tbuckley/cabot-search huggingface dataset:
Position paper for the organization of ECMO programs for cardiac failure in adults
Authors: Darryl Abrams, A Reshad Garan, Akram Abdelbary, Matthew Bacchetta, Robert H Bartlett, James Beck, Jan Belohlavek, Yih-Sharng Chen, Eddy Fan, Niall D Ferguson, Jo-Anne Fowles, John Fraser, Michelle Gong, Ibrahim F Hassan, Carol Hodgson, Xiaotong Hou, Katarzyna Hryniewicz, Shingo Ichiba, William A Jakobleff, Roberto Lorusso, Graeme MacLaren, Shay McGuinness, Thomas Mueller, Pauline K Park, Giles Peek, Vin Pellegrino, Susanna Price, Erika B Rosenzweig, Tetsuya Sakamoto, Leonardo Salazar, Matthieu Schmidt, Arthur S Slutsky, Christian Spaulding, Hiroo Takayama, Koji Takeda, Alain Vuylsteke, Alain Combes, Daniel Brodie
Journal: Intensive Care Medicine (2018)
Treatment Outcomes in the Primary Tube Versus Trabeculectomy Study after 1 Year of Follow-up
Authors: Steven J. Gedde, William J. Feuer, Wei Shi, Kin Sheng Lim, Keith Barton, Saurabh Goyal, Iqbal I.K. Ahmed, James Brandt, Steven Gedde, Michael Banitt, Donald Budenz, Richard Lee, Paul Palmberg, Richard Parrish, Luis Vazquez, Sarah Wellik, Mark Werner, Jeffrey Zink, Anup Khatana, Davinder Grover, Arvind Neelakantan, Keith Barton, Ahmed El Karmouty, Renata Puertas, Joseph Panarelli, Kateki Vinod, Saurabh Goyal, John Lind, Steven Shields, Kin Sheng Lim, Pouya Alaghband, James Brandt, Mark Sherwood, Mahmoud Khaimi, Prithvi Sankar, Husam Ansari, Eydie Miller-Ellis, Robert Feldman, Laura Baker, Nicholas Bell, Iqbal Ahmed, Donna Williams, Bruce Prum, Pradeep Ramulu, Henry Jampel, William Feuer, Luz Londono, Joyce Schiffman, Wei Shi, Yolanda Silva, Elizabeth Vanner, Philip Chen, William Feuer, Dale Heuer, Joyce Schiffman, Kuldev Singh, Martha Wright, Iqbal Ahmed, Keith Barton, James Brandt, Robert Feldman, Steven Gedde, Saurabh Goyal, Davinder Grover, Dale Heuer, Mahmoud Khaimi, John Lind, Kin Sheng Lim, Joseph Panarelli, Richard Parrish, Bruce Prum, Pradeep Ramulu, Prithvi Sankar, Mark Sherwood, Jeffrey Zink, Steven Gedde, Dale Heuer, Richard Parrish
Journal: Ophthalmology (2018)
Poor interrater reliability of hidradenitis suppurativa phenotypes
Authors: Kelsey R. van Straalen, Tim Verhagen, Barbara Horváth, Christine Ardon, Allard R.J.V. Vossen, Rieke Driessen, Jurr Boer, Angelique L.V. Rondags, Errol P. Prens, Hessel H. van der Zee
Journal: Journal of the American Academy of Dermatology (2018)
Traitement des polypes colorectaux bénins de 20 mm et plus du programme de dépistage organisé du cancer colorectal par test immunologique
Authors: B Denis, I Gendre, J Lacroute, P Perrin
Journal: Endoscopy (2018)

