bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apolipoprotein-mediated regulation of lipid metabolism induces distinctive effects in different types of breast cancer cells
Authors: Ben Hassen Céline , Gutierrez-Pajares Jorge L. , Guimaraes Cyrille , Guibon Roseline , Pinault Michelle , Fromont Gaëlle , Frank Philippe G. 
Published: April 2020

Abstract
Background
The highest incidence of breast cancer is in the Western world. Several aspects of the Western lifestyle are known risk factors for breast cancer. In particular, previous studies have shown that cholesterol levels can play an important role in the regulation of tumor progression.

Methods
In the present study, we modulated cholesterol metabolism in the human breast cancer cell lines MCF-7 and MDA-MB-231 using a genetic approach. Apolipoprotein A-I (apoA-I) and apolipoprotein E (apoE) were expressed in these cell lines to modulate cholesterol metabolism. The effects of these apolipoproteins on cancer cell properties were examined.

Results
Our results show that both apolipoproteins can regulate cholesterol metabolism and can control the epithelial-to-mesenchymal transition process. However, these effects were different depending on the cell type. We show that expressing apoA-I or apoE stimulates proliferation, migration, and tumor growth of MCF-7 cells. However, apoA-I or apoE reduces proliferation and migration of MDA-MB-231 cells.

Conclusions
These data suggest that modulating sterol metabolism may be most effective at limiting tumor progression in models of triple-negative cancers.
Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study
Authors: Kwon Taek-Geun , Jang Albert Youngwoo , Kim Sang Wook , Hong Young Joon , Bae Jang-Ho , Lee Sung Yun , Kim Sang-Hyun , Han Seung Hwan 
Published: April 2020

Abstract
Background
Despite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate.

Methods/design
The STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions.

Discussion
The STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD.

Trial registration
ClinicalTrials.gov, NCT02232360. Registered 9 February 2014.
https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2
Distribution and pyrethroid resistance status of Aedes aegypti and Aedes albopictus populations and possible phylogenetic reasons for the recent invasion of Aedes aegypti in Nepal
Authors: Kawada Hitoshi , Futami Kyoko , Higa Yukiko , Rai Ganesh , Suzuki Takashi , Rai Shiba Kumar 
Published: April 2020

AbstractBackgroundWhen the first systematic list of mosquitoes in Nepal was reported in 1990, there was no description ofAedes aegypti(L.), whileAedes albopictus(Skuse) has been included in theStegomyiasubgroup since the 1950s. The first record ofAe. aegyptiin Nepal was reported in 2009, suggesting some coincidence between the invasion of this species and the first record of dengue fever in Nepal in 2006.ResultsWe performed a field survey of the distribution and insecticide susceptibility ofAe. aegyptiandAe. albopictusin Nepal in 2017 and 2018. Mosquito larvae were collected from used tires located along the streets of Kathmandu, Bharatpur and Pokhara, and a simplified bioassay was used to assess the susceptibility of the larvae to pyrethroid insecticides usingd-allethrin. The presence or absence of point mutations in the voltage-gated sodium channel was also detected by direct sequencing. V1016G was detected at a high frequency and a strong correlation was observed between the frequencies of V1016G and susceptibility indices inAe. aegyptipopulations. F1534C was also detected at a relatively low frequency. InAe. albopictuspopulations, susceptibilities tod-allethrin were high and no point mutations were detected. Analysis of the cytochromecoxidase subunit 1 (cox1) gene was performed for assessing genetic diversity and the existence of two strains were identified inAe. aegyptipopulations. One consisted of 9 globally-distributed haplotypes while the other was derived from an African haplotype.ConclusionsThe high pyrethroid resistance, high V1016G frequency, and relatively low quantity of insecticides used to control dengue vectors in Nepal may have resulted in only weak selection pressure favoring insecticide resistance and could support the hypothesis that this species has recently been introduced from neighboring Asian countries where pyrethroid resistance is relatively widespread.
ATAC-seq normalization method can significantly affect differential accessibility analysis and interpretation
Authors: Reske Jake J. , Wilson Mike R. , Chandler Ronald L. 
Published: April 2020

Abstract
Background
Chromatin dysregulation is associated with developmental disorders and cancer. Numerous methods for measuring genome-wide chromatin accessibility have been developed in the genomic era to interrogate the function of chromatin regulators. A recent technique which has gained widespread use due to speed and low input requirements with native chromatin is the Assay for Transposase-Accessible Chromatin, or ATAC-seq. Biologists have since used this method to compare chromatin accessibility between two cellular conditions. However, approaches for calculating differential accessibility can yield conflicting results, and little emphasis is placed on choice of normalization method during differential ATAC-seq analysis, especially when global chromatin alterations might be expected.

