tbuckley/cabot-search huggingface dataset:
FRI0499 A multinational qualitative study in giant cell arteritis: patient perceptions of diagnosis, treatment, impact on health-related quality of life and contextual factors
Authors: J.C. Robson, C. Almeida, J. Dawson, A. Bromhead, S.L. Mackie, C. Hill, E. Hoon, C. Davis, R. Greenwood, R. Luqmani, B. Dasgupta, C. Guly, J.D. Pauling, R. Watts, E. Dures
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Giant cell arteritis (GCA) is the commonest form of systemic vasculitis caused by inflammation of the blood vessels around the head and neck, with the highest incidence in women aged 70–79 years (7.4 per 10 000 person-years). Patients present with headache, jaw claudication and polymyalgia rheumatica with visual loss in 20%. Treatment is with high dose glucocorticoids. <h3>Objectives</h3> Identify and define the range of patient experiences in relation to GCA, and effects on health related quality of life in patients from the United Kingdom and Australia. <h3>Methods</h3> Semi-structured qualitative interviews with patients from the UK and Australia explored health-related quality of life and patient perspectives on the experience of GCA. Interviews were recorded, transcribed and analysed. Patients were purposively sampled to include both genders, a range of disease durations and organ involvement (visual loss and large vessel involvement). Data were analysed with inductive thematic analysis and managed using NVivo 10. The sample size was determined by the point at which no new substantive themes emerged. <h3>Results</h3> Thirty-one interviews were conducted. Demographics and disease features shown in table 1. Individual sub-codes were identified then grouped into overarching themes: "Anxieties around getting a diagnosis of GCA", "Description of symptoms related to GCA and its treatment", "Lack of bodily strength, stability and stamina; difficulties with completing daily tasks", "Difficulties with participating in social activities, work and caring roles", "Not feeling normal and impact on general perception of health", "Anxiety and fear of the future". Contextual factors impacted on how patients experienced GCA including "Response to treatment and adverse effects", "Receiving support from family, friends and health care workers", "Adopting successful self-management techniques, e.g. keeping fit and active" and "Presence of pre-existing co-morbidities and development of secondary conditions e.g. cardiovascular disease, osteoporosis or diabetes". <h3>Conclusions</h3> Patients with GCA have described a range of themes of interest in relation to their disease. These data could be used as the basis of developing a patient reported measure of outcome in GCA. <h3>Disclosure of Interest</h3> None declared
Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses
Authors: Susan Yost, Philip Stashenko, Yoonhee Choi, Maria Kukuruzinska, Caroline A. Genco, Andrew Salama, Ellen O. Weinberg, Carolyn D. Kramer, Jorge Frias-Lopez
Journal: International Journal of Oral Science (2018)

Oral squamous cell carcinoma (OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients. A search of the oral microbiome has revealed a group of bacteria closely associated with the most common type of oral cancer, and whose activity may play a role in its development. Oral squamous cell carcinoma (OSCC) has been linked to tobacco and alcohol consumption, but there's increasing interest in the role bacteria might play in its initiation and growth. To better understand the behaviour of the various microbes present in the mouths of healthy people and those with OSCC, Jorge Frias-Lopez at the University of Florida in Gainesville and his colleagues carried out a metatranscriptome analysis, which identifies the most actively expressed genes. This revealed significant differences in their microbial communities, with Fusidobacteria particularly enriched and hyperactive in patients with OSCC. The team also identified microbial activities that were consistently associated with cancer.
Naloxone Accessibility Without a Prescriber Encounter Under Standing Orders at Community Pharmacy Chains in Texas
Authors: Kirk E. Evoy, Lucas G. Hill, Lindsey Groff, Lubna Mazin, Christian C. Carlson, Kelly R. Reveles
Journal: JAMA (2018)

This study evaluated naloxone accessibility from chain pharmacies in Texas 32 months after state legislation allowing pharmacists to dispense naloxone under standing orders from authorizing prescribers.
