tbuckley/cabot-search huggingface dataset:
Proinflammatory CXCL12–CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice
Authors: Achinto Saha, Songyeon Ahn, Jorge Blando, Fei Su, Mikhail G. Kolonin, John DiGiovanni
Journal: Cancer Research (2017)

Obesity is a prognostic risk factor in the progression of prostate cancer; however, the molecular mechanisms involved are unclear. In this study, we provide preclinical proof of concept for the role of a proinflammatory CXCL12-CXCR4/CXCR7 signaling axis in an obesity-driven mouse model of myc-induced prostate cancer. Analysis of the stromal vascular fraction from periprostatic white adipose tissue from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs encoding various chemokines, cytokines, growth factors, and angiogenesis mediators, with CXCL12 among the most significantly upregulated genes. Immunofluorescence staining of ventral prostate tissue from obese HiMyc mice revealed high levels of CXCL12 in the stromal compartment as well as high staining for CXCR4 and CXCR7 in the epithelial compartment of tumors. Prostate cancer cell lines derived from HiMyc tumors (HMVP2 and derivative cell lines) displayed increased protein expression of both CXCR4 and CXCR7 compared with protein lysates from a nontumorigenic prostate epithelial cell line (NMVP cells). CXCL12 treatment stimulated migration and invasion of HMVP2 cells but not NMVP cells. These effects of CXCL12 on HMVP2 cells were inhibited by the CXCR4 antagonist AMD3100 as well as knockdown of either CXCR4 or CXCR7. CXCL12 treatment also produced rapid activation of STAT3, NFκB, and MAPK signaling in HMVP2 cells, which was again attenuated by either AMD3100 or knockdown of CXCR4 or CXCR7. Collectively, these data suggest that CXCL12 secreted by stromal cells activates invasiveness of prostate cancer cells and may play a role in driving tumor progression in obesity. Targeting the CXCL12-CXCR4/CXCR7 axis could lead to novel approaches for offsetting the effects of obesity on prostate cancer progression. Cancer Res; 77(18); 5158-68. ©2017 AACR.
The yield of a positive MRI of the spine as imaging criterion in the ASAS classification criteria for axial spondyloarthritis: results from the SPACE and DESIR cohorts
Authors: Zineb Ez-Zaitouni, Pauline AC Bakker, Miranda van Lunteren, Manouk de Hooge, Rosaline van den Berg, Monique Reijnierse, Karen Minde Fagerli, Robert BM Landewé, Roberta Ramonda, Lennart TH Jacobsson, Alain Saraux, Gregory Lenczner, Antoine Feydy, Jean Baptiste Pialat, Fabrice Thévenin, Floris A van Gaalen, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

To assess the prevalence of spinal inflammation on MRI in patients with chronic back pain (CBP) of maximally 3 years duration and to evaluate the yield of adding a positive MRI-spine as imaging criterion to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA).Baseline imaging of the sacroiliac joints (X-SI), MRI of the sacroiliac joints (MRI-SI) and MRI-spine were scored by ≥2 experienced central readers per modality in the SPondyloArthritis Caught Early (SPACE) and DEvenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohorts. Inflammation suggestive of axSpA was assessed in the entire spine. A positive MRI-spine was defined by the presence of ≥5 inflammatory lesions. Alternative less strict definitions were also tested.In this study, 541 and 650 patients with CBP from the SPACE and DESIR cohorts were included. Sacroiliitis on X-SI and MRI-SI was found in 40/541 (7%) and 76/541 (14%) patients in SPACE, and in DESIR in 134/650 (21%) and 231/650 (36%) patients, respectively. In SPACE and DESIR, a positive MRI-spine was seen in 4/541 (1%) and 48/650 (7%) patients. Of the patients without sacroiliitis on imaging, 3/447 (1%) (SPACE) and 8/382 (2%) (DESIR) patients had a positive MRI-spine. Adding positive MRI-spine as imaging criterion led to new classification in only one patient in each cohort, as the other patients already fulfilled the clinical arm. Other definitions of a positive MRI-spine yielded similar results.In two cohorts of patients with CBP with a maximum symptom duration of 3 years, a positive MRI-spine was rare in patients without sacroiliitis on MRI-SI and X-SI. Addition of MRI-spine as imaging criterion to the ASAS axSpA criteria had a low yield of newly classified patients and is therefore not recommended.
Melanoma inhibitory activity (MIA) reflects chondrocyte anabolism in chronic inflammatory arthritis
Authors: B. Vandooren, M. Van Lierop, T. Cantaert, L. De Rycke, E. Kruithof, E. M. Veys, F. De Keyser, E. Bos, Annemieke Boots, D. Baeten
Journal: Annals of the Rheumatic Diseases (2006)
Factors associated with the large disparities in <i>BRCA </i>testing among high risk Black women.
Authors: Tuya Pal, Deborah Cragun, Devon Bonner, Lucia P Camperlengo, Emily Robinson, Susan Thomas Vadaparampil
Journal: Journal of Clinical Oncology (2015)

