bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attribute level overlap (and color coding) can reduce task complexity, improve choice consistency, and decrease the dropout rate in discrete choice experiments
Authors: Jonker Marcel F. , Donkers Bas , de Bekker‐Grob Esther , Stolk Elly A. 
Published: December 2018

AbstractA randomized controlled discrete choice experiment (DCE) with 3,320 participating respondents was used to investigate the individual and combined impact of level overlap and color coding on task complexity, choice consistency, survey satisfaction scores, and dropout rates. The systematic differences between the study arms allowed for a direct comparison of dropout rates and cognitive debriefing scores and accommodated the quantitative comparison of respondents' choice consistency using a heteroskedastic mixed logit model. Our results indicate that the introduction of level overlap made it significantly easier for respondents to identify the differences and choose between the choice options. As a stand‐alone design strategy, attribute level overlap reduced the dropout rate by 30%, increased the level of choice consistency by 30%, and avoided learning effects in the initial choice tasks of the DCE. The combination of level overlap and color coding was even more effective: It reduced the dropout rate by 40% to 50% and increased the level of choice consistency by more than 60%. Hence, we can recommend attribute level overlap, with color coding to amplify its impact, as a standard design strategy in DCEs.
Detection of circulating HPV16 DNA as a biomarker in the blood of patients with human papillomavirus‐positive oropharyngeal squamous cell carcinoma
Authors: Mazurek Agnieszka M. , Rutkowski Tomasz , Śnietura Mirosław , Pigłowski Wojciech , Suwiński Rafał , Składowski Krzysztof 
Published: December 2018

AbstractBackgroundDevelopment of biomarker analysis using the circulating cell‐free DNA (cfDNA) methodology is a challenge for noninvasive cancer diagnosis. In this study, a comparison between the plasma and tumor tissue HPV16 DNA viral loads (VLs) has been presented.MethodsReal‐time polymerase chain reaction was performed for quantitating of HPV16 DNA in the plasma and tumor samples of patients with oropharyngeal cancer.ResultsAmong the tissues, HPV16‐positive patients with oropharyngeal squamous cell carcinoma, nonsmoking patients, displayed significantly higher HPV16 DNA VLs in their tissue. No smoking and advanced N disease were the most important predictors for cHPV16 DNA (circulating HPV16 DNA) detection. The cHPV16‐positive women displayed significantly higher VLs in their tumor tissues compared to the men, although without notable impact on the blood detection.ConclusionsMany factors were responsible for human papillomavirus DNA circulation in blood. As a result of the small size of the analyzed group, some observed discrepancies need to be proven on a larger cohort.
Maternal di‐(2‐ethylhexyl) phthalate exposure alters hepatic insulin signal transduction and glucoregulatory events in rat F1 male offspring
Authors: Rajagopal Gokulapriya , Bhaskaran Ravi Sankar , Karundevi Balasubramanian 
Published: December 2018

AbstractDi‐(2‐ethylhexyl) phthalate (DEHP) is a commonly used plasticizer with endocrine disrupting properties. Its widespread use resulted in constant human exposure including fetal development and postnatal life. Epidemiological and experimental data have shown that DEHP has a negative influence on glucose homeostasis. However, the evidence regarding the effect of maternal DEHP exposure on hepatic glucose homeostasis is scarce. Hence, we investigated whether DEHP exposure during gestation and lactation disrupts glucose homeostasis in the rat F1 male offspring at adulthood. Pregnant rats were divided into three groups and administered with DEHP (10 and 100 mg/kg/day) or olive oil from gestational day 9 to postnatal day 21 (lactation period) through oral gavage. DEHP‐exposed offspring exhibited hyperglycemia, impaired glucose and insulin tolerances along with hyperinsulinemia at postnatal day 80. DEHP exposure significantly reduced the levels of insulin signaling molecules such as insulin receptors, IRS1, Akt and its phosphorylated forms. GSK3β and FoxO1 proteins increased in DEHP‐exposed groups whereas its phosphorylated forms decreased. Treated groups showed decreased glycogen synthase activity and glycogen concentration. Glucose‐6‐phosphatase and phosphoenolpyruvate carboxykinase mRNA level and enzyme activity increased in DEHP‐treated groups. The interaction between FoxO1‐glucose‐6‐phosphatase and FoxO1‐phosphoenolpyruvate carboxykinase was also increased. This study suggests that DEHP exposure impairs insulin signal transduction and alters glucoregulatory events leading to the development of type 2 diabetes in F1 male offspring.
Investigating the permeation properties of contact lenses and its influence on tear electrolyte composition
Authors: Mann Aisling , Sáez‐Martinez Virginia , Lydon Fiona , Tighe Brian 
Published: December 2018

