tbuckley/cabot-search huggingface dataset:
Abstract 412: Dissection of Thrombospondin-4 Domains Involved in Adaptive ER Stress Responsive Signaling and Secretory Pathway Functions
Authors: Matthew J Brody, Tobias G Schips, Onur Kaniscak, Jason Karch, N. S Blair, Jeffery D Molkentin
Journal: Circulation Research (2015)

Thrombospondins are a family of stress-inducible secreted glycoproteins with well-characterized roles in the extracellular matrix and tissue remodeling. We recently reported critical intracellular functions for thrombospondin-4 (Thbs4) by activation of an adaptive endoplasmic reticulum (ER) stress pathway in cardiomyocytes, in part by promoting activation of activating transcription factor 6α (Atf6α). Here, we dissect the domains of Thbs4 that mediate interactions with ER proteins and activation of this adaptive ER stress response, and determine the domains of Thbs4 involved in secretory pathway functions. We show that the N-terminal laminin G like domain (LamG) of Thbs4 exhibits intracellular localization almost exclusively at the Golgi apparatus and is robustly secreted in cultured cardiomyocytes, indicating rapid flux through the secretory pathway. We also generated a full length Thbs4 with mutations in calcium-binding motifs within the type III repeat (T3R) domain, including mutations homologous to human disease-causing mutations identified in THBS5/COMP. While wildtype Thbs4 localized to the ER and post-ER vesicles and was actively secreted in cardiomyocytes, the Thbs4 calcium-binding mutant localized predominately to the ER and was not secreted. We identified BiP (Grp78) as a novel binding partner of Thbs4 in cardiomyocytes in vitro and in vivo, and utilized adenoviruses overexpressing Thbs4 domain mutants in cardiomyocytes to map the TSP-C domain (L-type lectin domain) of Thbs4 as the BiP-interacting motif. Additionally, the TSP-C domain of Thbs4 bound Atf6α and overexpression of the TSP-C domain alone was sufficient to induce the adaptive ER stress pathway in cardiomyocytes, activate Atf6α, and protect against ER stress-induced cell death. These studies characterize the functional domains of Thbs4 and aid in parsing out the intracellular and extracellular roles of thrombospondins. Taken together, data indicate critical functions for the TSP-C and LamG domains of Thbs4 in ER stress-responsive and secretory pathway functions, respectively.
Long term aircraft noise is linked to incidence of high blood pressure
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Long term exposure to aircraft noise, particularly at night, is linked to an increased risk of developing high blood pressure and possibly cardiac arrhythmia and stroke, suggests research published online in Occupational and Environmental Medicine .1

In 2013 the researchers followed up 420 people living near Athens International Airport in Greece, which is used by as many as 600 planes a day, who had taken part in the HYENA study in 2004-06. The study assessed …
Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin
Authors: Nicholas C. Wu, Jia Xie, Tianqing Zheng, Corwin M. Nycholat, Geramie Grande, James C. Paulson, Richard A. Lerner, Ian A. Wilson
Journal: Cell Host & Microbe (2017)
Post-Transplant Outcomes in AML Patients ≥ 60 Years of Age Beyond CR1
Authors: Dhruv Bansal, Pavan Kumar Bhamidipati, Natasha Catherine Edwin, Michael Slade, John F DiPersio, Peter Westervelt, Ravi Vij, Mark A. Schroeder, Geoffrey L. Uy, Jingxia Liu, Rizwan Romee
Journal: Blood (2016)
Role of Activated Pleckstrin-2 and Down-Stream Effects on Ineffective Erythropoiesis in β-Thalassemic Mice
Authors: Maria Feola, Andrea Zamperone, Weili Bao, Tenzin Choesang, Huihui Li, Guiyuan Li, Shilpa M. Hattangadi, Christopher E. Mason, Peng Ji, Antonia Follenzi, Yelena Ginzburg
Journal: Blood (2016)
First safety results of an international phase II study evaluating oral vinorelbine as a single agent as first-line chemotherapy for metastatic breast cancer patients with bone metastases (NorBreast-228 trial).
Authors: Guenther G. Steger, Natalya Dobrovolskaya, Adriana Dominguez, Odile Switsers, Francesco Giotta, Iwona Glogowska, Nicole Tubiana-Mathieu, Martin Pecherstorfer, Andrea Ardizzoia, Philippe Bougnoux, Maria Blasinska-Morawiec, Corinne Veyret, Sheyla Garcia, Joan Dorca Ribugent, Christian Marth, Alexey Manikhas, Marco Benasso, Svetlana Protsenko, Gustavo Villanova, Enrique Espinosa
Journal: Journal of Clinical Oncology (2014)

