bluuebunny/crossref_metadata_2025 huggingface dataset:
The Klotho Variant rs36217263 Is Associated With Poor Response to Cardioselective Beta‐Blocker Therapy Among Filipinos
Authors: Sy Rody G. , Nevado Jose B. , Llanes Elmer Jasper B. , Magno Jose Donato A. , Ona Deborah Ignacia D. , Punzalan Felix Eduardo R. , Reganit Paul Ferdinand M. , Santos Lourdes Ella G. , Tiongco Richard Henry P. , Aherrera Jaime Alfonso M. , Abrahan Lauro L. , Agustin Charlene F. , Aman Aimee Yvonne Criselle L. , Bejarin Adrian John P. , Cutiongco – de la Paz Eva Maria C.
Published: July 2019

A common drug used for hypertension among Filipinos is beta‐blockers. Variable responses to beta‐blockers are observed, and genetic predisposition is suggested. This study investigated the association of genetic variants with poor response to beta‐blockers among Filipinos. A total of 76 Filipino adult hypertensive participants on beta‐blockers were enrolled in an unmatched case‐control study. Genotyping was done using DNA from blood samples. Candidate variants were correlated with clinical data using χ2 and logistic regression analysis. The deletion of at least one copy of allele A of rs36217263 near Klotho showed statistically significant association with poor response to beta‐blockers (dominant; odds ratio (OR) = 3.89; P = 0.017), adjusted for diabetes and dyslipidemia. This association is observed among participants using cardioselective beta‐blockers (crude OR = 5.60; P = 0.008) but not carvedilol (crude OR = 2.56; P = 0.67). The genetic variant rs36217263 is associated with poor response to cardioselective beta‐blockers, which may become a potential marker to aid in the management of hypertension.
Sorafenib Activity and Disposition in Liver Cancer Does Not Depend on Organic Cation Transporter 1
Authors: Chen Mingqing , Neul Claudia , Schaeffeler Elke , Frisch Franziska , Winter Stefan , Schwab Matthias , Koepsell Hermann , Hu Shuiying , Laufer Stefan , Baker Sharyn D. , Sparreboom Alex , Nies Anne T.
Published: July 2019

Systemic therapy of advanced hepatocellular carcinoma (HCC) with the small‐molecule multikinase inhibitor sorafenib is associated with large interindividual pharmacokinetic variability and unpredictable side effects potentially requiring dose reduction or treatment termination. Organic cation transporter (OCT1; gene SLC22A1) has been proposed as a clinical biomarker of HCC response. Because proof is lacking that OCT1 transports sorafenib, we used a combinatorial approach to define how OCT1 contributes to sorafenib transport. Overexpression of functional OCT1 protein in Xenopus laevis oocytes and mammalian cell lines did not facilitate sorafenib transport. Otherwise, sorafenib considerably accumulated in liver cancer cell lines despite negligible OCT1 mRNA and protein levels. Sorafenib pharmacokinetics was independent of OCT1 genotype in mice. Finally, SLC22A1 mRNA expression was significantly reduced by DNA methylation in The Cancer Genome Atlas HCC cohort. These results clearly demonstrate OCT1‐independent cellular sorafenib uptake indicating that OCT1 is apparently not a valid biomarker of sorafenib response in HCC.
C‐peptide is associated with NAFLD inflammatory and fibrotic progression in type 2 diabetes
Authors: Wang Ningjian , Wang Yuying , Zhang Wen , Chen Yi , Chen Xiaoman , Wang Chiyu , Li Qing , Chen Chi , Jiang Boren , Lu Yingli
Published: July 2019

Background

A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C‐peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults.

Methods

A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis.

Results

Individuals with a longer history of type 2 diabetes had a lower C‐peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C‐peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C‐peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1‐SD increment of ln(C‐peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively).

Conclusions

Significant but opposite associations between C‐peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.
Biophysical potential of crop residues for biochar carbon sequestration, and co‐benefits, in Uganda
Authors: Roobroeck Dries , Hood‐Nowotny Rebecca , Nakubulwa Dianah , Tumuhairwe John‐Baptist , Mwanjalolo Majaliwa Jackson Gilbert , Ndawula Isaac , Vanlauwe Bernard
Published: July 2019

