tbuckley/cabot-search huggingface dataset:
SP0071 Is obesity a risk for ra?
Authors: T. Uhlig
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> According to the World Health Organisation (WHO) guidelines, individuals with a BMI of &gt;30 kg/m<sup>2</sup> are classified as obese. Obesity is on a global scale rising in prevalence and is a recognised as a cause of chronic disability. As is threatens public health, obesity has attracted significant attention in the general population, especially due to its association with significant metabolic and cardiovascular complications. In research on rheumatoid arthritis (RA) BMI is frequently reported as a demographical variable, but obesity has not been thoroughly studied. A link between obesity and RA is plausible, as in adipose tissue biologic mechanisms of inflammation exist and may be linked to chronic systemic inflammation. Obesity has in performed studies been considered a controversial risk factor for RA. While several studies have examined the potential influence of obesity on the development of RA, the results have been inconsistent. While a few studies from the United States have found no or only modest association between obesity and the risk of RA, some European studies found significant risks for an association between RA and obesity.The prevalence of obesity has risen sharply in recent years which may increase our ability to better study possible associations between obesity and RA in the future. Existing evidence may thus point toward a slightly increased of obesity for the risk of RA. <h3>Disclosure of Interest</h3> None declared
Biological therapy for psoriasis and risk of cancer
Authors: I. Garcia-Doval, M.A. Descalzo, K.J. Mason, A.D. Cohen, A.D. Ormerod, F.J. Gómez-García, S. Cazzaniga, I. Feldhamer, H. Ali, E. Herrera-Acosta, C.E.M. Griffiths, R. Stern, L. Naldi
Journal: British Journal of Dermatology (2018)

Psoriasis is a common skin disease that affects up to 3% of people worldwide. Psoriasis is driven by faults in the immune system (which protects the body from infection), which leads to excess skin production. People with the most severe form of psoriasis are given therapies to dampen down the immune system. Systemic therapies (methotrexate and ciclosporin) work to reduce the whole immune system, while biologic therapies (adalimumab, etanercept, and ustekinumab) are targeted to specific immune pathways in the skin. However, there is concern that these therapies may increase the risk of cancer. This study of psoriasis patients in Ireland, Israel, Italy, Spain, and the U.K. aimed to find out if the amount of time spent on these therapies increases the risk of cancer. Each person who developed a cancer during the study was compared to four cancer‐free psoriasis patients (controls) of the same sex, age, dermatology centre, and year of entry into the study. The total time spent on systemic and biologic therapies was calculated for each patient. The authors did not find a difference in the time spent on systemic or biologic therapies between patients who developed a cancer and controls. This result remained unchanged after considering the possible effects of previous exposure to other systemic therapies, duration of psoriasis, smoking, previous exposure to phototherapy and other simultaneous diseases. This study showed that cancers were not more likely to develop after up to 8 years of treatment with biologic therapies.
CD28 and ICOS expression in human ovarian carcinoma cells
Authors: Jennifer Luth, Breton Barrier
Journal: Cancer Research (2007)