La résection endoscopique (RE) des gros polypes (GP) colorectaux (>= 20 mm) devient la règle. Certaines séries de petite taille et/ou monocentriques font état de taux de succès proches de 100%. D'autres, réalisées en population française, montrent que le recours à une résection chirurgicale (RC) n'est pas si rare, variant de 0 à 47% selon l'endoscopiste. But: évaluer le parcours de soins des patients porteurs de GP bénins en population.
Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study
Authors: Bruno Dubois, Stephane Epelbaum, Francis Nyasse, Hovagim Bakardjian, Geoffroy Gagliardi, Olga Uspenskaya, Marion Houot, Simone Lista, Federica Cacciamani, Marie-Claude Potier, Anne Bertrand, Foudil Lamari, Habib Benali, Jean-François Mangin, Olivier Colliot, Remy Genthon, Marie-Odile Habert, Harald Hampel, Christelle Audrain, Alexandra Auffret, Filippo Baldacci, Ismahane Benakki, Hugo Bertin, Laurie Boukadida, Enrica Cavedo, Patrizia Chiesa, Luce Dauphinot, Antonio Dos Santos, Marion Dubois, Stanley Durrleman, Gaëlle Fontaine, Alexis Genin, Pauline Glasman, Navichka Jungalee, Aurélie Kas, Maya Kilani, Valentina La Corte, Stephane Lehericy, Claire Letondor, Marcel Levy, Mark Lowrey, Juliette Ly, Ornella Makiese, Christiane Metzinger, Agnès Michon, Fanny Mochel, Catherine Poisson, Stephie Ratovohery, Marie Revillon, Katrine Rojkova, Perrine Roy, Katia Santos-Andrade, Rachel Schindler, Laure Seux, Valérie Simon, Marine Sole, Caroline Tandetnik, Marc Teichmann, Michel Thiebaut de Shotten, Nadjia Younsi
Journal: The Lancet Neurology (2018)
Hyperpigmentation in the skin folds
Authors: Xiao Ke Liu, Jun Li
Journal: BMJ (2018)

A 62 year old man presented with a one year history of asymptomatic hyperpigmentation of the flexural and intertriginous areas, especially in the groin (fig 1). He had thickened skin on his palms, feet, and neck, had lost 15 kg in three years, and had experienced nail dystrophy (melanonychia and onychoatrophy) for two years. He had recently received a diagnosis of unexplained hypothyroidism and hypogonadism. What is the most likely diagnosis?



Fig 1 
Hyperpigmented, velvety skin lesions in the groin



Acanthosis …
US public health agency to cut global surveillance by 80%
Authors: Janice Hopkins Tanne
Journal: BMJ (2018)

The US Centers for Disease Control and Prevention (CDC) will cut back its global epidemic surveillance and prevention efforts by 80% because it is running out of funds allocated during the 2014 Ebola epidemic.1

During the Ebola epidemic, Congress gave the agency almost $600m (£433m; €486m) in supplemental funds to help it assist countries prevent, detect, and respond to outbreaks of infectious diseases. It set up a Global Health …
Sialendoscopy enhances salivary gland function in Sjögren’s syndrome: a 6-month follow-up, randomised and controlled, single blind study
Authors: K Hakki Karagozoglu, Arjan Vissink, Tim Forouzanfar, Henk S Brand, Floor Maarse, Derk Hendrik Jan Jager
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To assess the effect of sialendoscopy of the major salivary glands on salivary flow and xerostomia in patients with Sjögren’s syndrome (SS). Methods Forty-nine patients with SS were randomly assigned to a control group (n=15) and two intervention groups: irrigation of the major glands with saline (n=16) or with saline followed by triamcinolone acetonide (TA) in saline (n=18). Unstimulated whole saliva flow (UWS), chewing-stimulated whole saliva flow (SWS), citric acid-stimulated parotid flow (SPF), Clinical Oral Dryness Score (CODS), Xerostomia Inventory (XI) score and the European League Against Rheumatism (EULAR) SS Patient-Reported Index (ESSPRI) were obtained 1 week (T0) before, and 1 (T1), 8 (T8), 16 (T16) and 24 (T24) weeks after sialendoscopy. Results Median baseline UWS, SWS and SPF scores were 0.14, 0.46 and 0.22 mL/min, respectively. After intervention, significant increases in UWS and SWS were observed in the saline group (at T8 (P=0.013) and T24 (P=0.004)) and the saline/TA group (at T24 (P=0.03) and T=16 (P=0.035)). SPF was increased significantly in the saline/TA group at T24 (P=0.03). XI scores declined after sialendoscopy in both intervention groups. Compared with the control group, CODS, XI and ESSPRI improved in the intervention groups. UWS, SWS and SPF were higher in the intervention groups compared with the control group, but these differences were not significant except for SPF in the saline/TA group at T24 (P=0.005). Conclusions Irrigation of the major salivary glands in patients with SS enhances salivary flow and reduces xerostomia up to 6 months after sialendoscopy.
Different interventions, same outcomes? Here are four good reasons
Authors: Chad E Cook, Steven Z George, Francis Keefe
Journal: British Journal of Sports Medicine (2018)

Conundrums in musculoskeletal research are common. Halliday and colleagues1 demonstrated similar outcomes for patients with chronic low back pain who received two seemingly different interventions: (1) a McKenzie approach and (2) motor control exercises. Chmielewski and associates2 reported similar knee function and psychosocial status scores in those who received either low intensity or high intensity plyometric exercise programmes. Finally, van Beijsterveildt et al found no differences in the prevention of injuries among amateur footballers when usual care was compared against an exercise strategy that consisted of core stability, eccentric training of thigh muscles, proprioceptive training, dynamic stabilisation and plyometrics exercises.3 These findings beg the question: Why do we see similar outcomes in randomised trials, which compare treatment strategies that are ostensibly different? Our goal is to provide explanations beyond the obvious answers —such as treatments that have similarly effective or ineffective causal mechanisms or failing to account for patient heterogeneity in trial design and consequent insufficient statistical power to detect differences. In this editorial, we present the reader with four additional yet plausible explanations for why trials report similar outcomes.

