bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive molecular and clinicopathological analysis of vascular malformations: A study of 319 cases
Authors: Ten Broek Roel W. , Eijkelenboom Astrid , van der Vleuten Carine J. M. , Kamping Eveline J. , Kets Marleen , Verhoeven Bas H. , Grünberg Katrien , Schultze Kool Leo J. , Tops Bastiaan B. J. , Ligtenberg Marjolijn J. L. , Flucke Uta 
Published: January 2019

AbstractVascular malformations are part of overgrowth syndromes characterized by somatic mosaic mutations or rarely by germline mutations. Due to their similarities and diversity, clinicopathological classification can be challenging. A comprehensive targeted Next Generation Sequencing screen using Unique Molecular Identifiers with a technical sensitivity of 1% mutant alleles was performed for frequently mutated positions in ≥21 genes on 319 formalin‐fixed paraffin‐embedded samples. In 132 out of 319 cases pathogenic mosaic mutations were detected affecting genes previously linked to vascular malformations e.g. PIK3CA (n=80), TEK (TIE2) (n=11), AKT1 (n=1), GNAQ (n=7), GNA11 (n=4), IDH1 (n=3), KRAS (n=9), and NRAS (n=1). Six cases harbored a combination of mutations in PIK3CA and in GNA11 (n=2), GNAQ (n=2), or IDH1 (n=2). Aberrations in PTEN and RASA1 with a variant allele frequency approaching 50% suggestive of germline origin were identified in six out of 102 cases tested; four contained a potential second hit at a lower allele frequency. Ninety‐one of the total 142 pathogenic mutations were present at a variant allele frequency <10% illustrating the importance of sensitive molecular analysis. Clinicopathological characteristics showed a broad spectrum and overlap when correlated with molecular data. Sensitive screening of recurrently mutated genes in vascular malformations may help to confirm the diagnosis and reveals potential therapeutic options with a significant contribution of PIK3CA/mTOR and RAS‐MAPK pathway mutations. The co‐existence of two activating pathogenic mutations in parallel pathways illustrates potential treatment challenges and underlines the importance of multigene testing. Detected germline mutations have major clinical impact.
Small Dense Low‐Density Lipoprotein Cholesterol Predicts Cardiovascular Events in Liver Transplant Recipients
Authors: Siddiqui Mohammad Bilal , Arshad Tamoore , Patel Samarth , Lee Emily , Albhaisi Somaya , Sanyal Arun J. , Stravitz R. Todd , Driscoll Carolyn , Sterling Richard K. , Reichman Trevor , Bhati Chandra , Siddiqui Mohammad Shadab 
Published: January 2019

Cardiovascular disease (CVD) is an important cause of morbidity and mortality after liver transplantation (LT). Although LT is associated with dyslipidemia, particularly atherogenic lipoprotein subparticles, the impact of these subparticles on CVD‐related events is unknown. Therefore, the aim of the current study was to evaluate the impact of small dense (sdLDL‐C) low‐density lipoprotein (LDL) cholesterol (LDL‐C) on CVD events. Prospectively enrolled patients (N = 130) had detailed lipid profile consisting of traditional lipid parameters and sdLDL‐C and were followed for CVD events. The primary endpoint was a CVD composite consisting of myocardial infarction (MI), angina, need for coronary revascularization, and cardiac death. Mean age of the cohort was 58 ± 11 years, and the most common etiology of liver disease (LD) was hepatitis C virus (N = 48) and nonalcoholic steatohepatitis (N = 23). A total of 20 CVD events were noted after median follow‐up of 45 months. The baseline traditional profile was similar in patients with and without CVD events. A serum LDL‐C cutoff of 100 mg/dL was unable to identify individuals at risk of a CVD event (P = 0.86). In contrast, serum concentration of atherogenic sdLDL‐C >25 mg/dL was predictive of CVD events with a hazard ratio of 6.376 (95% confidence interval, 2.65, 15.34; P < 0.001). This relationship was independent of diabetes, hypertension, sex, ethnicity, LD, obesity, and statin use. Conclusion: sdLDL‐C independently predicted CVD events whereas LDL‐C did not. Thus, sdLDL‐C may provide a useful clinical tool in risk stratifying and managing patients after LT.
The Senses of Birth intervention to decrease cesarean and prematurity rates in Brazil
Authors: Lansky Sônia , Oliveira Bernardo J. , Peixoto Eliane R.M. , Souza Kleyde V. , Fernandes Luísa M.M. , Friche Amélia A.L. 
Published: January 2019

