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https://www.readbyqxmd.com/read/28647567/stearoyl-coa-desaturase-regulates-sorafenib-resistance-via-modulation-of-er-stress-induced-differentiation
#1
Mark Kin Fai Ma, Eunice Yuen Ting Lau, Doris Hoi Wing Leung, Jessica Lo, Nicole Pui Yu Ho, Lily Kwan Wai Cheng, Stephanie Ma, Chi Ho Lin, John A Copland, Jin Ding, Regina Cheuk Lam Lo, Irene Oi Lin Ng, Terence Kin Wah Lee
We investigated the functional role and clinical significance of Stearoyl CoA desaturase-1 (SCD1) mediated endoplasmic reticulum (ER) stress in regulation of liver tumor-initiating cells (T-ICs) and sorafenib resistance, aiming to develop a novel therapeutic strategy against hepatocellular carcinomas (HCCs) METHODS We evaluated the clinic-pathological relevance of SCD1 and its correlation with sorafenib resistance in large cohorts of HCC clinical samples by qPCR and immunohistochemical analyses. Lentiviral-based overexpression and knockdown approaches were performed to characterize functional roles of SCD1 in regulation of liver T-ICs and sorafenib resistance...
June 21, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28647485/dynamic-network-model-with-continuous-valued-nodes-for-longitudinal-brain-morphometry
#2
Rong Chen, Yuanjie Zheng, Erika Nixon, Edward H Herskovits
Longitudinal brain morphometry probes time-related brain morphometric patterns. We propose a method called dynamic network modeling with continuous valued nodes to generate a dynamic brain network from continuous valued longitudinal morphometric data. The mathematical framework of this method is based on state-space modeling. We use a bootstrap-enhanced least absolute shrinkage operator to solve the network-structure generation problem. In contrast to discrete dynamic Bayesian network modeling, the proposed method enables network generation directly from continuous valued high-dimensional short sequence data, being free from any discretization process...
June 21, 2017: NeuroImage
https://www.readbyqxmd.com/read/28646906/modulation-of-oxidative-phosphorylation-and-redox-homeostasis-in-mitochondrial-ndufs4-deficiency-via-mesenchymal-stem-cells
#3
Marlen Melcher, Katharina Danhauser, Annette Seibt, Özer Degistirici, Fabian Baertling, Arun Kumar Kondadi, Andreas S Reichert, Werner J H Koopman, Peter H G M Willems, Richard J Rodenburg, Ertan Mayatepek, Roland Meisel, Felix Distelmaier
BACKGROUND: Disorders of the oxidative phosphorylation (OXPHOS) system represent a large group among the inborn errors of metabolism. The most frequently observed biochemical defect is isolated deficiency of mitochondrial complex I (CI). No effective treatment strategies for CI deficiency are so far available. The purpose of this study was to investigate whether and how mesenchymal stem cells (MSCs) are able to modulate metabolic function in fibroblast cell models of CI deficiency. METHODS: We used human and murine fibroblasts with a defect in the nuclear DNA encoded NDUFS4 subunit of CI...
June 24, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28646754/free-energy-analysis-of-cell-spreading
#4
Eóin McEvoy, Vikram S Deshpande, Patrick McGarry
In this study we present a steady-state adaptation of the thermodynamically motivated stress fiber (SF) model of Vigliotti et al. (2015). We implement this steady-state formulation in a non-local finite element setting where we also consider global conservation of the total number of cytoskeletal proteins within the cell, global conservation of the number of binding integrins on the cell membrane, and adhesion limiting ligand density on the substrate surface. We present a number of simulations of cell spreading in which we consider a limited subset of the possible deformed spread-states assumed by the cell in order to examine the hypothesis that free energy minimization drives the process of cell spreading...
June 7, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28645476/relation-of-coronary-artery-calcium-score-and-risk-of-cancer-from-a-danish-population-based-follow-up-study-in-patients-who-underwent-cardiac-computed-tomography
#5
Nicklas Vinter, Amanda M S Christesen, Leif S Mortensen, Jes S Lindholt, Søren P Johnsen, Anne Tjønneland, Lars Frost
Evidence of a causal link between atherosclerosis and cancer is sparse and conflicting. Therefore, we examined the association between extent of coronary atherosclerosis determined by coronary artery calcium score (CACS) and risk of cancer. We conducted a historical population-based cohort study of 28,549 cancer-free patients identified in the Western Denmark Heart Registry. All patients underwent cardiac computed tomography for measurement of CACS for suspected coronary artery disease. The outcome was an incident cancer diagnosis: total, tobacco-related, lung, prostate, breast, and colorectal...
