bluuebunny/crossref_metadata_2025 huggingface dataset:
Arterial occlusive events in chronic myeloid leukemia patients treated with ponatinib in the real‐life practice are predicted by the Systematic Coronary Risk Evaluation (SCORE) chart
Authors: Caocci Giovanni , Mulas Olga , Abruzzese Elisabetta , Luciano Luigiana , Iurlo Alessandra , Attolico Immacolata , Castagnetti Fausto , Galimberti Sara , Sgherza Nicola , Bonifacio Massimiliano , Annunziata Mario , Gozzini Antonella , Orlandi Ester Maria , Stagno Fabio , Binotto Gianni , Pregno Patrizia , Fozza Claudio , Trawinska Malgorzata Monika , De Gregorio Fiorenza , Cattaneo Daniele , Albano Francesco , Gugliotta Gabriele , Baratè Claudia , Scaffidi Luigi , Elena Chiara , Pirillo Francesca , Scalzulli Emilia , La Nasa Giorgio , Foà Robin , Breccia Massimo
Published: March 2019

Arterial occlusive events (AOEs) represent emerging complications in chronic myeloid leukemia (CML) patients treated with ponatinib. We identified 85 consecutive CML adult patients who were treated with ponatinib in 17 Italian centers. Patients were stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels.

The 60‐month cumulative incidence rate of AOEs excluding hypertension was 25.7%. Hypertension was reported in 14.1% of patients. The median time of exposure to ponatinib was 28 months (range, 3‐69 months). Patients with a high to very high SCORE risk showed a significantly higher incidence rate of AOEs (74.3% vs 15.2%, P < 0.001). Patients aged ≥60 years showed a significantly higher incidence rate of AOEs (51.5% vs 16.9%, P = 0.008). In multivariate analysis, no association was found between AOEs and positive history of CV disease, age, dose of ponatinib, previous exposure to nilotinib, and comorbidities. Only the SCORE risk was confirmed as a significant predictive factor (P = 0.01; HR = 10.9; 95% C.I. = 1.7‐67.8). Patients aged ≥60 years who were treated with aspirin had a lower incidence rate of AOEs (33.3% vs 61.8%). Among the 14 reported AOEs, 78.6% of them showed grade 3 to 4 toxicity. This real‐life study confirmed the increased incidence of AOEs in CML patients treated with ponatinib, with high to very high SCORE risk. We suggest that patients aged ≥60 years who were treated with ponatinib should undergo prophylaxis with 100 mg/day of aspirin. Our findings emphasize personalized prevention strategies based on CV risk factors.
Brinkman‐Forchheimer slip flow subject to exponential space and thermal‐dependent heat source in a microchannel utilizing SWCNT and MWCNT nanoliquids
Authors: Shehzad Sabir Ali , Mahanthesh Basavarajappa , Gireesha Bijjanal Jayanna , Shashikumar Nagavangala Shankarappa , Madhu Macha
Published: March 2019

This communication examines the impact of carbon nanotubes (single‐wall carbon nanotubes [SWCNT] and multi‐wall carbon nanotubes [MWCNT]) on magnetohydrodynamic Brinkman and Forchheimer flow in a planar microchannel with multiple slips. Flow through a porous medium is modeled via Brinkman and Forchheimer theory. The impacts of thermal‐dependent heat source (THS) and exponential space‐dependent heat source (ESHS) are deployed. Aspects of Joule and viscous dissipations are also retained. The dimensionless equations are solved using the Runge‐Kutta‐Fehlberg joint with shooting methodology. The significance of various nondimensional parameters on the flow distributions as well as skin‐friction and Nusselt number is illustrated and analyzed. Closed form solution of momentum quantity is developed for a particular case. Obtained numerical results are in perfect agreement with analytical results. Further, the results of SWCNT and MWCNT are compared.
Drivers of peatland water table dynamics in the central Andes, Bolivia and Peru
Authors: Cooper David J. , Sueltenfuss Jeremy , Oyague Eduardo , Yager Karina , Slayback Daniel , Caballero E. Marcelo Cabero , Argollo Jaime , Mark Bryan G.
Published: March 2019

Cushion plant dominated peatlands are key ecosystems in tropical alpine regions of the Andes in South America. The cushion plants have formed peat bodies over thousands of years that fill many valley bottoms, and the forage produced by the plants is critical for native and nonnative domesticated mammals. The sources and flow paths of water supporting these peatlands remain largely unknown. Some studies have suggested that glacier meltwater streams support some peatlands, and that the ongoing loss of glaciers and their meltwaters could lead to the loss or diminishment of peatlands. We analysed the hydrologic regime of 10 peatlands in four mountain regions of Bolivia and Peru using groundwater monitoring. Groundwater levels in peatlands were relatively stable and within 20 cm of the ground surface during the rainy season, and many sites had water tables 40–90 cm below the ground surface in the dry season. Topographic and groundwater elevations in the peatlands demonstrated that the water source of all 10 peatlands was hillslope groundwater flowing from lateral moraines, talus, colluvium, or bedrock aquifers into the peatlands. There was little to no input from streams, whether derived from glacier melt or other sources, and glacier melt could not have recharged the hillslope aquifers supporting peatlands. We measured the stable water isotopes in water samples taken during different seasons, distributed throughout the catchments, and the values are consistent with this interpretation. Our findings indicate that peatlands in the study region are recharged by hillslope groundwater discharge rather than stream water and may not be as vulnerable to glacial decline as other studies have indicated. However, both glaciers and peatlands are susceptible to changing thermal and precipitation regimes that could affect the persistence of peatlands.
Contextual and age‐related determinants of children's lie telling to conceal a transgression
Authors: Carl Talia , Bussey Kay
Published: March 2019