AbstractObjectiveTo increase knowledge and promote cultural change toward valuing normal birth, and to lower rates of cesarean and unnecessary interventions during childbirth in Brazil via the Senses of Birth (SoB) exhibition.MethodsThe SoB intervention targeted 22 621 participants in three Brazilian cities in 2015. The effects of the exhibition in knowledge, perceptions, and preferences regarding childbirth were analyzed in a multi‐method study. Pre‐ and post‐exhibition survey responses of 17 501 (77.0%) visitors, 1947 (8.6%) non‐pregnant women, and all pregnant women (n=1287) were collected at the exhibition. A follow‐up survey was completed by 555 (43.0%) postpartum women who had participated at SoB while pregnant. Univariate analyses were used to compare before and after changes.ResultsThere was a significant increase in knowledge about normal birth, varying from 10.0% to 25.0% among general visitors (P<0.001) and 27.3% to 42.0% among pregnant women (P<0.001). Perceptions and preferences for normal birth also changed, reaching 83.0% of general visitors and 87.4% of pregnant women.ConclusionSoB was found to effectively improve knowledge about and preference for normal birth. Scaling‐up the intervention might contribute to cultural change toward valuing normal birth, and might decrease the rate of unnecessary cesarean and premature birth in Brazil.
Ameliorating the antimicrobial resistance crisis: phage therapy
Authors: Saha Dibya , Mukherjee Raju 
Published: January 2019

AbstractPropelled by the overuse and inappropriate use of antibiotics, antimicrobial resistance is now widespread in the environment, leaving us with limited drugs for treating a large number of resistant pathogens. The use of bacteriophages that kill bacteria has come up as a viable alternative to circumvent the antimicrobial resistance crisis, and phage therapy‐based approaches are fast advancing in recent times. In this minireview, we try to describe the advantages associated with phage therapy and update the latest developments in the field including the clinical trials that are underway. Particularly, we highlight the synergistic bactericidal effect of phages in the presence of sub‐lethal dose of antibiotics and the potency of lytic phages, and their hydrolytic enzymes in expunging pathogens from drug‐tolerant biofilms and animal farm produce. We also discuss how major challenges, including human immune response to phage components, development of bacterial resistance and elimination of intracellular pathogens, presented as potential setbacks to the implementation of phage therapy is being removed using engineered phages and novel formulations. © 2019 IUBMB Life, 2019
Bone regeneration using three‐dimensional hexahedron channel structured BCP block in rabbit calvarial defects
Authors: Pae Hyung‐Chul , Kang Joo‐Hyun , Cha Jae‐Kook , Lee Jung‐Seok , Paik Jeong‐Won , Jung Ui‐Won , Choi Seong‐Ho 
Published: January 2019

AbstractThe purpose of this study is to evaluate the efficacy of bone regeneration and volume maintenance of the three‐dimensional (3D) structured biphasic calcium phosphate (BCP) block with porous hexahedron channels in a rabbit calvarial model. In this work, four circular defects (diameter: 8 mm) in calvarium of rabbits were randomly assigned to (1) negative control (control), (2) 3D hexahedron channel structured BCP block, (3) deproteinized bovine bone mineral particle, and (4) deproteinized porcine bone mineral particle. Animals were euthanized at 2 (n = 5) and 8 weeks (n = 5). Outcome measures included micro‐computed tomography (CT) and histomorphometrical analysis. Results indicated that in micro‐CT, BCP group showed the highest new bone volume with significant difference compared to control (p = 0.008) at 8 weeks. Histomorphometrically, total augmented area of BCP group was the highest with significant difference compared to control (p = 0.008) at 8 weeks. BCP group also maintained total volume of the original defect without collapsing. BCP block with 3D hexahedron channel structure seems to have favorable osteogenic and volume maintaining ability and highly porous structure might attribute to new bone formation. Further studies regarding the optimal internal structure and porosity of the BCP block bone substitute are needed. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2254–2262, 2019.
BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile
Authors: Guney Eskiler Gamze , Cecener Gulsah , Egeli Unal , Tunca Berrin 
Published: January 2019

