bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screen‐detected gallstone disease and risk of liver and pancreatic cancer: The Kailuan Cohort Study
Authors: Zhao Xinyu , Wang Na , Sun Yuanyuan , Zhu Guoling , Wang Yanhong , Wang Zhenyu , Zhang Yanmin , Cheng Kailiang , Wang Guodong , Wu Shouling , Wang Li 
Published: April 2020

AbstractBackgroundFew studies have examined the risk of gastrointestinal cancers in screen‐detected gallstone disease. This study aimed to investigate the association between screen‐detected gallstone disease and gastrointestinal cancers using the Kailuan cohort, a population‐based prospective cohort initiated in 2006.MethodsA total of 79 809 men who underwent gallbladder ultrasonography, were free of cancers in 2006 and did not have gastrointestinal cancers within one year were enrolled. A Cox proportional hazards model with age as the timescale was used to evaluate the association between screen‐detected gallstone disease and gastrointestinal cancers.ResultsWe identified 1264 cases with gastrointestinal cancers, including 303 cases with liver cancer and 94 cases with pancreatic cancer. Screen‐detected gallstone disease increased the risk of liver cancer, with an HR of 2.28 [95% confidence interval (CI): 1.20‐4.33, P = .012]. The association was modified by the hepatitis B surface antigen status. A non‐significant positive association was observed between pancreatic cancer and gallstone disease (HR 2.19, 95% CI: 0.95‐5.05, P = .065). However, the HR became significant after those individuals with diabetes were excluded (HR 2.60, 95% CI: 1.12‐6.01, P = .026).ConclusionScreen‐detected gallstone disease may predict the risk for liver and pancreatic cancer.
Limits of post‐secularism in Turkey: Comparing the attitudes of the Justice and Development Party towards the headscarf and Alevi issues
Authors: Konuralp Emrah 
Published: April 2020

AbstractThe debate on post‐secularism indicates both the inclusion of religious voices into the public sphere and the rising importance of religion in international politics as well as in domestic politics of Western nation‐states. The term “post‐secular” firstly emerged to describe the Western societies where pluralism has been a vital concern for liberal democracy. Nonetheless, the very same concern is prevalent across non‐Western societies. In this respect, the Turkish case having a secular state in a predominantly Muslim society provides a vibrant example for the analysis of post‐secularism as Islamic‐oriented Justice and Development Party (Adalet ve Kalkınma Partisi, AKP) has been ruling Turkey since November 2002. In this article, the success or failure of the AKP in representing a post‐secular moment in Turkish politics is analysed with reference to and in comparison of two issues. The first one is the Sunni‐Islamic demands on the visibility in the public sphere symbolised with the headscarf issue. The second issue is the demands of Alevis living in Turkey as they force the boundaries of the “secular” public sphere which has been dominated by the Sunni‐Turkish socio‐cultural identity.
LPIAT1/MBOAT7 depletion increases triglyceride synthesis fueled by high phosphatidylinositol turnover
Authors: Tanaka Yuki , Shimanaka Yuta , Caddeo Andrea , Kubo Takuya , Mao Yanli , Kubota Tetsuya , Kubota Naoto , Yamauchi Toshimasa , Mancina Rosellina Margherita , Baselli Guido , Luukkonen Panu , Pihlajamäki Jussi , Yki-Järvinen Hannele , Valenti Luca , Arai Hiroyuki , Romeo Stefano , Kono Nozomu 
Published: April 2020