Projecting incidence of post-stroke cognitive impairment and dementia in the Irish population aged 40–89 years in 2015 to 2025
Authors: Eithne Sexton, Nora Donnelly, Martin O'Flaherty, Maria Guzman-Castillo, Niamh Merriman, Anne Hickey, Maev-Ann Wren, Kathleen Bennett
Journal: The Lancet (2018)
The Privilege of Grief
Authors: Michelle M. Kittleson
Journal: Annals of Internal Medicine (2018)

On Being a Doctor20 November 2018The Privilege of GriefMichelle M. Kittleson, MD, PhDMichelle M. Kittleson, MD, PhDSmidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California (M.M.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-2049 Audio Reading - “The Privilege of Grief” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads "The Privilege of Grief" by M.M. Kittleson. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail As a cardiologist specializing in advanced heart failure and transplantation, I have saved lives and witnessed plenty of tragedy. The faces of the patients I have lost stay with me far longer than those of the patients I have saved. For years I lay awake at night grieving the losses, but this grief has nowhere to go. Loved ones may move through Elisabeth Kübler-Ross' stages of grief—from denial to anger to bargaining to sadness and, finally, to acceptance—but what is the trajectory of a doctor's grief? Through bitter experience and self-preservation, I have fashioned stages: Separate fault from fluke, distinguish ... Author, Article, and Disclosure InformationAffiliations: Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California (M.M.K.)Corresponding Author: Michelle M. Kittleson, MD, PhD, 8536 Wilshire Boulevard, Suite 301, Los Angeles, CA 90211; e-mail, michelle.[email protected]org. PreviousarticleNextarticle Advertisement Audio Reading - “The Privilege of Grief” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads "The Privilege of Grief" by M.M. Kittleson. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 20 November 2018Volume 169, Issue 10Page: 729-730KeywordsFearHeartHeart failureSleepStrokeSudden cardiac deathSyncopeTachycardiaTransplantationWalking ePublished: 20 November 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes
Authors: Timothy R. Hammond, Connor Dufort, Lasse Dissing-Olesen, Stefanie Giera, Adam Young, Alec Wysoker, Alec J. Walker, Frederick Gergits, Michael Segel, James Nemesh, Samuel E. Marsh, Arpiar Saunders, Evan Macosko, Florent Ginhoux, Jinmiao Chen, Robin J.M. Franklin, Xianhua Piao, Steven A. McCarroll, Beth Stevens
Journal: Immunity (2018)
Treatment experience of thymoma and thymic carcinoma in tertiary cancer institute in India
Authors: V. Tirumala, M.C. Suresh Babu, K. Govind Babu, D. Lokanatha, L.A. Jacob, K.N. Lokesh, A.H. Rudresha, L.K. Rajeev, S.C. Saldanha, G.V. Giri
Journal: Annals of Oncology (2018)
Antinuclear autoantibodies: discordance among four different assays
Authors: Yovana Pacheco, Diana M Monsalve, Yeny Acosta-Ampudia, Cilia Rojas, Juan-Manuel Anaya, Carolina Ramírez-Santana
Journal: Annals of the Rheumatic Diseases (2018)

Detection of antinuclear antibodies (ANAs) is of paramount importance for diagnosis and assessment of autoimmune diseases (ADs), but may vary depending on the method used. Therefore, we aimed to compare three different line immunoassays (LIAs) for ANAs testing in order to simultaneously evaluate their concordance with the results obtained by a well known and widely used ELISA. Sera from women with established systemic lupus erythematosus (SLE, n=62) and Sjogren’s syndrome (SS, n=28) were examined. Patients with SLE had an average age of 48.7 years (IQR 36.8–57.0) with a disease duration of 14.8 years (IQR 9.0–18.0). Patients with SS had an average age of 62.1 years (IQR 55.5–71.0) with a duration of disease of 13.1 years (IQR 8.3–17).

Table 1 shows the results from the two-by-two comparison for the four techniques. Different levels of agreement were observed among the assays. In general, they were deficient. The analysis showed only one ‘strong’ level of agreement between ELISA and IMTEC-ANA-LIA Maxx for anti-Ro measurement. Out of 39 comparisons, 14 did …
Prognostic and predictive clinical factors for progression to castration refractory prostate cancer in patients with hormone sensitive prostate cancer
Authors: M. Watanabe, K. Kanao, M. Sugie, S. Morinaga, H. Muramatsu, I. Kobayashi, K. Kajikawa, G. Nishikawa, K. Zennami, K. Nakamura, M. Sumitomo
Journal: Annals of Oncology (2018)
SP0055 How can integrated healthcare contribute to sustainable healthcare in rheumatology?
