tbuckley/cabot-search huggingface dataset:
Trois jours d’endoscopies digestive au Liban (étude realisée par la societé libanaise de gastroentérologie)
Authors: A Abou Rached, J Boujaoude, P Saniour
Journal: Endoscopy (2004)

Objectif: Etude conduite par la SLGE afin d’estimer le nombre d’endoscopie digestive pratique au Liban, l’âge et le sexe des patients, le lieu et les modalités de la pratique de l’endoscopie, les moyens de sédation utilisées. Patients et Méthodes: Suite à une lettre d’information, un questionnaire est adressé à tous les gastro-entérologues libanais. Trente cinq pour cent des gastro-entérologues interrogés ont répondus. Résultats: Durant ces trois jours, 358 endoscopies digestives ont été réalisées dont 179 gastroscopies, 136 coloscopies, 27 rectosigmoidoscopies et 16 cholangio pancréatographies rétrograde endoscopique (CPRE). L’âge moyen des patients dans chacun des groupes était de 43 ans, 55 ans, 45 ans et 45 ans pour les gastroscopies, coloscopies, rectosigmoidoscopies et CPRE respectivement. Pas de différence pour les 2 sexes dans les différents groupes. Concernant le lieu de la pratique des endoscopies, la majorité ont été réalisées à l’hôpital: 80% des gastroscopies, 92% des coloscopies, 60% des rectosigmoidoscopies, 100% des CPRE. Pour les modalités de la pratique d’endoscopie: la totalité des CPRE ont été réalisées pour des malades hospitalisés, alors que dans les groupes de gastroscopies, coloscopies et rectosigmoidoscopies les patients sont soit externes dans 55%, 48% et 60% ou hospitalisés dans 40%, 40% et 30% respectivement. Soixante dix pour cent des gastroscopies et 60% des coloscopies sont réalisées par une sédation intra veineuse donnée par le gastro-entérologue, seulement 40% des coloscopie sont pratiquées sous neuroleptanalgésie ainsi que 80% des CPRE. La majorité des rectosigmoidoscopies sont réalisées sans sédation. Conclusion: Cette étude donne une idée sur la pratique et les modalités d’endoscopie digestive au Liban et met l’accent sur les différences existante entre les différents gastro-entérologues concernant le mode de sédation utilisée d’où l’intérêt d’une étude prospective comparative (tolérance, coût) entre les différents groupes.
Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells
Authors: M. Mattii, M. Lovászi, N. Garzorz, A. Atenhan, M. Quaranta, F. Lauffer, A. Konstantinow, M. Küpper, C.C. Zouboulis, L. Kemeny, K. Eyerich, C.B. Schmidt-Weber, D. Törőcsik, S. Eyerich
Journal: British Journal of Dermatology (2017)

The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria. To analyse the functional communication between human sebocytes and T cells. Immunofluorescence stainings for CD4 and interleukin (IL)‐17 were performed on acne sections and healthy skin. Migration assays and T‐cell‐stimulation cultures were performed with supernatants derived from unstimulated or prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions. We showed that CD4+ IL‐17+ T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL8‐dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into T helper (Th)17 cells via the secretion of IL‐6, transforming growth factor‐β and, most importantly, IL‐1β. No direct effects of sebocytes on the function of CD4+ CD45RO+ memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells, leading to antigen‐presenting cells that preferentially prime Th17 cells. Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases.
Lyp I修飾Docetaxel/IR820Co含有ミセルによる乳癌の温和な光熱療法/光線力学療法/化学療法【Powered by NICT】
Authors: Li WenTing, Peng JinRong, Tan LiWei, Wu Jing, Shi Kun, Qu Ying, Wei XiaWei, Qian ZhiYong
Journal: Biomaterials (2016)
Abstract 389: Amino Terminal Region of Cardiac Myosin Binding Protein-C is Necessary for Cardiac Function
Authors: Thomas L Lynch, Diederik W Kuster, Mayandi Sivaguru, Michael J Previs, Kyounghwan Lee, Suresh Govindan, Roger Craig, David M Warshaw, Sakthivel Sadayappan
Journal: Circulation Research (2016)

