tbuckley/cabot-search huggingface dataset:
Characteristics of effective self-management interventions in patients with COPD: individual patient data meta-analysis
Authors: Nini H. Jonkman, Heleen Westland, Jaap C.A. Trappenburg, Rolf H.H. Groenwold, Erik W.M.A. Bischoff, Jean Bourbeau, Christine E. Bucknall, David Coultas, Tanja W. Effing, Michael Epton, Frode Gallefoss, Judith Garcia-Aymerich, Suzanne M. Lloyd, Evelyn M. Monninkhof, Huong Q. Nguyen, Job van der Palen, Kathryn L. Rice, Maria Sedeno, Stephanie J.C. Taylor, Thierry Troosters, Nicholas A. Zwar, Arno W. Hoes, Marieke J. Schuurmans
Journal: European Respiratory Journal (2016)

It is unknown whether heterogeneity in effects of self-management interventions in patients with chronic obstructive pulmonary disease (COPD) can be explained by differences in programme characteristics. This study aimed to identify which characteristics of COPD self-management interventions are most effective.Systematic search in electronic databases identified randomised trials on self-management interventions conducted between 1985 and 2013. Individual patient data were requested for meta-analysis by generalised mixed effects models.14 randomised trials were included (67% of eligible), representing 3282 patients (75% of eligible). Univariable analyses showed favourable effects on some outcomes for more planned contacts and longer duration of interventions, interventions with peer contact, without log keeping, without problem solving, and without support allocation. After adjusting for other programme characteristics in multivariable analyses, only the effects of duration on all-cause hospitalisation remained. Each month increase in intervention duration reduced risk of all-cause hospitalisation (time to event hazard ratios 0.98, 95% CI 0.97-0.99; risk ratio (RR) after 6 months follow-up 0.96, 95% CI 0.92-0.99; RR after 12 months follow-up 0.98, 95% CI 0.96-1.00).Our results showed that longer duration of self-management interventions conferred a reduction in all-cause hospitalisations in COPD patients. Other characteristics are not consistently associated with differential effects of self-management interventions across clinically relevant outcomes.
Denosumab treatment of giant cell tumor of bone: Interim analysis of an open-label phase II study
Authors: D. Thomas, S. P. Chawla, K. Skubitz, A. P. Staddon, R. Henshaw, J. Y. Blay, J. Smith, Z. Ye, M. Roudier, S. Jun
Journal: Journal of Clinical Oncology (2008)

