tbuckley/cabot-search huggingface dataset:
Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13
Authors: Marthe-Sandrine Eiymo Mwa Mpollo, Eric B. Brandt, Shiva Kumar Shanmukhappa, Paritha I. Arumugam, Swati Tiwari, Anastacia Loberg, Devin Pillis, Tilat Rizvi, Mark Lindsey, Bart Jonck, Peter Carmeliet, Vijay K. Kalra, Timothy D. Le Cras, Nancy Ratner, Marsha Wills-Karp, Gurjit K. Khurana Hershey, Punam Malik
Journal: Journal of Clinical Investigation (2015)

Airway hyperresponsiveness (AHR) affects 55%-77% of children with sickle cell disease (SCD) and occurs even in the absence of asthma. While asthma increases SCD morbidity and mortality, the mechanisms underlying the high AHR prevalence in a hemoglobinopathy remain unknown. We hypothesized that placenta growth factor (PlGF), an erythroblast-secreted factor that is elevated in SCD, mediates AHR. In allergen-exposed mice, loss of Plgf dampened AHR, reduced inflammation and eosinophilia, and decreased expression of the Th2 cytokine IL-13 and the leukotriene-synthesizing enzymes 5-lipoxygenase and leukotriene-C4-synthase. Plgf-/- mice treated with leukotrienes phenocopied the WT response to allergen exposure; conversely, anti-PlGF Ab administration in WT animals blunted the AHR. Notably, Th2-mediated STAT6 activation further increased PlGF expression from lung epithelium, eosinophils, and macrophages, creating a PlGF/leukotriene/Th2-response positive feedback loop. Similarly, we found that the Th2 response in asthma patients is associated with increased expression of PlGF and its downstream genes in respiratory epithelial cells. In an SCD mouse model, we observed increased AHR and higher leukotriene levels that were abrogated by anti-PlGF Ab or the 5-lipoxygenase inhibitor zileuton. Overall, our findings indicate that PlGF exacerbates AHR and uniquely links the leukotriene and Th2 pathways in asthma. These data also suggest that zileuton and anti-PlGF Ab could be promising therapies to reduce pulmonary morbidity in SCD.
Declining Incidence of Stroke and Dementia: Coincidence or Prevention Opportunity?
Authors: Luciano A. Sposato, Moira K. Kapral, Jiming Fang, Sudeep S. Gill, Daniel G. Hackam, Lauren E. Cipriano, Vladimir Hachinski
Journal: JAMA Neurology (2015)

This longitudinal population-based study explores trends in declining dementia rates using health care administrative data from the Canadian Institute for Health Information for the province of Ontario, Canada.
Responding to the needs of refugees
Authors: Frank Arnold, Cornelius Katona, Juliet Cohen, Lucy Jones, David McCoy
Journal: BMJ (2015)

Knowledge of and skills in human rights medicine will be needed

At the time of writing it is unclear how many people will eventually receive refuge in Britain from encampments in countries surrounding Syria through the UN vulnerable persons relocation scheme. The government’s current commitment to receive a maximum of 20 000 over five years, if delivered at a constant rate, would result in 4000 arrivals a year.1 It is also unclear when they will arrive and what financial and other arrangements are being made for local councils to support them. But even if the UK maintains its decision to opt out of the EU refugee sharing scheme, the number of asylum seekers reaching the UK by other routes may increase, given that more than half a million people seeking protection arrived in Europe by sea in 2015.

Whatever the numbers, many will have high levels of complex physical, psychological, social, and legal needs arising from their experiences in their countries of origin …
Hepatitis C viral infection increases the risk of lymphoid‐neoplasms: A population‐based cohort study
Authors: Tung‐Hung Su, Chun‐Jen Liu, Tai‐Chung Tseng, Shih‐Wan Chou, Chen‐Hua Liu, Hung‐Chih Yang, Shang‐Ju Wu, Pei‐Jer Chen, Ding‐Shinn Chen, Chi‐Ling Chen, Jia‐Horng Kao
Journal: Hepatology (2015)

