tbuckley/cabot-search huggingface dataset:
Aberrations of Genes Regulating NF Kappa B Pathway in B-Cell Malignant Lymphoma.
Authors: Motohiro Kato, Masashi Sanada, Itaru Kato, Yasuharu Sato, Junko Takita, Ryoichiro Kawahata, Kengo Takeuchi, Akira Niwa, Yuyan Chen, Kumi Nakazaki, Junko Nomoto, Yoshitaka Asakura, Yoshiki Akatsuka, Yasuhide Hayashi, Takashi Igarashi, Mineo Kurokawa, Shigeru Chiba, Shigeo Mori, Yuichi Ishikawa, Koji Okamoto, Kensei Tobinai, Hitoshi Nakagama, Tatsutoshi Nakahata, Tadashi Yoshino, Yukio Kobayashi, Seishi Ogawa
Journal: Blood (2009)
P0478 : NKG2D-dependent cross-talk between NK cells and CD4 T cells in chronic hepatitis B
Authors: W.-C. Huang, D. Peppa, N. Easom, X.-Z. Tang, H. Singh, G. Fusai, W. Rosenberg, I. Ghosh, R. Gilson, E. Nastouli, U. Gill, P. Kennedy, C.-W. Chang, J. Trowsdale, A. Toubert, M.K. Maini
Journal: Journal of Hepatology (2015)
MapMyFitness: tracking your training and routes
Authors: Edward Michael Caplan
Journal: British Journal of Sports Medicine (2016)

MapMyFitness (figure 1).



Figure 1 
MapMyFitness mobile interface.



Health and Fitness.

Apple (iOS 8.0 or later), Android (V.4.0.3 or later).

Free for standard version; Premium (MVP) version for £4.49/month or £22.99/year.

MapMyFitness is one of the fitness-related apps owned by Under Armour (which include MyFitnessPal, MapMyRun, MapMyRide). This app provides an integrated, comprehensive system to map training sessions and preferred routes using global positioning system (GPS) technology. It allows the user to track various physical activities (such as cycling, walking, hiking, running), obtain an extensive analysis of each workout and set personal goals. The following data are tracked live and uploaded onto the app and website following session completion: calories expended, distance travelled, elevation, duration, pace and route. This gives the user details for each completed workout and a record of workout history. Features …
TKI258, a novel, multitargeted tyrosine kinase inhibitor for the treatment of breast cancer
Authors: H. Liu, C. O. Schulz, A. C. Regierer, A. Dieing, K. Possinger, J. Eucker
Journal: Journal of Clinical Oncology (2009)

e14625 TKI258 (4-amino-5-fluor-3-[5-(4-metylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one, formerly known as CHIR258) is an ATP-competitive inhibitor with activities against class III or IV receptor kinases, which include FGFR, VEGFR, PDGFR, FLT3, and KIT. It has been demonstrated to possess strong anti-tumor and anti-angiogenetic activities in different tumor models, and, therefore, this compound is currently being clinically assessed for the treatment of diverse malignancies. In this study, we chose the breast cancer cell line MDA-MB-231, a cell line with high invasive capacities, as an in vitro model to analyze the effect and functional mechanism of TKI258 on the breast cancer invasiveness. Treatment of MDA-MB-231 cells with TKI258 resulted in reduced invasive capacities in a dose-dependent manner. In association with this effect, we observed that TKI258 down-regulated the phosphorylation of ERK1/2 and STAT3 and inhibited the VEGF production in the cell supernatants. Most interestingly, we found TKI258 had influence on the inflammatory chemokines CCL5 and CCL2 level if MDA-MB-231 cells were co-cultured with breast cancer stroma cells. We found that CCL5/CCL2 mRNA level in MDA-MB-231 cells, in stroma cells, or in co-culture of MDA-MB-231/breast cancer stroma was strongly inhibited by TKI258 as detected with real-time PCR. Parallel to this result, the dramatically elevated CCL2/CCL5 level in the media supernatants from co-cultured MDA-MB-231/stroma cells was reduced by TKI258 effectively. Furthermore, we demonstrated that the invasion-promoting effect of the tumor stroma cells was antagonized by TKI258 significantly. CCL5 stimulated invasion of MDA-MB-231 cells could be partially abrogated by TKI58 and/or by CCL5-neutralizing antibody. Therefore, it is most likely that the inhibitory effect of TKI258 on invasion of MDA-MB-231 cells in the presence of stroma cells is achieved, at least in part, by antagonizing the invasion-promoting effect of CCL5. Overall, our data show that TKI258 inhibited invasive capacities of aggressive breast cancer cell line MDA-MB-231, either in the absence or presence of tumor stroma cells in vitro. No significant financial relationships to disclose.
Complete mutational spectrum of the autophagy interactome: a novel class of tumor suppressor genes in myeloid neoplasms
Authors: V Visconte, B Przychodzen, Y Han, S T Nawrocki, S Thota, K R Kelly, B J Patel, C Hirsch, A S Advani, H E Carraway, M A Sekeres, J P Maciejewski, J S Carew
Journal: Leukemia (2016)
Superantigens and adhesins of infant gut commensal<i>Staphylococcus aureus</i>strains and association with subsequent development of atopic eczema
Authors: F.L. Nowrouzian, G. Lina, E. Hodille, E. Lindberg, B. Hesselmar, R. Saalman, I. Adlerberth, A.E. Wold
Journal: British Journal of Dermatology (2016)