Increasing organic matter/carbon contents of soils is one option proposed to offset climate change inducing greenhouse gas (GHG) emissions, under the auspices of the UNFCC Paris Agreement. One of the complementary practices to sequester carbon in soils on decadal time scales is amending it with biochar, a carbon rich byproduct of biomass gasification. In sub‐Saharan Africa (SSA), there is a widespread and close interplay of agrarian‐based economies and the use of biomass for fuel, which makes the co‐benefits of biochar production for agriculture and energy supply explicitly different from the rest of the world. To date, the quantities of residues available from staple crops for biochar production, and their potential for carbon sequestration in farming systems of SSA have not been comprehensively investigated. We assessed the productivity and usage of biomass waste from maize, sorghum, rice, millet, and groundnut crops; specifically quantifying straw, shanks, chaff, and shells, based on measurements from multiple farmer fields and household surveys in eastern Uganda. Moreover, allometric models were tested, using grain productivity, plant height, and density as predictors. These models enable rapid and low‐cost assessment of the potential availability of feedstocks at various spatial scales: individual cropland, farm enterprise, region, and country. Ultimately, we modeled the carbon balance in soils of major cropping systems when amended with biochar from biomass residues, and up‐scaled this for basic scenario analysis. This interdisciplinary approach showcases that there is significant biophysical potential for soil carbon sequestration in farming systems of Uganda through amendment of biochar derived from unused residues of cereals and legume crops. Furthermore, information about these biomass waste flows is used for estimating the rates of biochar input that could be made to farmlands, as well as the amounts of energy that could be produced with gasifier appliances.
The Female Athlete Body project study: 18‐month outcomes in eating disorder symptoms and risk factors
Authors: Stewart Tiffany M. , Pollard Tarryn , Hildebrandt Tom , Wesley Nicole Y. , Kilpela Lisa S. , Becker Carolyn B.
Published: July 2019

Objective

To evaluate the efficacy of the Female Athlete Body project (FAB) in reducing eating disorder (ED) symptoms and risk factors.

Method

This study was a community participatory three‐site, two‐arm, cluster randomized controlled trial (RCT). Female collegiate athletes (N = 481) were randomly assigned by team to the FAB intervention, a behavioral ED risk factor reduction program, or a waitlist control condition. Primary analyses examined 18‐month effects for ED pathology. Secondary analyses examined risk factors and correlates (e.g., thin‐ideal internalization, negative mood, Female Athlete Triad knowledge, and body mass index [BMI]).

Results

Linear mixed effects models with team as a cluster level variable and study condition as a between‐subjects variable revealed significantly reduced dietary restraint in FAB teams relative to control teams. FAB teams also reported significantly fewer objective and subjective binge episodes than control teams. Finally, FAB teams showed significantly lower thin‐ideal internalization and increased BMI at 18‐months. No other significant differences were found.

Discussion

This RCT examined the effects of a short intervention on ED pathology and risk factors in female collegiate athletes through 18‐month follow‐up. This trial is one of only three trials with female athletes that have shown long‐term reductions in any ED symptoms or produced positive effects on ED risk factors. The present study is the first to find such effects with athletes using a brief (i.e., 4 hr) intervention at 18‐month follow‐up. Although small effects were found, the current trial provides valuable lessons about future design and implementation of similar trials with athletes.

Trial Registration

Clinical trials NCT01735994.
Acoustic accelerometry reveals diel activity patterns in premigratory Port Jackson sharks
Authors: Kadar Julianna , Ladds Monique , Mourier Johann , Day Joanna , Brown Culum
Published: July 2019

Distinguishing the factors that influence activity within a species advances understanding of their behavior and ecology. Continuous observation in the marine environment is not feasible but biotelemetry devices provide an opportunity for detailed analysis of movements and activity patterns. This study investigated the detail that calibration of accelerometers measuring root mean square (RMS) acceleration with video footage can add to understanding the activity patterns of male and female Port Jackson sharks (Heterodontus portusjacksoni) in a captive environment. Linear regression was used to relate RMS acceleration output to time‐matched behavior captured on video to quantify diel activity patterns. To validate captive data, diel patterns from captive sharks were compared with diel movement data from free‐ranging sharks using passive acoustic tracking. The RMS acceleration data showed captive sharks exhibited nocturnal diel patterns peaking during the late evening before midnight and decreasing before sunrise. Correlation analysis revealed that captive animals displayed similar activity patterns to free‐ranging sharks. The timing of wild shark departures for migration in the late breeding season corresponded with elevated diel activity at night within the captive individuals, suggesting a form of migratory restlessness in captivity. By directly relating RMS acceleration output to activity level, we show that sex, time of day, and sex‐specific seasonal behavior all influenced activity levels. This study contributes to a growing body of evidence that RMS acceleration data are a promising method to determine activity patterns of cryptic marine animals and can provide more detailed information when validated in captivity.
Maternal genomic variability of the wild boar (Sus scrofa) reveals the uniqueness of East‐Caucasian and Central Italian populations
Authors: Khederzadeh Saber , Kusza Szilvia , Huang Cui‐Ping , Markov Nickolay , Scandura Massimo , Babaev Elmar , Šprem Nikica , Seryodkin Ivan V. , Paule Ladislav , Esmailizadeh Ali , Xie Hai‐Bing , Zhang Ya‐Ping
Published: July 2019

The phylogeography of the European wild boar was mainly determined by postglacial recolonization patterns from Mediterranean refugia after the last ice age. Here we present the first analysis of SNP polymorphism within the complete mtDNA genome of West Russian (n = 8), European (n = 64), and North African (n = 5) wild boar. Our analyses provided evidence of unique lineages in the East‐Caucasian (Dagestan) region and in Central Italy. A phylogenetic analysis revealed that these lineages are basal to the other European mtDNA sequences. We also show close connection between the Western Siberian and Eastern European populations. Also, the North African samples were clustered with the Iberian population. Phylogenetic trees and migration modeling revealed a high proximity of Dagestan sequences to those of Central Italy and suggested possible gene flow between Western Asia and Southern Europe which was not directly related to Northern and Central European lineages. Our results support the presence of old maternal lineages in two Southern glacial refugia (i.e., Caucasus and the Italian peninsula), as a legacy of an ancient wave of colonization of Southern Europe from an Eastern origin.
Seedling recruitment correlates with seed input across seed sizes: implications for coexistence
Authors: Maron John L. , Hajek Karyn L. , Hahn Philip G. , Pearson Dean E.
Published: July 2019