6549 Background: Concerns about genomic advances to increase health disparities have been raised. We sought to explore factors associated with receipt of BRCA1 and BRCA2 (BRCA) testing and assess for racial disparities through a population-based sample of young breast cancer survivors. Methods: Women diagnosed with invasive breast cancer at or below age 50 in 2009-2012 were recruited through the Florida State Cancer Registry with oversampling of Blacks compared to non-Hispanic Whites (NHW). Participants were asked to complete a baseline questionnaire and a medical records release for verification of genetic test results. Summary statistics, Pearson Chi-square tests and multivariable logistic regression were used to examine associations between dichotomous demographic and clinical variables and access to BRCA testing rates prior to enrollment. Results: Of the 877 participants included in this analysis, 36.7% (165/450) of Blacks versus 67.7% (289/427) of NHW had BRCA testing (p < 0.001). Medical record verification of the BRCA test result was achieved in over 75% of the sample. In the final logistic regression model, controlling for educational attainment and household income age at breast cancer diagnosis and triple negative status, NHW race remained the strongest predictor for having had BRCA testing with an odds ratio (OR) of 4.2 (95% Confidence Interval: 3.0-6.1). Other highly significant predictors of having BRCA testing included: 1) breast cancer diagnosis at or below age 40 (OR: 3.4); 2) annual income of $25,000 or greater (OR: 2.6); 3) triple negative disease (OR: 1.9); and 4) college education or higher (OR: 1.7) (all p-values < 0.005). Variables not significantly associated with having BRCA testing included having private insurance at the time of diagnosis and having children. Conclusions: Our results demonstrate the enormous disparity in BRCA testing among high risk Black women compared to NHW, which is not explained by socioeconomic factors. The rapid diffusion of gene-based care to refine cancer prevention and treatment and ultimately improve patient outcomes underscores the need to systematically understand and address these disparities so all populations may benefit from these scientific advances.
Pattern of First Relapse in Multiple Myeloma (MM) Patients (Pts) after a Cybord Induction Regimen and Autologous Stem Cell Transplantation (ASCT): Impact of Maintenance Therapy in the Real-World Setting
Authors: Julie Cote, Madeline Phillips, Eshetu G Atenafu, Esther Masih-Khan, Donna Reece, Christine Chen, Anca Prica, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
Journal: Blood (2016)
Stem Cells: A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair (Adv. Healthcare Mater. 13/2017)
Authors: Gwangjun Go, Jiwon Han, Jin Zhen, Shaohui Zheng, Ami Yoo, Mi-Jeong Jeon, Jong-Oh Park, Sukho Park
Journal: Advanced Healthcare Materials (2017)

Autologous cell-based therapy using scaffold has attracted great interests in articular cartilage regeneration. In article number 1601378, a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell delivery for articular cartilage regeneration is described by Sukho Park and co-workers. They show that the porous microscaffold can not only assist in cell adhesion but also move to the target site using external magnetic field control.
Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study
Authors: Mamta Jaiswal, Jasmin Divers, Dana Dabelea, Scott Isom, Ronny A. Bell, Catherine L. Martin, David J. Pettitt, Sharon Saydah, Catherine Pihoker, Debra A. Standiford, Lawrence M. Dolan, Santica Marcovina, Barbara Linder, Angela D. Liese, Rodica Pop-Busui, Eva L. Feldman
Journal: Diabetes Care (2017)