Rationale: Cardiac myosin binding protein-C (cMyBP-C) is a thick filament-associated protein that has been suggested to regulate cardiac contraction via its amino terminal (N’) region. However, the necessity of the N’-C0-C1f region (domains C0 through C1 and the first 17 residues of the M-domain) of cMyBP-C in regulating cardiac function in vivo has not been elucidated. Hypothesis: The N’-C0-C1f region of cMyBP-C is critical for normal cardiac function in vivo . Methods and Results: Transgenic mice with 80±4% expression of a truncated cMyBP-C missing the N’-C0-C1f region (cMyBP-C 110kDa ) were generated and characterized at 3-months of age. cMyBP-C 110kDa animals exhibited cardiac hypertrophy as suggested by an increased heart weight to body weight ratio (5.0±0.1 mg/g NTG vs. 6.9±0.1 mg/g cMyBP-C 110kDa , p&lt;0.0001) and an elevation in pathological hypertrophy markers determined by real-time PCR. Histopathological analysis showed increased cardiac fibrosis in cMyBP-C 110kDa hearts compared to hearts from non-transgenic (NTG) littermates. Intriguingly, increased phosphorylation of cMyBP-C at Ser-282 and Ser-302, sites important for cMyBP-C’s regulation of actomyosin interactions, was observed in cMyBP-C 110kDa hearts compared to controls. Electron microscopy revealed normal sarcomere structure in cMyBP-C 110kDa hearts but with apparently weaker cMyBP-C stripes. Furthermore, the ability of cMyBP-C to slow actin-filament sliding within the C-zone of native thick filaments isolated from NTG hearts was lost on thick filaments from cMyBP-C 110kDa hearts. Short-axis M-mode echocardiography indicated a significant elevation in left ventricular internal diameter and a significant reduction in fractional shortening (31±5% NTG vs. 16±3% cMyBP-C 110kDa , p=0.0003) in cMyBP-C 110kDa hearts compared to controls. Finally, global longitudinal strain analysis revealed abnormal wall motion in cMyBP-C 110kDa hearts. Based upon these data, we propose that the N’-region of cMyBP-C is a critical regulator of actomyosin interactions and controls aberrant contraction kinetics within the cardiac sarcomere. Conclusion: The N’-C0-C1f region of cMyBP-C regulates cardiac contractility and is necessary for maintaining normal cardiac function in vivo .
Progranulin deficiency causes impairment of autophagy and TDP-43 accumulation
Authors: Michael C. Chang, Karpagam Srinivasan, Brad A. Friedman, Eric Suto, Zora Modrusan, Wyne P. Lee, Joshua S. Kaminker, David V. Hansen, Morgan Sheng
Journal: The Journal of Experimental Medicine (2017)

Loss-of-function mutations in GRN cause frontotemporal dementia (FTD) with transactive response DNA-binding protein of 43 kD (TDP-43)-positive inclusions and neuronal ceroid lipofuscinosis (NCL). There are no disease-modifying therapies for either FTD or NCL, in part because of a poor understanding of how mutations in genes such as GRN contribute to disease pathogenesis and neurodegeneration. By studying mice lacking progranulin (PGRN), the protein encoded by GRN, we discovered multiple lines of evidence that PGRN deficiency results in impairment of autophagy, a key cellular degradation pathway. PGRN-deficient mice are sensitive to Listeria monocytogenes because of deficits in xenophagy, a specialized form of autophagy that mediates clearance of intracellular pathogens. Cells lacking PGRN display reduced autophagic flux, and pathological forms of TDP-43 typically cleared by autophagy accumulate more rapidly in PGRN-deficient neurons. Our findings implicate autophagy as a novel therapeutic target for GRN-associated NCL and FTD and highlight the emerging theme of defective autophagy in the broader FTD/amyotrophic lateral sclerosis spectrum of neurodegenerative disease.
Plan for army-style conscription of doctors is reconsidered
Authors: Abi Rimmer
Journal: BMJ (2017)

The Department of Health in England has said that it will reconsider its plan to require doctors to work in the NHS after qualification or to pay for some of their training.

The department said that it would “continue to consider return on taxpayer investment” in its response to a consultation on the expansion of undergraduate medical education.1

The consultation had proposed a system similar to that in the armed forces, “whereby medical students receive funding to support them to complete their degree in return for agreeing to serve for a given period.”2 It said that, if doctors do not complete the required amount of time in the NHS, “then they could be required to repay a sum of money in addition to their loan repayments.”