Understanding controls on recruitment is critical to predicting community assembly, diversity, and coexistence. Theory posits that at mean fecundity, recruitment of highly fecund small‐seeded plants should be primarily microsite limited, which is indicated by a saturating recruitment function. In contrast, species that produce fewer large seeds are more likely to be seed‐limited, which is characterized by a linear recruitment function. If these patterns hold in nature, seed predation that disproportionately affects larger‐seeded species can limit their establishment. We tested these predictions by comparing recruitment functions among 16 co‐occurring perennial forb species that vary by over two orders of magnitude in seed size. We also assessed how postdispersal seed predation by mice influenced recruitment. We added seeds at densities from zero to three times natural fecundity of each species to undisturbed plots and examined spatial variation in recruitment by conducting experiments across 10 grassland sites that varied in productivity and resource availability. Consistent across two replicated years, most species had linear recruitment functions across the range of added seed densities, indicative of seed‐limited recruitment. Depending on year, the recruitment functions of only 19–37% of target species saturated near their average fecundity, and this was not associated with seed size. Recruitment was strongly inhibited by rodent seed predation for large‐seeded species but not for smaller‐seeded species. Proportional recruitment was more sensitive to spatial variation in recruitment conditions across sites for some small‐seeded species than for large‐seeded species. These results contradict the common belief that highly fecund small‐seeded species suffer from microsite‐limited recruitment. Rather, they imply that, at least episodically, recruitment can be strongly correlated to plant fecundity. However, proportional recruitment of small‐seeded species was inhibited at productive sites to a greater extent than large‐seeded species. Results also show that in a system where the dominant granivore prefers larger seeds, low‐fecundity large‐seeded species can suffer from even greater seed‐limited recruitment than would occur in the absence of predators.
Quantifying evenness and linking it to diversity, beta diversity, and similarity
Authors: Chao Anne , Ricotta Carlo
Published: July 2019

An enormous number of measures based on different criteria have been proposed to quantify evenness or unevenness among species relative abundances in an assemblage. However, a unified approach that can encompass most of the widely used indices is still lacking. Here, we first present some basic requirements for an evenness measure. We then propose that unevenness among species relative abundances in an assemblage can be measured by a normalized divergence between the vector of species relative abundances and the mean vector, where the mean vector represents the species relative abundances of a completely even assemblage. Thus, evenness among species relative abundances is measured by the corresponding normalized extent of closeness between these two vectors. We consider five divergence measures, leading to five classes of evenness indices. All our evenness measures are in terms of diversity (Hill number) of order q > 0 (here q controls the weighting of species relative abundances) and species richness (diversity of order q = 0). We propose quantifying evenness through a continuous profile that depicts evenness as a function of diversity order q > 0. The profiles can be easily and visually compared across multiple assemblages. Our evenness indices satisfy all the requirements presented in this paper and encompass many widely used evenness measures as special cases. When there are multiple assemblages, the abundance‐based Jaccard‐ and Sørensen‐type dissimilarity measures (which are monotonic functions of beta diversity) can be expressed as weighted averages of the individual species’ compositional unevenness values; here, each individual species’ compositional unevenness is calculated based on that species’ abundances among assemblages. The contribution of a species to each dissimilarity measure can be clearly disentangled and quantified in terms of this single species’ compositional unevenness among assemblages. Thus, our framework links the concepts of evenness, diversity, beta diversity, and similarity. Moreover, the framework can be readily extended to a phylogenetic version. A real data example is used to illustrate our approach. We also discuss some criteria and other measures that were previously proposed in the literature.
Increased ILC3s associated with higher levels of IL‐1β aggravates inflammatory arthritis in mice lacking phagocytic NADPH oxidase
Authors: Chan Tzu‐Yi , Yen Chia‐Liang , Huang Ya‐Fang , Lo Pei‐Chi , Nigrovic Peter A. , Cheng Chia‐Ying , Wang Wei‐Zhi , Wu Szu‐Yu , Shieh Chi‐Chang
Published: July 2019

