tbuckley/cabot-search huggingface dataset:
Pediatric Cancer Predisposition and Surveillance: An Overview, and a Tribute to Alfred G. Knudson Jr
Authors: Garrett M. Brodeur, Kim E. Nichols, Sharon E. Plon, Joshua D. Schiffman, David Malkin
Journal: Clinical Cancer Research (2017)

Abstract The prevalence of childhood cancer attributable to genetic predisposition was generally considered very low. However, recent reports suggest that at least 10% of pediatric cancer patients harbor a germline mutation in a cancer predisposition gene. Although some of these children will have a family history suggestive of a cancer predisposition syndrome, many others will not. Evidence from recent pediatric studies suggests that surveillance and early detection of cancer in individuals carrying a germline cancer predisposing mutation may result in improved outcomes. However, there is a lack of consistency in the design of cancer surveillance regimens across centers both nationally and internationally. To standardize approaches, the Pediatric Cancer Working Group of the American Association for Cancer Research (AACR) convened a workshop, during which consensus screening recommendations for children with the most common cancer predisposition syndromes were developed. In general, we considered a 5% or greater chance of developing a childhood cancer to be a reasonable threshold to recommend screening. Conditions for which the cancer risk was between 1% to 5% were addressed individually. In a series of manuscripts accompanying this article, we provide recommendations for surveillance, focusing on when to initiate and/or discontinue specific screening measures, which modalities to use, and the frequency of screening. Points of controversy are also reviewed. We present the outcome of our deliberations on consensus screening recommendations for specific disorders in 18 position articles as Open Access publications, which are freely available on an AACR-managed website. Clin Cancer Res; 23(11); e1–e5. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.
Incidence, presentation and outcome of toxoplasmosis in HIV infected in the combination antiretroviral therapy era
Authors: Raquel Martin-Iguacel, Magnus Glindvad Ahlström, Madeleine Touma, Frederik Neess Engsig, Nina Breinholt Stærke, Mette Stærkind, Niels Obel, Line D. Rasmussen
Journal: Journal of Infection (2017)
The Authors' reply
Authors: D. E. Stange, B. Radlwimmer
Journal: Gut (2010)

We would like to thank Mr Adrian Jubb and his colleagues for sharing their interesting findings.1 In our opinion their data provide additional support for our study2 but fall short of sufficiently addressing the question of the correlation between 11p15.5 DNA copy number gain and ASCL2 expression in liver metastases of colorectal cancer.

Consistent with our findings, Jubb et al did not detect copy number aberrations on chromosome band 11p15.5 in two additional sets of primary colorectal cancers (pCRC). Nevertheless, over-expression of ASCL2 RNA was …
Human thymoproteasome variations influence CD8 T cell selection
Authors: Takeshi Nitta, Yuta Kochi, Ryunosuke Muro, Yoshihiko Tomofuji, Tadashi Okamura, Shigeo Murata, Harumi Suzuki, Takayuki Sumida, Kazuhiko Yamamoto, Hiroshi Takayanagi
Journal: Science Immunology (2017)

The proteasome is a multi-subunit protease complex essential for housekeeping protein degradation and the production of the major histocompatibility complex (MHC) class I-bound antigen peptides that are essential for recognition by CD8 T cells. MHC variations dramatically contribute to T cell selection and autoimmunity, but genetic variations of peptide processing machinery including proteasome genes have been poorly explored in this context. In the computational analysis of human proteasome gene variation, we documented that PSMB11 was highly enriched for nucleotide changes that interfere with protein function. This gene encodes β5t, a thymus-specific catalytic subunit that regulates positive selection of CD8 T cells by producing a distinct set of MHC class I-bound peptides. The introduction of PSMB11 variations into the mouse genome by genome-editing revealed that these variations impaired the development of CD8 T cells in vivo. One of the PSMB11 polymorphisms altered the CD8 T cell repertoire in mice and was associated with a higher risk of an autoimmune disease in humans. Our findings suggest that, in addition to the MHC haplotype, proteasome variations influence T cell repertoire selection and may contribute to the difference in individual susceptibility to autoimmunity.
HAMSTRING MUSCLE INJURY IS THE FIRST INJURY DIAGNOSIS DURING MAJOR ATHLETICS CHAMPIONSHIPS
Authors: Pascal Edouard, Pedro Branco, Juan-Manue Alonso
Journal: British Journal of Sports Medicine (2017)