Chronic hepatitis C viral (HCV) infection has been associated with non‐Hodgkin's lymphoma (NHL); however, the results are inconsistent among regions with different HCV prevalence rates. The temporal relationship, risk estimates, and association between HCV and lymphoid‐neoplasms remain unclear. This study investigated the temporal relationship between HCV infection and lymphoid‐neoplasms using a nationwide population‐based cohort. Patients with chronic HCV infection were retrieved from the Taiwan National Health Insurance Research Database during 2001‐2005 and designated as the HCV cohort. Those with prior malignancies or coinfected with hepatitis B or human immunodeficiency virus were excluded. The age, sex, and comorbidities, including rheumatological disorders and diabetes, were matched by propensity scores to another non‐HCV cohort. Both cohorts were followed longitudinally until 2009 for a new diagnosis of any lymphoid‐neoplasms or NHL. A total of 11,679 HCV and 46,716 non‐HCV patients were included and followed for 8 years. The incidence rates of any lymphoid‐neoplasms and NHL were significantly greater in the HCV cohort than the non‐HCV cohort (48.4 versus 22.1, and 37.0 versus 17.5 per 100,000 person‐years, respectively, both P &lt; 0.001), even after we excluded lymphoid‐neoplasms developed within the first year of follow‐up. Cox proportional hazards regression analysis (after adjustment for age, sex, numbers of annual medical visits during follow‐up, and comorbidities) indicated that HCV infection was associated with an increased risk of either any lymphoid‐neoplasms (hazard ratio = 2.30, 95% confidence interval 1.55‐3.43, P &lt; 0.0001) or NHL (hazard ratio = 2.00, 95% confidence interval 1.27‐3.16, P = 0.003). Conclusion: After adjustment for confounders and biases, chronic HCV infection is temporally associated with a two‐fold increased risk of lymphoid‐neoplasms, especially NHL, in Asian patients; additional large studies are needed to explore whether HCV eradication can reduce the incidence of lymphoid‐neoplasms. (H epatology 2016;63:721–730)
The A20210 Allele of the Prothrombin Gene Is Not Frequently Associated With the Factor V Arg 506 to Gln Mutation in Thrombophilic Families
Authors: Martine Alhenc-Gelas, Véronique Le Cam-Duchez, Joseph Emmerich, Thierry Frebourg, Jean-Noël Fiessinger, Jeanne-Yvonne Borg, Martine Aiach
Journal: Blood (1997)
The incidence of severe alpha-1-antitrypsin (AAT) deficiency alleles in COPD patients – Update from Central Eastern European (CEE) AAT Network
Authors: Joanna Chorostowska-Wynimko, Anna Kubincova, Nikolay Yanev, Ruxandra Ulmeanu, Radoslaw Struniawski, Pavol Pobeha, Nikolay Kyuchukov, Oana Deleanu, Beata Poplawska-Wisniewska, Ruzena Tkacova, Yavor Ivanov, Florin Mihaltan, Arunas Valiulis
Journal: European Respiratory Journal (2014)

Data concerning the prevalence of AAT deficiency in general population or respiratory patients in CEE countries are limited or non-existent. The overwhelming majority of individuals with AAT deficiency remains undiagnosed. We present data from the CEE A1AT Network established in 2013.

DBS samples were collected in 2013 from 866 COPD patients in Poland (n=372), Bulgaria (n=74), Lithuania (n=21), Romania (n=272) and Slovakia (n=127). AAT serum concentration in DBS was measured by nephelometry and PI*S and PI*Z alleles were identified by real-time PCR.

Results: PI*S or PI*Z deficiency alleles were observed respectively in 31 (3,6%) and 42 (4,8 %) patients. In total, any AAT mutation was diagnosed in 72 COPD patients (8,3%). The calculated frequency for PI*Z and PI*S alleles in overall tested population was 30,6 (95% CI: 22,5-38,7) and 17,9 (95% CI: 11,6-24,1), respectively. The AAT gene prevalence calculated by Hardy-Weinberg equilibrium was: 1/1.10 for non-S non-Z, 1/29 for S non-Z, 1/3122 for SS, 1/17 for non-S Z, 1/913 for SZ and 1/1068 for ZZ.

