tbuckley/cabot-search huggingface dataset:
PTU-061 Determining a value of faecal calprotectin above which colonoscopy is indicated in the county durham and darlington population
Authors: R Dunn, D Kejariwal, I Malik, O Ogunrinde, A Kannan, S Farook
Journal: Gut (2017)

Introduction  NICE guidelines1 have suggested the introduction of an ‘indeterminate’ range in faecal calprotectin that would include values that are above the reference range but not clinically significant in assessing for inflammatory bowel disease (IBD).2 BSG guidance has suggested that the value of faecal calprotectin above which colonoscopy is required should be determined by local audit. This audit is designed to determine that value for the County Durham and Darlington population.  Method  A total of two-hundred colonoscopies requested at County Durham and Darlington Foundation Trust (CDDFT) between 1stDecember 2014 and 21st September 2015 with an indication of ‘raised faecal calprotectin’ were analysed. We looked at: the value of faecal calprotectin; findings at colonscopy; histological findings; and findings of small bowel imaging. CCDFT uses the EliA Calprotectin test and a raised value is defined as >50 mg/kg.  Results  Fifty-five out of 200 (27.5%) of patients had an endoscopic, histological or radiological abnormality. 25 of the 47 patients with endoscopic inflammation did not have significant histological findings. All patients with abnormal histological or radiological findings had a faecal calprotectin >69 mg/kg.  Patients with a faecal calprotectin  200 mg/kg (30/38=78.9%). All patients with a definite diagnosis of IBD had a faecal calprotectin >147 mg/kg and the majority of these patients (18/22) had a faecal calprotectin >300 mg/kg.  Fifty-seven patients had a faecal calprotectin >300 mg/kg but normal histology following colonoscopy. Of these 57 patients, 19 had subsequent small bowel imaging of which 4 patients had abnormal findings.  Conclusion  Based on these findings, we would suggest that the indeterminate value of faecal calprotectin for CDDFT patients is between 50 mg/kg and 200 mg/kg. Colonoscopy should be considered in these patients depending on clinical history. Colonoscopy should be offered to those with a faecal calprotectin >200 mg/kg. In addition to this, small bowel imaging should be considered in those with a faecal calprotectin >300 mg/kg who have normal findings at colonoscopy.  References  . National Institute for Health and Clinical Excellence. Faecal Calprotectin diagnostic tests for inflammatory diseases of the bowel. NICE Diagnostics guidance. London: NICE; 2013: https://www.nice.org.uk/guidance/dg11 (accessed 20th January 2017)  . Bristish Society of Gastroenterology. BSG Guidance on the use of faecal calprotectin testing in IBD.London: BSG; 2016: http://www.bsg.org.uk/clinical-guidance/ibd/bsg-guidance-on-the-use-of-faecal-calprotectin-testing-in-ibd.html (accessed 20th January 2017)  Disclosure of Interest  None Declared
自然のプラットフォームから調製した機能的改変されたヒト心臓パッチは急性心筋梗塞後の心臓機能を改善する【Powered by NICT】
Authors: Wang Qingjie, Yang Hui, Bai Aobing, Jiang Wei, Li Xiuya, Wang Xinhong, Mao Yishen, Lu Chao, Qian Ruizhe, Guo Feng, Ding Tianling, Chen Haiyan, Chen Sifeng, Zhang Jianyi, Liu Chen, Sun Ning
Journal: Biomaterials (2016)
ATF3 regulates lovastatin-induced apoptosis in squamous cell carcinoma cells
Authors: Nima Niknejad, Wei Ma, Jim Dimitroulakos
Journal: Cancer Research (2008)