According to the hygiene hypothesis, insufficient immune activation by microbes increases the risk of allergy development. Staphylococcus aureus, which is part of the skin and gut microbiota of infants in Western countries, produces a variety of T-cell-activating enterotoxins, called superantigens.To investigate whether early (0-2 months of age) gut colonization by S. aureus strains that carry specific superantigens and adhesins was related to subsequent development of atopic eczema in a Swedish birth cohort.Staphylococcus aureus was isolated from rectal swabs and cultured quantitatively from faecal samples, with individual strains being tested for carriage of genes for superantigens and adhesins. Atopic eczema was diagnosed at onset of symptoms and at 18 months of age.Although the frequency of early gut colonization by S. aureus was not related to subsequent eczema development, the S. aureus strains that were found to colonize those infants who developed atopic eczema were less likely to carry the gene encoding the superantigen SElM (P = 0·008) and the gene for elastin-binding protein (P = 0·03), compared with strains that were isolated from infants who had not developed atopic eczema by 18 months of age.Gut colonization by S. aureus strains carrying a certain combination of superantigen and adhesin genes was negatively associated with subsequent development of atopic eczema. Such strains may provide stimulation and promote maturation of the infant immune system.
Phase I/II study of sorefenib and erlotinib for patients with recurrent glioblastoma (GBM) (NABTC 05–02)
Authors: M. Prados, M. Gilbert, J. Kuhn, K. Lamborn, T. Cloughesy, F. Lieberman, V. Puduvalli, H. I. Robins, A. Lassman, P. Y. Wen
Journal: Journal of Clinical Oncology (2009)

2005 Background: Single agent targeted therapy has been disappointing in GBM. Combination therapy simultaneously targeting both EGFR and the MAP kinase pathway may be more effective. Methods: The NABTC conducted a phase I/II study of sorafenib (VEGFR/PDGFR/Raf inhibitor) in combination with erlotinib (EGFR inhibitor) in recurrent GBM. Eligibility criteria included histologically proven GBM, radiologic progression, &gt; 18 yrs old, KPS &gt; 60, adequate bone marrow reserve, and organ function. There was no limit on the number of prior therapies for phase I and no more than two prior relapses for phase II. No enzyme-inducing antiepileptic drugs were allowed. Dose-finding used a standard 3 + 3 design and the MTD was defined as the dose with DLTs in 1/6 or fewer patients. The primary endpoint for the phase II component was PFS6 (p0 = 15%; p1 = 35%). A 2-stage design was used. If &gt; 4 of the initial 19 patients achieved PFS6, an additional 14 patients would be accrued for a total of 33 patients. Results: In phase I, 17 patients were enrolled. Median age 50 years (35–69); median prior chemotherapy 1 (1–3). The initial doses were sorafenib 200 mg bid and erlotinib 100mg qd. MTD was 400 mg bid of sorafenib daily combined with 100 mg of erlotinib daily. At this dose 1/6 evaluable patients had a DLT (grade 4 lipase). Other grade 3 or 4 toxicities included transaminitis, hypertension, hypophosphatemia, and increased lipase. Pharmacokinetic studies showed no alterations in sorafenib PK, but no accumulation of erlotinib, suggesting a drug-drug interaction with sorafenib altering erlotinib metabolism or clearance. In phase II, 19 patients were accrued to stage I. Median age 51 years (30–75); median prior chemotherapy 2 (range 1–3). Phase II toxicity and outcome data are not yet mature but will be available at the time of presentation. Conclusions: This combination was moderately well-tolerated. MTD was below other combination phase I studies. Sorafenib affected the PK of erlotinib preventing drug accumulation. Phase II toxicity and outcome data will be reported. [Table: see text]
ERCC1 as biomarker of response to oxaliplatin in colorectal cancer: To induce or not induce … this is the problem. preliminary data from liquid biopsy
Authors: M. Di Salvatore, A. Orlandi, C. Paolillo, M.G. Rodriquenz, E. Rossi, M. Basso, A. Strippoli, E. Capoluongo, C. Pozzo, A. Astone, A. Cassano, C. Barone
Journal: Annals of Oncology (2015)
Globoside accelerates the differentiation of dental epithelial cells into ameloblasts
Authors: Takashi Nakamura, Yuta Chiba, Masahiro Naruse, Kan Saito, Hidemitsu Harada, Satoshi Fukumoto
Journal: International Journal of Oral Science (2016)

