tbuckley/cabot-search huggingface dataset:
Discontinuation of tumour necrosis factor inhibitors in patients with rheumatoid arthritis in low-disease activity: persistent benefits. Data from the Corrona registry
Authors: Arthur Kavanaugh, Susan J Lee, Jeffrey R Curtis, Jeffrey D Greenberg, Joel M Kremer, Lilian Soto, Carol J Etzel, Vanessa Cox, Kazuki Yoshida, George W Reed, Daniel H Solomon
Journal: Annals of the Rheumatic Diseases (2014)

There is increasing interest in discontinuing biological therapies for patients with rheumatoid arthritis (RA) achieving good clinical responses, provided patients maintain clinical benefit.We assessed patients with RA from the Corrona registry who discontinued treatment with their first tumour necrosis factor inhibitor (TNFi) while in low-disease activity (LDA) or lower levels of disease activity. Patients were followed until they lost clinical benefit, defined as increased disease activity or change in RA medications. Duration of maintenance of clinical benefit was estimated using the Kaplan-Meier method. Cox proportional hazard models were assessed to identify factors related to maintenance of benefit.We identified 717 eligible patients with RA from 35,656 in the Corrona registry. At discontinuation, patients had a median RA duration of 8 years, mean clinical disease activity score of 4.3±0.11; 41.8% were using TNFi as monotherapy. 73.4% of patients maintained benefit for >12 months after discontinuing therapy and 42.2% did so through 24 months. Factors predictive of maintaining clinical benefit in multivariate analysis included lower disease activity, less pain and better functional status at the time of TNFi discontinuation. Among 301 patients initiating their first TNFi within the registry, faster responders (ie, those who achieved LDA in 4 months or less) did better than slower responders (HR 1.54 (95% CI 1.17 to 2.04)). RA disease duration did not affect maintenance of clinical benefit.Discontinuation of a first course of TNFi may be associated with persistent clinical benefit. Half of patients maintained response through 20 months. Several patient characteristics may help predict persistent benefit.
Food System Policy, Public Health, and Human Rights in the United States
Authors: Kerry L. Shannon, Brent F. Kim, Shawn E. McKenzie, Robert S. Lawrence
Journal: Annual Review of Public Health (2015)

The US food system functions within a complex nexus of social, political, economic, cultural, and ecological factors. Among them are many dynamic pressures such as population growth, urbanization, socioeconomic inequities, climate disruption, and the increasing demand for resource-intensive foods that place immense strains on public health and the environment. This review focuses on the role that policy plays in defining the food system, particularly with regard to agriculture. It further examines the challenges of making the food supply safe, nutritious, and sustainable, while respecting the rights of all people to have access to adequate food and to attain the highest standard of health. We conclude that the present US food system is largely unhealthy, inequitable, environmentally damaging, and insufficiently resilient to endure the impacts of climate change, resource depletion, and population increases, and is therefore unsustainable. Thus, it is imperative that the US embraces policy reforms to transform the food system into one that supports public health and reflects the principles of human rights and agroecology for the benefit of current and future generations.
Identifying protein–protein interactions in somatic hypermutation
Authors: Myron F. Goodman, Matthew D. Scharff
Journal: The Journal of Experimental Medicine (2005)

Somatic hypermutation (SHM) in immunoglobulin genes is required for high affinity antibody–antigen binding. Cultured cell systems, mouse model systems, and human genetic deficiencies have been the key players in identifying likely SHM pathways, whereas “pure” biochemical approaches have been far less prominent, but change appears imminent. Here we comment on how, when, and why biochemistry is likely to emerge from the shadows and into the spotlight to elucidate how the somatic mutation of antibody variable (V) regions is generated.
Comparison between different routes of progesterone administration as luteal phase support in infertility treatments
Authors: A. Tavaniotou
Journal: Human Reproduction Update (2000)

Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.
PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non–Small-Cell Lung Cancer
Authors: Luis G. Paz-Ares, Filippo de Marinis, Mircea Dediu, Michael Thomas, Jean-Louis Pujol, Paolo Bidoli, Olivier Molinier, Tarini Prasad Sahoo, Eckart Laack, Martin Reck, Jesús Corral, Symantha Melemed, William John, Nadia Chouaki, Annamaria H. Zimmermann, Carla Visseren-Grul, Cesare Gridelli
Journal: Journal of Clinical Oncology (2013)

Purpose In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P &lt; .001). Here we report final overall survival (OS) and updated safety data. Patients and Methods In all, 939 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m 2 on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). Results The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Conclusion Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.
Anxiety Disorders During Childhood and Adolescence: Origins and Treatment
Authors: Ronald M. Rapee, Carolyn A. Schniering, Jennifer L. Hudson
Journal: Annual Review of Clinical Psychology (2009)

The present review summarizes our current knowledge of the development and management of anxiety in children and adolescents. Consideration is given to limitations of this knowledge and directions for future research. The review begins with coverage of the development and demographic correlates of anxiety in young people and then moves to systematic discussion of some of the key etiological factors, including genetics, temperament, parenting, and individual experiences. The second part of the review describes current treatment strategies and efficacy as well as factors thought to influence treatment outcome, including treatment features, child factors, and parent factors. The review concludes with brief coverage of some more recent developments in treatment including alternative models of delivery and prevention strategies.
THE PREPARATION, PURIFICATION, AND AMINO ACID SEQUENCE OF A POLYPEPTIDE RENIN SUBSTRATE
Authors: Leonard T. Skeggs, Joseph R. Kahn, Kenneth Lentz, Norman P. Shumway
Journal: The Journal of Experimental Medicine (1957)

A purified preparation of a polypeptide renin substrate prepared by tryptic degradation of the protein renin substrate has been analyzed by the fluorodinitrobenzene method and after degradation with renin, carboxypeptidase, and phenylisothiocyanate, has been found to possess the amino acid sequence; asp-arg-val-tyr-ileu-his-pro-phe-his-leu-leu-val-tyr-ser. The first 10 of these amino acids constitutes hypertensin I which is released by cleavage of the leucyl-leucine bond by renin. The remaining 4 amino acids, leu, val, tyr, ser, apparently link hypertensin I to the protein renin substrate.
Efficacy of Multilayered Hosiery in Reducing In-Shoe Plantar Foot Pressure in High-Risk Patients With Diabetes
Authors: Adam P. Garrow, Carine H.M. van Schie, Andrew J.M. Boulton
Journal: Diabetes Care (2005)

High plantar pressure is an acknowledged risk factor in the development of plantar ulcers in the diabetic neuropathic foot. This study examines the ability of preventive foot care (PFC) socks to reduce plantar foot pressures in a sample of high-risk patients with diabetes.Nineteen patients with established peripheral neuropathy attending a complications clinic of the Manchester Diabetes Centre were recruited to the study. Fifteen (78%) of the patients were male, 40-80 years of age, and ulcer-free at the time of recruitment. In-shoe plantar pressure measurements were recorded using the F-Scan and compared PFC socks with ordinary supermarket socks. The analysis measured differences in maximum foot contact area and plantar pressure for the whole foot, forefoot, and peak plantar pressure areas.The results showed a significant increase in maximum foot contact area of 11 cm2 (95% CI 7-11) when subjects wore the PFC socks (P < 0.01). This was accompanied by 5.4 kPa (3.5-7.3) or 9% reduction in total foot pressure (P < 0.01). Similar results were observed at the forefoot, which showed a 14.2% increase in contact area and a 10.2% reduction in peak forefoot pressure.These results suggest that the wearing of PFC socks increases the underfoot contact area and hence decreases plantar foot pressures. Further studies are required to determine whether the pressure and friction reductions achieved by this simple intervention would be effective in reducing the incidence of foot ulcers in high-risk patients.
Postmarketing surveillance study of a non-chlorofluorocarbon inhaler according to the safety assessment of marketed medicines guidelines
Authors: J G Ayres, C D Frost, W F Holmes, D R R Williams, S M Ward
Journal: BMJ (1998)

