bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dental Fluorosis Trends in US Oral Health Surveys: 1986 to 2012
Authors: Neurath C. , Limeback H. , Osmunson B. , Connett M. , Kanter V. , Wells C.R. 
Published: March 2019

Introduction: Dental fluorosis has been assessed only 3 times in nationally representative oral health surveys in the United States. The first survey was conducted by the National Institute of Dental Research from 1986 to 1987. Subsequently, the National Health and Nutrition Examination Survey (NHANES) conducted fluorosis assessments from 1999 to 2004 and more recently from 2011 to 2012. A large increase in prevalence and severity of fluorosis occurred between the 1986–1987 and 1999–2004 surveys. Objectives: To determine whether the trend of increasing fluorosis continued in the 2011–2012 survey. Methods: We analyzed publicly available data from the 2011–2012 NHANES, calculating fluorosis prevalence and severity using 3 measures: person-level Dean’s Index score, total prevalence of those with Dean’s Index of very mild degree and greater, and Dean’s Community Fluorosis Index. We examined these fluorosis measures by several sociodemographic factors and compared results with the 2 previous surveys. Analyses accounted for the complex design of the surveys to provide nationally representative estimates. Results: Large increases in severity and prevalence were found in the 2011–2012 NHANES as compared with the previous surveys, for all sociodemographic categories. For ages 12 to 15 y—an age range displaying fluorosis most clearly—total prevalence increased from 22% to 41% to 65% in the 1986–1987, 1999–2004, and 2011–2012 surveys, respectively. The rate of combined moderate and severe degrees increased the most, from 1.2% to 3.7% to 30.4%. The Community Fluorosis Index increased from 0.44 to 0.67 to 1.47. No clear differences were found in fluorosis rates among categories for most of the sociodemographic variables in the 2011–2012 survey. Conclusion: Large increases in fluorosis prevalence and severity occurred. We considered several possible spurious explanations for these increases but largely ruled them out based on counterevidence. We suggest several possible real explanations for the increases. Knowledge Transfer Statement: The results of this study greatly increase the evidence base indicating that objectionable dental fluorosis has increased in the United States. Dental fluorosis is an undesirable side effect of too much fluoride ingestion during the early years of life. Policy makers and professionals can use the presented evidence to weigh the risks and benefits of water fluoridation and early exposure to fluoridated toothpaste.
Inactivation of platelet-derived TGF-β1 attenuates aortic stenosis progression in a robust murine model
Authors: Varshney Rohan , Murphy Brennah , Woolington Sean , Ghafoory Shahrouz , Chen Sixia , Robison Tyler , Ahamed Jasimuddin 
Published: March 2019

AbstractAortic stenosis (AS) is a degenerative heart condition characterized by fibrosis and narrowing of aortic valves (AV), resulting in high wall shear stress (WSS) across valves. AS is associated with high plasma levels of transforming growth factor-β1 (TGF-β1), which can be activated by WSS to induce organ fibrosis, but the cellular source of TGF-β1 is not clear. Here, we show that platelet-derived TGF-β1 plays an important role in AS progression. We first established an aggressive and robust murine model of AS, using the existing Ldlr−/−Apob100/100 (LDLR) breed of mice, and accelerated AS progression by feeding them a high-fat diet (HFD). We then captured very high resolution images of AV movement and thickness and of blood flow velocity across the AV, using a modified ultrasound imaging technique, which revealed early evidence of AS and distinguished different stages of AS progression. More than 90% of LDLR animals developed AS within 6 months of HFD. Scanning electron microscopy and whole-mount immunostaining imaging of AV identified activated platelets physically attached to valvular endothelial cells (VEC) expressing high phosphorylated Smad2 (p-Smad2). To test the contribution of platelet-derived TGF-β1 in AS, we derived LDLR mice lacking platelet TGF-β1 (TGF-β1platelet-KO-LDLR) and showed reduced AS progression and lower p-Smad2 and myofibroblasts in their AV compared with littermate controls fed the HFD for 6 months. Our data suggest that platelet-derived TGF-β1 triggers AS progression by inducing signaling in VEC, and their subsequent transformation into collagen-producing-myofibroblasts. Thus, inhibiting platelet-derived TGF-β1 might attenuate or prevent fibrotic diseases characterized by platelet activation and high WSS, such as AS.
Inadequate assessment of adherence to maintenance medication leads to loss of power and increased costs in trials of severe asthma therapy: results from a systematic literature review and modelling study
Authors: Mokoka Matshediso C. , McDonnell Melissa J. , MacHale Elaine , Cushen Breda , Boland Fiona , Cormican Sarah , Doherty Christina , Doyle Frank , Costello Richard W. , Greene Garrett 
Published: March 2019