Tooth crown morphogenesis is tightly regulated by the proliferation and differentiation of dental epithelial cells. Globoside (Gb4), a globo-series glycosphingolipid, is highly expressed during embryogenesis as well as organogenesis, including tooth development. We previously reported that Gb4 is dominantly expressed in the neutral lipid fraction of dental epithelial cells. However, because its functional role in tooth development remains unknown, we investigated the involvement of Gb4 in dental epithelial cell differentiation. The expression of Gb4 was detected in ameloblasts of postnatal mouse molars and incisors. A cell culture analysis using HAT-7 cells, a rat-derived dental epithelial cell line, revealed that Gb4 did not promote dental epithelial cell proliferation. Interestingly, exogenous administration of Gb4 enhanced the gene expression of enamel extracellular matrix proteins such as ameloblastin, amelogenin, and enamelin in dental epithelial cells as well as in developing tooth germs. Gb4 also induced the expression of TrkB, one of the key receptors required for ameloblast induction in dental epithelial cells. In contrast, Gb4 downregulated the expression of p75, a receptor for neurotrophins (including neurotrophin-4) and a marker of undifferentiated dental epithelial cells. In addition, we found that exogenous administration of Gb4 to dental epithelial cells stimulated the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase signalling pathways. Furthermore, Gb4 induced the expression of epiprofin and Runx2, the positive regulators for ameloblastin gene transcription. Thus, our results suggest that Gb4 contributes to promoting the differentiation of dental epithelial cells into ameloblasts.
Abstract B03: Control of pancreatic cancer metabolism and histone acetylation by the tumor microenvironment
Authors: Mara H. Sherman, Ronald M. Evans
Journal: Cancer Research (2016)

Abstract Though the significance of reciprocal interactions between genetically altered tumor cells and adjacent stroma is increasingly appreciated, this complex crosstalk remains poorly understood. Pancreatic ductal adenocarcinoma (PDAC) has a particularly prominent stromal compartment, shown to exert both tumor-supportive and tumor-suppressive or homeostatic functions in the context of the wound-like tumor microenvironment. To investigate the paracrine effects of PDAC stromal elements on pancreatic cancer cells, we developed a “stromal” culture system, which incorporates structural and diffusible stroma-derived elements into homotypic PDAC cell cultures amenable to functional genomics and metabolomics. These analyses revealed that microenvironmental cues co-regulate cancer metabolism and gene expression. Stromal inputs broadly influenced histone acetylation in the PDAC epigenome, which coincided with induction of genes implicated in anabolic metabolism and inflammation. The gene expression and metabolic changes induced by stromal factors overlap with those previously identified following oncogenic Kras, suggesting functional complementarity between cell-autonomous and microenvironmental pathways characteristic of PDAC. As epigenome modification results in changes in gene expression through the functions of readers, such as the bromodomain-containing BET proteins, we tested JQ1, a small molecule inhibitor of BET family bromodomain-containing proteins, for the capacity to inhibit gene expression changes downstream of stromal factors. Paracrine induction of pro-growth and inflammatory genes was inhibited by JQ1, suggesting that the BET family serves as a key transducer of stromal inputs to drive alterations in gene expression. Inhibition of acetyl-lysine sensing by the BET family reduced pancreatic tumor growth and associated inflammation in vivo, with significant reduction in expression of genes implicated in macromolecule biosynthesis and tumor-permissive immune regulation. This work suggests paracrine epigenome regulation as a conduit through which stromal signals drive metabolic and immune adaptation to a challenging tumor microenvironment. Citation Format: Mara H. Sherman, Ronald M. Evans. Control of pancreatic cancer metabolism and histone acetylation by the tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B03.
Official Executive Summary of an American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults
Authors: Gregory A. Schmidt, Timothy D. Girard, John P. Kress, Peter E. Morris, Daniel R. Ouellette, Waleed Alhazzani, Suzanne M. Burns, Scott K. Epstein, Andres Esteban, Eddy Fan, Miguel Ferrer, Gilles L. Fraser, Michelle Ng Gong, Catherine L. Hough, Sangeeta Mehta, Rahul Nanchal, Sheena Patel, Amy J. Pawlik, William D. Schweickert, Curtis N. Sessler, Thomas Strøm, Kevin C. Wilson, Jonathon D. Truwit
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