The role of redox regulation in immune‐mediated arthritis has been previously described. However, the relationship between innate immune cells, including innate lymphoid cells (ILCs) and phagocyte‐derived ROS, in this process remains unclear. Here, we characterize ILCs and measure the IL‐1 family cytokines along with other cytokines relevant to ILC functions and development in serum‐induced arthritic joints in wild type and phagocytic NADPH oxidase (NOX2)‐deficient Ncf1−/− mice. We found more severe serum‐induced joint inflammation and increased NCR+ ILC3s in inflamed joints of Ncf1−/− mice. Furthermore, in vitro stimulation with IL‐1β on Tbet+ ILC1s from joints facilitated their differentiation into ROR‐γt+ ILC3s. Moreover, treatment with IL‐1 antagonists effectively lowered the proportions of NCR+ ILC3s and IL‐17A producing ILC3s in Ncf1−/− arthritic mice and ameliorated the joint inflammation. These results suggest that NOX2 is an essential regulator of ILC transdifferentiation and may mediate this process in a redox‐dependent manner through IL‐1β production in the inflammatory joint. Our findings shed important light on the role of ILCs in the initiation and progression in tissue inflammation and delineate a novel innate immune cell‐mediated pathogenic mechanism through which redox regulation may determine the direction of immune responses in joints.
The Cascade Methylation/Cyclization of ortho‐Cyanoarylacrylamides with Dicumyl Peroxide
Authors: Yang Tao , Xia Wen‐Jin , Zhou Bin , Xin Yangchun , Shen Yuehai , Li Ya‐Min
Published: July 2019

A radical cascade methylation/cyclization of ortho‐cyanoarylacrylamides was developed by utilizing dicumyl peroxide as a methylation reagent. This transformation provides a simple and straightforward approach to methylated quinoline‐2,4(1H,3H)‐diones, and exhibits a wide substrate scope. Furthermore, this reaction could be readily scaled up. A possible mechanism is also proposed.
Use of recycled aggregates in pressed fly ash geopolymer concrete
Authors: Wongsa Ampol , Siriwattanakarn Apinun , Nuaklong Peem , Sata Vanchai , Sukontasukkul Piti , Chindaprasirt Prinya
Published: July 2019

In this study, the physical, mechanical, and thermal properties of pressed geopolymer concrete (PRGC) mixed with recycled concrete aggregate (RC) and recycled concrete block aggregate (RB) were investigated. Lignite coal fly ash, sodium hydroxide solution (NaOH), and sodium silicate solution were used as source materials to make geopolymer paste. The effect of fly ash to aggregate ratios and concentrations of NaOH on PRGC properties were tested. Test results were also compared to those of PRGCs mixed with conventional aggregate (limestone dust, SD). The test results showed that PRGCs containing RC and RB exhibited lower dry density, thermal conductivity, and compressive strength than those of PRGCs containing SD. Nevertheless, the compressive strength of PRGCs mixed with recycled aggregates was close to the compressive strength for moderate strength lightweight concrete as per ACI 213. Moreover, the lower thermal conductivity and dry density indicated better insulating properties than that of PRGCs containing SD. The developed PRGCs containing RC and RB in the study can be used for the manufacturing of hollow geopolymer‐based concrete block which are green material with improved insulating properties.
Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1
Authors: Osumi Tomoo , Watanabe Akihiro , Okamura Kohji , Nakabayashi Kazuhiko , Yoshida Masanori , Tsujimoto Shin‐ichi , Uchiyama Meri , Takahashi Hiroyuki , Tomizawa Daisuke , Hata Kenichiro , Kiyokawa Nobutaka , Kato Motohiro
Published: July 2019

Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17) (q24;q21), although cases without this translocation exist. These cases are referred to as “cryptic” or “masked” translocations. Additionally, fewer than 5% of APL cases have another partner gene fused to the RARA gene. The TBL1XR1‐RARA fusion gene has recently been reported as a novel RARA‐associated fusion gene. We report a case with TBL1XR1‐RARA and a masked translocation that was not detected by conventional tests for RARA‐associated translocations. Three‐year‐old girl was diagnosed with APL based morphological findings, although conventional tests for RARA‐associated chimeric genes were negative. She received all‐trans retinoic acid treatment, but that was not effective. She achieved a complete remission (CR) by conventional multidrug chemotherapy, but had extramedullary relapse 2 years after onset. She underwent cord blood transplantation (CBT) in her second CR and is currently alive. To investigate the underlying pathogenesis of this unique case, we performed whole‐genome sequencing and found a cryptic insertion of RARA gene into the TBL1XR1 gene. The transcript of the chimeric gene, TBL1XR1‐RARA, was confirmed as an in‐frame fusion by RT‐PCR. In conclusion, we found using next‐generation sequencing (NGS) a TBL1XR1‐RARA fusion in a child with variant APL without the classic karyotype. Cryptic insertion could also occur in cases other than APL with PML‐RARA. Variant APL has many variants and NGS analysis should therefore be considered for APL variant cases, even for those without RARA translocation detected by conventional analysis.
Cut and covered: Subfossil trees in buried soils reflect medieval forest composition and exploitation of the central European uplands
Authors: Kaiser Knut , Hrubý Petr , Tolksdorf Johann Friedrich , Alper Götz , Herbig Christoph , Kočár Petr , Petr Libor , Schulz Lars , Heinrich Ingo
Published: July 2019