AbstractThe health of the cornea is paramount; the aim of this study was to assess the permeation of essential tear electrolytes through a range of commercial contact lenses. Donor/receiver conductivity measurements were recorded using a dual‐chamber diffusion system which allowed material permeability profiles and coefficients to be calculated. Water structuring properties of the contact lenses were measured by differential scanning calorimetry. Freezing water was subdivided into “ice‐like” water (free, non‐bound and has a melting point close to that of pure water) and polymer‐associated water (free but loosely bound to the polymer matrix). Each material interacts differently with each of the three salts, for example; lotrafilcon B (34% equilibrium water content [EWC]) shows a higher and larger range of receiver concentrations post KCl, NaCl, CaCl2 permeation (76, 59 and 42 mM, respectively) compared with the lower and tighter range exhibited by lotrafilcon A (22% EWC) (36, 22, and 18 mM, respectively). Additionally, in terms of the relationship between permeation and water structure, balafilcon A (34% EWC) has a high KCl permeation (P60 258 × 10−8 cm2/s) and ice‐like water (14%), but narafilcon A (44% EWC) has a low ion permeation (P60 3.9 × 10−8 cm2/s) and significantly less ice‐like water (4%). The permeation trends for the silicone hydrogel materials could not be fully explained by water content and structuring. Composition and, in particular, the microstructure and morphology of these materials must impart a greater influence on permeation capability. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1997–2005, 2019.
A shared comparison of diabetes mellitus and neurodegenerative disorders
Authors: Morsi Mahmoud , Kobeissy Firas , Magdeldin Sameh , Maher Ahmed , Aboelmagd Omnia , Johar Dina , Bernstein Larry 
Published: December 2018

AbstractDiabetes mellitus (DM), one of the most prevalent metabolic diseases in the world population, is associated with a number of comorbid conditions including obesity, pancreatic endocrine changes, and renal and cardio‐cerebrovascular alterations, coupled with peripheral neuropathy and neurodegenerative disease, some of these disorders are bundled into metabolic syndrome. Type 1 DM (T1DM) is an autoimmune disease that destroys the insulin‐secreting islet cells. Type 2 DM (T2DM) is diabetes that is associated with an imbalance in the glucagon/insulin homeostasis that leads to the formation of amyloid deposits in the brain, pancreatic islet cells, and possibly in the kidney glomerulus. There are several layers of molecular pathologic alterations that contribute to the DM metabolic pathophysiology and its associated neuropathic manifestations. In this review, we describe the general signature metabolic features of DM and the cross‐talk with neurodegeneration. We will assess the underlying molecular key players associated with DM‐induced neuropathic disorders that are associated with both T1DM and T2DM. In this context, we will highlight the role of tau and amyloid protein deposits in the brain as well in the pancreatic islet cells, and possibly in the kidney glomerulus. Furthermore, we will discuss the central role of mitochondria, oxidative stress, and the unfolded protein response in mediating the DM‐associated neuropathic degeneration. This study will elucidate the relationship between DM and neurodegeneration which may account for the evolution of other neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease as discussed later.
Galectin‐3 deficiency protects lipopolysaccharide‐induced chondrocytes injury via regulation of TLR4 and PPAR‐γ‐mediated NF‐κB signaling pathway
Authors: Wang Jian‐sheng , Xiao Wei‐wei , Zhong Yong‐sheng , Li Xue‐dong , Du Shi‐xin , Xie Peng , Zheng Gui‐zhou , Han Jing‐ming 
Published: December 2018

