tbuckley/cabot-search huggingface dataset:
The burden of cutaneous adnexal carcinomas and the risk of associated squamous cell carcinoma: a population‐based study
Authors: V. De Giorgi, L. Salvati, A. Barchielli, A. Caldarella, A. Gori, F. Scarfì, I. Savarese, N. Pimpinelli, C. Urso, D. Massi
Journal: British Journal of Dermatology (2018)

Background Recent studies have shown an increasing incidence of cutaneous adnexal carcinomas (CACs). Objectives The aim of our study was to evaluate incidence and survival for cases of CACs and investigate their association with other skin neoplasms. Methods We conducted a population-based study. Data on incident cases of CACs were obtained from the Tuscany Cancer Registry between 1985 and 2010. In order to determine whether the occurrence of squamous cell carcinoma (SCC) among patients with CAC is higher or lower than expected in the general population, the standardized incidence ratio (SIR) was calculated. Results A total of 242 patients with CAC were observed; the age-standardized incidence rate was 3·8 cases per million person-years. From 1997 to 2010 crude incidence rates increased by 159%. Age-specific incidence was higher in men over 80 years old than in women of the same age and younger individuals. Carcinomas of sweat gland origin prevailed; the most common histotype was porocarcinoma and the most frequently affected site was the head/neck. Overall, 88% of CACs were diagnosed at a localized stage. The 5-year overall survival and disease-specific survival rates were 59% [95% confidence interval (CI) 53–65] and 94% (95% CI 91–98), respectively. In the observation cohort, the number of SCCs was significantly higher than expected as the SIR was calculated to be 33·7 (P < 0·001). Conclusions Increasing incidence warrants awareness and early diagnosis of CACs. Increased SCC incidence among patients with these tumours highlights the relevance of careful skin examination and follow-up.
Progranulin reduces insoluble TDP-43 levels, slows down axonal degeneration and prolongs survival in mutant TDP-43 mice
Authors: Sander Beel, Sarah Herdewyn, Raheem Fazal, Mathias De Decker, Matthieu Moisse, Wim Robberecht, Ludo Van Den Bosch, Philip Van Damme
Journal: Molecular Neurodegeneration (2018)

TAR DNA binding protein 43 (TDP-43) is the main disease protein in most patients with amyotrophic lateral sclerosis (ALS) and about 50% of patients with frontotemporal dementia (FTD). TDP-43 pathology is not restricted to patients with missense mutations in TARDBP, the gene encoding TDP-43, but also occurs in ALS/FTD patients without known genetic cause or in patients with various other ALS/FTD gene mutations. Mutations in progranulin (GRN), which result in a reduction of ~ 50% of progranulin protein (PGRN) levels, cause FTD with TDP-43 pathology. How loss of PGRN leads to TDP-43 pathology and whether or not PGRN expression protects against TDP-43-induced neurodegeneration is not yet clear. We studied the effect of PGRN on the neurodegenerative phenotype in TDP-43(A315T) mice. PGRN reduced the levels of insoluble TDP-43 and histology of the spinal cord revealed a protective effect of PGRN on the loss of large axon fibers in the lateral horn, the most severely affected fiber pool in this mouse model. Overexpression of PGRN significantly slowed down disease progression, extending the median survival by approximately 130 days. A transcriptome analysis did not point towards a single pathway affected by PGRN, but rather towards a pleiotropic effect on different pathways. Our findings reveal an important role of PGRN in attenuating mutant TDP-43-induced neurodegeneration.
Abstract 16797: Identification of Malondialdehyde-Acetaldehyde-Modified Proteins From Affected Tissues in Rheumatoid Arthritis and Cardiovascular Disease
Authors: Michael J Duryee, Dahn L Clemens, Lynell W Klassen, Ted R Mikuls, Morgan C Pomplun, Daniel R Anderson, Geoffrey M Thiele
Journal: Circulation (2017)