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is a common prelude to cirrhosis and hepatocellular carcinoma. The geneticrs641738 C>Tvariant in the lysophosphatidylinositol acyltransferase 1 (LPIAT1)/membrane bound O-acyltransferase domain-containing 7, which incorporates arachidonic acid into phosphatidylinositol (PI), is associated with the entire spectrum of NAFLD. In this study, we investigated the mechanism underlying this association in mice and cultured human hepatocytes.DesignWe generated the hepatocyte-specificLpiat1knockout mice to investigate the function of Lpiat1 in vivo. We also depletedLPIAT1in cultured human hepatic cells using CRISPR-Cas9 systems or siRNA. The effect of LPIAT1-depletion on liver fibrosis was examined in mice fed high fat diet and in liver spheroids. Lipid species were measured using liquid chromatography-electrospray ionisation mass spectrometry. Lipid metabolism was analysed using radiolabeled glycerol or fatty acids.ResultsThe hepatocyte-specificLpiat1knockout mice developed hepatic steatosis spontaneously, and hepatic fibrosis on high fat diet feeding. Depletion ofLPIAT1in cultured hepatic cells and in spheroids caused triglyceride accumulation and collagen deposition. The increase in hepatocyte fat content was due to a higher triglyceride synthesis fueled by a non-canonical pathway. Indeed, reduction in the PI acyl chain remodelling caused a high PI turnover, by stimulating at the same time PI synthesis and breakdown. The degradation of PI was mediated by a phospholipase C, which produces diacylglycerol, a precursor of triglyceride.ConclusionWe found a novel pathway fueling triglyceride synthesis in hepatocytes, by a direct metabolic flow of PI into triglycerides. Our findings provide an insight into the pathogenesis and therapeutics of NAFLD.
Combined Cohesin–RUNX1 Deficiency Synergistically Perturbs Chromatin Looping and Causes Myelodysplastic Syndromes
Authors: Ochi Yotaro , Kon Ayana , Sakata Toyonori , Nakagawa Masahiro M , Nakazawa Naotaka , Kakuta Masanori , Kataoka Keisuke , Koseki Haruhiko , Nakayama Manabu , Morishita Daisuke , Tsuruyama Tatsuaki , Saiki Ryunosuke , Yoda Akinori , Okuda Rurika , Yoshizato Tetsuichi , Yoshida Kenichi , Shiozawa Yusuke , Nannya Yasuhito , Kotani Shinichi , Kogure Yasunori , Kakiuchi Nobuyuki , Nishimura Tomomi , Makishima Hideki , Malcovati Luca , Yokoyama Akihiko , Takeuchi Kengo , Sugihara Eiji , Sato Taka-Aki , Sanada Masashi , Takaori-Kondo Akifumi , Cazzola Mario , Kengaku Mineko , Miyano Satoru , Shirahige Katsuhiko , Suzuki Hiroshi I. , Ogawa Seishi 
Published: April 2020

Abstract

STAG2 encodes a cohesin component and is frequently mutated in myeloid neoplasms, showing highly significant comutation patterns with other drivers, including RUNX1. However, the molecular basis of cohesin-mutated leukemogenesis remains poorly understood. Here we show a critical role of an interplay between STAG2 and RUNX1 in the regulation of enhancer–promoter looping and transcription in hematopoiesis. Combined loss of STAG2 and RUNX1, which colocalize at enhancer-rich, CTCF-deficient sites, synergistically attenuates enhancer–promoter loops, particularly at sites enriched for RNA polymerase II and Mediator, and deregulates gene expression, leading to myeloid-skewed expansion of hematopoietic stem/progenitor cells (HSPC) and myelodysplastic syndromes (MDS) in mice. Attenuated enhancer–promoter loops in STAG2/RUNX1–deficient cells are associated with downregulation of genes with high basal transcriptional pausing, which are important for regulation of HSPCs. Downregulation of high-pausing genes is also confirmed in STAG2–cohesin-mutated primary leukemia samples. Our results highlight a unique STAG2–RUNX1 interplay in gene regulation and provide insights into cohesin-mutated leukemogenesis.

Significance:
We demonstrate a critical role of an interplay between STAG2 and a master transcription factor of hematopoiesis, RUNX1, in MDS development, and further reveal their contribution to regulation of high-order chromatin structures, particularly enhancer–promoter looping, and the link between transcriptional pausing and selective gene dysregulation caused by cohesin deficiency.
This article is highlighted in the In This Issue feature, p. 747
Collateral Recruitment Is Impaired by Cerebral Small Vessel Disease
Authors: Lin Michelle P. , Brott Thomas G. , Liebeskind David S. , Meschia James F. , Sam Kevin , Gottesman Rebecca F. 
Published: April 2020

Background and Purpose—
Cerebral small vessel disease (SVD) is associated with increased stroke risk and poor stroke outcomes. We aimed to evaluate whether chronic SVD burden is associated with poor recruitment of collaterals in large-vessel occlusive stroke.