AbstractThe aim of the present study was to identify the functional role of galectin‐3 (Gal‐3) in lipopolysaccharide (LPS)‐induced injury in ATDC5 cells and to explore the probable molecular mechanisms. Here, we identified that LPS is sufficient to enhance the expression of Gal‐3 in ATDC5 cells. In addition, repression of Gal‐3 obviously impeded LPS‐stimulated inflammation damage as exemplified by a reduction in the release of inflammatory mediators interleukin (IL)‐1β, IL‐6, and tumor necrosis factor‐α, as well as the production of nitric oxide and prostaglandin E2 (PGE2) concomitant with the downregulation of matrix metalloproteinases (MMP)‐13 and MMP‐3 expression in ATDC5 cells after LPS administration. Moreover, ablation of Gal‐3 dramatically augmented cell ability and attenuated cell apoptosis accompanied by an increase in the expression of antiapoptotic protein Bcl‐2 and a decrease in the expression of proapoptotic protein Bax and caspase‐3 in ATDC5 cells subjected with LPS. Importantly, we observed that forced expression of TLR4 or blocked PPAR‐γ with the antagonist GW9662 effectively abolished Gal‐3 inhibition–mediated anti‐inflammatory and antiapoptosis effects triggered by LPS. Mechanistically, depletion of Gal‐3 prevents the NF‐κB signaling pathway. Taken together, these findings indicated that the absence of Gal‐3 exerted chondroprotective properties dependent on TLR4 and PPAR‐γ‐mediated NF‐κB signaling, indicating that Gal‐3 functions as a protector in the development and progression of osteoarthritis.
Long noncoding RNA–antisense noncoding RNA in the INK4 locus accelerates wound healing in diabetes by promoting lymphangiogenesis via regulating miR‐181a/Prox1 axis
Authors: He Zhi‐You , Wei Tian‐Hong , Zhang Pi‐Hong , Zhou Jie , Huang Xiao‐Yuan 
Published: December 2018

AbstractBackgroundSlow lymphangiogenesis is one crucial reason for the impaired wound healing process in diabetes. Accumulative evidence showed that long noncoding RNA–antisense noncoding RNA in the INK4 locus (ANRIL) could influence lymphangiogenesis. Besides, miR‐181a has been reported to regulate Prox1 that is essential for lymphangiogenesis. However, the relationship between ANRIL and miR‐181a as well as the definitive function of ANRIL in lymphangiogenesis is not clear.MethodsThe diabetic mouse model was set up to assess the wound healing rate in vivo. Quantitative real‐time polymerase chain reaction was performed to measure the expressions of ANRIL, miR‐181a, and Prox1. Western blot analysis was used to assess the expressions of vascular endothelial growth factor receptor‐3, lymphatic vessel hyaluronan receptor‐1, Prox1, and epithelial–mesenchymal transition (EMT)‐related proteins. Flow cytometry was used to assess the cell apoptosis. Wound healing assay was used to determine the effect of ANRIL on cell migration. Tube‐formation assay and immunofluorescence staining were performed to determine tube‐formation capacity of human dermal lymphatic endothelial cells (LECs).ResultsANRIL and Prox1 were downregulated, whereas miR‐181a was upregulated in the diabetic wound healing mouse model and high glucose (HG)‐induced LECs. The wound healing rate and EMT were inhibited during the diabetic wound healing process. Dual‐luciferase assay proved that miR‐181a could bind Prox1 to repress its expression, whereas ANRIL could sponge miR‐181a to recover Prox1 expression. Overexpression of ANRIL or inhibition of miR‐181a rescued the impairments of survival, migration, EMT formation, and tube formation of LECs caused by HG.ConclusionANRIL could promote lymphangiogenesis during the diabetic wound healing process via sponging miR‐181a to enhance Prox1 expression, which might help design new therapy to improve the wound healing efficacy for diabetes.
Clusterin enhances AKT2‐mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit
Authors: Bertacchini Jessika , Mediani Laura , Beretti Francesca , Guida Marianna , Ghalali Aram , Brugnoli Federica , Bertagnolo Valeria , Petricoin Emanuel , Poti Francesco , Arioli Jessica , Anselmi Laura , Bari Alessia , McCubrey James , Martelli Alberto M. , Cocco Lucio , Capitani Silvano , Marmiroli Sandra 
Published: December 2018