The government’s …
Plasma Epstein–Barr Virus DNA for Screening
Authors: Richard F. Ambinder
Journal: New England Journal of Medicine (2017)

In this issue of the Journal, Chan et al.1 report on the monitoring of Epstein–Barr virus (EBV) DNA in plasma samples to screen a population that was at high risk for nasopharyngeal carcinoma. Although interest in monitoring circulating cell-free tumor DNA has surged, the application of this method to early detection of tumors remains challenging.2,3 Among the challenges are assay sensitivity and specificity. In healthy persons, circulating cell-free DNA is composed of DNA originating from normal cells. In early-stage cancer, only a small fraction of cell-free DNA is derived from tumor. Sensitive screening for cancer-associated mutations in turn yields false . . .
Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic): a multinational observational analysis
Authors: Kåre I Birkeland, Marit E Jørgensen, Bendix Carstensen, Frederik Persson, Hanne L Gulseth, Marcus Thuresson, Peter Fenici, David Nathanson, Thomas Nyström, Jan W Eriksson, Johan Bodegård, Anna Norhammar
Journal: The Lancet Diabetes & Endocrinology (2017)
Tumour necrosis factor antagonist-induced lupus: a Critically Appraised Topic
Authors: S.E. Momen, B. Kirkham, J.N. Barker, C.H. Smith
Journal: British Journal of Dermatology (2017)

TNF antagonist induced lupus is diagnosed upon a temporal relationship of TNF antagonist therapy and the development of four of the 11 American college of rheumatology (ACR) diagnostic criteria for lupus.

We critically appraise the literature on TNF antagonist induced lupus, focusing on the diagnostic criteria, dermatological manifestations, management and outcome.

Eighty cases of TNF antagonist induced lupus that met the ACR criteria were included and analysed. Infliximab was the most commonly reported agent (58.8%, n=47). Cutaneous manifestations were the most common presentation (67.5%, n=54,), specifically malar rash (26.3%, n=21) and photosensitivity (23.4%, n=19). Lupus symptoms resolved in all cases (n=80), withdrawal of the TNF antagonist was sufficient in 18.8% of cases (n=15), additional immunosuppression was required in the remaining cases. Four patients were treated with a second, different TNF antagonist, with no recurrence of symptoms. TNF antagonist induced lupus appears to have a good prognosis and treatment should be tailored to each individual case. As cutaneous features are the most common manifestation it is important that dermatologists are aware of the ACR diagnostic criteria of lupus to ensure accurate diagnoses of TNF antagonist induced lupus.

