tbuckley/cabot-search huggingface dataset:
Progress Toward Regional Measles Elimination — Worldwide, 2000–2015
Authors: Minal K. Patel, Marta Gacic-Dobo, Peter M. Strebel, Alya Dabbagh, Mick N. Mulders, Jean-Marie Okwo-Bele, Laure Dumolard, Paul A. Rota, Katrina Kretsinger, James L. Goodson
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Adopted in 2000, United Nations Millennium Development Goal 4 set a target to reduce child mortality by two thirds by 2015, with measles vaccination coverage as one of the progress indicators. In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of measles-containing vaccine (MCV1) for children aged 1 year to ≥90% nationally and ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per 1 million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (1,2).* In 2012, WHA endorsed the Global Vaccine Action Plan† with the objective to eliminate measles in four World Health Organization (WHO) regions by 2015. Countries in all six WHO regions have adopted measles elimination goals. Measles elimination is the absence of endemic measles transmission in a region or other defined geographical area for ≥12 months in the presence of a well performing surveillance system. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2015. During this period, annual reported measles incidence decreased 75%, from 146 to 36 cases per 1 million persons, and annual estimated measles deaths decreased 79%, from 651,600 to 134,200. However, none of the 2015 milestones or elimination goals were met. Countries and their partners need to act urgently to secure political commitment, raise the visibility of measles, increase vaccination coverage, strengthen surveillance, and mitigate the threat of decreasing resources for immunization once polio eradication is achieved.
Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells
Authors: Philipp Karschnia, Justin T. Jordan, Deborah A. Forst, Isabel C. Arrillaga-Romany, Tracy T. Batchelor, Joachim M. Baehring, Nathan F. Clement, L. Nicolas Gonzalez Castro, Aline Herlopian, Marcela V. Maus, Michaela H. Schwaiblmair, Jacob D. Soumerai, Ronald W. Takvorian, Ephraim P. Hochberg, Jeffrey A. Barnes, Jeremy S. Abramson, Matthew J. Frigault, Jorg Dietrich
Journal: Blood (2019)
Regulatory T Cell Selective IL-2-Fc Fusion Proteins for the Treatment of Autoimmune Diseases
Authors: Rajat Varma, Ke Liu, Kendra Avery, Rumana Rashid, Suzanne Schubbert, Irene Leung, Christine Bonzon, Liz Bogaert, John Desjarlais, Matthew J. Bernett
Journal: Blood (2018)
Yemen’s Deadly Cholera Epidemic
Authors: M.J. Friedrich
Journal: JAMA (2019)

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
Longitudinal Evolution and Clinical Impact of Subclonal Mutational Architecture in Adult T Cell Leukemia/Lymphoma
Authors: Ambroise Marçais, Ludovic Lhermitte, Maria Artesi, Keith Durkin, Vincent Hahaut, Véronique Avettand Fenoel, Julie Bruneau, Felipe Suarez, Claudine Pique, Anne Van den Broeke, Vahid Asnafi, Olivier Hermine
Journal: Blood (2018)
Potent in vitro and in vivo radiosensitisation by the selective DNA-dependent protein kinase inhibitor KU-0060648
Authors: Mark Albertella, Andrew Slade, Kerry Shea, Julia Bardos, Caroline Richardson, Michael Batey, Marc Hummersone, Laurent Rigoreau, Yan Zhao, Helen Jenkins, Roger Griffin, Keith Menear, David Newell, Nicola Curtin, Graeme Smith
Journal: Cancer Research (2008)

