bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of bioactive polysaccharide from Lachnum sp. acts synergistically with 5‐fluorouracil against human hepatocellular carcinoma
Authors: Zong Shuai , Li Jinglei , Yang Liu , Huang Qianli , Hou Guohua , Ye Ziyang , Ye Ming 
Published: February 2019

AbstractThe antimetabolite 5‐fluorouracil (5‐FU) is a widely used antitumor agent, however the overall response rate to 5‐FU as a single agent is usually limited. Herein, how Lachnum expolysaccharide (LEP‐2a), a type of active polysaccharide isolated from
Lachnum sp., acted synergistically with 5‐FU on HepG2 cells was investigated. It was found that LEP‐2a notably enhanced 5‐FU sensitivity in HepG2 cells in a synergistic manner. After combination treatment of 5‐FU and LEP‐2a, Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathway were inactivated. In addition, combination treatment induced generation of reactive oxygen species, decreased the levels of intracellular antioxidant enzymes and triggered mitochondrial apoptosis pathway. Furthermore, 5‐FU combined with LEP‐2a also resulted in p53 activation and NF‐κB inhibition, and cell cycle arrest in the S phase as well as cell metastasis stagnation. Interestingly, LEP‐2a treatment also blocked the DNA damage repair procedure. These findings demonstrate that LEP‐2a enhanced 5‐FU sensitivity and combination of 5‐FU and LEP‐2a exerts synergistic antitumor efficiency through multiple approaches.
Strategies to inhibit arsenic trioxide‐induced cardiotoxicity in acute promyelocytic leukemia
Authors: Haybar Habib , Shahrabi Saeid , Rezaeeyan Hadi , Jodat Hosein , Saki Najmaldin 
Published: February 2019

AbstractObjectiveArsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO‐induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity.MethodsThe key search terms were “arsenic trioxide,” “acute promyelocytic leukemia,” “cardiotoxicity,” “molecular pathway,” and “biomarker.”ResultsStudies have indicated the involvement of several molecular pathways in ATO‐induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity.ConclusionFinally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO‐induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.
8‐chloro‐adenosine activity in FLT3‐ITD acute myeloid leukemia
Authors: Buettner Ralf , Nguyen Le Xuan Truong , Kumar Bijender , Morales Corey , Liu Chao , Chen Lisa S. , Pemovska Tea , Synold Timothy W. , Palmer Joycelynne , Thompson Ryan , Li Ling , Hoang Dinh Hoa , Zhang Bin , Ghoda Lucy , Kowolik Claudia , Kontro Mika , Leitch Calum , Wennerberg Krister , Yu Xiaochun , Chen Ching‐Cheng , Horne David , Gandhi Varsha , Pullarkat Vinod , Marcucci Guido , Rosen Steven T. 
Published: February 2019

AbstractNucleoside analogs represent the backbone of several distinct chemotherapy regimens for acute myeloid leukemia (AML) and combination with tyrosine kinase inhibitors has improved survival of AML patients, including those harboring the poor‐risk FLT3‐ITD mutation. Although these compounds are effective in killing proliferating blasts, they lack activity against quiescent leukemia stem cells (LSCs), which contributes to initial treatment refractoriness or subsequent disease relapse. The reagent 8‐chloro‐adenosine (8‐Cl‐Ado) is a ribose‐containing, RNA‐directed nucleoside analog that is incorporated into newly transcribed RNA rather than in DNA, causing inhibition of RNA transcription. In this report, we demonstrate antileukemic activities of 8‐Cl‐Ado in vitro and in vivo and provide mechanistic insight into the mode of action of 8‐Cl‐Ado in AML. 8‐Cl‐Ado markedly induced apoptosis in LSC, with negligible effects on normal stem cells. 8‐Cl‐Ado was particularly effective against AML cell lines and primary AML blast cells harboring the FLT3‐ITD mutation. FLT3‐ITD is associated with high expression of miR‐155. Furthermore, we demonstrate that 8‐Cl‐Ado inhibits miR‐155 expression levels accompanied by induction of DNA‐damage and suppression of cell proliferation, through regulation of miR‐155/ErbB3 binding protein 1(Ebp1)/p53/PCNA signaling. Finally, we determined that combined treatment of NSG mice engrafted with FLT3‐ITD
+ MV4−11 AML cells with 8‐Cl‐Ado and the FLT3 inhibitor AC220 (quizartinib) synergistically enhanced survival, compared with that of mice treated with the individual drugs, suggesting a potentially effective approach for FLT3‐ITD AML patients.
Use of stem cells as carriers of oncolytic viruses for cancer treatment
Authors: Zendedel Elham , Atkin Stephen L. , Sahebkar Amirhossein 
Published: February 2019

