tbuckley/cabot-search huggingface dataset:
Globally inclusive investments in health: benefits at home and abroad
Authors: Vin Gupta, Vanessa B Kerry
Journal: BMJ (2017)

Support for global health programs yields direct domestic benefits

At a time when disease pandemics and the health effects of climate change are viewed as primary threats to global stability,1 the rise of right wing populism among the world’s highest donors of official development assistance (fig 1⇓) is threatening aid budgets and progress across many global health movements. The value of international engagement across all sectors is being questioned as the perspective on globalization is becoming increasingly isolationist.2



Fig 1  Distribution of total official development assistance (ODA) across the 28 member states of the OECD’s development assistance committee in 2015 according to whether they have seen an upsurge in right wing populism since 2010



In the US the future of global health initiatives in President Donald Trump’s new administration is uncertain.3 Several of these initiatives are critically linked to US national and global security—bolstering pandemic preparedness, mitigating the health effects of climate change (for example, the rising prevalence of zoonotic diseases and the increased prevalence of severe weather patterns, such as Hurricane Sandy), tackling antimicrobial drug …
Abstract P3-07-05: CDK8 inhibition improves the efficacy of ER- and HER2-targeted drugs in breast cancer
Authors: MS McDermott, A Chumanevich, J Liang, M Chen, S Altilia, C Hennes, IB Roninson, EV Broude
Journal: Cancer Research (2017)

Abstract Over 70% of breast cancer patients are estrogen receptor (ER) positive and 25% of patients over-express HER2 making these patients susceptible to therapeutic intervention with ER- and HER2-targeted therapies, respectively. However, intrinsic and acquired resistance to targeted therapies is a significant clinical issue and new therapeutic approaches aimed to preventing and overcoming resistance are urgently needed. We have previously shown that high expression of CDK8, a transcription regulating kinase, is associated with shorter relapse free survival in both ER and HER2 positive breast cancer. We have found that CDK8 inhibition by a selective small molecule inhibitor (Senexin B), by shRNA knockdown or by CRISPR/CAS9 knockout, strongly inhibits estrogen signaling in ER-positive breast cancer cells. Senexin B produces a synergistic growth inhibitory effect with an antiestrogen fulvestrant in all the tested ER-positive breast cancer cell lines in vitro and in MCF7 xenograft model in vivo. Senexin B treatment also inhibited invasive growth of MCF7 xenografts. CDK8 inhibition suppressed the emergence of estrogen independence upon long-term estrogen deprivation. A highly synergistic growth inhibitory effect occurred when Senexin B was combined with an anti-HER2 monoclonal antibody (a biosimilar of trastuzumab) or with the HER2/EGFR small molecule inhibitor lapatinib. These synergistic effects were observed in all HER2 positive breast cancer cell lines tested including those that exhibit innate and acquired resistance to HER2 targeting therapy. Furthermore, combining lapatinib with Senexin B completely abrogated the emergence of acquired lapatinib resistance. Taken together these results suggest that CDK8 inhibition, when combined with either ER- or HER2-targeted therapies, offers a rational approach to improving the efficacy of targeted drugs in breast cancer. Citation Format: McDermott MS, Chumanevich A, Liang J, Chen M, Altilia S, Hennes C, Roninson IB, Broude EV. CDK8 inhibition improves the efficacy of ER- and HER2-targeted drugs in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-07-05.
Abstract BS3-1: Unfolding the unfolded protein response in breast cancer
Authors: X Chen
Journal: Cancer Research (2017)

Abstract During tumor development and progression, cancer cells encounter cytotoxic conditions such as hypoxia, nutrient deprivation, and low pH due to inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive stress response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), which is induced by factors affecting the endoplasmic reticulum (ER). Triple negative breast cancer (TNBC) is a highly aggressive malignancy with limited treatment options and TNBC-targeted therapies do not yet exist. We found that XBP1, a key component of the UPR, is activated in TNBC and plays a pivotal role in the tumorigenicity and progression of this human breast cancer subtype. Depletion of XBP1 blocked primary tumor growth, inhibited tumor relapse and reduced the population of chemotherapy-resistant tumor initiating cells (TICs). Genome-wide mapping of the XBP1 transcriptional regulatory network revealed that XBP1 regulates the hypoxia response through controlling HIF1α transcriptional activity and the expression of HIF1α targets. Notably, we identified a gene expression signature indicative of XBP1 pathway activation that is associated with poor prognosis in two independent cohorts of patients with TNBC. Our findings reveal a key function for this branch of the UPR in TNBC, opening new therapeutic avenues for patients with TNBC. Citation Format: Chen X. Unfolding the unfolded protein response in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr BS3-1.
FISH Reveals Abnormalities of Unsuspected Regions in Chromosomally Normal De Novo Myelodysplastic Syndromes (MDS).
Authors: Paolo Bernasconi, Irene Dambruoso, Marina Boni, Paola Maria Cavigliano, Ilaria Giardini, Barbara Rocca, Rita Zappatore, Celeste Calvello, Marilena Caresana, Mario Lazzarino
Journal: Blood (2009)
Response to Rituximab, Cyclophosphamide and Dexamethasone as Initial or Salvage Therapy in Low Grade Lymphoma and Immune Hemolytic Anemia.
Authors: Neetu Radhakrishnan, Rajasree Roy, Reuven Yakubov, Matthew Kaufman, Kanti Rai, Bhoomi Mehrotra, Dilip Patel
Journal: Blood (2006)
Abstract P3-04-17: Global transcriptional repression by the coactivator SRC-1 mediates disease progression in treatment-resistant breast cancer
Authors: E Ward, D Varešlija, A Fagan, A Hill, L Young
Journal: Cancer Research (2017)