2267  Background: In this study, we examined the role of activating transcription factor 3  (ATF3) as a regulator of lovastatin-induced apoptosis. We recently demonstrated the role of the integrated stress response (ISR) in mediating apoptotic effects of lovastatin in squamous cell carcinoma (SCC) cells. The major events of the ISR include phosphorylation of eIF2-α by several kinases, including GCN2, followed by inhibition of global protein translation and selective translational induction of ATF4 and its target genes, such as ATF3 and CHOP. ATF3, a member of the ATF/cyclic AMP response element-binding family of transcription factors has been identified as an oncogene or pro-apoptotic factor in a cell type- or stimulant-dependent manner.  Methods: Mouse embryonic fibroblasts (MEFs) lacking ATF3, ATF4, and GCN2 or wild type MEFs were subjected to 0-50μM lovastatin treatment from 3-24hrs. As a positive control for the induction of the ISR, cells were also treated with thapsigargin and MG132. Cells were subjected to cell viability assays and protein lysates were extracted for immunoblotting assays. MCF-7 (breast carcinoma) and SCC25 (head and neck squamous cell carcinoma), a nonresponsive and responsive tumor derived cell line respectively, were subjected to lovastatin treatment for 24hrs followed by immunoblotting or real-time PCR analysis.  Results: In ATF3-/- MEFs, lovastatin-induced apoptosis was attenuated indicating a role for ATF3 in this response. Time course experiments showed a strong correlation between the cleavage of PARP-a marker of apoptotic cell- and induction of ATF3 following lovastatin treatment. Moreover, lack of PARP cleavage in ATF3 nulls was in agreement with their attenuated response to lovastatin induced cell death. Using ATF4 -/- MEFs, we identified this gene as a prerequisite for induction of ATF3 by lovastatin. In agreement with our previous data, immunoblot assays in GCN2 -/- cells showed that induction of ATF3 by lovastatin similar to its upstream gene, ATF4 is highly dependent on the presence of the eIF2-α kinase, GCN2. Furthermore, using Western blotting and immunofluorescence microscopy, we demonstrate that induction of CHOP by lovastatin-a target of ATF3- and its nuclear localization is respectively disrupted by deletion of ATF3 in null cell lines. Interestingly, the level of ATF3 expression in MCF-7, unlike SCC25 cells, was not induced in response to lovastatin while thapsigargin treatment led to potent induction of ATF3 in MCF7 cells.  Conclusions:  In this report we demonstrate for the first time a strong pro-apoptotic role for ATF3 in lovastatin-induced apoptosis in a GNC2 dependent manner. These data suggest that targeting the ISR and particularly ATF3 expression represents a more refined therapeutic approach in lovastatin-sensitive tumor cells.
Association Between Chronic Pulmonary Conditions and Neurocognitive Function in Long-Term Survivors of Childhood Hodgkin Lymphoma
Authors: Yin Ting Cheung, Noah D. Sabin, Daniel A. Mulrooney, Kirsten K. Ness, Matthew J Krasin, Tara M. Brinkman, Pia Banerjee, Deokumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Blood (2016)
生物学的組織での線維様構造の3次元構造の自動定量化【Powered by NICT】
Authors: Liu Zhiyi, Pouli Dimitra, Sood Disha, Sundarakrishnan Aswin, K Hui Mingalone Carrie, M Arendt Lisa, Alonzo Carlo, P Quinn Kyle, Kuperwasser Charlotte, Zeng Li, Schnelldorfer Thomas, L Kaplan David, Georgakoudi Irene
Journal: Biomaterials (2017)
The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors
Authors: Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Journal: JNCI Journal of the National Cancer Institute (2017)

Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided. The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004). ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.