AbstractTherapeutic application of stem cells and oncolytic viruses in cancer treatment has rapidly increased in the last decade. Oncolytic viruses are considered as a new class of anticancer agents because of their ability to selectively infect and destroy cancer cells. Furthermore, regarding the specific migratory capacity of stem cells, they can be used as carriers or vectors targeting metastatic cancer. Promising results have been reported regarding the use of stem cells and oncolytic viruses as a therapeutic approach for the treatment of metastatic cancer. The present review aimed to determine the approaches involved in the use of the tumor‐homing capacity of stem cells for cancer treatment.
The roles of signaling pathways in liver repair and regeneration
Authors: Valizadeh Amir , Majidinia Maryam , Samadi‐Kafil Hossein , Yousefi Mehdi , Yousefi Bahman 
Published: February 2019

AbstractThe liver has remarkable regeneration potency that restores liver mass and sustains body hemostasis. Liver regeneration through signaling pathways following resection or moderate damages are well studied. Various cell signaling, growth factors, cytokines, receptors, and cell types implicated in liver regeneration undergo controlled hypertrophy and proliferation. Some aspects of liver regeneration have been discovered and many investigations have been carried out to identify its mechanisms. However, for optimizing liver regeneration more should be understood about mechanisms that control the growth of hepatocytes and other liver cell types in adults. The current paper deals with the possible applicability of liver regeneration signaling pathways as a target for therapeutic approaches and preventing various liver damages. Furthermore, the latest findings of spectrum‐specific signaling pathway mechanisms that underlie liver regeneration are briefly described.
Criss‐cross heart with double‐outlet right ventricle, subpulmonary ventricular septal defect, and bicuspid pulmonary valve
Authors: Ren Sihua , Ma Chunyan , Li Songbai 
Published: February 2019

AbstractCriss‐cross heart (CCH) is an extremely rare complex congenital heart malformation. It accounts for less than 0.1% of congenital heart diseases. Here, we describe a unique case of CCH with double‐outlet right ventricle, huge subpulmonary ventricular septal defect, bicuspid pulmonary valve, and right‐hand aortic arch. The anatomic features were observed with echocardiography, and the diagnosis was confirmed at surgery. Many variations of CCH have been described. The present case expands the spectrum of this entity and may provide new insight into this complex anatomy.
A novel approach to offering additional genomic findings—A protocol to test a two‐step approach in the healthcare system
Authors: Martyn Melissa , Kanga‐Parabia Anaita , Lynch Elly , James Paul A. , Macciocca Ivan , Trainer Alison H. , Halliday Jane , Keogh Louise , Wale Janney , Winship Ingrid , Bogwitz Michael , Valente Giulia , Walsh Maie , Downie Lilian , Amor David , Wallis Mathew , Cunningham Fiona , Burgess Matthew , Brown Natasha J. , Jarmolowicz Anna , Lunke Sebastian , Goranitis Ilias ,   Melbourne Genomics Health Alliance, Gaff Clara L. 
Published: February 2019

AbstractInternationally, the practice of offering additional findings (AFs) when undertaking a clinically indicated genomic test differs. In the USA, the recommendation is to include analysis for AFs alongside diagnostic analysis, unless a patient opts‐out, whereas European and Canadian guidelines recommend opt‐in models. These guidelines all consider the offer of AFs as an activity concurrent with the offer of diagnostic testing. This paper describes a novel two‐step model for managing AFs within the healthcare system in Victoria, Australia and presents the study protocol for its evaluation. Adults who have received results of diagnostic whole exome sequencing undertaken within the healthcare system are invited to attend a genetic counseling appointment to consider reanalysis of their stored genomic data for AFs. The evaluation protocol addresses uptake, decision‐making, understanding, counseling challenges, and explores preferences for future models of care. Recruitment commenced in November 2017 and will cease when 200 participants have been approached. When the study is concluded, the evaluation results will contribute to the evidence base guiding approaches to counseling and models of care for AFs.
Evaluation of polyol‐made Gd3+‐substituted Co0.6Zn0.4Fe2O4 nanoparticles as high magnetization MRI negative contrast agents
Authors: Mnasri Walid , Bentahar Lotfi , Nowak Sophie , Sandre Olivier , Boissière Michel , Ammar Souad 
Published: February 2019