May 30, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28645462/analgosedation-practices-and-the-impact-of-sedation-depth-on-clinical-outcomes-among-patients-requiring-mechanical-ventilation-in-the-emergency-department-a-cohort-study
#6
Robert J Stephens, Enyo Ablordeppey, Anne M Drewry, Christopher Palmer, Brian T Wessman, Nicholas M Mohr, Brian W Roberts, Stephen Y Liang, Marin H Kollef, Brian M Fuller
BACKGROUND: Analgesia and sedation are cornerstone therapies for mechanically ventilated patients. Despite data showing that early deep sedation in the intensive care unit influences outcome, this has not been investigated in the emergency department (ED). Therefore, ED-based sedation practices, and their influence on outcome, remain incompletely defined. This study's objectives were to describe ED sedation practices in mechanically ventilated patients, and to test the hypothesis that ED sedation depth is associated with worse outcomes METHODS: This was a cohort study on a prospectively compiled ED registry of adult, mechanically ventilated patients at a single academic medical center...
June 20, 2017: Chest
https://www.readbyqxmd.com/read/28645370/xenopus-laevis-as-model-system-to-study-dna-damage-response-and-replication-fork-stability
#7
Vincenzo Sannino, Federica Pezzimenti, Stefania Bertora, Vincenzo Costanzo
Although many players of the DNA damage response and DNA repair have been identified in several systems their biochemical role is still poorly understood. The use of the Xenopus laevis egg extract cell-free system allowed biochemical dissection of DNA replication and cell cycle events in a complex biological context. The possibility of manipulating the protein content by using protein depletion procedures makes egg extract a powerful system to study proteins whose inactivation results in cellular lethality...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28644151/ecg-based-4d-dose-reconstruction-of-cardiac-arrhythmia-ablation-with-carbon-ion-beams-application-in-a-porcine-model
#8
Daniel Richter, H Immo Lehmann, Anna Eichhorn, Anna M Constantinescu, Robert Kaderka, Matthias Prall, Patrick Lugenbiel, Mitsuru Takami, Dierk Thomas, Christoph Bert, Marco Durante, Douglas L Packer, Christian Graeff
Noninvasive ablation of cardiac arrhythmia by scanned particle radiotherapy is highly promising, but especially challenging due to cardiac and respiratory motion. Irradiations for catheter-free ablation in intact pigs were carried out at the GSI Helmholtz Center in Darmstadt using scanned carbon ions. Here, we present real-time electrocardiogram (ECG) data to estimate time-resolved (4D) delivered dose. For 11 animals, surface ECGs and temporal structure of beam delivery were acquired during irradiation. R waves were automatically detected from surface ECGs...
June 23, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28644144/meta-analysis-of-the-clinical-characteristics-and-prognostic-relevance-of-notch1-and-fbxw7-mutation-in-t-cell-acute-lymphoblastic-leukemia
#9
Rong-Bin Liu, Jian-Gui Guo, Tian-Ze Liu, Cheng-Cheng Guo, Xin-Xiang Fan, Xiao Zhang, Xiu-Yu Cai, Wei-Han Hu
The NOTCH1 signaling pathway is crucial for T-cell development, and NOTCH1 and/or FBXW7 mutations are frequently detected in T-cell acute lymphoblastic leukemia (T-ALL). We performed a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) to assess the prognostic impact of mutations in the NOTCH1 pathway. After retrieving relevant articles from PubMed, EMBASE, and the Cochrane Library, we investigated overall survival (OS) and event-free survival (EFS) with hazard ratios (HRs) using fixed-effects or random-effects models and conducted subgroup analyses based on population and mutation status...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643458/treatment-outcomes-for-hodgkin-lymphoma-first-report-from-the-brazilian-prospective-registry
#10
Irene Biasoli, Nelson Castro, Marcia Delamain, Talita Silveira, James Farley, Belinda Pinto Simões, Cristiana Solza, Monica Praxedes, Otávio Baiocchi, Rafael Gaiolla, Fernanda Franceschi, Caroline Bonamin Sola, Carla Boquimpani, Nelma Clementino, Guilherme Perini, Kátia Pagnano, Giovanna Steffenello, Jacques Tabacof, Gilberto de Freitas Colli, Andrea Soares, Carmino de Souza, Carlos Sérgio Chiattone, Cristiane Milito, José Carlos Morais, Nelson Spector
Data about Hodgkin lymphoma (HL) in developing countries are scarce and suggest the existence of substantial disparities in healthcare and outcomes in large areas of the world. In 2009, a prospective registry of HL was implemented in Brazil. Web-based data were contributed by 20 institutions across the country participating in the Brazilian Prospective Hodgkin's Lymphoma Registry. The aim of this study was to present the clinical features and outcomes of newly diagnosed patients with HL aged 13 to 90 years...