10500 Background: Giant cell tumor (GCT) of bone is a benign, locally aggressive osteolytic neoplasm that is associated with significant skeletal morbidity and can be lethal. GCT is rich in RANKL, a key mediator of osteoclast formation, function, and survival, suggesting a role for the RANK pathway in the pathogenesis of GCT and a potential therapeutic effect on tumor growth from denosumab, a fully human monoclonal antibody against RANKL. Methods: Patients were adults with resectable or unresectable GCT. Denosumab 120 mg was administered subcutaneously once monthly with loading doses on days 8 and 15 of month 1. The primary endpoint was tumor response (elimination of ≥90% of giant cells or no radiographic progression of the target lesion) at week 25. Of 35 patients enrolled, 25 were eligible for this interim analysis, 24 received denosumab, and 15 were evaluable for efficacy based on available pre- and post-treatment radiology or histology assessments. Results: Thirteen of 15 patients (87%) had a tumor response: 9 of 9 had a histologic response, and 4 of 6 had a radiographic response. The 2 patients who did not meet radiographic response criteria had stable disease per investigators. Substantial clinical benefit was reported in 9 patients, including reduced pain, increased range of motion, and return to work. Evidence of bone repair was reported in 3 patients. Adverse events (AEs) were reported in 19 patients. One death from disease progression (not treatment-related) occurred during follow-up. No treatment-related serious AEs or neutralizing anti-denosumab antibodies were reported. Conclusions: In this analysis, 87% of patients with recurrent or unresectable GCT responded to denosumab treatment. Further investigation of denosumab as a new therapy for GCT is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen, GlaxoSmithKline, Novartis, Pfizer, PharmaMar Amgen Inc. GlaxoSmithKline, Novartis, Pfizer, PharmaMar Amgen, Novartis Amgen Inc.
Relationship Between Epidemiologic and Endocrinologic Aspects of Cervical Cancer
Authors: Mitsuo Kodama, Toshiko Kodama, Ryozo Totani, Kunio Aoki
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Relationship Between Epidemiologic and Endocrinologic Aspects of Cervical Cancer Get access Mitsuo Kodama, Mitsuo Kodama 2Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Chikusa-Ku, Nagoya, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Toshiko Kodama, Toshiko Kodama 2Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Chikusa-Ku, Nagoya, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ryozo Totani, Ryozo Totani 3Department of Obstetrics and Gynecology, Nagoya National Hospital, Nagoya, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kunio Aoki Kunio Aoki 4Department of Preventive Medicine, Nagoya University School of Medicine, Nagoya, Japan. 5We thank Dr. K. Oshima, Primate Research Institute, Kyoto University, Kyoto, Japan, and Dr. Y. Suzuoki, Nagoya National Hospital, for valuable information, and we are grateful to Mrs. K. Yamauchi, Miss T. Yokochi, Miss M. Takayanagi, and Miss T. Hayashi for excellent technical assistance. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 1, July 1978, Pages 35–39, https://doi.org/10.1093/jnci/61.1.35 Published: 01 July 1978 Article history Received: 24 May 1977 Accepted: 01 February 1978 Published: 01 July 1978
SAT0374 IL-36A Axis is Modulated in Patients with Primary Sjogren's Syndrome and Implicated in the Regulation of Gamma-Delta T Cells Immune Functions
Authors: F. Ciccia, R. Alessandro, C. Alessandri, R. Priori, G. Guggino, S. Raimondo, R. Giacomelli, G. Valesini, A. Rizzo, G. Triolo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> IL-36a is a cytokine that predominantly acts on naive CD4+ T cells and gamma-delta T cells via the IL-36 receptor. IL-36a has been recently demonstrated to be involved in human disease, such as psoriasis, by modulating innate and adaptive immune responses. <h3>Objectives</h3> In this study we aimed to investigate the expression of IL-36 axis and to assess the role of γδ T cells in patients with primary Sjogren9s syndrome (pSS). <h3>Methods</h3> Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 nSS patients. Serum IL-36a was assayed by ELISA. IL-36a, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19, expression in MSGs was assessed by rt-PCR and tissue IL-36a and IL-38 expression also investigated by immuno-histochemistry (IHC). ab and gδ T cells and CD68+ cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. <h3>Results</h3> IL-36a was significantly over-expressed in the serum and in the salivary glands of pSS. Salivary gland IL-36a mRNA expression was correlated with the expression levels of IL-17, IL-22 and IL-23p19 (r<sup>2</sup>=0.45, r<sup>2</sup>=0.66, r<sup>2</sup>=0.73, respectively; p&lt;0.05). IL-38 mRNA that acts as inhibitor of IL-36a was also up-regulated in pSS. In pSS the expression of IL-36α was essentially observed in inflammatory infiltrates among lymphoid cells and cells displaying dendritic morphology. IL-38 was also up-regulated at protein level in the salivary glands of pSS being mainly expressed among acinar epithelial cells and infiltrating mononuclear cells. By confocal microscopy analysis and flow cytometry, ab+CD3+ T cells and CD68<sup>+</sup> cells were confirmed to be the major source of IL-36a in minor salivary glands of pSS. gδ T cells were not significantly expanded in the salivary glands of pSS but produced more IL-17 being their percentage correlated with the focus score. Higher expression of IL-36a and IL-36R was also demonstrated in γδ T cells isolated from pSS compared to controls. <h3>Conclusions</h3> In this study we demonstrate that a significant increase in circulating and tissue levels of IL-36a occurs in pSS and provide also the first evidence of a putative role of IL-17<sup>+</sup>/IL-36<sup>+</sup> γδ T lymphocytes. <h3>Disclosure of Interest</h3> None declared
Endothelial lipid phosphate phosphatase-3 deficiency that disrupts the endothelial barrier function is a modifier of cardiovascular development
Authors: Ishita Chatterjee, Jugajyoti Baruah, Erin E. Lurie, Kishore K. Wary
Journal: Cardiovascular Research (2016)

