bluuebunny/crossref_metadata_2025 huggingface dataset:
5q21 deletion is often heterogeneous in prostate cancer
Authors: Kluth Martina , Al Kilani Zaid , Özden Cansu , Hussein Khakan , Frogh Sohall , Möller‐Koop Christina , Burandt Eike , Steurer Stefan , Büscheck Franziska , Jacobsen Frank , Luebke Andreas M. , Minner Sarah , Tsourlakis Maria Christina , Hoeflmayer Doris , Wittmer Corinna , Schlomm Thorsten , Sauter Guido , Simon Ronald , Wilczak Waldemar
Published: January 2019

Cancer heterogeneity represents a challenge for the analysis of prognostic molecular markers but can be used to study the evolution of molecular events in tumors. To assess the degree of heterogeneity of 5q21 deletions and their relationship with TMPRSS2:ERG status and 6q15 deletions in prostate cancer, a heterogeneity tissue microarray including 10 tissue spots from 10 different areas of 317 cancers was analyzed by fluorescence in situ hybridization for 5q21 deletion. Data on 6q and ERG were available from earlier studies. Deletions of 5q21 were found in 23% of 265 interpretable cancers and showed marked intratumoral heterogeneity. In the subset of 246 cancers with at least 3 interpretable spots, 23% had a 5q21 deletion. Heterogeneous 5q21 deletions were found in 71% and homogeneous in 29% of these cancers. The likelihood of 5q21 deletion was twice as high in ERG‐negative (28%) than in ERG‐positive cancers (16%, P = .024). In all 21 cases harboring both alterations, the tumor area containing a 5q21 deletion was smaller or equally large than the ERG‐positive area but never larger. Deletions of 5q and 6q were significantly linked. However, the analysis of 32 tumors harboring both deletions did not suggest a specific order of appearance of these deletions. The 5q21 deletion preceded 6q15 in 10 tumors and 6q15 preceded 5q21 in 14 tumors. In summary, our study identifies 5q21 deletion as a highly heterogeneous aberration in prostate cancer that usually occurs late during cancer progression. This is a severe limitation for using 5q21 testing as a prognostic tool.
How does de‐globalization affect location decisions? A study of managerial perceptions of risk and return
Authors: Ambos Tina C. , Cesinger Beate , Eggers Felix , Kraus Sascha
Published: January 2019

Research Summary

Our understanding of how managers take international location decisions is still scarce. Building on the microfoundations view, we explore managers' perceptions of risk and return in a discrete choice experiment with 2,618 decisions in 2013 (a globalizing world) and 2017 (a de‐globalizing world). While managerial perceptions vary over time due to economic and political changes, such as the current de‐globalization trend, decision heuristics remain remarkably stable: locations perceived as least risky offer the highest expected returns. We also find that distance is a good proxy for managerial perceptions. Investigating the microfoundations of decision‐making we show that international experience, risk‐taking propensity, and shareholder status affect heuristics. In sum, our study provides novel insights into the microfoundations of location decisions and extends the behavioral perspective on internationalization.

Managerial Summary

While many researchers in the field of international business and global strategy have studied internationalization, surprisingly few of them put the actual decision maker in the spotlight. This study investigates the decision heuristics of managers who are confronted with international location decisions. We show that their perceptions of risk and return in the context of a globalizing world (in 2013) and in the context of a de‐globalizing world (in 2017) vary. However, the underlying heuristic—locations that are perceived as least risky offer the highest expected returns—remains stable. Our study also indicates that distance is a good proxy for managerial decisions and that managers' international experience, risk‐taking propensity, and shareholder status affect their decision‐making patterns.
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

Dynamic 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

Background

We explored whether the volumetric reduction ratio of target lesion after induction chemotherapy (IC) had any prognostic value in nasopharyngeal carcinoma (NPC).

Methods

From 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.

Results

For 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.

Conclusion

Volumetric 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

This 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

The 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

Hesperidin (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.
Systematic Evaluation of Psychometric Characteristics of the Michigan Alcoholism Screening Test 13‐Item Short (SMAST) and 10‐Item Brief (BMAST) Versions
Authors: Minnich Amelia , Erford Bradley T. , Bardhoshi Gerta , Atalay Zümra , Chang Catharine Y. , Muller Lauren A.
Published: January 2019

The psychometric properties of the Michigan Alcohol Screening Test (MAST) 13‐item short (SMAST) and 10‐item brief (BMAST) versions were aggregated and synthesized across 40 and 21 studies, respectively. Results for reliability, validity, and nonclinical descriptive statistics were reported separately for the SMAST and BMAST, and implications for counseling practice and research were discussed.
A Systematic Review of Online Response Rates in Four Counseling Journals
Authors: Poynton Timothy A. , DeFouw Emily R. , Morizio Laura J.
Published: January 2019

