bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronic Nicotine Delivery Systems and Serum Folate: A Case Study
Authors: Croff Julie M , Chiaf Ashleigh L , Hartwell Micah L , Crockett Erica K , Tan Chibing , Teague Kent 
Published: November 2019

Introduction: In 2018, the US Surgeon General declared youth electronic nicotine delivery systems (ENDS) use as an epidemic. Combustible cigarettes have been shown to adversely affect folate status; however, no study to date has explored how ENDS impact folate status. Methods: In this case study, a white 18-year-old woman was followed for a 1-month period as part of a larger study. During her participation in the study, a self-report of dietary folate consumption and use of alcohol, tobacco, and other drugs (ATOD) was collected. Each week, dried blood spots were collected to assess red blood cell (RBC) and serum folate. Results: During the first 2 weeks of the study, she used ENDS and her serum folate values were depleted in the ranges of 1.91 to 4.39 µg/L. During the third week, when no ENDS were used, her serum folate value was measured at 29.44 µg/L. When ENDS use resumed during the fourth week, her serum folate value fell to 7.50 µg/L. Conclusions: This relationship suggests the need for additional studies on ENDS use and serum folate status, particularly among adolescent women who already have the lowest folate status nationally.
Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease
Authors: Elshazly Mohamed B , Mani Preethi , Nissen Steven , Brennan Danielle M , Clark Donald , Martin Seth , Jones Steven R , Quispe Renato , Donnellan Eoin , Nicholls Stephen J , Puri Rishi 
Published: November 2019

Aim Remnant cholesterol has been proposed to promote atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol, yet the underlying mechanisms are not well understood. We aimed to study the association of remnant cholesterol with coronary atheroma progression and clinical events. Methods We analyzed data from 5754 patients with coronary artery disease undergoing serial intravascular ultrasonography who were enrolled in 10 trials examining various medical therapies. Remnant cholesterol was calculated as (non-high-density lipoprotein cholesterol – low-density lipoprotein cholesterol (estimated using the Hopkins–Martin equation)). Changes in percentage atheroma volume and 2-year major adverse cardiovascular events were compared across various levels of remnant cholesterol, and multivariable models were used to assess the independent relationship of remnant cholesterol with changes in percentage atheroma volume. Results The mean age was 58.1 ± 9.2 years, 28% were women and 96% received a statin. Percentage atheroma volume progression (changes in percentage atheroma volume > 0) occurred in a linear fashion at on-treatment remnant cholesterol levels of 25 mg/dL or greater. The highest on-treatment remnant cholesterol quartile demonstrated greater percentage atheroma volume progression (+0.53 ± 0.26 vs. –0.15 ± 0.25%, P < 0.001) and 2-year major adverse cardiovascular events (23% vs. 14%, log–rank P < 0.001) compared with the lowest. In multivariable analyses, changes in percentage atheroma volume significantly correlated with on-treatment remnant cholesterol ( P < 0.001] independent of low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, high-density lipoprotein cholesterol levels and clinical risk factors. Changes in percentage atheroma volume also significantly correlated with changes in remnant cholesterol following multivariable adjustment. Conclusions In statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol was associated with coronary atheroma progression regardless of conventional lipid parameters, C-reactive protein or clinical risk factors. Higher remnant cholesterol levels also correlated with higher major adverse cardiovascular events. These data support further investigations into remnant cholesterol-lowering interventions in statin-treated patients harboring residual atherosclerotic cardiovascular disease risk.
Thrombospondin inhibits adhesion of platelets to glass and protein- covered substrata
Authors: Lahav J 
Published: November 2019