406  An important determinant of the susceptibility of cancer cells to DNA damaging anti-cancer therapeutics is the ability of the cells to repair the DNA damage inflicted upon them. It has therefore been proposed that inhibition of DNA repair processes could lead to the potential therapeutic endpoints of radio- and chemosensitisation. A key kinase involved in the detection, signaling and repair of DNA double strand breaks (DSBs) is the DNA-dependent protein kinase (DNA-PK). DNA-PK is intimately involved in the repair of DNA DSBs by the process of non-homologous end joining (NHEJ). Inhibition of DNA-PK activity through the probe compounds LY294002 (non-selective, IC50 1.5uM) and NU7441 (selective; IC50=13nM) has previously been shown to lead to cellular radio- and chemo-sensitisation. Through the generation of a focused compound library based around NU7441 to improve this compound’s overall biopharmaceutical properties, we have identified the compound KU-0060648. This agent exhibits 20-1000 fold selectivity for DNA-PK over related PIKK enzymes and PI3K family members. KU-0060648 was found not to radio-potentiate DNA-PKcs deficient cells, further highlighting its selective nature in vitro. KU-0060648 was able to inhibit the serine-2056 auto-phosphorylation site of DNA-PKcs with an IC50 of 60nM in FaDu cells and abrogated the phosphorylation of H2AX in response to ionizing radiation (IR). Doses of as little as 100nM were found to radiosensitise FaDu cells (Enhancement Ratio at 10% survival of 2.3), using clonogenic assays as an endpoint. KU-0060648 was able to radiopotentiate 2Gy of IR after only 2 hours of exposure, highlighting its role in disrupting the NHEJ dependent fast component of DNA DSB repair. KU-0060648 was also found to preferentially kill BRCA2-defective and ATM-defective cells in combination with IR or etoposide, suggesting that DNA repair defective tumour cells may provide a therapeutic advantage for this class of agent. Pharmacokinetic profiling of KU-0060648 in mice revealed that the compound showed 100% bioavailability, with a t1/2 of 142 minutes after p.o. dosing. In a fractionated IR (5x2Gy) FaDu xenograft model, KU-0060648, dosed at either 10 or 25mg/kg qd 30 minutes before IR caused significant growth delay compared to the control 5x2Gy group. PK/PD relationships were established to define the exposures and level of DNAPK inhibition required for effective radiosensitisation. Our results to date support the further in vivo evaluation of this novel class of agent as a radiosensitiser prior to clinical evaluation.
Somatic mutations in Luminal HER2 negative tumors from young breast cancer patients.
Authors: Giselly Encinas, Maria Del Pilar Estevez-Diz, Eduardo C. Lyra, Maria Lucia Hirata Katayama, Fatima Solange Pasini, Simone Maistro, Veronica Sabelnykova, Paul Boutros, Maria Mitzi Brentani, Ricardo Basso, Ana Carolina Ribeiro Chaves De Gouvea, Roger Chammas, Joao Carlos Guedes Sampaio Goes, Maria A. A. Koike Folgueira
Journal: Journal of Clinical Oncology (2015)

1544 Background: Early age patients less than 36 years represent 4% of breast cancer cases and have a higher probability of being BRCA1/2 mutation carriers. There are indications that tumors from young patients are biologically distinct from older women, however, these tumors have been less studied. Our aim was to identify somatic mutations in luminal tumors from BRCA1/2 wild type young breast cancer patients. Methods: Seventy-nine unselected young patients were enrolled. BRCA1/2 mutations were screened by Sanger sequencing and Multiplex Ligation-Dependent Probe amplification (MLPA). Tumor and blood samples from eight patients (hormone receptor positive, HER2 negative) were selected for whole exome sequencing using Nextera Rapid Capture Enrichment in an Illumina HiSeq 1000, analyzed through MuTect (v1.14), SomaticSniper (v1.0.2) and Strelka (v1.0.1.2). Results: Median age of the 79 patients was 32 years (22-35) and luminal subtype was the most frequent (63.1%). Deleterious mutation in BRCA1/2 genes was detected in 13 patients (BRCA1, n = 4 and BRCA2, n = 9). One novel mutation was detected in BRCA1 gene: a stop codon in exon 6 (c.483T > A; p.Cys161Ter). Somatic mutations were evaluated in eight luminal samples and a median of 60 alterations/tumor was detected, varying from 49 to 113. A total of 537 individual genomic alterations were found, comprising 77 non-synonymous and four nonsense base substitutions and 2 splice donor variants. Among these 83 mutations, 56 were detected in potentially driver genes, including genes involved in Hedgehog signaling pathway and GSK3B interactions. Five to ten driver genes were mutated per tumor sample. For non-synonymous point mutations, only PIK3CA was repeatedly mutated in three samples; TP53 was mutated in one sample. Conclusions: Besides PIK3CA mutation, which is the most frequent alteration in luminal tumors, and TP53 mutation, at least five other different driver genes may be mutated in tumors from young breast cancer patients.
Abortion: RCGP supports decriminalisation
Authors: Abi Rimmer
Journal: BMJ (2019)

