bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic functional network connectivity in Huntington's disease and its associations with motor and cognitive measures
Authors: Espinoza Flor A. , Liu Jingyu , Ciarochi Jennifer , Turner Jessica A. , Vergara Victor M. , Caprihan Arvind , Misiura Maria , Johnson Hans J. , Long Jeffrey D. , Bockholt Jeremy H. , Paulsen Jane S. , Calhoun Vince D. 
Published: January 2019

AbstractDynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting‐state fMRI (rs‐fMRI) sample from the PREDICT‐HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] and N = 78 healthy control [HC] participants) to examine whole‐brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs‐fMRI data to obtain whole‐brain resting state networks. FNC was defined as the correlation between RSN time‐courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k‐means clustering algorithm. HDgmc individuals spent significantly more time in State‐1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State‐4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State‐1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex.
The prognostic value of volumetric reduction of the target lesions after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma
Authors: Xiang Zhong‐zheng , Liu Fang , Yan Ruo‐nan , Zeng Yuan‐yuan , He Tao , Zeng Zhen , Zhu Zhi‐hui , Bai Long , Ma Jia‐chun , Liu Lei 
Published: January 2019

AbstractBackgroundWe explored whether the volumetric reduction ratio of target lesion after induction chemotherapy (IC) had any prognostic value in nasopharyngeal carcinoma (NPC).MethodsFrom 2013 to 2016, 72 NPC patients treated with PCF (paclitaxel, cisplatin, 5‐fluorouracil) IC followed by cisplatin‐based concurrent chemoradiotherapy were analyzed. The volumes of target lesions before and after IC and survival conditions were assessed.ResultsFor all cases, volumetric reduction ratios of the total tumor load ≥ optimal cutoff values were significantly associated with increased 2‐year progression‐free survival, locoregional failure‐free survival, and distant metastasis‐free survival (DMFS) rates, and for cervical lymph nodes, the volumetric reduction ratio ≥ optimal cutoff value was significant for DMFS (all P < .05). Accordingly, the optimal cutoff values were 24.56% (AUC = 60.5%), 23.91% (AUC = 57.7%), 29.77% (AUC = 75.8%), and 34.17% (AUC = 62.5%), respectively.ConclusionVolumetric reductions of target lesions after IC are independent survival predictors for NPC, especially for those with N2/N3 disease.
Implementing a Decision Framework in SysML Integrating MDAO Tools
Authors: Dzielski John , Blackburn Mark 
Published: January 2019

ABSTRACTThis article describes an implementation of a decision framework modeled in SysML that we can execute with two different parametric analyzers. One of those analyzers supplies the kind of cross‐tool and cross‐domain integration of simulation and analysis tools that engineers will require to implement model‐based design at large scales. The paper describes the decision framework and illustrates its implementation in SysML in the context of the design of a notional surveillance drone. The paper concludes with some observations about future directions and some of the difficulties that were met.
Acute and subacute oral toxicity of copper oxide nanoparticles in female albino Wistar rats
Authors: Bugata Lakshmi Sai Pratyusha , Pitta Venkata Prabhakar , Gundu Ananth Reddy , Mohammed Fazlur Rahman , Reddy Utkarsh A. , Kumar Jerald Mahesh , Mekala Venugopala Reddy , Bojja Sreedhar , Mahboob Mohammed 
Published: January 2019