AbstractClusterin (CLU) is a chaperone‐like protein with multiple functions. sCLU is frequently upregulated in prostate tumor cells after chemo‐ or radiotherapy and after surgical or pharmacological castration. Moreover, CLU has been documented to modulate the cellular homolog of murine thymoma virus akt8 oncogene (AKT) activity. Here, we investigated how CLU overexpression influences phosphatidylinositol 3′‐kinase (PI3K)/AKT signaling in human normal and cancer epithelial prostate cells. Human prostate cells stably transfected with CLU were broadly profiled by reverse phase protein array (RPPA), with particular emphasis on the PI3K/AKT pathway. The effect of CLU overexpression on normal and cancer cell motility was also tested. Our results clearly indicate that CLU overexpression enhances phosphorylation of AKT restricted to isoform 2. Mechanistically, this can be explained by the finding that the phosphatase PH domain leucine‐rich repeat‐containing protein phosphatase 1 (PHLPP1), known to dephosphorylate AKT2 at S474, is markedly downregulated by CLU, whereas miR‐190, a negative regulator of PHLPP1, is upregulated. Moreover, we found that phosphatase and tensin homolog (PTEN) was heavily phosphorylated at the inhibitory site S380, contributing to the hyperactivation of AKT signaling. By keeping AKT2 phosphorylation high, CLU dramatically enhances the migratory behavior of prostate epithelial cell lines with different migratory and invasive phenotypes, namely prostate normal epithelial 1A (PNT1A) and prostatic carcinoma 3 (PC3) cells. Altogether, our results unravel for the first time a circuit by which CLU can switch a low migration phenotype toward a high migration phenotype, through miR‐190‐dependent downmodulation of PHLPP1 expression and, in turn, stabilization of AKT2 phosphorylation.
MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen‐activated protein kinase pathway
Authors: Zhou Yihong , Chu Xi , Yi Ye , Hao Zheng , Zheng Xiaoping , Yuxin Tang , Dai Yingbo 
Published: December 2018

AbstractBladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well‐studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell‐cycle arrest. Next, MRS1754 inhibited cell migration and Bay60‐6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p‐P38, p‐JNK, and phospho‐extracellular signal‐regulated kinase (p‐ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen‐activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC.
Safety Exposure‐Response Analysis for Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV‐Infected Subjects
Authors: Osawa Mayu , Ueno Takayo , Shiozaki Tomomi , Li Hanbin , Garimella Tushar 
Published: December 2018

AbstractThe combination regimen of daclatasvir, asunaprevir, and beclabuvir has been developed for the treatment of hepatitis C virus infection. The objectives of this analysis were to characterize the relationship between the exposures of the daclatasvir, asunaprevir, and beclabuvir regimen and liver‐related laboratory elevations (Grade 3 or 4 alanine aminotransferase [ALT] and total bilirubin [Tbili]), and to evaluate the impact of selected covariates on the exposure‐response relationships. The exposure‐response analysis was performed with data from 1 phase 2 and 3 phase 3 studies in hepatitis C virus–infected subjects. The probability of liver‐related laboratory elevations were modeled using linear logistic regression. Selected covariates were tested using a forward‐addition and backward‐elimination approach. The final model for ALT elevation included Asian race, body weight in non‐Asian subjects, and asunaprevir exposure. The final model for Tbili elevation included Asian race, fibrosis score (F0‐F3 or F4) and asupanprevir exposure. Asian subjects had greater the Grade 3 or 4 ALT and Tbili elevation rates than non‐Asians. The Grade 3 or 4 ALT elevation rate increased with decreasing body weight in non‐Asian subjects. Subjects with F4 fibrosis score had a higher rate of Grade 3 or 4 Tbili elevation compared to subjects with F0 to F3 fibrosis score. Higher asunaprevir exposure was associated with increases in Grade 3 or 4 ALT and Tbili elevation rates; however, the impact on the ALT elevation was not clinically relevant and the effect on Tbili elevation was smaller than the other significant covariates.
Population Pharmacokinetics and Exposure‐Response Analyses for CPX‐351 in Patients With Hematologic Malignancies
Authors: Wang Qi , Banerjee Kamalika , Vasilinin Grygoriy , Marier J.F. , Gibbons Jacqueline A. 
Published: December 2018

