tbuckley/cabot-search huggingface dataset:
Dynamic tracking of functional gene modules in treated juvenile idiopathic arthritis
Authors: Nan Du, Kaiyu Jiang, Ashley D. Sawle, Mark Barton Frank, Carol A. Wallace, Aidong Zhang, James N. Jarvis
Journal: Genome Medicine (2015)

We have previously shown that childhood-onset rheumatic diseases show aberrant patterns of gene expression that reflect pathology-associated co-expression networks. In this study, we used novel computational approaches to examine how disease-associated networks are altered in one of the most common rheumatic diseases of childhood, juvenile idiopathic arthritis (JIA). Using whole blood gene expression profiles derived from children in a pediatric rheumatology clinical trial, we used a network approach to understanding the impact of therapy and the underlying biology of response/non-response to therapy. We demonstrate that therapy for JIA is associated with extensive re-ordering of gene expression networks, even in children who respond inadequately to therapy. Furthermore, we observe distinct differences in the evolution of specific network properties when we compare children who have been treated successfully with those who have inadequate treatment response. Despite the inherent noisiness of whole blood gene expression data, our findings demonstrate how therapeutic response might be mapped and understood in pathologically informative cells in a broad range of human inflammatory diseases.
Fortnightly Review: How can impact factors be improved?
Authors: E. Garfield
Journal: BMJ (1996)

Impact factors are widely used to rank and evaluate journals. They are also often used inappropriately as surrogates in evaluation exercises. The inventor of the Science Citation Index warns against the indiscriminate use of these data. Fourteen year cumulative impact data for 10 leading medical journals provide a quantitative indicator of their long term influence. In the final analysis, impact simply reflects the ability of journals and editors to attract the best papers available.
Phase I study of paclitaxel and topotecan in patients with advanced tumors: a cancer and leukemia group B study.
Authors: R C Lilenbaum, M J Ratain, A A Miller, J B Hargis, D R Hollis, G L Rosner, S M O'Brien, L Brewster, M R Green, R L Schilsky
Journal: Journal of Clinical Oncology (1995)

PURPOSE To define the dose-limiting toxicities (DLTs) and the recommended phase II doses of paclitaxel combined with topotecan, without and with filgrastim support. PATIENTS AND METHODS Patients with advanced solid tumors and a maximum of one prior chemotherapy regimen for metastatic disease were eligible if they had a performance status of 0 to 1 and normal renal, hepatic, and bone marrow function. Prior treatment with taxanes or comptothecin analogs, and prior pelvic irradiation were not allowed. Patients with a history of cardiac disease or on medications known to affect cardiac conduction were excluded. The dose of topotecan was fixed at 1.0 mg/m2/d for 5 days. The dose of paclitaxel was escalated until the maximum-tolerated dose (MTD), without and with filgrastim 5 micrograms/kg subcutaneously (SC) on days 6 to 14, was reached. Paclitaxel was administered over 3 hours on day 1 before topotecan. Treatment cycles were repeated every 21 days. RESULTS Of 46 patients entered, 45 were assessable for toxicity and 34 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 80 mg/m2 on day 1 in combination with topotecan 1.0 mg/m2/d for 5 days. With filgrastim, the dose of paclitaxel was escalated to 230 mg/m2 in combination with the same dose of topotecan. At this dose level, one patient had hematologic DLT and a second patient developed neuromuscular DLT. Three patients had a partial response (PR): one with head and neck cancer, a second with non-small-cell lung cancer, and the third with colon cancer. CONCLUSION We conclude that paclitaxel can be given at clinically relevant doses in combination with topotecan and filgrastim. The recommended dose for phase II studies is paclitaxel 230 mg/m2 on day 1 and topotecan 1.0 mg/m2/day for 5 days with filgrastim 5 micrograms/kg on days 6 to 14.
High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome.
Authors: U Popat, D Przepiork, R Champlin, W Pugh, K Amin, R Mehra, J Rodriguez, S Giralt, J Romaguera, A Rodriguez, A Preti, B Andersson, I Khouri, D Claxton, M de Lima, M Donato, P Anderlini, J Gajewski, F Cabanillas, K van Besien
Journal: Journal of Clinical Oncology (1998)