Background During top-level international athletics championships, thigh muscle tear (hamstring muscle tear in particular) was the most commonly reported injury diagnosis. However, there has been no detailed characterisation of hamstring muscle injuries at this top level of athletics, which represent the main challenge for athletes and their stakeholders. Objective To analyse the incidence and characteristics of hamstring muscle injuries (hamstring injuries) occurring during top-level international athletics championships. Design Prospective study. Setting 9 international athletics championships from 2007 to 2015; Elite athletics level. Participants A total of 8212 registered athletes. Main Outcome Measurements Prevalence and incidences of hamstring injuries in male and female athletes. Results Hamstring injury frequencies were significantly higher in male (19.3%) than female (13.5%) athletes (Chi2=6.1; p=0.01). Hamstring injuries represented 39.8% of all muscle injuries and 74.6% of all thigh muscle injuries, without any differences in the distribution between male and female athletes. The rate of hamstring injuries per 1000 registered athletes was significantly higher in male (22.4±3.4) than in female (11.5±2.6) athletes (relative risk (RR)=1.94; 95% CI: 1.42–2.66, moderate effect size). Overuse with sudden onset was the main cause of hamstring injuries, followed by non-contact trauma. Hamstring injury incidences were higher in combined events, sprints, and hurdles than in other events for male athletes, and in combined events, sprints and hurdles than in other events for female athletes. Conclusions During 9 top-level international Athletics championships, hamstring injury was the most common injury diagnosis (19.3% in male and 13.5% female athletes), with a two fold higher risk in males than females. Athletes in explosive-power events and male athletes seem to be more at risk of hamstring muscle injuries. Injury prevention strategies should be sex-specific including screening of athletes at risk, particular attention to athletes at risk and to small signs, and adapted physical and strengthening conditioning.
In-Depth Molecular Profiling of Multiple Myeloma in African Americans
Authors: Zarko Manojlovic, Austin Christofferson, Christophe Legendre, Gill Spreyer, Seungchan Kim, Winnie Liang, George Mulligan, Pamela G. Kidd, Scott Jewell, Mary Derome, Jen Troups, Daniel Auclair, Sagar Lonial, David Craig, Jonathan J Keats, John David Carpten
Journal: Blood (2015)
Abstract 14396: Characterizing Pulse Deficits in Atrial Fibrillation Using Simple ECG Features
Authors: Vinayak Venkataraman, Albert Y Sun, Rachel Yang, Jason I Koontz, Kristen B Campbell, Zachary S Finn, Robert Schumann, Steve Guerrant, Craig Henriquez, James P Daubert
Journal: Circulation (2016)

Introduction: Atrial fibrillation can cause pulse deficits, or absence of a pulse wave following ventricular depolarization. We sought to characterize pulse deficits based on ECG features and corre...
PTU-092 Crohn's disease associated NOD2 variants show differential activation of NF-κb in response to auto-signalling and muramyl dipeptide
Authors: J Van Limbergen, F Soares, R K Russell, S Girardin, A Griffiths, D Philpott
Journal: Gut (2012)