1048 Background: Oral chemotherapy (CT) is an attractive treatment option for hormone receptor positive, metastatic breast cancer (MBC) patients (pts) pretreated by a hormone therapy. In our phase II study, we evaluated the role of single-agent Oral Vinorelbine (OV) as first-line CT in pts presenting bone metastases without visceral involvement. In this abstract, first safety results of this trial are presented. Methods: Main eligibility criteria included: age ≥18 years, documented bone involvement previously untreated by CT, hormone receptor positive disease previously treated by at least one hormone therapy, HER2-negative disease, Karnofsky PS ≥70 and absence of visceral metastases. Study treatment (until progression): OV 80 mg/m2 weekly (following a first cycle at 60 mg/m2 and dose escalation to 80 in the absence of grade 3 or 4 toxicity). One cycle was defined as four weeks of treatment. Results: Main pts characteristics in the full population were (n=70): median age: 60.6 years (34% ≥65 years); median Karnofsky PS 90%. Prior hormone therapy 100% (53% in advanced setting); prior (neo)adjuvant CT 63%; prior anthracyclines/taxanes 59/24%; prior palliative radiotherapy 41%. Bone involvement 100%; other metastatic sites: lymph nodes 14%, soft tissue 3%. Median duration of treatment 5.5 months (range 0.9-18.3), median number of cycles: 6 (range: 1-18);61% of pts received at least 6 cycles, 37% of ptsreceived more than 6 cycles and 29% received at least 9 cycles; median relative dose intensity: 83.5%; dose escalation was performed in 79% ofpts.Grade 3/4 adverse events per pt: neutropenia 37%, anemia 4%, diarrhoea 3%, nausea 3%, asthenia 1%, liver toxicity 1%, neutropenic infection 1%, non-neutropenic infection 1%. Grade 2 alopecia was reported in 6% of pts. Conclusions: In this particular population of metastatic pts, with hormone receptor positive disease and bone involvement, OV showed an optimal safety profile. These data shows that OV is a well tolerated first-line CT option in this setting, allowing prolonged active treatment in non-progressing pts.
Evaluation of coagulopathy before and during induction chemotherapy for acute lymphoblastic leukaemia, including assessment of global clotting tests
Authors: K Burley, J Salem, T Phillips, C Reilly-Stitt, D I Marks, O Tunstall, J Moppett, A Mumford, C A Bradbury
Journal: Blood Cancer Journal (2017)

Evaluation of coagulopathy before and during induction chemotherapy for acute lymphoblastic leukaemia, including assessment of global clotting tests
Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group
Authors: Fernando Ramos, Cristina Robledo, Arturo Pereira, Carmen Pedro, Rocío Benito, Raquel de Paz, Mónica del Rey, Andrés Insunza, Mar Tormo, María Díez‐Campelo, Blanca Xicoy, Eduardo Salido, Javier Sánchez‐del‐Real, Leonor Arenillas, Lourdes Florensa, Elisa Luño, Consuelo del Cañizo, Guillermo F. Sanz, Jesús María Hernández‐Rivas
Journal: American Journal of Hematology (2017)