AbstractThe objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild‐type (MDA‐MB‐231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA‐MB‐231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis‐related genes (P < 0.01). Additionally, BMN 673 indicated no toxicity on MCF‐10A control cells until a certain concentration and incubation time. However, BMN 673, a novel and selective poly ADP ribose polymerase inhibitor, was more potent in TNBC cells bearing BRCA1 mutant than those with wild‐type BRCA1. In conclusion, our study, for the first time, demonstrated a molecular mechanism of the induction of apoptosis by BMN 673 in TNBC with different genetic profile. However, further investigations regarding the exact molecular mechanisms underlying BMN 673‐inducing apoptotic death and gene‐cell line associations are required.
Heat attenuates sensitivity of mammalian cells to capsaicin
Authors: Sugimoto Naotoshi , Matsuzaki Kentaro , Katakura Masanori , Nakamura Hiroyuki , Ueda Yoshibumi , Yachie Akihiro , Shido Osamu 
Published: January 2019

AbstractThe transient receptor potential (TRP) channels are thermo‐sensors, and transient receptor potential vanilloid (TRPV)1 and V4 are widely expressed in primary afferent neurons and nonneuronal cells. Although heat acclimation is considered as changes of thermoregulatory responses by thermo‐effectors to heat, functional changes of TRP channels in heat acclimation has not been fully elucidated. Here, we investigated whether heat acclimation induces capsaicin tolerance. NIH3T3 cells were incubated at 39.5°C. We determined the expression level of TRPV1 and TRPV4 messenger RNA (mRNA), performed cellular staining of TRPV1 and TRPV4, and investigated actin assembly and activation of the extracellular signal‐regulated kinase (ERK). Exposure to moderate heat decreased the levels of TRPV1 but not TRPV4 mRNA. It also induced stress fiber formation and the intensity of TRPV1 seemed to be decreased by chronic heat stimuli. In addition, heat acclimation attenuated the capsaicin‐induced activation of ERK. Heat acclimation may induce capsaicin tolerance via the downregulation of TRPV1.
Crocin inhibits proliferation and induces apoptosis through suppressing MYCN expression in retinoblastoma
Authors: Deng Liya , Li Jincun , Lu Shiyou , Su Yan 
Published: January 2019

AbstractThe pathogenetic mechanisms of retinoblastoma are still not yet fully elucidated, putting limits to efficacious treatment. Crocin is the main component of saffron, which exhibits significant antitumorigenic properties. The aim of this paper is to investigate the effect of crocin on retinoblastoma. The effects of crocin on the proliferation of human retinoblastoma cells were determined by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, cell number assay, and colony formation assay. Cell apoptosis induced by crocin was measured by flow cytometry analysis. Cleaved poly(ADP‐ribose) polymerase and cleaved caspase‐3 were tested by western blot analysis. The expression levels of MYCN were assessed by western blot and quantitative polymerase chain reaction and the stability of MYCN messenger RNA was determined by in vitro RNA degradation assays. We found that crocin significantly inhibited the cell proliferation and clonogenicity and induced cell apoptosis in Y79 and WERI‐RB‐1 cells. In addition, crocin treatment significantly reduced the expression and the stability of MYCN. Besides, overexpression of MYCN rescued the inhibitory effect of crocin in Y79 cells. Our findings suggest that crocin exhibits antitumorigenic effects in human retinoblastoma cell lines through a MYCN‐dependent manner, which may provide guidance to logical therapeutic designs in prevention and treatment of retinoblastoma.
Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway
Authors: Song Jianping , Shu Hongchun , Zhang Ling , Xiong Jianping 
Published: January 2019

AbstractObjectiveAngiogenesis plays a key role in the tumorigenesis and progression of colorectal cancer (CRC). In this study, we investigated the effect of long noncoding RNA (lncRNA) GAS5 on the angiogenesis, invasion, and metastasis of CRC, and the involvement of the Wnt/β‐catenin signaling pathway.MethodsCRC tissues and adjacent normal tissues were collected from 52 patients with CRC. GAS5 expression was determined in vivo and in vitro by real‐time quantitative polymerase chain reaction (RT‐qPCR). Then RT‐qPCR and Western blot were used to identify expression of key genes of Wnt/β‐catenin signaling pathway. CRC cells with lowest GAS5 expression were selected and subjected to si‐GAS5, oe‐GAS5, or XAV939 to validate the effect of GAS5 and Wnt/β‐catenin signaling pathway on CRC cell activities. The activation of Wnt/β‐catenin signaling pathway was determined in response to GAS5. Subcutaneous tumor growth and microvascular density were observed in nude mice, in which in vivo metastasis was observed following tail vein injection of CRC cells.ResultsInitially, poor expression of GAS5 was observed in CRC tissues and cells. Upregulated GAS5 repressed CRC cell invasion and migration in vitro, as well as subcutaneous tumor growth, angiogenesis, and liver metastases in vivo. Furthermore, the Wnt/β‐catenin signaling pathway was determined to be activated in CRC tissues and cells, while its activation was inhibited by GAS5. The Wnt/β‐catenin signaling pathway promoted the CRC cell invasion and migration in vitro, subcutaneous tumor growth, angiogenesis and, liver metastases in vivo.ConclusionTaken together, the results of the study conclude that lncRNA GAS5 inhibited the activation of the Wnt/β‐catenin signaling pathway, thereby suppressing the angiogenesis, invasion, and metastasis of CRC.
Construction of a chimeric antigen receptor bearing a nanobody against prostate a specific membrane antigen in prostate cancer
Authors: Hassani Mahmoud , Hajari Taheri Fatemeh , Sharifzadeh Zahra , Arashkia Arash , Hadjati Jamshid , van Weerden Wytske M. , Modarressi Mohammad Hossein , Abolhassani Mohsen 
Published: January 2019

