tbuckley/cabot-search huggingface dataset:
Abstract 13809: Serial Paraoxonase-1-associated Serum Arylesterase Activity and Outcomes in Ambulatory Patients With Heart Failure
Authors: Muhammad Hammadah, Andreas P Kalogeropoulos, Vasiliki Georgiopoulou, Malory Weber, Yuping Wu, Javed Butler, W.H.Wilson Tang
Journal: Circulation (2015)

Introduction: Decreased arylesterase (ArylE) activity of paraoxonase-1, a HDL-associated protein with anti-inflammatory and antioxidant properties, has been associated with increased risk of cardiac events in ischemic heart failure (HF) patients. However, the change of ArylE activity over time and its association with HF adverse outcomes has not been reported. Methods: We examined the association between baseline and follow up serum ArylE activity and HF outcomes (death, cardiac transplantation or ventricular assist device implantation) in 304 patients with HF enrolled in the Atlanta Cardiomyopathy Consortium, a prospective cohort study in the metropolitan Atlanta GA area from 1/2008 to 7/2009. ArylE activity was assessed on enrollment for all patients, and for 152 patients after 1 year of follow up. Significant drop in ArylE activity on follow up was defined as a drop of ≥25% vs. baseline levels. Results: In our population (age 56.5±12 years, male 63.9%, CAD 39.1%, EF 30±15 %), mean baseline and follow up ArylE activity levels were 110.5 ± 29.8 μmol/min/ml and 105.2±27.7 μmol/min/ml, respectively. Mean ArylE activity change between follow up and baseline levels was -5.9 ± 28.6 μmol/min/ml, p = 0.015. After mean follow up of 2.8 ± 1.1 years, 53 events were reported. Low baseline ArylE activity was associated with increased risk of adverse HF outcomes [HR (95CI%) for lowest tertile vs highest tertile of 2.6 (1.3-5.5), p=0.01] (Figure A). This association remained significant after adjustment for age, gender, diabetes, creatinine clearance and CAD. Patients who had significant drop in ArylE activity (≥25% of baseline levels, n=18), had significantly increased risk of HF events [HR(95%CI) of 4.9 (1.6-14.6), p=0.005], even after adjustment for baseline levels of ArylE activity (Figure B). Conclusions: Reduced baseline ArylE activity and decreased levels on follow up are associated with adverse outcomes in stable outpatients with HF.
On the road to universal health care in Indonesia, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Authors: Nafsiah Mboi, Indra Murty Surbakti, Indang Trihandini, Iqbal Elyazar, Karen Houston Smith, Pungkas Bahjuri Ali, Soewarta Kosen, Kristin Flemons, Sarah E Ray, Jackie Cao, Scott D Glenn, Molly K Miller-Petrie, Meghan D Mooney, Jeffrey L Ried, Dina Nur Anggraini Ningrum, Fachmi Idris, Kemal N Siregar, Pandu Harimurti, Robert S Bernstein, Tikki Pangestu, Yuwono Sidharta, Mohsen Naghavi, Christopher J L Murray, Simon I Hay
Journal: The Lancet (2018)

As Indonesia moves to provide health coverage for all citizens, understanding patterns of morbidity and mortality is important to allocate resources and address inequality. The Global Burden of Disease 2016 study (GBD 2016) estimates sources of early death and disability, which can inform policies to improve health care.We used GBD 2016 results for cause-specific deaths, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth, healthy life expectancy, and risk factors for 333 causes in Indonesia and in seven comparator countries. Estimates were produced by location, year, age, and sex using methods outlined in GBD 2016. Using the Socio-demographic Index, we generated expected values for each metric and compared these against observed results.In Indonesia between 1990 and 2016, life expectancy increased by 8·0 years (95% uncertainty interval [UI] 7·3-8·8) to 71·7 years (71·0-72·3): the increase was 7·4 years (6·4-8·6) for males and 8·7 years (7·8-9·5) for females. Total DALYs due to communicable, maternal, neonatal, and nutritional causes decreased by 58·6% (95% UI 55·6-61·6), from 43·8 million (95% UI 41·4-46·5) to 18·1 million (16·8-19·6), whereas total DALYs from non-communicable diseases rose. DALYs due to injuries decreased, both in crude rates and in age-standardised rates. The three leading causes of DALYs in 2016 were ischaemic heart disease, cerebrovascular disease, and diabetes. Dietary risks were a leading contributor to the DALY burden, accounting for 13·6% (11·8-15·4) of DALYs in 2016.Over the past 27 years, health across many indicators has improved in Indonesia. Improvements are partly offset by rising deaths and a growing burden of non-communicable diseases. To maintain and increase health gains, further work is needed to identify successful interventions and improve health equity.The Bill & Melinda Gates Foundation.
Diagnosing Fractures With AI
Authors: Rebecca Voelker
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
An inhibitor screen identifies histone-modifying enzymes as mediators of polymer-mediated transgene expression from plasmid DNA
Authors: Matthew D. Christensen, Rajeshwar Nitiyanandan, Seyedehmelika Meraji, René Daer, Sudhakar Godeshala, Sheba Goklany, Karmella Haynes, Kaushal Rege
Journal: Journal of Controlled Release (2018)
Correlates and Outcomes of Physician Burnout—Reply
Authors: Kathryn Martinez, Amy K. Windover, Michael B. Rothberg
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Macrophage CD31 Signaling in Dissecting Aortic Aneurysm
Authors: Francesco Andreata, Varouna Syvannarath, Marc Clement, Sandrine Delbosc, Kevin Guedj, Giulia Fornasa, Jamila Khallou-Laschet, Marion Morvan, Guillaume Even, Emanuele Procopio, Anh-Thu Gaston, Marie Le Borgne, Lydia Deschamps, Antonino Nicoletti, Giuseppina Caligiuri
Journal: Journal of the American College of Cardiology (2018)
What Can We Learn From Voluntary Bundled Payment Programs?
Authors: Karen E. Joynt Maddox
Journal: JAMA Cardiology (2018)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Cardiology journal
Neurocognitive Benefits from Breastfeeding May Not Endure
Authors: Anita Slomski
Journal: JAMA (2018)