Knowledge of historic changes in vegetation, relief, and soil is key in understanding how the uplands in central Europe have changed during the last millennium, being an essential requirement for measures on forest conversion and nature conservation in that area. Evidence of forest‐clearing horizons from the medieval period could be systematically documented at four low‐ to mid‐altitudinal sites (360–640 meters above mean sea level) in the Harz (Harz Mountains), Erzgebirge (Ore Mountains), and Českomoravská vrchovina (Bohemian‐Moravian Highlands). Subfossil trees with traces of human cutmarks and burning were recovered from buried wet‐organic soils (paleosols) within a context of mining and settlement archaeology, applying a multiproxy‐approach by using data from archaeology, paleobotany, geochronology, dendrochronology, and pedology. Tree stumps and trunks, as well as small‐scale wood remains represent an in situ record of local conifer stands (spruce, fir, and pine). Some deciduous tree taxa also occur. Dating of the tree remains yielded ages from the 10th/11th to the 13th/14th centuries A.D. After deforestation, the tree remains were buried by technogenic and alluvial–colluvial deposits. The reconstructed conifer‐dominated woodlands on wet soils mirror the local vegetation structure immediately before the medieval deforestation. As such wet sites are common in the uplands, conifers were significantly present in the natural vegetation even at mid and lower altitudes.
Astroglial endfeet exhibit distinct Ca2+ signals during hypoosmotic conditions
Authors: Eilert‐Olsen Martine , Hjukse Jarand B. , Thoren Anna E. , Tang Wannan , Enger Rune , Jensen Vidar , Pettersen Klas H. , Nagelhus Erlend A.
Published: July 2019

Astrocytic endfeet cover the brain surface and form a sheath around the cerebral vasculature. An emerging concept is that endfeet control blood–brain water transport and drainage of interstitial fluid and waste along paravascular pathways. Little is known about the signaling mechanisms that regulate endfoot volume and hence the width of these drainage pathways. Here, we used the genetically encoded fluorescent Ca2+ indicator GCaMP6f to study Ca2+ signaling within astrocytic somata, processes, and endfeet in response to an osmotic challenge known to induce cell swelling. Acute cortical slices were subjected to artificial cerebrospinal fluid with 20% reduction in osmolarity while GCaMP6f fluorescence was imaged with two‐photon microscopy. Ca2+ signals induced by hypoosmotic conditions were observed in all astrocytic compartments except the soma. The Ca2+ response was most prominent in subpial and perivascular endfeet and included spikes with single peaks, plateau‐type elevations, and rapid oscillations, the latter restricted to subpial endfeet. Genetic removal of the type 2 inositol 1,4,5‐triphosphate receptor (IP3R2) severely suppressed the Ca2+ responses in endfeet but failed to affect brain water accumulation in vivo after water intoxication. Furthermore, the increase in endfoot Ca2+ spike rate during hypoosmotic conditions was attenuated in mutant mice lacking the aquaporin‐4 anchoring molecule dystrophin and after blockage of transient receptor potential vanilloid 4 channels. We conclude that the characteristics and underpinning of Ca2+ responses to hypoosmotic stress differ within the astrocytic territory and that IP3R2 is essential for the Ca2+ signals only in subpial and perivascular endfeet.
A comparison of automated lesion segmentation approaches for chronic stroke T1‐weighted MRI data
Authors: Ito Kaori L. , Kim Hosung , Liew Sook‐Lei
Published: July 2019

Accurate stroke lesion segmentation is a critical step in the neuroimaging processing pipeline for assessing the relationship between poststroke brain structure, function, and behavior. Many multimodal segmentation algorithms have been developed for acute stroke neuroimaging, yet few algorithms are effective with only a single T1‐weighted (T1w) anatomical MRI. This is a critical gap because multimodal MRI is not commonly available due to time and cost constraints in the stroke rehabilitation setting. Although several attempts to automate the segmentation of chronic lesions on single‐channel T1w MRI have been made, these approaches have not been systematically evaluated on a large dataset. We performed an exhaustive review of the literature and identified one semiautomated and three fully automated approaches for segmentation of chronic stroke lesions using T1w MRI within the last 10 years: Clusterize, automated lesion identification (ALI), Gaussian naïve Bayes lesion detection (lesionGnb), and lesion identification with neighborhood data analysis (LINDA). We evaluated each method on a large T1w stroke dataset (N = 181). LINDA was the most computationally expensive approach, but performed best across the three main evaluation metrics (median values: dice coefficient = 0.50, Hausdorff's distance = 36.34 mm, and average symmetric surface distance = 4.97 mm). lesionGnb had the highest recall/least false negatives (median = 0.80). However, across the automated methods, many lesions were either misclassified (ALI: 28, lesionGnb: 39, LINDA: 45) or not identified (ALI: 24, LINDA: 23, lesionGnb: 0). Segmentation accuracy in all automated methods were influenced by size (small: worst) and stroke territory (brainstem, cerebellum: worst) of the lesion. To facilitate reproducible science, our analysis files have been made publicly available online.
Real world utilization of EGFR TKIs and prognostic factors for survival in NSCLC during 2010–2016 in Sweden: A nationwide observational study
Authors: Bergqvist Michael , Christensen Helene N. , Wiklund Fredrik , Bergström Stefan
Published: July 2019