Abstract Despite the effectiveness of endocrine therapy in treating estrogen receptor (ER) positive breast cancer, nearly 40% of breast cancer patients may develop resistance which can lead to metastatic disease progression. Steroid receptor co-activator-1 (SRC-1), a key regulator of ER signalling, is overexpressed in 35% of breast cancer patients and is strongly associated with the development of endocrine resistant metastasis(1). Recent studies highlighted the ability of SRC-1 to also act as transcriptional repressor. SRC-1 can therefore bi-directionally regulate gene expression to promote the resistant phenotype (2). This study employed a genome-wide multi-omics sequencing approach to determine the SRC-1 repression signature in endocrine resistance and elucidate the mechanism by which SRC-1 mediates this repression. RNA-sequencing identified 736 genes significantly downregulated by SRC-1, with common functional pathways such as differentiation, cell morphogenesis and extracellular matrix enriched in the gene set. Parallel global methylation sequencing analysis revealed distinct differentially methylated regions specific to SRC-1 repressed target genes. Mechanistic studies in endocrine resistant cells revealed a role for methylation proteins, DNMTs and MBD, in SRC-1 directed repression. Through combined analysis of our global sequencing data we identified a network hub of five differentiation genes directly repressed by SRC-1. High expression of this signature predicts enhanced recurrence free survival in tamoxifen treated patients (n=335, p=0.032). A reduction in expression of these genes was shown to have functional output on proliferation, migration and mammosphere formation. Finally, we use tumour explant models to show that targeting DNA methylation can be used to reverse the SRC-1 driven suppression of this differentiation hub. Here we report a novel mechanism by which SRC-1 may be driving endocrine resistant tumorigenesis. Our genome-wide discovery approach revealed a global epigenetic re-programming pathway whereby concerted differential DNA methylation is potentiated by the activation of SRC-1 in the presence of tamoxifen in the endocrine resistant setting. This study suggests that therapeutic strategies of combined targeted epigenetic therapy with estrogen deprivation could be a successful strategy to prevent acquired resistance to endocrine therapy. Citation Format: Ward E, Varešlija D, Fagan A, Hill A, Young L. Global transcriptional repression by the coactivator SRC-1 mediates disease progression in treatment-resistant breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-04-17.
Expression of miR-188 and 362 Induced by Erythropoietin Stimulation in a Human Erythrocytic Leukemia Cell Line.
Authors: Keiichi Sugiura, Nobuyoshi Kosaka, Yusuke Yamamoto, Yusuke Yoshioka, Hiroshi Miyazaki, Norio Komatsu, Takahiro Ochiya, Takashi Kato
Journal: Blood (2007)
Subclinical Hypothyroidism and Hypothyroxinemia in Pregnancy — Still No Answers
Authors: David S. Cooper, Elizabeth N. Pearce
Journal: New England Journal of Medicine (2017)

Transplacental passage of maternal thyroxine (T4) is essential for the maintenance of pregnancy and for normal fetal development, especially in the first half of gestation. Mild or subclinical hypothyroidism in pregnancy has been linked to adverse outcomes, including miscarriage, preterm delivery, low birth weight, and lower-than-normal IQ in offspring,1 although the data are conflicting.2 Subclinical hypothyroidism is defined as a normal serum free T4 level and an elevated serum thyrotropin level. In pregnancy, human chorionic gonadotropin stimulates the thyroid, raising the free T4 level and lowering the thyrotropin level. Thus, the reference ranges for thyrotropin in . . .
Treatment with Erythropoietic Stimulating Agents in IPSS Lower Risk MDS: Outcome Comparison Between 5q- and Non 5q- MDS Cases
Authors: Alessandro Sanna, Roberto Latagliata, Daniela Gioia, Antonella Gozzini, Francesca Sassolini, Giuliana Alimena, Alessandro Levis, Alberto Bosi, Valeria Santini
Journal: Blood (2011)
Safety of idelalisib in B-cell malignancies: Integrated analysis of eight clinical trials.
Authors: Steven Coutre, Jacqueline Claudia Barrientos, Jennifer R. Brown, Sven De Vos, Richard R. Furman, Michael J. Keating, Susan Mary O'Brien, John M. Pagel, Jeff Porter Sharman, Andrew David Zelenetz, Terry Newcomb, Yoonjin Cho, Christopher Aguilar, Lyndah Dreiling
Journal: Journal of Clinical Oncology (2015)