The neurocognitive benefits of breastfeeding that are present in early school-aged children may not extend into adolescence, according to a 16-year follow-up of the Promotion of Breastfeeding Intervention Trial (PROBIT). This follow-up study was published in PLOS Medicine.
Case 20-2018: A 64-Year-Old Man with Fever, Arthralgias, and Testicular Pain
Authors: Chana A. Sacks, Aoife Kilcoyne, Zachary S. Wallace, Krzysztof Glomski
Journal: New England Journal of Medicine (2018)

A 64-year-old man was evaluated for fever, arthralgias, and testicular pain. Laboratory tests revealed leukocytosis, an elevated blood level of C-reactive protein, and microscopic hematuria. Ultrasonography revealed testicular engorgement. Diagnostic tests were performed.
Cardiovascular disease and atopic dermatitis: epidemiological strengths and limitations
Authors: J. P. Thyssen, A. Egeberg
Journal: British Journal of Dermatology (2018)

Linked Articles: Drucker and Flohr. Br J Dermatol 2018; doi.10.1111/bjd.16891 Drucker and Flohr. Br J Dermatol 2018; 178:1235–6.
Abstract 2: CXCR2+ tumor cells mediate vascular mimicry driving anti-angiogenic therapy (AAT) resistance in glioblastoma (GBM)
Authors: Kartik P. Angara, Thaiz F. Borin, Mohammad H. Rashid, Roxan Ara, Bhagelu R. Achyut, Ali S. Arbab
Journal: Cancer Research (2018)

Abstract Glioblastoma (GBM) is a hypervascular and hypoxic neoplasia of the central nervous system with an extremely high rate of mortality. Owing to its hypervascularity, anti-angiogenic therapies (AAT) have been used as an adjuvant to the traditional surgical resection, chemotherapy, and radiation to normalize blood vessels and control abnormal vasculature. The benefits of AAT have been transient, and evidence of relapse exemplified in the progressive tumor growth following AAT reflects development of resistance and alternative neovascularization mechanisms in these resilient tumors to counter the AAT therapy insult. Vascular mimicry (VM) is the uncanny ability of tumor cells to acquire endothelial-like properties and lay down vascular patterned networks reminiscent of host endothelial blood vessels. The VM channels serve as an irrigation system for the tumors to meet with the increasing metabolic and nutrient demands of the tumor. In our current studies to understand the tumor-inherent mechanisms of AAT resistance, we identified a crucial pro-migratory and pro-angiogenic chemokine, CXCL8 or IL-8, to be highly upregulated in the GBM tumors treated with AAT. AAT-treated groups had significantly higher populations of CXCR2+ stem and endothelial-like subpopulations and these cells lined the VM-like vascular structures carrying functional RBCs in the tumors. These stem cell-like and endothelial-like populations were decreased following treatment with HET0016 or SB225002. Furthermore, knocking down CXCR2 led to smaller tumor size in the animals and improperly developed vascular structures without CXCR2+ GBM cells lining them. Also, HET0016 and SB225002 disrupt the tube-forming capability of U251 GBM cells in an in vitro Matrigel angiogenesis assay. This confirms our hypothesis that CXCR2+ GBM cells initiate VM and contribute to AAT resistance in GBM. Our present study suggests that tumor cell autonomous IL-8/CXCR2 pathway contributes to VM-mediated AAT resistance in GBM and that HET0016 and SB225002 have a great potential to target therapeutic resistance and can be combined with other chemotherapeutic agents in preclinical and clinical trials. Citation Format: Kartik P. Angara, Thaiz F. Borin, Mohammad H. Rashid, Roxan Ara, Bhagelu R. Achyut, Ali S. Arbab. CXCR2+ tumor cells mediate vascular mimicry driving anti-angiogenic therapy (AAT) resistance in glioblastoma (GBM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2.
Human carboxylesterases: a comprehensive review
Authors: Dandan Wang, Liwei Zou, Qiang Jin, Jie Hou, Guangbo Ge, Ling Yang
Journal: Acta Pharmaceutica Sinica B (2018)

Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.
Abstract 2945: Arsenic trioxide sensitizes glioma stem cells to brain penetrant PI3K and mTOR inhibitor GDC-0084
Authors: Jianwen Dong, Emmanuel Martinez-Ledesma, Nghi Nguyen, Caroline Carrillo, Yuji Piao, Verlene Henry, Soon Young Park, Ningyi Tiao, Clifford Stephan, Roel Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F. de Groot
Journal: Cancer Research (2018)

Abstract Glioblastoma is the most aggressive primary malignant brain tumor with few effective therapies. The current study evaluated arsenic trioxide (As2O3, ATO), a small-molecular agent that inhibits tumor growth via promoting promyelocytic leukemia protein (PML) degradation, in combination with multiple PI3K/mTOR inhibitors using high-throughput screening (HTS) to validate if ATO reverses glioblastoma resistance to PI3K/mTOR-targeted therapy. Quantitative single-agent and 2-drug combinations (5 drug doses, maximal concentration of 1 uM of each agent) were evaluated in 20 patient-derived glioma stem-like cells (GSCs). ATO was applied as an “anchor” drug and several mTOR and EGFR inhibitors as “probe” drugs to explore potential combination efficacy. Data from single-agent screening demonstrated that brain penetrant PI3K/mTOR inhibitor GDC-0084 potently inhibited cell viability with an IC50 ranging from 0.12μM to 5.78μM under normoxic conditions. Under hypoxic conditions, 10 of the 16 GSC cell lines remained sensitive, indicating less efficacy of GDC-0084 in the setting of a hypoxic microenvironment. Evaluation of drug combinations identified ATO and GDC-0084 as the most effective combination in vitro. ATO was synergistic with GDC-0084 in several GSCs resistant to GDC-0084 monotherapy. GSC sensitivity to GDC-0084 as single agent and in combination correlated with apoptosis, angiogenesis and PI3K/Akt pathways using gene set enrichment analyses (GSEA). In vitro combination treatment significantly inhibited PML, p-S6, p-AKT and p-mTOR expressions compared to single agent. In an orthotopic mouse model of glioma, targeting PI3K/mTOR with GDC-0084 prolonged the median survival to 81 days compared to 69 days in the control group. The efficacy of combining ATO and GDC-0084 in an orthotopic GSC mouse model is ongoing. Our studies confirm prior work demonstrating the efficacy of combining GDC-0084 with ATO, which now requires clinical validation. Citation Format: Jianwen Dong, Emmanuel Martinez-Ledesma, Nghi Nguyen, Caroline Carrillo, Yuji Piao, Verlene Henry, Soon Young Park, Ningyi Tiao, Clifford Stephan, Roel Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F. de Groot. Arsenic trioxide sensitizes glioma stem cells to brain penetrant PI3K and mTOR inhibitor GDC-0084 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2945.
Prophylaxis against Upper Gastrointestinal Bleeding in Hospitalized Patients
Authors: Deborah Cook, Gordon Guyatt
Journal: New England Journal of Medicine (2018)