Adherence to inhaled maintenance therapy in severe asthma is rarely adequately assessed, and its influence on trial outcomes is unknown. We systematically determined how adherence to maintenance therapy is assessed in clinical trials of “add-on” therapy for severe asthma. We model the improvement in trial power that could be achieved by accurately assessing adherence.A systematic search of six major databases identified randomised trials of add-on therapy for severe asthma. The relationship between measuring adherence and study outcomes was assessed. An estimate of potential improvements in statistical power and sample size was derived using digitally recorded adherence trial data.87 randomised controlled trials enrolling 22 173 participants were included. Adherence assessment was not reported in 67 trials (n=13 931, 63%). Studies that reported adherence used a range of self-report and subjective methods. None of the studies employed an objective assessment of adherence. Studies that reported adherence had a significantly reduced pooled variance in forced expiratory volume in 1 s (FEV1) compared to those that did not assess adherence: s2=0.144 L2versuss2=0.168 L2, p<0.0001. Power to detect clinically relevant changes in FEV1was significantly higher in trials that reported adherence assessment (mean power achieved 59%versus49%). Modelling suggests that up to 50% of variance in FEV1outcomes is attributable to undetected variations in adherence. Controlling for such variations could potentially halve the required sample size.Few trials of add-on therapy monitor adherence to maintenance inhaled therapy, resulting in a greater variance in trial outcomes and inadequate power for determining efficacy.
RETRACTED ARTICLE: Downregulation of CDKL1 suppresses neuroblastoma cell proliferation, migration and invasion
Authors: Li Weiyi , Cao Jing , Liu Jian , Chu Wenli , Zhang Congqing , Chen Shuiling , Kang Zefeng 
Published: March 2019

Abstract

Background
Cyclin-dependent kinase-like 1 (CDKL1) is a member of the cell division control protein 2-related serine–threonine protein kinase family. It is known to occur in various malignant tumors, but its role in neuroblastoma (NB) remains unclear.

Methods
We constructed a CDKL1-silenced NB cell strain (SH-SY5Y) and used real-time PCR and western blotting to confirm the silencing. Functional analyses were performed using the MTT, colony-formation, FACS, wound-healing and transwell invasion assays.

Results
The expression of CDKL1 was significantly upregulated in NB tissue as compared to the adjacent normal tissue. CDKL1 knockdown significantly suppressed cell viability and colony formation ability. It also induced cell cycle G0/G1 phase arrest and apoptosis, and suppressed the migration and invasion ability of SH-SY5Y cells. CDKL1 knockdown decreased the CDK4, cyclin D1 and vimentin expression levels, and increased the caspase-3, PARP and E-cadherin expression levels in SH-SY5Y cells.

Conclusions
Our findings suggest that CDKL1 plays an important role in NB cell proliferation, migration and invasion. It might serve as a potential target for NB therapy.
An enhanced procedure for the analysis of organic binders in Pompeian’s wall paintings from Insula Occidentalis
Authors: Gelzo Monica , Corso Gaetano , Pecce Rita , Arcari Ottavia , Piccioli Ciro , Dello Russo Antonio , Arcari Paolo 
Published: March 2019

Abstract
Quantitation of paint powders of ancient wall paintings is often hindered by the calcite contamination during samples withdrawal. To overcome this problem, a new approach was explored based on the mechanical pulverization of the paint powder followed by the evaluation of its true concentration, namely binders, pigments, and decaying compounds, from the comparison of the calcite FT-IR peak area at 2510 cm−1 with that of the corresponding underlying calcite used as calibrator. After extraction of the pulverized paint powder with polar and nonpolar solvents, liquid chromatography, gas chromatography with flame ionization detection, and gas chromatography–mass spectrometry were used to estimate the free amino acids, and fatty acids profiles. Compared to our previous investigation, the results obtained showed a better yield of the extracted organic materials as mg/kg of powder and also a qualitative improvement of the lipids profile.
Impact of testosterone replacement therapy after radical prostatectomy on prostate cancer outcomes.
Authors: Sarkar Reith , Parsons J Kellogg , Einck John Paul , Mundt Arno James , Kader A. Karim , Kane Christopher J. , Riviere Paul , McKay Rana R. , Murphy James Don , Rose Brent Shane 
Published: March 2019