To evaluate the safety of a non-chlorofluorocarbon metered dose salbutamol inhaler.This was a postmarketing surveillance study, conducted under formal guidelines for company sponsored safety assessment of marketed medicines (SAMM). A non-randomised, non-interventional, observational design compared patients prescribed metered doses of salbutamol delivered by inhalers using either hydrofluoroalkane or chlorofluorocarbon as the propellant. Follow up was three months.646 general practices throughout the United Kingdom.6614 patients with obstructive airways disease (1667 patient years of exposure).Proportions of patients who were: admitted to hospital for respiratory diseases, reported adverse side effects, or withdrew because of adverse affects.There were no significant differences between the hydrofluoroalkane (HFA 134a) and chlorofluorocarbon inhaler groups in relation to the proportions of patients admitted to hospital for respiratory diseases (odds ratio 0.75; 95% confidence interval 0.51 to 1.08) or the proportions who reported adverse events (1.01; 0.88 to 1.17). However, more patients using the hydrofluoroalkane inhaler than the chlorofluorocarbon inhaler withdrew because of adverse events (3.8% and 0.9% respectively).The hydrofluoroalkane inhaler was as safe as the chlorofluorocarbon inhaler when judged by hospital admissions and adverse affects. The study design successfully fulfilled the recommendations of the guidelines. Differences between postmarketing surveillance studies and randomised clinical trials in assessing safety were identified. These may lead to difficulties in the design of postmarketing surveillance studies.
The role of androgens in determining acne severity in adult women
Authors: D. Cibula, M. Hill, O. Vohradnikova, D. Kuzel, M. Fanta, J. Zivny
Journal: British Journal of Dermatology (2000)

Journal Article The role of androgens in determining acne severity in adult women Get access D. Cibula, D. Cibula Departments of Obstetrics and Gynecology and D.Cibula. E‐mail: david.cibula@iol.cz Search for other works by this author on: Oxford Academic Google Scholar M. Hill, M. Hill Institute of Endocrinology, Prague, Czech Republic Search for other works by this author on: Oxford Academic Google Scholar O. Vohradnikova, O. Vohradnikova Dermatology, General Teaching Hospital in Prague, Charles University, Apolinarska 18, 120 00 Prague 2, Czech Republic Search for other works by this author on: Oxford Academic Google Scholar D. Kuzel, D. Kuzel Departments of Obstetrics and Gynecology and Search for other works by this author on: Oxford Academic Google Scholar M. Fanta, M. Fanta Departments of Obstetrics and Gynecology and Search for other works by this author on: Oxford Academic Google Scholar J. Zivny J. Zivny Departments of Obstetrics and Gynecology and Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 2, 1 August 2000, Pages 399–404, https://doi.org/10.1046/j.1365-2133.2000.03669.x Published: 01 August 2000
Phylogenomics of Eukaryotes: Impact of Missing Data on Large Alignments
Authors: Hervé Philippe, Elizabeth A. Snell, Eric Bapteste, Philippe Lopez, Peter W. H. Holland, Didier Casane
Journal: Molecular Biology and Evolution (2004)