The UK Council of the Royal College of General Practitioners has passed a motion to support the decriminalisation of abortion. The college said that abortion should be governed by medical regulatory frameworks, not the criminal justice system.

At the end of 2018 the college sent a survey to 53 724 members to gather their views on the issue. It received 4429 responses (8.2% response rate). Members were asked whether the RCGP should have …
Baseline Demographics and Characteristics of 466 Patients with Atypical Hemolytic Uremic Syndrome in the Global aHUS Registry
Authors: Christoph Licht, Gianluigi Ardissino, Gema Ariceta, David Cohen, Christoph Gasteyger, Laurence A. Greenbaum, Masayo Ogawa, Franz Schaefer, Johan Vande Walle, Veronique Fremeaux-Bacchi
Journal: Blood (2014)
P078 Transforming growth factor-beta dampens pro-inflammatory interleukin-6 signaling in chondrocytes by decreasing the interleukin-6 receptor
Authors: R Wiegertjes, A van Caam, H van Beuningen, P van der Kraan, F van de Loo, E Blaney Davidson
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Young investigator <h3>Introduction</h3> The pro-inflammatory cytokine interleukin-6 (IL-6) is present in high levels in arthritic diseases and has been implicated in cartilage degeneration. In contrast, transforming growth factor-β (TGF-β) is a homeostatic regulator of cartilage that decreases the catabolic effects of pro-inflammatory cytokines in chondrocytes. In tissues other than cartilage, multiple mechanisms of cross-talk between TGF-β and IL-6 are reported. <h3>Objectives</h3> In this study, we investigated whether TGF-β is able to control IL-6 signaling in chondrocytes. <h3>Methods</h3> Human primary chondrocytes and the human G6 chondrocyte cell line were stimulated with rhTGF-β1 (1.0 ng/ml). We determined mRNA expression levels of IL-6 and IL-6 receptor (IL-6R) using qPCR, measured IL-6 protein release using Luminex technology and IL-6R protein levels by Western Blot. rhIL-1β was used as a positive control for IL-6 induction. Induction of signal transducer and activator of transcription (STAT)3 phosphorylation by TGF-β was determined using Western Blot in presence of the IL-6R inhibitor Tocilizumab. Induction of suppressor of cytokine signaling (SOCS)3 gene expression was used as a read-out for IL-6/STAT3 mediated transcriptional activity. <h3>Results</h3> TGF-β increased both IL-6 mRNA expression and protein release in G6 and primary chondrocytes. Moreover, we observed activation of the main IL-6R downstream signaling protein STAT3 after TGF-β exposure, which could be completely prevented by blockade of the IL-6R, suggesting IL-6 dependency. Surprisingly however, TGF-β did not increase expression of the well known IL-6 target gene SOCS3, despite the increased levels of IL-6 and p-STAT3 we observed in these cells. Moreover, the effect of exogenously added rhIL-6 was markedly inhibited by TGF-β, as 6h pre-treatment prevented rhIL-6-mediated induction of both SOCS3 and p-STAT3. Interestingly, we observed decreased expression of the IL-6R in both primary and G6 chondrocytes after exposure to TGF-β, which might explain the decreased intracellular IL-6 signaling. This effect was not dependent on IL-6 itself, as IL-1β did not affect IL-6R expression, despite being a strong inducer of IL-6. Finally, we showed that rescuing IL-6R levels using soluble IL-6R dose-dependently restored induction of SOCS3 and p-STAT3 by rhIL-6 in the presence of TGF-β. <h3>Conclusions</h3> Our study reveals a novel, protective effect of TGF-β that could help preserve cartilage homeostasis under inflammatory conditions by dampening IL-6 signaling via IL-6R down regulation. In arthritic diseases, the presence of soluble IL-6R might bypass this protective TGF-β effect and contribute to cartilage damage. <h3>Disclosure of Interest</h3> None declared
Techniques and Thresholds for Quantifying Circulating Tumor Cells in Breast Cancer
Authors: Baihui Liu, Kuiran Dong, Rui Dong
Journal: JAMA Oncology (2019)