AbstractThe extensive use of copper oxide nanoparticles (CuO‐NPs) in various industries and their wide range of applications have led to their accumulation in different ecological niches of the environment. This excess exposure raises the concern about its potential toxic effects on various organisms including humans. However, the hazardous potential of CuO‐NPs in the literature is elusive, and it is essential to study its toxicity in different biological models. Hence, we have conducted single acute dose (2000 mg/kg) and multiple dose subacute (30, 300 and 1000 mg/kg daily for 28 days) oral toxicity studies of CuO‐NPs in female albino Wistar rats following OECD guidelines 420 and 407 respectively. Blood analysis, tissue aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and acetylcholinesterase, superoxide dismutase, catalase, lipid malondialdehyde and reduced glutathione assays, and histopathology of the tissues were carried out. The higher dose treatments of the acute and subacute study caused significant alterations in biochemical and antioxidant parameters of the liver, kidney and brain tissues of the rat. In addition, histopathological evaluation of these three organs of treated rats showed significantly high abnormalities in their histoarchitecture when compared to control rats. We infer from the results that the toxicity observed in the liver, kidney and brain of treated rats could be due to the increased generation of reactive oxygen species by CuO‐NPs.
Hesperidin regresses cardiac hypertrophy by virtue of PPAR‐γ agonistic, anti‐inflammatory, antiapoptotic, and antioxidant properties
Authors: Bhargava Poorva , Verma Vipin Kumar , Malik Salma , Khan Sana Irfan , Bhatia Jagriti , Arya Dharamvir Singh 
Published: January 2019

AbstractHesperidin (HES), a flavanone glycoside, predominant in citrus fruits, has an agonistic activity on peroxisome proliferator‐activated receptor gamma (PPAR‐γ). PPAR‐γ is an inhibitor of cardiac hypertrophy (CH) signaling pathways. In this study, we investigated the cardioprotective effect of HES in isoproterenol (ISO)‐induced CH through PPAR‐γ agonistic activity. For this, male albino Wistar rats were divided into six groups (n = 6), that is, normal, ISO‐control, HES treatment group (200 mg kg−1; p.o.), HESper se(200 mg kg−1; p.o.), enalapril treatment group (30 mg kg−1; p.o.), and combination group (HES 200 mg kg−1; p.o.+enalapril 30 mg kg−1; p.o.). ISO (3 mg kg−1; s.c.) was administered to all groups except normal andper seto induce CH. HES or enalapril treatment of 28 days significantly attenuated pathological changes, improved cardiac hemodynamics, suppressed oxidative stress, and apoptosis along with an increased PPAR‐γ expression. The combination of enalapril with HES exhibited an effect similar to that of HES or enalapril alone on all the aforementioned parameters. Therefore, HES may be further evaluated as a promising molecule for the alleviation of CH.
SNHG15 functions as a tumor suppressor in thyroid cancer
Authors: Liu Yongcun , Li Junli , Li Feng , Li Meng , Shao Yuan , Wu Liping 
Published: January 2019

AbstractSmall nucleolar RNA host gene 15 (SNHG15) has been suggested to be overexpressed, and function as an oncogenic long noncoding RNA (lncRNA) in various types of human malignancies. However, the expression status and function of SNHG15 were still unknown in thyroid cancer. In our study, we assessed the expression status and clinical value in thyroid cancer samples, and explored the effect of SNHG15 on thyroid cancer cell proliferation, migration, and invasion. In results, SNHG15 expression was downregulated in thyroid cancer tissues and cells, and correlated with age, pathology classification, clinical stage, tumor size, distant metastasis, and disease‐free survival. The in vitro studies suggested SNHG15 overexpression suppressed cell proliferation, migration, and invasion in thyroid cancer. In summary, SNHG15 serves as tumor suppressive role in thyroid cancer.
NEAT1 is a potential prognostic biomarker for patients with nasopharyngeal carcinoma
Authors: Liu Zhuoxing , Wu Kunpeng , Wu Jian , Tian Dan , Chen Yue , Yang Zhixiong , Wu Aibing 
Published: January 2019