This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy.A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995.Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression.Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.
Administration of BCG vaccination: Survey of practice in the Mersey region, UK
Authors: Sean Mackin, Syed M.H. Kazmi, Nick Coombes, Mohammed Hussain, Clifford Bisacre, Peter Davies
Journal: European Respiratory Journal (2012)

Background  A UK wide survey in 2005 showed wide variation in BCG practice and that the providers were uncertain in various aspects of the administration. The National Institute of Clinical Excellence (NICE) published guidelines in 2006, which along with Department of Health guidance aimed to standardise practice. We intended to assess regional BCG service 6 years later.  Method  4 TB centres providing BCG vaccination across Mersey region were contacted and data regarding current practice of BCG administration was collected.  Results  The adherence to the guidelines was recorded as compliance. See table.  * The other sites used were right upper arm or upper thigh. Reasons included patient preference or confusing scar.  There were no recorded episodes of anaphylaxis in the past 12 months. All centres referred patients with severe adverse local reactions appropriately.  Conclusions  Our survey demonstrates that NICE recommendations and their implementation were essential in elucidating areas of uncertainty in the administration of BCG vaccination and subsequently the practice is now uniform across the Mersey region. We intend to extend this survey to national level.
Abstract 1088: Acute Hypoglycemia Induces Mitochondria-Mediated Superoxide Production and Apoptosis in Endothelial Cells: Inhibition by AMP Kinase Activation Through an eNOS Dependent Mechanism
Authors: Michael Widlansky, Jingli Wang, Anna Alexanian, David D Gutterman
Journal: Circulation (2009)

Background: Recent studies employing intense glycemic control in type 2 diabetic and critically ill patients have highlighted the excessive cardiovascular risk associated with the development of hy...
The Effect of the New Method of Neoadjuvant Chemotherapy on the Oxidative Processes in Patients with Soft Tissue Sarcomas
Authors: E.I. Surikova, P.S. Kachesova, I.A. Goroshinskaja, E.A. Andrejko, E.V. Shalashnaja, L.A. Nemashkalova, T.V. Ausheva
Journal: Annals of Oncology (2014)
Yemen's health system buckles under Saudi led bombardment and blockade
Authors: O. Dyer
Journal: BMJ (2015)

Yemen has ground to a halt and faces a humanitarian catastrophe under the twin pressures of war and blockade, say the United Nations and the Red Cross and other international aid agencies.

The country’s health system is in a state of collapse, with at least 158 medical facilities completely shut down, Unicef has reported, and many more operating with little or no electricity.

After three months of Saudi bombing, and with street fighting between contending Yemeni forces, at least 2800 people have been killed and 12 500 wounded. But away from the direct violence it is the naval blockade imposed by the Saudi led coalition that is hurting the most. 

The mostly Saudi and Egyptian warships enforcing the blockade are charged with denying alleged attempts by Iran to deliver arms to the Houthi militia, an armed group of the Shi’ite Zaidi sect that overthrew the government in February. But the blockade has actually turned away 80% of commercial shipping from a country heavily dependent on imports for daily survival.

The United Kingdom’s foreign secretary, Philip Hammond, promised in March to support the Saudi effort in “every practical way short of engaging in combat,” and the UK has provided many of the bombs dropped on Yemen. But the UK government has become concerned about the effects of the blockade and has urged its coalition partners to focus on “intelligence driven” interdictions only of ships suspected of carrying weapons, though so far to no avail.