Abstract
Glass and protein-covered surfaces when treated with the platelet- secreted glycoprotein thrombospondin lose their capacity to bind unstimulated platelets. In comparison to the number that bind to fibronectin-covered glass surfaces, less than 3% bind to thrombospondin- covered glass surfaces. When the fibronectin-covered surface is incubated with thrombospondin, it loses 87% of its binding capacity for platelets. The inhibitory effect of thrombospondin on platelet binding increases with increasing amounts of the adsorbed protein and reaches maximal values at 65% saturation of the adsorption of thrombospondin to the surface. Platelet spreading on the surface is also completely inhibited by thrombospondin. These data suggest that thrombospondin is nonthrombogenic and can modulate platelet adhesion to the subendothelium.
Non-del(5q) myelodysplastic syndromes–associated loci detected by SNP-array genome-wide association meta-analysis
Authors: McGraw Kathy L. , Cheng Chia-Ho , Chen Y. Ann , Hou Hsin-An , Nilsson Björn , Genovese Giulio , Cluzeau Thomas , Pellagatti Andrea , Przychodzen Bartlomiej P. , Mallo Mar , Arenillas Leonor , Mohamedali Azim , Adès Lionel , Sallman David A. , Padron Eric , Sokol Lubomir , Moreilhon Chimene , Raynaud Sophie , Tien Hwei-Fang , Boultwood Jacqueline , Ebert Benjamin L. , Sole Francesc , Fenaux Pierre , Mufti Ghulam J. , Maciejewski Jaroslaw P. , Kanetsky Peter A. , List Alan F. 
Published: November 2019

Key PointsWe report here the findings from the first known MDS genome-wide association study and meta-analysis identifying 8 unique loci. Genes harboring suggested MDS-associated loci, including EYA2, are innate immune regulators and may have clinical and biological relevance.
Mendelian randomisation analysis of red cell distribution width in pulmonary arterial hypertension
Authors: Ulrich Anna , Wharton John , Thayer Timothy E. , Swietlik Emilia M. , Assad Tufik R. , Desai Ankit A. , Gräf Stefan , Harbaum Lars , Humbert Marc , Morrell Nicholas W. , Nichols William C. , Soubrier Florent , Southgate Laura , Trégouët David-Alexandre , Trembath Richard C. , Brittain Evan L. , Wilkins Martin R. , Prokopenko Inga , Rhodes Christopher J. 
Published: November 2019

Pulmonary arterial hypertension (PAH) is a rare disease that leads to premature death from right heart failure. It is strongly associated with elevated red cell distribution width (RDW), a correlate of several iron status biomarkers. High RDW values can signal early-stage iron deficiency or iron deficiency anaemia. This study investigated whether elevated RDW is causally associated with PAH.A two-sample Mendelian randomisation (MR) approach was applied to investigate whether genetic predisposition to higher levels of RDW increases the odds of developing PAH. Primary and secondary MR analyses were performed using all available genome-wide significant RDW variants (n=179) and five genome-wide significant RDW variants that actviasystemic iron status, respectively.We confirmed the observed association between RDW and PAH (OR 1.90, 95% CI 1.80–2.01) in a multicentre case–control study (cases n=642, disease controls n=15 889). The primary MR analysis was adequately powered to detect a causal effect (odds ratio) between 1.25 and 1.52 or greater based on estimates reported in the RDW genome-wide association study or from our own data. There was no evidence for a causal association between RDW and PAH in either the primary (ORcausal1.07, 95% CI 0.92–1.24) or the secondary (ORcausal1.09, 95% CI 0.77–1.54) MR analysis.The results suggest that at least some of the observed association of RDW with PAH is secondary to disease progression. Results of iron therapeutic trials in PAH should be interpreted with caution, as any improvements observed may not be mechanistically linked to the development of PAH.
Inhaled corticosteroid use and the incidence of lung cancer in COPD
Authors: Suissa Samy , Dell'Aniello Sophie , Gonzalez Anne V. , Ernst Pierre 
Published: November 2019

BackgroundInhaled corticosteroids (ICS) are suggested for potential chemoprevention of lung cancer. Several observational studies in patients with chronic obstructive pulmonary disease (COPD) reported inconsistent results, either significant reductions in lung cancer incidence with ICS use or no effect. We assessed this association, using an approach that avoided biases affecting some of the studies.MethodsA cohort of patients with COPD, new users of long-acting bronchodilators over 2000–2014, was formed using the Quebec healthcare databases, and followed until 2015 for a first diagnosis of lung cancer. A 1-year delay after cohort entry was used to avoid protopathic bias and a 1-year latency period was included after the initiation of ICS use. A time-dependent Cox regression model was used to estimate the hazard ratio (HR) of lung cancer associated with ICS exposure, adjusted for covariates.ResultsThe cohort involved 63 276 subjects, including 63% receiving ICS, with 3743 lung cancers occurring during a mean follow-up of 5 years. The adjusted HR of lung cancer associated with any ICS exposure was 1.01 (95% CI 0.94–1.08), relative to no ICS use. The HR with longer time (>4 years) since ICS initiation was 0.92 (95% CI 0.83–1.03), while with higher mean daily ICS dose (>1000 μg fluticasone equivalents) was 1.36 (95% CI 1.03–1.81).ConclusionsInhaled corticosteroid use is not associated with a reduction in lung cancer incidence in patients with COPD. Observational studies reporting such reduction may have been affected by time-related biases and the inclusion of patients with asthma. The proposition of a randomised trial warrants some caution.
Evaluation of free and total fluoride concentration in mouthwashes via measurement with ion-selective electrode
Authors: Reshetnyak Vladimir Yu. , Nesterova Olga V. , Admakin Oleg I. , Dobrokhotov Denis A. , Avertseva Irina N. , Dostdar Samira A. , Khakimova Dinara F. 
Published: November 2019