AbstractNuclear paraspeckle assembly transcript 1 (NEAT1) has been found to be dysregulated and associated with clinical progression in various human cancers. The clinical and prognostic value of NEAT1 in nasopharyngeal carcinoma (NPC) was still controversial. The aim of our study was to provide more sufficient evidence that NEAT1 expression is correlated with overall survival in patients with NPC. NEAT1 expression was detected in NPC tissue samples, and the relationship between NEAT1 expression and clinical parameters, including prognosis, was analyzed. The meta‐analysis was performed to further assess the prognostic significance of NEAT1 expression in patients with NPC. In our study, we found that the levels of NEAT1 expression were increased in NPC clinical tissue specimens, and associated with advanced M classification and clinical stages. Moreover, the Kaplan‐Meier analysis suggested that the levels of NEAT1 expression were negatively associated with the overall survival of patients with NPC. Furthermore, univariate and multivariate Cox regression analyses showed that NEAT1 high‐expression was an independent unfavorable prognostic factor in patients with NPC. Finally, we conducted a meta‐analysis including 297 patients with NPC from the three studies, and found the pooled HR (95% confidence interval [CI]) was 1.64 (95% CI: 0.68‐3.93) for the random effects model and 2.04 (95% CI: 1.42‐2.95) for the fixed effect model. In conclusion, NEAT1 is a potential prognostic biomarker for NPC, but more studies are needed to further verify the prognostic value of NEAT1 in patients with NPC.
Early diagnostic value of circulating microRNAs in patients with suspected acute myocardial infarction
Authors: Li Long , Li Sufang , Wu Manyan , Chi Cheng , Hu Dan , Cui Yuxia , Song Junxian , Lee Chongyou , Chen Hong 
Published: January 2019

AbstractBackground/AimsEvidence has shown that several microRNAs (miRNAs) may be involved in coronary plaque rupture and local thrombus. However, the diagnostic ability of these miRNAs in acute myocardial infarction (AMI) is less known. The aim of this study is to explore the diagnostic value of these circulating miRNAs in patients presenting with acute chest pain in the emergency department.Methods and resultsIn a nested case–control study, 140 of 1,206 patients finally diagnosed with AMI were matched with 70 unstable angina and 70 noncardiac chest pain patients. Five candidate miRNAs (miR‐483‐5p, miR‐155‐5p, miR‐451, miR‐19b, and miR‐223) were selected for validation. Among them, miR‐19b, miR‐223, and miR‐483‐5p were significantly higher in AMI patients compared with those without AMI. A multivariate analysis showed that these miRNAs were independent predictors of AMI. The overall areas under the receiver operating curves (AUCs) for miR‐19b, miR‐223, and miR‐483‐5p were 0.74, 0.65, and 0.70, respectively. However, serial sampling in AMI patients showed that these miRNAs already peaked on admission, which was earlier than troponin I. Among 170 patients with a negative troponin result at presentation, a panel of three miRNAs improved the discrimination ability to a clinical model. In 119 patients presenting within 3 hr after chest‐pain onset, the diagnostic accuracy of each miRNAs was higher than Point of care (POC) troponin assay. And a panel of these miRNAs had an AUC of 0.92.ConclusionCirculating miR‐19b, miR‐223, and miR‐483‐5p may provide clinically useful information for diagnosis in the early phases of AMI.
Human unrestricted somatic stem cells ameliorate sepsis‐related acute lung injury in mice
Authors: Behjani Zeinab Zarei , Ai Jafar , Soleimani Masoud , Atashi Amir , Taheri Behnaz , Ebrahimi‐Barough Somayeh , Siavashi Vahid , Shirian Sadegh , Hamidieh Amir Ali 
Published: January 2019

AbstractBackground AimsSepsis and related disorders, especially acute lung injury (ALI), are the most challenging life‐threatening diseases in the hospital intensive care unit. Complex pathophysiology, unbalanced immune condition, and high rate of mortality complicate the treatment of sepsis. Recently, cell therapy has been introduced as a promising option to recover the sepsis symptoms. The aim of this study was to investigate the therapeutic potential of human unrestricted somatic stem cells (USSCs) isolated from human umbilical cord blood in the mouse model of ALI. USSCs significantly enhanced the survival rate of mice suffering from ALI and suppressed concentrations of proinflammatory mediators TNF‐α, and interleukin (IL)‐6, and the level of anti‐inflammatory cytokine IL‐10. ALI mice injected by USSCs showed notable reduction in lung and liver injury, pulmonary edema, and hepatic enzymes, compared with the control group. These results determined the in vivo immunomodulatory effect of USSCs for recovery of immune balance and reduction of tissue injury in the mouse model of ALI. Therefore, USSCs can be a suitable therapeutic approach to manage sepsis disease through the anti‐inflammatory potential.
The Bcl‐2 inhibitor venetoclax inhibits Nrf2 antioxidant pathway activation induced by hypomethylating agents in AML
Authors: Nguyen Le Xuan Truong , Troadec Estelle , Kalvala Arjun , Kumar Bijender , Hoang Dinh Hoa , Viola Domenico , Zhang Bin , Nguyen Dang Quan , Aldoss Ibrahim , Ghoda Lucy , Budde Elizabeth , Pichiorri Flavia , Rosen Steven , Forman Stephen J. , Marcucci Guido , Pullarkat Vinod 
Published: January 2019