Methods—
Consecutive patients with middle cerebral artery or internal carotid artery occlusion presenting within 6 hours after stroke symptom onset who underwent thrombectomy from 2012 to 2017 were included. The prespecified primary outcome was poor collateral flow, which was assessed on baseline computed tomographic angiography (poor, ≤50% filling; good, >50% filling). Markers of chronic SVD on brain magnetic resonance imaging were rated for the extent of white matter hyperintensities, enlarged perivascular spaces, chronic lacunar infarctions and cerebral microbleeds using the Standards for Reporting Vascular Changes on Neuroimaging criteria. Severity of SVD was quantified by adding the presence of each SVD feature, with a total possible score of 0 to 4; each SVD type was also evaluated separately. Multivariable logistic regression analyses were performed to evaluate the relationships between SVD and poor collaterals, with adjustment for potential confounders.

Results—

Of the 100 eligible patients, the mean age was 65±16 years, median National Institutes of Health Stroke Scale score was 15, and 68% had any SVD. Poor collaterals were observed in 46%, and those with SVD were more likely to have poor collaterals than patients without SVD (aOR, 1.9 [95% CI, 1.1–3.2]). Of the SVD types, poor collaterals were significantly associated with white matter hyperintensities (aOR, 2.9 per Fazekas increment [95% CI, 1.6–5.3]) but not with enlarged perivascular spaces (adjusted odds ratio [aOR], 1.3 [95% CI, 0.4–4.0]), lacunae (aOR, 2.1 [95% CI, 0.6–7.1]), or cerebral microbleeds (aOR, 2.1 [95% CI, 0.6–7.8]). Having a greater number of different SVD markers was associated with a higher odds of poor collaterals (crude trend
P
<0.001; adjusted
P
=0.056). There was a dose-dependent relationship between white matter hyperintensity burden and poor collaterals: adjusted odds of poor collaterals were 1.5, 3.0, and 9.7 across Fazekas scores of 1 to 3 (
P
trend=0.015). No patient with an SVD score of 4 had good collaterals.

Conclusions—
Chronic cerebral SVD is associated with poor recruitment of collaterals in large vessel occlusive stroke. A prospective study to elucidate the potential mechanism of how SVD may impair the recruitment of collaterals is ongoing.
Plasma 25-hydroxyvitamin D level and the risk of frailty among Chinese community-based oldest-old: evidence from the CLHLS study
Authors: Xiao Qi , Wu Meiliyang , Cui Jinrui , Yuan Mengmei , Chen Ye , Zeng Tieying 
Published: April 2020

Abstract
Background
Vitamin D deficiency has been linked to the risk of frailty. However, there are limited methods for evaluations of the potential association of vitamin D with frailty in a longevous (80+) population. The aim of this study was to examine the association between plasma 25-hydroxyvitamin D [25(OH)D] levels and the risk of frailty among the Chinese community based oldest-old.

Methods
Secondary analysis of data compiled in the 2011 wave of the Chinese Longitudinal Healthy Longevity Survey (n = 1324) was performed. Frailty was assessed by the Study of Osteoporotic Fractures (SOF) index. Multivariate logistic regression and spline smoothing with threshold effect analysis were performed to investigate the association between 25(OH) D level and the risk of frailty after adjusting for socio-demographic variables, health characteristics and confounding biomarkers.

Results
The mean age was 92.89 ± 7.92 years, and 844 (63.7%) participants were women. In all, data from 426 (33.2, 95% confidence interval, CI: 29.66–34.69) frail participants were recorded. After adjustment for confounding covariates, the level of 25(OH) D was significantly related to frailty. By spline smoothing with threshold effect analysis, a monotonically negative association between 25(OH) D and frailty was identified. Subgroup analyses revealed that the association did not differ by sex or age.

Conclusions
The 25(OH) D level was inversely associated with the risk of frailty among the Chinese community-based oldest-old.
Plasmodium yoelii 17XL infection modified maturation and function of dendritic cells by skewing Tregs and amplificating Th17
Authors: Chen Guang , Du Ji-wei , Nie Qing , Du Yun-ting , Liu Shuang-chun , Liu De-hui , Zhang Hui-ming , Wang Fang-fang 
Published: April 2020

Abstract
Background
Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL).

Methods
DCs detection/analysis dynamically was performed by Tregs depletion or Th17 neutralization in P.y17XL infected BALB/c mice via flow cytometry. Then the levels of cytokines production were detected using enzyme-linked mmunosorbent assay (ELISA).