Children frequently tell lies to conceal their transgressions. Evidence to date, using the temptation resistance paradigm (TRP), indicates that antisocial lie telling to conceal a transgression increases into middle childhood (4–8 years) but decreases during early adolescence (8–14 years). However, these age‐related conclusions have emerged from different studies that have involved different age groups, using one of two different TRP tasks. Before accepting this age‐related trend, this study aimed to remove the confound of age and task type by using the two most frequently used TRP tasks (guessing game and school‐achievement task) across a broad age range (4‐ to 14‐year‐olds) of 443 students in one laboratory study. Results revealed the same age‐related decrease in lie telling after 8 years reported in previous research, indicating that the age‐related decrement in lie telling cannot be attributed to task type. However, across all ages, there was an overall difference in the amount of lie telling with respect to the TRP task. Implications for understanding the independent role of age and task type in children's lie telling and suggestions for future research are discussed.

Highlights

Unconfounded age and task type effects for children's antisocial lying by using two TRP tasks across a broad age range in one study.

Results revealed that task type does not contribute to the established age‐related decrement in lie telling. However, task type does affect the overall amount of children's lie telling.

Findings support the importance of context (i.e., task type), in addition to other factors, in determining lie telling. Highlights need to also consider task type in future research.
The court's power to appoint provisional liquidators to carry out rescue roles: Rethinking Legend
Authors: Qu Charles Zhen
Published: March 2019

A dictum in a 2006 Hong Kong Court of Appeal decision had since halted the use of provisional liquidation as a restructuring device in Hong Kong, where no purpose‐built moratorium is provided, until recently, where the Court of First Instance reaffirmed the role of provisional liquidation in restructuring. The Court of First Instance (CFI) judges did so without appearing to contradict the Court of Appeal (CA) position by reconstructing the CA dictum. This paper argues that the CA dictum does not make sense in the first place and pointing out why this is so is more helpful in clarifying the governing rule than a reconstruction of CA's words, which may mislead.
Lymphatic endothelium contributes to colorectal cancer growth via the soluble matrisome component GDF11
Authors: Ungaro Federica , Colombo Piergiuseppe , Massimino Luca , Ugolini Giovanni Stefano , Correale Carmen , Rasponi Marco , Garlatti Valentina , Rubbino Federica , Tacconi Carlotta , Spaggiari Paola , Spinelli Antonino , Carvello Michele , Sacchi Matteo , Spanò Salvatore , Vetrano Stefania , Malesci Alberto , Peyrin‐Biroulet Laurent , Danese Silvio , D'Alessio Silvia
Published: March 2019

Colorectal cancer (CRC) is one of the most malignant tumors worldwide. Stromal cells residing in the tumor microenvironment strongly contribute to cancer progression through their crosstalk with cancer cells and extracellular matrix. Here we provide the first evidence that CRC‐associated lymphatic endothelium displays a distinct matrisome‐associated transcriptomic signature, which distinguishes them from healthy intestinal lymphatics. We also demonstrate that CRC‐associated human intestinal lymphatic endothelial cells regulate tumor cell growth via growth differentiation factor 11, a soluble matrisome component which in CRC patients was found to be associated with tumor progression. Our data provide new insights into lymphatic contribution to CRC growth, aside from their conventional role as conduits of metastasis.
Endocrine disrupting‐chemicals and biochemical recurrence of prostate cancer after prostatectomy: A cohort study in Guadeloupe (French West Indies)
Authors: Brureau Laurent , Emeville Elise , Helissey Carole , Thome Jean Pierre , Multigner Luc , Blanchet Pascal
Published: March 2019

Previous studies have suggested that exposure to environmental chemicals with hormonal properties, also called endocrine disrupting chemicals, may be involved in the occurrence of prostate cancer (PCa). Such exposure may also influence the treatment outcome as it is still present at the time of diagnosis, the beginning of therapy, and beyond. We followed 326 men in Guadeloupe (French West Indies) who underwent radical prostatectomy as primary treatment of localized PCa. We analyzed the relationship between exposure to the estrogenic chlordecone, the antiandrogenic dichlorodiphenyldichloroethylene (DDE, the main metabolite of the insecticide DDT), and the nondioxin‐like polychlorinated biphenyl congener 153 (PCB‐153) with mixed estrogenic/antiestrogenic properties and the risk of biochemical recurrence (BCR) after surgery. After a median follow‐up of 6.1 years after surgery, we found a significant increase in the risk of BCR, with increasing plasma chlordecone concentration (adjusted hazard ratio = 2.51; 95% confidence interval: 1.39–4.56 for the highest vs. lowest quartile of exposure; p trend = 0.002). We found no associations for DDE or PCB‐135. These results shown that exposure to environmental estrogens may negatively influence the outcome of PCa treatment.
Surface analysis of sheep menisci after meniscectomy via infrared attenuated total reflection spectroscopy
Authors: López‐Lorente Ángela I. , Wang Pei , Stein Svenja , Balko Jonas , Lu Rui , Dürselen Lutz , Mizaikoff Boris
Published: March 2019