This systematic review of articles published in 4 counseling journals found 207 articles that used online recruitment, of which 98 (47.3%) reported a response rate. These 98 studies collectively contained 22,466 individual participants. Results showed that nearly one third of all empirical articles used online recruitment, and the average response rate was 34.2% (SD= 22.6). Response rates are further described by journal, population, research methodology, and recruitment strategy. Researcher‐reported issues with online recruitment and data collection were also analyzed qualitatively, and recommendations for researchers are discussed.
Defining Wellness in Older Adulthood: Toward a Comprehensive Framework
Authors: Fullen Matthew C.
Published: January 2019

Despite the counseling profession’s widespread interest in wellness, little research has been conducted on wellness in older adulthood. The author reviews the literature to identify current trends in research on wellness among older adults. Out of 273 articles, only 40 (14.63%) used a multidimensional, holistic framework. Further analysis revealed a lack of multidimensional models that were normed on older adults or tailored to their needs. The author concludes with an 8‐dimensional wellness framework to guide future research.
Trends in Ethical Complaints Leading to Professional Counseling Licensing Boards Disciplinary Actions
Authors: Wilkinson Tyler , Smith Dannielle , Wimberly Ramona
Published: January 2019

This article presents findings of a content analysis of the types of ethical violations that led to disciplinary actions (N= 936) across state counseling licensing boards for professional counselors during the time frame of 2010 to 2014. The most frequent types of ethical violations included failure to acquire the appropriate amount of continuing education, dual relationships (sexual and nonsexual), and misrepresentation of credentials. Implications of the findings and future research needs are discussed.
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

Small 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

Nuclear 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.
An efficient one‐pot synthesis of 2‐aminopyrimidinomethylnaphtols under solvent‐free conditions
Authors: Safarzaei Mohyeddin , Maghsoodlou Malek Taher , Mollashahi Ebrahim , Hazeri Nourallah , Lashkari Mojtaba
Published: January 2019

A novel one‐pot three‐component condensation reaction of an aldehyde, 2‐aminopyrimidine and 2‐naphthol to afford the corresponding 2‐aminopyrimidinomethylnaphtols in good yields. The remarkable features of this new procedure are high conversions, short reaction time, clean reaction profiles, and environmentally benign and simple work‐up procedures.
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

Background/Aims

Evidence 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 results

In 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.

Conclusion

Circulating 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

Background Aims

Sepsis 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

Induction 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

Type 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

Toll‐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

Interleukin‐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

Allometric 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.
Fatigue in celiac disease: A review of the literature
Authors: Skjellerudsveen Berit M , Omdal Roald , Grimstad Tore
Published: January 2019

Fatigue is increasingly recognized as a significant problem in patients with chronic inflammatory and autoimmune diseases. In celiac disease, a chronic immune‐mediated disease triggered by dietary gluten, conflicting opinions exist regarding both the size of the problem and the effect of a gluten‐free diet (GFD) on fatigue. We reviewed the existing literature regarding fatigue in celiac disease. We conducted a systematic search in the Embase, Ovid Medline, and Cochrane databases using subject terms from controlled vocabularies. Articles were reviewed based on language, type of article, title, and abstract or full text. Eighteen articles were finally selected for review. Fatigue was significantly greater in patients with celiac disease compared to healthy control subjects. Fatigue prevalence ranged from 8 to 100%. Fatigue severity was assessed in six studies. The fatigue visual analogue scale was the most frequently used fatigue instrument with scores from 57 to 79 prior to starting a GFD and from 39 to 59 in patients on a GFD. Seven studies investigated the effect of a GFD on fatigue, including five studies that reported less fatigue while on the diet and two studies that showed no significant difference. This review concludes that fatigue is a substantial complaint in patients with celiac disease. A GFD seems to reduce fatigue, but existing data are limited.
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

Background

The 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.

Methods

We 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.

Results

Of 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.

Conclusions

We propose using a more conservative treatment for patients who experience LAP after PD.
Domain‐specific data augmentation for segmenting MR images of fatty infiltrated human thighs with neural networks
Authors: Gadermayr Michael , Li Kexin , Müller Madlaine , Truhn Daniel , Krämer Nils , Merhof Dorit , Gess Burkhard
Published: January 2019

Background

Fat‐fraction has been established as a relevant marker for the assessment and diagnosis of neuromuscular diseases. For computing this metric, segmentation of muscle tissue in MR images is a first crucial step.