The purpose of our study was to investigate time trends in treatment pattern and prognostic factors for overall survival (OS) in epidermal growth factor receptor (EGFR) targeting tyrosine kinase inhibitors (TKIs) treated nonsmall cell lung cancer (NSCLC) patients. Utilizing Swedish nationwide registers, we identified all Stage IIIB–IV NSCLC patients treated with EGFR TKIs and followed them from diagnosis (2010–2015) until death or end of observation (2016). Multivariable Cox regression analyses were performed to test associations of patient‐, tumor‐related factors with OS. Of 9,992 Stage IIIB–IV NSCLC patients, the 1,419 (14%) who initiated EGFR TKI treatment during observation were younger (median age 68 vs. 71 years), less ≥1 comorbidities (34% vs. 46%), more often female (59% vs. 47%), Stage IV (89% vs. 85%) and adenocarcinoma (85% vs. 66%) compared to non‐TKI treated patients. After TKI initiation, 7% (n = 100) of the patients switched, 4% (n = 62) rechallenged a TKI treatment, 65% (n = 919) discontinued and 24% (n = 338) had died. A more recent diagnosis demonstrated shorter time to EGFR TKI initiation, prolonged treatment length and longer median OS (15.3 months 2010–2011; 14.4 months 2012–2013; 18.6 months 2014–2015). Prognostic factors for longer OS when treated with EGFR TKIs were younger age, adenocarcinoma, less advanced clinical stage and less comorbid disease. In conclusion, during the observation period, survival improved for EGFR TKI treated NSCLC patients, as did the accessibility for targeted therapies for these patients.
Serum ghrelin and esophageal and gastric cancer in two cohorts in China
Authors: Pritchett Natalie R. , Maziarz Marlena , Shu Xiao‐Ou , Kamangar Farin , Dawsey Sanford M. , Fan Jin‐Hu , Ji Bu‐Tian , Gao Yu‐Tang , Xiang Yong‐Bing , Qiao You‐Lin , Li Honglan , Yang Gong , Wang Shao‐Ming , Stanczyk Frank Z. , Chow Wong‐Ho , Katki Hormuzd A. , Zheng Wei , Lan Qing , Freedman Neal D. , Rothman Nat , Abnet Christian C. , Murphy Gwen
Published: July 2019

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p‐trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p‐trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p‐trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45–0.92; p‐trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.
Private mobile edge cloud for 5G network applications
Authors: Shah Sayed Chhattan
Published: July 2019

Resource‐intensive real‐time IoT and 5G network applications require low latency, high data rates, and considerable computing and storage resources. Mobile cloud computing systems cannot fulfill the requirements of these applications due to high communication latency. Consequently, recently proposed edge computing implementations require adding new infrastructure or updating existing infrastructure. In addition, edge computing does not exploit the capabilities of end devices, which have become more powerful than supercomputers in the last decade. To overcome the drawbacks of mobile cloud and edge computing systems, we have proposed a private mobile edge cloud in which multiple mobile and stationary devices such as sensors, robots, home appliances, and smartphones, interconnected through infrastructure‐less and infrastructure‐based wireless local area networks are combined to create a small‐scale cloud data center at a local physical area such as a home. We have also discussed opportunities and research challenges associated with development of proposed system and a high‐level architecture based on a cross layer design for an efficient management of resources.
Freeze‐dry processing of three‐dimensional cell constructs for bone graft materials
Authors: Sasaki Jun‐Ichi , Yoshimoto Itsumi , Katata Chihiro , Tsuboi Ririko , Imazato Satoshi
Published: July 2019

Freeze‐dry processing improves the operability and stability of cell‐based biomaterials and facilitates sterilization for clinical application. However, there is no established freeze‐drying protocol for engineered tissues. Recently, we reported that biomimetic bone tissues can be fabricated using scaffold‐free three‐dimensional (3D) cell constructs with potential applications as bone graft materials. The purpose of this study was to assess the influence of freeze drying on the morphology and components of 3D cell constructs. Cell constructs freeze dried in phosphate buffered saline (PBS) maintained organic and inorganic components; whereas sodium citrate buffer (SCB)‐treated constructs had significantly lower amounts of calcium and bone‐related proteins. Alkaline phosphatase (ALP) activity in cell constructs was maintained by freeze drying in 10% sucrose‐containing PBS, whereas cell constructs treated with PBS without sucrose or with sucrose‐containing SCB showed significant reductions of ALP activity. In this study, we found that sucrose‐containing phosphate buffer was suitable for freeze drying to maintain minerals and protein functions within 3D cell constructs, whereas citrate buffer was inappropriate. The insights gained by this study may facilitate the development of novel cell‐based biomaterials fabricated by tissue engineering approaches and bone graft biomaterials.
Changes in glucose‐lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease
Authors: Lei Yi , Yang Jun , Li Hua , Zhong Haihua , Wan Qin
Published: July 2019

Background

Autoimmune thyroid disease (AITD) is a common organ‐specific autoimmune disorder, and genetic, environmental, and endogenous factors are responsible for initiation of thyroid autoimmunity. Some AITD patients suffer from a certain degree of glucose‐lipid metabolism disorder. This study aims to explore the changes in glucose‐lipid metabolism, insulin resistance, and inflammatory factors in patients with AITD.