100 Background: Currently there is little data to guide the use of post-radical prostatectomy (RP) testosterone replacement therapy in prostate cancer. We sought to evaluate the impact of post-RP testosterone replacement on prostate cancer outcomes in a large national cohort. Methods: We conducted a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure. We identified node-negative and non-metastatic prostate cancer patients diagnosed between 2001-2015 treated with RP. We excluded patients for missing covariate and follow-up data. We then coded receipt of testosterone replacement after RP as a time-dependent covariate. Other covariates included: age, Charlson Comorbidity index, diagnosis year, body mass index, race, PSA, clinical T/N/M stage, Gleason score, and receipt of hormone therapy. Biochemical recurrence was defined as a post-RP PSA≥0.2. We evaluated prostate cancer-specific survival, overall survival, and biochemical recurrence free survival using multivariable Cox regression. Results: Our cohort included 28,651 patients, of whom 469 (1.6%) received testosterone replacement after RP. Median follow up was 7.4 years. There were no differences in clinical T stage, median post-RP PSA (testosterone: 0 non-testosterone: 0; p = 0.18), or hormone therapy use between treatment groups. Testosterone patients were more likely to be of younger age, have higher comorbidity, non-black, have a lower median pre-treatment PSA (5.0 vs 5.8; p < 0.001), and have higher BMI. The median time from RP to TRT was 3.0 years. After controlling for potential confounders, we found no difference in prostate cancer specific mortality (HR 0.73; 95% CI 0.32-1.62; p = 0.43), overall survival (HR 1.11; 95% CI 0.86-1.44; p = 0.43), non-cancer mortality (HR 1.17; 95% CI 0.89-1.55; p = 0.26) biochemical recurrence free survival (HR 1.07; 95% CI 0.84-1.36; p = 0.59) between testosterone users and non-users. Conclusions: Our results suggest that testosterone replacement is safe in prostate cancer patients who have undergone RP, though prospective data is necessary to confirm this finding.
External validation of prostatectomy incontinence nomogram (PIN).
Authors: Pinkhasov Rubin , Pinkhasov Alexandr M. , Attwood Kristopher , Abaev Michall , Underwood Willie 
Published: March 2019

106 Background: Using previously developed prostatectomy incontinence nomogram (PIN) we sought to externally validate the nomogram that predicts probability of incontinence at 6-, 12-, and 24-months after robot assisted radical prostatectomy (RARP). Methods: Prospective data from 663 men with prostate cancer that underwent RARP from 2010 to 2014 at two comprehensive cancer centers and three large group practices was queried. The performance of the previously developed model was evaluated using calibration plots (predicted continence rates versus observed continence rates with 95% CI obtained using Jeffrey’s prior method) and receiver operating curves (ROC). Using Expanded Prostate Cancer Index Composite (EPIC-50) Urinary Function questionnaire, perfect continence was defined as 0 pads, social continence was defined as 1 or 2 pads, and incontinence was defined as ≥ 3 pads used after RARP. Results: The 6-, 12-, and 24- month social continence rates were 77%, 88%, and 93%, respectively. Similar to the 6- and 12-month model development cohort, the external validation cohort has modest predictability with a 6- and 12- month AUC of 0.61, and 0.62, respectively. The 24-month AUC of 0.62 in the external validation cohort is worse than what was reported in the development cohort (AUC 0.80). Conclusions: The externally validated prostatectomy incontinence nomogram is generalizable but has modest 6-, 12-, and 12-month predictability in risk of incontinence after RARP.
MRI-based prostate specific antigen density predicts Gleason score upgrade in an active surveillance cohort.
Authors: Washington Samuel L. , Baskin Avi Lefridge , Ameli Niloufar , Nguyen Hao Gia , Westphalen Antonio C. , Shinohara Katsuto , Carroll Peter 
Published: March 2019