Introduction: We have shown that MAA-modified proteins co-localize with citrullinated antigen in rheumatoid arthritis (RA) synovium. Although both MAA-adducts and citrullinated antigen have been id...
Inmunohistochemical (IHQ) classification of DLBCL into CGB and non-CGB subtypes to predict survival after chemoimmunotherapy at the Virgen de la Victoria University Hospital
Authors: L. Galvez Carvajal, C. Quero Blanco, M. Robles Lasarte, I. Moreno Perez, L. Vicioso, I. Ramos Garcia, C. Bandera Lopez, J. Baena Espinar, C. Ithurbisquy, E. Alba
Journal: Annals of Oncology (2018)
Identification of genetic causes for sporadic steroid-resistant nephrotic syndrome in adults
Authors: Olivier Gribouval, Olivia Boyer, Aurélie Hummel, Jacques Dantal, Frank Martinez, Rebecca Sberro-Soussan, Isabelle Etienne, Dominique Chauveau, Michel Delahousse, Arnaud Lionet, Julien Allard, Claire Pouteil Noble, Marie-Josèphe Tête, Laurence Heidet, Corinne Antignac, Aude Servais
Journal: Kidney International (2018)
P3.16-43 Is Sublobar Resection for Stage I Invasive Adenocarcinoma (≤2-cm) Feasible?
Authors: Y. Terada, T. Takahashi, J. Nitadori, K. Kitano, K. Nagayama, M. Anraku, M. Sato, A. Shinozaki-Ushiku, S. Morita, J. Nakajima
Journal: Journal of Thoracic Oncology (2018)
Safety, tolerability, and preliminary efficacy of an IGF-1 mimetic in patients with spinal and bulbar muscular atrophy: a randomised, placebo-controlled trial
Authors: Christopher Grunseich, Ram Miller, Therese Swan, David J Glass, Mohamed El Mouelhi, Mara Fornaro, Olivier Petricoul, Igor Vostiar, Ronenn Roubenoff, Matthew N Meriggioli, Angela Kokkinis, Robert D Guber, Maher S Budron, John Vissing, Gianni Soraru, Tahseen Mozaffar, Albert Ludolph, John T Kissel, Kenneth H Fischbeck, Christopher Grunseich, Ram Miller, Therese Swan, David J Glass, Mohamed El Mouelhi, Mara Fornaro, Olivier Petricoul, Igor Vostiar, Ronenn Roubenoff, Matthew N Meriggioli, Julia Dahlqvist, Nanna Witting, John Vissing, Ilaria Martinelli, Giorgia Querin, Gianni Soraru, Namita A Goyal, Tiyonnoh M Cash, Brian Minton, Tahseen Mozaffar, Angela Rosenbohm, Ulrike Weiland, Patrick Weydt, Albert Ludolph, Sharon Chelnick, Stanley Iyadurai, Wendy King, John T Kissel, Maher S Budron, Robert D Guber, Angela Kokkinis, Kenneth H Fischbeck
Journal: The Lancet Neurology (2018)
The application of indocyanine green fluorescence navigation method to a sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer
Authors: K. Yamagami, H. Matsumoto, T. Hashimoto, S. Yanai, S. Yuen, Y. Yata, Y. Ichinose, T. Deai, M. Toi
Journal: Annals of Oncology (2018)
Neoadjuvant cytoreductive treatment with BRAF/MEK inhibition of prior unresectable regionally advanced melanoma to allow complete surgical resection, REDUCTOR trial
Authors: S. Blankenstein, M.W. Rohaan, W.M.C. Klop, B. van der Hiel, B. van de Wiel, D. Peeper, A.C.J. van Akkooi, J.B.A.G. Haanen
Journal: Annals of Oncology (2018)
Role of Allergic Inflammatory Cells in Coronary Artery Disease
Authors: Giampaolo Niccoli, Rocco A. Montone, Vito Sabato, Filippo Crea
Journal: Circulation (2018)