Abstract
Background
The aim of this study was to compare free fluoride concentration and total fluoride concentration in mouthwashes.

Methods
Fluorine-containing mouthwashes from various companies and manufacturers (Colgate Total Plax Classic Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Gentle Mint®, Colgate-Palmolive, New York, USA; Colgate Total Plax Fresh Mint®, Colgate-Palmolive, New York, USA; Oral B Advantage®, Procter&Gamble, Cincinnati, USA; Reach Fresh Mint®, Johnson&Johnson, New Brunswick, USA; Foramen®, Laboratorios Foramen, Guarnizo, Spain; Lacalut Sensitive®, Dr. THEISS, Homburg, Germany; Sensodyne®, GlaxoSmithKline, London, UK; Vesna F®, Vita, Saint Petersburg, Russia; Lacalut Fresh®, Dr. THEISS, Homburg, Germany) were selected as study objects. Fluoride measurements were carried out using the fluoride selective electrode.

Results
Free fluoride:total fluoride ratio was more than 80% for six samples (Colgate Total Plax Gentle Mint® - 88%, Colgate Total Plax Fresh Mint® - 99%, Oral B Advantage® - 92%, Reach Fresh Mint® - 92 and 89% for the mouthwash of another batch, Lacalut Sensitive® - 94%) and less than 63% for three samples (Colgate Total Plax Classic Mint® - 56%, Foramen® - 62%, Vesna F® - 61%). Two samples had more than 70% and less than 80% of unbound fluoride, respectively (Sensodyne® - 77%, another batch of Oral B Advantage® mouthwash - 74%). Rinse containing sodium monofluorophosphate (Na2PO3F) (Vesna F®) had more than 50% of free fluoride, while the rinse containing amine fluoride (AmF) (Lacalut Sensitive®) had 94%. The difference in the free fluoride:total fluoride ratio can be explained by binding of fluoride ions by components contained in mouthwashes, such as coloring agents and polymeric compounds. The lowest concentration of free fluoride ions (0.000093 mol/L) was observed for aluminum fluoride (AlF3) rinse (Lacalut Fresh®), while the total fluoride amount was not determined due to possible generation of strong fluoride complexes. This implies that fluoride ions will not be uptaken by tooth tissue and may even be washed away from it, compromising the efficacy of mouthwashes.

Conclusions
The differences in free fluoride: total fluoride ratio between analyzed mouthwashes reveal a need to develop a method for evaluation of free fluorides in mouthwashes for proper updating of national and international guidelines.
Chest wall lymph node metastasis from follicular thyroid carcinoma: a rare case report
Authors: Li Taolang , Ma Zhiyuan , Lu Chengli , Zhou Quanzhong , Feng Zelong , Wu Xinglong , Luo Yi , Li Dan , Cheng Xiaoming , Liu Xuemei 
Published: November 2019

Abstract
Background
Distant metastases from follicular thyroid carcinoma are mainly hematogenous and are commonly observed in the lungs and bones. Other rare sites are the parotid gland, skin, brain, ovary, adrenal gland, kidney, pancreas and breast, with chest wall lymph node metastasis being even more rare.

Case presentation
Over the past 10 years, three surgeries were performed on a 69-year-old women with a history of follicular thyroid cancer and its metastatic lesions. The patient presented with a 3-month history of masses in the left chest. She underwent detailed examination of the chest wall tumors, and surgery was then performed to resect all of the tumors. Based on the histopathology, these lymph nodes were confirmed to harbor metastatic follicular thyroid carcinoma.