Results
Our results indicated that Tregs depletion or Th17 neutralization in BALB/c mice infected with P.y17XL significantly up-regulated the percentages of mDC and pDC, increased the expressions of major histocompatibility complex (MHC) class II, CD80, CD86 on DCs and the levels of IL-10/IL-12 secreted by DCs, indicating that abnormal amplification of Tregs or Th17 may damage the maturation and function of DCs during the early stage of malaria infection. Interestingly, we also found that the abnormal amplification of Th17, as well as Tregs, could inhibit the maturation of DCs.

Conclusions
Tregs skewing or Th17 amplification during the early stage of malaria infection may inhibit the maturation and function of DCs by modifying the subsets of DCs, expressions of surface molecules on DCs and secretion mode of cytokines.
Risk scores for predicting incident chronic kidney disease among rural Chinese people: a village-based cohort study
Authors: Wen Jiangping , Hao Jie , Zhang Ye , Cao Kai , Zhang Xiaohong , Li Jiang , Lu Xinxin , Wang Ningli 
Published: April 2020

Abstract
Background
Few chronic kidney disease (CKD) risk prediction models have been investigated in low- and middle-income areas worldwide. We developed new risk scores for predicting incident CKD in low- and middle-income rural Chinese populations.

Methods
Data from the Handan Eye Study, which was a village-based cohort study and conducted from 2006 to 2013, were utilized as part of this analysis. The present study utilized data generated from 3266 participants who were ≥ 30 years of age. Two risk models for predicting incident CKD were derived using two-thirds of the sample cohort (selected randomly) using stepwise logistic regression, and were subsequently validated using data from the final third of the sample cohort. In addition, two simple point systems for incident CKD were generated according to the procedures described in the Framingham Study. CKD was defined as reduced renal function (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2) or the presence of albuminuria (urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g).

Results
The Simple Risk Score included waist circumference, systolic blood pressure (SBP), diabetes, sex, and education. The Best-fit Risk Score included urinary albumin-to-creatinine ratio, SBP, C-reactive protein, triglyceride, sex, education, and diabetes. In the validation sample, the areas under the receiver operating curve of the Simple Risk Score and Best-fit Risk Score were 0.717 (95% CI, 0.689–0.744) and 0.721 (95% CI, 0.693–0.748), respectively; the discrimination difference between the score systems was not significant (P = 0.455). The Simple Risk Score had a higher Youden index, sensitivity, and negative predictive value, with an optimal cutoff value of 14.

Conclusions
Our Simple Risk Score for predicting incident CKD in a low- and middle-income rural Chinese population will help identify individuals at risk for developing incident CKD.
The contribution of iron deficiency to the risk of peripartum transfusion: a retrospective case control study
Authors: VanderMeulen H. , Strauss R. , Lin Y. , McLeod A. , Barrett J. , Sholzberg M. , Callum J. 
Published: April 2020

Abstract
Background
Iron deficiency in pregnancy is associated with inferior maternal and fetal outcomes. Postpartum depression, prematurity, intrauterine growth restriction, impaired childhood cognition and transfusion are all sequelae of maternal iron deficiency anemia. Transfusion to women of childbearing age has important consequences including increasing the risk of hemolytic disease of the fetus and newborn with future pregnancies. The relative contribution of iron deficiency to transfusion rates in the peripartum period is unknown. This study aimed to identify the prevalence of iron deficiency and anemia in pregnant women that received peripartum transfusions relative to age-matched non-transfused controls.

Methods
We performed a retrospective case-control study of all women that were transfused in the peripartum period from January, 2014 to July, 2018. Cases were compared to the next age matched control to deliver at our institution. The primary objective was to determine the proportion of patients with iron deficiency in pregnancy or anemia in pregnancy in cases and controls. Charts were reviewed for predisposing risk factors for iron deficiency, laboratory measures of iron deficiency and anemia, iron supplementation history and maternal and fetal outcomes. Factors associated with peripartum transfusion were analyzed using a multivariate logistic regression.