Menisci are very important fibrocartilaginous tissue, which maintain biomechanical functions and physiological stabilization of knee joint. Meniscectomy is known as a surgery to recover partial functions from acute meniscus tears. However, the late consequences of total or partial meniscectomy include signs of osteoarthritis and even ligament instability. Infrared attenuated total reflection (IR‐ATR) spectroscopy is a very useful technique, which can reveal molecular characteristics via the analysis of vibrational bands. The present study has employed IR‐ATR spectroscopy to investigate sheep menisci samples after meniscectomy in a label‐free fashion. Several differences of peak absorbance change and peak shift were observed between the native healthy samples and the meniscectomy samples in distinct IR wavenumber regions, such as amide I band, amide II band, C‐H bending band as well as the sugar band region. Combining the results from the collagen protein IR spectra, it can be speculated that six months after meniscectomy collagen fibrils on the incision lose its ordered arrangement and a decrease in the triple helical structure of collagen fibril is observed. In addition, the collagen fibrils and proteoglycan content might also be slight varied after meniscectomy.
Influence of processing parameters on mechanical properties of a 3D‐printed trabecular bone microstructure
Authors: Amini Morteza , Reisinger Andreas , Pahr Dieter H.
Published: March 2019

Natural bone microstructure has shown to be the most efficient choice for the bone scaffold design. However, there are several process parameters involved in the generation of a microCT‐based 3D‐printed (3DP) bone. In this study, the effect of selected parameters on the reproducibility of mechanical properties of a 3DP trabecular bone structure is investigated. MicroCT images of a distal radial sample were used to reconstruct a 3D ROI of trabecular bone. Nine tensile tests on bulk material and 54 compression tests on 8.2 mm cubic samples were performed (9 cases × 6 specimens/case). The effect of input‐image resolution, STL mesh decimation, boundary condition, support material, and repetition parameters on the weight, elastic modulus, and strength were studied. The elastic modulus and the strength of bulk material showed consistent results (CV% = 9 and 6%, respectively). The weight, elastic modulus, and strength of the cubic samples showed small intragroup variation (average CV% = 1.2, 9, and 5.5%, respectively). All studied parameters had a significant effect on the outcome variables with less effect on the weight. Utmost care to every step of the 3DP process and involved parameters is required to be able to reach the desired mechanical properties in the final printed specimen. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:38–47, 2020.
Electrospun nanofiber mesh with fibroblast growth factor and stem cells for pelvic floor repair
Authors: Hansen Signe Gellert , Taskin Mehmet Berat , Chen Menglin , Wogensen Lise , Vinge Nygaard Jens , Axelsen Susanne Maigaard
Published: March 2019

Surgical outcome following pelvic organ prolapse (POP) repair needs improvement. We suggest a new approach based on a tissue‐engineering strategy. In vivo, the regenerative potential of an electrospun biodegradable polycaprolactone (PCL) mesh was studied. Six different biodegradable PCL meshes were evaluated in a full‐thickness abdominal wall defect model in 84 rats. The rats were assigned into three groups: (1) hollow fiber PCL meshes delivering two dosages of basic fibroblast growth factor (bFGF), (2) solid fiber PCL meshes with and without bFGF, and (3) solid fiber PCL meshes delivering connective tissue growth factor (CTGF) and rat mesenchymal stem cells (rMSC). After 8 and 24 weeks, we performed a histological evaluation, quantitative analysis of protein content, and the gene expression of collagen‐I and collagen‐III, and an assessment of the biomechanical properties of the explanted meshes. Multiple complications were observed except from the solid PCL‐CTGF mesh delivering rMSC. Hollow PCL meshes were completely degraded after 24 weeks resulting in herniation of the mesh area, whereas the solid fiber meshes were intact and provided biomechanical reinforcement to the weakened abdominal wall. The solid PCL‐CTGF mesh delivering rMSC demonstrated improved biomechanical properties after 8 and 24 weeks compared to muscle fascia. These meshes enhanced biomechanical and biochemical properties, demonstrating a great potential of combining tissue engineering with stem cells as a new therapeutic strategy for POP repair. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:48–55, 2020.
Meta-Analysis of Genomewide Association Studies Reveals Genetic Variants for Hip Bone Geometry
Authors: Hsu Yi-Hsiang , Estrada Karol , Evangelou Evangelos , Ackert-Bicknell Cheryl , Akesson Kristina , Beck Thomas , Brown Suzanne J , Capellini Terence , Carbone Laura , Cauley Jane , Cheung Ching-Lung , Cummings Steven R , Czerwinski Stefan , Demissie Serkalem , Econs Michael , Evans Daniel , Farber Charles , Gautvik Kaare , Harris Tamara , Kammerer Candace , Kemp John , Koller Daniel L , Kung Annie , Lawlor Debbie , Lee Miryoung , Lorentzon Mattias , McGuigan Fiona , Medina-Gomez Carolina , Mitchell Braxton , Newman Anne , Nielson Carrie , Ohlsson Claes , Peacock Munro , Reppe Sjur , Richards J Brent , Robbins John , Sigurdsson Gunnar , Spector Timothy D , Stefansson Kari , Streeten Elizabeth , Styrkarsdottir Unnur , Tobias Jonathan , Trajanoska Katerina , Uitterlinden André , Vandenput Liesbeth , Wilson Scott G , Yerges-Armstrong Laura , Young Mariel , Zillikens M Carola , Rivadeneira Fernando , Kiel Douglas P , Karasik David
Published: March 2019