This article is protected by copyright. All rights reserved.
03.13 Synovial tissue of ra patients in remission contains a unique population of regulatory macrophages
Authors: Aziza Elmesmari, Stefano Alivernini, Barbara Tolusso, Diane Vaughan, Gabriele Di Sante, Luca Petricca, Elisa Gremese, Gianfranco Ferraccioli, Iain B McInnes, Mariola Kurowska-Stolarska
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The majority of RA treatments target inflammation or the adaptive immune response. Partial- or non-response is common and only a minority have sustained remission. There is a knowledge gap in understanding the mechanisms that could reinstate synovial homeostasis in RA. Tissue macrophages may have a role in this process; they are present in healthy synovium and aid resolution of the inflammation in experimental models of RA. However, little is known about the regulatory properties of human synovial tissue macrophages. Our hypothesis is that healthy and RA synovium in remission contain macrophages with anti-inflammatory/repair properties and identifying the effector pathways that drive their function could facilitate therapeutic restoration of synovial homeostasis in RA. <h3>Methods and materials</h3> We developed a flow cytometry sorting strategy for harvesting tissue-resident macrophages obtained from digested synovial biopsies of RA patients (n=21, including in remission n=5; and active RA n=16). Cells were labelled with cell lineage specific antibodies; and then macrophages were gated based on their expression of CD64<sup>pos</sup>CD11b<sup>pos</sup>MHCII<sup>pos</sup>Lineage<sup>neg</sup>. The potential homeostatic/repair macrophage was preliminary identified by the presence of CD206 marker. CD206<sup>pos</sup> and CD206<sup>neg</sup> macrophages were sorted using a FACS Aria III and RNAseq preformed to characterise their functional signature. In some experiment, macrophages were seeded on collagen-coated plates and production of TNFα evaluated. <h3>Results</h3> All synovial tissue macrophages from RA in remission were CD206<sup>pos</sup> whereas a substantial number of synovial macrophages from active RA tissue were CD206<sup>neg</sup>. Gene expression analyses and functional assays suggest that these populations represent distinct phenotypes in the activation spectrum. CD206<sup>neg</sup> macrophages have high expression of microRNA-155, which drives production of inflammatory mediators eg, TNFα. In contrast, CD206<sup>pos</sup> macrophages showed regulatory properties characterised by increased expression of soluble (eg,<i> IL10, TGFB</i>), surface (eg,<i> IL4/14</i><i>R, TGFBR1/2</i>) and cellular (eg,<i> SHIP1, TAM, SMAD2, STAT6</i>) inhibitors of inflammatory activation, and increased expression of repair markers (eg,<i> ARG2 and CCL18</i>). <h3>Conclusions</h3> We propose therefore that anti-inflammatory/repair macrophages may be present in human synovial tissues in remission representing a hitherto unnoticed regulatory tissue mechanism.
Case 9-2000
Authors: Randy N. Rosier, Andrew E. Rosenberg
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 41-year-old man was admitted to the hospital because of pain in multiple bones.The patient had been well until eight years earlier, when he had a mandibular abscess that resulted in the loss of his lower central incisors. He had an uneventful recovery, but in the ensuing years he began to have diffuse bone pain. He was told that he had mild diabetes mellitus. Eighteen months before admission, he began to limp because of increasing pain in the knees and ankles, and six months later, he began to use a cane. Subsequently, he had two fractures . . .
Prognostic value of P53 and thymidylate synthase (TS) overexpression in patients with squamous cell carcinoma of the head and neck treated with neoadjuvant chemotherapy
Authors: M. E. Abderkader, W. H. Elsawy, M. Abdalla, Y. T. Dorgham, M. M. Elnemr
Journal: Journal of Clinical Oncology (2007)

6081 Background: Neoadjuvant cisplatin-based chemotherapy has been widely used in the last decade for organ preservation or unresectable disease in advanced stage head and neck cancer. Thymidylate synthase (TS) and p53 are central molecules in the regulation of cell growth. Differences in the intracellular expression of these proteins by tumor cells may have predictive value for response to chemotherapy and early failure in patients with squamous cell cancer of the head and neck (SCCHN). We examined the expression of P53 and TS that have been associated with chemotherapy resistance. Methods: Immunohistochemistry was used to assess the tumor cell expression of TS and p53 in pre-therapy biopsies from 65 patients with SCCHN treated with induction chemotherapy. Results: The overall response rate for cisplatin-based neoadjuvant treatment was 80%. The expression of P53 and TS was associated with resistance to neoadjuvant treatment, but none reached statistical significance. Overall survival (OS) was strongly correlated with the absence of p53 expression. The OS at 3 years was 80% in the p53-negative group, whereas it was 29% in the p53-positive group for patients treated with neoadjuvant chemotherapy (P &lt; 0.0001). Expression of TS was also significantly correlated with decreased OS after neoadjuvant treatment. In the TS-negative group, the 3-year OS rate was 69% compared with 38% in the TS-positive group (P = 0.0063). Conclusions: Our data showed that p53 and TS may be clinically important predictors of survival in patients receiving neoadjuvant chemotherapy for head and neck cancer. No significant financial relationships to disclose.
PTH-023 Developing patient reported experience measures for gi endoscopy: results of patient interviews
Authors: LJ Neilson, L Sharp, J Patterson, P Hewitson, Cvon Wagner, CJ Rees
Journal: Endoscopy (2017)