AbstractInduction of reactive oxygen species (ROS), an important process for the cytotoxicity of various acute myeloid leukemia (AML) therapies including hypomethylating agents (HMAs), concurrently activates the NF‐E2‐related factor 2 (Nrf2) antioxidant response pathway which in turn results in induction of antioxidant enzymes that neutralize ROS. In this study, we demonstrated that Nrf2 inhibition is an additional mechanism responsible for the marked antileukemic activity in AML seen with the combination of HMAs and venetoclax (ABT‐199). HMA and venetoclax combined treatment augmented mitochondrial ROS induction and apoptosis compared with treatment HMA alone. Treatment of AML cell lines as well as primary AML cells with venetoclax disrupted HMA decitabine‐increased nuclear translocation of Nrf2 and induction of downstream antioxidant enzymes including heme oxygenase‐1 and NADP‐quinone oxidoreductase‐1. Venetoclax treatment also leads to dissociation of B‐cell lymphoma 2 from the Nrf2/Keap‐1 complex and targets Nrf2 to ubiquitination and proteasomal degradation. Thus, our results here demonstrated an undiscovered mechanism underlying synergistic effect of decitabine and venetoclax in AML cells, elucidating for impressive results in antileukemic activity against AML in preclinical and early clinical studies by combined treatment of these drugs.
Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging
Authors: Pan Fenghui , He Xuan , Feng Jie , Cui Wenxia , Gao Lei , Li Man , Yang Haiyan , Wang Chun , Hu Yun 
Published: January 2019

AbstractType 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age‐related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC‐MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and
p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas‐derived peptides and that certain peptides may be involved in the etiology of diabetes.
Impact of curcumin on toll‐like receptors
Authors: Boozari Motahare , Butler Alexandra E. , Sahebkar Amirhossein 
Published: January 2019

AbstractToll‐like receptors (TLRs) have a pivotal role in the activation of innate immune response and inflammation. TLRs can be divided into two subgroups including extracellular TLRs that recognize microbial membrane components (TLR1, 2, 4, 5, 6, and 10), and intracellular TLRs that recognize microbial nucleic acids (TLR3, 7, 8, and 9). Curcumin is a dietary polyphenol from Curcuma longa L. that is reputed to have diverse biological and pharmacological effects. Extensive research has defined the molecular mechanisms through which curcumin mediates its therapeutic effects. One newly defined and important target of curcumin is the TLR, where it exerts an inhibitory effect. In the current study, we focus upon the TLR antagonistic effect of curcumin and curcumin's therapeutic effect as mediated via TLR inhibition. The available evidence indicates that curcumin inhibits the extracellular TLR 2 and 4 and intracellular TLR9 and thereby exerts a therapeutic effect in diseases such as cancer, inflammation, infection, autoimmune, and ischemic disease. Curcumin effectively modulates the TLR response and thereby exerts its potent therapeutic effects.
Protein modeling, molecular network and molecular dynamics study of newly sequenced interleukin‐18 (IL‐18) gene in Mus musculus
Authors: Yadav Brijesh S. , Chaturvedi Navaneet , Yadav Pavan K. , Marina Ninoslav , Ganash Magdah , Barreto George E. , Ashraf Ghulam Md , Ahmad Khurshid , Baig Mohammad H. 
Published: January 2019