June 23, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28643430/platinum-containing-regimens-for-metastatic-breast-cancer
#11
REVIEW
Sam J Egger, Melina L Willson, Jenna Morgan, Harriet S Walker, Sue Carrick, Davina Ghersi, Nicholas Wilcken
BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. Most of these studies were conducted prior to the 'intrinsic subtype' era, and did not specifically focus on metastatic triple-negative breast cancers (mTNBCs). OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer...
June 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28643310/-establishment-of-a-prognostic-nomogram-to-predict-long-term-survival-in-non-metastatic-colorectal-cancer-patients
#12
Xiaojie Wang, Pan Chi, Huiming Lin, Xingrong Lu, Ying Huang, Zongbin Xu, Shenghui Huang, Yanwu Sun, Daoxiong Ye
OBJECTIVE: To establish a nomogram to predict long-term survival in non-metastatic colorectal cancer patients. METHODS: A retrospective analysis was conducted in patients with non-metastatic colorectal cancer who underwent radical surgery in the Department of Colorectal Surgery of Affiliated Union Hospital of Fujian Medical University between January 2000 and December 2014. Univariate and multivariate analyses on disease-free survival (DFS) were performed using the Cox proportional regression model...
June 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28643235/design-and-evaluation-of-rgd-modified-gemini-surfactant-based-lipoplexes-for-targeted-gene-therapy-in-melanoma-model
#13
Waleed Mohammed-Saeid, Jackson Chitanda, Mays Al-Dulaymi, Ronald Verrall, Ildiko Badea
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28642696/how-accumulated-real-life-stress-experience-and-cognitive-speed-interact-on-decision-making-processes
#14
Eva Friedel, Miriam Sebold, Sören Kuitunen-Paul, Stephan Nebe, Ilya M Veer, Ulrich S Zimmermann, Florian Schlagenhauf, Michael N Smolka, Michael Rapp, Henrik Walter, Andreas Heinz
Rationale: Advances in neurocomputational modeling suggest that valuation systems for goal-directed (deliberative) on one side, and habitual (automatic) decision-making on the other side may rely on distinct computational strategies for reinforcement learning, namely model-free vs. model-based learning. As a key theoretical difference, the model-based system strongly demands cognitive functions to plan actions prospectively based on an internal cognitive model of the environment, whereas valuation in the model-free system relies on rather simple learning rules from operant conditioning to retrospectively associate actions with their outcomes and is thus cognitively less demanding...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28642595/3d-bayesian-cluster-analysis-of-super-resolution-data-reveals-lat-recruitment-to-the-t-cell-synapse
#15
Juliette Griffié, Leigh Shlomovich, David J Williamson, Michael Shannon, Jesse Aaron, Satya Khuon, Garth L Burn, Lies Boelen, Ruby Peters, Andrew P Cope, Edward A K Cohen, Patrick Rubin-Delanchy, Dylan M Owen
Single-molecule localisation microscopy (SMLM) allows the localisation of fluorophores with a precision of 10-30 nm, revealing the cell's nanoscale architecture at the molecular level. Recently, SMLM has been extended to 3D, providing a unique insight into cellular machinery. Although cluster analysis techniques have been developed for 2D SMLM data sets, few have been applied to 3D. This lack of quantification tools can be explained by the relative novelty of imaging techniques such as interferometric photo-activated localisation microscopy (iPALM)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642591/donor-and-recipient-age-gender-and-abo-incompatibility-regardless-of-donor-source-validated-criteria-for-donor-selection-for-hematopoietic-transplants
#16
Y Wang, D-P Wu, Q-F Liu, L-P Xu, K-Y Liu, X-H Zhang, Y Xu, F Huang, X-J Huang