Acid suppression is widely used to lower the risk of gastrointestinal bleeding in critically ill patients, and the practice has spread to patients at low risk. In view of its adverse effects, however, acid suppression may not provide a net benefit even in high-risk patients.
The Combination of the PARP Inhibitor Olaparib and the WEE1 Inhibitor AZD1775 as a New Therapeutic Option for Small Cell Lung Cancer
Authors: Alice Lallo, Kristopher K. Frese, Christopher J. Morrow, Robert Sloane, Sakshi Gulati, Maximillian W. Schenk, Francesca Trapani, Nicole Simms, Melanie Galvin, Stewart Brown, Cassandra L. Hodgkinson, Lynsey Priest, Adina Hughes, Zhongwu Lai, Elaine Cadogan, Garima Khandelwal, Kathryn L. Simpson, Crispin Miller, Fiona Blackhall, Mark J. O'Connor, Caroline Dive
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Introduced in 1987, platinum-based chemotherapy remains standard of care for small cell lung cancer (SCLC), a most aggressive, recalcitrant tumor. Prominent barriers to progress are paucity of tumor tissue to identify drug targets and patient-relevant models to interrogate novel therapies. Following our development of circulating tumor cell patient–derived explants (CDX) as models that faithfully mirror patient disease, here we exploit CDX to examine new therapeutic options for SCLC. Experimental Design: We investigated the efficacy of the PARP inhibitor olaparib alone or in combination with the WEE1 kinase inhibitor AZD1775 in 10 phenotypically distinct SCLC CDX in vivo and/or ex vivo. These CDX represent chemosensitive and chemorefractory disease including the first reported paired CDX generated longitudinally before treatment and upon disease progression. Results: There was a heterogeneous depth and duration of response to olaparib/AZD1775 that diminished when tested at disease progression. However, efficacy of this combination consistently exceeded that of cisplatin/etoposide, with cures in one CDX model. Genomic and protein analyses revealed defects in homologous recombination repair genes and oncogenes that induce replication stress (such as MYC family members), predisposed CDX to combined olaparib/AZD1775 sensitivity, although universal predictors of response were not noted. Conclusions: These preclinical data provide a strong rationale to trial this combination in the clinic informed by prevalent, readily accessed circulating tumor cell–based biomarkers. New therapies will be evaluated in SCLC patients after first-line chemotherapy, and our data suggest that the combination of olaparib/AZD1775 should be used as early as possible and before disease relapse. Clin Cancer Res; 24(20); 5153–64. ©2018 AACR.
Beyond oestrogens: towards a broader evaluation of the hormone profile in pulmonary arterial hypertension
Authors: Jessica B. Badlam, Eric D. Austin
Journal: European Respiratory Journal (2018)

<b>Baird and colleagues contribute further evidence that the justification for sex-associated investigations in pulmonary arterial hypertension extend beyond oestrogen signalling. Evaluation of the entire steroid hormone milieu is crucial.</b>http://ow.ly/7wbz30kp5VQ
India’s unofficial medical watchdog shows its teeth
Authors: Dinsa Sachan
Journal: BMJ (2018)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following India’s unofficial medical watchdog shows its teeth Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Spatio-temporal patterns of highly pathogenic avian influenza virus subtype H5N8 spread, France, 2016 to 2017
Authors: Claire Guinat, Gaëlle Nicolas, Timothée Vergne, Anne Bronner, Benoit Durand, Aurélie Courcoul, Marius Gilbert, Jean-Luc Guérin, Mathilde C. Paul
Journal: Eurosurveillance (2018)

IntroductionFrance is one of Europe's foremost poultry producers and the world's fifth largest producer of poultry meat. In November 2016, highly pathogenic avian influenza (HPAI) virus subtype H5N8 emerged in poultry in the country. As of 23 March 2017, a total of 484 confirmed outbreaks were reported, with consequences on animal health and socio-economic impacts for producers. Methods: We examined the spatio-temporal distribution of outbreaks that occurred in France between November 2016 and March 2017, using the space-time K-function and space-time permutation model of the scan statistic test. Results: Most outbreaks affected duck flocks in south-west France. A significant space-time interaction of outbreaks was present at the beginning of the epidemic within a window of 8 km and 13 days. This interaction disappeared towards the epidemic end. Five spatio-temporal outbreak clusters were identified in the main poultry producing areas, moving sequentially from east to west. The average spread rate of the epidemic front wave was estimated to be 5.5 km/week. It increased from February 2017 and was negatively associated with the duck holding density. Conclusion: HPAI-H5N8 infections varied over time and space in France. Intense transmission events occurred at the early stages of the epidemic, followed by long-range jumps in the disease spread towards its end. Findings support strict control strategies in poultry production as well as the maintenance of high biosecurity standards for poultry holdings. Factors and mechanisms driving HPAI spread need to be further investigated.
Inhaled Corticosteroids and LABAs — Removal of the FDA’s Boxed Warning
Authors: Sally M. Seymour, Robert Lim, Changming Xia, Eugenio Andraca-Carrera, Badrul A. Chowdhury
Journal: New England Journal of Medicine (2018)

Inhaled Corticosteroids and LABAs In December, the FDA removed the boxed warning on combination products containing an inhaled corticosteroid and a long-acting beta-agonist. The decision was based on results from recently completed large safety trials that the agency required manufacturers to conduct.