Results
169 of 18, 294 (0.9%) women were transfused in the peripartum period and 64 (44%) of those transfused received 1 unit. Iron deficiency or anemia were present in 103 (71%) transfused women and 74 (51%) control women in pregnancy (OR 2.34, 95% CI: 3.7–18.0). Multivariate analysis identified social work involvement (adjusted OR 4.1, 95% CI: 1.8–10.1), intravenous iron supplementation in pregnancy (adjusted OR 3.8, 95% CI: 1.2–17.4) and delivery by unscheduled cesarean section (adjusted OR 2.8, 95% CI: 1.3–6.2) as significant predictors of peripartum transfusion.

Conclusions
Pregnant women being followed by a social worker, receiving intravenous iron supplementation in pregnancy or who deliver by unscheduled cesarean section are more likely to receive a red blood cell transfusion. Women with iron deficiency or anemia in pregnancy are at increased risk of peripartum blood transfusions and warrant early and rigorous iron supplementation.
CD45dimCD34+CD38−CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia
Authors: Heo Sook-Kyoung , Noh Eui-Kyu , Ju Lan Jeong , Sung Jun Young , Jeong Yoo Kyung , Cheon Jaekyung , Koh Su Jin , Min Young Joo , Choi Yunsuk , Jo Jae-Cheol 
Published: April 2020

Abstract
Background
Leukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.

Methods
We examined the levels of CD45dimCD34+CD38−CD133+ cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cytometry.

Results
Interestingly, the CD45dimCD34+CD38−CD133+ cells were highly expressed in the bone marrow of patients with AML compared to that in healthy controls (HC). Moreover, the proportions of CD45dimCD34+CD38−CD133+ cells were also examined in diverse hematological malignancies, including AML, CML, DLBCL, MM, MDS, HL, ALL, and CLL. LSCs were prominently detected in the BMCs isolated from patients with AML and CML, but rarely in BMCs isolated from patients with DLBCL, MM, MDS, ALL, CLL, and HL. Additionally, the high CD45dimCD34+CD38−CD133+ cell counts in AML patients served as a significantly poor risk factor for overall and event free survival.

Conclusions
Therefore, our results suggest that CD45dimCD34+CD38−CD133+ cells in AML might potentially serve as LSCs. In addition, this cell population might represent a novel therapeutic target in AML.
Dietary factors and risk of mortality among patients with esophageal cancer: a systematic review
Authors: Sun Li-Ping , Yan Lu-Bin , Liu Zhen-Zhen , Zhao Wen-Jing , Zhang Cai-Xia , Chen Yu-Min , Lao Xiang Qian , Liu Xudong 
Published: April 2020

Abstract
Background
The effects of dietary factors on prognosis of esophageal cancer remain unclear. This systematic review and meta-analysis aimed to assess the association between dietary intake and the risk of mortality among patients with esophageal cancer.

Methods
Six electronic databases (PubMed, Web of Science, OVID, ProQuest, CNKI and Wanfang) were searched for studies published up to Oct. 2019 that examined the association between dietary intake and all-cause mortality, esophageal cancer-specific mortality and esophageal cancer recurrence. The pooled hazard ratio (HR) with 95% confidence interval (CI) were derived by comparing the highest with the lowest categories of each dietary item and by using random effect models.

Results
A total of 15 cohort studies were included in this study and all reported pre-diagnosis dietary exposure; two focused on dietary folate, 12 on alcohol consumption and three on other dietary components (sugary beverages, phytochemicals and preserved vegetables). When comparing the highest with the lowest categories, dietary folate intake was associated with a reduced risk of esophageal cancer-specific mortality in patients with esophageal squamous cell carcinoma (HR: 0.41, 95% CI: 0.25–0.69), with low heterogeneity (I2 = 0%, P = 0.788). When comparing the highest with the lowest categories of alcohol consumption, alcohol consumption was associated with an increased risk of all-cause mortality in patients with esophageal squamous cell carcinoma (HR: 1.29, 95% CI: 1.07–1.55; heterogeneity: I2 = 53%, P = 0.030), but this increased risk was not significant in patients with esophageal adenocarcinoma (HR = 1.05, 95% CI: 0.84–1.32).

Conclusions
This review with pre-diagnostic dietary exposure showed that dietary folate intake was associated with a reduced risk of mortality of esophageal squamous cell carcinoma, whereas alcohol consumption was associated with an increased risk. More studies are needed to investigate effect of dietary factors, especially post-diagnosis dietary consumption, on esophageal cancer prognosis.