Hip geometry is an important predictor of fracture. We performed a meta-analysis of GWAS studies in adults to identify genetic variants that are associated with proximal femur geometry phenotypes. We analyzed four phenotypes: (i) femoral neck length; (ii) neck-shaft angle; (iii) femoral neck width, and (iv) femoral neck section modulus, estimated from DXA scans using algorithms of hip structure analysis. In the Discovery stage, 10 cohort studies were included in the fixed-effect meta-analysis, with up to 18,719 men and women ages 16 to 93 years. Association analyses were performed with ∼2.5 million polymorphisms under an additive model adjusted for age, body mass index, and height. Replication analyses of meta-GWAS significant loci (at adjusted genomewide significance [GWS], threshold p ≤ 2.6 × 10–8) were performed in seven additional cohorts in silico. We looked up SNPs associated in our analysis, for association with height, bone mineral density (BMD), and fracture. In meta-analysis (combined Discovery and Replication stages), GWS associations were found at 5p15 (IRX1 and ADAMTS16); 5q35 near FGFR4; at 12p11 (in CCDC91); 11q13 (near LRP5 and PPP6R3 (rs7102273)). Several hip geometry signals overlapped with BMD, including LRP5 (chr. 11). Chr. 11 SNP rs7102273 was associated with any-type fracture (p = 7.5 × 10–5). We used bone transcriptome data and discovered several significant eQTLs, including rs7102273 and PPP6R3 expression (p = 0.0007), and rs6556301 (intergenic, chr.5 near FGFR4) and PDLIM7 expression (p = 0.005). In conclusion, we found associations between several genes and hip geometry measures that explained 12% to 22% of heritability at different sites. The results provide a defined set of genes related to biological pathways relevant to BMD and etiology of bone fragility. © 2019 American Society for Bone and Mineral Research.
Interferon Gamma-1b Does Not Increase Markers of Bone Resorption in Autosomal Dominant Osteopetrosis
Authors: Imel Erik A , Liu Ziyue , Acton Dena , Coffman Melissa , Gebregziabher Netsanet , Tong Yan , Econs Michael J
Published: March 2019

In autosomal dominant osteopetrosis type 2 (ADO2) CLCN7 mutations cause impaired osteoclast function. Severe consequences include skeletal fragility despite high bone mass, osteomyelitis, osteonecrosis, bone marrow failure, and severe cranial nerve impingement. There is no effective medical treatment for ADO2. We recruited subjects with ADO2 into a 14-week, open-label, pilot clinical trial of interferon gamma-1b. Doses were titrated based on tolerability and if fasting serum C-telopeptide (CTX) was <25% above baseline at week 8, targeting doses of 100 µg/m2 three times a week. The primary outcomes were change from baseline in CTX and N-telopeptide/creatinine ratio (NTX/Cr) at week 14. Secondary outcomes included changes in urine calcium/creatinine ratio, bone formation markers and tolerability. Nine adults and three children were recruited. Severe manifestations of ADO2 included histories of fractures (100%), osteomyelitis (16.7%), vision loss (50%), and anemia (58.3%). Baseline CTX and NTX/Cr were generally low-normal. Procollagen type I N-terminal propeptide was elevated or in the upper-normal range in 11 of 12 (91.6%) subjects. Elevations of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were common. One subject withdrew due to rash. Five subjects achieved doses of 50 µg/m2 3 days a week, while six reached the full dose of 100 µg/m2 3 days a week. Only 3 of 11 (27.3%) completing subjects achieved the primary outcome of increasing CTX ≥25% above baseline at week 14. The mean ± SD change from baseline in CTX at week 14 was +2.2% ± 43.2%, p = 0.86). Likewise, there was no significant change in NTX/Cr (mean change –2.1%, p = 0.81). Interferon gamma-1b was poorly tolerated. Most subjects had adverse events, and the Mental Health and Mental Component Scales of the SF-36v2 health survey declined slightly (p < 0.05). Over 14 weeks, interferon gamma-1b failed to significantly increase bone turnover markers in ADO2 and was poorly tolerated. Consequently, interferon gamma-1b is unlikely to be effective for decreasing bone mass in ADO2. © 2019 American Society for Bone and Mineral Research.
Growth Plate Borderline Chondrocytes Behave as Transient Mesenchymal Precursor Cells
Authors: Mizuhashi Koji , Nagata Mizuki , Matsushita Yuki , Ono Wanida , Ono Noriaki
Published: March 2019

The growth plate provides a substantial source of mesenchymal cells in the endosteal marrow space during endochondral ossification. The current model postulates that a group of chondrocytes in the hypertrophic zone can escape from apoptosis and transform into cells that eventually become osteoblasts in an area beneath the growth plate. The growth plate is composed of cells with various morphologies; particularly at the periphery of the growth plate immediately adjacent to the perichondrium are “borderline” chondrocytes, which align perpendicularly to other chondrocytes. However, in vivo cell fates of these special chondrocytes have not been revealed. Here we show that borderline chondrocytes in growth plates behave as transient mesenchymal precursor cells for osteoblasts and marrow stromal cells. A single-cell RNA-seq analysis revealed subpopulations of Col2a1-creER-marked neonatal chondrocytes and their cell type–specific markers. A tamoxifen pulse to Pthrp-creER mice in the neonatal stage (before the resting zone was formed) preferentially marked borderline chondrocytes. Following the chase, these cells marched into the nascent marrow space, expanded in the metaphyseal marrow, and became Col(2.3 kb)-GFP+ osteoblasts and Cxcl12-GFPhigh reticular stromal “CAR” cells. Interestingly, these borderline chondrocyte-derived marrow cells were short-lived, as they were significantly reduced during adulthood. These findings demonstrate based on in vivo lineage-tracing experiments that borderline chondrocytes in the peripheral growth plate are a particularly important route for producing osteoblasts and marrow stromal cells in growing murine endochondral bones. A special microenvironment neighboring the osteogenic perichondrium might endow these chondrocytes with an enhanced potential to differentiate into marrow mesenchymal cells. © 2019 American Society for Bone and Mineral Research.
Icariin promotes osteogenic differentiation of bone marrow stromal cells and prevents bone loss in OVX mice via activating autophagy
Authors: Liang Xiaoxiao , Hou Zhiqiang , Xie Yuanlong , Yan Feifei , Li Sisi , Zhu Xiaobin , Cai Lin
Published: March 2019

