bluuebunny/crossref_metadata_2025_split huggingface dataset:
Garlic Supplementation Modified Enzymatic Omega‐6 Polyunsaturated Fatty Acid Oxidation in Mild Hypercholesterolemia
Authors: Leung Ho Hang , Yau Yu Fung , Leung Kin Sum , Lee Yiu Yiu , Oger Camille , Durand Thierry , Galano Jean‐Marie , Loke Wai Mun , Lee Jetty Chung‐Yung 
Published: April 2019

Dietary garlic has been shown to alleviate hypercholesterolemia, a condition associated with the development of cardiovascular disease. Reactive oxygen species take part in the disease progression, but it is unknown if antioxidant rich garlic arrests lipid and cholesterol oxidation in hypercholesterolemia. This study provides fermented garlic or non‐fermented garlic to mild hypercholesterolemia (total cholesterol: 5.2–6.2 mmol L−1) and determines its ability to relieve in vivo oxidative stress by measuring multiple oxidized lipid products of polyunsaturated fatty acid (PUFA) and cholesterol oxidation products (COPs) in plasma. Plasma fatty acids levels are also analyzed. After 13 weeks supplementation, both groups show a significant increase in α‐linolenic acid level (p < 0.05). Levels of arachidic acid increase and palmitoleic acid decreases in the group supplemented with non‐fermented garlic. Of the oxidized PUFA products, notably those derived from enzymatic oxidation of arachidonic acid, namely hydroxyeicosatetraenoic acid (HETE), show a significant difference. Levels of lipoxygenase mediate 5‐HETE and 12‐HETE, and CYP‐P450 mediates 9‐HETE and 11‐HETE decreases after non‐fermented garlic supplementation only (p < 0.05). Non‐enzymatic PUFA oxidation and COPs are not altered by garlic supplementation. Overall, only non‐fermented garlic intake shows selective antioxidant properties in mild hypercholesterolemia where limited effect is found in reducing lipid oxidation.Practical Applications: Current research provides a new insight for the use of garlic extract as a nutraceutical to reduce in vivo oxidative stress. The modified enzymatic oxidation of arachidonic acid in mild hypercholesterolemia after non‐fermented garlic extract intake potentially preventes the progression of chronic inflammation that can lead to complicated pathologies such as arthritis, cardiovascular diseases, and non‐alcoholic fatty liver disease.Garlic is a claimed functional food. The fermented form is proposed to have stronger antioxidant properties. Analysis of mild hypercholesterolemia plasma before and after fermented or non‐fermented garlic extract intake for 13 weeks revealed augmented α‐linolenic acid. Garlic appeared to be selective in the antioxidant property. Pro‐inflammatory lipid mediators (5‐, 9‐, 11‐, and 12‐HETE) released via enzymatic polyunsaturated fatty acid (PUFA) oxidation reduced after non‐fermented garlic extract intake only. However, intake of both garlic types did not reduce non‐enzymatic PUFA oxidation status.
Computationally efficient nonstationary nearest‐neighbor Gaussian process models using data‐driven techniques
Authors: Konomi B. A. , Hanandeh A. A. , Ma P. , Kang E. L. 
Published: April 2019

AbstractDue to the increased availability of measurements of various geophysical processes, a need has arisen for statistical methods suitable for the analysis of very large nonstationary spatial data sets. The nearest‐neighbor Gaussian process (NNGP) models are one of the latest and most popular Gaussian process‐based models, which reduce computational complexity and memory storage. The Bayesian inference is based on the assumption of a parametric covariance function that is often assumed stationary or known. Given that NNGP models are sensitive in the stationary assumption in comparison to other reduction methods, there is a need to build nonstationary covariance functions within the NNGP models. However, the construction of a nonstationary covariance function and/or matrix may be computationally expensive by itself in the presence of big data. In this paper, we develop an efficient two‐stage approach that deals with nonstationarity and the computational complexity in the presence of a big spatial data set. We propose a new low‐cost data‐driven tree‐structured partitioning technique to divide the spatial region into distinct subregions. Given the partitions, we construct computationally efficient nonstationary covariance functions for NNGP models. We demonstrate the performance of our approach through simulation experiments and an application to the global Total Ozone Matrix Spectrometer (TOMS) data set, in which the proposed approach performs well in terms of both prediction accuracy and computational complexity.
Determinants of self‐ and carer‐rated quality of life and caregiver burden in Alzheimer disease
Authors: Schumann Christin , Alexopoulos Panagiotis , Perneczky Robert 
Published: April 2019