Authors: B. Vrijhoef
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> According to the World Health Organisation (WHO) "an integrated, people-centred approach is crucial to the development of health systems that can respond to emerging and varied health challenges, including urbanisation, the global tendency towards unhealthy lifestyles, ageing populations, the dual disease burden of communicable and non-communicable diseases, multi-morbidities, rising health care costs, disease outbreaks and other health-care crises". In supporting health services to become more integrated and people-centred a Framework was developed that proposes five interdependent strategies: 1. Empowering and engaging people and communities; 2. Strengthening governance and accountability; 3. Reorienting the model of care; 4. Coordinating services within and across sectors; 5. Creating an enabling environment. Given that health systems are highly context-specific, the Framework does not propose a single model but interdependent (sub) strategies, policy options, and interventions that need to be adopted.<sup><sup>1</sup></sup> What is known about the adoption of these strategies for people with rheumatic and musculoskeletal diseases? <h3>Methods</h3> A convenience sample of recently published reports about redesigning health care for people with rheumatic and musculoskeletal diseases is assessed against the WHO Framework on integrated-people centred health services. The five interdependent strategies, including the policy options and interventions as defined under the Framework, are assessed for presence, implementation fidelity and outcomes. Implementation fidelity refers to the degree to which an intervention is delivered as intended (i.e. in line with the Framework). Outcomes of people-centred care include: equity in access, quality, responsiveness and participation, efficiency, and resilience. <h3>Results</h3> To be presented at the conference. <h3>Discussion</h3> It is anticipated to find a plethora of examples of mainly single policy options and interventions, but hardly any examples of combinations of strategies. This would indicate a need for a systems approach in achieving sustainable healthcare in rheumatology. <h3>Reference</h3> [1] WHO. Framework on integrated, people-centred health services. <i>Sixty-ninth World Health Assembly</i>2016. http://apps.who.int/gb/ebwha/pdf_files/WHA69/A69_39-en.pdf?ua=1&amp;ua=1 (accessed 15 March 2018). <h3>Disclosure of Interest</h3> None declared
AB0122 Rp53 induces ectodomain shedding of tnf receptor 1 and thereby inhibits inflammatory responses in rheumatoid fibroblast-like synoviocytes
Authors: J. Kim, H.S. Byun, K. Kang, S.-J. Yoo, S.W. Kang, G.M. Hur
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease by autoimmune disorder that primarily affects joints. Usually RA has been treated with disease modifying anti-rheumatic drugs but biological response modifiers has developed the treatment of RA. Among these anti-tumour necrosis factor (TNF) agents were the first to be successfully used in treating RA. Various anti-TNF-α therapy might be lead to substantial functional improvement in RA patients. <h3>Objectives</h3> We studied the isolated two polypeptides (Rp53, Rp54) from <i>Rubia philippinensis</i>, traditional medicine plant, about anti-inflammation effects in fibroblast-like synoviocytes (FLS) derived from patients with RA. <h3>Methods</h3> The effects of polypeptides on anti-inflammation were measured by cytokine assay kits (TNF-α, IL-6). The underlying for NF-κB signalling pathway was examined by western blot and NF-kB reporter activity. We examined the effect of Rp53 on the formation of the TNFR1 signalling complex, recruitment of TRADD, RIP in response to TNF by immunoprecipitation experiments. To determine whether Rp53 induced TNF receptor 1 shedding were exposed to these compounds for 1 hour, and then culture media and cell lysates were analysed by Western blotting using anti-TNF receptor 1 antibody. <h3>Results</h3> Pretreatment with Rp53 resulted in a remarkable decrease of the secretion of TNF-induced proinflammatory cytokines TNF-α and IL-6 in RA–FLS. Rp53 strongly inhibited the nuclear factor kB (NF-κB) signalling pathway induced by TNF-α, but not that induced by IL-1β. Analysis of the upstream signalling events affected by Rp53 revealed that it strikingly inhibited the TNF-induced recruitment of TNFR1-associated death domain protein (TRADD) and receptor-interacting protein (RIP) to TNFR1. Rp53 reduced the interaction with TNFR1 to TNF cytokines and enhanced the activation of the p38 mitogen-activated protein (MAP) kinase. Rp53, the polypeptides induced the proteolytic cleavage of TNF-R1 and its release into the culture medium by shedding of TNF receptor 1 ectodomain by TNF-α-converting enzyme (TACE). Along with the TACE inhibitor TAPI-2, the p38 kinase inhibitor SB203580 suppressed the ectodomain shedding of TNF receptor 1 induced by Rp53. <h3>Conclusions</h3> Rp53 induces the TACE-dependent ectodomain shedding of TNF receptor 1 through the activation of p38 MAP kinase, and thereby inhibits the TNF-α induced NF-κB signalling pathway in RA-FLS cells. <h3>Disclosure of Interest</h3> None declared