オリゴデンドロサイト前駆細胞補給とミエリン形成のニューロンホスファチジルイノシトール(3,4,5)トリスリン酸依存的プログラム
Authors: Goebbels Sandra, Wieser Georg L, Pieper Alexander, Spitzer Sonia, Weege Bettina, Yan Kuo, Edgar Julia M, Yagensky Oleksandr, Wichert Sven P, Agarwal Amit, Karram Khalad, Renier Nicolas, Tessier‐Lavigne Marc, Rossner Moritz J, Karadottir Ragnhildur Thora, Nave Klaus‐Armin
Journal: Nature Neuroscience (2017)
Risk Behaviors for Contact Lens–Related Eye Infections Among Adults and Adolescents — United States, 2016
Authors: Jennifer R. Cope, Sarah A. Collier, Hannah Nethercut, Jefferson M. Jones, Kirsten Yates, Jonathan S. Yoder
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Contact lens-related eye infections, which can lead to serious outcomes, including blindness, are associated with several risk factors, including sleeping in lenses, exposing lenses to water, not adhering to replacement schedules, and reusing disinfecting solution (1). In some studies, adolescent and young adult contact lens wearers have been reported to be more likely than older adult contact lens wearers to develop eye infections (2,3) and more likely to have poor contact lens hygiene practices (2). In 2015, CDC reported the number and demographics of adult contact lens wearers in the United States to define the population at risk for contact lens-related eye infections (4); however, this estimate did not include adolescents. To better understand this group of younger contact lens wearers and guide prevention efforts, a population-based survey was used to assess contact lens wear, care behaviors, risk factors, and demographics among persons aged 12-17 years (referred to as adolescents in this report), young adults aged 18-24 years, and older adults aged ≥25 years in the United States. In 2016, an estimated 3.6 million adolescents (14.5%) wore contact lenses. Of the adolescents who wore contact lenses, 85% reported at least one behavior that put them at risk for a contact lens-related eye infection, compared with 81% of young adults, and 88% of older adults. These findings can inform the creation of age-specific targeted prevention messages aimed at contact lens wearers and establish a baseline for evaluating trends in contact lens wear, care habits, and contact lens-related risk behaviors.
Systematic review of overuse in oncology.
Authors: Shrujal S. Baxi, Minal Kale, Benjamin R Roman, Annie Yang, Antonio Derosa, Azalea Kim, Salomeh Keyhani, Deborah Korenstein
Journal: Journal of Clinical Oncology (2016)

e18257 Background: Overuse is an increasingly important target for improving health outcomes and reducing cost in oncology. To inform policies for reducing overuse, we performed a systematic review of the evidence on the prevalence of overuse in cancer care. Methods: We searched MEDLINE, EMBASE, Cochrane, Scopus and Web of Science (2011-5), augmented by reference tracking, for studies documenting the prevalence of overuse of any service in patients with cancer. Four authors reviewed titles/abstracts and 5 reviewed full text for inclusion. We included articles measuring overuse compared to a specific standard (practice guideline, panel consensus recommendation, or Choosing Wisely item). Results: Our search identified 11,091 papers; we included 55 articles. The majority were retrospective (87%), completed in the US (75%) and assessed use of imaging (65%). The most common cancers were prostate (44%), breast (36%), lung (9%) and colorectal (9%); phase of cancer care included diagnostic (55%), active treatment (31%), post-treatment (22%), and end of life (4%). SEER-Medicare was the most frequent data source (36%). Seventeen (31%) studies assessed the use of high-tech imaging (e.g., bone scan, CT, MR, or PET) in the diagnostic evaluation of men with low-risk prostate cancer; rates of overuse varied from 3% to 65% depending on service addressed and source of data. Nine (16%) studies evaluated diagnostic work-up in early stage breast cancer; rates of overuse ranged from 2% for brain imaging to 80% for any non-recommended imaging. The 17 (31%) studies of active treatment covered many cancers and therapeutic modalities; only 2 (1 US, 1 French) evaluated chemotherapy use in metastatic cancer. Only 2 studies evaluated an intervention to reduce overuse. Conclusions: Despite increased attention to value in cancer care, we found limited literature estimating rates of actual overuse compared to published standards. Almost half of the studies addressed diagnostic evaluation in early stage prostate or breast cancer. Recent estimates of overuse in oncology are narrow in scope (e.g, cancers and services addressed). Reducing overuse in cancer care requires a better evidence base to identify services to target and intervention strategies to improve the value proposition in oncology.