e18030 Background: Idelalisib (Zydelig), a first-in-class, selective, oral inhibitor of PI3Kδ, is approved in the US and EU for the treatment of chronic lymphocytic leukemia (CLL) in combination with rituximab and as monotherapy for patients with follicular lymphoma who have received at least two prior systemic therapies. Methods: An integrated analysis of safety was conducted for 760 subjects with CLL, indolent non-Hodgkin lymphoma, or other B-cell malignancy who received IDELA alone (doses = 50 mg BID to 350 mg BID) or as part of a combination regimen (IDELA doses = 100 or 150 mg BID). Most subjects were heavily pre-treated with relapsed disease. Results: Common adverse events (AEs) are presented in the table, along with important laboratory results. AEs leading to dose modification included transaminase elevations (13%), diarrhea/colitis (11%), and rash (5%); discontinuations due to these AEs were infrequent (3%, 5%, and 2%, respectively); dose interruption allowed successful re-challenge in most patients. Pneumonitis occurred in 2.3% (monotherapy) and 3.9% (combo therapy) of subjects. Grade ≥ 3 diarrhea/colitis had a later onset (peak incidence of 9% between 6-12 mo.); other AEs occurred most often in the first 6 months and declined thereafter. Conclusions: As well-characterized in this large dataset, IDELA has an acceptable safety profile. N (%) Monotherapy N = 354 Combo therapy N = 406 Any Gr. ≥Gr. 3 Any Gr. ≥Gr. 3 Adverse Events Diarrhea/colitis 131 (37) 38 (11) 161 (40) 68 (17) Pyrexia 96 (27) 7 (2) 169 (42) 47 (12) Nausea 91 (26) 5 (1) 125 (31) 30 (7) Cough 80 (22) 3 (1) 118 (29) 21(5) Rash 60 (17) 7 (2) 99 (24) 30 (7) Chills 49 (14) 0 86 (21) 23 (6) Pneumonia 47 (13) 40 (11) 74 (18) 56 (14) Vomiting 53 (15) 5 (1) 60 (15) 18 (4) Dyspnea 43 (12) 7 (2) 68 (17) 20 (5) Laboratory Abnormalities Neutropenia 162 (46) 83 (23) 234 (58) 151 (37) Anemia 102 (29) 18 (5) 145 (36) 34 (8) Thrombocytopenia 94 (27) 37 (11) 143 (35) 50 (12) Transaminase increase 176 (50) 56 (16) 190 (47) 53 (13)
Isothiocyanates are important as haptens in contact allergy to chloroprene rubber
Authors: A.G. Ramzy, K. Lammintausta, M. Matura, J Bråred Christensson, U. Nilsson, L. Hagvall
Journal: British Journal of Dermatology (2017)

Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate.To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates.Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates.All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm-2 . At 35 °C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission.Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.
Dendritic Cell Tumor Fusion Vaccination in Conjunction with Autologous Transplantation for Multiple Myeloma.
Authors: Jacalyn Rosenblatt, Irit Avivi, Baldev Vasir, Tami Katz, Lynne Uhl, Zekui Wu, Poorvi Somaiya, Heidi Mills, Robin Joyce, James D. Levine, Dimitrios Tzachanis, Vassiliki Boussiotis, Brett Glotzbecker, Karen Francoeur, Dilani Dombagoda, Michal Tsumer, Lina Bisharat, Nancy Giallombardo, Katharine Conway, Donna Fitzgerald, Rachal Barhad, Paul Richardson, Kenneth C. Anderson, Nikhil C. Munshi, Jacob M. Rowe, Donald Kufe, David Avigan
Journal: Blood (2009)
Improved tissue cryopreservation using inductive heating of magnetic nanoparticles
Authors: Navid Manuchehrabadi, Zhe Gao, Jinjin Zhang, Hattie L. Ring, Qi Shao, Feng Liu, Michael McDermott, Alex Fok, Yoed Rabin, Kelvin G. M. Brockbank, Michael Garwood, Christy L. Haynes, John C. Bischof
Journal: Science Translational Medicine (2017)