AbstractAdoptive transfer of T cells expressing chimeric antigen receptors (CARs) is considered to be a novel anticancer therapy. To date, in most cases, single‐chain variable fragments (scFvs) of murine origin have been used in CARs. However, this structure has limitations relating to the potential immunogenicity of mouse antigens in humans and the relatively large size of scFvs. For the first time, we used camelid nanobody (VHH) to construct CAR T cells against prostate specific membrane antigen (PSMA). The nanobody against PSMA (NBP) was used to show the feasibility of CAR T cells against prostate cancer cells. T cells were transfected, and then the surface expression of the CAR T cells was confirmed. Then, the functions of VHH‐CAR T cell were evaluated upon coculture with prostate cancer cells. At the end, the cytotoxicity potential of NBPII‐CAR in T cells was approximated by determining the cell surface expression of CD107a after encountering PSMA.Our data show the specificity of VHH‐CAR T cells against PSMA+ cells (LNCaP), not only by increasing the interleukin 2 (IL‐2) cytokine (about 400 pg/mL), but also the expression of CD69 by almost 38%. In addition, VHH‐CAR T cells were proliferated by nearly 60% when cocultured with LNCaP, as compared with PSMA negative prostate cancer cell (DU‐145), which led to the upregulation of CD107a in T cells upto 31%.These results clearly show the possibility of using VHH‐based CAR T cells for targeted immunotherapy, which may be developed to target virtually any tumor‐associated antigen for adoptive T‐cell immunotherapy of solid tumors.
lncRNA MIR503HG functioned as a tumor suppressor and inhibited cell proliferation, metastasis and epithelial‐mesenchymal transition in bladder cancer
Authors: Qiu Feng , Zhang Ming‐ran , Zhou Zhen , Pu Jin‐xian , Zhao Xiao‐jun 
Published: January 2019

AbstractBladder cancer is the most common malignancy with high recurrence. Currently, the long noncoding RNAs (lncRNAs) have been suggested to play vital roles in the pathogenesis of bladder cancer. The present study investigated the role of lncRNA MIR503 host gene (MIR503HG) in the pathogenesis of bladder cancer by using both in vitro and in vivo functional assays. The expression of MIR503HG was downregulated in bladder cancer tissues and cell lines. Low expression of MIR503HG was associated with advanced tumor stage, advanced histological grade, and lymph node metastasis. Ectopic expression of MIR503HG inhibited cell proliferation, cell growth, cell invasion, and migration, and also promoted cell apoptosis and inhibited cell cycle progression in SW780 cells. In parallel, T24 cells were used for loss‐of‐function studies. Knockdown of MIR503HG promoted the cancer cell proliferation and increased the migration and invasion abilities of T24 cells. In addition, knockdown of MIR503HG reduced the cell apoptotic rate in cancer cells and promoted cell cycle progression. Furthermore, MIR503HG overexpression decreased the epithelial‐mesenchymal transition‐related mRNA and protein levels of ZEB1, Snail, N‐cadherin, and vimentin, with an increase in E‐cadherin level. Consistently, knockdown of MIR503HG showed the opposite effects. In vivo xenograft, nude mice results showed that overexpression of MIR503HG suppressed the tumor growth and tumor metastasis. In conclusion, our results identified a novel lncRNA MIR503HG that exhibited significant antiproliferation, antimigration/invasion effects on bladder cancer cells both in vitro and in vivo, which may hold a therapeutic promise to treat bladder cancer.
Changes in mindfulness facets in a dialectical behaviour therapy skills training group program for borderline personality disorder
Authors: Mitchell Roberta , Roberts Rachel , Bartsch Dianna , Sullivan Thomas 
Published: January 2019