Sonic hedgehog-dependent activation of adventitial fibroblasts promotes neointima formation
Authors: Jochen Dutzmann, Alexander Koch, Simona Weisheit, Kristina Sonnenschein, Laura Korte, Marco Haertlé, Thomas Thum, Johann Bauersachs, Daniel G Sedding, Jan-Marcus Daniel
Journal: Cardiovascular Research (2017)

Abstract Aims Adventitial cells have been suggested to contribute to neointima formation, but the functional relevance and the responsible signalling pathways are largely unknown. Sonic hedgehog (Shh) is a regulator of vasculogenesis and promotes angiogenesis in the adult. Methods and results Here we show that proliferation of vascular smooth muscle cells (SMC) after wire-induced injury in C57BL/6 mice is preceded by proliferation of adventitial fibroblasts. Simultaneously, the expression of Shh and its downstream signalling protein smoothened (SMO) were robustly increased within injured arteries. In vitro, combined stimulation with Shh and platelet-derived growth factor (PDGF)-BB strongly induced proliferation and migration of human adventitial fibroblasts. The supernatant of these activated fibroblasts contained high levels of interleukin-6 and -8 and strongly induced proliferation and migration of SMC. Inhibition of SMO selectively prevented fibroblast proliferation, cytokine release, and paracrine SMC activation. Mechanistically, we found that PDGF-BB activates protein kinase A in fibroblasts and thereby induces trafficking of SMO to the plasma membrane, where it can be activated by Shh. In vivo, SMO-inhibition significantly prevented the proliferation of adventitial fibroblasts and neointima formation following wire-induced injury. Conclusions The initial activation of adventitial fibroblasts is essential for the subsequent proliferation of SMC and neointima formation. We identified SMO-dependent Shh signalling as a specific process for the activation of adventitial fibroblasts.
非ウイルス操作されたヒト脂肪間葉系幹細胞はBMP4,標的脳腫瘍を生産し,生存を延長する【Powered by NICT】
Authors: Mangraviti Antonella, Y Tzeng Stephany, Gullotti David, L Kozielski Kristen, E Kim Jennifer, Seng Michael, Abbadi Sara, Schiapparelli Paula, Sarabia-Estrada Rachel, Vescovi Angelo, Brem Henry, Olivi Alessandro, Tyler Betty, J Green Jordan, Quinones-Hinojosa Alfredo
Journal: Biomaterials (2016)
Climate Change
Authors: William G. Kaelin
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
AB0115 Comparison of the bacterial stool microbiota in established psoriatic arthritis (PSA) and psoriasis (PSC) - exploratory analysis of pilot data
Authors: M Castelino, M Tutino, J Moat, UZ Ijaz, R Parslew, A Al-Sharqi, RB Warren, C Quince, P Ho, M Upton, S Eyre, A Barton
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriatic arthritis (PsA) is a complex inflammatory condition with both genetic and environmental risk factors contributing to disease. A potential environmental risk factor, known to modify the immune system, is the intestinal microbiota. In PsA there is evidence of intestinal inflammation [1,2] and recently dysbiosis of the gut microbiota has been reported in treatment naïve PsA patients [3]. However, there is no information on the temporal stability of the microbiota over time in established PsA on treatment compared to matched PsC controls. <h3>Objectives</h3> To explore the temporal stability of gut microbiota composition and reveal associations with PsA compared to PsC while on stable on treatment with methotrexate. <h3>Methods</h3> Patients with PsA and PsC were recruited to the study if they had been on a stable dose of methotrexate for 6 months. Bacterial DNA was extracted and the V3-V4 hypervariable region of the 16S rRNA was amplified and sequenced on MiSeq. The resultant data was analysed using a bespoke bioinformatics pipeline and taxa were assigned using the Ribosomal Database Project classifier according to the SILVA119 database. The Wilcoxon rank sum test was used to assess alpha diversity indices, while permanova testing using Bray Curtis distance and DESeq2 values corrected for false-discovery rate (FDR) were used to compare beta diversity indices after removing low abundance (&lt;0.5%) Operational Taxonomic Units (OTU). The ALDEx2 analysis package was used to