Inflammation is an important player both for the initiation and progression of coronary artery disease and for coronary plaque instability. Moreover, inflammation contributes to stent thrombosis and in-stent restenosis after percutaneous coronary intervention. In the past several decades, most studies evaluated the involvement of cellular effectors of classic inflammatory responses, such as monocytes/macrophages, neutrophils, and T cells. Yet, besides classic inflammation, mounting evidence derived from both experimental and clinical studies suggests an important, often unrecognized, role for effector cells of allergic inflammation in both the pathogenesis of coronary artery disease and adverse events following stent implantation. In this review, we discuss the role of effector cells of allergic inflammation in the setting of coronary artery disease progression and instability, and in the occurrence of adverse events following stent implantation, as well. Moreover, we discuss possible therapeutic approaches targeting different specific pathways of allergic inflammatory activation.
How data science can advance mental health research
Authors: Tom C. Russ, Eva Woelbert, Katrina A. S. Davis, Jonathan D. Hafferty, Zina Ibrahim, Becky Inkster, Ann John, William Lee, Margaret Maxwell, Andrew M. McIntosh, Rob Stewart, Margaret Anderson, Kate Aylett, Suzy Bourke, Anna Burhouse, Felicity Callard, Kathy Chapman, Matt Cowley, James Cusack, Katrina A. S. Davis, Jaime Delgadillo, Sophie Dix, Richard Dobson, Gary Donohoe, Nadine Dougall, Johnny Downs, Helen Fisher, Amos Folarin, Thomas Foley, John Geddes, Joardana Globerman, Jonathan D. Hafferty, Lamiece Hassan, Joseph Hayes, Helen Hodges, Zina Ibrahim, Becky Inkster, Eddie Jacob, Rowena Jacobs, Ann John, Cynthia Joyce, Suky Kaur, Maximilian Kerz, James Kirkbride, Gerard Leavey, Glyn Lewis, Keith Lloyd, Wendy Matcham, Margaret Maxwell, Erin McCloskey, Andrew M. McIntosh, Andrew McQuillin, Tamsin Newlove Delgado, Catherine Newsome, Kristin Nicodemus, David Porteous, Daniel Ray, Tom C. Russ, Simran Sanhu, Daniel Smith, Robert Stewart, Laura Tutu, Ayath Ullah, Bill Vance, Eva Woelbert, Miranda Wolpert, Cathy Wyse, Stanley Zammit
Journal: Nature Human Behaviour (2018)
Abstract IA07: Influence of cancer initiation on tumor progression in SCLC
Authors: Dian Yang, Monte M. Winslow, Julien Sage
Journal: Clinical Cancer Research (2018)

Abstract The vast majority of cancer patients die from metastatic disease, but the molecular and cellular mechanisms that drive metastatic progression often remain poorly understood. Small cell lung cancer (SCLC) is a neuroendocrine form of lung cancer and one of the most metastatic and lethal cancers. Most SCLC patients are usually first diagnosed when they already have metastatic disease, and SCLC tumors are thus thought to acquire metastatic ability early in the course of tumor development. However, how early events shape the evolution and metastatic progression of SCLC is largely unknown. We will present evidence, using genetically engineered mouse models of SCLC, that distinct mechanisms drive metastatic progression depending on the cell of origin. In one mouse model, we found that tumors gain metastatic ability through amplification of the transcription factor Nfib; this amplification is accompanied by a striking opening of the chromatin at many sites in the genome. In the second model, metastatic progression is not associated with Nfib-driven chromatin alterations. Gene expression profiling studies reveal distinct mechanisms of metastatic progression in the two groups, as well as markers predictive of the two metastatic paths. Our data indicate that Nfib-independent metastases arise from pulmonary neuroendocrine cells. These observations demonstrate that the identity of tumor-initiating cells can determine the molecular mechanisms of tumor evolution. Citation Format: Dian Yang, Monte M. Winslow, Julien Sage. Influence of cancer initiation on tumor progression in SCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA07.
What did the party conferences tell us about the NHS and social care?
Authors: Andy Cowper
Journal: BMJ (2018)

The signs were that for neither major party is health near the top of the agenda

The first thing we learnt, from the main UK party conferences in the past couple of weeks, was that despite Jonathan Ashworth’s generally strong performance as Labour shadow health secretary he may not be liked by the party’s fixers, as he was given a 9 am slot on the day of Jeremy Corbyn’s speech. Given the traditional nocturnal socialising at party conferences, and the oxygen of media coverage inevitably going to Corbyn, this was not a prime slot for the party’s health lead in the year of the NHS’s 70th birthday.