### Reason 1: the type of outcome assessment may bias findings

Our first explanation is the most obvious one. Outcome measures that capture direct measurements of strength and/or flexibility, or other indices of physical performance, may yield findings that are notably different from outcome measures that capture self-reports of pain, function, overall health status or quality of life. Therefore, null findings (no difference among groups) may be related to the fact that different sets of outcome measures are being used to compare the groups being studied.

Examples of variant findings among outcomes are present in the literature. One month after total hip arthroplasty, Dayton and colleagues4 report that performance-based function (eg, timed up and go, 6 min walk test and stair climbing test) declined compared with baseline, whereas self-reported …
Hsp27 blockade selectively inhibits growth of tumors with an activated PI3K pathway by regulating Akt and PEA-15
Authors: Norihiro Hayashi, James Peacock, Amina Zoubeidi, Martin Gleave, Christopher Ong
Journal: Cancer Research (2008)

3553   Hsp27 is a cytoprotective chaperone that is over-expressed in a wide range of malignancies and is associated with poor prognosis and therapeutic resistance. OGX-427, a selective inhibitor of Hsp27 expression has recently entered Phase I clinical trials for treatment of patients with prostate, breast, ovarian and lung cancers. Here we show that Hsp27 blockade selectively inhibits growth of cancer cells with an activated PI3K pathway and the Hsp27 chaperone is required for Akt stability and activity that, in turn, regulates phosphorylation and function of PEA-15. Hsp27 induces dual coordinated effects resulting in protection from Fas-induced apoptosis and promotion of cell proliferation through regulation of PEA-15 phosphorylation and function in an Akt dependent manner. Hsp27 overexpression induced activation of Akt and increased phosphorylation of its downstream target PEA15 resulting in enhanced ERK translocation to nucleus and increased Elk-1 activity which correlated with increased cyclin D1 and CDK2 expression with a concomitant decrease in p27kip1 expression and increased cell proliferation. Furthermore, Hsp27 overexpression also led to increased association of PEA-15 with FADD and decreased sensitivity of cells to Fas-induced apoptosis . Conversely, Hsp27 knockdown led to reduced Akt activity and decreased phosphorylation of PEA-15 leading to reduced association of PEA-15 with FADD and increased sensitivity of cells to Fas induced apoptosis. Significantly, siRNA mediated Hsp27 knockdown in a panel of cell lines and in PTEN Tet-ON LNCaP cells that express PTEN in a doxycycline inducible manner demonstrated selective inhibition of growth of cancer cells that have an activated PI3K pathway. Collectively, these data identify a dual role of Hsp27 in regulating cell proliferation and Fas-induced apoptosis through regulation of Akt and PEA-15 and suggest that improved clinical responsiveness to Hsp27 targeted therapy may be achieved by stratifying patient populations based on the dependence of cancer cells on the PI3K pathway.
hsa-mir183/EGR1–mediated regulation of E2F1 is required for CML stem/progenitor cell survival
Authors: Francesca Pellicano, Laura Park, Lisa E. M. Hopcroft, Mansi M. Shah, Lorna Jackson, Mary T. Scott, Cassie J. Clarke, Amy Sinclair, Sheela A. Abraham, Alan Hair, G. Vignir Helgason, Mark Aspinall-O’Dea, Ravi Bhatia, Gustavo Leone, Kamil R. Kranc, Anthony D. Whetton, Tessa L. Holyoake
Journal: Blood (2018)
Steroid hormone-induced prostate carcinogenesis in the Noble (NBL) rat: the effects of an aromatase inhibitor and catechol estrogens
Authors: Katherine Vega, Nilesh Gaikwad, Elli Rogan, Ercole Cavalieri, Maarten Bosland
Journal: Cancer Research (2007)