A scalable technology using iron oxide nanoparticles and inductive radiofrequency heating rapidly and uniformly rewarms vitrified tissues.
For Health Disparities, Don’t Ignore the Microbiome
Authors: Jennifer Abbasi
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Is there any clinical prognostic index of resistance to 5-Fluorouracil in the treatment of colorectal cancer? Preliminary results of a mono-institutional experience
Authors: A. Paganoni, G Martignoni, M Meregalli, Quinte'A, M Pirovano, L Tedeschi, S Masseroni, R Valsecchi, G Luporini
Journal: Annals of Oncology (2000)
Development and validation of multivariable models to predict mortality and hospitalization in patients with heart failure
Authors: Adriaan A. Voors, Wouter Ouwerkerk, Faiez Zannad, Dirk J. van Veldhuisen, Nilesh J. Samani, Piotr Ponikowski, Leong L. Ng, Marco Metra, Jozine M. ter Maaten, Chim C. Lang, Hans L. Hillege, Pim van der Harst, Gerasimos Filippatos, Kenneth Dickstein, John G. Cleland, Stefan D. Anker, Aeilko H. Zwinderman
Journal: European Journal of Heart Failure (2017)
Abstract P4-01-05: In vivo, intraoperative margin detection utilizing the Lumicell margin assessment system
Authors: U Rai, R Tang, JK Plichta, T Rice-Stitt, MA Gadd, MC Specht, DS Strasfeld, JM Ferrer, EF Brachtel, BL Smith
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
Protect children from alcohol harm, says expert group
Authors: Bryan Christie
Journal: BMJ (2017)

Severe curbs are needed on alcohol advertising in Scotland, including sports sponsorship, to protect children from unhealthy products, a group of experts on alcohol policy from the UK and overseas have told the Scottish government.

The recommendations are made in a report published by the charity Alcohol Focus Scotland,1 which commissioned the report after being asked for advice by the Scottish government.

Although the alcohol …
Nilotinib (AMN107) Can Induce Complete Cytogenetic Responses (CCyR) and Molecular Responses in Patients (Pts) with Advanced Chronic Myeloid Leukemia (CML) Resistant or Intolerant to Imatinib Mesylate (IM). Report of the Compassionate Use Program of Nilotinib in Mexico
Authors: Manuel Ayala, Rafael Hurtado Monroy, Luis Meillon, Nancy Delgado, Elena Garcia, Jorge Vela-Ojeda, Pablo Vargas, Norma Tapia, Martha Alvarado, Jose de Diego, Patricio Azaola, Roberto Hernandez, Gustavo Reyes, Martín de Jesús Gonzalez, Alvaro Aguayo, Juan Julio Kassack, Sergio Cleto, Olga Cantu, Kevin Nacho, Angel Herrera, Ingrid Mucius
Journal: Blood (2008)
Continuity of care generates a bespoke medical service
Authors: Denis Pereira Gray
Journal: BMJ (2017)

Barker and colleagues’ research is exceptionally important, showing a 12.5% reduction in hospital admissions for ambulatory care conditions among older patients who received continuity of GP care.1 Despite their claim, however, this is not the first such report, as Menec et al (2006) made the same finding with …
Abstract P1-04-05: RNA immunoprecipitation reveals lncRNA-protein interactions in basal-like breast cancer
Authors: K Northwood, J Saunus, M Milevskiy, S Lakhani, M Brown
Journal: Cancer Research (2017)

Abstract Interactions between long non-coding RNAs (lncRNAs) and proteins contribute to the epigenetic regulation of gene expression, and defects in such interactions have been implicated in several diseases, including cancer. Basal-like breast cancer accounts for approximately 15% of all breast cancer and is a major clinical problem given its poor survival and lack of responsiveness to targeted breast cancer treatments. DNA methylation is non-random and is much more pronounced in basal-like breast cancer (BLBC) compared to other molecular subtypes of breast cancer, raising the possibility that hypermethylation could be important in the genesis of BLBCs. LncRNAs are aberrantly expressed in multiple subtypes of breast cancer, including BLBC, and are considered to have significant prognostic potential. In order to explore the potential roles of DNA methylation and lncRNAs in BLBC, we investigated lncRNA-protein interactions using bioinformatics and molecular techniques, focusing on proteins that actively perform DNA methylation - the DNA methyltransferase (DNMT) family. Our novel bioinformatic methods revealed that BLBC may be sub-classified according to methylation profile in a way that could predict disease survival. We then identified candidate lncRNAs that are over-expressed in BLBC and statistically predicted to interact with DNMT proteins. Using RNA immunoprecipitation of BLBC cell lines, we have identified potential lncRNA-protein interactions that may be involved in epigenetic remodelling in BLBC. The role of these lncRNAs in epigenetic gene regulation and BLBC is currently being explored. Citation Format: Northwood K, Saunus J, Milevskiy M, Lakhani S, Brown M. RNA immunoprecipitation reveals lncRNA-protein interactions in basal-like breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-04-05.