ObjectiveWe aimed to investigate factors associated with self‐ and carer‐rated quality of life (QoL) and caregiver burden related to very mild to severe clinical Alzheimer disease (AD).MethodsOne hundred patient‐carer dyads were recruited, and assessments of relevant outcomes were performed, including sociodemographic characteristics, QoL, activities of daily living (ADL), cognitive performance, behavioural and psychological symptoms of dementia (BPSD), caregiver burden, and health resource utilisation.ResultsThere was a strong correlation between carer‐ and self‐rated QoL, with patients consistently rating their QoL higher than caregivers. Duration of illness did not affect the QoL ratings. There was an inverse association between both self‐ and carer‐rated QoL with age, age at symptom onset, impairment of ADL, time spent on assisting the patient, and depression. Both self‐ and carer‐rated QoL ratings were higher if the caregiver was a spouse vs a child. Carer‐rated QoL was inversely associated with severity of dementia, BPSD, caregiver burden, and requirement to supervise the patient. The variables age at symptom onset, ADL, and living together with the primary caregiver explained 34.50% of the variance in self‐rated QoL, whereas age at symptom onset, ADL, and BPSD explained 48.20% of the variance in carer‐rated QoL. For caregiver burden, 26% of the variance was explained by the variables ADL, living together with the primary caregiver, and agitation.ConclusionOur study highlights the need for a stronger focus on QoL in clinical AD research by providing further pieces of evidence on the key determinants, including the important aspect of caregiver burden.
Recategorization of tumor stage in patients with node‐negative oral tongue cancer: Impact of the eighth edition American Joint Committee staging system
Authors: Dang Rushil R. , Qureshi Muhammad M. , Caldroney Steven J. , Salama Andrew R. , Truong Minh Tam 
Published: April 2019

AbstractBackgroundTo evaluate recategorization of pT1‐3N0 oral tongue cancer, from seventh to eighth editions of the American Joint Committee on Cancer (AJCC) staging classification, and impact on overall survival (OS).MethodsUsing the National Cancer Database, 1277 patients were categorized using tumor size and depth of invasion with seventh and eighth AJCC staging systems and evaluated for OS.ResultsTumor‐category was unchanged in 82.9% and upstaged in 17.1% patients with eighth AJCC. The 3‐year OS was 85.3%, 76.6%, and 77.0% with seventh AJCC compared to 87.1%, 75.1%, and 81% with eighth AJCC, for patients with pT1N0, pT2N0, and pT3N0 disease, respectively. Improved discrimination of pT1N0 vs pT2N0 for OS on multivariate analysis was seen for eighth AJCC (hazard ratio [HR] = 1.43, 95% confidence interval [CI]: 1.03‐1.98, P = .03) but not for patients with pT3N0, with seventh AJCC (HR = 1.02, 95% CI:0.53‐1.98, P = .95), and eighth AJCC (HR = 0.86, 95% CI: 0.52‐1.42, P = .55).ConclusionEighth edition AJCC staging leads to improved discrimination of OS between pT1N0 and pT2N0 but not for patients with pT3N0.
Enhanced phosphorylation of AMPK by lutein and oxidised lutein that lead to mitochondrial biogenesis in hyperglycemic HepG2 cells
Authors: Nanjaiah Hemalatha , Vallikannan Baskaran 
Published: April 2019

AbstractThe stimulation of adenosine monophosphate‐activated protein kinase (AMPK) is a prime target to decrease the hyperglycemic condition, hence it is a lutein (L) and oxidised lutein (OXL) is a target molecule for the treatment of type II diabetes. In the current study, a plausible interaction of L and OXL with AMPK was investigated by molecular docking. In addition, the effect of L and OXL for the activation of AMPK that triggers the downstream regulator peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), TFAM expression, mitochondrial DNA (mtDNA), mitochondrial biogenesis and superoxide dismutase 2 (SOD2) in high glucose treated HepG2 cells were investigated by quantitative polymerase chain reaction and Western blot analysis. Molecular docking reveals higher binding affinity of L (ΔG = −6.3 kcal/mol) and OXL (ΔG = −15.5 kcal/mol) with AMPK, compared with metformin (ΔG = −5.0 kcal/mol). The phosphorylation of AMPK increased by 1.3‐ and 1.5‐fold with L and OXL treatment, respectively, in high glucose induced HepG2 cells. The activation of PGC‐1α is significant (P < 0.05) in OXL group than L. Similarly, TFAM expression is increased with L and OXL compared with the high glucose group. Further increase in SOD2 and mtDNA, confirms the efficacy of L and OXL in restoring the mitochondrial biogenesis in high glucose induced cells through AMPK, PGC‐1α, and TFAM.
EphA8 acts as an oncogene and contributes to poor prognosis in gastric cancer via regulation of ADAM10
Authors: Wang Yingjing , Zhou Nan , Li Peng , Wu Han , Wang Qingqing , Gao Xiaodong , Wang Xudong , Huang Jianfei 
Published: April 2019