We assessed the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the SEARCH for Diabetes in Youth (SEARCH) study.
Abstract 14467: A Randomized, Open-Label, Crossover, Multicenter Study of the Antiplatelet Effects of Ticagrelor versus Clopidogrel in Hispanic Patients With Stable Coronary Artery Disease (CAD)
Authors: Leonardo C Clavijo, Juan Maya, Glenn Carlson, Renli Teng, Richard Caplan, Matthew J Price
Journal: Circulation (2013)
Analysis retrospective from efficacy with TAS-102 in patients with metastatic colorectal cancer refractory: Experience at two hospitals
Authors: Beatriz González-Astorga, Irene González Cebrián, Teresa Delgado Ureña Ma, Verónica Conde, Carmen Sánchez-Toro, Javier García-García, Encarnación González-Flores
Journal: Annals of Oncology (2017)
Phase II study of gemcitabine (G), trastuzumab (H), and pertuzumab (P) for HER2-positive metastatic breast cancer (MBC) after prior pertuzumab-based therapy.
Authors: Neil M. Iyengar, Lillian Mary Smyth, Diana Lake, Ayca Gucalp, Jasmeet Chadha Singh, Tiffany A. Traina, Patricia Anne DeFusco, Maura N. Dickler, Monica N. Fornier, Shari Beth Goldfarb, Komal L. Jhaveri, Shanu Modi, Tiffany A. Troso-Sandoval, Kellie Jack, Gary Ulaner, Maxine S. Jochelson, Jose Baselga, Larry Norton, Clifford A. Hudis, Chau T. Dang
Journal: Journal of Clinical Oncology (2017)

1037 Background: The combination of taxanes with HP for first line treatment of HER2-positive MBC is associated with improved progression-free (PFS) and overall survival (OS). Treatment per physician’s choice with anti-HER2 therapy after second line therapy is associated with a median PFS of 3 months. While continued use of H in therapeutic combinations after progression on H-based therapy is standard, the efficacy of continuing HP-based treatment after progression on P-based therapy is unknown. Methods: This is a single arm phase II trial of G with HP. Eligible patients (pts) had HER2-positive (IHC 3+ or FISH &gt; 2.0) MBC with prior HP-based treatment and ≤ 3 prior chemotherapies. Pts received G (1200 mg/m 2 ) on days 1 and 8 of a q 3 week (w) cycle, and H (8 mg/kg load → 6 mg/kg) and P (840 mg load → 420 mg) q3w. The primary endpoint is PFS at 3 months. Secondary endpoints include OS, safety and tolerability. An exploratory endpoint is to compare PFS by RECIST criteria versus 18-F FDG-PET response criteria. The study therapy will be considered successful if at least 27/45 (60%) patients are progression free at 3 months. Results: As of 1-27-17, 41 of 45 pts are enrolled; 34 are evaluable at 3 months and 7 have not had 3-month evaluation. At 3 months, 26/34 (76%) are progression free (1 CR, 8 PR, 17 SD); 8 pts progressed. There are no cardiac or febrile neutropenic events to date. 4 pts required G dose reduction (3 grade 3 neutropenia and 1 grade 3 vomiting) and the study was amended to lower initial G dose to 1000 mg/m 2 . Conclusions: The preliminary 3 month-PFS is 76% in evaluable pts (95% CI 60% to 88%). The updated 3 month-PFS results will be presented. Continuation of P beyond progression is associated with apparent clinical benefit. A randomized trial is justified to confirm this clinically important observation. Clinical trial information: NCT02252887.
Hepatitis E virus infection in Europe: surveillance and descriptive epidemiology of confirmed cases, 2005 to 2015
Authors: Esther J Aspinall, Elisabeth Couturier, Mirko Faber, Bengü Said, Samreen Ijaz, Lara Tavoschi, Johanna Takkinen, Cornelia Adlhoch
Journal: Eurosurveillance (2017)