The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates. The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96-4.66, P < 0.001), and mutational analysis significantly improved prediction of leukemic evolution (HR 2.64, 1.56-4.46, P < 0.001). Non-leukemic death was strongly linked to patient condition (HR 2.71, 1.72-4.25, P < 0.001), but not to IPSS-R score (P = 0.35) or mutational status (P = 0.75). Adjustment for exposure to disease-modifying therapy, evaluated as a time-dependent covariate, had no effect on the proposed model's predictive ability. In conclusion, patient condition, assessed by the multidimensional Lee index and patient mutational status can improve the prediction of clinical outcomes of patients with MDS already stratified by IPSS-R.
Efficacy of the Ribvd Regimen in High Risk Mantle Cell Lymphoma Patients As Defined By the Mipic Prognostic Score: Identification of KI67, LDH and Performance Status As Most Important Prognostic Factors (PF). a French Lysa Group Study
Authors: Remy Gressin, Anne Moreau, Nicolas Daguindau, Adrien Tempescul, Sylvain Carras, Jean-Michel Pignon, Guillaume Cartron, Roch Houot, Caroline Dartigeas, Anne Schmitt, Krimo Bouabdallah, Jehan Dupuis, Christiane Mounier, Lionel Karlin, Fabrice Jardin, Luc Mathieu Fornecker, Selim Corm, Joel Fleury, Barbara Burroni, Loic Ysebaert, Steven Le Gouill
Journal: Blood (2016)
Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice
Authors: Peng-Fei Ma, Chun-Chen Gao, Jing Yi, Jun-Long Zhao, Shi-Qian Liang, Yang Zhao, Yu-Chen Ye, Jian Bai, Qi-Jun Zheng, Ke-Feng Dou, Hua Han, Hong-Yan Qin
Journal: Journal of Hepatology (2017)
Abstract 12977: Neladenoson, a Partial Adenosine A1-receptor Agonist, Improves Mitochondrial Function in Left Ventricular Cardiomyocytes Isolated From Dogs With Chronic Heart Failure
Authors: Hani N Sabbah, Ramesh C Gupta, Vinita Singh-Gupta, Kefei Zhang, Jiang Xu, Barbara Albrecht-Küpper
Journal: Circulation (2016)

Background: Mitochondria (MITO) of failing cardiomyocytes (CMs) manifest structural and functional abnormalities characterized by hyperplasia, reduced organelle size and reduced respiration. These abnormalities lead to reduced rate of ATP synthesis and excess production of reactive oxygen species. We previously showed that chronic therapy with a partial adenosine A1-receptor agonist (pA1RA) improves LV function and normalizes tissue levels of MITO uncoupling proteins 2 and 3 in dogs with heart failure (HF). Hypothesis: Neladenoson, a new pA1RA, improves MITO function in freshly isolated CMs from dogs with chronic HF. Methods: CMs were isolated from LV of 7 microembolization-induced HF dogs (LV ejection fraction &lt;30%) and from 6 normal (NL) dogs using a collagenase-based enzymatic process that yielded ~70% rod-shaped CMs that excluded trypan blue. Equal aliquotes of CMs were incubated in 0 (vehicle), 3, 10, and 30 nM concentration of Neladenoson for one hour at 37°C. MITO ADP-stimulated state-3 respiration, maximum rate of ATP synthesis and complex-IV activity (COX-IV) were measured at end of incubation. Respiration was measured with a Strathkelvin respirometer and COX-IV activity was measured polarographically and both expressed as nAtom Oxygen/min/mg protein. Rate of ATP synthesis was measured using the bioluminescent ApoSENSOR assay and quantified in RFU/μg protein. Results: Data are shown in the table. Increasing concentration of Neladenoson had no effect on measures of MITO function in CMs from NL dogs. In CMs from HF dogs, depressed levels of MITO respiration, ATP synthesis and COX-IV increased significantly and in a dose-dependent manner after exposure to Neladenoson. Conclusions: Neladenoson has beneficial effects on MITO function in CMs from HF dogs. Furthermore, the improvement in MITO function after treatment with Neladenoson can occur early after initiation of therapy (within one hour) and is dose-dependent up to concentrations of 30 nM.
Inhibition of Pancreatic Cancer by RhIL1RA—Response
Authors: Paul J. Chiao, Jianhua Ling, Jie Fu, Yu Lu, Yi-Chen Sun
Journal: Clinical Cancer Research (2017)

