bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bladder cancer and occupational exposure to metalworking fluid mist: a counter-matched case–control study in French steel-producing factories
Authors: Colin Régis , Grzebyk Michel , Wild Pascal , Hédelin Guy , Bourgkard Ève 
Published: January 2018

ObjectivesTo assess the relationship between occupational exposure to metalworking fluids (MWFs) in the steel-producing industry and bladder cancer incidence.MethodsA nested case–control study on bladder cancer was set up in a cohort of workers from six French steel-producing factories. Three controls were randomly selected for each incident bladder cancer case diagnosed from 2006 to 2012. Controls were matched to cases on age at diagnosis and counter-matched on a surrogate measure of exposure to MWFs derived from a job-exposure matrix. Cases (n=84) and controls (n=251) were face-to-face interviewed. Experts assessed occupational exposure to MWFs (straight, soluble and synthetic) using questionnaires and reports from factory visits. Occupational exposures were based on three metrics: duration, frequency-weighted duration and cumulative exposure index. Conditional multiple logistic regressions were used to determine ORs and 95% CIs, taking non-occupational and occupational exposure into account.ResultsIn the 25 years before diagnosis, ORs increased significantly with duration of exposure to straight MWFs (OR=1.13 (1.02–1.25)) and increased with frequency-weighted duration of exposure to straight MWFs (OR=1.44 (0.97–2.14)). These results remained valid after adjusting for duration of smoking, average number of cigarettes smoked per day, time since smoking cessation and exposure to polycyclic aromatic hydrocarbons (PAHs). ORs also increased with soluble MWFs but not significantly. No significant association was found with older exposures to MWFs or with exposure to synthetic MWFs.ConclusionThe increased risk of bladder cancer observed among workers exposed to straight MWFs and to a lesser extent to soluble MWFs may be explained by the presence of carcinogens (such as PAH) in mineral oils component of straight and soluble oils. Prevention therefore remains necessary in sectors using MWFs.
Incidence of cardiovascular disease in a historical cohort of Danish firefighters
Authors: Pedersen Julie Elbæk , Ugelvig Petersen Kajsa , Ebbehøj Niels Erik , Bonde Jens Peter , Hansen Johnni 
Published: January 2018

ObjectivesFirefighters are exposed to multiple cardiovascular hazards, but few epidemiological studies have addressed their cardiovascular morbidity. The objective of this study was therefore to examine the incidence of cardiovascular diseases (CVD) in Danish firefighters.MethodsWe used individual historical employment records on 11.691 male Danish firefighters supplied by trade unions and fire agencies. The Supplementary Pension Fund Register was used to establish two occupational reference groups (a random sample from the male employed population and military employees). Information on CVD incidence was retrieved from the nationwide Danish National Patient Registry. SIRs and Poisson regression analyses (incidence rate ratio) were used for estimation of risks, including 95% CIs.ResultsIn comparison with the population sample, the age-adjusted and calendar time-adjusted SIR for all CVDs combined was increased in firefighters (SIR=1.10, 95% CI 1.05 to 1.15). The risk was also elevated for the most frequent outcomes, including angina pectoris (SIR=1.16, 95% CI 1.08 to 1.24), acute myocardial infarction (SIR=1.16, 95% CI 1.06 to 1.26), chronic ischaemic heart disease (SIR=1.15, 95% CI 1.06 to 1.24) and atrial fibrillation/flutter (SIR=1.25, 95% CI 1.14 to 1.36). This analysis showed the most elevated SIRs for CVD in full-time firefighters compared with part-time/volunteer firefighters. Both types of firefighters employed <15 years had an increased risk of CVD. Similar risk patterns appeared in comparisons with the military. Internal analysis supported external findings.ConclusionThe risk of overall CVD, including the most frequent subtypes was modestly increased in Danish firefighters and was most elevated in full-time firefighters compared with other male employees.
Recent advances in the understanding of endothelial barrier function and fluid therapy
Authors: Thind Guramrinder Singh , Zanders Steve , Baker Joanne K 
Published: January 2018