Purpose

To tackle the high degree of variability in combination with the high annotation effort for training supervised segmentation models (such as fully convolutional neural networks).

Study Type

Prospective.

Subjects

In all, 41 patients consisting of 20 patients showing fatty infiltration and 21 healthy subjects.

Field Strength/Sequence: The T1‐weighted MR‐pulse sequences were acquired on a 1.5T scanner.

Assessment

To increase performance with limited training data, we propose a domain‐specific technique for simulating fatty infiltrations (i.e., texture augmentation) in nonaffected subjects' MR images in combination with shape augmentation. For simulating the fatty infiltrations, we make use of an architecture comprising several competing networks (generative adversarial networks) that facilitate a realistic artificial conversion between healthy and infiltrated MR images. Finally, we assess the segmentation accuracy (Dice similarity coefficient).

Statistical Tests

A Wilcoxon signed rank test was performed to assess whether differences in segmentation accuracy are significant.

Results

The mean Dice similarity coefficients significantly increase from 0.84–0.88 (P < 0.01) using data augmentation if training is performed with mixed data and from 0.59–0.87 (P < 0.001) if training is conducted with healthy subjects only.

Data Conclusion

Domain‐specific data adaptation is highly suitable for facilitating neural network‐based segmentation of thighs with feasible manual effort for creating training data. The results even suggest an approach completely bypassing manual annotations.

Level of Evidence: 4

Technical Efficacy: Stage 3
Dynamic susceptibility contrast parametric imaging using accelerated dual‐contrast echo planar imaging with keyhole
Authors: Caldeira Liliana L. , Yun Seong Dae , da Silva Nuno A. , Filss Christian , Shah N. Jon
Published: January 2019

Background

Echo planar imaging (EPI) is one of the methods of choice in dynamic susceptibility contrast MRI (DSC‐MRI) because it provides a sufficient temporal resolution. However, the relatively long readout duration of EPI often imposes limitations on increased spatial coverage or the use of multiple contrasts.

Purpose

To develop a DSC‐MRI method using EPIK (EPI with keyhole) to provide dual‐contrast (TE1 and TE2) information with a higher spatial coverage than EPI. To compare results from the community‐standard EPI method and the proposed EPIK method.

Study Type

Prospective.

Subjects

One healthy subject and 17 brain tumor patients.

Field Strength/Sequence

3 T/accelerated EPI and dual‐contrast EPIK sequences.

Assessment

After an initial evaluation using healthy in vivo images, the use of the proposed method for DSC‐MRI was verified with brain tumor patients. The parametric images (eg, CBF and CBV) and arterial input function (AIF), obtained from both the EPI and EPIK, were compared.

Statistical Tests

The ratio of AIF peak height of the proposed method to that of EPI was computed. The ratio computation was also performed for the time‐to‐peak (TTP) in the AIF curves. From the obtained CBF and CBV maps, the tumor‐to‐brain (TBR) ratio was also calculated for each imaging method and the results were compared.

Results

For the same temporal resolution (1.5 sec), EPIK yielded dual‐contrast (TEs of 13/33 msec) with an increased spatial coverage (24 slices) and less geometric distortions than EPI; EPI provided single contrast (TE of 32 msec) with 20 slices. The obtained parametric values (eg, AIF peak, TTP, and TBR) had similar characteristics between EPI and the proposed method.

Data Conclusion

The dual‐contrast data produced by EPIK in DSC‐MRI allowed T1‐corrected parametric images without the need of second contrast injection and an enhanced estimation of the AIF.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;50:628–640.
Assessment of actual evapotranspiration variability over global land derived from seven reanalysis datasets
Authors: Feng Taichen , Su Tao , Zhi Rong , Tu Gang , Ji Fei
Published: January 2019