AbstractCPX‐351, a dual‐drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved in the United States for adults with newly diagnosed therapy‐related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia‐related changes. Population pharmacokinetics analyses were performed using nonlinear mixed‐effect modeling on pooled data from 3 clinical studies, and the impact of CPX‐351 exposures on efficacy and safety was assessed. The pharmacokinetics of cytarabine and daunorubicin were described using 2‐compartment models with linear elimination. None of the evaluated covariates had a clinically significant impact on plasma exposure to total cytarabine or daunorubicin, while bilirubin and formulation showed statistically significant effects on pharmacokinetic parameters of cytarabine and daunorubicin, respectively. In patients with mild/moderate renal impairment or serum bilirubin ≤3 mg/dL, plasma exposures to cytarabine and daunorubicin following CPX‐351 were within the variability range for patients with normal kidney function or serum bilirubin levels. Exposure‐response analysis demonstrated that better efficacy outcomes were associated with higher CPX‐351 exposure quartiles. Early mortality rates in all CPX‐351 exposure quartiles were lower vs the 7 + 3 control group, and lower mortality rates were associated with higher exposure quartiles. A trend toward greater frequency of grade 3 treatment‐emergent adverse events (but not grade 4/5 events) was observed at higher CPX‐351 exposure quartiles. Overall, the population pharmacokinetic analyses indicate no adjustments to the recommended dose and schedule of CPX‐351 are warranted for patients with mild/moderate renal impairment or serum bilirubin ≤3 mg/dL. Results from the exposure‐response analyses suggest the current CPX‐351 regimen provides a favorable risk‐benefit profile.
Vitamin D supplements for trunk muscle morphology in older adults: secondary analysis of a randomized controlled trial
Authors: Cuellar William A. , Blizzard Leigh , Hides Julie A. , Callisaya Michele L. , Jones Graeme , Cicuttini Flavia , Wluka Anita E. , Ding Changhai , Winzenberg Tania M. 
Published: December 2018

AbstractBackgroundThe effect of vitamin D supplementation on postural muscles of the trunk is of particular interest because low 25‐hydroxyvitamin D [25(OH) D] levels are associated with decreased postural balance and increased risk of falls. Understanding the role of vitamin D supplementation plays in trunk muscle function of older adults is necessary, as this is a potentially modifiable factor to improve postural muscle function and decrease the risk of falling of older adults. The objective of this randomized controlled trial was to evaluate the effect of 12 months of vitamin D supplementation compared with placebo, on morphology and function of the trunk muscles of adults aged 50 to 79 years with low serum 25(OH) D levels.MethodsThis was a secondary analysis of a randomized, placebo‐controlled, and double‐blind clinical trial conducted between June 2010 and December 2013 in Tasmania, Australia. The clinical trial was registered with the Australian New Zealand clinical trial registration agency, ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN 12610000495022. Participants were aged 50–79 years with ongoing symptoms of knee osteoarthritis and with low serum [25(OH) D] (12.5 to 60 nmol/L, 5.2 to 24 ng/mL). Participants were randomly assigned to either monthly 50 000 IU oral vitamin D3 (n = 104) or an identical placebo (n = 113) for 24 months as per clinical trial protocol. The primary outcomes in this pre‐specified secondary analysis were between‐group differences in change in size of rectus abdominis, transversus abdominis, internal oblique, external oblique, and lumbar multifidus muscles and function (assessed by change in thickness on contraction) of these muscles (excepting rectus abdominis) from baseline to 12 months. Muscle size was assessed using ultrasound imaging.ResultsOf 217 participants (mean age 63 years, 48% women), 186 (85.7%) completed the study. There were no significant between‐group differences in change in size or function of the abdominal or multifidus muscles after 12 months of vitamin D supplementation.ConclusionsA monthly dose of 50 000 IU of vitamin D3 alone for 12 months does not affect the size or ability to contract trunk muscles of independent community‐dwelling older adults with symptomatic knee osteoarthritis and low serum 25(OH) D levels regardless of body mass index status or degree of vitamin D deficiency. An effect of vitamin D supplementation on other aspects of trunk muscle function such as strength, power, or physical function cannot be ruled out.