AbstractInterleukin‐18 (IL‐18) belongs to the superfamily of IL‐1 protein and exerts a pleiotropic pro‐inflammatory effect on the body. Generally, this protein is significantly involved in immune defense during infection in cells, but sometimes its anomalous activities produce some inflammatory diseases like rheumatoid arthritis and Crohn’s disease. In the present study, the IL‐18 gene was isolated from mice and was subsequently cloned and sequenced. Further, the network analysis was carried out to explore the functional role of IL‐18 protein in animals. The 3D protein structure of the IL‐18 protein was generated and docked with appropriate 3‐([3‐cholamidopropyl]dimethylammonio)‐1‐propanesulfonate (CPS) ligand. Later the complex structure of the protein was subjected to molecular dynamics simulation (MDS) for 50 ns to determine the effect of ligand on protein. The network analysis explored the correlation of IL‐18 protein with others proteins and their involvement in the different significant pathway to defend the cell from various diseases. As confirmed by MDS, the CPS:IL‐18 complex was found to be highly stable. Our results further indicated that CPS ligand has the potential to act as a drug molecule, in future, for counteracting IL‐18 activity. To date, no structural details were available for animal IL‐18. Hence, the finding of this study will be useful in broadening the horizon towards a better understanding of the functional and structural aspects of IL‐18 in animals.
Initiation of Pediatric Clinical Trials for Coagulation Factors: Application of Pharmacokinetics and Allometry to First‐in‐Pediatric Dose Selection
Authors: Mahmood Iftekhar 
Published: January 2019

AbstractAllometric scaling is a method that can be used for the extrapolation of pharmacokinetic parameters from adults to children. Subsequently, these allometrically predicted PK parameters can be used to project a suitable dose to initiate a pediatric clinical trial. The objective of this study was to predict clearance and in vivo recovery of coagulation factors VIII and IX allometrically in children from 1 year of age to adolescents and then project the first‐in‐children dose. The values for observed clearance, in vivo recovery, and dose for pediatric as well as adult subjects for 7 factor VIII and 3 factor IX products were obtained from the US Food and Drug Administration package insert and the allometrically predicted clearance, in vivo recovery, and dose were compared with the observed values. The clearance of factors VIII and IX were predicted with reasonable accuracy. Of 27 predicted clearance values, all 27 (100%) were predicted with ≤30% prediction error (range, 5%–28%). Of 27 predicted in vivo recovery values, 26 (96%) were predicted with ≤30% prediction error (range, 0%–45%). The projected doses of factor VIII or IX, either by clearance or in vivo recovery, were generally within the recommended dose range indicating an accurate prediction of pediatric dose for both factors. The proposed allometric methods can be used to select first‐in‐children dose in pediatric clinical trials.
Late acute pancreatitis after pancreaticoduodenectomy: incidence, outcome, and risk factors
Authors: Yen Hung‐Hsuan , Ho Te‐Wei , Wu Chien‐Hui , Kuo Ting‐Chun , Wu Jin‐Ming , Yang Ching‐Yao , Tien Yu‐Wen 
Published: January 2019

AbstractBackgroundThe pancreatoenteric anastomotic stricture (PEAS) is a common long‐term complication after pancreaticoduodenectomy (PD), some of which present as acute pancreatitis requiring emergency care. This important topic has never been reported. In this study, we focus on the incidence, radiological features, clinical outcome, and risk factors of late‐occurring acute pancreatitis (LAP) after PD.MethodsWe retrospectively reviewed a prospectively collected database of 539 patients who underwent PD at a single tertiary referral center between June 2005 and December 2014. Only patients with at least 3 years of follow‐up and available pre‐ and post‐operative images were included.ResultsOf the 539 patients, 23 (15 [65%] with and eight [35%] without PEAS) were diagnosed with LAP after PD. The cumulative incidence of LAP was 3.6% (1‐year), 4.4% (2‐year), and 5.1% (5‐year). The median time to the first LAP episode was 22 months (range 8–38 months) after PD. All the first and recurrent LAP events were mild in severity and resolved after conservative treatment. Multivariate analysis showed that a history of acute pancreatitis before PD (P = 0.001, HR 5.24, 95% CI 1.95–14.10) and PEAS (P = 0.047, HR 2.75, 95% CI 1.01–7.49) were two significant risk factors.ConclusionsWe propose using a more conservative treatment for patients who experience LAP after PD.