LB-341  Many factors have been suggested to contribute to the rapid autonomous proliferation of epithelial ovarian carcinoma, but current understanding does not explain this observed behavior. We report the unanticipated finding of combined CD28, ICOS and ICOS ligand (ICOSL; B7-H2) expression in the OVCAR-3 ovarian adenocarcinoma cell line. CD28 is a lymphocyte-restricted trans-membrane receptor kinase required for lymphocyte activation. CD28 interacts with antigen-presenting cell B7 protein resulting in initiation of the cell cycle and expression of anti-apoptotic proteins such as Bcl XL. ICOS (inducible co-stimulator) is a costimulatory receptor homologous to CD28 that is upregulated on activated T-cells after CD28 engagement. ICOS engages ICOSL expressed on antigen presenting cells and leads to both sustained lymphocyte proliferation and secretion of IL-10. Objective: Characterize CD28, ICOS, ICOSL and B7 molecule expression and function in human ovarian carcinoma cell line NIH: OVCAR-3. Methods: RT-PCR was used to amplify CD28, ICOS, ICOSL and B7 (CD80/CD86) cDNA produced from the OVCAR-3 cell line. “No-RT” negative controls were employed. Amplified product was sequenced for identity confirmation of each gene product. Western blot analysis was employed using polyclonal antibodies specific for CD28, ICOS, ICOSL and B7 protein. All experiments were repeated at least twice with fresh cells. Results: CD28, ICOS, ICOSL and CD86 mRNA were confirmed in the OVCAR-3 cell line. Expression of CD80 mRNA was absent. “No RT” controls were negative and sequence results confirmed each. Western analysis confirmed CD28, ICOS and ICOSL protein in OVCAR-3 cell lysate, while CD86 protein was absent. Conclusions: The novel finding that CD28, ICOS and ICOSL are all co-expressed in a non-lymphocyte lineage cancer has important implications both in cancer immuno-biological and cell cycle/apoptosis research. If future studies demonstrate evidence of function in cell proliferation or cytokine secretion similar to that found in lymphocytes, the door may be opened for novel therapeutic tools for treatment of ovarian cancer.
Abstract 12565: Transitional Care Model Decreases Readmission in the Left Ventricular Assist Device Patients
Authors: Jackeline Iseler
Journal: Circulation (2016)

Decreasing 30-day readmission rates is critical to minimizing penalties from Medicare and Medicaid. Hospital readmission rates in the Left Ventricular Assist Device (LVAD) programs are 26% to 76% and are highly contingent on successful transitions to home. A Transitional Care Model (TCM) approach is comprehensive, holistic and involves collaboration between the patient and their caregiver. The efforts guided by the TCM, in managing symptoms, education of self-management, coordinating care, and maintaining relationships, are patient and caregiver focused. The principles of the TCM involve patient screening to evaluate for their risk for readmission. The purpose of this pilot study is to evaluate the effectiveness of an intervention based on the TCM in reducing readmission rate. This pilot of the TCM was conducted at a single major medical center which places approximately 60 LVADs yearly. A total of ten participants were enrolled using convenience sampling between June and August of 2015. The eight-week program consisted of an individualized self-management care plan and a combination of weekly follow-up home visits or phone calls. Medical records were reviewed in addition to obtaining participant satisfaction surveys. Pilot evaluation is based on the 30-day readmission rate, participant satisfaction, and program costs. Of the ten participants, six completed the program. The 30-day readmission rate for the six was 16.7%, as compared to the hospital’s readmission rate of non-enrolled participants at 32.1%. The participants expressed overall satisfaction with the program and would willingly use the program if needed; they also said they would recommend the program to family and friends. The total program costs were estimated at $125,444. The cost of readmission at the 32.1% rate and 16.7% are $674,100 and $350,700 respectfully; with a potential cost avoidance of the TCM program of $248,356. Patients with an LVAD experience compounding stressors of managing a chronic illness, an acute surgical intervention, and a life-sustaining device. The TCM pilot was able to achieve successful outcomes in the midst of these stressors. Further inquiry in interventions consistent with TCM is needed to advance care and transitions in the LVAD patient population.
Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity
Authors: Benjamin Knier, Michael Hiltensperger, Christopher Sie, Lilian Aly, Gildas Lepennetier, Thomas Engleitner, Garima Garg, Andreas Muschaweckh, Meike Mitsdörffer, Uwe Koedel, Bastian Höchst, Percy Knolle, Matthias Gunzer, Bernhard Hemmer, Roland Rad, Doron Merkler, Thomas Korn
Journal: Nature Immunology (2018)
Alteration of mesenchymal stem cells polarity by laminar shear stimulation promoting β-catenin nuclear localization
Authors: Wei-Ta Chen, Wei-Tse Hsu, Meng-Hua Yen, Chun A Changou, Chia-Li Han, Yu-Ju Chen, Ji-Yen Cheng, Tzu-Hao Chang, Oscar Kuang-Sheng Lee, Jennifer Hui-Chun Ho
Journal: Biomaterials (2018)
Long-term follow-up after switching from originator infliximab to its biosimilar CT-P13: the weight of nocebo effect
Authors: Vincent Germain, Marc Scherlinger, Thomas Barnetche, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2018)

To date, all available data regarding the switch from bio-originator to its biosimilar are reassuring, and the switch has been recommended as a shared patient–physician decision in recent consensus-based recommendations.1 In particular, the Norway's infliximab switching study (NOR-SWITCH study), a 52-week randomised double-blind trial, strongly supports the efficacy and safety of the switch from originator infliximab (OI) to its biosimilar CT-P13 in patients with a stable disease.2 However, long-term follow-up data are required to confirm the efficacy and safety of the switch.