AbstractElucidation of the structural basis of endothelial barrier function and the study of transcapillary fluid exchange dynamics are areas of active research. There has been significant enhancement in our understanding of the ultrastructural basis of endothelial barrier function. The role of glycocalyx has received special attention. Experimental evidence has called for a revision in the classic Starling principle of transcapillary exchange. The glycocalyx model provides a potential structural mechanism for the revised Starling principle. This knowledge can provide the framework for understanding the volume expansion effect of fluid therapy and the physiological basis of fluid therapy.
Healthcare utilisation and costs of home mechanical ventilation
Authors: Nonoyama Mika L , McKim Douglas A , Road Jeremy , Guerriere Denise , Coyte Peter C , Wasilewski Marina , Avendano Monica , Katz Sherri L , Amin Reshma , Goldstein Roger , Zagorski Brandon , Rose Louise 
Published: January 2018

BackgroundIndividuals using home mechanical ventilation (HMV) frequently choose to live at home for quality of life, despite financial burden. Previous studies of healthcare utilisation and costs do not consider public and private expenditures, including caregiver time.ObjectivesTo determine public and private healthcare utilisation and costs for HMV users living at home in two Canadian provinces, and examine factors associated with higher costs.MethodsLongitudinal, prospective observational cost analysis study (April 2012 to August 2015) collecting data on public and private (out-of-pocket, third-party insurance, caregiving) costs every 2 weeks for 6 months using the Ambulatory and Home Care Record. Functional Independence Measure (FIM) was used at baseline and study completion. Regression models examined variables associated with total monthly costs selected a priori using Andersen and Newman’s framework for healthcare utilisation, relevant literature, and clinical expertise. Data are reported in 2015 Canadian dollars ($C1=US$0.78=₤0.51=€0.71).ResultsWe enrolled 134 HMV users; 95 with family caregivers. Overall median (IQR) monthly healthcare cost was $5275 ($2291–$10 181) with $2410 (58%) publicly funded; $1609 (39%) family caregiving; and $141 (3%) out-of-pocket (<1% third-party insurance). Median healthcare costs were $8733 ($5868–$15 274) for those invasively ventilated and $3925 ($1212–$7390) for non-invasive ventilation. Variables associated with highest monthly costs were amyotrophic lateral sclerosis (1.88, 95% CI 1.09 to 3.26, P<0.03) and lower FIM quintiles (higher dependency) (up to 6.98, 95% CI 3.88 to 12.55, P<0.0001) adjusting for age, sex, tracheostomy and ventilation duration.ConclusionsFor HMV users, most healthcare costs were publicly supported or associated with family caregiving. Highest costs were incurred by the most dependent users. Understanding healthcare costs for HMV users will inform policy decisions to optimise resource allocation, helping individuals live at home while minimising caregiver burden.
Erosional valleys at a major Late Jurassic–Early Cretaceous unconformity offshore Germany and The Netherlands: potential reservoirs or deteriorated seals?
Authors: Wolf Marco , Vis Annelieke , Asschert Annemiek 
Published: January 2018

Abstract
Joint results of two independent international studies on the erosional impact of the ‘Late Cimmerian Unconformity’ (LCU), a Late Jurassic–Early Cretaceous erosional event, are presented. The potential impact on the reservoir and sealing potential of adjacent strata are discussed. Results are based on a seismic mapping campaign in the NE part of the Dutch offshore region and the Central German North Sea sector. The geological evolution of potential traps at the level of the LCU was studied to obtain a better understanding of reservoir potential. Erosion or leaching of the evaporitic Triassic intervals at the LCU caused a locally strong topographical relief with prominent elongated depressions along Permian salt structures (interpreted as erosional valleys). The infill of the erosional valleys may consist of remnants of initial strata as breccia or material from nearby eroded strata, possibly Lower Triassic sandstone or clays. These valleys may be overlain conformably by Upper Jurassic–Early Cretaceous sediments or may be filled with a combination of both. The lithological composition of the infill determines the sealing or the reservoir potential of the valleys, which is essential for further evaluation of the resource exploration possibilities in this locality and across the basin.
RNF6 Promotes Colorectal Cancer by Activating the Wnt/β-Catenin Pathway via Ubiquitination of TLE3
Authors: Liu Lei , Zhang Yanquan , Wong Chi Chun , Zhang Jingwan , Dong Yujuan , Li Xiangchun , Kang Wei , Chan Francis K.L. , Sung Joseph J.Y. , Yu Jun 
Published: January 2018