Ashworth’s speech was a competent critique of the government’s record.1 Last year his conference speech had set out a spending offer of £45bn extra funding for health and social care, and in June this year the Conservatives promised just over £20bn extra by 2023-24.2 Ashworth’s …
KEYNOTE-427 cohort A: Pembrolizumab monotherapy as first-line therapy in advanced clear cell renal cell carcinoma (ccRCC)
Authors: F. Donskov, D.F. McDermott, J.L. Lee, C. Szczylik, J. Malik, B.Y. Alekseev, J.M.G. Larkin, V.B. Matveev, R. Airatovich Gafanov, P. Tomczak, S.S. Tykodi, P.F. Geertsen, P. Wiechno, S.J. Shin, F. Pouliot, T. Alonso Gordoa, R. Kloss Silverman, R.F. Perini, C. Schloss, M.B. Atkins
Journal: Annals of Oncology (2018)
Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue
Authors: S. Ciavarella, M.C. Vegliante, M. Fabbri, S. De Summa, F. Melle, G. Motta, V. De Iuliis, G. Opinto, A. Enjuanes, S. Rega, A. Gulino, C. Agostinelli, A. Scattone, S. Tommasi, A. Mangia, F. Mele, G. Simone, A.F. Zito, G. Ingravallo, U. Vitolo, A. Chiappella, C. Tarella, A.M. Gianni, A. Rambaldi, P.L. Zinzani, B. Casadei, E. Derenzini, G. Loseto, A. Pileri, V. Tabanelli, S. Fiori, A. Rivas-Delgado, A. López-Guillermo, T. Venesio, A. Sapino, E. Campo, C. Tripodo, A. Guarini, S.A. Pileri
Journal: Annals of Oncology (2018)

BackgroundGene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited.Patients and methodsHere, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens.ResultsIn silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology.ConclusionsOur study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.
Survey of end-of-life medical care of lung cancer
Authors: Tomohiro Sakamoto, Yasuhiko Teruya, Natsumi Tanaka, Kosuke Yamaguchi, Kenichi Takeda, Haruhiko Makino, Masahiro Kodani, Akira Yamasaki, Tadashi Igishi, Eiji Shimizu
Journal: Annals of Oncology (2018)
Relationship between androgen receptor and tumor-infiltrating lymphocytes in triple-negative breast cancer
Authors: L.F. Sánchez-Cousido, A. López-González, E. Honrado Franco, E. Vallejo Pascual, O. Sanz, L. Lopez Gonzalez, I. Delgado, M. López-Flores, A. García Palomo
Journal: Annals of Oncology (2018)
A detailed evaluation method of CD4 + T cell subsets
Authors: Banri Tsuda, Asuka Miyamoto, Mari Mizuno, Kozue Yokoyama, Risa Oshitanai, Mayako Terao, Toru Morioka, Naoki Niikura, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yoshie Kametani, Yutaka Tokuda
Journal: Annals of Oncology (2018)
GW29-e1716 Analysis of efficacy and safety of epicardial ablation of ventricular arrhythmia: a single center experience
Authors: Yuxi Wang, Wenjie Yu, Jing Shao, Chunlan Zhang, Yashu Yang, Xingxing Zhu, Dongdong Que, Pingzhen Yang
Journal: Journal of the American College of Cardiology (2018)
Inflammation induced by influenza virus impairs human innate immune control of pneumococcus
Authors: Simon P. Jochems, Fernando Marcon, Beatriz F. Carniel, Mark Holloway, Elena Mitsi, Emma Smith, Jenna F. Gritzfeld, Carla Solórzano, Jesús Reiné, Sherin Pojar, Elissavet Nikolaou, Esther L. German, Angie Hyder-Wright, Helen Hill, Caz Hales, Wouter A. A. de Steenhuijsen Piters, Debby Bogaert, Hugh Adler, Seher Zaidi, Victoria Connor, Stephen B. Gordon, Jamie Rylance, Helder I. Nakaya, Daniela M. Ferreira
Journal: Nature Immunology (2018)
The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging
Authors: Benjamin M. Larimer, Emily Bloch, Sarah Nesti, Emily E. Austin, Eric Wehrenberg-Klee, Genevieve Boland, Umar Mahmood
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The lack of a timely and reliable measure of response to cancer immunotherapy has confounded understanding of mechanisms of resistance and subsequent therapeutic advancement. We hypothesized that PET imaging of granzyme B using a targeted peptide, GZP, could be utilized for early response assessment across many checkpoint inhibitor combinations, and that GZP uptake could be compared between therapeutic regimens and dosing schedules as an early biomarker of relative efficacy. Experimental Design: Two models, MC38 and CT26, were treated with a series of checkpoint inhibitors. GZP PET imaging was performed to assess tumoral GZP uptake, and tumor volume changes were subsequently monitored to determine response. The average GZP PET uptake and response of each treatment group were correlated to evaluate the utility of GZP PET for comparing therapeutic efficacy. Results: In both tumor models, GZP PET imaging was highly accurate for predicting response, with 93% sensitivity and 94% negative predictive value. Mean tumoral GZP signal intensity of treatment groups linearly correlated with percent response across all therapies and schedules. Moreover, GZP PET correctly predicted that sequential dose scheduling of PD-1 and CTLA-4 targeted therapies demonstrates comparative efficacy to concurrent administration. Conclusions: Granzyme B quantification is a highly sensitive and specific early measure of therapeutic efficacy for checkpoint inhibitor regimens. This work provides evidence that GZP PET imaging may be useful for rapid assessment of therapeutic efficacy in the context of clinical trials for both novel drugs as well as dosing regimens.
Functional Conservation of a Developmental Switch in Mammals since the Jurassic Age
Authors: Jayati Mookerjee-Basu, Xiang Hua, Lu Ge, Emmanuelle Nicolas, Qin Li, Philip Czyzewicz, Dai Zhongping, Suraj Peri, Juan I FuxmanBass, Albertha J M Walhout, Dietmar J Kappes
Journal: Molecular Biology and Evolution (2018)