Osteoporosis (OP) results from the impaired function of endogenous bone marrow mesenchymal stem cells (BMSCs). Icariin (ICA) has shown potential osteoprotective effects. However, the molecular mechanism for the anabolic action of ICA remains largely unknown. The objective of the present study is to investigate whether ICA prevents bone loss by acting on BMSCs via affecting the level of autophagy after ovariectomy (OVX). The BMSCs were extracted from BALB/c mice treated with ICA, chloroquine (CQ, an autophagy inhibitor) or ICA + CQ. The OVX mice were injected with ICA, CQ, or ICA + CQ for 1 month. We performed Alizarin Red staining and alkaline phosphatase staining to detect osteogenic differentiation of BMSCs. Micro‐CT, hematoxylin and eosin staining, Oil Red O staining, and tartrate‐resistant acid phosphatase staining were used to assess the bone mass, lipid droplets and osteoclasts in femurs. Autophagy activity in BMSCs from different groups was evaluated by Western blot analysis. The osteogenic differentiation of BMSCs from OVX‐induced OP mice was decreased. Treatment with ICA reduced bone loss and formation of osteoclasts and increased osteogenic differentiation of BMSCs in vitro and vivo. In addition, autophagy was enhanced in BMSCs of OVX mice treated with ICA. Our results indicate that ICA prevents OVX‐induced bone loss possibly by strengthening the osteogenic differentiation of BMSCs via increasing autophagic activity.
Identifying potential metastasis‐related long non‐coding RNAs, microRNAs, and message RNAs in the esophageal squamous cell carcinoma
Authors: Yang Fei , Wen Shiwang , Zhang Yuefeng , Xu Yanzhao , Lv Huilai , Zhu Yonggang , Wang Mingbo , Su Peng , Huang Chao , Tian Ziqiang
Published: March 2019

Esophageal squamous cell carcinoma (ESCC) is the predominant form with the highest incidence. We aimed to find metastasis‐related differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNA (mRNAs) in ESCC. We first obtained the lncRNAs, miRNAs, and mRNAs profiles. The differentially expressed lncRNAs, miRNAs, and mRNAs were obtained, followed by the functional annotation. Then the interaction networks of miRNA‐mRNA, lncRNA‐mRNA coexpression, lncRNA‐miRNA, and lncRNA‐miRNA‐mRNA were constructed. In addition, systematic expression pattern analysis of differentially expressed lncRNAs, miRNA, and mRNA in the normal, metastasis, and nonmetastasis was performed. Survivability of differentially expressed lncRNAs, miRNAs, and mRNA was analyzed. A total of 613 differentially expressed lncRNAs, 35 differentially expressed miRNAs, and 1586 differentially expressed mRNAs were obtained. Several interactions of H19‐hsa‐mir‐222‐chromobox 2 (CBX2), H19‐hsa‐mir‐330‐phosphoinositide‐3‐kinase regulatory subunit 4 (PIK3R4), KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1)/CTB‐89H12.4‐hsa‐mir‐374a‐vascular endothelial growth factor A (VEGFA), MALAT1/X inactive specific transcript (XIST)/XIST antisense RNA (TSIX)‐hsa‐mir‐340‐tumor necrosis factor receptor superfamily member 10A (NFRSF10A) were identified to play key roles in the metastasis of ESCC. In addition, KCNQ1OT1, TSIX, and XIST were significantly associated with the survival time of patients. In conclusion, our study may be helpful in understanding the pathological mechanism and providing new diagnostic and therapeutic biomarkers for ESCC.
An interaction between BRG1 and histone modifying enzymes mediates lipopolysaccharide‐induced proinflammatory cytokines in vascular endothelial cells
Authors: Zhang Yuanyuan , Yuan Yibiao , Li Zilong , Chen Huan , Fang Mingming , Xiao Pingxi , Xu Yong
Published: March 2019

Vascular inflammation is the culprit for a host of human diseases. The underlying mechanism, however, is not definitively elucidated. In the present study, we investigated the interplay between different epigenetic factors during lipopolysaccharide (LPS) induced synthesis of proinflammatory cytokines in cultured vascular endothelial cells. We report that in response to LPS treatment, NF‐κB was deplored to its target promoters along with the chromatin remodeling protein BRG1. Paralleling these changes trimethylated H3K9 became erased from while trimethylated H3K4 started to accumulate on the NF‐κB target promoters. Further analysis revealed that LPS stimulation resulted in sequential recruitment of the H3K9 tri‐demethylase JMJD2A and the H3K4 trimethyltransferase SET1A to the NF‐κB target promoters. JMJD2A mediated–H3K9 demethylation served as a prerequisite for SET1A to bind to the NF‐κB target promoters. Both JMJD2A and SET1A were essential for LPS‐induced transactivation of proinflammatory cytokines by sustaining the binding of NF‐κB. Of key importance, BRG1 coordinated the sequential recruit of and the interplay between JMJD2A and SET1A. In conclusion, our data unveil a novel epigenetic mechanism that contributes to LPS‐induced vascular inflammation.
Exogenous noggin binds the BMP‐2 receptor and induces alkaline phosphatase activity in osteoblasts
Authors: Hashimi Saeed M.
Published: March 2019