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 Oncology 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 Oncology journal
Progress Toward Global Eradication of Dracunculiasis, January 2016–June 2017
Authors: Donald R. Hopkins, Ernesto Ruiz-Tiben, Mark L. Eberhard, Sharon L. Roy, Adam J. Weiss
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on a lower limb (1). Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination,* and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund, CDC, and other partners, began assisting ministries of health in countries with endemic dracunculiasis. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia (2). Since then, although the goal of eradicating dracunculiasis has not been achieved, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2016 has declined by >99%, and cases are confined to three countries with endemic disease. This report updates published (3-4) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication during January 2016-June 2017. In 2016, a total of 25 cases were reported from three countries (Chad [16], South Sudan [six], Ethiopia [three]), compared with 22 cases reported from the same three countries and Mali in 2015 (Table 1). The 14% increase in cases from 2015 to 2016 was offset by the 25% reduction in number of countries with indigenous cases. During the first 6 months of 2017, the overall number of cases declined to eight, all in Chad, from 10 cases in three countries (Chad [four], South Sudan [four] and Ethiopia [two]) during the same period of 2016. Continued active surveillance, aggressive detection, and appropriate management of cases are essential eradication program components; however, epidemiologic challenges, civil unrest, and insecurity pose potential barriers to eradication.
Impact of Inotersen on Subgroups of Patients with Hereditary TTR Amyloidosis: Results from a Double-Blind Placebo-Controlled Trial
Authors: Aaron Yarlas, Giampaolo Merlini, Michelle K White, Asia Sikora Kessler, Andrew Lovley, Spencer D Guthrie, Michael Pollock, Morie A. Gertz
Journal: Blood (2018)
Abstract P5-15-02: Withdrawn
Authors: KD Crew, G Anderson, DL Hershman, MB Terry, P Tehranifar, DL Lew, M Yee, EA Brown, SS Kairouz, LM Minasian, L Ford, ML Neuhouser, BK Arun, PH Brown
Journal: Cancer Research (2018)

Abstract This abstract was withdrawn by the authors.
Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients With Schizophrenia
Authors: T. Scott Stroup, Tobias Gerhard, Stephen Crystal, Cecilia Huang, Zhiqiang Tan, Melanie M. Wall, Chacku Mathai, Mark Olfson
Journal: JAMA Psychiatry (2019)