Conclusion
This study reports the first case of follicular thyroid carcinoma metastasis to the chest wall lymph node.
LncRNA MAGI2-AS3 is involved in cervical squamous cell carcinoma development through CDK6 up-regulation
Authors: Liu Qifang , Liu Shuang , Wang Xiaoying , Zhang Jin , Liu Kuiran 
Published: November 2019

Abstract
Background
It has been reported that lncRNA MAGI2-AS3 can promote many types of cancer, such as breast cancer and bladder cancer, by regulating cell behaviors, such a proliferation, invasion, and migration. However, its role in cervical squamous cell carcinoma (CSCC) is unclear. This study aims to investigate the role of MAGI2-AS3 in CSCC.

Methods
Sixty-four CSCC patients (36 to 68 years, 46.3 ± 5.1 years) out of 136 CSCC patients admitted by Shengjing hospital affiliated to China Medical University from June 2010 to October 2013 were included in the present study. Among the 64 enrolled patients, 20 were HPV-16 positive cases, 24 were HPV-18 positive cases and 20 were HPV negative. CSCC and non-tumor biopsies from CSCC patients as well as C-33A cell lines were used. Cells were transfected with MAGI2-AS3 and CDK6 expression vectors as well as with MAGI2-AS3 siRNA to analyze gene interactions. Cell cycle analysis was performed to analyze the effects of transfections on cell cycle progression. qPCR and western blot were applied to analyze gene expression. Paired t-test and ANOVA (one-way) combined with Tukey test were used for data comparisons. Survival analysis was performed by plotting and comparing survival curves.

Results
qRT-PCR results showed that CDK6 and MAGI2-AS3 were both up-regulated in CSCC and positively correlated with each other. MAGI2-AS3 and CDK6 expression was not significantly affected by HPV infections. High levels of MAGI2-AS3 were associated with the poor survival of CSCC patients. In CSCC cells, MAGI2-AS3 over-expression up-regulated CDK6, while MAGI2-AS3 siRNA down-regulated CDK6. In CCK-8 assay, MAGI2-AS3 and CDK6 over-expression led to increased proliferation rate of CSCC cells by reducing CDK6 levels, while MAGI2-AS3 siRNA didn’t. In addition, CDK6 over-expression attenuated the effect of MAGI2-AS3 siRNA silencing.

Conclusions
In conclusion, MAGI2-AS3 promoted CSCC cell proliferation by up-regulating CDK6.
Body composition indices in a sample of female adolescents with postural deformity: a case control study
Authors: Golalizadeh Dina , Toopchizadeh Vahideh , Fasaie Negar , Dolatkhah Neda 
Published: November 2019

Abstract
Objectives
Normal posture is considered to be an indicative of good musculoskeletal health in school aged adolescents. Little is known about the body composition indices in relation with postural deformities in adolescents. The aim of this study was to assess relation of body composition analysis indices with postural deformities in a sample of female high school adolescents.

Results
In this case–control study, 37 eligible female adolescents with any postural deformities and 33 normal posture subjects enrolled in the study by random cluster sampling. Body composition analysis performed by bioelectrical impedance analysis (BIA) method to quantity body fat mass (BFM), soft lean mass (SLM) and lean body mass (LBM). The binary logistic regressions were performed to evaluate the associations of body composition indices which were significantly different between two groups at significance level of 0.05 with postural disorders in the two groups. There was no significant difference between subjects with postural disorders with their normal controls concerning demographic variables. We observed an inverse association between postural deformity risk and LBM (OR = 0.803; 95% CI 0.690–0.934) and SLM (OR = 0.774; 95% CI 0.649–0.922) after adjusting the analysis by height of participants.
Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma
Authors: Holderried Tobias A. W. , de Vos Luka , Bawden Emma Grace , Vogt Timo J. , Dietrich Joern , Zarbl Romina , Bootz Friedrich , Kristiansen Glen , Brossart Peter , Landsberg Jennifer , Dietrich Dimo 
Published: November 2019

Abstract
Background
The T cell immunoglobulin and mucin-domain containing-3 receptor TIM-3 (also known as hepatitis A virus cellular receptor 2, encoded by HAVCR2) and its ligand galectin 9 (LGALS9) are promising targets for immune checkpoint inhibition immunotherapies. However, little is known about epigenetic regulation of the encoding genes. This study aimed to investigate the association of TIM-3 and LGALS9 DNA methylation with gene expression, patients’ survival, as well as molecular and immune correlates in malignant melanoma.