<h3>Introduction</h3> Single nucleotide polymorphisms (SNPs) located of the NOD2/CARD15 gene (nucleotide-binding oligomerization domain containing 2/caspase recruitment domain family, member 15) are associated with increased susceptibility to Crohn9s disease (CD). These SNPs are thought to disrupt the sensing of bacterial muramyl dipeptide (MDP) at the C-terminus of the NOD2 protein. The precise contribution of each of these SNPs (SNP5, 8, 12 and 13) to NF-κB activation by means of NOD2-auto-signalling and stimulation with MDP has not been investigated at low levels of NOD2 expression. Data regarding the linkage disequilibrium (LD) between these CD-associated SNPs are scarce. <h3>Methods</h3> NOD2 variant constructs (rs2066842 (SNP5), rs2066844 (SNP8), rs2066845 (SNP12) and rs2066847 (SNP13), SNP5+8, SNP5+12 and SNP5+13) were created by site-directed mutagenesis of a pCMV plasmid containing wild-type N-terminal FLAG-NOD2. NF-κB luciferase assays were performed on HEK293 cells following transient transfection (20 h) with wildtype (WT) and NOD2 variant constructs, titrating NOD2 from 1 to 100 ng/well. The NF-κB luciferase response of NOD2 (1 ng)-transfected HEK293 cells to MDP (10 μg/well) was measured. Two-way ANOVA and unpaired t-tests were used. By means of Haploview-analysis of sequencing data of the exons and exon-intron boundaries in 24 paediatric Caucasian Crohn9s disease patients, we assessed the LD between SNP5 and SNP8, 12 and 13. <h3>Results</h3> Two-way ANOVA demonstrated an effect of NOD2 genotype and concentration on auto-signalling at low levels of expression (p&lt;0.0001). This was due to the significant difference of auto-activation between WT and SNP5, SNP8 and SNP12 (p&lt;0.001). At low levels of NOD2 expression (1–2 ng), the presence of SNP5 modified the auto-activating potential of SNP12 (p&lt;0.01). Based on these titration experiments, a low NOD2 transfection of 1 ng/well was chosen for the MDP-stimulation experiment. MDP stimulation led to a significant increase of NF-κB luciferase activity in WT and all NOD2 variant constructs, except SNP13 and SNP5+13 (p&lt;0.0001). Haplotype analysis of 11 NOD2 SNPs, identified through direct sequencing in 24 children with CD, showed that LD between SNP5 and the other CD-associated variants is low (r<sup>2</sup>&lt;0.1), in spite of close physical proximity (D9 1.0). <h3>Conclusion</h3> Our combined genetic and functional analyses demonstrate that the association of SNP5 with Crohn9s disease is unlikely due to LD with other SNPs. At low levels of NOD2 expression, NOD2 variant constructs differ from WT in their auto-signalling and MDP-stimulated activation of NF-κB. <h3>Competing interests</h3> None declared.
Direct-acting antiviral treatment against hepatitis C virus infection in HIV-Infected patients – “En route for eradication”?