Conclusion: Our results confirm the relatively high frequency of AAT deficiency in COPD patients CEE region. CEE A1AT Network is the very first attempted to establish the diagnostic and scientific collaboration for AATD in CEE.
The Epidemic of HPV-Associated Oropharyngeal Cancer Is Here: Is It Time to Change Our Treatment Paradigms?
Authors: Erich M. Sturgis, K. Kian Ang
Journal: Journal of the National Comprehensive Cancer Network (2011)

Although relatively uncommon, oropharyngeal cancers are increasing in incidence despite declining prevalence of smoking and in direct opposition to a decreasing incidence of all other head and neck cancers. An epidemic of human papillomavirus (HPV)–associated oropharyngeal cancers seems to account for these incidence trends. Important demographic, behavioral, and prognostic characteristics define this unique population. Changes in prevention, diagnosis, evaluation, staging, and treatment are needed. This article summarizes the epidemiology and clinical behavior of HPV-associated oropharyngeal cancer and discusses evolving/potential paradigms of treatment. However, data are currently insufficient to change treatment paradigms for HPV-associated oropharyngeal cancer outside of a closely monitored clinical trial.
Complete metastasectomy after high-dose interleukin-2 (HD IL-2) therapy for melanoma
Authors: Melinda Chu, Eddy Hsueh, John Richart
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Our aim was to describe our experience with surgery after High-dose Interleukin-2 (HD IL-2) therapy in patients who were eligible for complete metastasectomy after treatment. A retrospective chart review was performed on patients with metastatic melanoma seen at Saint Louis
Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection
Authors: H Kelly, S Barry, K Laurie, G Mercer
Journal: Eurosurveillance (2010)

Four Canadian studies have suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed infection with 2009 pandemic influenza A(H1N1). During the influenza season of 2009 in Victoria, Australia, this virus comprised 97% of all circulating influenza viruses for which sub-typing was available. We found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus. Ferret experiments have suggested protection against pandemic influenza A(H1N1) 2009 from multiple prior seasonal influenza infections but not from prior seasonal vaccination. Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity which is initially almost complete. We suggest these observations together can explain the apparent discrepant findings in Canada and Victoria. In Victoria there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection. In Canada seasonal influenza preceded circulation of the pandemic virus. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a proportion of vaccinated members of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza. It may therefore have appeared as if seasonal vaccination increased the risk of infection with pandemic influenza A(H1N1) virus.
Pneumatic displacement of submacular hemorrhage11The following letter addresses an article that appeared in the October 1999 issue of the Journal: Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. (Ophthalmology 1999;106:1900–6)
Authors: Lutz Hesse, Peter Kroll
Journal: Ophthalmology (2000)
Silent IL2RG Gene Editing in Human Pluripotent Stem Cells
Authors: Li B Li, Chao Ma, Geneve Awong, Marion Kennedy, German Gornalusse, Gordon Keller, Dan S Kaufman, David W Russell
Journal: Molecular Therapy (2015)

Many applications of pluripotent stem cells (PSCs) require efficient editing of silent chromosomal genes. Here, we show that a major limitation in isolating edited clones is silencing of the selectable marker cassette after homologous recombination and that this can be overcome by using a ubiquitous chromatin opening element (UCOE) promoter-driven transgene. We use this strategy to edit the silent IL2RG locus in human PSCs with a recombinant adeno-associated virus (rAAV)-targeting vector in the absence of potentially genotoxic, site-specific nucleases and show that IL2RG is required for natural killer and T-cell differentiation of human PSCs. Insertion of an active UCOE promoter into a silent locus altered the histone modification and cytosine methylation pattern of surrounding chromatin, but these changes resolved when the UCOE promoter was removed. This same approach could be used to correct IL2RG mutations in X-linked severe combined immunodeficiency patient-derived induced PSCs (iPSCs), to prevent graft versus host disease in regenerative medicine applications, or to edit other silent genes.
Induction Therapy With Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) For Primary Plasma Cell Leukemia (pPCL)
Authors: Madeline Phillips, Christine I. Chen, Rodger E. Tiedemann, Frcpa, Suzanne Trudel, Esther Masih-Khan, Victor H Jimenez-Zepeda, Vishal Kukreti
Journal: Blood (2013)
FIRST Trial—Decision to Publish a Description of the Study
Authors: Julie Ann Sosa, Howard Bauchner
Journal: JAMA Surgery (2015)