Results
Methylation of all six TIM-3 CpGs correlated significantly with TIM-3 mRNA levels (P ≤ 0.05). A strong inverse correlation (Spearman’s ρ = − 0.49) was found in promoter regions, while a strong positive correlation (ρ = 0.63) was present in the gene body of TIM-3. High TIM-3 mRNA expression (hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.81–0.97], P = 0.007) was significantly associated with better overall survival. Seven of the eight LGALS9 CpG sites correlated significantly with LGALS9 mRNA levels (P ≤ 0.003). Methylation at five CpG sites showed a strong inverse correlation (Spearman’s ρ = − 0.67) and at two sites a weak positive correlation (Spearman’s ρ = 0.15). High LGALS9 mRNA expression was significantly associated with increased overall survival (HR = 0.83, 95%CI [0.75–0.93], P = 0.001). In addition, we found significant correlations between TIM-3 and LGALS9 methylation and mRNA expression with immune cell infiltrates and significant differences among distinct immune cell subsets.

Conclusions
Our study points toward an epigenetic regulation of TIM-3 and LGALS9 via DNA methylation and might provide an avenue for the development of a predictive biomarker for response to immune checkpoint blockade.
Enhanced serum immunoglobulin G clearance in myotonic dystrophy-associated hypogammaglobulinemia: a case series and review of the literature
Authors: Sasson Sarah C. , Corbett Alastair , McLachlan Andrew J. , Chen R. , Adelstein S. A. , Riminton Sean , Limaye Sandhya 
Published: November 2019

AbstractBackgroundMyotonic dystrophy type 1 is an autosomal dominant disorder characterized by muscle weakness, myotonia, cataracts, and cardiac conduction defects; it is associated with expansions of cytosine-thymine-guanine repeats in the myotonic dystrophy protein kinase. Hypogammaglobulinemia is a lesser known association of myotonic dystrophy type 1 and the underlying pathogenesis of immunoglobulin G depletion remains unclear.Case presentationHere we report a kindred of two members (a 62-year-old white woman and a 30-year-old white man; mother and son) with myotonic dystrophy type 1-associated hypogammaglobulinemia associated with altered intravenous immunoglobulin elimination kinetics and reduced half-life. There was no history of systemic immunosuppression or renal or gastrointestinal protein loss in either patient, and no underlying case for a secondary immunodeficiency could be found. One patient required fortnightly intravenous immunoglobulin to maintain adequate trough immunoglobulin G levels.ConclusionsOngoing study of myotonic dystrophy type 1-associated hypogammaglobulinemia using contemporary tools of genomic medicine may help to further delineate the pathogenesis of this entity.
Standard coagulation assays alone are not sufficient to exclude surgically relevant rivaroxaban plasma concentrations
Authors: Kaserer Alexander , Schedler Andreas , Seifert Burkhardt , Spahn Donat R. , Studt Jan-Dirk , Stein Philipp 
Published: November 2019

Abstract
Background
While mainly larger hospitals have introduced routine anti-Xa assays for rivaroxaban (RXA), these are not readily available to smaller hospitals often relying on routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT).
The aim of our study was to investigate the effect of RXA plasma concentration on the standard coagulation tests PT (Quick test and INR) and aPTT in a large group of real-life patients. We further assessed whether normal results of these standard coagulation assays are sufficient to exclude surgically relevant RXA plasma concentration, defined as > 50 mcg/l.

Methods
This retrospective study included all patients between 2012 and 2016 where anti-Xa (calibrated for RXA), PT (Quick test and INR), and/or aPTT were determined from the same sample. PT is expressed as Quick value (% of normal plasma pool). In total, 1027 measurements in 622 patients were eligible for analysis: 752 measurements of 505 patients for Quick/INR and 594 measurements of 417 patients for aPTT.

Results
A moderate correlation of PT/Quick (Pearson's correlation coefficient − 0.59; p < 0.001), INR (Pearson's correlation coefficient 0.5; p < 0.001), and aPTT (Pearson's correlation coefficient 0.53; p < 0.001) with RXA plasma concentration was observed. However, in 50% of all samples with a normal PT/Quick, in 25% of all samples with a normal INR and in 80% of all samples with a normal aPTT residual RXA plasma concentration was surgically relevant.

Conclusion
Although a moderate correlation of RXA plasma concentration with PT/Quick, INR, and aPTT was observed, standard coagulation assays are not sufficient to exclude surgically relevant RXA plasma concentrations.