Lipid phosphate phosphatase-3 (LPP3) is expressed at high levels in endothelial cells (ECs). Although LPP3 is known to hydrolyse the phosphate group from lysolipids such as spingosine-1-phosphate and its structural homologues, the function of Lpp3 in ECs is not completely understood. In this study, we investigated how tyrosine-protein kinase receptor (TEK or Tie2) promoter–dependent deletion of Lpp3 alters EC activities. Lpp3fl/fl mice were crossed with the tg.Tie2Cre transgenic line. Vasculogenesis occurred normally in embryos with Tie2Cre-mediated deletion of Lpp3 (called Lpp3ECKO), but embryonic lethality occurred in two waves, the first wave between E8.5 and E10.5, while the second between E11.5 and E13.5. Lethality in Lpp3ECKO embryos after E11.5 was accompanied by vascular leakage and haemorrhage, which likely resulted in insufficient cardiovascular development. Analyses of haematoxylin- and eosin-stained heart sections from E11.5 Lpp3ECKO embryos showed insufficient heart growth associated with decreased trabeculation, reduced growth of the compact wall, and absence of cardiac cushions. Staining followed by microscopic analyses of Lpp3ECKO embryos revealed the presence of apoptotic ECs. Furthermore, Lpp3-deficient ECs showed decreased gene expression and protein levels of Cyclin-D1, VE-cadherin, Fibronectin, Klf2, and Klf4. To determine the underlying mechanisms of vascular leakage and barrier disruption, we performed knockdown and rescue experiments in cultured ECs. LPP3 knockdown decreased transendothelial electrical resistance and increased permeability. Re-expression of β-catenin cDNA in LPP3-knockdown ECs partially restored the effect of the LPP3 loss, whereas re-expression of p120ctn cDNA did not. These findings demonstrate the essential roles of LPP3 in the maturation of EC barrier integrity and normal cardiovascular development.
Soundings: Graduation for oldies
Authors: James Owen Drife
Journal: BMJ (2002)

Happier than funerals, less fraught than christenings, and cheaper than weddings, graduations are the most enjoyable of family milestones. They are also the most exclusive. With only two tickets per graduand and no black market, most of the family has to be content with the official video.

After years of gazing impassively over the audience as one of the gowned academics on the platform, it comes as a mild shock to find yourself in your Sunday best among the mums and dads. You have noticed that all parents somehow act alike on these occasions and, when your turn comes, you effortlessly follow the pattern.

Your basic instinct is to whoop and whistle at the climactic moment and to accost passers by throughout the day and tell them what a smart kid you've got. Your superego tells you this would be a mistake. New graduates are perceptive and tolerant, but there are limits.

Moreover, says your superego sternly, remember this is our kid's day and you are supporting cast. Hence the dad's characteristic air of controlled pride. He carries his smallest camera and tries to snap discreetly. There is also a tinge of anxiety. Will his choice of restaurant impress the new generation?

Graduations are of two types—at the alma mater and elsewhere. At the University of Elsewhere you expect to get lost so you turn up too early and then try to look casual among the bustling Elsewherians.

At the alma mater you think you know your way around. Big mistake. How can so many one way systems and office blocks appear in only 30 years? Once inside the hall the nostalgia is overwhelming. The first time you were here was as a fresher, waiting in a long queue for the mass chest x ray. When did they decide that tuberculosis was no longer a problem?

No matter where the ceremony, medical or not, you bump into old friends. Once you have exhausted the main topic of conversation (retirement dates) you fall silent and watch the happy graduates—mainly women now, whatever the profession.

It is an odd feeling, being one of the grey brigade. Passing on the baton, what? As we leave the hall, the organ music ends in a huge crescendo. Nobody seems to notice. We're heading for the Pimms.
P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer
Authors: S. Jagadeeshan, A. Subramanian, S. Tentu, S. Beesetti, M. Singhal, S. Raghavan, R.P. Surabhi, J. Mavuluri, H. Bhoopalan, J. Biswal, R.S. Pitani, S. Chidambaram, S. Sundaram, R. Malathi, J. Jeyaraman, A.S. Nair, G. Venkatraman, S.K. Rayala
Journal: Annals of Oncology (2016)
P0042 : Safety and efficacy of sofosbuvir and simeprevir treatment in hepatitis C genotype 1 liver transplant recipients with advanced fibrosis/recurrent cirrhosis
Authors: A.F. Carrion, A. Peyton, D. Avalos, E. Martin, J. Gutierrez, C. O’Brien, P. Martin, K.R. Bhamidimarri
Journal: Journal of Hepatology (2015)
Incidence of oral cancer therapy medication errors at a private university hospital: Rationale for oral cancer therapy specific policies and procedures
Authors: S. D. Stelts, C. C. Nesheiwat, J. Ashley, T. McKibbin, R. Jennifer, A. R. Williams
Journal: Journal of Clinical Oncology (2008)