Results
Using an in vivo ATAC-seq data set generated in our recent report, we observed differences in chromatin accessibility patterns depending on the data normalization method used to calculate differential accessibility. This observation was further verified on published ATAC-seq data from yeast. We propose a generalized workflow for differential accessibility analysis using ATAC-seq data. We further show this workflow identifies sites of differential chromatin accessibility that correlate with gene expression and is sensitive to differential analysis using negative controls.

Conclusions
We argue that researchers should systematically compare multiple normalization methods before continuing with differential accessibility analysis. ATAC-seq users should be aware of the interpretations of potential bias within experimental data and the assumptions of the normalization method implemented.
Epigenetic prediction of complex traits and mortality in a cohort of individuals with oropharyngeal cancer
Authors: Langdon Ryan J. , Beynon Rhona A. , Ingarfield Kate , Marioni Riccardo E. , McCartney Daniel L. , Martin Richard M. , Ness Andy R. , Pawlita Michael , Waterboer Tim , Relton Caroline , Thomas Steven J. , Richmond Rebecca C. 
Published: April 2020

AbstractBackgroundDNA methylation (DNAm) variation is an established predictor for several traits. In the context of oropharyngeal cancer (OPC), where 5-year survival is ~ 65%, DNA methylation may act as a prognostic biomarker. We examined the accuracy of DNA methylation biomarkers of 4 complex exposure traits (alcohol consumption, body mass index [BMI], educational attainment and smoking status) in predicting all-cause mortality in people with OPC.ResultsDNAm predictors of alcohol consumption, BMI, educational attainment and smoking status were applied to 364 individuals with OPC in the Head and Neck 5000 cohort (HN5000; 19.6% of total OPC cases in the study), followed up for median 3.9 years; inter-quartile range (IQR) 3.3 to 5.2 years (time-to-event—death or censor). The proportion of phenotypic variance explained in each trait was as follows: 16.5% for alcohol consumption, 22.7% for BMI, 0.4% for educational attainment and 51.1% for smoking. We then assessed the relationship between each DNAm predictor and all-cause mortality using Cox proportional-hazard regression analysis. DNAm prediction of smoking was most consistently associated with mortality risk (hazard ratio [HR], 1.38 per standard deviation (SD) increase in smoking DNAm score; 95% confidence interval [CI] 1.04 to 1.83;P0.025, in a model adjusted for demographic, lifestyle, health and biological variables). Finally, we examined the accuracy of each DNAm predictor of mortality. DNAm predictors explained similar levels of variance in mortality to self-reported phenotypes. Receiver operator characteristic (ROC) curves for the DNAm predictors showed a moderate discrimination of alcohol consumption (area under the curve [AUC] 0.63), BMI (AUC 0.61) and smoking (AUC 0.70) when predicting mortality. The DNAm predictor for education showed poor discrimination (AUC 0.57).Ztests comparing AUCs between self-reported phenotype ROC curves and DNAm score ROC curves did not show evidence for difference between the two (alcohol consumptionP0.41, BMIP0.62, educational attainmentP0.49, smokingP0.19).ConclusionsIn the context of a clinical cohort of individuals with OPC, DNAm predictors for smoking, alcohol consumption, educational attainment and BMI exhibit similar predictive values for all-cause mortality compared to self-reported data. These findings may have translational utility in prognostic model development, particularly where phenotypic data are not available.
Vitamin C improves the therapeutic potential of human amniotic epithelial cells in premature ovarian insufficiency disease
Authors: Hou Shunyu , Ding Chenyue , Shen Han , Qian Chunfeng , Zou Qinyan , Lu Jiafeng , Huang Boxian , Tan Jichun , Li Hong 
Published: April 2020

Abstract
Background
Human amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application.