Resolving the relationships between Metazoa and other eukaryotic groups as well as between metazoan phyla is central to the understanding of the origin and evolution of animals. The current view is based on limited data sets, either a single gene with many species (e.g., ribosomal RNA) or many genes but with only a few species. Because a reliable phylogenetic inference simultaneously requires numerous genes and numerous species, we assembled a very large data set containing 129 orthologous proteins ( approximately 30,000 aligned amino acid positions) for 36 eukaryotic species. Included in the alignments are data from the choanoflagellate Monosiga ovata, obtained through the sequencing of about 1,000 cDNAs. We provide conclusive support for choanoflagellates as the closest relative of animals and for fungi as the second closest. The monophyly of Plantae and chromalveolates was recovered but without strong statistical support. Within animals, in contrast to the monophyly of Coelomata observed in several recent large-scale analyses, we recovered a paraphyletic Coelamata, with nematodes and platyhelminths nested within. To include a diverse sample of organisms, data from EST projects were used for several species, resulting in a large amount of missing data in our alignment (about 25%). By using different approaches, we verify that the inferred phylogeny is not sensitive to these missing data. Therefore, this large data set provides a reliable phylogenetic framework for studying eukaryotic and animal evolution and will be easily extendable when large amounts of sequence information become available from a broader taxonomic range.
Krupin Eye Valve with Disk for Filtration Surgery
Authors: Theodore Krupin, Lisa F. Rosenberg, Jon M. Ruderman, Marianne E. Feitl, Michael A. Kass, Allan E. Kolker, Martin B. Wax, Carl B. Camras, Jeffrey M. Liebmann, Robert Ritch, Steven M. Podos, Janet B. Serle, Robert A. Schumer, Paul L. Kaufman, Todd W. Perkins
Journal: Ophthalmology (1994)
Safe TNF-based antitumor therapy following p55TNFR reduction in intestinal epithelium
Authors: Filip Van Hauwermeiren, Marietta Armaka, Niki Karagianni, Ksanthi Kranidioti, Roosmarijn E. Vandenbroucke, Sonja Loges, Maarten Van Roy, Jan Staelens, Leen Puimège, Ajay Palagani, Wim Vanden Berghe, Panayiotis Victoratos, Peter Carmeliet, Claude Libert, George Kollias
Journal: Journal of Clinical Investigation (2013)

TNF has remarkable antitumor activities; however, therapeutic applications have not been possible because of the systemic and lethal proinflammatory effects induced by TNF. Both the antitumor and inflammatory effects of TNF are mediated by the TNF receptor p55 (p55TNFR) (encoded by the Tnfrsf1a gene). The antitumor effect stems from an induction of cell death in tumor endothelium, but the cell type that initiates the lethal inflammatory cascade has been unclear. Using conditional Tnfrsf1a knockout or reactivation mice, we found that the expression level of p55TNFR in intestinal epithelial cells (IECs) is a crucial determinant in TNF-induced lethal inflammation. Remarkably, tumor endothelium and IECs exhibited differential sensitivities to TNF when p55TNFR levels were reduced. Tumor-bearing Tnfrsf1a⁺⁺/⁻ or IEC-specific p55TNFR-deficient mice showed resistance to TNF-induced lethality, while the tumor endothelium remained fully responsive to TNF-induced apoptosis and tumors regressed. We demonstrate proof of principle for clinical application of this approach using neutralizing anti-human p55TNFR antibodies in human TNFRSF1A knockin mice. Our results uncover an important cellular basis of TNF toxicity and reveal that IEC-specific or systemic reduction of p55TNFR mitigates TNF toxicity without loss of antitumor efficacy.
Social Media and Diabetes: Can Facebook and Skype Improve Glucose Control in Patients With Type 1 Diabetes on Pump Therapy? One-Year Experience
Authors: Goran Petrovski, Marija Zivkovic, Slavica Subeska Stratrova
Journal: Diabetes Care (2015)

Health care providers are faced with enormous numbers of patients and visits due to the increase in diabetes prevalence (1). As the world is changing, traditional health care services should be adapted for the new era of technology and Internet. Patients use Internet to seek, meet, and interact with a community of patients with similar problems; to share clinical information; and to provide and receive support (2,3). Facebook, with over 1.2 billion registered users worldwide, (4) has specific groups for disease information.