<h3>Introduction</h3> Patient experience is increasingly recognised as a key measure of quality of care. Ensuring positive experience is important to patients and fundamental in maximising participation in screening programmes and re-attendance for surveillance procedures. Current measures of patient experience of gastrointestinal (GI) endoscopy are clinician derived.<sup>1</sup>Patient Reported Experience Measures (PREMs) should be patient derived and incorporate pre-and post-procedure experience. We aimed to identify themes considered as important to patients undergoing GI procedures as a basis for developing PREMs. <h3>Method</h3> Patients who had undergone upper or lower GI investigations (gastroscopy, colonoscopy and CT pneumocolon) were invited to attend for a semi-structured interview. 32 interviewees were purposefully sampled to ensure diversity. Interviews were conducted by a research fellow trained in qualitative methods and were audio recorded and transcribed verbatim. Recruitment continued until saturation was achieved. Analysis used qualitative thematic methods focusing on anticipated and emergent themes, using constant comparison to ensure that all perspectives were included in the explanation of the data. <h3>Results</h3> 168 patients were approached. 32 interviews were completed (12 gastroscopy, 10 colonoscopy and 10 CT pneumocolon), with a male:female ratio of 18:14. The time interval from examination to procedure ranged from 5 to 44 days. Mean age was 63.1 years (SD 11.5) The interviews provided an in-depth understanding of patient experience of GI procedures. 6 over-arching and inter-linking themes emerged across all procedures; anxiety, expectations, choice/control, communication/information, comfort and embarrassment/dignity. Relation of themes was seen e.g. if the procedure appointment was sooner than expected, patients were anxious about the potential outcome. Choice was important in terms of appointment, endoscopist and choice of pre-medication, however it was highly individualised. Communication prepared patients and managed expectations, with one patient describing poor endoscopist communication affecting the whole experience. Patients described embarrassment related to changing and waiting areas; sensitive nature of the test; exposure and physical reaction. Discomfort during the procedure was attributed to instrument and air insertion. <h3>Conclusion</h3> Despite heterogeneity between procedures consistent themes related to patient experience emerged. This work will be used to develop PREMs for GI Endoscopy. <h3>Reference</h3> . Brown S, et al. Patient-derived measures of GI endoscopy: a meta-narrative review of the literature. Gastrointest Endosc2015;81(5):1130–40 <h3>Disclosure of Interest</h3> None Declared
強化された癌免疫療法のためのpH応答性金属‐有機フレームワークに基づく簡単で強力な共送達システム【Powered by NICT】
Authors: Duan Fei, Feng Xiaochen, Yang Xinjian, Sun Wentong, Jin Yi, Liu Huifang, Ge Kun, Li Zhenhua, Zhang Jinchao
Journal: Biomaterials (2017)
Abstract A38: A PERK inhibitor that blocks HER2-driven tumorigenesis and suppresses metastasis by targeting single disseminated tumor cells
Authors: Veronica Calvo, Kirk A. Staschke, Maria Cristina Garcia Paredes, Alvaro Avivar-Valderas, Julie Cheung, Robert Wild, Alan C. Rigby, Eduardo F. Farias, Julio Aguirre-Ghiso
Journal: Cancer Research (2016)

Abstract The unfolded protein response (UPR) is a critical survival and adaptation pathway in cancer cells. The endoplasmic reticulum kinase PERK serves as a survival UPR factor for different tumor types, including those driven by the oncogene HER2, and it can also promote survival of dormant cancer cells. We wanted to evaluate the effect of a potent and selective new PERK inhibitor (LY4) on MMTV-HER2-driven tumorigenesis that, through genetic experiments, was shown to depend on a full complement of PERK for progression. Here we show that, from ductal carcinoma in situ (DCIS) through invasive cancer, MMTV-HER2-driven tumors and also HER2+ human cancer cell lines are exquisitely sensitive to this novel PERK inhibitor. We found that early MMTV-HER2+ lesions require PERK for HER2-driven alterations in ductal epithelial organization, and that LY4 impairs the expansion of established HER2+ tumor cells in 3D organotypic cultures and in vivo. Importantly, PERK inhibition blunted metastasis development. This effect was linked to the ability of the PERK inhibitor to eradicate solitary HER2+ disseminated tumor cells that, in their majority, are dormant or slow-cycling, but that represent the seeds for further metastases. Mechanism analyses revealed that PERK inhibition indirectly blocked the phosphorylation of HER2 and EGFR and their downstream signaling activation in response to EGF, possibly by altering receptor protein quality control. Our data suggest that in HER2-driven cancers PERK inhibition might be a novel therapeutic strategy to treat primary and metastatic lesions. Citation Format: Veronica Calvo, Kirk A. Staschke, Maria Cristina Garcia Paredes, Alvaro Avivar-Valderas, Julie Cheung, Robert Wild, Alan C. Rigby, Eduardo F. Farias, Julio Aguirre-Ghiso. A PERK inhibitor that blocks HER2-driven tumorigenesis and suppresses metastasis by targeting single disseminated tumor cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A38.