Osteogenesis is an important process in bone remodeling and is under strict cellular signaling governed by growth factors and antagonists. Bone morphogenetic protein 2 (BMP‐2) is an important osteogenic factor involved in the transcription of key osteogenic genes such as alkaline phosphatase (ALP). While, antagonists such as noggin effectively restrict osteoblast differentiation through binding to BMP‐2. In this study, we sought to understand the effect of exogenous noggin in osteoblasts and its role in BMP‐2 activation of osteogenesis. Enzymatic activity of ALP was monitored to ascertain the effect of the noggin. Fluorescently labelled noggin was used to determine the binding of noggin to the BMP‐2 receptor. The results demonstrated that noggin significantly increases the activity of ALP at concentrations of 50 to 400 ng/mL. While, it inhibited the activity of exogenous BMP‐2. Furthermore, fluorescently labelled noggin showed strong binding to osteoblasts which were perturbed when cells were preincubated with BMP‐2 suggesting that noggin shares a common receptor with BMP‐2. These results suggest that exogenous noggin facilitates osteogenic differentiation and provide a novel mechanism for its interplay with BMP‐2.
Upregulated long noncoding RNA Linc00261 in pre‐eclampsia and its effect on trophoblast invasion and migration via regulating miR‐558/TIMP4 signaling pathway
Authors: Cheng Dan , Jiang Shan , Chen Jiao , Li Jie , Ao Liangfei , Zhang Ying
Published: March 2019

Pre‐eclampsia (PE) is a leading cause of maternal and perinatal morbidity and mortality but the exact underlying mechanisms of PE pathogenesis remain elusive. Accumulated data suggested that the long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of PE. The present study identified the changes of lncRNA Linc00261 in PE and its effects on trophoblasts invasion and migration. Our results showed that the expression of Linc00261 was upregulated in placental tissues of PE women compared with those of healthy pregnant women. Overexpression of Linc00261 suppressed cell invasion and migration, induced cell apoptosis, and caused cell‐cycle arrest at G0/G1 phase of HTR‐8/SVneo cells; while knockdown of Linc00261 had the opposite effects on the HTR‐8/SVneo cells. Mechanistic studies showed Linc00261 functioned as a competing endogenous RNA for miR‐558 in HTR‐8/SVneo cells, and miR‐558 was negatively regulated by Linc00261. The expression level of miR‐558 in the PE group was significantly lower than the control group, and the expression level of Linc00261 was negatively correlated with the expression level of miR‐558 in the placental tissues of women with PE. Furthermore, miR‐558 was found to negatively regulate the expression of TIMP metallopeptidase inhibitor 4 (TIMP4) via targeting the 3′ untranslated region in the HTR‐8/SVneo cells. Overexpression of miR‐558 increased HTR‐8/SVneo cell invasion and migration, which was attenuated by TIMP4 overexpression. More importantly, both overexpression of miR‐558 and knockdown of TIMP4 partially reversed the suppressive effects of Linc00261 overexpression on cell invasion and migration of HTR‐8/SVneo cells. Collectively, our results for the first time showed the upregulation of Linc00261 in the placental tissues of severe PE patients. The mechanistic results indicated that Linc00261 exerted the suppressive effects on the trophoblast invasion and migration via targeting miR‐558/TIMP4 axis, which may involve in the pathogenesis of PE.
Achieving band convergence by tuning the bonding ionicity in n‐type Mg3Sb2
Authors: Sun Xin , Li Xin , Yang Jiong , Xi Jinyang , Nelson Ryky , Ertural Christina , Dronskowski Richard , Liu Weishu , Snyder Gerald J. , Singh David J. , Zhang Wenqing
Published: March 2019

Identifying strategies for beneficial band engineering is crucial for the optimization of thermoelectric (TE) materials. In this study, we demonstrate the beneficial effects of ionic dopants on n‐type Mg3Sb2. Using the band‐resolved projected crystal orbital Hamilton population, the covalent characters of the bonding between Mg atoms at different sites are observed. By partially substituting the Mg at the octahedral sites with more ionic dopants, such as Ca and Yb, the conduction band minimum (CBM) of Mg3Sb2 is altered to be more anisotropic with an enhanced band degeneracy of 7. The CBM density of states of doped Mg3Sb2 with these dopants is significantly enlarged by band engineering. The improved Seebeck coefficients and power factors, together with the reduced lattice thermal conductivities, imply that the partial introduction of more ionic dopants in Mg3Sb2 is a general solution for its n‐type TE performance. © 2019 Wiley Periodicals, Inc.
The gram‐negative outer membrane modeler: Automated building of lipopolysaccharide‐rich bacterial outer membranes in four force fields
Authors: Baltoumas Fotis A. , Hamodrakas Stavros J. , Iconomidou Vassiliki A.
Published: March 2019

Outer membranes are a crucial component of Gram‐negative bacteria, containing standard lipids in their inner leaflet, lipopolysaccharides (LPSs) in their outer leaflet, and transmembrane β‐barrels known as outer membrane proteins (OMPs). OMPs regulate functions such as substrate transport and cell movement, while LPSs act as a protective barrier for bacteria and can cause toxic reactions in humans. However, the experimental study of outer membranes is challenging. Molecular dynamics simulations are often used for the computational study of membrane systems, but the preparation of complex, LPS‐rich outer membranes is not straightforward. The Gram‐Negative Outer Membrane Modeler (GNOMM) is an automated pipeline for preparing simulation systems of OMPs embedded in LPS‐containing membranes in four different force fields. Given the physiological and clinical importance of outer membranes and their components, GNOMM can be a useful tool in the study of their structure, function, and implications in diseases. GNOMM is available at http://bioinformatics.biol.uoa.gr/GNOMM. © 2019 Wiley Periodicals, Inc.
microRNAs: New prognostic, diagnostic, and therapeutic biomarkers in cervical cancer
Authors: Nahand Javid Sadri , Taghizadeh‐boroujeni Sima , Karimzadeh Mohammad , Borran Sarina , Pourhanifeh Mohammad Hossein , Moghoofei Mohsen , Bokharaei‐Salim Farah , Karampoor Sajad , Jafari Amir , Asemi Zatollah , Tbibzadeh Alireza , Namdar Afshin , Mirzaei Hamed
Published: March 2019