AbstractThe structural, microstructural, and magnetic properties of ~5‐nm‐sized Co0.6Zn0.4Fe2 − xGdxO4 nanoparticles were investigated in order to evaluate their capability to enhance the magnetic resonance imaging contrast as high magnetization agents. A focus was made on the solubility of Gd3+ cations within the spinel lattice. By coupling X‐ray diffraction to X‐ray fluorescence spectroscopy, we demonstrated that only a limited fraction of Gd3+ can substitute Fe3+ ions into the whole crystal structure and does not exceed 6 at.‐%. At this concentration, the room temperature (27°C) saturation magnetizations of the prepared superparamagnetic nanocrystals were found to be close to 80 emu g−1. Coating these nanoparticles with hydrophilic dopamine ligands leads to the formation of ~50‐nm‐sized clusters in water. As a consequence, relatively high r2/r1 ratios of transverse to longitudinal proton relaxivities and high r2 values were measured in the resulting colloids at physiological temperature (37°C) for an applied magnetic field of 1.41 T: 33 and 188 mM−1 sec−1, respectively, for the richest system in gadolinium. Moreover, after incubation with healthy human model cells (fibroblasts) at doses as high as 10 μg mL−1, they induce neither cellular death nor acute cellular damage making the engineered probes particularly valuable for negative magnetic resonance imaging contrasting.
Unraveling the host's immune response to infection: Seeing is believing
Authors: Scott Brittney N V , Sarkar Tina , Kratofil Rachel M , Kubes Paul , Thanabalasuriar Ajitha 
Published: February 2019

Abstract
It has long been appreciated that understanding the interactions between the host and the pathogens that make us sick is critical for the prevention and treatment of disease. As antibiotics become increasingly ineffective, targeting the host and specific bacterial evasion mechanisms are becoming novel therapeutic approaches. The technology used to understand host-pathogen interactions has dramatically advanced over the last century. We have moved away from using simple in vitro assays focused on single-cell events to technologies that allow us to observe complex multicellular interactions in real time in live animals. Specifically, intravital microscopy (IVM) has improved our understanding of infection, from viral to bacterial to parasitic, and how the host immune system responds to these infections. Yet, at the same time it has allowed us to appreciate just how complex these interactions are and that current experimental models still have a number of limitations. In this review, we will discuss the advances in vivo IVM has brought to the study of host-pathogen interactions, focusing primarily on bacterial infections and innate immunity.
Modified MR dispersion imaging in prostate dynamic contrast‐enhanced MRI
Authors: Sung Kyunghyun 
Published: February 2019