With the motivation to identify whether global warming would lead to an increase in the rate of actual evapotranspiration (AE) over land, an assessment is made of AE variability from an ensemble of seven reanalyses (NCEP‐NCAR, NCEP‐DOE, MERRA, MERRA V2, ERA‐Interim, JRA‐55, and CFSR). By subdividing global land into nine climatic regions using the aridity index (AI), we examine the variability and long‐term trend of regional AE and various related factors. Results indicate that AE shows a significant increasing trend during 1979–2015 in the humid, wet, and arctic regions. Overall, three main parameters, namely, precipitation, surface net solar radiation, and wet‐day frequency, strongly influence the temporal variations of AE over most regions. The possible causes of trends in AE are examined in view of the linear trends of the related meteorological variables. Accordingly, increasing potential evapotranspiration and increasing vapour pressure are the main contributors to increasing AE in humid regions. Increasing temperature is the main contributor to increasing AE in wet regions. Both increasing energy supply and water supply on AE largely explain the significant increasing trend of AE in arctic regions. In view of data availability, a correlation analysis was conducted between AE in individual reanalyses and the results from the Mezentsev–Choudhury–Yang equation and the ensemble of the seven reanalyses. On average, NCEP‐NCAR is the worst among the seven reanalysis datasets in revealing temporal characteristics of AE.
Dysregulation of miR‐146a by periodontal pathogens: A risk for acute coronary syndrome
Authors: Bagavad Gita J. , George Ann V. , Pavithra N. , Chandrasekaran S. C. , Latchumanadhas K. , Gnanamani A.
Published: January 2019

Background

Periodontitis is a polymicrobial, chronic inflammatory disease leading to loss of tooth‐supporting structures. The bacteremia, endotoxemia, and systemic low‐grade inflammation associate periodontitis with systemic illnesses such as diabetes mellitus and coronary artery disease. Periodontal pathogens have been detected from atheromatous plaque by amplification of the genetic material by using specific oligonucleotide primers in polymerase chain reaction. Though the association between periodontitis and cardiovascular diseases has been ascertained by systematic reviews and meta‐analyses, its pathophysiology is not lucid. MicroRNAs are currently implicated in the regulation of many cellular processes including inflammation and may play a vital role in our understanding of this disease association. In this case‐control study, we explored the role of the inflammatory microRNA, miR‐146a, in acute coronary syndrome (ACS) subjects with and without chronic periodontitis (CP) and its regulation of the innate immune host response to periodontal pathogens.

Methods

Three groups each comprising 66 patients each, namely group 1 (ACS patients without CP), group 2 (ACS patients with CP) and group 3 (CP only) formed the study population. Subgingival plaque samples and serum samples were subjected to quantitative Polymerase Chain Reaction (qPCR) for detection of Porphyromonas gingivalis, a keystone pathogen and to assess the levels of circulating miR‐146a and associated proinflammatory cytokines.

Results

miR‐146a associated significantly in group 2 subjects with an odds ratio 1.434, 95% confidence interval 1.013‒2.030, P < 0.042, and a predictive percentage of 83.3% and group 1 with a predictive percentage of 76.0.% The associated cytokines interleukin‐6 (IL‐6), tumor necrosis factor‐α, and IL‐1β also showed an upregulation with statistical significance (P < 0.05).

Conclusion

microRNA‐146a is a key molecule associating periodontitis with acute coronary syndrome.
Cellular antioxidant activity and in vitro intestinal permeability of phenolic compounds from four varieties of mango bark (Mangifera indica L.)
Authors: Vazquez‐Olivo Gabriela , Antunes‐Ricardo Marilena , Gutiérrez‐Uribe Janet A , Osuna‐Enciso Tomás , León‐Félix Josefina , Heredia José Basilio
Published: January 2019

BACKGROUND

Mango bark is an important agro‐industrial residue from mango pruning. In traditional medicine, the aqueous extract from mango bark (MBE) has been used in ethnomedicine for the treatment of many diseases. However, there is scarce information using cellular models to evaluate the potential use of this plant material for human consumption. In this study, the phenolic content from the MBE from four varieties (Kent, Keitt, Ataulfo and Tommy Atkins) was analyzed by high‐performance liquid chromatography coupled to photodiode array detector (HPLC‐DAD) and liquid chromatography coupled with time‐of‐flight mass spectrometry (LC/MS‐TOF). Additionally, the cellular antioxidant activity of the MBE from the four mango varieties were compared. Finally, the intestinal permeability of the main polyphenols found in the MBE (mangiferin and gallic acid) was evaluated.

RESULTS

Mangiferin and gallic acid were the main constituents in the MBE from the four mango varieties. Furthermore, the Ataulfo variety showed the highest cellular antioxidant activity (67%) at the concentration of 100 µg mL−1. The intestinal permeability of mangiferin present in the bark extracts was 3‐ to 4.8‐fold higher than those of mangiferin as standard, whereas the intestinal permeability of gallic acid varied among the tested extracts.