Cervical cancer is as a kind of cancer beginning from the cervix. Given that cervical cancer could be observed in women who infected with papillomavirus, regular oral contraceptives, and multiple pregnancies. Early detection of cervical cancer is one of the most important aspects of the therapy of this malignancy. Despite several efforts, finding and developing new biomarkers for cervical cancer diagnosis are required. Among various prognostic, diagnostic, and therapeutic biomarkers, miRNA have been emerged as powerful biomarkers for detection, treatment, and monitoring of response to therapy in cervical cancer. Here, we summarized various miRNAs as an employable platform for prognostic, diagnostic, and therapeutic biomarkers in the treatment of cervical cancer.
Hepatoprotective effect of Aloe vera against cartap‐ and malathion‐induced toxicity in Wistar rats
Authors: Gupta Vivek K. , Siddiqi Nikhat J. , Ojha Anil K. , Sharma Bechan
Published: March 2019

Exposure to mixture of pesticides in agricultural practices pose a serious threat to the nontarget animals. In present work, we have evaluated the synergistic effect of cartap and malathion on rat liver followed by impact of Aloe vera leaves aqueous extract, which is not known. The animals in eight groups were used; each containing six rats: Group 1 acted as a control, Group 2—control with
A. vera leaves aqueous extract, Group 3—with cartap, Group 4—with malathion, Group 5—with mixture of cartap and malathion, Group 6—cartap with the pretreatment of
A. vera leaf extract, Group 7—malathion with the pretreatment of
A. vera leaf extract, Group 8—mixture of cartap and malathion with the pretreatment of
A. vera leaf extract
. The animals treated for 15 days were killed after 24hr of last treatment. The biochemical studies in the rat liver demonstrated significant perturbations in the levels of nonenzymatic (glutathione and malondialdehyde) and enzymatic (superoxide dismutase, catalase, and glutathione‐
S‐transferase) antioxidative indices. The histopathological examination of liver revealed serious congestion in central vein and the disorganization of hepatic cords due to pesticide treatment. The administration of
A. vera leaves aqueous extract was able to markedly protect rat liver from the pesticides‐induced toxicity. The data indicated that pesticides were able to significantly induce oxidative stress which was substantially reduced by the application of plant extract
.
Functions and roles of long noncoding RNA in cholangiocarcinoma
Authors: Li Jinglin , Huang Lining , Li Zhenglong , Zhong Xiangyu , Tai Sheng , Jiang Xingming , Cui Yunfu
Published: March 2019

Cholangiocarcinoma (CCA) is one of the most fatal cancers in humans, with a gradually increasing incidence worldwide. The efficient diagnostic and therapeutic measures for CCA to reduce mortality are urgently needed. Long noncoding RNAs (lncRNAs) may provide the potential diagnostic and therapeutic option for suppressing the CCA development. LncRNAs are a type of non‐protein‐coding RNAs, which are larger than 200 nucleotides in length. Increasing evidence reveals that lncRNAs exhibit critical roles in the carcinogenesis and development of CCA. Deregulation of lncRNAs impacts the proliferation, migration, invasion, and antiapoptosis of CCA cells by multiple sophisticated mechanisms. Consequently, lncRNAs likely represent promising biomarkers or intervention targets of CCA. In this review, we summarize current studies regarding the biological functions and regulatory mechanisms of diverse lncRNAs in CCA.
Prognostic value of prognostic nutritional index and systemic immune‐inflammation index in patients with osteosarcoma
Authors: Huang Xin , Hu Hongzhi , Zhang Weiyue , Shao Zengwu
Published: March 2019

The aim of this study was to evaluate the relationship between prognostic nutritional index (PNI) and systemic immune‐inflammation index (SII) and clinical features and prognosis of osteosarcoma patients. We retrospectively investigated 126 patients with surgery for osteosarcoma between 2012 and 2018 at our hospital. The preoperative PNI was calculated as albumin level (g/L) + 5 × total lymphocyte count (109/L). The SII was defined as platelet × neutrophil/lymphocyte counts. The optimal cut‐off values for PNI and SII were evaluated with receiver operating curve analysis. Clinical features and PNI and SII were tested with theχ2test. The effects of PNI and SII on overall survival (OS) was investigated by Kaplan–Meier method and Cox proportional hazards model. A low preoperative PNI was remarkably correlated with tumor size, Enneking stage, pathological fracture, local recurrence, metastasis, and neoadjuvant chemotherapy (p < 0.05). Whereas, a high SII was significantly associated with tumor size, histological type, Enneking stage, and neoadjuvant chemotherapy (p < 0.05). There was a significant negative relationship between the PNI and SII (r = 0.384;p < 0.001). For univariate analyses, the results revealed that tumor size, local recurrence, metastasis, PNI, and SII were predictors of OS (p < 0.05). In multivariate analyses, local recurrence (p = 0.010), metastasis (p < 0.001), PNI (p < 0.001), and SII (p = 0.029) as independent prognostic factors were significantly correlated with OS. This study suggested that PNI and SII could be important prognostic parameters for patients with osteosarcoma.
Efficacy of reciprocating systems for removing root filling material plus complementary cleaning methods in flattened canals: Microtomography and scanning electron microscopy study
Authors: Borges Mariana M. B. , Duque Jussaro A. , Zancan Rafaela F. , Vivan Rodrigo R. , Bernardes Ricardo A. , Duarte Marco A. H.
Published: March 2019