In a previous real-life study, we demonstrated a high acceptance of 89% (89/100) and a 72% (64/89) retention rate after a median follow-up of 33 weeks in a cohort of patients with stable rheumatic diseases switched from OI to CT-P13.3 This retention rate was lower compared with two control cohorts: a historic cohort of 82 patients treated with OI in 2013, and …
Research to Promote Longevity and Health Span in Companion Dogs: A Pediatric Perspective
Authors: Benjamin S. Wilfond, Kathryn M. Porter, Kate E. Creevy, Matt Kaeberlein, Daniel Promislow
Journal: The American Journal of Bioethics (2018)

"Research to Promote Longevity and Health Span in Companion Dogs: A Pediatric Perspective." The American Journal of Bioethics, 18(10), pp. 64–65
COPD biomarkers and phenotypes: opportunities for better outcomes with precision imaging
Authors: George R. Washko, Grace Parraga
Journal: European Respiratory Journal (2018)

A number of chronic diseases have benefited from both imaging and personalised medicine, but unfortunately, for patients with chronic obstructive pulmonary disease (COPD), there has been little clinical uptake or recognition of the key advances in thoracic imaging that might help detect disease early, or, perhaps more importantly, might help develop and phenotype patients for novel or personalised therapies that may halt disease progression. We outline our vision for how computed tomography and magnetic resonance imaging may be used to better inform COPD patient care, and, perhaps more importantly, how these may be used to help develop new therapies directed at early disease. We think that imaging and precision medicine should be considered and used together as “precision imaging” at specific stages of COPD when the major pathologies may be more responsive to therapy. While “precision medicine” is the tailoring of medical treatment to individual patients, we define “precision imaging” as the tailoring of specific therapies and interventions to individual patients with a detailed quantitative understanding of their specific imaging phenotypes and measurements. Finally, we stress the importance of “seeing” the pathology, because without this understanding, you can neither treat nor cure patients with COPD.
GECP 1605/NIVEX TRIAL nivolumab in the real world: The SPANISH expanded access program experience in pretreated advanced NSCLC
Authors: M. Majem Tarruella, J. Campillo, J.F. Grau Béjar, E. Carcereny, R. Bernabe Caro, Y. Garcia, A. Artal-Cortes, M. González Cao, P. Lianes, A. Paredes Lario, M. Sereno Moyano, X. Mielgo Rubio, J.A. Macias, M. Provencio Pulla, D. Rodriguez-Abreu
Journal: Annals of Oncology (2018)
Activated β-catenin in Foxp3+ regulatory T cells links inflammatory environments to autoimmunity
Authors: Tomokazu Sumida, Matthew R. Lincoln, Chinonso M. Ukeje, Donald M. Rodriguez, Hiroshi Akazawa, Tetsuo Noda, Atsuhiko T. Naito, Issei Komuro, Margarita Dominguez-Villar, David A. Hafler
Journal: Nature Immunology (2018)
Using Brain-Based Phenotyping to Improve Discovery in Psychiatry
Authors: Carol A. Tamminga, Elena I. Ivleva
Journal: JAMA Psychiatry (2018)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Abstract LB-330: A novel role of tumor suppressor BRCA1 in regulating integrity of heterochromatin structure.
Authors: Quan Zhu, Gerald Pao, Nina Tonnu, Inder M Verma
Journal: Cancer Research (2008)