107 Background: Elevated prostate specific antigen density (PSAD) based on transrectal ultrasound (TRUS) measurements has been shown to be strongly associated with clinically significant disease and to predict progression on active surveillance for men with low stage/grade disease. We hypothesize that elevated MRI PSAD is similarly associated with increased risk of progression on subsequent biopsy. Methods: Patients with Gleason grade 3+3 on diagnostic transrectal ultrasound-guided biopsy who were managed with active surveillance and underwent at least one additional biopsy were included. Patients who underwent MRI greater than 6 months after diagnosis were excluded. Summary statistics were generated for demographic and clinical characteristics. MRI PSAD was calculated using prostate volume on MRI and PSA temporally closest to the MRI. Multivariable logistics regression models were used to evaluate the association between MRI PSAD and predictors of upgrade on serial biopsy. Results: 166 patients were included in the study. Of these patients, 74 of them were upgraded to Gleason grade ≥7 on follow up biopsy. TRUS volume was noted be strongly correlated with MRI prostate volume (Pearson’s r=0.82, p<0.01). MRI PSAD 0.15-0.225 ng/ccl and ≥0.0225 ng/cc were significantly associated with upgrade to Gleason grade 7 compared to MRI PSAD <0.075 ng/ml/ml after controlling for age and time since diagnosis. MRI PSAD less than 0.15 was not associated with upgrade on follow up biopsy (in any patient, if so, state that no one with a PSAD < 0.15 upgraded). Conclusions: MRI PSAD is significantly associated with Gleason upgrading on follow up biopsy for men initially diagnosed with Gleason grade 3+3 disease. This finding is important because surveillance MRI is increasingly being used to monitor men on active surveillance.
MRI targeted biopsy dramatically increases detection of clinically significant prostate cancer while reducing the risk of indolent cancer detection.
Authors: Ahdoot Michael , Lebastchi Amir H , Gharam Sandeep , Gomella Patrick H , Dibianco John , Bloom Jonathan , Hale Graham , Gold Samuel A , Turkbey Baris , Pinto Peter A. , Sanford Thomas , Choyke Peter L. , Parnes Howard L. 
Published: March 2019

108 Background: MRI fusion prostate biopsy has been shown to improve detection of clinically significant prostate cancer, however the degree of this benefit is poorly characterized in large clinical trials. Methods: 1750 MRI targeted plus sextant biopsies were performed in 1742 male patients from 2007 to 2017. Patient demographics, PSA, prostate volume, primary and secondary Gleason scores, Johns Hopkins Grade Groups, number of MRI targeted lesions, number of cores obtained, and biopsy yield were recorded. Results: The patient population consisted of men averaging 62.9-year-old (36-86) with a mean PSA 9.6ng/mL, and prostate volume of 59.2 ml. A total of 804 cancers were detected on sextant biopsy and 839 were detected on MRI targeted biopsy. Relative to targeted biopsy, sextant biopsy detected only significantly more Gleason 6 disease (14% vs 21.5%, p < 0.0001) than targeted biopsy. Targeted biopsy detected more Gleason 7 (21% vs 16.6%, p = 0.0009) and Gleason 8-10 (13.4% vs 9.4%). Additionally, Gleason 7 sub-stratification demonstrated substantially more Gleason 4+3 detection in targeted group vs sextant biopsy (4% vs 0.5%, p < 0.0001). When stratified by Grade Group targeted biopsy detected 76% more Grade Group 3-5 cancers (p < 0.0001) and 17.7% less Gleason Group 1-2 cancers (p < 0.0001). Only 1.7% of Grade Group 3-5 cancers were detected on sextant biopsy alone, where as 15.7% of Grade Group 3-5 cancers were detected on targeted biopsy alone. Conclusions: MRI targeted biopsy significantly increases the likelihood of detecting clinically significant cancer and decreases the risk of indolent cancer detection. These finding strongly support the use of MRI targeted biopsy when possible.
Optimizing the use of androgen deprivation therapy in men with localized intermediate-risk prostate cancer in the era of modern dose-escalated radiation therapy.
Authors: Patel Sagar Anil , Nguyen Kevin H. , Lee Alan K. , Demanes David Jeffrey , Chang Albert 
Published: March 2019