<h3>Importance</h3> People with schizophrenia are commonly treated with psychotropic medications in addition to antipsychotics, but there is little evidence about the comparative effectiveness of these adjunctive treatment strategies. <h3>Objective</h3> To study the comparative real-world effectiveness of adjunctive psychotropic treatments for patients with schizophrenia. <h3>Design, Setting, and Participants</h3> This comparative effectiveness study used US national Medicaid data from January 1, 2001, to December 31, 2010, to examine the outcomes of initiating treatment with an antidepressant, a benzodiazepine, a mood stabilizer, or another antipsychotic among adult outpatients (aged 18-64 years) diagnosed with schizophrenia who were stably treated with a single antipsychotic. Data analysis was performed from January 1, 2017, to June 30, 2018. Multinomial logistic regression models were used to estimate propensity scores to balance covariates across the 4 medication groups. Weighted Cox proportional hazards regression models were used to compare treatment outcomes during 365 days on an intention-to-treat basis. <h3>Main Outcomes and Measures</h3> Risk of hospitalization for a mental disorder (primary), emergency department (ED) visits for a mental disorder, and all-cause mortality. <h3>Results</h3> The study cohort included 81 921 adult outpatients diagnosed with schizophrenia (mean [SD] age, 40.7 [12.4] years; 37 515 women [45.8%]) who were stably treated with a single antipsychotic and then initiated use of an antidepressant (n = 31 117), a benzodiazepine (n = 11 941), a mood stabilizer (n = 12 849), or another antipsychotic (n = 26 014) (reference treatment). Compared with initiating use of another antipsychotic, initiating use of an antidepressant was associated with a lower risk (hazard ratio [HR], 0.84; 95% CI, 0.80-0.88) of psychiatric hospitalization, whereas initiating use of a benzodiazepine was associated with a higher risk (HR, 1.08; 95% CI, 1.02-1.15); the risk associated with initiating use of a mood stabilizer (HR, 0.98; 95% CI, 0.94-1.03) was not significantly different from initiating use of another antipsychotic. A similar pattern of associations was observed in psychiatric ED visits for initiating use of an antidepressant (HR, 0.92; 95% CI, 0.88-0.96), a benzodiazepine (HR, 1.12; 95% CI, 1.07-1.19), and a mood stabilizer (HR, 0.99; 95% CI, 0.94-1.04). Initiating use of a mood stabilizer was associated with an increased risk of mortality (HR, 1.31; 95% CI, 1.04-1.66). <h3>Conclusions and Relevance</h3> In the treatment of schizophrenia, initiating adjunctive treatment with an antidepressant was associated with reduced risk of psychiatric hospitalization and ED visits compared with initiating use of alternative psychotropic medications. Associations of benzodiazepines and mood stabilizers with poorer outcomes warrant clinical caution and further investigation.
396. Development of GD2-Specific Immunoliposomes for Immunotherapy of Neuroblastoma
Authors: Wei Huang, Daofeng Liu, Linjie Guo, Ekaterina Marinova, Andras Heczey, Leonid Metelitsa
Journal: Molecular Therapy (2016)

Tumor microenvironment (TME) impairs immune effector cell localization, persistence, or the execution of their anti-tumor function. This represents a major and as yet unsolved critical challenge to the development of effective adoptive immunotherapy of solid tumors. To selectively target TME in neuroblastoma and make it permissible for survival and function of tumor-specific effector cells, we have developed a novel nanoparticle (NP) delivery platform which consists of 150 nm immunoliposomes rendered specific for neuroblastoma cells using a single-chain variable fragment (scFv) from the anti-GD2 14g2a mAb. GD2-specific but not control NPs could specifically bind GD2-positive but not GD2-negative neuroblastoma cells in vitro as determined by FACS. To examine the in vivo biodistribution of NPs, DiR-labeled GD2-specific or non-specific NPs were injected to NSG mice implanted with human neuroblastoma xenografts. Tumor tissues and normal organs were analyzed after 72 hours using ex vivo fluorescence imaging. Up to 58% of GD2-specific NPs accumulated at the tumor sites. NPs loaded with human IL-15 effectively delivered cytokine to the tumor site. A combined immunotherapy using human NKT cells expressing a GD2-specific chimeric antigen receptor (CAR) and IL-15-containing NPs resulted in potent in vivo expansion of CAR NKT cells and tumor eradication. In contrast, soluble IL-15 failed to support long-term CAR NKT cell persistence that resulted in tumor recurrence. These results inform design of cancer immunotherapy in combination with TME-modifying NPs.