gingival epithelial cells and PDL fibroblasts was higher on collagen than on polylactide membrane. Lysates of the periodontopathogenic bacteria inhibited attachment of PDL fibroblasts to membranes. CHX decreased in a concentration-dependend manner the number of attached gingival epithelial cells and PDL fibroblasts.ConclusionsThe present in-vitro results appear to indicate that membranes in GTR should only be used when bacteria being associated with periodontal disease have been eliminated. An exposure of the membrane should be avoided. Rinsing with CHX may prevent or at least retard bacterial colonization on membrane exposed to the oral activity. However, a certain negative effect on wound healing cannot be excluded.
Comprehensive analysis of DNA methylation and gene expression profiles in cholangiocarcinoma
Authors: Zhang Cheng , Zhang Bingye , Meng Di , Ge Chunlin 
Published: December 2019

Abstract
Background
The incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis.

Methods
The gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database.

Results
We identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA.

Conclusions
Our study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.
Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity
Authors: Lubell Yoel , Chandna Arjun , Smithuis Frank , White Lisa , Wertheim Heiman F. L. , Redard-Jacot Maël , Katz Zachary , Dondorp Arjen , Day Nicholas , White Nicholas , Dittrich Sabine 
Published: December 2019

AbstractMalaria is no longer a common cause of febrile illness in many regions of the tropics. In part, this success is a result of improved access to accurate diagnosis and effective anti-malarial treatment, including in many hard-to-reach rural areas. However, in these settings, management of other causes of febrile illness remains challenging. Health systems are often weak and other than malaria rapid tests no other diagnostics are available. With millions of deaths occurring annually due to treatable bacterial infections and the ever increasing spread of antimicrobial resistance, improvement in the management of febrile illness is a global public health priority. Whilst numerous promising point-of-care diagnostics are in the pipeline, substantial progress can be made in the interim with existing tools: C-reactive protein (CRP) is a highly sensitive and moderately specific biomarker of bacterial infection and has been in clinical use for these purposes for decades, with dozens of low-cost devices commercially available. This paper takes a health-economics approach to consider the possible advantages of CRP point-of-care tests alongside rapid diagnostic tests for malaria, potentially in a single multiplex device, to guide antimicrobial therapy for patients with febrile illness. Three rudimentary assessments of the costs and benefits of this approach all indicate that this is likely to be cost-effective when considering the incremental costs of the CRP tests as compared with either (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns in areas of low transmission. While CRP-guided antibiotic therapy alone cannot resolve all challenges associated with management of febrile illness in remote tropical settings, in the short-term a multiplexed CRP and malaria RDT could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs. These findings should spark further interest amongst industry, academics and policy-makers in the development and deployment of such diagnostics, and discussion on their geographically appropriate use.
Indigenously developed digital handheld Android-based Geographic Information System (GIS)-tagged tablets (TABs) in malaria elimination programme in Mangaluru city, Karnataka, India
Authors: Baliga B. Shantharam , Jain Animesh , Koduvattat Naren , Kumar B. G. Prakash , Kumar Manu , Kumar Arun , Ghosh Susanta K. 
Published: December 2019

Abstract
Background
Under-reporting, delayed diagnosis, incomplete treatment and inadequate vector management are few among many factors responsible for uninterrupted transmission of malaria in India. Information technology (IT) and mobile apps can be utilized effectively to overcome these hurdles. Indigenously developed digital handheld geographic information system (GIS)-tagged Android-based tablets (TABs) has been designed especially for implementation of digitization protocol. This has changed the effectiveness of malaria surveillance and intervention strategies in a malaria endemic area of Mangaluru city, Karnataka, India.

Methods
A software was developed and implemented for control measures to create a digital database of each malaria case. Secondary data analyses were carried out to determine and compare differences in malariometric indices between pre- and post-digitization years. With the introduction of this software active surveillance, information education and communication (IEC), and anti-vector measures were made ‘incidence-centric’. This means that the entire control measures were carried out in the houses where the malaria cases (index cases) were reported and also in surrounding houses.

Results
Annual blood examination rate (ABER) increased from 13.82 to 32.8%. Prompt reporting of new cases had improved (36% within 24 h and 80% within 72 h). Complete treatment and parasite clearance time were documented in 98% of cases. In the second post-digitization year untraceable cases reduced from 11.3 to 2.7%; contact blood smears collection also increased significantly (p < 0.001); Slide Positivity Rate (SPR) decreased from 15.5 to 10.48%; malaria cases reduced by 30%.