This clinical practice guideline addresses six questions related to liberation from mechanical ventilation in critically ill adults. It is the result of a collaborative effort between the American Thoracic Society and the American College of Chest Physicians.A multidisciplinary panel posed six clinical questions in a Population, Intervention, Comparator, and Outcomes format. A comprehensive literature search and evidence synthesis was performed for each question, which included appraising the certainty in the evidence (i.e., the quality of evidence) using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The Evidence-to-Decision framework was applied to each question, requiring the panel to evaluate and weigh the importance of the problem, the confidence in the evidence, the certainty about how much the public values the main outcomes, the magnitude and balance of desirable and undesirable outcomes, the resources and costs associated with the intervention, the impact on health disparities, and the acceptability and feasibility of the intervention.Evidence-based recommendations were formulated and graded initially by subcommittees and then modified after full-panel discussions. The recommendations were confirmed by confidential electronic voting; approval required that at least 80% of the panel members agree with the recommendation.The panel provides recommendations regarding liberation from mechanical ventilation. The details regarding the evidence and rationale for each recommendation are presented in the American Journal of Respiratory and Critical Care Medicine and Chest.
Functional (PET/CT) compared to conventional (mammography [M], sonography [US], MRI) imaging: Defining novel assessment modalities for inflammatory breast cancer (IBC)
Authors: W. T. Yang, H. T. Le-Petross, A. Gonzalez-Angulo, H. Macapinlac, H. Macapinlac, S. Dawood, E. Resetkova, G. N. Hortobagyi, M. Cristofanilli
Journal: Journal of Clinical Oncology (2007)