Methods

A total of 91 patients with Hashimoto's thyroiditis were retrospectively analyzed and divided into hypothyroidism group (n = 42) and normal thyroid group (n = 49), while 50 healthy people were selected as control group. The changes in glucose‐lipid metabolism, insulin resistance, and inflammatory factors in each group were compared, and their correlations with the thyroid function were analyzed.

Results

The levels of serum interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), IL‐12, IL‐10, (FINS), and homeostasis model assessment of insulin resistance (HOMA‐IR) were gradually declined in sequence of hypothyroidism group, normal thyroid group, and control group (P < 0.05). In hypothyroidism group, the levels of serum‐free triiodothyronine (FT3), free thyroxine (FT4), (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) were significantly lower than those in normal thyroid group (P < 0.05), while the level of serum thyroid stimulating hormone (TSH) was significantly higher than that in normal thyroid group (P < 0.05). However, the fasting blood glucose and 2‐hour postprandial blood glucose levels had no statistically significant differences among the three groups (P > 0.05).

Conclusion

Autoimmune thyroid disease patients are prone to fat metabolism disorder, and the serum thyroid hormone level has a close correlation with blood lipid metabolism, insulin metabolism, and inflammatory factors.
Characterization of human pegivirus infection in liver transplantation recipients
Authors: Izumi Takuma , Sakata Kazuhito , Okuzaki Daisuke , Inokuchi Shoichi , Tamura Tomokazu , Motooka Daisuke , Nakamura Shota , Ono Chikako , Shimokawa Masahiro , Matsuura Yoshiharu , Mori Masaki , Fukuhara Takasuke , Yoshizumi Tomoharu
Published: July 2019

Approximately 2% of healthy persons are infected with human pegivirus (HPgV). HPgV is transmitted via vertical, sexual, and blood‐borne routes. Recently, the association of HPgV infection with the risk of lymphoma was reported. Here, we examined the prevalence of chronic HPgV infection in liver transplantation (LT) recipients and patients with hepatectomy and the influence of HPgV infection after LT on clinical and perioperative factors. We enrolled 313 LT recipients and 187 patients with hepatectomy who received care at the Kyusyu University Hospital between May 1997 and September 2017. Of the 313 recipients and 187 patients enrolled in this study, 44 recipients (14.1%) and 2 patients (1.1%) had HPgV viremia, respectively. There was no significant association between HPgV infection and LT outcomes. Interestingly, one recipient was infected with HPgV during the peritransplant period, which was likely transmitted via blood transfusion because HPgV RNA was detected from the blood bag transfused to the recipient during LT. We reviewed the available literature on the prevalence HPgV infections in other organ‐transplanted patients and whether they impacted clinical outcomes. They also had the higher prevalence of HPgV infection, while it appears to be of low or no consequences. In addition, HPgV infection induced the upregulation of interferon‐stimulated gene (ISG) expression in peripheral blood mononuclear cells. LT recipients had higher HPgV viremia compared to patients with hepatectomy. Although HPgV infection was not associated with LT‐related outcomes, it induced ISG expression in recipients.
Secondary Perforation Risk in Plate Osteosynthesis of Unstable Proximal Humerus Fractures: A Biomechanical Investigation of the Effect of Screw Length
Authors: Ciric Daniel , Mischler Dominic , Qawasmi Feras , Wenzel Lisa , Richards R. Geoff , Gueorguiev Boyko , Windolf Markus , Varga Peter
Published: July 2019

Secondary perforation of screws into the joint surface is a commonly reported mechanical fixation failure mode in locked plating of proximal humerus fractures (PHF). This study investigated the influence that screws tip to joint distance (TJD) has on the biomechanical risk of secondary screw perforation and the stability of PHF. Ten pairs of cadaveric proximal humeri with a wide range of bone mineral density were used. Each specimen was osteotomized and instrumented with the PHILOS plate, simulating a highly unstable 3‐part fracture. Bones were randomized into a long screw group (LSG) with 4 mm TJD, or a short screw group (SSG) with 8 mm TJD. A custom biomechanical setup was used to test the samples to failure cyclically with a constant valley load and an increasing ramp. The number of cycles to the initial screw loosening event was significantly higher for the LSG (mean ± standard deviation: 17,532 ± 6,458) compared with the SSG (11,102 ± 5,440) (p < 0.01). The mode of failure during testing was lateral‐inferior displacement combined with varus collapse, with calcar screws perforating first. The number of cycles to failure event for LSG (27,849 ± 5,648) was not significantly different compared with SSG (28,782 ± 7,307) (p = 0.50). Screws that purchase closer to the joint had better initial stability and resistance against loosening. Placing longer screws, within limits dictated by the surgical guide, is expected to decrease the risk of secondary perforation failures in unstable PHF. These findings require clinical corroboration. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2625–2633, 2019
The use of interdental brushes or oral irrigators as adjuvants to conventional oral hygiene associated with recurrence of periodontitis in periodontal maintenance therapy: A 6‐year prospective study
Authors: Costa Fernando Oliveira , Costa Amanda Almeida , Cota Luís Otávio Miranda
Published: July 2019

Background

Prospective studies investigating the influence of adjuvants to oral hygiene procedures on the recurrence of periodontitis (RP) during periodontal maintenance therapy (PMT) programs have not been previously reported. The aim of this study was to compare the effect of oral irrigator devices or interdental brushes as adjuncts to toothbrushing associated with dental flossing to improving periodontal condition and reducing RP among individuals under PMT.