A spokesman for the US Department of State said that it continued “to urge all sides, including the Saudis, to exercise restraint and avoid unnecessary violence. We also urge all parties to allow the entry and delivery of urgently needed food, medicine, fuel, and other necessary assistance.” Accelerated US arms sales …
Regular review: Management of chronic uveitis
Authors: P. J McCluskey
Journal: BMJ (2000)

To many, uveitis is an acute problem that resolves after treatment with topical corticosteroids. While this may be true of acute anterior uveitis, many forms of uveitis are chronic in nature and often require continuous treatment. The uveitis may be anterior, posterior, or both, and there can be considerable ocular morbidity. Of people aged under 65 who are registered legally blind, 10% are visually compromised because of uveitis and its complications—very nearly the same number affected by diabetic retinopathy. 1 2 Given that uveitis is a much rarer disorder than diabetes (about 250 times less common), this gives some indication of the severity of the problems that can occur. This article describes the management of chronic uveitis, including its diagnosis and differential diagnosis, indications for and types of treatment, and the management of complications.

#### Summary points

Intraocular inflammation has various causes and can be acute or chronic

In either case the inflammatory process can be apparently localised to the eye or be part of a systemic disease such as sarcoidosis or Beh¸et's disease

The inflammation can occur in any part of the eye—anterior, posterior, or both—and visual loss can occur with any type

Treatment depends on the location and severity of the inflammation, with systemic drugs being reserved for sight threatening posterior disease

Complications are common and include cataract, glaucoma, macular oedema—all of which can reduce vision

Chronic uveitis encompasses a heterogeneous group of diseases, many of which are idiopathic in origin.3 Systemic diseases, including sarcoidosis and Beh¸et's syndrome, can be associated with either acute or chronic uveitis. Chronic uveitis can be differentiated from acute recurrent anterior uveitis by its rate of progression4 and can usefully be defined as active uveitis that persists longer than three months. Chronic uveitis is associated with a high incidence of vision threatening complications such …
Supportive Care Organization Compared Between Patients and Oncologist National Survey
Authors: F. Scotte, C. Herve, J. Tourani, R. Bugat, M. Rouge-Bugat, F. Farsi, N. Jovenin, M. Namer, C. Tournigand, P. Leroy, S. Oudard, I. Krakowski
Journal: Annals of Oncology (2014)
California ends vaccine exemptions on grounds of belief—will other states follow?
Authors: Michael McCarthy
Journal: BMJ (2015)

This week California ended all non-medical exemptions to mandatory vaccines, Michael McCarthy reports

After a bitter battle, California has ended vaccine exemptions on the basis of religion or personal belief. Under the new law, signed by Governor Jerry Brown on 30 June, unvaccinated children in the state will not be allowed to attend school, day care programs, and nurseries, unless they have a medical reason, such as an allergy, for not receiving a vaccination. Previously, just two other US states, West Virginia and Mississippi, limited exemptions to medical reasons.

Supporters of the bill, called SB 277, argue that high exemption rates in some communities are responsible for recent outbreaks of measles and pertussis in California and other states and pose a growing threat to public health.1 2 3 4 In a floor debate before the vote in the State Assembly last week, Assemblywoman Catharine B Baker, a Republican from San Ramon, in the San Francisco Bay area, said, “We should fight for the liberty of not just only those who want not to vaccinate their kids but for those who can’t, those who are most vulnerable in our community, whether it is the newborn infants, the immunosuppressed, or the elderly.”