Methods
Vitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTX-damaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function.

Results
Our results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs.

Conclusion
Treatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.
Runx1t1 promotes the neuronal differentiation in rat hippocampus
Authors: Zou Linqing , Li Haoming , Han Xiao , Qin Jianbing , Song Guoqi 
Published: April 2020

Abstract
Background
Runt-related transcription factor 1 translocated to 1 (Runx1t1) is one of the members of the myeloid translocation gene family. Our previous work showed that Runx1t1 induced the neuronal differentiation of radial glia cells in vitro.

Methods
To better uncover the role of Runx1t1 in hippocampal neurogenesis, in this study, we further explore its localization and function during the hippocampal neurogenesis.

Results
Our results showed that insufficient expression of Runx1t1 reduced the neuronal differentiation, and overexpression of Runx1t1 promoted the neuronal differentiation in vitro. We also found that Runx1t1 localized in neurons but not astrocytes both in vivo and in vitro. Furthermore, we found that Runx1t1 overexpression elevated the number of newborn neurons in the hippocampal dentate gyrus.

Conclusions
Taken together, our results further proved that Runx1t1 could be worked as a regulator in the process of hippocampal neurogenesis.
Bedside prediction of intradialytic hemodynamic instability in critically ill patients: the SOCRATE study
Authors: Bigé Naïke , Lavillegrand Jean-Rémi , Dang Julien , Attias Philippe , Deryckere Stéphanie , Joffre Jérémie , Dubée Vincent , Preda Gabriel , Dumas Guillaume , Hariri Geoffroy , Pichereau Claire , Baudel Jean-Luc , Guidet Bertrand , Maury Eric , Boelle Pierre-Yves , Ait-Oufella Hafid 
Published: April 2020

Abstract
Background
Despite improvements in intermittent hemodialysis management, intradialytic hemodynamic instability (IHI) remains a common issue that could account for increased mortality and delayed renal recovery. However, predictive factors of IHI remain poorly explored. The objective of this study was to evaluate the relationship between baseline macrohemodynamic, tissue hypoperfusion parameters and IHI occurrence.

Methods
Prospective observational study conducted in a 18-bed medical ICU of a tertiary teaching hospital. Cardiovascular SOFA score, index capillary refill time (CRT) and lactate level were measured just before (T0) consecutive intermittent hemodialysis sessions performed for AKI. The occurrence of IHI requiring a therapeutic intervention was recorded.

Results
Two hundred eleven sessions, corresponding to 72 (34%) first sessions and 139 (66%) later sessions, were included. As IHI mostly occurred during first sessions (43% vs 12%, P < 0.0001), following analyses were performed on the 72 first sessions. At T0, cardiovascular SOFA score ≥1 (87% vs 51%, P = 0.0021) was more frequent before IHI sessions, as well as index CRT ≥ 3 s (55% vs 15%, P = 0.0004), and hyperlactatemia > 2 mmol/L (68% vs 29%, P = 0.0018). Moreover, the occurrence of IHI increased with the number of macrohemodynamic and tissue perfusion impaired parameters, named SOCRATE score (cardiovascular SOFA, index CRT and lactATE): 10% (95% CI [3%, 30%]), 33% (95% CI [15%, 58%]), 55% (95% CI [35%, 73%]) and 80% (95% CI [55%, 93%]) for 0, 1, 2 and 3 parameters, respectively (AUC = 0.79 [0.69–0.89], P < 0.0001). These results were confirmed by analyzing the 139 later sessions included in the study.

Conclusions
The SOCRATE score based on 3 easy-to-use bedside parameters correlates with the risk of IHI. By improving risk stratification of IHI, this score could help clinicians to manage intermittent hemodialysis initiation in critically ill AKI patients.
Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study
Authors: Grensemann Jörn , Busse David , König Christina , Roedl Kevin , Jäger Walter , Jarczak Dominik , Iwersen-Bergmann Stefanie , Manthey Carolin , Kluge Stefan , Kloft Charlotte , Fuhrmann Valentin 
Published: April 2020

Abstract
Background
Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF).

Methods
In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cut-off values for Enterobacterales (4 × 0.25 mg/L) and Pseudomonas spp. (4 × 2 mg/L).