Abstract
Gene amplification is a hallmark of cancer and is frequently observed in colorectal cancer. Previous whole-genome sequencing of colorectal cancer clinical specimens identified amplification of Ring finger protein 6 (RNF6), a RING-domain E3 ubiquitin ligase. In this study, we showed that RNF6 is upregulated in 73.5% (147/200) of patients with colorectal cancer and was positively associated with RNF6 gene amplification. Furthermore, RNF6 expression and its gene amplification were independent prognostic factors for poor outcome of patients with colorectal cancer. RNF6 promoted cell growth, cell-cycle progression, and epithelial-to-mesenchymal transition in colorectal cancer cells; RNF6 also promoted colorectal tumor growth and lung metastasis in mouse models. Mechanistic investigations revealed that RNF6 bound and ubiquitylated transducin-like enhancer of split 3 (TLE3), a transcriptional repressor of the β-catenin/TCF4 complex. RNF6-mediated degradation of TLE3 significantly suppressed the association of TLE3 with TCF4/LEF, which in turn led to recruitment of β-catenin to TCF4/LEF, triggering Wnt/β-catenin activation. Restoration of TLE3 expression abolished the oncogenic effects of RNF6. Taken together, these results demonstrate that RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis.
Significance: RNF6-mediated ubiquitination and degradation of TLE3 activates the Wnt/β-catenin pathway in colorectal carcinogenesis. Cancer Res; 78(8); 1958–71. ©2018 AACR.
Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and Therapeutic Response Evaluation in Hepatocellular Carcinoma
Authors: Guo Wei , Sun Yun-Fan , Shen Min-Na , Ma Xiao-Lu , Wu Jiong , Zhang Chun-Yan , Zhou Yan , Xu Yang , Hu Bo , Zhang Min , Wang Gang , Chen Wei-Qin , Guo Lin , Lu Ren-Quan , Zhou Chao-Hui , Zhang Xin , Shi Ying-Hong , Qiu Shuang-jian , Pan Bai-shen , Cao Ya , Zhou Jian , Yang Xin-Rong , Fan Jia 
Published: January 2018

Abstract
Background: In the present study, we assessed the clinical value of circulating tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and surveillance in hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) by an optimized qPCR-based detection platform.
Methods: Differing subsets of CTCs were investigated, and a multimarker diagnostic CTC panel was constructed in a multicenter patient study with independent validation (total n = 1,006), including healthy individuals and patients with chronic hepatitis B infection (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC, with area under the receiver operating characteristic curve (AUC-ROC) reflecting diagnostic accuracy. The role of the CTC panel in treatment response surveillance and its prognostic significance were further investigated.
Results: The AUC of the CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%, positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8] and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV = 89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and α-fetoprotein–negative HCC, as well as differentiating HCC from CHB, LC, and BHL. The CTC load was decreased significantly after tumor resection, and patients with persistently high CTC load showed a propensity of tumor recurrence after surgery. The prognostic significance of the CTC panel in predicting tumor recurrence was further confirmed [training: HR = 2.692; 95% confidence interval (CI), 1.617–4.483; P &lt; 0.001; and validation: HR = 3.127; 95% CI, 1.360–7.190; P = 0.007].
Conclusions: Our CTC panel showed high sensitivity and specificity in HCC diagnosis and could be a real-time parameter for risk prediction and treatment monitoring, enabling early decision-making to tailor effective antitumor strategies. Clin Cancer Res; 24(9); 2203–13. ©2018 AACR.
Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study
Authors: George Daniel J. , Martini Jean-François , Staehler Michael , Motzer Robert J. , Magheli Ahmed , Escudier Bernard , Gerletti Paola , Li Sherry , Casey Michelle , Laguerre Brigitte , Pandha Hardev S. , Pantuck Allan J. , Patel Anup , Lechuga Maria J. , Ravaud Alain 
Published: January 2018