Conclusions
IT is very useful in translation of digitized surveillance to core interventions thereby effectively reduce incidence of malaria. This technology can be used effectively to translate smart surveillance to core interventions following the ‘1-3-7-14’ strategy.
Empirically derived dietary patterns and constipation among a middle-aged population from China, 2016–2018
Authors: Li Li , Huang Ai-Ping , Wang Li-Qin , Yu Xiao-Long 
Published: December 2019

Abstract
Background
The association of dietary patterns with constipation is not well established, particularly in Chinese population. Therefore, the present study aimed to determine the relationship between dietary patterns and the risk of constipation in a middle-aged Chinese population.

Methods
A total of 2267 participants aged 45–59 years were recruited in Hangzhou city, the capital of Zhejiang Province, east China from August 2016 to October 2018. Dietary intake was estimated using a semi-quantitative food frequency questionnaire (FFQ) containing 138 food items. Constipation was defined using the Rome II criteria. Multivariate logistic regression was used to examine the association between dietary patterns and the risk of constipation.

Results
Three major dietary patterns were extracted by factor analysis and labeled as the traditional southern Chinese, Western and grains-vegetables patterns. The prevalence of constipation in our study population was 13.28%. Compared with the participants in the lowest quartile, the participants in the highest quartile of the traditional southern Chinese pattern were associated with reduced odds of constipation (odd ratios (OR) = 0.79; 95%confidence interval (CI): 0.626–0.981; P < 0.05), after adjusting for confounding variables. In contrast, we found no significant associations between the Western and grains-vegetables patterns and the risk of constipation (P > 0.05).

Conclusions
Our study demonstrated that the traditional southern Chinese pattern was associated with a reduced risk of constipation. Further longitudinal studies are needed to confirm our findings.
Tracking research trends and hotspots in sperm DNA fragmentation testing for the evaluation of male infertility: a scientometric analysis
Authors: Baskaran Saradha , Agarwal Ashok , Panner Selvam Manesh Kumar , Finelli Renata , Robert Kathy Amy , Iovine Concetta , Pushparaj Peter Natesan , Samanta Luna , Harlev Avi , Henkel Ralf 
Published: December 2019

AbstractBackgroundThis article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999–2018) using a scientometric approach.MethodsA stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology.ResultsA total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 ton = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933).ConclusionsOur analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes.
Hedgehog/GLI signaling in tumor immunity - new therapeutic opportunities and clinical implications
Authors: Grund-Gröschke Sandra , Stockmaier Georg , Aberger Fritz 
Published: December 2019

AbstractUncontrolled activation of the Hedgehog/Glioma-associated oncogene (HH/GLI) pathway is a potent oncogenic driver signal promoting numerous cancer hallmarks such as proliferation, survival, angiogenesis, metastasis and metabolic rewiring. Several HH pathway inhibitors have already been approved for medical therapy of advanced and metastatic basal cell carcinoma and acute myeloid leukemia with partially impressive therapeutic activity. However, de novo and acquired resistance as well as severe side effects and unexplained lack of therapeutic efficacy are major challenges that urgently call for improved treatment options with more durable responses. The recent breakthroughs in cancer immunotherapy have changed our current understanding of targeted therapy and opened up promising therapeutic opportunities including combinations of selective cancer pathway and immune checkpoint inhibitors. Although HH/GLI signaling has been intensely studied with respect to the classical hallmarks of cancer, its role in the modulation of the anti-tumoral immune response has only become evident in recent studies. These have uncovered HH/GLI regulated immunosuppressive mechanisms such as enhanced regulatory T-cell formation and production of immunosuppressive cytokines. In light of these exciting novel data on oncogenic HH/GLI signaling in immune cross-talk and modulation, we summarize and connect in this review the existing knowledge from different HH-related cancers and chronic inflammatory diseases. This is to provide a basis for the investigation and evaluation of novel treatments combining immunotherapeutic strategies with approved as well as next-generation HH/GLI inhibitors. Further, we also critically discuss recent studies demonstrating a possible negative impact of current HH/GLI pathway inhibitors on the anti-tumoral immune response, which may explain some of the disappointing results of several oncological trials with anti-HH drugs.
The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS
Authors: Zhou Yile , Yang Yajie , Liang Tao , Hu Yan , Tang Haihong , Song Dongli , Fang Hao 
Published: December 2019

Abstract
Background
Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress.

Methods
The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms.

Results
In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation.