We thank Prof. Shusen Zheng and colleagues for their interest in our work and for their questions about our results and conclusions in our publication (1).The authors in the letter stated: “The article showed that gemcitabine induced NF-κB and ERK activation in gemcitabine-resistant PDAC cells can be reversed by Anakinra. . … However, there are still some key points should be discussed with more details.” Our study found that Anakinra, when given with or without gemcitabine, can reduce tumor growth by inhibiting IL1α-induced NF-κB activity. For example, Fig. 5D of ref. 1 illustrates our point. This result suggests that anakinra might be a novel therapeutic agent pending on further studies, but our published data did not address the phenotype of gemcitabine resistance that can be reversed by the inhibition of NF-κB.There are numerous publications from various laboratories that demonstrate NF-κB activation by gemcitabine. For example, NF-κB activation is shown in Figs. 1 and 5A in the publication by Toriuchi and colleagues (2), Fig. 7A in the publication by Zhang and colleagues (3), and Fig. 4C in the publication by Qian and colleagues (4). It is known that cell lines with the same name used by different laboratories over years may have altered phenotypes. Thus, we cannot conclude that the pancreatic ductal adenocarcinoma cells used in our publication are gemcitabine resistant.We thank the authors' comments on our work, and we agree with the authors that further evidence is required to elucidate the mechanism of gemcitabine resistance. We hope that our comments will help to clarify the issues.See the original Letter to the Editor, p. 3223No potential conflicts of interest were disclosed.
Correction: Article on TLC-D99, Paclitaxel, Trastuzumab in HER-2 Breast Cancer
Journal: Clinical Cancer Research (2009)

In the article by Cortes and colleagues in the January 1, 2009, issue of Clinical Cancer Research, the name of one of the authors was presented incorrectly. The correct author name is Serena Di Cosimo.Cortes J, Di Cosimo S, Climent MA, et al. Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Clin Cancer Res 2009;15:307–14.
An Anchoring-Based Intervention to Increase Patient Willingness to Use Injectable Medication in Psoriasis
Authors: Elias Oussedik, Leah A. Cardwell, Nupur U. Patel, Omobola Onikoyi, Steven R. Feldman
Journal: JAMA Dermatology (2017)

Phospho-PKCε seems to be positive in 8 of 11 MCC specimens (73%) (grading mean [SD], 1.27 [0.39]; median, 1.00) (Table ).Interestingly, all MCC specimens positive for MCPyV were also positive for phospho-PKCε.Total PKCε, including active and inactive forms, was positive in all (11 of 11 [100%]) MCC specimens with a mean (SD) grading of 3.55 (0.52) (median, 4.00); MCPyV was positive in 8 of 11 cases of MCC (73%), with a mean (SD) grading of 2.64 (1.75) (median, 3.00).Discussion | Merkel cell carcinoma is an older-age-onset-preference tumor 1 that was initially attributed to be of spontaneous origin from Merkel cells.However, it is now well-recognized that MCPyV is a trigger in most cases of MCC. 4 About 80% of MCC presents with MCPyV positivity, 5 although this percentage varies among different geographic areas. 6 In this report, we used immunohistochemistry (Figure ) for phospho-PKCε to investigate the presence of these molecules in MCC specimens.There was an extremely strong correlation between PKCε activation and MCPyV positivity.Our hypothesis is that treatments targeting PKCε in MCC may augment current therapies for MCC caused by MCPyV, including immunotherapy, chemotherapy and radiation therapy.
Evidence-based recommendations for the management of acne fulminans and its variants
Authors: Tanya Greywal, Andrea L. Zaenglein, Hilary E. Baldwin, Neal Bhatia, Karen A. Chernoff, James Q. Del Rosso, Lawrence F. Eichenfield, Marc H. Levin, James J. Leyden, Diane M. Thiboutot, Guy F. Webster, Sheila Fallon Friedlander
Journal: Journal of the American Academy of Dermatology (2017)
Changes in uninvolved immunoglobulins during induction therapy for newly diagnosed multiple myeloma
Authors: P Ravi, S Kumar, W Gonsalves, F Buadi, M Q Lacy, R S Go, A Dispenzieri, P Kapoor, J A Lust, D Dingli, Y Lin, S J Russell, N Leung, M A Gertz, R A Kyle, P L Bergsagel, S V Rajkumar
Journal: Blood Cancer Journal (2017)