AbstractObjectiveWe examined the relationship between mindfulness skills acquisition and symptom reduction.MethodParticipants were adults (n = 35) with a diagnosis of borderline personality disorder (BPD) who completed a 20‐week dialectical behaviour therapy (DBT) skills training group program in a community mental health setting. We used the Five Facet Mindfulness Questionnaire, which measures five dimensions of mindfulness: observing, describing, acting with awareness, nonjudging of inner experience, and nonreactivity to inner experience.ResultsLinear mixed model results suggested that increases in some mindfulness facets, especially in acting with awareness and nonjudging of inner experience were more strongly related to changes during treatment including reductions in BPD symptomology, depression, and distress with increases in nonjudging also predicting a reduction in the hospital use.ConclusionsThese results suggest the usefulness of emphasising mindfulness skills that develop awareness and encourage a nonjudgmental stance.
Increased long noncoding RNA LASP1‐AS is critical for hepatocellular carcinoma tumorigenesis via upregulating LASP1
Authors: Yin Ling , Chen Yihong , Zhou You , Deng Ganlu , Han Ying , Guo Cao , Li Yiyi , Zeng Shan , Shen Hong 
Published: January 2019

AbstractAberrant long noncoding RNAs (lncRNA) have been proved to be associated with the many types of malignant tumors (including hepatocellular carcinoma [HCC]). In this study, a lncRNAs and mRNAs microarray analysis was performed in three pairs of HCC patitents’ tumor. We found lncRNA LIM and SH3 protein 1 antisense (LASP1‐AS) and its sense‐cognate gene LIM and SH3 protein 1 (LASP1) were upregulated in HCC and both are correlated with poorer prognosis and lower survival of HCC patients. Meanwhile, the expression of LASP1‐AS correlated positively with LASP1 expression in HCC tissues. LASP1‐AS promoted the proliferation, migration, and invasion abilities of HCC in vitro and vivo by enhancing LASP1 expression. Our study explored lncRNA LASP1‐AS as an oncogene in HCC and promoted proliferation and metastasis capabilities of HCC via increasing the expression of its sense‐cognate gene LASP1. LncRNA LASP1‐AS might be a potential valuable prognostic biomarker and potential therapeutic target of HCC.
Characterization of Cre recombinase  mouse lines enabling cell type‐specific targeting of postnatal intervertebral discs
Authors: Zheng Yixin , Fu Xuejie , Liu Qingbai , Guan Shengqi , Liu Cunchang , Xiu Chunmei , Gong Tingting , Jin Hongting , Saijilafu  , Zhang Zunyi , Chen Di , Chen Jianquan 
Published: January 2019

AbstractCre/loxP technology is an important tool for studying cell type‐specific gene functions. Cre recombinase mouse lines, including Agc1‐CreERT2, Col2a1‐Cre; Col2a1‐CreERT2, Shh‐Cre, Shh‐CreERT2, and Osx‐Cre, have been proven to be valuable tools to elucidate the biology of long bones, yet the information for their activity in postnatal intervertebral disc (IVD) tissues was very limited. In this study, we used R26‐mTmG fluorescent reporter to systematically analyze cell specificity and targeting efficiency of these six mouse lines in IVD tissues at postnatal growing and adult stages. We found that Agc1‐CreERT2 is effective to direct recombination in all components of IVDs, including annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplate (CEP), upon tamoxifen induction at either 2 weeks or 2 months of ages. Moreover, Col2a1‐Cre targets most of the cells in IVDs, except for some cells in the outer AF (OAF) and NP. In contrast, the activity of Col2a1‐CreERT2 is mainly limited to the IAF of IVD tissues at either stage of tamoxifen injection. Similarly, Shh‐Cre directs recombination specifically in all NP cells, whereas Shh‐CreERT2 is active only in a few NP cells when tamoxifen is administered at either stage. Finally, Osx‐Cre targets cells in the CEP, but not in the NP or AF of IVDs tissues at these two stages. Thus, our data demonstrated that all these Cre lines can direct recombination in IVD tissues at postnatal stages with different cell type specificity and/or targeting efficiency, and can, therefore, serve as valuable tools to dissect cell type‐specific gene functions in IVD development and homeostasis.