But opponents of the bill argued that it was wrong for the state to intrude in what should be a parental decision. “We do not have the right nor should we have the power to take away a parent’s right to choose what to put into their children,” said Assemblyman Devon Mathis, a Republican from Visalia, north of Los Angeles. …
Widespread non-additive and interaction effects within HLA loci modulate the risk of autoimmune diseases
Authors: Tobias L Lenz, Aaron J Deutsch, Buhm Han, Xinli Hu, Yukinori Okada, Stephen Eyre, Michael Knapp, Alexandra Zhernakova, Tom W J Huizinga, Gonçalo Abecasis, Jessica Becker, Guy E Boeckxstaens, Wei-Min Chen, Andre Franke, Dafna D Gladman, Ines Gockel, Javier Gutierrez-Achury, Javier Martin, Rajan P Nair, Markus M Nöthen, Suna Onengut-Gumuscu, Proton Rahman, Solbritt Rantapää-Dahlqvist, Philip E Stuart, Lam C Tsoi, David A van Heel, Jane Worthington, Mira M Wouters, Lars Klareskog, James T Elder, Peter K Gregersen, Johannes Schumacher, Stephen S Rich, Cisca Wijmenga, Shamil R Sunyaev, Paul I W de Bakker, Soumya Raychaudhuri
Journal: Nature Genetics (2015)
The effect of treating obstructive sleep apnea with positive airway pressure on depression and other subjective symptoms: A systematic review and meta-analysis
Authors: Madhulika A. Gupta, Fiona C. Simpson, Danika C.A. Lyons
Journal: Sleep Medicine Reviews (2015)

Patients with obstructive sleep apnea (OSA) frequently present with symptoms of depression and anxiety. The objective of this study is to determine if treatment with positive airway pressure (PAP) improves symptoms of depression and anxiety. A systematic review was conducted to identify clinical trials of PAP that contained a validated measure of depression severity. Meta-analysis was conducted for depression, anxiety, excessive daytime sleepiness (EDS), quality of life (QoL) and respiratory variables. The systematic review included 33 reports. Pre-post-test analysis of PAP showed a moderate effect size (Hedge's g, 95% CI) for depression 0.524 [0.401-0.647], but a low effect size compared to oral placebo (0.355 [0.187-0.524]) and no effect when compared to dental appliances (0.107 [-0.72-0.287]) and sham PAP (-0.049 [-0.292-0.194]). Anxiety, EDS, and QoL showed similar improvement in pre-post-test analysis, but a lack of superiority to dental appliances and sham PAP. PAP was superior to all comparators for respiratory variables. PAP has a moderate clinical effect on symptoms of depression and anxiety in OSA, but it is not superior to dental appliances or sham PAP. The improvement in subjective symptoms, such as depression and anxiety, may be mediated by patient expectations and contact with healthcare providers.
Prognostic factors for progression-free and overall survival in advanced biliary tract cancer
Authors: J. Bridgewater, A. Lopes, H. Wasan, D. Malka, L. Jensen, T. Okusaka, J. Knox, D. Wagner, D. Cunningham, J. Shannon, D. Goldstein, M. Moehler, T. Bekaii-Saab, M.G. McNamara, J.W. Valle
Journal: Annals of Oncology (2015)
The expression of dual-specificity phosphatase 1 mRNA is downregulated in lesional psoriatic skin
Authors: R.B. Kjellerup, C. Johansen, K. Kragballe, L. Iversen
Journal: British Journal of Dermatology (2012)

The p38 mitogen-activated protein kinase (MAPK) plays an important role in inflammatory processes and displays increased activity in psoriasis. Dual-specificity phosphatase 1 (DUSP1) is an important negative regulator of p38 MAPK activity.To study mRNA expression of DUSP1 in normal human epidermal keratinocytes (NHEKs) stimulated with proinflammatory cytokines and to investigate DUSP1 in psoriatic skin.NHEKs were cultured in vitro and punch biopsies were obtained from the skin of patients with psoriasis vulgaris and atopic dermatitis. mRNA expression was analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).In NHEKs, interleukin (IL)-1β induced DUSP1 mRNA expression in a rapid and time-dependent manner through the p38 MAPK/mitogen- and stress-activated kinase (MSK) signalling pathway. DUSP1 mRNA expression was demonstrated to be significantly downregulated in psoriatic skin lesions compared with paired samples of nonlesional psoriatic skin. This was in contrast to atopic dermatitis. The downregulation of DUSP1 mRNA in lesional psoriatic skin was not explained by the difference in the mRNA expression of the potential DUSP1 transcript stability-affecting proteins Hu antigen R or tristetraprolin. Furthermore, DUSP1 mRNA expression was shown not to increase during the early course of treatment with the antitumour necrosis factor-α antibody adalimumab.In lesional psoriatic skin, the p38 MAPK negative feedback mechanism provided by DUSP1 seems to be inhibited. Downregulation of DUSP1 may contribute to the sustained inflammatory response seen in psoriasis.
Improving Patient Outcomes With Cancer Genomics
Authors: Robert W. Schnepp, Kristopher R. Bosse, John M. Maris
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 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
Local suppression of Epstein-Barr virus (EBV)-specific cytotoxicity in biopsies of EBV-positive Hodgkin's disease
Authors: T Frisan, J Sjoberg, R Dolcetti, M Boiocchi, V De Re, A Carbone, C Brautbar, S Battat, P Biberfeld, M Eckman
Journal: Blood (1995)
Prostate Cancer Screening and Determining the Appropriate Prostate-Specific Antigen Cutoff Values
Authors: William J. Catalona, Stacy Loeb
Journal: Journal of the National Comprehensive Cancer Network (2010)