The aim of this study was to evaluate three reciprocating systems and complementary cleaning methods on filling material removal during retreatment of flattened canals. Thirty‐six mandibular incisors were prepared using rotary instruments up to size 25.08 and filled using the single‐cone technique. Subsequently, the teeth were divided into three groups (n = 12) according to retreatment procedures: Reciproc Blue (RB): 25/0.08 and 40/0.06; ProDesign R (PDR): 25/0.06 and 35/0.05; and WaveOne Gold (WOG): 25/0.07 and 35/0.06. The remaining filling volume materials were assessed by means of micro‐CT imaging before and after retreatment. After this, the specimens were subdivided into three groups according to complementary cleaning methods: XP‐Endo Shaper (30/0.01); passive ultrasonic irrigation (PUI); 60° oscillatory instrumentation with #30 H‐file, and micro‐CT scan was taken. Then, the roots were cut in half and the samples were analyzed by scanning electron microscope (SEM). The data were analyzed statistically using Kruskal–Wallis and Dunn's Multiple Comparison test with significance level of 5%. None of the reciprocating files promoted complete removal of filling material and there was no statistical difference between the groups, regardless instrument size (p > 0.05). Complementary cleaning methods increased remnant filling removal (p < 0.05). XP‐endo Shaper significantly reduced the amount of filling material in the apical and middle thirds, compared with H‐files (p < 0.05), with no difference with PUI. In the SEM, there was no statistical difference among the instruments (p > 0.05). The reciprocating systems showed similar effectiveness in removing root filling material. Complementary cleaning method with the XP‐Shaper enhanced filling material removal.
Genetics professionals’ attitudes toward prenatal exome sequencing
Authors: Brew Casey E. , Castro Brian A. , Pan Vivian , Hart Alexa , Blumberg Bruce , Wicklund Catherine
Published: March 2019

Prenatal exome sequencing (ES) currently has limited use in the clinical setting, but research suggests that it has added diagnostic utility over karyotyping and array techniques for prenatal diagnosis of fetuses presenting with ultrasound abnormalities. The purpose of this study was to assess the attitudes of genetics professionals toward the clinical implementation of prenatal ES in order to guide development of professional guidelines. A survey was developed using themes identified in previous qualitative studies and was distributed to members of the American College of Medical Genetics and Genomics (ACMG), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC).

A total of 498 participants completed some portion of the survey. There was consensus among participants that there would be clinical utility of prenatal ES when used for diagnosis, pregnancy management, and termination decisions. The majority also agreed that prenatal ES was distinct from its current use in the pediatric and adult settings. There were many areas of contention regarding which types of results should be returned to families and whether or not the current ACMG guidelines for return of incidental findings should also apply to the prenatal setting. Overall, professional guidance is needed to address the continuing concerns surrounding prenatal ES as its utilization in this setting is expected to grow.
Microwave‐Assisted Solvent‐Free Synthesis of Ipsapirone
Authors: Kułaga Damian , Jaśkowska Jolanta , Jasiński Radomir
Published: March 2019

The currently applied synthetic methods of serotonin receptor ligands belonging to the group of long‐chain arylpiperazines, including ipsapirone, require the use of toxic solvents and comprise numerous synthetic steps. Moreover, the reaction yield does not exceed 60% in the majority of cases. These factors lead to an increased energy consumption and negatively impact the environment. This paper describes a more environmentally friendly method of ipsapirone synthesis that we decided to use. Ipsapirone was obtained in two different methods. The first method involved N‐alkylation of bromobutyl saccharin with 1‐(2‐pyrimidyl)piperazine dihydrochloride, while the second was a one‐pot method. Neither of these requires the use of toxic and expensive solvents. A shortened synthesis time, not exceeding 10 min due to the use of microwave radiation, is also another advantage of these methods. The yield of the final product, ipsapirone, was 85% and 67% in the first and the second method, respectively. We also attempted to obtain ipsapirone using saccharin and arylpiperazine salt (method III) as starting materials, but to no avail in the tested conditions. As described herein, the green chemistry method for ipsapirone synthesis is rapid, cost‐effective, and environment friendly.
Piperidinium Hydrogen Sulfate (PHS) as an Efficient Ionic Liquid Catalyst for the Synthesis of Imidazole Derivative under Solvent‐Free Condition
Authors: Albayati Mustafa R. , Marzouk Adel. A. , Abdelhamid Antar A.
Published: March 2019

Piperidinium hydrogen sulfate is used as a very important new catalyst for the synthesis of the biologically active compounds from a series of multi‐substituted imidazole components by the simple reaction of benzyl with different aromatic aldehydes, ammonium acetate, and phenethylamine or butylamine as amine derivatives. The key merits of this method are very shorter reaction times, excellent yield, and ease of stabilization. Furthermore, the produced products can be purified by a non‐chromatographic technique, and the catalyst is reusable. All of these new synthesized components have been characterized and checked from spectral data: IR, 1H‐NMR, and 13C‐NMR spectra and elemental analyses.
Remittances and Asset Accumulation in Bangladesh: A Study Using Generalised Propensity Score
Authors: Chowdhury Mehdi , Radicic Dragana
Published: March 2019

Drawing on a sample of households in Bangladesh, we utilise the generalised propensity score method to investigate the impact of internal and international remittances on households' net assets. The analysis suggests an inverted U‐shaped relationship between the amount of internal remittances and the net assets of households. The effect of international remittances on net assets is similarly inverted U‐shaped. The paper also indicates not only the source but also the size of remittances effects of the utilisation of remittances for asset accumulation. © 2019 The Authors Journal of International Development Published by John Wiley & Sons Ltd.