Hepatitis E virus (HEV) is an under-recognised cause of acute hepatitis in high-income countries. The purpose of this study was to provide an overview of testing, diagnosis, surveillance activities, and data on confirmed cases in the European Union/European Economic Area (EU/EEA). A semi-structured survey was developed and sent to 31 EU/EEA countries in February 2016, 30 responded. Twenty of these countries reported that they have specific surveillance systems for HEV infection. Applied specific case definition for HEV infection varied widely across countries. The number of reported cases has increased from 514 cases per year in 2005 to 5,617 in 2015, with most infections being locally acquired. This increase could not be explained by additional countries implementing surveillance for HEV infections over time. Hospitalisations increased from less than 100 in 2005 to more than 1,100 in 2015 and 28 fatal cases were reported over the study period. EU/EEA countries are at different stages in their surveillance, testing schemes and policy response to the emergence of HEV infection in humans. The available data demonstrated a Europe-wide increase in cases. Standardised case definitions and testing policies would allow a better understanding of the epidemiology of HEV as an emerging cause of liver-related morbidity.
Reflux gastro-oesophagien après POEM: une étude cas contrôle multicentrique
Journal: Endoscopy (2017)

Décrite en 2008 par Inoue, la myotomie endoscopique du muscle œsophagien selon la technique du POEM s’est imposée en moins de 10 ans comme un traitement de référence de l’achalasie du sphincter inférieur de l’œsophage. Après des données de sécurité rassurantes, des publications récentes confirment l’efficacité à long terme du POEM œsophagien, comparables à celles de la myotomie chirurgicale selon Heller.
The effect of ambient temperature on blood pressure in a rural West African adult population: a cross-sectional study
Authors: Setor K Kunutsor, John W Powles
Journal: Cardiovascular Research (2010)

Introduction : Associations between ambient temperature and blood pressure have been demonstrated in countries where the temperature varies between the seasons. This phenomenon has been overlooked in blood pressure surveys in sub-Saharan Africa. We assessed the effect of ambient temperature on blood pressure in an adult population in a West African country.
Methods : A cross-sectional survey was carried out on a rural Ghanaian population, investigating the effect of ambient temperature on blood pressure in 574 randomly sampled adults aged between 18 and 65 years.
Results : There was a significant inverse relationship between ambient temperature and systolic (SBP) (p < 0.019) and diastolic blood pressure (DBP) (p < 0.036). SBP fell by 5 mmHg per 10°C rise in ambient temperature.
Conclusion : Higher ambient temperatures are associated with lower blood pressures. To enhance comparability of data from epidemiological surveys, ambient temperature should be recorded for each blood pressure reading and findings standardised to a fixed ambient temperature.
Neratinib Efficacy and Circulating Tumor DNA Detection of <i>HER2</i> Mutations in <i>HER2</i> Nonamplified Metastatic Breast Cancer
Authors: Cynthia X. Ma, Ron Bose, Feng Gao, Rachel A. Freedman, Melinda L. Telli, Gretchen Kimmick, Eric Winer, Michael Naughton, Matthew P. Goetz, Christy Russell, Debu Tripathy, Melody Cobleigh, Andres Forero, Timothy J. Pluard, Carey Anders, Polly Ann Niravath, Shana Thomas, Jill Anderson, Caroline Bumb, Kimberly C. Banks, Richard B. Lanman, Richard Bryce, Alshad S. Lalani, John Pfeifer, Daniel F. Hayes, Mark Pegram, Kimberly Blackwell, Philippe L. Bedard, Hussam Al-Kateb, Matthew J.C. Ellis
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2mut detection. Experimental Design: Tumor tissue positive for HER2mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2mut). Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2mut cases were identified locally. Twenty-one of these 22 HER2mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31–74) years and three (2–10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%–55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8–31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%–94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%–100%). In addition, ctDNA HER2mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression. Conclusions: Neratinib is active in HER2mut, nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687–95. ©2017 AACR.
Obestatin Increases the Regenerative Capacity of Human Myoblasts Transplanted Intramuscularly in an Immunodeficient Mouse Model
Authors: Icia Santos-Zas, Elisa Negroni, Kamel Mamchaoui, Carlos S. Mosteiro, Rosalia Gallego, Gillian S. Butler-Browne, Yolanda Pazos, Vincent Mouly, Jesus P. Camiña
Journal: Molecular Therapy (2017)
Haploidentical Hematopoietic Stem Cell Transplant Compared with Matched Sibling and Unrelated Transplants in Adults with Philadelphia-Negative Acute Lymphoblastic Leukemia in First Complete Remission
Authors: Qifa Liu, Lijie Han, Zhiping Fan, Fen Huang, Xuan LI, Na Xu, Ren Lin, Jing Sun
Journal: Blood (2016)
β 1 -Blockade Prevents Post-Ischemic Myocardial Decompensation Via β 3 AR-Dependent Protective Sphingosine-1 Phosphate Signaling
Authors: Alessandro Cannavo, Giuseppe Rengo, Daniela Liccardo, Andres Pun, Ehre Gao, Alvin J. George, Giuseppina Gambino, Antonio Rapacciuolo, Dario Leosco, Borja Ibanez, Nicola Ferrara, Nazareno Paolocci, Walter J. Koch
Journal: Journal of the American College of Cardiology (2017)
Targeting toll-like receptor 7/8 improves host anti-infective response in alcoholic cirrhosis
Authors: Emanuele Albano, Felix Stickel
Journal: Gut (2017)