Efficacy of TAS-120, an irreversible fibroblast growth factor receptor inhibitor (FGFRi), in patients with cholangiocarcinoma and FGFR pathway alterations previously treated with chemotherapy and other FGFRi’s
Authors: B. Tran, F. Meric-Bernstam, H.-T. Arkenau, R. Bahleda, R.K. Kelley, C. Hierro, D. Ahn, A. Zhu, M. Javle, R. Winkler, H. He, J. Huang, L. Goyal
Journal: Annals of Oncology (2018)
Knockdown of ANT2 reduces adipocyte hypoxia and improves insulin resistance in obesity
Authors: Jong Bae Seo, Matthew Riopel, Pedro Cabrales, Jin Young Huh, Gautam K. Bandyopadhyay, Aleksander Yu Andreyev, Anne N. Murphy, Scott C. Beeman, Gordon I. Smith, Samuel Klein, Yun Sok Lee, Jerrold M. Olefsky
Journal: Nature Metabolism (2018)
Therapeutic strategies involving survivin inhibition in cancer
Authors: David Martínez‐García, Noemí Manero‐Rupérez, Roberto Quesada, Luís Korrodi‐Gregório, Vanessa Soto‐Cerrato
Journal: Medicinal Research Reviews (2018)

Abstract Survivin is a small protein that belongs to the inhibitor of apoptosis protein family. It is abundantly expressed in tumors compared with adult differentiated tissues, being associated with poor prognosis in many human neoplasms. This apoptotic inhibitor has a relevant role in both the promotion of cancer cell survival and in the inhibition of cell death. Consequently, aberrant survivin expression stimulates tumor progression and confers resistance to several therapeutic strategies in a variety of tumors. In fact, efficient survivin downregulation or inhibition results in spontaneous apoptosis or sensitization to chemotherapy and radiotherapy. Therefore, all these features make survivin an attractive therapeutic target to treat cancer. Currently, there are several survivin inhibitors under clinical evaluation, although more specific and efficient survivin inhibitors are being developed. Moreover, novel combination regimens targeting survivin together with other therapeutic approaches are currently being designed and assessed. In this review, recent progress in the therapeutic options targeting survivin for cancer treatment is analyzed. Direct survivin inhibitors and their current development status are explored. Besides, the major signaling pathways implicated in survivin regulation are described and different therapeutic approaches involving survivin indirect inhibition are evaluated. Finally, promising novel inhibitors under preclinical or clinical evaluation as well as challenges of developing survivin inhibitors as a new therapy for cancer treatment are discussed.
Neonatal Pulmonary Magnetic Resonance Imaging of Bronchopulmonary Dysplasia Predicts Short-Term Clinical Outcomes
Authors: Nara S. Higano, David R. Spielberg, Robert J. Fleck, Andrew H. Schapiro, Laura L. Walkup, Andrew D. Hahn, Jean A. Tkach, Paul S. Kingma, Stephanie L. Merhar, Sean B. Fain, Jason C. Woods
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current National Institute of Child Health and Human Development (NICHD)/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes.Objectives: We hypothesized that magnetic resonance imaging (MRI) of structural parenchymal abnormalities will correlate with NICHD-defined BPD disease severity and predict short-term respiratory outcomes.Methods: A total of 42 neonates (20 severe BPD, 6 moderate, 7 mild, 9 non-BPD control subjects; 40 ± 3-wk postmenstrual age) underwent quiet-breathing structural pulmonary MRI (ultrashort echo time and gradient echo) in a neonatal ICU–sited, neonatal-sized 1.5 T scanner, without sedation or respiratory support unless already clinically prescribed. Disease severity was scored independently by two radiologists. Mean scores were compared with clinical severity and short-term respiratory outcomes. Outcomes were predicted using univariate and multivariable models, including clinical data and scores.Measurements and Main Results: MRI scores significantly correlated with severities and predicted respiratory support at neonatal ICU discharge (P < 0.0001). In multivariable models, MRI scores were by far the strongest predictor of respiratory support duration over clinical data, including birth weight and gestational age. Notably, NICHD severity level was not predictive of discharge support.Conclusions: Quiet-breathing neonatal pulmonary MRI can independently assess structural abnormalities of BPD, describe disease severity, and predict short-term outcomes more accurately than any individual standard clinical measure. Importantly, this nonionizing technique can be implemented to phenotype disease, and has potential to serially assess efficacy of individualized therapies.