BackgroundAn estimation of an intravascular dispersion parameter was previously proposed to improve the overall accuracy and precision of the model parameters, but the high computation complexity can limit its practical usability in prostate dynamic contrast‐enhanced MRI (DCE‐MRI).PurposeTo compare and evaluate the model fitting uncertainty and error in the model parameter estimation using different DCE‐MRI analysis models and to evaluate the ability of the intravascular dispersion parameter to delineate between noncancerous and cancerous prostate tissue in the transition and peripheral zones.Study TypeRetrospective.PopulationFifty‐three patients who underwent radical prostatectomy.Field Strength/Sequence3 T/3D RF‐spoiled gradient echo sequence.AssessmentThe coefficient of variation was used to assess the model fitting uncertainty by adding random noise to the time–concentration curves, and the Akaike information criterion was used to assess the model fitting error. The parametric maps derived from four DCE‐MRI analysis models were evaluated by evaluating the delineation between noncancerous tissue and prostate cancer or clinically significant prostate cancer.Statistical TestsThe receiver operating curve analysis was performed to compare the ability to delineate between noncancerous and prostate cancer tissue in the transition and peripheral zones.ResultsBoth MR dispersion imaging (MRDI) and Weinmann analysis models had the maximum coefficient of variation in different tissue types, while the model fitting uncertainty of modified (m)MRDI was similar to the standard Toft model. In mMRDI, the model fitting error was minimum, and the delineation between noncancerous and clinically significant prostate cancer tissue was improved in both transition (area under the curve [AUC] = 0.92) and peripheral zones (AUC = 0.92), in comparison with MRDI (AUC = 0.89 and AUC = 0.85, respectively).Data ConclusionThe mMRDI showed promising results in detecting prostate cancer while maintaining a similar model fitting uncertainty.Level of Evidence: 3Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2019;50:1307–1317.
Variation in cardiovascular magnetic resonance myocardial contouring: Insights from an international survey
Authors: Moody William E. , Hudsmith Lucy E. , Holloway Ben , Treibel Thomas A. , Davies Rhodri , Kozor Rebecca , Hamilton‐Craig Christian , Edwards Nicola C. , Bradlow William M. , Moon James C. , Steeds Richard P. ,   On behalf of the British Society of Cardiovascular Magnetic Resonance and the Australia and New Zealand Working Group for Cardiovascular Magnetic Resonance
Published: February 2019

Level of Evidence: 5Technical Efficacy Stage: 2J. Magn. Reson. Imaging 2019;50:1336–1338.
Optimization and repeatability of multipool chemical exchange saturation transfer MRI of the prostate at 3.0 T
Authors: Evans Vincent Stephen , Torrealdea Francisco , Rega Marilena , Brizmohun Appayya Mrishta , Latifoltojar Arash , Sidhu Harbir , Kim Mina , Kujawa Aaron , Punwani Shonit , Golay Xavier , Atkinson David 
Published: February 2019

BackgroundChemical exchange saturation transfer (CEST) can potentially support cancer imaging with metabolically derived information. Multiparametric prostate MRI has improved diagnosis but may benefit from additional information to reduce the need for biopsies.PurposeTo optimize an acquisition and postprocessing protocol for 3.0 T multipool CEST analysis of prostate data and evaluate the repeatability of the technique.Study TypeProspective.SubjectsFive healthy volunteers (age range: 24–47 years; median age: 28 years) underwent two sessions (interval range: 7–27 days; median interval: 20 days) and two biopsy‐proven prostate cancer patients were evaluated once. Patient 1 (71 years) had a Gleason 3 + 4 transition zone (TZ) tumor and patient 2 (55 years) had a Gleason 4 + 3 peripheral zone (PZ) tumor.Field Strength3.0 T. Sequences run: T2‐weighted turbo‐spin‐echo (TSE); diffusion‐weighted imaging; CEST; WASABI (for B0 determination).AssessmentSaturation, readout, and fit‐model parameters were optimized to maximize in vivo amide and nuclear Overhauser effect (NOE) signals. Repeatability (intrasession and intersession) was evaluated in healthy volunteers. Subsequently, preliminary evaluation of signal differences was made in patients. Regions of interest were drawn by two post‐FRCR board‐certified readers, both with over 5 years of experience in multiparametric prostate MRI.Statistical TestsRepeatability was assessed using Bland–Altman analysis, coefficient of variation (CV), and 95% limits of agreement (LOA). Statistical significance of CEST contrast was calculated using a nonparametric Mann–Whitney U‐test.ResultsThe optimized saturation scheme was found to be 60 sinc‐Gaussian pulses with 40 msec pulse duration, at 50% duty‐cycle with continuous‐wave pulse equivalent B1 power (B1CWPE) of 0.92 μT. The magnetization transfer (MT) contribution to the fit‐model was centered at –1.27 ppm. Intersession coefficients of variation (CVs) of the amide, NOE, and magnetization transfer (MT) and asymmetric magnetization transfer ratio (MTRasym) signals of 25%, 23%, 18%, and 200%, respectively, were observed. Fit‐metric and MTRasym CVs agreed between readers to within 4 and 10 percentage points, respectively.Data ConclusionSignal differences of 0.03–0.10 (17–43%) detectable depending upon pool, with MT the most repeatable (signal difference of 17–22% detectable).Level of Evidence: 2Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:1238–1250.
New insights into the degradation mechanism of cellulose nitrate in cinematographic films by Raman microscopy
Authors: Neves Artur , Angelin Eva Mariasole , Roldão Élia , Melo Maria João 
Published: February 2019