6624 Background: Medication errors with oral cancer therapies such as methotrexate and temozolomide have resulted in fatalities. A national survey by Weingart S et al. of pharmacy directors from major cancer centers indicated that safe practices are inconsistently applied to oral cancer therapies. The primary objective of this study is to determine the incidence of medication errors associated with oral cancer therapy (defined as cytotoxic or targeted oral therapies for the treatment of cancer excluding corticosteroids and hormonal therapies) at our institution. Methods: A retrospective medical record review was conducted on patients admitted to our institution within 18 months prior to the start of the study. Patients were included if they received at least one of 10 oral cancer therapies (identified as high risk and frequently prescribed cancer therapies at our institution) during their hospitalization and were at least 18 years old. The 10 oral cancer therapies included in the analysis were capecitabine, cyclophosphamide, erlotinib, etoposide, hydroxyurea, imatinib, lenalidomide, methotrexate, temozolomide, and thalidomide. Results: One hundred and eighty four patients met inclusion criteria and 1,774 treatment days were included. Twenty-six charts been analyzed to date with an incidence of 9 medication errors per 201 treatment days. None of these errors were previously reported at our institution. Oral cancer therapies involved were hydroxyurea (n = 3), imatinib (n = 1), methotrexate (n = 2), temozolomide (n = 1), and thalidomide (n = 2). Medical services included hematology, internal medicine, neurology and oncology. Errors occurred during prescribing, dispensing, administering and monitoring. All errors reached the patient. Conclusions: Our preliminary data suggest a need for clearer recommendations to improve oral cancer therapy safe practices at our institution. No significant financial relationships to disclose.
COX‐1 Inhibitors: Beyond Structure Toward Therapy
Authors: Paola Vitale, Andrea Panella, Antonio Scilimati, Maria Grazia Perrone
Journal: Medicinal Research Reviews (2016)

Biosynthesis of prostaglandins from arachidonic acid (AA) is catalyzed by cyclooxygenase (COX), which exists as COX-1 and COX-2. AA is in turn released from the cell membrane upon neopathological stimuli. COX inhibitors interfere in this catalytic and disease onset process. The recent prominent discovery involvements of COX-1 are mainly in cancer and inflammation. Five classes of COX-1 inhibitors are known up to now and this classification is based on chemical features of both synthetic compounds and substances from natural sources. Physicochemical interactions identification between such molecules and COX-1 active site was achieved through X-ray, mutagenesis experiments, specific assays and docking investigations, as well as through a pharmacometric predictive model building. All these insights allowed the design of new highly selective COX-1 inhibitors to be tested into those disease models in which COX-1 is involved. Particularly, COX-1 is expressed at high levels in the early to advanced stages of human epithelial ovarian cancer, and it also seems to play a pivotal role in cancer progression. The refinement of COX-1 selective inhibitor structure has progressed to the stage that some of the inhibitors described in this review could be considered as promising active principle ingredients of drugs and hence part of specific therapeutic protocols. This review aims to outline achievements, in the last 5 years, dealing with the identification of highly selective synthetic and from plant extracts COX-1 inhibitors and their theranostic use in neuroinflammation and ovarian cancer. Their gastrotoxic effect is also discussed.
TCTAP C-129 Once Naughty Child Complicates ‘Right Main'
Authors: Monique Priscilla Fransiska Rotty, Johan Senihardja, Soetandar Widjaja, Hendro Adi Kuncoro, Rizki Francis Pandelaki, Yosua Arthur Iskandar, Benny Mulyanto Setiadi, Bambang Budiono, Edmond Jim, Janry Anton Pangemanan, Agnes Lucia Panda
Journal: Journal of the American College of Cardiology (2016)
Eradication of prostatic high grade intraepithelial neoplasia: Hypothesis and clinical proof
Authors: J. I. Zweig
Journal: Journal of Clinical Oncology (2007)