Abstract
Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC) in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively designed exploratory analysis of tissue biomarkers was conducted to identify predictors of treatment benefit.
Experimental Design: Tissue blocks were used for immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1), CD4, CD8, and CD68. DFS was compared between &lt; versus ≥ median IHC parameter using the Kaplan–Meier method. For biomarkers with predictive potential, receiver operating characteristics curves were generated.
Results: Baseline characteristics were similar in patients with (n = 191) and without (n = 419) IHC analysis. Among patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell density ≥ versus &lt; median [median (95% CI), not reached (6.83–not reached) versus 3.47 years (1.73–not reached); hazard ratio (HR) 0.40 (95% CI, 0.20–0.81); P = 0.009] treated with sunitinib (n = 101), but not with placebo (n = 90). The sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604 and 0.658, respectively. Shorter DFS was observed in placebo-treated patients with PD-L1+ versus PD-L1− tumors (HR 1.75; P = 0.103). Among all patients with PD-L1+ tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P = 0.175).
Conclusions: Greater CD8+ T-cell density in tumor tissue was associated with longer DFS with sunitinib but not placebo, suggesting predictive treatment effect utility. Further independent cohort validation studies are warranted. The prognostic value of PD-L1 expression in primary tumors from patients with high-risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7); 1554–61. ©2018 AACR.
Wide Expression and Significance of Alternative Immune Checkpoint Molecules, B7x and HHLA2, in PD-L1–Negative Human Lung Cancers
Authors: Cheng Haiying , Borczuk Alain , Janakiram Murali , Ren Xiaoxin , Lin Juan , Assal Amer , Halmos Balazs , Perez-Soler Roman , Zang Xingxing 
Published: January 2018

Abstract
Purpose: Immunotherapy targeting the PD-1/PD-L1 pathway has changed the treatment landscape of non–small cell lung carcinoma (NSCLC). We demonstrated that HHLA2, a newly identified immune inhibitory molecule, was widely expressed in NSCLC. We now compared the expression and function of PD-L1 with alternative immune checkpoints, B7x and HHLA2.
Experimental Design: Expression was examined in tissue microarrays consisting of 392 resected NSCLC tumors. Effects of PD-L1, B7x, and HHLA2 on human T-cell proliferation and cytokine production were investigated.
Results: PD-L1 expression was identified in 25% and 31% of tumors in the discovery and validation cohorts and was associated with higher stage and lymph node involvement. The multivariate analysis showed that stage, TIL status, and lymph node involvement were independently associated with PD-L1 expression. B7x was expressed in 69% and 68%, whereas HHLA2 was positive in 61% and 64% of tumors in the two sets. The coexpression of PD-L1 with B7x or HHLA2 was infrequent, 6% and 3%. The majority (78%) of PD-L1–negative cases expressed B7x, HHLA2, or both. The triple-positive group had more TIL infiltration than the triple-negative group. B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation of CD4 and CD8 T cells more robustly than PD-L1-Ig. All three significantly suppressed cytokine productions by T cells.
Conclusions: The majority of PD-L1–negative lung cancers express alternative immune checkpoints. The roles of the B7x and HHLA2 pathway in mediating immune evasion in PD-L1–negative tumors deserve to be explored to provide the rationale for an effective immunotherapy strategy in these tumors. Clin Cancer Res; 24(8); 1954–64. ©2018 AACR.
Small-Cell Neuroendocrine Tumors: Cell State Trumps the Oncogenic Driver
Authors: Oser Matthew G. , Jänne Pasi A. 
Published: January 2018

Abstract
Small-cell neuroendocrine cancers often originate in the lung but can also arise in the bladder or prostate. Phenotypically, small-cell carcinoma of the bladder (SCCB) shares many similarities with small-cell lung cancer (SCLC). It is unknown whether SCCB and SCLC share common genetic driver mutations. Clin Cancer Res; 24(8); 1775–6. ©2018 AACR.
See related article by Chang et al., p. 1965
Relationships between Neighborhood Walkability and Objectively Measured Physical Activity Levels in Hemodialysis Patients
Authors: Han Maggie , Ye Xiaoling , Preciado Priscila , Williams Schantel , Campos Israel , Bonner Marcee , Young Candace , Marsh Daniel , Larkin John W. , Usvyat Len A. , Maddux Franklin W. , Pecoits-Filho Roberto , Kotanko Peter 
Published: January 2018