120   While it is known that estrogens regulate various functions in males, their role in prostate carcinogenesis remains unclear. To better understand the possible role of estrogens in the etiology of this disease, we have conducted studies in the Noble (NBL) rat, a strain that develops prostate tumors following chronic treatment (6-12 months) with steroid hormones. Treatment with testosterone (T) by s.c. Silastic tubing (approx. 45 microg/day) results in approx. 35-40% dorsolateral prostate (DLP) tumor incidence; the addition of estradiol-17β (E 2 , approx. 1.6 μg/day s.c.) increases tumor incidence to 100%. Inflammatory changes and dysplasia (= intraepithelial neoplasia) in the lateral prostate are evident after 13-16 weeks in T+E 2 -treated rats. Because T can be converted to E 2  by the enzyme aromatase, estrogens and their putatively carcinogenic catechol metabolites may play a role in this model. Therefore, we tested the effect of aromatase inhibition by letrozole in male NBL rats. Letrozole (up to 133 μg/day) or catechol estrogens (approx. 4.8 μg/day) were given by s.c. implant (Innovative Technologies) for 3 weeks with and without T. Letrozole reversed the T-induced increased weight selectively in the DLP in a dose-dependent manner, suggesting conversion of T to E 2  as a mechanism of action for T-induced weight increase and possibly carcinogenicity in the DLP. However, LC-MS-MS analysis of serum and tissue samples from these animals revealed complex patterns and considerable inter-individual variability in estrogen metabolites, with no discernible pattern that could explain the DLP weight differences. The catechol estrogen metabolites 2-hydroxyestradiol and 4-hydroxyestradiol (4-OHE 2 ) were neither toxic (no effect on growth) nor estrogenic (no pituitary enlargement) when given to male rats for up to 13 weeks by s.c implant. After 3 weeks, levels of these catechol estrogens and their metabolites were increased by approx. 2- to 4-fold in serum and prostate tissue in these rats. Furthermore, considerably increased levels of the N7-guanine and N3-adenine DNA adducts of 4-hydroxyestrogen were found in the serum and prostate of rats given 4-OHE 2 . In addition, there was no evidence of inflammatory changes and dysplasia seen in the lateral prostate following T+E 2  treatment. These data indicate that (1) aromatase inhibition may not a suitable approach to study the role of estrogen metabolism in testosterone-induced prostate carcinogenesis, and (2) 4-hydroxylated estrogen metabolites cause DNA adducts but appear not to be sufficient for induction of pre-neoplastic lesions that occur in the prostate of T+E 2  treated NBL rats, perhaps because these metabolites lack estrogenic activity. (Supported by Grants No. CA104334, CA49210, and DAMD17-02-1-0660.)
Lung Cancer in Brazil
Authors: Clarissa Mathias, Gustavo Faibischew Prado, Eldsamira Mascarenhas, Paula Antonia Ugalde, Ana Carolina Zimmer Gelatti, Elizangela Santos Carvalho, Lilian Dantonino Faroni, Ricardo Oliveira, Vladmir Claudio Cordeiro de Lima, Gilberto de Castro
Journal: Journal of Thoracic Oncology (2020)
The<i>STAT4</i>SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE
Authors: Niklas Hagberg, Martin Joelsson, Dag Leonard, Sarah Reid, Maija-Leena Eloranta, John Mo, Magnus K Nilsson, Ann-Christine Syvänen, Yenan T Bryceson, Lars Rönnblom
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ + cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. Results In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8 + T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8 + and CD4 + T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively. Conclusions T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.
Les données de l'endoscopie digestive haute réalisée en urgence. A propos de 890 cas
Authors: MS Tahir, A Bellabah, M Tahiri Joutei Hassani, F Haddad, W Hliwa, W Badre
Journal: Endoscopy (2018)

L'endoscopie digestive haute réalisée en urgence permet dans la majorité des cas de poser le diagnostic, d'évaluer le pronostic et de proposer un geste thérapeutique. Le but de notre travail est de rapporter les différentes indications ainsi que les données des fibroscopies digestives hautes réalisées en urgence.
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor–Positive Breast Cancer
Authors: Ivana Sestak, Richard Buus, Jack Cuzick, Peter Dubsky, Ralf Kronenwett, Carsten Denkert, Sean Ferree, Dennis Sgroi, Catherine Schnabel, Frederick L. Baehner, Elizabeth Mallon, Mitch Dowsett
Journal: JAMA Oncology (2018)

Multiple molecular signatures are available for managing estrogen receptor (ER)-positive breast cancer but with little direct comparative information to guide the patient's choice.
Successful Treatment of Scleredema Diabeticorum With Tranilast: Three Case Reports
Authors: Min Sun, Feng Yang, Maihua Hou
Journal: Diabetes Care (2018)

Scleredema is a rare disease that is characterized by symmetrical and nonpitting induration of the skin due to thickened dermis with abundant mucin deposition among large collagen bundles (1). Although many methods have been tried, there is currently no standard treatment.