ThPOK is a “master regulator” of T lymphocyte lineage choice, whose presence or absence is sufficient to dictate development to the CD4 or CD8 lineages, respectively. Induction of ThPOK is transcriptionally regulated, via a lineage-specific silencer element, SilThPOK. Here, we take advantage of the available genome sequence data as well as site-specific gene targeting technology, to evaluate the functional conservation of ThPOK regulation across mammalian evolution, and assess the importance of motif grammar (order and orientation of TF binding sites) on SilThPOK function in vivo. We make three important points: First, the SilThPOK is present in marsupial and placental mammals, but is not found in available genome assemblies of nonmammalian vertebrates, indicating that it arose after divergence of mammals from other vertebrates. Secondly, by replacing the murine SilThPOK in situ with its marsupial equivalent using a knockin approach, we demonstrate that the marsupial SilThPOK supports correct CD4 T lymphocyte lineage-specification in mice. To our knowledge, this is the first in vivo demonstration of functional equivalency for a silencer element between marsupial and placental mammals using a definitive knockin approach. Finally, we show that alteration of the position/orientation of a highly conserved region within the murine SilThPOK is sufficient to destroy silencer activity in vivo, demonstrating that motif grammar of this “solid” synteny block is critical for silencer function. Dependence of SilThPOK function on motif grammar conserved since the mid-Jurassic age, 165 Ma, suggests that the SilThPOK operates as a silenceosome, by analogy with the previously proposed enhanceosome model.
Randomized phase III study of gemcitabine, cisplatin plus S-1 (GCS) versus gemcitabine, cisplatin (GC) for advanced biliary tract cancer (KHBO1401-MITSUBA)
Authors: D. Sakai, M. Kanai, S. Kobayashi, H. Eguchi, H. Baba, S. Seo, A. Taketomi, T. Takayama, H. Yamaue, C. Ishioka, M. Sho, Y. Takeyama, J. Fujimoto, M. Toyoda, J. Shimizu, T. Goto, K. Yoshimura, E. Hatano, H. Nagano, T. Ioka
Journal: Annals of Oncology (2018)