Methods

From a 6‐year prospective PMT cohort study (n = 268), 142 individuals who attended at least one PMT visit within 12 months were determined to be eligible. According to oral hygiene adjuvants use, they were categorized into three groups: 1) manual brushing/dental flossing + interdental brushes (BDF + Ib; n = 44); 2) manual brushing/dental flossing + oral irrigator (BDF + Oi; n = 36); and 3) only manual brushing/dental flossing (BDF; n = 62). Full‐mouth periodontal examination and oral hygiene habits were evaluated at two time points: T1 (after active periodontal therapy) and T2 (6 years).

Results

RP was significantly higher among BDF when compared with BDF + Ib and BDF + Oi. The final logistic model in T2 for RP included the following items: manual brushing/dental flossing alone (odds ratio [OR] = 1.94); age > 50 years (OR = 1.98), smoking (OR = 3.51), bleeding on probing >30% sites (OR = 4.10), and the interaction between manual brushing/dental flossing alone and smoking (OR = 6.1). A protective effect on RP was observed in BDF + Oi individuals (OR = 0.52).

Conclusions

BDF + Ib and BDF + Oi individuals presented lower rates of RP and better periodontal condition when compared to BDF individuals. Including these adjuvants to conventional oral hygiene have shown to improve biofilm control during PMT leading to a better periodontal status maintenance.
From by‐product to food ingredient: evaluation of compositional and technological properties of olive‐leaf phenolic extracts
Authors: Flamminii Federica , Di Mattia Carla Daniela , Difonzo Graziana , Neri Lilia , Faieta Marco , Caponio Francesco , Pittia Paola
Published: July 2019

BACKGROUND

Most olive by‐products, like olive leaves, are still undervalued despite their strong potential as a source of healthy and functional components. To exploit their potential use as active ingredients in complex food systems, it is of primary importance the knowledge of their composition and technological functionality which represented the objective of this work.

RESULTS

Phenolic extracts from olive leaves, obtained by extraction with pure water (Eth0) and two different water‐ethanol solutions (Eth30, Eth70), were characterized for their composition and technological properties such as water‐ / oil‐ holding ability, air/water surface activity, and emulsifying capacity at pH 4.5 and 7. Their chemical stability over time, at constant temperature, was also investigated. The technological properties were affected by extraction media and pH. Phenolic extracts displayed significant surface activity, showing dose‐dependent behavior. Surface properties were affected by pH and this result was confirmed by the emulsifying capacity. The extracts showed good oil‐holding capacity but limited water‐binding capacity. Eth70 showed the highest chemical stability, which was confirmed by the rate parameters obtained by modeling data using a Weibull model.

CONCLUSION

The results of this study highlight that olive leaves extracts can represent a useful ingredient in acidic lipid‐containing foods. © 2019 Society of Chemical Industry
Antitumor bioactivity of porphyran extracted from Pyropia yezoensis Chonsoo2 on human cancer cell lines
Authors: He Dan , Wu Siya , Yan Liping , Zuo Jihui , Cheng Yang , Wang Hanfei , Liu Jian , Zhang Xu , Wu Mingjiang , Choi Jong‐il , Tong Haibin
Published: July 2019

BACKGROUND

Pyropia yezoensis, rich in porphyran, is a medicine‐edible red alga. In the present study, the physicochemical characteristics, conformational states and antitumor activities of a novel porphyran extracted from the high‐yield algal strain Pyropia yezoensis Chonsoo2 and its two degraded derivatives by gamma irradiation were investigated.

RESULTS

Pyropia yezoensis porphyran is a water‐soluble, triple‐helical sulfated hetero‐galactopyranose, named PYP. PYP was degraded by gamma irradiation at 20 kGy and 50 kGy, giving two low molecular weight derivatives comprising PYP‐20 and PYP‐50, respectively. PYP with a higher molecular weight has a solution conformation different from PYP‐20 and PYP‐50. Three porphyrans had no toxicity in normal human liver cells (HL‐7702) and showed antitumor effects on Hep3B, HeLa and MDA‐MB‐231. They had better antitumor against HeLa cells, exhibiting a similar inhibition ratio compared to 5‐fluorouracil, with PYP especially exhibiting a higher inhibition ratio than 5‐fluorouracil. With respect to HeLa cells, the different antitumor activities might be related to porphyran molecular weight and solution conformation. Furthermore, the HeLa cell cycle was blocked in the G2/M phase after PYP treatment, leading to cell proliferation inhibition. The induction of cell cycle arrest was related to the changes in the expression of p21, p53, Cyclin B1 and cyclin‐dependent kinase 1.

CONCLUSION

Pyropia yezoensis porphyran, as applied to medicine and functional food, could potentially be used as a non‐toxic natural adjuvant in cancer therapy. © 2019 Society of Chemical Industry