1534 Background: Recently normal prostate tissue has been found to contain a high concentration of retinoid X receptors (RXRs), they are found in the highest concentrations in ectodermal tissue. Loss of these receptors is associated with prostatic intraepithelial neoplasia (PIN), and can be present in patients with a normal PSA. There are 115,000 cases of high grade PIN discovered yearly in the United States.The drug bexarotene used to treat cutaneous T cell lymphoma (CTCL). The compound is not a true retinoid in structure, perusal of the structure reveals two aromatic rings one of which contains a carboxy group which would make one anticipate strong hydrogen bonding when it undergoes binding to the RXRs as if it were a retinoid, resulting in “up regulation” of the tissue with increase in differentiation to normal tissue. Based upon this it was felt that it would be fruitful to try bexarotene in High Grade PIN. Method: The diagnosis was based upon 12 biopsies which were done in conjunction with ultrasound localization of the biopsy site, with careful recording of there anatomical position. The patient was started on bexarotene 225 mg per day. The drug was given as a single dose once daily; this dose is 40% of the dose normally used to treat CTCL. The drug was administered for 30 doses During the period of therapy the patient was on Atorvastin T4 total was within the normal range. Results: Four weeks following the last dose of bexarotene the prostate was rebiopsied with 12 biopsies taken. Six of the biopsies were taken from the putative area, the rest in an enlarging target like pattern. The repeat biopsy was negative for the presence of PIN. 14 months later 12 more biopsies were obtained using the same technique, these repeat biopsies were also found to be negative; ie. 24 negative biopsies over 14 months. It is unlikely that the previously involved area was missed. Conclusion: If a mechanism of action were to be formulated, the induction of and increase in RXRs in normal prostate cells would be reasonable. Cells that undergo the formation of PIN, strong hydrogen bonding and inability of those cells to produce more receptors could result in apoptosis. Undoubtedly further study is required to evaluate the effect of this drug in high grade PIN. No significant financial relationships to disclose.
Effectiveness of a Layer-by-Layer Microbubbles-Based Delivery System for Applying Minoxidil to Enhance Hair Growth
Authors: Ai-Ho Liao, Ying-Jui Lu, Yi-Chun Lin, Hang-Kang Chen, Huey-Kang Sytwu, Chih-Hung Wang
Journal: Theranostics (2016)

Minoxidil (Mx) is a conventional drug for treating androgenetic alopecia, preventing hair loss, and promoting hair growth.The solubility of Mx has been improved using chemical enhancement methods to increase its skin permeability over the long term.This study created a new ultrasound (US) contrast agent-albumin-shelled microbubbles (MBs) that absorb chitosan oligosaccharide lactate (COL) and Mx-and combined it with sonication by US energy in the water phase to enhance hair growth while shortening the treatment period.COL and Mx grafted with MBs (mean diameter of 1480 nm) were synthesized into self-assembled complexes of COL-MBs and Mx-COL-MBs that had mean diameters of 4150 and 4500 nm, respectively.The US was applied at 3 W/cm 2 for 1 min, and combined with Mx-COL-MBs containing 0.3% Mx.The diffusion of Mx through the dialysis membrane from Mx-COL-MB during US (US+Mx-COL-MB) was more rapid at pH 4 than at pH 7.4, which is favorable given that the environment of the scalp is mildly acidic (pH=4.5-5.5).In Franz diffusion experiments performed in vitro, the release rates at 18 hours in the US+Mx-COL-MBs and US+MBs+Mx groups resulted in 2.3 and 1.7 times the penetration and deposition, respectively, of Mx relative to the group with Mx alone.During 21 days treatment in animal experiments, the growth rates at days 10 and 14 in the US+Mx-COL-MBs group increased by 22.6% and 64.7%, respectively, and there were clear significant differences (p<0.05) between the US+Mx-COL-MBs group and the other four groups.The use of US+Mx-COL-MB in the water phase can increased the effects of Mx so as to shorten the telogen phase, and also increase both the diameter of keratinized hair shafts and the size of hair follicles without causing skin damage.