Prostate-specific antigen (PSA) in combination with digital rectal examination forms the basis for current prostate cancer (CaP) screening programs. Although PSA screening was recently shown to reduce CaP-specific mortality in the European randomized trial, its limitations include the risk for unnecessary prostate biopsy and the diagnosis and treatment of some CaP that might never have caused suffering or death. A potential way to minimize these pitfalls is through the use of derivatives of PSA, particularly PSA kinetics, to increase the specificity for clinically relevant CaP. CaP is the second-leading cause of cancer death in men in the United States and many other westernized countries; accordingly, judicious screening of healthy men allows for diagnosis sufficiently early that all options (i.e., treatment or surveillance) are still available in most cases.
The relative contributions of histamine and prostanoids to bronchoconstriction provoked by isocapnic hyperventilation in asthma
Authors: JP Finnerty, A Harvey, ST Holgate
Journal: European Respiratory Journal (1992)

It has been proposed that exercise provokes bronchoconstriction in asthma by inducing mast cell degranulation, and that this occurs secondary to the hyperpnoea of exercise causing hypertonicity of the airway lining fluid. We investigated the contribution of the mast cell products, histamine and prostaglandins, to the bronchoconstriction induced by isocapnic hyperventilation (ISH) using single doses of terfenadine, a specific histamine H1-receptor antagonist, and flurbiprofen, a potent cyclooxygenase inhibitor. We also investigated the effect of flurbioprofen in single dose on bronchial histamine reactivity. Eleven asthmatics took part in a two phase, double-blind, randomized study. In phase 1, subjects attended on three occasions and received either terfenadine 180 mg, flurbiprofen 150 mg, or placebo, prior to 6 min of ISH. The mean maximum percentage fall in forced expiratory volume in one second (FEV1) induced by ISH was 31.5(+/- 3.2)% following placebo, 29.7(+/- 4.4)% following flurbiprofen (NS), and reduced to 16.6(+/- 3.7)% following terfenadine (p less than 0.01). In phase 2, subjects received bronchial challenge with histamine following either flurbiprofen 150 mg or placebo. No significant change in bronchial reactivity following flurbiprofen was seen. We conclude that as administered in this study, flurbiprofen has no effect on baseline bronchial reactivity to histamine. The inhibitory effect of terfenadine indicates that histamine, probably from airway mast cells, makes an important contribution to bronchoconstriction induced by isocapnic hyperventilation, whereas prostaglandin release has no significant role.
Up-regulation of micro-RNA765 in human failing hearts is associated with post-transcriptional regulation of protein phosphatase inhibitor-1 and depressed contractility
Authors: Wen‐Feng Cai, Guan‐Sheng Liu, Chi Keung Lam, Stela Florea, Jiang Qian, Wen Zhao, Tracy Pritchard, Kobra Haghighi, Djamel Lebeche, Long Jason Lu, Jingyuan Deng, Guo‐Chang Fan, Roger J. Hajjar, Evangelia G. Kranias
Journal: European Journal of Heart Failure (2015)