assess effect size. <h3>Results</h3> Stool samples were available 9 PsA (n=13) and 6 PsC (n=12) individuals. Second stool samples were also obtained from the PsA (n=5) and PsC (n=4) groups. No significant difference in the alpha diversity indices was observed between PsA and PsC. The beta diversity index showed no significant difference between the two conditions using permanova test. However, using the DESeq2-FDR analysis, 8 OTUs were identified which had significantly (p&lt;0.01) different abundances in PsA compared to PsC. The taxa (Lachnospiraceae &amp; Ruminococcaeceae) predominantly belonged to the Firmicutes phylum, family Lachnospiraceae and Actinobacteria phylum, family Bifidobacteriaceae (Bifidobacteriaceae). The significant OTUs with DESEq2 had an effect size &gt;1 using ALDEx2 but the BH p-value was not significant (p&lt;0.01), which may be due to the small sample size. There were no significant differences in the diversity measures over time. <h3>Conclusions</h3> These results suggest that a gut enterotype with predominant Firmicutes/Actinobacteria composition is associated with stable/well controlled disease and is stable over time. This requires replication in a larger cohort. <h3>References</h3> Lindqvist, 2006. Scarpa, 2000. Scher, 2015. <h3>Disclosure of Interest</h3> None declared
Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study
Authors: Christina Yoon, Fred C Semitala, Elly Atuhumuza, Jane Katende, Sandra Mwebe, Lucy Asege, Derek T Armstrong, Alfred O Andama, David W Dowdy, J Luke Davis, Laurence Huang, Moses Kamya, Adithya Cattamanchi
Journal: The Lancet Infectious Diseases (2017)
Abstract 11162: Hypothermia Attenuates Postresuscitation Myocardial Dysfunction by Inhibiting Beta Adrenergic Signaling
Authors: Wei Wang, Tianfeng Hua, Hao Li, Xiaobo Wu, Mary A Peberdy, Joseph P Ornato, Wanchun Tang
Journal: Circulation (2016)

Introduction: Therapeutic hypothermia reduce the severity of post-resuscitation myocardial dysfunction caused by epinephrine administered during cardiopulmonary resuscitation (CPR) , and the mechanism remains unclear. Hypothesis: hypothermia may reduce the concentration of cyclic adenosine monophosphate (cAMP), a second messenger of beta-adrenergic receptor activity. Methods: Thirty two male Sprague-Dawley rats were randomized to four groups: 1) normothermic placebo control; 2) normothermic epinephrine; 3) hypothermic placebo control; and 4) hypothermic epinephrine. Ventricular fibrillation was induced electrically and untreated for 8 mins. Hypothermia was initiated coincident with the start of CPR and maintained at 33 ± 0.2°C for 4 hrs after resuscitation and animals were then euthanized. Either placebo or epinephrine was administered 5 mins after the start of CPR and 3 mins before defibrillation. Post-resuscitation ejection fraction was measured hourly for 4 hrs. The hearts were then harvested for cAMP and Inositol 1,4,5-trisphosphate (IP3) assay analysis. Results: All animals were successfully resuscitated except one in normothermic placebo group. Epinephrine significantly increased coronary perfusion pressure during CPR (26.5±6.23mmHg vs 21.14±1.95 mmHg P&lt;0.05). Post-resuscitation myocardial function was significantly impaired in normothermic epinephrine group compared with other three groups (figure 1). The concentration of myocardial cAMP was double in normothermic epinephrine group (655.06±447.63 umol/L) when compared to that in hypothermic epinephrine group (302.51±97.98 umol/L P&lt;0.05). However, there was no difference in the concentration of IP3 in all four groups. Conclusions: The potential mechanism of myocardial protective effect of hypothermia may involve the reduced activities of β-receptors.
Does Flow-mediated Dilation of Brachial Artery Predict Development of Cardiac Allograft Vasculopathy in Heart Transplant Recipients?-Prospective Observational Study-
Authors: Watanabe Takuya, Seguchi Osamu, Yanase Masanobu, Fujita Tomoyuki, Ohta Yuko, Sato Takuma, Sunami Haruki, Nakajima Seiko, Nishimura Kunihiro, Hisamatsu Eriko, Kuroda Kensuke, Okada Norihiro, Hayashi Shinichiro, Hata Hiroki, Miyamoto Yoshihiro, Kobayashi Junjiro, Nakatani Takeshi
Journal: Circulation (2016)