We report three cases of scleredema diabeticorum treated with tranilast. It is well established that histopathology of pathogenic skin in patients with scleredema diabeticorum shows collagen fiber thickening and type I collagen metabolism abnormalities. In our inspection, a higher level of TGF-β can be seen by immunohistochemistry in patients with scleredema diabeticorum compared with healthy patients. It has been reported that tranilast was able to suppress the TGF-β–induced upregulation of type I collagen mRNA expression and the basal level of type I collagen mRNA in human …
Pharmacological targeting of MYC-regulated IRE1/XBP1 pathway suppresses MYC-driven breast cancer
Authors: Na Zhao, Jin Cao, Longyong Xu, Qianzi Tang, Lacey E. Dobrolecki, Xiangdong Lv, Manisha Talukdar, Yang Lu, Xiaoran Wang, Dorothy Z. Hu, Qing Shi, Yu Xiang, Yunfei Wang, Xia Liu, Wen Bu, Yi Jiang, Mingzhou Li, Yingyun Gong, Zheng Sun, Haoqiang Ying, Bo Yuan, Xia Lin, Xin-Hua Feng, Sean M. Hartig, Feng Li, Haifa Shen, Yiwen Chen, Leng Han, Qingping Zeng, John B. Patterson, Benny Abraham Kaipparettu, Nagireddy Putluri, Frank Sicheri, Jeffrey M. Rosen, Michael T. Lewis, Xi Chen
Journal: Journal of Clinical Investigation (2018)

The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enzyme 1 (IRE1)/X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms. We found that MYC directly controls IRE1 transcription by binding to its promoter and enhancer. Furthermore, MYC forms a transcriptional complex with XBP1, a target of IRE1, and enhances its transcriptional activity. Importantly, we demonstrate that XBP1 is a synthetic lethal partner of MYC. Silencing of XBP1 selectively blocked the growth of MYC-hyperactivated cells. Pharmacological inhibition of IRE1 RNase activity with small molecule inhibitor 8866 selectively restrained the MYC-overexpressing tumor growth in vivo in a cohort of preclinical patient-derived xenograft models and genetically engineered mouse models. Strikingly, 8866 substantially enhanced the efficacy of docetaxel chemotherapy, resulting in rapid regression of MYC-overexpressing tumors. Collectively, these data establish the synthetic lethal interaction of the IRE1/XBP1 pathway with MYC hyperactivation and provide a potential therapy for MYC-driven human breast cancers.
Abstract 191: Atherosclerosis risk and Carotid Intima-Media Thickness after Kawasaki Disease in Mexican Children
Authors: Luis M Garrido-Garcia, Sara Solorzano, Francisco J Espinosa-Rosales, Silvestre Garcia-De La Puente
Journal: Circulation (2015)

Background: Kawasaki disease (KD) is an acute febrile illness characterized by systemic vasculitis of unknown etiology. Recent studies have shown that even after resolution of the disease, endothelial dysfunction persists and may progress to premature atherosclerosis. Carotid intima-media thickness (cIMT) is a well-established indicator for atherosclerosis in both pediatric an adult patients. Objective: To assess whether patients after Kawasaki disease (KD) have increased risk factors and abnormalities suggestive of premature atherosclerosis by measuring the cIMT compared with healthy control subjects. Material and Methods: One hundred and three patients with KD aged 102.12 ± 41.82 months (61.94 ± 33.23 after the acute episode) and 83 age-matched healthy control subjects were examined for family, medical and dietary history, serum markers of atherosclerotic risk and inflammation and carotid intimal-medial thickness (CIMT) with vascular ultrasound scanning. Results: Patients and control subjects were similar in age, gender, family and dietary history, body mass index and blood pressure. We found no difference in the levels of triglycerides and glucose. And the levels of total cholesterol (162 ± 39.2 vs 150 ± 37.4), low-density lipoprotein cholesterol (102.57 ± 32.3 vs 89.6 ± 33.5), and high-density lipoprotein cholesterol (47.38 ± 17.65 vs 39.5 ± 17.54) were slightly higher with no statistical significance. The cIMT was slightly higher in the KD group (0.48 ± 0.1 vs 0.45 ± 0.15) We did found higher levels in the lipid profile and in the cIMT in children with or with regression of coronary aneurysms compared with children without coronary aneurysms. Conclusions: There is no clear evidence of increased atherosclerosis in Mexican children with KD, but there is evidence of an altered lipid profile and in the cIMT in patients with KD with coronary lesions compared with children with KD without coronary lesions the warrant further study