Prior data indicate similar outcomes after transplants from HLA-haplotype-matched relatives, HLA-identical siblings and HLA-matched unrelated donors. We used our prospective dataset to answer a clinically important question: who is the best donor for a person with acute leukemia transplanted in 1st complete remission. Patients were randomly divided into training (n=611) and validation (n=588) sets. 1199 consecutive subjects received a transplant from an HLA-haplotype-matched relative using granulocyte colony-stimulating factor (G-CSF) and anti-thymocyte globulin (ATG) (n=685) or an HLA-identical sibling (n=514); 3-year leukaemia-free survivals (LFSs) were 75 and 74% (P=0...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28641499/a-comprehensive-model-for-heat-induced-radio-sensitization
#17
Sarah Catharina Brüningk, Jannat Ijaz, Ian Rivens, Simeon Nill, Gail Ter Haar, Uwe Oelfke
Combined radiotherapy (RT) and hyperthermia (HT) treatments may improve treatment outcome by heat induced radio-sensitization. We propose an empirical cell survival model (AlphaR model) to describe this multimodality therapy. The model is motivated by the observation that heat induced radio-sensitization may be explained by a reduction in the DNA damage repair capacity of heated cells. We assume that this repair is only possible up to a threshold level above which survival will decrease exponentially with dose...
June 23, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28641472/long-term-health-related-quality-of-life-in-transplant-ineligible-patients-with-newly-diagnosed-multiple-myeloma-receiving-lenalidomide-and-dexamethasone
#18
Dan T Vogl, Michel Delforge, Kevin Song, Shien Guo, Craig J Gibson, Annette Ervin-Haynes, Thierry Facon
The FIRST trial demonstrated that continuous therapy with lenalidomide and dexamethasone (Rd) prolongs overall survival (OS) and improves health-related quality of life (HRQoL) during the first 18 months of therapy in newly diagnosed multiple myeloma (NDMM) patients. However, patient-reported HRQoL data were not collected after 18 months. We therefore estimated HRQoL scores based on time-varying data collected during progression-free follow-up after 18 months. During the initial 18 months of Rd, observed changes from baseline were within the 95% confidence interval of the predictive models at 33 of 35 time points across 7 HRQoL scores...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28641443/dissecting-the-accountability-of-parameterized-and-parameter-free-single-hybrid-and-double-hybrid-functionals-for-photophysical-properties-of-tadf-based-oleds
#19
Mojtaba Alipour, Niloofar Karimi
Organic light emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) emitters are an attractive category of materials that have witnessed a booming development in recent years. In the present contribution, we scrutinize the accountability of parameterized and parameter-free single-hybrid (SH) and double-hybrid (DH) functionals through the two formalisms, full time-dependent density functional theory (TD-DFT) and Tamm-Dancoff approximation (TDA), for the estimation of photophysical properties like absorption energy, emission energy, zero-zero transition energy, and singlet-triplet energy splitting of TADF molecules...
June 21, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28641432/local-structure-of-dilute-aqueous-dmso-solutions-as-seen-from-molecular-dynamics-simulations
#20
Abdenacer Idrissi, Bogdan A Marekha, Mohammed Barj, François Alexandre Miannay, Toshiyuki Takamuku, Vasilios Raptis, Jannis Samios, Pál Jedlovszky
The information about the structure of dimethyl sulfoxide (DMSO)-water mixtures at relatively low DMSO mole fractions is an important step in order to understand their cryoprotective properties as well as the solvation process of proteins and amino acids. Classical MD simulations, using the potential model combination that best reproduces the free energy of mixing of these compounds, are used to analyze the local structure of DMSO-water mixtures at DMSO mole fractions below 0.2. Significant changes in the local structure of DMSO are observed around the DMSO mole fraction of 0...
June 21, 2017: Journal of Chemical Physics
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