600 Background: IBC is an aggressive frequently lethal form of breast cancer that is defined by sudden onset breast erythema often without an associated clinical or radiological breast mass. Tissue diagnosis remains problematic due to inability to define an area for biopsy. The aim of this study was to compare conventional [M, US, MRI] vs. functional imaging [PET/CT] in detecting a primary breast parenchymal lesion (BPL) at initial presentation of IBC. Methods: Patients (pts) with a new clinical diagnosis of IBC evaluated at the M. D. Anderson Cancer Center between January 2003 to December 2006 who had M, US, MRI, or PET/CT were included in this study. The visibility of a BPL and skin abnormality on each imaging modality was compared. Regional (axillary, supraclavicular, internal mammary) nodal disease confirmed by pathology was assessed at US and PET/CT. The presence of metastatic disease at diagnosis with PET/CT was documented. Results: Sixty-seven pts met eligibility criteria. Median age was 51 years, (range, 25 to 78). Of these, 61 (91%) had M, 62 (93%) had US, 21 (31%) had MRI, and 13 (19%) had PET/CT. By M, no BPL (mass or calcifications) was observed in 16% (10/61), skin-only abnormality (SOA) in 14% (9/61), and a BPL in 84% (51/61). By US, no BPL (mass or architectural distortion) and SOA were noted in 6% (4/62), and a PBL in 94% (58/62). By MRI, 21/21 (100%) showed malignant enhancing BPL and skin thickening. By PET/CT, 100% (13/13) showed hypermetabolic BPL and skin thickening. Pathologically confirmed regional nodal disease was diagnosed in 96% (59/62) by US and in 69% (9/13) by PET/CT. Distant metastases in the bone and lung were diagnosed in 15% (2/13) by PET/CT, one of which was visible on bone scan. Conclusions: MRI and PET/CT showed a primary BPL in all cases of IBC while conventional imaging (M and US) failed to reveal a BPL amenable to biopsy in up to 16%. US can diagnose regional nodal disease to facilitate loco-regional therapeutic planning. PET/CT provides additional information on distant metastasis and should be considered in the initial staging of IBC. No significant financial relationships to disclose.
A neuronal PI(3,4,5)P3-dependent program of oligodendrocyte precursor recruitment and myelination
Authors: Sandra Goebbels, Georg L Wieser, Alexander Pieper, Sonia Spitzer, Bettina Weege, Kuo Yan, Julia M Edgar, Oleksandr Yagensky, Sven P Wichert, Amit Agarwal, Khalad Karram, Nicolas Renier, Marc Tessier-Lavigne, Moritz J Rossner, Ragnhildur Thóra Káradóttir, Klaus-Armin Nave
Journal: Nature Neuroscience (2016)
Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association
Authors: Barbara S. Wiggins, Joseph J. Saseen, Robert L. Page, Brent N. Reed, Kevin Sneed, John B. Kostis, David Lanfear, Salim Virani, Pamela B. Morris
Journal: Circulation (2016)
Equivalent Outcome Between Reduced Intensity Versus Conventional Myeloablative Conditioning Hematopoietic Stem Cell Transplantation for Patients Older Than 35 Years with Acute Myeloid Leukemia.
Authors: Marie Sebert, Raphaël Porcher, Marie Robin, Lionel Ades, Emmanuel Raffoux, Alienor Xhaard, Nathalie Dhedin, Jerome Larghero, Chantal Himberlin, Alain Delmer, Pierre Fenaux, Hervé Dombret, Gérard Socié, Regis Peffault de Latour
Journal: Blood (2012)
Systematic Analysis of Known Candidate Genes in 58 Probands with Previously Uncharacterized Congenital Sideroblastic Anemia: Evidence for Genetic Heterogeneity and Identification of Novel Mutations in ALAS2 and PUS1
Authors: Anke K. Neuwirth, Dean R. Campagna, Mark D. Fleming, Sylvia S. Bottomley, Ellis J. Neufeld
Journal: Blood (2008)
Emergence of the Noncoding Cancer Genome: A Target of Genetic and Epigenetic Alterations
Authors: Stanley Zhou, Aislinn E. Treloar, Mathieu Lupien
Journal: Cancer Discovery (2016)

Abstract The emergence of whole-genome annotation approaches is paving the way for the comprehensive annotation of the human genome across diverse cell and tissue types exposed to various environmental conditions. This has already unmasked the positions of thousands of functional cis-regulatory elements integral to transcriptional regulation, such as enhancers, promoters, and anchors of chromatin interactions that populate the noncoding genome. Recent studies have shown that cis-regulatory elements are commonly the targets of genetic and epigenetic alterations associated with aberrant gene expression in cancer. Here, we review these findings to showcase the contribution of the noncoding genome and its alteration in the development and progression of cancer. We also highlight the opportunities to translate the biological characterization of genetic and epigenetic alterations in the noncoding cancer genome into novel approaches to treat or monitor disease. Significance: The majority of genetic and epigenetic alterations accumulate in the noncoding genome throughout oncogenesis. Discriminating driver from passenger events is a challenge that holds great promise to improve our understanding of the etiology of different cancer types. Advancing our understanding of the noncoding cancer genome may thus identify new therapeutic opportunities and accelerate our capacity to find improved biomarkers to monitor various stages of cancer development. Cancer Discov; 6(11); 1215–29. ©2016 AACR.
Reduce NHS’s reliance on migrants, HEE is told
Authors: Abi Rimmer
Journal: BMJ (2016)

Health Education England has been told by the government that it must produce a plan by September 2017 to reduce the NHS’s reliance on migrant workers.

Earlier this month Jeremy Hunt, health secretary for England, announced plans to increase medical school places by 25% in a bid to expand the number of home grown doctors and to replace doctors recruited from overseas.1

As part of HEE’s mandate from the government for April 2016 to March 2017, the Department of Health said that the …
Discrimination of an Early Unfavorable Risk Group Has Significant Impact On Treatment Outcome in Early-Stage Hodgkin Lymphoma: An Analysis of International Staging Definitions and Risk Factors
Authors: Beate Klimm, Helen Goergen, Michael Fuchs, Bastian von Tresckow, Volker Diehl, Hans Theodor Eich, Andreas Engert, Peter Borchmann
Journal: Blood (2012)