AbstractEphA8 is a member of the erythropoietin‐producing hepatocellular receptor (Eph) family of receptor tyrosine kinases. Ephs and their ephrins ligands play crucial roles in many cellular processed by mediating intracellular signaling resulting from cell–cell interactions. But the underlying mechanisms of EphA8 in gastric cancer (GC) remains unclearly. 298 clinical specimens in tissues microarray, and was found to be significantly higher in GC tissues compared with nontumor tissues (p < 0.001). EphA8 expression was also strongly associated with differentiation level (p = 0.025), tumor‐node‐metastasis stage (p = 0.019), and poor 5 years survival (p < 0.001). A panel of GC cell lines showed reduced proliferation, invasion, and migration capacities after RNA‐mediated knockdown of EphA8, concomitant with downregulation of the proliferation‐related proteins (cyclin A, cyclin D1, and cyclin‐dependent kinase 4) and the metastasis‐related (matrix metalloproteinases MMP2, and MMP9). EphA8 knockdown also decreased expression of the protease ADAM10 (a disintegrin and metalloproteinase domain‐containing protein 10) and ADAM10‐related protein AKT, suggesting an interaction between EphA8 and ADAM10. In conclusion, we found that EphA8, which is highly expressed in GC tissues, stimulates proliferation, invasion, and migration of cancer cells, and is an independent risk factor for poor prognosis of GC. These dates suggest that EphA8 could be new diagnostic and/or therapeutic targets for GC.
Sclerostin inhibits odontogenic differentiation of human pulp‐derived odontoblast‐like cells under mechanical stress
Authors: Liao Chufang , Ou Yanjing , Wu Yun , Zhou Yi , Liang Shanshan , Wang Yining 
Published: April 2019

AbstractSclerotic dentin is a natural self‐protective barrier beneath non‐carious cervical lesions (NCCLs), which are mainly induced by mechanical stress. Sclerostin is a mechanosensory protein and serves as an inhibitor of dentinogenesis. However, its function on mechanotransduction in dentine–pulp complex has not been elucidated yet. In this study, decreased sclerostin expression was detected in odontoblasts beneath NCCL‐affected sclerotic dentin. Then human pulp‐derived odontoblast‐like cells (hOBs) were subjected to mechanical strain (MS) in vitro: the results showed that MS‐induced upregulation of odontogenic differentiation markers (dentin sialophosphoprotein, osteopontin, osteocalcin, and runt‐related transcription factor 2) in hOBs with downregulated sclerostin expression, and this inductive differentiation was attenuated when sclerostin was overexpressed. Additionally, MS activated ERK1/2 pathway and ERK1/2 inhibition restored MS‐induced downregulation of sclerostin. Proteasome inhibitor MG132 could also rescue MS‐induced decrease of sclerostin. Furthermore, MS suppressed STAT3 pathway, which could be reversed by sclerostin overexpression. STAT3 inhibition was shown to ameliorate the reduction of odontogenic markers induced by sclerostin overexpression. Taken together, we conclude that MS downregulates sclerostin expression via the ERK1/2 and proteasome signaling pathways to promote odontogenic differentiation of hOBs through the STAT3 signaling pathway. It can therefore be inferred that under mechanical stress, sclerostin inhibition promotes reactive dentin formation by enhancing odontogenic differentiation of odontoblasts, which might be one of potential forming mechanisms of sclerotic dentin beneath NCCLs.
GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway
Authors: Li Shuang , Fu Yuying , Pang Yusheng , Tong Huili , Li Shufeng , Yan Yunqin 
Published: April 2019