Conclusions
TCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process.
SUPREME-HN: a retrospective biomarker study assessing the prognostic value of PD-L1 expression in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Authors: Pai Sara I. , Cohen Ezra E. W. , Lin Derrick , Fountzilas George , Kim Edward S. , Mehlhorn Holger , Baste Neus , Clayburgh Daniel , Lipworth Loren , Resteghini Carlo , Shara Nawar , Fujii Takashi , Zhang Jun , Stokes Michael , Wang Huifen , Twumasi-Ankrah Philip , Wildsmith Sophie , Khaliq Asud , Melillo Giovanni , Shire Norah 
Published: December 2019

Abstract
Background
Programmed cell death ligand-1 (PD-L1) expression on tumor cells (TCs) is associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy, although its role as a prognostic factor is controversial. This study investigates whether tumoral expression of PD-L1 is a prognostic marker in patients with recurrent and/or metastatic (R/M) HNSCC treated with standard chemotherapy.

Methods
This retrospective, multicenter, noninterventional study assessed PD-L1 expression on archival R/M HNSCC tissue samples using the VENTANA PD-L1 (SP263) Assay. PD-L1 high was defined as PD-L1 staining of ≥ 25% TC, with exploratory scoring at TC ≥ 10% and TC ≥ 50%. The primary objective of this study was to estimate the prognostic value of PD-L1 status in terms of overall survival (OS) in patients with R/M HNSCC.

Results
412 patients (median age, 62.0 years; 79.9% male; 88.2% Caucasian) were included from 19 sites in seven countries. 132 patients (32.0%) had TC ≥ 25% PD-L1 expression; 199 patients (48.3%) and 85 patients (20.6%) had TC ≥ 10% and ≥ 50%, respectively. OS did not differ significantly across PD-L1 expression (at TC ≥ 25% cutoff median OS: 8.2 months vs TC < 25%, 10.1 months, P = 0.55) or the ≥ 10% and ≥ 50% cutoffs (at TC ≥ 10%, median OS: 9.6 months vs TC < 10%, 9.4 months, P = 0.32, and at TC ≥ 50%, median OS 7.9 vs TC < 50%, 10.0 months, P = 0.39, respectively).

Conclusions
PD-L1 expression, assessed using the VENTANA PD-L1 (SP263) Assay, was not prognostic of OS in patients with R/M HNSCC treated with standard of care chemotherapies.
Trial registration ClinicalTrials.gov, NCT02543476. Registered September 4, 2015.
Effect of oral L-citrulline on brachial and aortic blood pressure defined by resting status: evidence from randomized controlled trials
Authors: Yang Huan-Huan , Li Xin-Li , Zhang Wei-Guo , Figueroa Arturo , Chen Li-Hua , Qin Li-Qiang 
Published: December 2019

Abstract
Background
Experimental evidence indicates that oral L-citrulline (L-Cit) may reduce resting blood pressure (BP) as well as BP responses to exercise and cold exposure (non-resting). However, results from human intervention trials are inconsistent. This study aims to summarize the clinical evidence regarding the effects of L-Cit supplementation on brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), in addition to aortic SBP and aortic DBP at rest and non-resting conditions.

Methods
Multiple databases including PubMed, Embase, Cochrane library, Web of Science, and Clinical Trials were searched systematically. Randomized controlled trials of human participants were quantitatively meta-analyzed.

Results
Fourteen trials contained in eight studies were available for quantitative syntheses for brachial BP. Results showed that L-Cit supplementation significantly reduced both brachial SBP (− 4.490 mmHg, 95% CI: − 7.332 to − 1.648, P = 0.002) and brachial DBP (− 3.629 mmHg, 95% CI: − 5.825 to − 1.434, P = 0.001). Nine of the trials were meta-analyzed for aortic BP which showed that L-Cit intervention significantly reduced aortic SBP (− 6.763 mmHg, 95% CI: − 10.991 to − 2.534, P = 0.002), but not aortic DBP (− 3.396 mmHg, 95% CI: − 7.418 to 0.627, P = 0.098). The observed reducing effects of L-Cit appeared stronger for non-resting than for resting brachial SBP (P for difference = 0.044).

Conclusion
L-Cit supplementation significantly decreased non-resting brachial and aortic SBP. Brachial DBP was significantly lowered by L-Cit regardless of resting status. Given the relatively small number of available trials in the stratified analyses and the potential limitations of these trials, the present findings should be interpreted cautiously and need to be confirmed in future well-designed trials with a larger sample size.