Little is known about the impact of multiple myeloma (MM) treatment on uninvolved immunoglobulins (Ig). We identified 448 patients who received high-dose dexamethasone (HD-DEX), lenalidomide and dexamethasone (RD), bortezomib and dexamethasone (VD), bortezomib, cyclophosphamide and dexamethasone (VCD) or bortezomib, lenalidomide and dexamethasone (VRD) for newly diagnosed MM at our institution between 2000 and 2013, and who had available data on absolute lymphocyte count (ALC) and quantitative uninvolved Ig at baseline and at the end of four cycles of therapy. Changes in ALC and uninvolved Ig were significantly different across treatments, with VCD and HD-DEX producing reductions in uninvolved Ig, and RD, VD and VRD leading to increases in uninvolved Ig. In addition, treatment with RD, VD and VRD was independently associated with higher odds of achieving a ⩾25% increase in or normalization of the primary uninvolved Ig on multivariate analysis. Although achievement of a humoral response in the primary uninvolved Ig was associated with a higher odds of achieving VGPR or better after four cycles of therapy, it was not associated with improved overall survival. These data highlight the different mechanisms of action of MM drugs and point toward a possible role for the use of VCD in treating antibody-mediated autoimmune disease.
Mutations at 3' Untranslated Region (3'UTR) of NOTCH1 Are Associated with Low CD20 Expression Levels in Chronic Lymphocytic Leukemia
Authors: Tamara Bittolo, Federico Pozzo, Riccardo Bomben, Tiziana D'Agaro, Vanessa Bravin, Pietro Bulian, Francesca Rossi, Antonella Zucchetto, Massimo Degan, Paolo Macor, Giovanni D'Arena, Annalisa Chiarenza, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Davide Rossi, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei, Michele Dal Bo
Journal: Blood (2016)
Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing
Authors: Jianguo Wen, Wenjing Tao, Suyang Hao, Youli Zu
Journal: Journal of Hematology & Oncology (2017)

Sickle cell disease (SCD) is a disorder of red blood cells (RBCs) expressing abnormal hemoglobin-S (HbS) due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT) carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. This study is an exploration of genome editing of SCD HSPCs.
Abstract 17263: Healthcare Contacts Before Sudden Out-of-Hospital Cardiac Arrest Can Help Identify Young Patients at Risk of Sudden Cardiac Death
Authors: Peter Weeke, Fredrik Folke, Gunnar H Gislason, Freddy K Lippert, Jonas B Olesen, Charlotte Andersson, Mads Wissenberg, Henrik E Poulsen, Søren L Nielsen, Lars Køber, Christian Torp-Pedersen
Journal: Circulation (2011)

Background The underlying etiology of sudden cardiac death varies with age and is likely to be reflected in type and number of healthcare contacts. We aimed to determine the specific type of healthcare contact shortly before out-of-hospital cardiac arrest (OHCA) across ages. Methods Patients with OHCA were identified in the nationwide Danish Cardiac Arrest Register and Copenhagen Medical Emergency Care Unit from 2001-2006. We matched every OHCA patients with 10 controls on sex and age. Healthcare contacts were evaluated 30 days before event by individual-level-linkage of nationwide registers. Healthcare contact associations to OHCA were evaluated using conditional multivariate logistic regression. Results We identified 16,924 OHCA patients, median age was 70.0 years (IQR: 59-80) and 65.8% were male. In general, the association between OHCA and hospital admissions and pharmacotherapy was more pronounced among the youngest (14-34 years) OHCA patients 30 days before OHCA compared to older patients (≥75 years): antidepressants (OR=4.5, CI:2.7-7.5 and OR=1.1; CI:1.0-1.2), sedatives and anxiolytics (OR=11.1, CI:6.8-18.4 and OR=1.1, CI:1.0-1.2), anti-psychotic medication (OR=5.6, CI:2.9-11.7 and OR=1.5, CI:1.3-1.7), bronchial dilators (OR=3.4, CI:1.9-6.0 and OR=2.1, CI:1.9-2.3), and corticosteroids (OR=4.0, CI:1.0-16.4 and OR=1.8, CI:1.6-2.0). Furthermore, patients aged &lt;40 years were &gt;6 times more likely to be in contact with the healthcare services (than the control population whereas OHCA patients &gt;60 years were only 2 times more likely to be in contact with the healthcare services shortly before OHCA compared to the control population (Figure 1). Conclusion Young OHCA patients are far more likely to be in contact with the healthcare services compared with an age and sex matched control population suggestive of traits that make them stand out from the general population and make them potentially identifiable before cardiac arrest.