Abstract Introduction: BRCA1, as well as BRCA2, were identified as the hereditary breast and ovarian cancer susceptibility genes that can account for almost all of inherited cases of breast cancers. BRCA1 is a multifunctional nuclear protein with a RING domain at the N-terminus. Heterochromatin is chromatin containing inactive genes. Pericentromeric heterochromatin is composed of highly repetitive tandem DNA repeats whose transcription is constitutively silenced. In mice, the repeats are classified as major and minor satellite repeats. Heterochromatin protein 1 (HP1) plays a critical role in maintaining heterochromatin structure. Methods: To study the biological function of the tumor suppressor BRCA1, we deleted BRCA1 in nestin positive neuronal stem cells in the brain and showed that the animals displayed severe neuro-developmental deficits. In the course of this work we discovered a novel molecular defect in BRCA1 deficient cells, i.e., a failure to maintain integrity of the heterochromatic structure. Results: In the absence of BRCA1, the number of heterochromatic centers is severely reduced in mouse neuronal cells. HP1 proteins are destabilized, and more importantly, the transcription of satellite DNA is derepressed in mouse neural progenitor cells, mouse fibroblasts, and human cancer cells, including a BRCA1 deficient breast cancer cell line. The defect in silencing invariably appears after the loss of the BRCA1 allele in our paradigm prior to exhibiting any neoplastic phenotype. What is the mechanism of BRCA1 in regulating the heterochromatin integrity? ChIP analysis showed that BRCA1 physically associates with both major satellite DNA and minor satellite DNA, whereas the association is diminished in the BRCA1 knockout animals. More intriguingly, the absence of BRCA1 binding to satellite DNA correlates with a drastic reduction of ubiquitinated histone H2A at the constitutive heterochromatin region. Because BRCA1 contains an E3 ubiquitin ligase activity which is enhanced by BARD1 and the complex ubiquitinate histone H2A in vitro, we examined the heterochromatin silencing in cells with different BRCA1 mutants. These experiments showed that the E3 ligase activity of BRCA1 is required for repression of satellite DNA transcription. Conclusions: Our working model is that mutations of BRCA1 may destabilize the protein complex and lead to defects in the heterochromatin integrity, thereby affecting the stability of the genome which is a hallmark of cancer. Given that mutants in the RING domains are the same as in women who have pathological diseases, we hypothesize that deregulation of satellite DNA transcription can be explored as an early detection marker for breast cancer progression in BRCA1 patients.
GW29-e1038 Relationship between medical insurance status and reperfusion therapy in patients 75 years and older with STEMI: findings from the CCC-ACS Project
Authors: Yongchen Hao, Jing Liu, Jun Liu, Na Yang, Sidney C. Smith, Yong Huo, Gregg C. Fonarow, Junbo Ge, Kathryn A. Taubert, Louise Morgan, Changsheng Ma, Yaling Han, Dong Zhao
Journal: Journal of the American College of Cardiology (2018)
Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis
Authors: Laurien M Buffart, Maike G Sweegers, Anne M May, Mai J Chinapaw, Jonna K van Vulpen, Rob U Newton, Daniel A Galvão, Neil K Aaronson, Martijn M Stuiver, Paul B Jacobsen, Irma M Verdonck-de Leeuw, Karen Steindorf, Melinda L Irwin, Sandi Hayes, Kathleen A Griffith, Alejandro Lucia, Fernando Herrero-Roman, Ilse Mesters, Ellen van Weert, Hans Knoop, Martine M Goedendorp, Nanette Mutrie, Amanda J Daley, Alex McConnachie, Martin Bohus, Lene Thorsen, Karl-Heinz Schulz, Camille E Short, Erica L James, Ronald C Plotnikoff, Gill Arbane, Martina E Schmidt, Karin Potthoff, Marc van Beurden, Hester S Oldenburg, Gabe S Sonke, Wim H van Harten, Rachel Garrod, Kathryn H Schmitz, Kerri M Winters-Stone, Miranda J Velthuis, Dennis R Taaffe, Willem van Mechelen, Marie José Kersten, Frans Nollet, Jennifer Wenzel, Joachim Wiskemann, Johannes Brug, Kerry S Courneya
Journal: JNCI Journal of the National Cancer Institute (2018)

Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment.Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided.Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values.Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.
Inhibitory killer cell immunoglobulin-like receptors strengthen CD8 <sup>+</sup> T cell–mediated control of HIV-1, HCV, and HTLV-1
Authors: Lies Boelen, Bisrat Debebe, Marcos Silveira, Arafa Salam, Julia Makinde, Chrissy h. Roberts, Eddie C. Y. Wang, John Frater, Jill Gilmour, Katie Twigger, Kristin Ladell, Kelly L. Miners, Jyothi Jayaraman, James A. Traherne, David A. Price, Ying Qi, Maureen P. Martin, Derek C. Macallan, Chloe L. Thio, Jacquie Astemborski, Gregory Kirk, Sharyne M. Donfield, Susan Buchbinder, Salim I. Khakoo, James J. Goedert, John Trowsdale, Mary Carrington, Simon Kollnberger, Becca Asquith
Journal: Science Immunology (2018)

Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8
Uremic Toxin Indoxyl Sulfate Promotes Proinflammatory Macrophage Activation Via the Interplay of OATP2B1 and Dll4-Notch Signaling
Authors: Toshiaki Nakano, Shunsuke Katsuki, Mingxian Chen, Julius L. Decano, Arda Halu, Lang Ho Lee, Diego V. S. Pestana, Angelo S. T. Kum, Rodrigo K. Kuromoto, Whitney S. Golden, Mario S. Boff, Gabriel C. Guimaraes, Hideyuki Higashi, Kevin J. Kauffman, Takashi Maejima, Takehiro Suzuki, Hiroshi Iwata, Albert-László Barabási, Jon C. Aster, Daniel G. Anderson, Amitabh Sharma, Sasha A. Singh, Elena Aikawa, Masanori Aikawa
Journal: Circulation (2018)

Chronic kidney disease (CKD) increases cardiovascular risk. Underlying mechanisms, however, remain obscure. The uremic toxin indoxyl sulfate is an independent cardiovascular risk factor in CKD. We explored the potential impact of indoxyl sulfate on proinflammatory activation of macrophages and its underlying mechanisms.We examined in vitro the effects of clinically relevant concentrations of indoxyl sulfate on proinflammatory responses of macrophages and the roles of organic anion transporters and organic anion transporting polypeptides (OATPs). A systems approach, involving unbiased global proteomics, bioinformatics, and network analysis, then explored potential key pathways. To address the role of Delta-like 4 (Dll4) in indoxyl sulfate-induced macrophage activation and atherogenesis in CKD in vivo, we used 5/6 nephrectomy and Dll4 antibody in low-density lipoprotein receptor-deficient (Ldlr-/-) mice. To further determine the relative contribution of OATP2B1 or Dll4 to proinflammatory activation of macrophages and atherogenesis in vivo, we used siRNA delivered by macrophage-targeted lipid nanoparticles in mice.We found that indoxyl sulfate-induced proinflammatory macrophage activation is mediated by its uptake through transporters, including OATP2B1, encoded by the SLCO2B1 gene. The global proteomics identified potential mechanisms, including Notch signaling and the ubiquitin-proteasome pathway, that mediate indoxyl sulfate-triggered proinflammatory macrophage activation. We chose the Notch pathway as an example of key candidates for validation of our target discovery platform and for further mechanistic studies. As predicted computationally, indoxyl sulfate triggered Notch signaling, which was preceded by the rapid induction of Dll4 protein. Dll4 induction may result from inhibition of the ubiquitin-proteasome pathway, via the deubiquitinating enzyme USP5. In mice, macrophage-targeted OATP2B1/Slco2b1 silencing and Dll4 antibody inhibited proinflammatory activation of peritoneal macrophages induced by indoxyl sulfate. In low-density lipoprotein receptor-deficient mice, Dll4 antibody abolished atherosclerotic lesion development accelerated in Ldlr-/- mice. Moreover, coadministration of indoxyl sulfate and OATP2B1/Slco2b1 or Dll4 siRNA encapsulated in macrophage-targeted lipid nanoparticles in Ldlr-/- mice suppressed lesion development.These results suggest that novel crosstalk between OATP2B1 and Dll4-Notch signaling in macrophages mediates indoxyl sulfate-induced vascular inflammation in CKD.