Authors: Pierre Pradat, Pascal Pugliese, Isabelle Poizot-Martin, Marc-Antoine Valantin, Lise Cuzin, Jacques Reynes, Eric Billaud, Thomas Huleux, Firouze Bani-Sadr, David Rey, Anne Frésard, Christine Jacomet, Claudine Duvivier, Antoine Cheret, Laurent Hustache-Mathieu, Bruno Hoen, André Cabié, Laurent Cotte, L. Cotte, C. Chidiac, T. Ferry, F. Ader, F. Biron, A. Boibieux, P. Miailhes, T. Perpoint, I. Schlienger, J. Lippmann, E. Braun, J. Koffi, C. Longuet, V. Guéripel, C. Augustin-Normand, C. Brochier, S. Degroodt, P. Pugliese, C. Ceppi, E. Cua, J. Cottalorda, J. Courjon, P. Dellamonica, E. Demonchy, A. De Monte, J. Durant, C. Etienne, S. Ferrando, J.G. Fuzibet, R. Garraffo, A. Joulie, K. Risso, V. Mondain, A. Naqvi, N. Oran, I. Perbost, S. Pillet, B. Prouvost-Keller, S. Wehrlen-Pugliese, E. Rosenthal, S. Sausse, V. Rio, P.M. Roger, S. Brégigeon, O. Faucher, V. Obry-Roguet, M. Orticoni, M.J. Soavi, P. Geneau de Lamarlière, H. Laroche, E. Ressiot, M. Carta, M.J. Ducassou, I. Jacquet, S. Gallie, A. Galinier, A.S. Ritleng, A. Ivanova, C. Blanco-Betancourt, C. Lions, C. Debreux, V. Obry-Roguet, I. Poizot-Martin, R. Agher, C. Katlama, M.A. Valantin, C. Duvivier, O. Lortholary, F. Lanternier, C. Charlier, C. Rouzaud, C. Aguilar, B. Henry, D. Lebeaux, G. Cessot, A. Gergely, P.H. Consigny, F. Touam, C. Louisin, M. Alvarez, N. Biezunski, L. Cuzin, A. Debard, P. Delobel, C. Delpierre, C. Fourcade, B. Marchou, G. Martin-Blondel, M. Porte, M. Mularczyk, D. Garipuy, K. Saune, I. Lepain, M. Marcel, E. Puntis, N. Atoui, M.L. Casanova, V. Faucherre, J.M. Jacquet, V. Le Moing, A. Makinson, C. Merle De Boever, A. Montoya-Ferrer, C. Psomas, J. Reynes, F. Raffi, C. Allavena, E. Billaud, C. Biron, B. Bonnet, S. Bouchez, D. Boutoille, C. Brunet, T. Jovelin, N. Hall, C. Bernaud, P. Morineau, V. Reliquet, O. Aubry, P. Point, M. Besnier, L. Larmet, H. Hüe, S. Pineau, E. André-Garnier, A. Rodallec, Ph. Choisy, S. Vandame, Th. Huleux, F. Ajana, I. Alcaraz, V. Baclet, T.H. Huleux, H. Melliez, N. Viget, M. Valette, E. Aissi, Ch. Allienne, A. Meybeck, B. Riff, F. Bani-Sadr, C. Rouger, J.L. Berger, Y. N'Guyen, D. Lambert, I. Kmiec, M. Hentzien, D. Lebrun, C. Migault, D. Rey, M.L. Batard, C. Bernard-Henry, C. Cheneau, E. de Mautort, P. Fischer, M. Partisani, M. Priester, F. Lucht, A. Frésard, E. Botelho-Nevers, A. Gagneux-Brunon, C. Cazorla, C. Guglielminotti, F. Daoud, M.F. Lutz, C. Jacomet, H. Laurichesse, O. Lesens, M. Vidal, N. Mrozek, V. Corbin, C. Aumeran, O. Baud, S. Casanova, D. Coban, L. Hustache-Mathieu, M.C. Thiebaut-Drobacheff, A. Foltzer, V. Gendrin, F. Bozon, C. Chirouze, S. Abel, A. Cabié, R. Césaire, G. Dos Santos, L. Fagour, F. Najioullah, M. Ouka, S. Pierre-François, M. Pircher, B. Rozé, B. Hoen, R. Ouissa, I. Lamaury
Journal: Journal of Infection (2017)
NK cell heparanase controls tumor invasion and immune surveillance
Authors: Eva M. Putz, Alyce J. Mayfosh, Kevin Kos, Deborah S. Barkauskas, Kyohei Nakamura, Liam Town, Katharine J. Goodall, Dean Y. Yee, Ivan K.H. Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D. Hulett, Mark J. Smyth
Journal: Journal of Clinical Investigation (2017)

NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Hpsefl/fl NKp46-iCre mice were also more susceptible to tumor growth than were their littermate controls when challenged with the established mouse lymphoma cell line RMA-S-RAE-1β, which overexpresses the NK cell group 2D (NKG2D) ligand RAE-1β, or when inoculated with metastatic melanoma, prostate carcinoma, or mammary carcinoma cell lines. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase. Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. Our data suggest that heparanase plays a critical role in NK cell invasion into tumors and thereby tumor progression and metastases. This should be considered when systemically treating cancer patients with heparanase inhibitors, since the potential adverse effect on NK cell infiltration might limit the antitumor activity of the inhibitors.
Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines
Authors: Vimalkumar Balasubramanian, Zehua Liu, Jouni Hirvonen, Hélder A. Santos
Journal: Advanced Healthcare Materials (2017)

Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.
The future is in our hands
Authors: Kamran Abbasi
Journal: BMJ (2017)

The future demands attention this week. With a UK general election imminent we explore what motivates doctors to stand for parliament (doi:10.1136/bmj.j2601). Thirty two doctors are seeking election across the political spectrum. They are hospital consultants, general practitioners, and doctors in training. A recurring theme is how working as a doctor is good preparation for a career in politics.

“When the NHS is on its knees someone needs to stand up—and that is what I am doing,” explains John Dean, a consultant cardiologist standing for the …
Adding abiraterone to standard prostate treatment improves survival by 40%, studies find
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

The hormone blocking drug abiraterone extended life in men with prostate cancer when used first line at the start of standard treatment, two studies have found.

Abiraterone is usually used in men whose prostate cancer has spread and has stopped responding to standard hormone therapy. But the two studies, published in the New England Journal of Medicine ,12 suggest that it could benefit all men at the start of treatment, whether they have metastatic prostate cancer or prostate cancer that has not spread.

In the first study,1 part of the Systemic Therapy in …
French comment on article Double-guidewire technique in difficult biliary cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis1 La technique du double fil guide en cas de canulation difficile dans la prévention de la pancréatite aiguë post CPRE: une méta-analyse
Journal: Endoscopy (2017)

La pancréatite aiguë (PA) est la complication la plus sévère de la cholangiopancréatographie rétrograde (CPRE), survenant dans 5 – 10 % des cas, mais jusqu’à 25 % pour les patients à haut risque. En cas de canulation difficile, lorsque les techniques standard (assitées par un guide ou par injection) échouent, différentes procédures avancées peuvent être utilisées comme une précoupe ou la technique du double fil guide (TDFG). La TDFG consiste à insérer un premier guide dans le canal pancréatique, puis à cathétériser en parallèle de celui-ci avec un second guide. Le rationnel de cette technique serait de stabiliser la papille, de réaxer la voie biliaire et d’obturer le canal pancréatique. Toutefois, le risque de PA de cette technique est mal évalué dans la littérature. Le but de cette méta-analyse est d’évaluer l’efficacité et la morbidité de la TDFG.
What Can Be and What Cannot Be Accomplished With PET
Authors: Abass Alavi, Thomas J. Werner, Poul Flemming Høilund-Carlsen
Journal: Clinical Nuclear Medicine (2017)

Alavi, Abass MD (Hon), PhD (Hon), DSc (Hon); Werner, Thomas J. MSc; Høilund-Carlsen, Poul Flemming MD, DMSci Author Information
Feasibility, efficacy, and cosmetic effect of three-dimensional conformal external beam partial breast irradiation for the selected early-stage breast cancer patients after breast-conserving surgery in China.
Authors: Min Xu, Jianbin Li
Journal: Journal of Clinical Oncology (2012)

e11520 Background: To explore the feasibility, efficacy and cosmetic effect of three-dimensional conformal external beam partial breast irradiation after breast-conserving surgery for the selected Chinese early stage breast cancer patients Methods: Forty four early stage breast cancer patients undertaken EB-PBI after breast-conserving surgery. Twenty patients undertaken CT simulation scan in the state of moderate deep inspiration breathing hold (mDIBH), and twenty-four patients during free breathing (FB). The surgical cavity marked by silver clips was delineated and defined as gross tumor volume (GTV), and planning target volume (PTV) was defined as the area encompassed GTV with extended margin of 15 mm for the patients treated in the state of mDIBH or 20 mm for the patients treated in the state of FB. EB-PBI was planned and carried out by three-dimensional conformal radiotherapy (3DCRT) , the total prescribed dosage was 34 Gy delivered in 3.4 Gy per fractions in thirty nine patients and 38.5Gy delivered in 3.85 Gy per fractions in five patients, twice per day at intervals of at least six hours, in five consecutive days Results: Grade 1 of acute radiation-induced dermatitis was observed in 38.6% (17/44) of all the patients, no equal or more than grade 2 of radiation-induced dermatitis was observed, and no any grade of acute radiation-induced pneumonitis was observed. Cosmesis scored basing on Harris critieria was good or excellent in all cases at the time of six months after radiotherapy and in 94.9% cases at the time of two years after radiotherapy. The 2-, 3- and 5-year local control rates were 100% (39/39), 98.8% (30/31) and 93.8% (15/16), respectively. The 2-, 3-, and 5-year survival rates were all 100% and no metastases occurred Conclusions: EB-PBI delivered by 3DCRT is feasible for the selected Chinese early stage breast cancer patients after breast-conserving surgery, satisfactory cosmetic effect, local control rate and long-term survival rate are obtained, meanwhile, acute radiation response rate is lower.