AbstractThe glucose‐regulated endoplasmic reticulum chaperone protein 94 (GRP94) is required for many biological processes, such as secretion of immune factors and mesoderm induction. Here, we demonstrated that GRP94 promotes muscle differentiation in vitro and in vivo. Moreover, GRP94 inhibited the PI3K/AKT/mTOR signaling pathway. Using both in vitro and in vivo approaches, in myoblasts, we found that this inhibition resulted in reduced proliferation and increased differentiation. To further investigate the mechanism of GRP94‐induced muscle differentiation, we used co‐immunoprecipitation and proximity ligation assays and found that GRP94 interacted with PI3K‐interacting protein 1 (Pik3ip1). The latter protein promoted muscle differentiation by inhibiting the PI3K/AKT/mTOR pathway. Furthermore, GRP94 was found to regulate Pik3ip1 expression. Finally, when Pik3ip1 expression was inhibited, GRP94‐induced promotion of muscle differentiation was diminished. Taken together, our data demonstrated that GRP94 promoted muscle differentiation, mediated by Pik3ip1‐dependent inhibition of the PI3K/AKT/mTOR signaling pathway.
The role of inflammation and its related microRNAs in breast cancer: A narrative review
Authors: Bahiraee Alireza , Ebrahimi Reyhane , Halabian Raheleh , Aghabozorgi Amirsaeed Sabeti , Amani Jafar 
Published: April 2019

AbstractBreast cancer is recognized as the most common type of cancer among women with a high rate of mortality all over the world. Over the past years, growing attention has been regarded to realize more about the mechanisms underlying the disease process. It is revealed that the progression of breast cancer may be strongly linked to chronic inflammation owing to the role of inflammatory factors in genetic instability and subsequent cancer predisposition. Although the association between breast cancer and inflammatory pathways has been well‐defined now, only recent evidence pointed towards the inflammation‐related microRNAs (miRNAs) as potential biomarkers and therapeutic targets involved in the crosstalk of multiple pathways during breast cancer development. Moreover, the practical interactions between these miRNAs and inflammatory factors are also a little characterized. In this review, we intended to describe the effects of predominant inflammatory pathways such as cytokines, phosphoinositide 3‐kinase/protein kinase B, and nuclear factor kappa B in association with tumor promoting and tumor suppressing miRNAs on breast cancer progression. Providing new studies in the field of combining biomarkers for early diagnosis, prognosis, and monitoring breast cancer are very important. Notably, understanding the underlying mechanisms of miRNAs as a possible link between inflammation and tumorigenesis may offer a novel insight for combating this epidemic.
Retracted: Long noncoding RNA CHRF exacerbates IL‐6‐induced inflammatory damages by downregulating microRNA‐146a in ATDC5 cells
Authors: Yu Chuandong , Shi Donglei , Li Zhilin , Wan Guang , Shi Xuefeng 
Published: April 2019

AbstractOsteoarthritis (OA) is a frequent chronic musculoskeletal disorder which lacks applicably effective therapeutic strategy. In this study, we attempted to investigate whether long noncoding RNA (lncRNA) cardiac hypertrophy‐related factor (CHRF) participated in mediating interleukin‐6 (IL‐6)‐induced in vitro inflammatory damages as well as the regulatory mechanisms. ATDC5 cells were stimulated with IL‐6, and then cellular damages were evaluated on the basis of cell viability by CCK‐8, apoptotic cells by observation with flow cytometry, apoptosis‐associated proteins by western blot analysis, and accumulation of inflammatory factors by quantitative reverse transcription polymerase chain reaction (RT‐qPCR), enzyme‐linked immunosorbent assay (ELISA), and western blot analysis. Then, effects of lncRNA CHRF on IL‐6‐treated cells were evaluated. We further explored the downstream factor of lncRNA CHRF and demonstrated whether lncRNA CHRF functioned through the downstream factor. Afterwards, crucial signaling cascades were anatomized. We found that IL‐6 reduced cell viability, elevated apoptosis, induced upregulation of inflammatory factors, as well as upregulated lncRNA CHRF and down‐regulated miR‐146a expression. Then, we found lncRNA CHRF overexpression aggravated IL‐6‐induced alterations, and lncRNA CHRF knockdown showed the opposite effects. Furthermore, miR‐146a was identified to be negatively regulated by lncRNA CHRF, and its overexpression abrogated the roles of lncRNA CHRF in IL‐6‐treated cells. IL‐6‐induced the accumulation of IκBα, p65, JAK1, and STAT3 at phosphorylated level was further facilitated by lncRNA CHRF whereas repressed by miR‐146a. In conclusion, lncRNA CHRF aggravated the IL‐6‐induced inflammatory damages in ATDC5 cells. We further outlined a possible mechanism that through downregulating miR‐146a, lncRNA CHRF evoked the activation of NF‐κB and JAK1/STAT3 signaling cascades.
n‐3 Docosapentaenoic Acid Intake and Relationship with Plasma Long‐Chain n‐3 Fatty Acid Concentrations in the United States: NHANES 2003–2014
Authors: Richter Chesney K. , Bisselou Karl Stessy , Nordgren Tara M. , Smith Lynette , Appiah Adams Kusi , Hein Nicholas , Anderson‐Berry Ann , Kris‐Etherton Penny , Hanson Corrine , Skulas‐Ray Ann C. 
Published: April 2019