<b><i>Background/Aims:</i></b><i></i> Neighborhood walkability is associated with indicators of health in the general population. We explored the association between neighborhood walkability and daily steps in hemodialysis (HD) patients. <b><i>Methods:</i></b><i></i> We measured daily steps over 5 weeks using Fitbit Flex (Fitbit, San Francisco, CA, USA) and retrieved Walk Score® (WS) data by patient’s home ZIP code (www.walkscore.com; 0 = poorest walkability; 100 = greatest walkability). <b><i>Results:</i></b><i></i> HD patients took a mean of 6,393 ± 3,550 steps/day (<i>n</i> = 46). Median WS of the neighborhood where they resided was 28. Patients in an above-median WS (<i>n</i> = 27) neighborhood took significantly more daily steps compared to those (<i>n</i> = 19) in a below-median WS neighborhood (7,514 ± 3,900 vs. 4,800 ± 2,228 steps/day; <i>p</i> &#x3c; 0.001, <i>t</i> test). Daily steps and WS were directly correlated (R = 0.425; <i>p</i> = 0.0032, parametric test; R = 0.359, <i>p</i> = 0.0143, non-parametric test). <b><i>Conclusion:</i></b><i></i> This is the first study conducted among HD patients to indicate a direct relationship between neighborhood walkability and the actual steps taken. These results should be considered when designing initiatives to increase and improvise exercise routines in HD populations.
МОРФОМЕТРИЧНА ОЦІНКА ОСОБЛИВОСТЕЙ РЕМОДЕЛЮВАННЯ СТРУКТУР ПОРОЖНЬОЇ КИШКИ ПРИ РЕЗЕКЦІЯХ РІЗНИХ ОБ’ЄМІВ ПЕЧІНКИ
Authors: Tatarchuk L. V. 
Published: January 2018

Пострезекційна портальна гіпертензія, що виникає після видалення великих об′ємів паренхіми печінки, призводить до венозного застою та структурних змін в органах портальної системи. Адаптаційно-компенсаторні процеси у травній системі при резекціях різних об′ємів печінки досліджені недостатньо.Мета – кількісне морфологічне вивчення особливостей ремоделювання структур порожньої кишки при резекціях різних об’ємів печінки.Матеріали та методи. Дослідження проведені на 43 статевозрілих щурах-самцях, які були розділені на 4 групи. 1-а група нараховувала 12 інтакних тварин, 2-а – 11 щурів після резекції 31,5 % паренхіми печінки, 3-я – 12 тварин після резекції 42,0 % об’єму печінки, 4-а – 8 щурів після резекції 58,1 % печінки. Евтаназія дослідних тварин здійснювалася кровопусканням в умовах тіопенталового наркозу через 1 місяць від початку експерименту. Вирізані шматочки із порожньої кишки фіксували в 10 % нейтральному розчині формаліну і після відповідного проведення через етилові спирти зростаючої концентрації заливали у парафінові блоки за загальноприйнятою методикою. Гістологічні зрізи товщиною 5–7 мкм після депарафінізації фарбували гематоксилін-еозином, за ван-Гізоном, Маллорі, Вейгертом, толуїдиновим синім. Морфометрично на гістологічних препаратах порожньої кишки визначали товщини слизової, м’язової, серозної оболонок та підслизового прошарку, довжину, ширину ворсинок, глибину, ширину крипт, висоту покривних епітеліоцитів, діаметр їх ядер, ядерно-цитоплазматичні відношення в епітеліоцитах, відносний об’єм уражених епітеліоцитів, вичисляли підслизово-слизовий та підслизово-м’язовий індекси. Кількісні величини оброблялися статистично.Результати й обговорення. Усестороннім аналізом отриманих морфометричних даних встановлено, що через місяць після резекції 31,5 % паренхіми печінки вони змінювалися незначно. Після резекції 42 % паренхіми печінки ремоделювання структур порожньої кишки було більш вираженим. У даних умовах експерименту нерівномірно та диспропорційно змінювалися морфометричні показники оболонок порожньої кишки, порушувалися відношення між ними, виникали патогістологічні зміни у стінці досліджуваного органа. Найбільш виражено зміненими виявилися морфометричні параметри порожньої кишки через місяць після резекції 58,1 % паренхіми печінки. Нерівномірні зміни просторових характеристик оболонок кишки призводили до збільшення підслизово-слизового індекса на 35,2 %, а підслизово-м’язового – на 26,1 %, кількість пошкоджених епітеліоцитів – у 30,5 рази порівняно з контрольними морфометричними показниками.Висновки. Резекція 42 % та більше паренхіми печінки призводить до вираженого ремоделювання структур порожньої кишки, яке характеризується вираженими змінами морфометричних параметрів слизової, м’язової оболонок, підслизового прошарку, ворсинок, крипт, епітеліоцитів, порушенням співвідношень між просторовими характеристиками оболонок, ядром та цитоплазмою епітеліоцитів, істотним їх ураженням, що може призводити до дисфункції ушкодженого органа.