CONCLUSION

MBE has the potential to exert antioxidant activity at the cellular level and can have an impact on human health. It may also be a good source for the extraction of polyphenols mainly mangiferin. © 2019 Society of Chemical Industry
Climate change and nutria range expansion in the Eastern United States
Authors: Hilts Dylan J. , Belitz Michael W. , Gehring Thomas M. , Pangle Kevin L. , Uzarski Donald G.
Published: January 2019

Nutria (Myocastor coypus) are an introduced invasive species expanding their range in North America and may have detrimental effects on wetlands. Little is known about habitat covariates that may limit or enhance range expansion of nutria, especially when combined with predicted changes in climate. We used a hierarchical modeling approach to develop broad‐ and local‐scale maximum entropy (MaxEnt) models based on nutria harvest records in the eastern United States from 2006–2015. We developed models for current conditions and for climate change projections in 2050. At a broad scale, nutria habitat was located in areas with ≤80 annual freezing days. At local scales, nutria were found in areas with high proportions of freshwater forested‐shrub wetlands close to other wetlands. Managers who are concerned about possible nutria range expansion can use this hierarchical modeling framework to identify areas for surveillance and prioritize control efforts. © 2019 The Wildlife Society.
Sediment yield at southwest Ethiopia's forest frontier
Authors: Kassa Henok , Frankl Amaury , Dondeyne Stefaan , Poesen Jean , Nyssen Jan
Published: January 2019

Deforestation is one of the major factors affecting soil erosion in tropical regions but to what extent does the crop growth in deforested areas protect the land from erosion? We evaluated the effect of deforestation on suspended sediment yield at the scale of zero‐order catchments by contrasting five paired small forest and cropland catchments at Ethiopia's southwestern forest frontier. Suspended sediment samples were collected from nine San Dimas flumes and one V‐notch weir installed in catchments draining the natural forest and cropland, at different altitudes. The suspended sediment data were collected from June 8 to October 30, 2013 and 2014. The suspended sediment yield of both land‐use types was strongly correlated with the corresponding runoff discharge. The results show that the average seasonal suspended sediment yield from cropland (17.0 ± 7.6 Mg ha−1) is four times higher than from the paired forests (4.0 ± 1.9 Mg ha−1). High sediment yields from forests are related to livestock grazing, but forests still have an important role in the protection of the surface soil from erosion at southwest Ethiopia's forest frontier. Land management in southwestern Ethiopia's highlands will need a strong change in paradigm, in which the overall belief in the recently imported mahrasha ard plough is abandoned, oxen and other cattle decreased in number and kept in homesteads, the forests being protected from human and livestock interferences and the open farmlands turned into agroforestry. Such an approach is still possible as all required elements are available in the landscape.
Secchi Day: Bridging the Gap between Source and Tap
Authors: Rich Matthew W.
Published: January 2019

Individual knowledge of the source of one's drinking water is imperative in preserving that source for future generations. Ensuring that drinking water sources remain viable is a goal that researchers, water treatment managers, and water quality conservationists can work toward for the entirety of a career. However, without public buy‐in, the monumental task of source water protection, in the face of cultural eutrophication, would not be possible. In an effort to educate the citizenry of Northwest Arkansas about the source of their safe, clean drinking water, Beaver Water District has initiated Secchi Day on Beaver Lake, a citizen science engagement program, now in its 13th year, that aims to bridge the gap between source and tap. One of the most difficult aspects of a citizen science project as large as this one is the recruitment and retention of interested volunteers that help build this valuable long‐term data set. We hope that you will learn from our mistakes and successes and find helpful information that you can use to bolster support for your own project.
Analyzing Thermal Conductivity of Polyethylene‐Based Compounds Filled with Copper
Authors: Weingrill Helena , Hohenauer Wolfgang , Resch‐Fauster Katharina , Zauner Christoph
Published: January 2019

The thermal conductivity (TC) of different polymeric materials is measured via four commercially available testing devices: TPS2500S by Hot Disk (Hot Disk), Transient Hot Bridge (THB) by Linseis, the Laser Flash Analysis (LFA) by NETZSCH, and the DTC‐300 by TA Instruments. The investigated materials include high‐density polyethylene (HDPE) and linear low‐density polyethylene (LLDPE) which are analyzed as received and after being compounded with copper particles. The filler geometry and ratio are varied systematically. Major differences in the TC generated by the different measurement methods are revealed and analyzed in detail. Moreover, material‐induced impacts on the TC as well as technology‐induced impacts on the TC are outlined comprehensively.
Amenable Köthe co‐echelon algebras
Authors: Piszczek Krzysztof
Published: January 2019

In this note we investigate amenability properties in the class of the so‐called DF‐algebras. We also characterize, in terms of the defining sequence of weights, amenable Köthe co‐echelon algebras.