Karl Y. Bilimoria, MD, MS; Jeanette W. Chung, PhD; Larry V. Hedges, PhD; Allison R. Dahlke, MPH; Remi Love, BS; Mark E. Cohen, PhD; John Tarpley, MD; John Mellinger, MD; David M. Mahvi, MD; Rachel R. Kelz, MD, MSCE; Clifford Y. Ko, MD, MS, MSHS; David B. Hoyt, MD; Frank H. Lewis, MD
SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression
Authors: Masamitsu Tanaka, Shintaro Shimamura, Sei Kuriyama, Daichi Maeda, Akiteru Goto, Namiko Aiba
Journal: Cancer Research (2015)

Abstract Tumor-associated macrophages (TAM) play complex and pivotal roles during cancer progression. A subset of metastasis-associated macrophages accumulates within metastatic sites to promote the invasion and growth of tumor cells. Src kinase–associated phosphoprotein 2 (SKAP2), a substrate of Src family kinases, is highly expressed in macrophages from various tumors, but its contribution to the tumor-promoting behavior of TAMs is unknown. Here, we report that SKAP2 regulates podosome formation in macrophages to promote tumor invasion and metastasis. SKAP2 physically interacted with Wiskott–Aldrich syndrome protein (WASP) and localized to podosomes, which were rarely observed in SKAP2-null macrophages. The invasion of peritoneal macrophages derived from SKAP2-null mice was significantly reduced compared with wild-type macrophages, but could be rescued by the restoration of functional SKAP2 containing an intact tyrosine phosphorylation site and the ability to interact with WASP. Furthermore, SKAP2-null mice inoculated with lung cancer cells exhibited markedly decreased lung metastases characterized by reduced macrophage infiltration compared with wild-type mice. Moreover, intravenously injected SKAP2-null macrophages failed to efficiently infiltrate established tumors and promote their growth. Taken together, these findings reveal a novel mechanism by which macrophages assemble the appropriate motile machinery to infiltrate tumors and promote disease progression, and implicate SKAP2 as an attractive candidate for therapeutically targeting TAMs. Cancer Res; 76(2); 358–69. ©2015 AACR.
The role of toxin A and toxin B in Clostridium difficile-associated disease
Authors: Glen P. Carter, Julian I. Rood, Dena Lyras
Journal: Gut Microbes (2010)

Recently, we constructed and characterized isogenic tcdA and tcdB mutants of a virulent Clostridium difficile strain and used a hamster model of disease to demonstrate that toxin B, not toxin A, is essential for virulence of this emerging pathogen. Earlier studies had shown that purified toxin A alone was able to induce C. difficile disease pathology and that purified toxin B was not effective unless it was co-administered with toxin A, suggesting that the toxins act synergistically. In this addendum we discuss this paradigm-shifting conclusion in the context of current strain epidemiology, particularly with respect to naturally occurring toxin A-negative, toxin B-positive isolates and the NAP1/027 epidemic isolates. The role of toxin receptors and how variant toxins might exert their effects is also discussed in relation to the published data. We conclude that it is critical to use the natural infection process to dissect the role of toxins in disease, and that future studies are contingent on such work. The impact and importance of animal models of C. difficile virulence are therefore considered within this frame of reference.
US Preventive Services Task Force
Authors: Alfred O. Berg
Journal: JAMA (1988)

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 Journals 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 2024 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
Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer
Authors: Dawn L. Hershman, Joseph M. Unger, Jason D. Wright, Scott Ramsey, Cathee Till, Catherine M. Tangen, William E. Barlow, Charles Blanke, Ian M Thompson, Maha Hussain
Journal: JAMA Oncology (2015)