AbstractThe long‐chain n‐3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a crucial role in health, but previous National Health and Nutrition Examination Survey (NHANES) analyses have shown that EPA and DHA intake in the United States is far below recommendations (~250–500 mg/day EPA + DHA). Less is known about docosapentaenoic acid (DPA), the metabolic intermediate of EPA and DHA; however, evidence suggests DPA may be an important contributor to long‐chain n‐3 fatty acid intake and impart unique benefits. We used NHANES 2003–2014 data (n = 45,347) to assess DPA intake and plasma concentrations, as well as the relationship between intake and plasma concentrations of EPA, DPA, and DHA. Mean DPA intake was 22.3 ± 0.8 mg/day from 2013 to 2014, and increased significantly over time (p < 0.001), with the lowest values from 2003 to 2004 (16.2 ± 1.2 mg/day). DPA intake was higher in adults (20–55 years) and seniors (55+ years) compared to younger individuals. In regression analyses, DPA intake was a significant predictor of plasma EPA (β = 138.5; p < 0.001) and DHA (β = 318.9; p < 0.001). Plasma DPA was predicted by EPA and DHA intake (β = 13.15; p = 0.001 and β = 7.4; p = 0.002), but not dietary DPA (p = 0.3). This indicates that DPA intake is not a good marker of plasma DPA status (or vice versa), and further research is needed to understand the factors that affect the interconversion of EPA and DPA. These findings have implications for future long‐chain n‐3 fatty acids dietary recommendations.
Advantages of large medical record database for outcomes research: Insights into post‐menopausal hormone therapy
Authors: Tannen Richard L. , Barnhart Kurt T. , Rubin Joshua C. 
Published: April 2019

AbstractApproximately 25 years ago, our team initiated studies to determine whether outcome results from a large medical record database would yield valid results. We utilized the data in the United Kingdom (UK) General Practice Research Database (GPRD) to replicate the randomized controlled trial (RCT) study result and compared them to confirm the database results. The initial studies compared favorably, but some subsequent studies did not. This prompted development of a new strategy to determine and correct for unrecognized confounding in the database. This strategy divided outcome rates prior to initiation of therapy in the database study (which should include both identified and unidentified confounders) into the outcome rates during the treatment interval. When they differed from Cox‐adjusted results, it reflected unrecognized confounding. We called this strategy Prior Event Rate Ratio (PERR)–adjusted outcome.One of our previously published observational studies replicated the Women's Health Initiative (WHI) RCT study of hormone therapy in post‐menopausal women. Our study results replicated the WHI RCT results except it did not exhibit an increase in heart attack in contrast to the RCT. Furthermore, we could not evaluate death reliably since our analytic approach to overcome unrecognized confounding does not work for this outcome. In Volume 1, Issue 1 of the Learning Health Systems open access journal, we published a new study (titled “A new method to address unmeasured confounding of mortality in observational studies”) that reported a novel death method, based on our prior methodology, that could analyze unrecognized confounding of the death outcome. This new methodology, termed Post Treatment Event Rate Ratio (PTERR), permitted a reliable examination of mortality in post‐menopausal women undergoing hormone therapy. These results are reported in this manuscript. The study used the data from our previous observational study. It demonstrates that estrogen therapy markedly reduced death in post‐menopausal women.This work also illuminates principles of database construction and correspondingly demonstrates the use of novel methodologies for obtaining valid results, which can be applied to enable learning from such databases. Work to advance such methodologies is essential to advancing the scientific integrity Core Value underpinning learning health systems (LHSs). Indeed, in the absence of such efforts to develop and refine methodologies for learning trustworthy lessons from real‐world data, we risk inadvertently creating mis‐learning systems.
Distal and non‐distal behavior in pairs
Authors: Nell Travis 
Published: April 2019

AbstractThe aim of this work is an analysis of distal and non‐distal behavior in dense pairs of o‐minimal structures. A characterization of distal types is given through orthogonality to a generic type in , non‐distality is geometrically analyzed through Keisler measures, and a distal expansion for the case of pairs of ordered vector spaces is computed.