109 Background: While level one evidence has shown an overall survival (OS) advantage with the addition of androgen deprivation therapy (ADT) to radiotherapy (RT) for intermediate risk prostate cancer (PCa), the benefit in the era of modern dose escalation is controversial, especially given the heterogeneity within this risk group. We assessed the impact of adding ADT to high dose RT on OS for intermediate risk PCa stratified by number of intermediate risk factors (IRF). Methods: We identified 114,339 men with intermediate risk PCa (Gleason 7, clinical stage T1-2, PSA < 20 ng/mL) using the National Cancer Database. Men were stratified into the following subgroups based on the number of IRFs (Gleason 7, cT2b-c, PSA > 10-20 ng/mL): A) Gleason 3+4 and no other IRF, B) Gleason 4+3 and no other IRF, C) two IRFs, and D) three IRFs. The addition of ADT to dose-escalated external beam RT (DE-EBRT, ≥ 75.6 Gy), brachytherapy (BT), or combination EBRT+BT on OS was assessed within each subgroup using Kaplan-Meier and log-rank tests in propensity score-matched cohorts in all men and subsequently only in those with Charlson-Deyo comorbidity index (CDI) of zero. Results: There was no OS benefit with the addition of ADT to DE-EBRT, BT, or EBRT+BT in groups A, B, and C, even after limiting the cohort to men with CDI = 0. However, in group D, the addition of ADT to DE-EBRT was associated with a trend for OS improvement in patients with CDI = 0 only (8-year OS with and without ADT 68.3% and 62.4%, respectively, log-rank P= .07). Conversely, there was a trend for OS decrement with the addition of ADT to DE-EBRT in men with CDI ≥ 1 (8-year OS with and without ADT 61.8% and 67.5%, respectively, log-rank P= .06). There was no OS benefit of ADT in group D treated with BT or EBRT+BT, regardless of comorbidity status. Conclusions: The OS benefit of ADT in men with intermediate risk PCa may be limited to those with 3 IRFs and minimal comorbidities treated with DE-EBRT. If prospectively validated, extreme dose escalation achieved with BT (alone or in combination with EBRT) may obviate the addition of ADT in all men with intermediate risk disease, especially in an era of advanced molecular imaging.
Incidence and pathological features of metachronous bladder cancer in prostate cancer patients treated with brachytherapy or radical prostatectomy in a single institution.
Authors: Obayashi Kotaro 
Published: March 2019

111 Background: Although previous studies have reported that the incidence of metachronous bladder cancer (MBC) is not significantly different after brachytherapy (BT) compared to radical prostatectomy (RP), few studies have reported differences in the pathological features (PF) of MBC between them. This study was conducted to clarify differences in the incidence and PF of MBC between BT and RP in our hospital. Methods: We reviewed 504 patients treated with BT and 471 referred patients treated with RP from 2006 to 2017 in our hospital. We checked the incidence of MBC in all patients and examined the PF including the tumor number, location within the bladder, histology, and time from BT or RP to the occurrence. The chi-square test and Mann-Whitney U test were performed to analyze the differences between the two groups. Results: After a median follow-up time of 66 months, a total of 8 cases of BC occurred in the BT group (1.6 %) and 5 in the RP group (1.1 %). The median time from initial treatment to the occurrence of MBC was 56 months (12-121) in BT and 71 months (4-126) in RP (p = 0.622). Average tumor number was not significantly different (BT:1.38, RP: 2.2, p = 0.265). The incidence of MBC in each location within the bladder for BT vs. RP was 4 vs 0 in the right wall, 3 vs 0 in the left wall, 0 vs 3 in the posterior wall, 0 vs 2 in the dome, and 1 vs 0 in the trigone. The incidence in the lateral wall was significantly higher in BT than in RP (p = 0.00466). There were 3 muscle-invasive cases in BT and 1 case in RP (p = 1.00). High-grade urothelial cancer occurred more in BT 8 than in RP 1 (p = 0.00699). Conclusions: The risk of MBC after BT appeared to be equivalent to patients after RP. MBC after BT occurred more in the lateral wall with worse PF compared to those after RP.