Results
Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (V2) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L, p = .05). PTA for Enterobacterales was achieved in 100% for all dosing regimens. PTA for Pseudomonas spp. in ACLF on day 1/7 was: A: 18%/80%, B: 94%/88%, C: 85%/98% D: 100%/100% and NLF: A: 48%/65%, B: 91%/83%, C: 91%/93%, D: 100%/100%.

Conclusion
ALCF patients receiving CVVHD had a higher V2 and may require a higher loading dose of meropenem. For Pseudomonas, high doses or continuous infusion are required to reach PTA in ACLF patients.
Conditions for prosperity and depression of a stochastic R&D model under regime switching
Authors: Zhang Mengqing , Zhang Qimin 
Published: April 2020

AbstractThe stochastic research and development (R&D) model plays an important role in economic growth theories. To explain the growth performance of the economy under regime switching, we first establish sufficient criteria that ensure economic prosperity, nonprosperity and depression in the R&D model disturbed by white and color noise. Then, we determine the threshold between prosperity and depression. Furthermore, we estimate an upper bound of the growth rates of technological progress and capital accumulation in the prosperity case. The results indicate that color noise sensitively impacts the growth performance of the economy in the R&D model. Finally, numerical simulations are conducted to verify our theoretical work.
Orthorexic tendencies are linked with difficulties with emotion identification and regulation
Authors: Vuillier L. , Robertson S. , Greville-Harris M. 
Published: April 2020

AbstractBackgroundOrthorexia nervosa (ON) is characterised by an unhealthy obsession with healthy eating and while it is not recognised as an eating disorder (or any disorder), current research is exploring similarities and differences with such disorders. The literature has shown that individuals with eating disorders have difficulties identifying and describing emotions (known as alexithymia) as well as regulating them. However no research to date has looked at whether people with orthorexic tendencies also suffer from difficulties with emotions. In this paper, we refer to people with orthorexic tendencies but do not assume that their healthy eating is at a pathological level needing clinical attention.MethodsThe current study examined this by asking 196 healthy adults with an interest in healthy eating to complete four questionnaires to measure ON (ORTO-15 – reduced to ORTO-7CS), eating psychopathology (EAT-26), alexithymia (TAS-20) and emotion dysregulation (DERS-16).ResultsWe found that difficulties identifying and regulating emotions was associated with symptoms of ON, similar to what is found in other eating disorders. We suggest that ON behaviours may be used as a coping strategy in order to feel in control in these participants who have poor emotion regulation abilities.ConclusionsOur results show that individuals with ON tendencies may share similar difficulties with emotions compared to other eating disorders. While important, our results are limited by the way we measured ON behaviours and we recommend that further research replicate our findings once a better and more specific tool is developed and validated to screen for ON characteristics more accurately.
Prevalence and heritability of handedness in a Hong Kong Chinese twin and singleton sample
Authors: Zheng Mo , McBride Catherine , Ho Connie Suk-Han , Chan Jonathan Ka-Chun , Choy Kwong Wai , Paracchini Silvia 
Published: April 2020

Abstract
Background
Left-handedness prevalence has been consistently reported at around 10% with heritability estimates at around 25%. Higher left-handedness prevalence has been reported in males and in twins. Lower prevalence has been reported in Asia, but it remains unclear whether this is due to biological or cultural factors. Most studies are based on samples with European ethnicities and using the preferred hand for writing as key assessment. Here, we investigated handedness in a sample of Chinese school children in Hong Kong, including 426 singletons and 205 pairs of twins, using both the Edinburgh Handedness Inventory and Pegboard Task.

Results
Based on a binary definition of writing hand, we found a higher prevalence of left-handedness (8%) than what was previously reported in Asian datasets. We found no evidence of increased left-handedness in twins, but our results were in line with previous findings showing that males have a higher tendency to be left-handed than females. Heritability was similar for both hand preference (21%) and laterality indexes (22%). However, these two handedness measures present only a moderate correlation (.42) and appear to be underpinned by different genetic factors.

Conclusion
In summary, we report new reference data for an ethnic group usually underrepresented in the literature. Our heritability analysis supports the idea that different measures will capture different components of handedness and, as a consequence, datasets assessed with heterogeneous criteria are not easily combined or compared.