Although intermittent androgen-deprivation therapy (ADT) has not been associated with better overall survival in prostate cancer (PC), it has the potential for lower adverse effects. To our knowledge, the incidence of long-term adverse health events has not been reported.To examine long-term late events in elderly patients randomized to intermittent or continuous ADT to determine whether late cardiovascular and endocrine events would be lower in patients treated with intermittent ADT.This was a secondary analysis of a multicenter clinical trial using linkage between patient data from S9346, a randomized SWOG trial of intermittent vs continuous ADT in men with metastatic PC, and corresponding Medicare claims.Intermittent or continuous ADT.The main outcome was to identify long-term adverse health events by treatment arm. Patients were classified as having an adverse health event if they had any hospital claim--or at least 2 physician or outpatient claims at least 30 days apart--for any of the following diagnoses: ischemic and thrombotic events, endocrine events, sexual dysfunction, dementia, and depression. To incorporate time from beginning of observation through evidence of an event, we determined the cumulative incidence of each event. Competing risks Cox regression was used, adjusting for covariates.In total, 1134 eligible US-based male patients with metastatic PC were randomized to continuous vs intermittent ADT in the S9346 trial. A total of 636 of trial participants (56%) had at least 1 year of continuous Medicare parts A and B coverage and no health maintenance organization participation. The median age was 71.3 years. The most common long-term events were hypercholesterolemia (31%) and osteoporosis (19%). The 10-year cumulative incidence of ischemic and thrombotic events differed by arm; 24% for continuous and 33%for intermittent ADT (hazard ratio, 0.69; P = .02). There were no statistically significant differences by arm in any other adverse health events.Contrary to our hypothesis that intermittent ADT would reduce long-term health-related events compared with continuous ADT, we found that older men assigned to intermittent ADT had no apparent reduction in bone, endocrine, or cognitive events and an increased incidence of ischemic and thrombotic events.clinicaltrials.gov Identifier: NCT00002651.
Web Resources for Metagenomics Studies
Authors: Pravin Dudhagara, Sunil Bhavsar, Chintan Bhagat, Anjana Ghelani, Shreyas Bhatt, Rajesh Patel
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract The development of next-generation sequencing (NGS) platforms spawned an enormous volume of data. This explosion in data has unearthed new scalability challenges for existing bioinformatics tools. The analysis of metagenomic sequences using bioinformatics pipelines is complicated by the substantial complexity of these data. In this article, we review several commonly-used online tools for metagenomics data analysis with respect to their quality and detail of analysis using simulated metagenomics data. There are at least a dozen such software tools presently available in the public domain. Among them, MGRAST, IMG/M, and METAVIR are the most well-known tools according to the number of citations by peer-reviewed scientific media up to mid-2015. Here, we describe 12 online tools with respect to their web link, annotation pipelines, clustering methods, online user support, and availability of data storage. We have also done the rating for each tool to screen more potential and preferential tools and evaluated five best tools using synthetic metagenome. The article comprehensively deals with the contemporary problems and the prospects of metagenomics from a bioinformatics viewpoint.
Mode of action of maintenance immunotherapy therapy with the TLR-9 agonist MGN1703 in metastatic colorectal carcinoma: the Phase III IMPALA study
Authors: Alexander Stein, Kerstin Kapp, Werner Scheithauer, Ramon Salazar, Michel Ducreux, Tom Waddell, Dirk Arnold, Christophe Tournigand, Alberto Sobrero, Eric Van Cutsem, Manuel Schmidt, David Cunningham
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts MGN1703, a potent immunomodulatory Toll-like receptor 9 (TLR-9) agonist, was compared to placebo in the previous double-blind, randomized Phase II IMPACT study. The drug was given as switch maintenance in 59 patients with metastatic colorectal cancer (mCRC) not progressing after 4
Mental Health Reform Will Not Reduce US Gun Violence, Experts Say
Authors: Rita Rubin
Journal: JAMA (2015)

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