AbstractThe degradation of cellulose nitrate cinematographic films stored inside an aluminum can was studied by infrared spectroscopy and Raman microscopy. Cellulose nitrate image heritage is strongly susceptible to degradation, being a major conservation challenge. Infrared spectroscopy has been the traditional technique in the assessment of the polymer degradation, but new in situ diagnostic tools to monitor the initial stages of degradation are needed. In this work, cellulose nitrate films were produced and irradiated as aging references to understand how chemical changes were observed in Raman spectroscopy. In comparison with infrared spectroscopy, this technique confirmed the mechanisms proposed in the literature and, at advanced stages of degradation, provided new relevant information detecting an intense peak at 1046 cm−1 associated to nitric acid. Comparing these results with the cinematographic films, it was observed that the plasticizers, which identification was more straightforward using Raman microscopy, have contributions in the regions were chemical changes occur, making it difficult to draw conclusions. Nevertheless, nitric acid and silver nitrate peaks were found in Raman spectra confirming the unstable and noxious environment inside de aluminum can and proving that Raman microscopy can be a valuable complementary in situ technique for cellulose nitrate degradation studies.
DFT computational schemes for 15N NMR chemical shifts of the condensed nitrogen‐containing heterocycles
Authors: Semenov Valentin A. , Samultsev Dmitry O. , Krivdin Leonid B. 
Published: February 2019

AbstractA systematic density functional theory (DFT) study of the accuracy factors (functionals, basis sets, and solvent effects) for the computation of 15N NMR chemical shifts has been performed in the series of condensed nitrogen‐containing heterocycles. The behavior of the most representative functionals was examined based on the benchmark calculations of 15N NMR chemical shifts in the reference set of compounds. It was found that the best agreement with experiment was achieved with OLYP functional in combination with aug‐pcS‐3(N)//pc‐2 locally dense basis set scheme providing mean absolute error of 5.2 ppm in the range of about 300 ppm. Taking into account solvent effects was performed within a general Tomasi's polarizable continuum model scheme. It was also found that computationally demanding supermolecular solvation model computations essentially improved some “difficult” cases, as was illustrated with phenanthroline dissolved in methanol. Based on the performed calculations, some 200 unknown 15N NMR chemical shifts were predicted with a high level of confidence for about 50 real‐life condensed nitrogen‐containing heterocycles, which could serve as a practical guide in structural elucidation of this class of compounds.
Measurement of synovial tissue volume in knee osteoarthritis using a semiautomated MRI‐based quantitative approach
Authors: Perry Thomas A. , Gait Andrew , O’Neill Terence W. , Parkes Matthew J. , Hodgson Richard , Callaghan Michael J. , Arden Nigel K. , Felson David T. , Cootes Timothy F. 
Published: February 2019

PurposeSynovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation.MethodsThirty‐two sagittal T1‐weighted fat‐suppressed contrast‐enhanced MRIs were assessed for STV by a single observer using 1) manual segmentation and 2) a semiautomated approach. We compared the STV analysis using the semiautomated and manual segmentation methods, including the time taken to complete the assessments. We also examined the reliability of STV assessment using the semiautomated method in a subset of 12 patients who had participated in a clinical trial of vitamin D therapy in knee osteoarthritis.ResultsThere was no significant difference in STV using the semiautomated quantitative method compared to manual segmentation, mean difference = 207.2 mm3 (95% confidence interval −895.2 to 1309.7). The semiautomated method was significantly quicker than manual segmentation (18 vs. 71 min). For the semiautomated method, intraobserver agreement was excellent (intraclass correlation coefficient (3,1) = 0.99) and interobserver agreement was very good (intraclass correlation coefficient (3,1) = 0.83).ConclusionWe describe the application of a semiautomated method that is accurate, reliable, and quicker than manual segmentation for assessment of STV. The method may help increase efficiency of image assessment in large imaging studies and may also assist investigation of treatment efficacy in knee osteoarthritis.