The production of reactive oxygen species (ROS) by activated macrophages and neutrophil granulocytes represents an important cause of alcohol-induced oxidative stress and significantly contributes to the pathogenesis of alcoholic liver disease (ALD).1 Furthermore, diffuse neutrophil infiltration of the liver is a key feature of acute alcoholic hepatitis actively participating to parenchymal injury.2 However, during ALD progression to cirrhosis, neutrophil functions such as ROS production, bacterial phagocytosis and granule exocytosis are impaired leading to an increased susceptibility to bacterial infections of cirrhotic patients.3 Indeed, the development of bacterial peritonitis is a common complication of cirrhosis, while sepsis is a major cause of mortality in  patients with decompensated alcoholic cirrhosis being also associated with multiorgan failure and immune deficiencies.4 

The key role of neutrophils in antibacterial defences mainly relies on the capacity of the enzyme NADPH oxidase 2 (NOX2) to generate superoxide anion (O2 −) during a process known as oxidative burst. Superoxide anion, in fact, by conversion to hydrogen peroxide, fuels myeloperoxidase-mediated production of the powerful bactericidal agents, hypochlorite and chloramine.5 NOX2 is a multiprotein enzymatic system consisting of the transmembrane proteins gp91 phox and p22 phox forming the …
Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy
Authors: Keehoon Jung, Takahiro Heishi, Omar F. Khan, Piotr S. Kowalski, Joao Incio, Nuh N. Rahbari, Euiheon Chung, Jeffrey W. Clark, Christopher G. Willett, Andrew D. Luster, Seok Hyun Yun, Robert Langer, Daniel G. Anderson, Timothy P. Padera, Rakesh K. Jain, Dai Fukumura
Journal: Journal of Clinical Investigation (2017)

Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro. Intravital microscopy revealed that CX3CR1 is critical for Ly6Clo monocyte transmigration across the endothelium in murine CRC tumors. Moreover, Ly6Clo monocytes recruit Ly6G+ neutrophils via CXCL5 and produce IL-10, which inhibits adaptive immunity. Preventing Ly6Clo monocyte or Ly6G+ neutrophil infiltration into tumors enhanced inhibition of tumor growth with anti-VEGFR2 therapy. Furthermore, a gene therapy using a nanoparticle formulated with an siRNA against CX3CL1 reduced Ly6Clo monocyte recruitment and improved outcome of anti-VEGFR2 therapy in mouse CRCs. Our study unveils an immunosuppressive function of Ly6Clo monocytes that, to our knowledge, has yet to be reported in any context. We also reveal molecular mechanisms underlying antiangiogenic treatment resistance, suggesting potential immunomodulatory strategies to enhance the long-term clinical outcome of anti-VEGF therapies.
Neuroleptics for Delirium: More Research Is Needed
Authors: Aimée C. C. F. Bogman, Jan N. M. Schieveld
Journal: JAMA Internal Medicine (2017)

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