The Facebook group “Diabetes Macedonia” was formed in 2008. It is a closed group that helps patients to share diabetes information and experience. The enormous growth of new users (1,430 patients, family members, and others by September 2014) led to the development of a structured platform by health …
Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial
Authors: Sil Kordes, Michael N Pollak, Aeilko H Zwinderman, Ron A Mathôt, Mariëtte J Weterman, Aart Beeker, Cornelis J Punt, Dick J Richel, Johanna W Wilmink
Journal: The Lancet Oncology (2015)
Eosinophils, mast cells, and basophils in induced sputum from patients with seasonal allergic rhinitis and perennial asthma: Relationship to methacholine responsiveness☆☆☆★
Authors: Antonio Foresi, Clementina Leone, Andrea Pelucchi, Berardino Mastropasqua, Alfredo Chetta, Raffaele D'Ippolito, Luigi Marazzini, Dario Olivieri
Journal: Journal of Allergy and Clinical Immunology (1997)
Fibrosing alveolitis and polymyositis
Authors: P. L. Thompson, I. R. Mackay
Journal: Thorax (1970)

A case of fibrosing alveolitis and polymyositis is described. We think that this, in association with previously published reports, favours a real and not fortuitous association. The basis for the association may be an abnormality of immunity, but this could not be established in the present case nor from those previously published.
H2A.Z landscapes and dual modifications in pluripotent and multipotent stem cells underlie complex genome regulatory functions
Authors: Manching Ku, Jacob D Jaffe, Richard P Koche, Esther Rheinbay, Mitsuhiro Endoh, Haruhiko Koseki, Steven A Carr, Bradley E Bernstein
Journal: Genome biology (2012)

The histone variant H2A.Z has been implicated in nucleosome exchange, transcriptional activation and Polycomb repression. However, the relationships among these seemingly disparate functions remain obscure. We mapped H2A.Z genome-wide in mammalian ES cells and neural progenitors. H2A.Z is deposited promiscuously at promoters and enhancers, and correlates strongly with H3K4 methylation. Accordingly, H2A.Z is present at poised promoters with bivalent chromatin and at active promoters with H3K4 methylation, but is absent from stably repressed promoters that are specifically enriched for H3K27 trimethylation. We also characterized post-translational modification states of H2A.Z, including a novel species dually-modified by ubiquitination and acetylation that is enriched at bivalent chromatin. Our findings associate H2A.Z with functionally distinct genomic elements, and suggest that post-translational modifications may reconcile its contrasting locations and roles.
Idelalisib: First-in-Class PI3K Delta Inhibitor for the Treatment of Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia, and Follicular Lymphoma
Authors: Qingshan Yang, Prexy Modi, Terry Newcomb, Christophe Quéva, Varsha Gandhi
Journal: Clinical Cancer Research (2015)

Idelalisib [Zydelig (Gilead Sciences, Inc.), also known as CAL-101 and GS-1101] was approved in 2014 in the United States and European Union for the treatment of three indolent B-cell neoplasms: relapsed/refractory chronic lymphocytic leukemia (CLL, in combination with rituximab), relapsed follicular lymphoma, and relapsed small lymphocytic lymphoma (as monotherapy). Furthermore, it was approved in the European Union as first-line therapy for poor-prognosis CLL with 17p deletions or TP53 mutations and in patients unsuitable for chemoimmunotherapy. Idelalisib is an orally bioavailable ATP-competitive kinase inhibitor that targets the PI3K p110 isoform δ (PI3Kδ) with high potency and selectivity. PI3Kδ is hyperactivated in B-cell malignancies and plays a pivotal role in the B-cell receptor pathway, a key oncogenic driver in B-cell malignancies. The near exclusive expression of the PI3Kδ isoform in hematopoietic cells and the selectivity of idelalisib for the PI3Kδ isoform are essential for its efficacy and tolerability, even in elderly patients unfit for chemotherapy. Idelalisib is the first PI3K inhibitor approved by the regulatory agencies; this approval will change the treatment landscape of indolent B-cell malignancies.