tbuckley/cabot-search huggingface dataset:
Marked Impact of Different Cytokines on Phenotype and Cytotoxic Activity of CD19-Specific CAR T Cells
Authors: Jean-Marc Hoffmann, Lei Wang, Angela Hückelhoven, Anita Schmitt, Ulrike Gern, Leopold Sellner, Christian Kleist, Jessica Wenthe, Patrick Wuchter, Maria-Luisa Schubert, Hyeon Joo Yoo, Ming Ni, Susanne Hofmann, Peter Dreger, Anthony D. Ho, Angelica Loskog, Michael Schmitt
Journal: Blood (2016)
Pulmonary haemodynamics and mortality in chronic hypersensitivity pneumonitis
Authors: Rudolf K.F. Oliveira, Jaquelina S. Ota-Arakaki, Paula S. Gomes, Andrea Gimenez, Carolina M.S. Messina, Roberta P. Ramos, Eloara V.M. Ferreira, David M. Systrom, Carlos A.C. Pereira
Journal: European Respiratory Journal (2018)

Chronic hypersensitivity pneumonitis (CHP) is a common interstitial lung disease (ILD) frequently associated with lung fibrosis [1]. Among patients with CHP, the degree of pulmonary function impairment and the extent of fibrosis are known predictors of mortality [2, 3]. In other forms of ILD, such as idiopathic pulmonary fibrosis (IPF) and sarcoidosis, abnormal pulmonary haemodynamics measured during resting supine right heart catheterisation (RHC) are additionally associated with poor prognosis [4–7]. In CHP, however, the prognostic value of RHC is unknown. Indices of pulmonary vascular dysfunction are associated with mortality in chronic hypersensitivity pneumonitis <http://ow.ly/1nwG30jwTSm>
Tuberculosis, social determinants and co-morbidities (including HIV)
Authors: R. Duarte, K. Lönnroth, C. Carvalho, F. Lima, A.C.C. Carvalho, M. Muñoz-Torrico, R. Centis
Journal: Pulmonology (2017)

The risk of exposure, progression to active tuberculosis (TB) and then to cure is a process affected by several risk factors. Along with well known risk factors such as human immunodeficiency virus (HIV), use of immunosuppressive drugs and being of young age, emerging risk factors such socio-economic and behavioral aspects play a significant role in increasing the susceptibility to infection, and unsuccessful treatment outcomes. This paper summarizes the effects of these socio-economic determinants and co-morbidities (including HIV) on TB infection and disease.
<i>MYC</i> Drives a Subset of High-Risk Pediatric Neuroblastomas and Is Activated through Mechanisms Including Enhancer Hijacking and Focal Enhancer Amplification
Authors: Mark W. Zimmerman, Yu Liu, Shuning He, Adam D. Durbin, Brian J. Abraham, John Easton, Ying Shao, Beisi Xu, Shizhen Zhu, Xiaoling Zhang, Zhaodong Li, Nina Weichert-Leahey, Richard A. Young, Jinghui Zhang, A. Thomas Look
Journal: Cancer Discovery (2017)

The amplified MYCN gene serves as an oncogenic driver in approximately 20% of high-risk pediatric neuroblastomas. Here, we show that the family member MYC is a potent transforming gene in a separate subset of high-risk neuroblastoma cases (∼10%), based on (i) its upregulation by focal enhancer amplification or genomic rearrangements leading to enhancer hijacking, and (ii) its ability to transform neuroblastoma precursor cells in a transgenic animal model. The aberrant regulatory elements associated with oncogenic MYC activation include focally amplified distal enhancers and translocation of highly active enhancers from other genes to within topologically associating domains containing the MYC gene locus. The clinical outcome for patients with high levels of MYC expression is virtually identical to that of patients with amplification of the MYCN gene, a known high-risk feature of this disease. Together, these findings establish MYC as a bona fide oncogene in a clinically significant group of high-risk childhood neuroblastomas.Significance: Amplification of the MYCN oncogene is a recognized hallmark of high-risk pediatric neuroblastoma. Here, we demonstrate that MYC is also activated as a potent oncogene in a distinct subset of neuroblastoma cases through either focal amplification of distal enhancers or enhancer hijacking mediated by chromosomal translocation. Cancer Discov; 8(3); 320-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 253.
Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases in vitro and in vivo
Authors: Emiel De Jaeghere, Elly De Vlieghere, Jasper Van Hoorick, Sandra Van Vlierberghe, Glenn Wagemans, Leen Pieters, Elodie Melsens, Marleen Praet, Jo Van Dorpe, Matthieu N. Boone, Rouba Ghobeira, Nathalie De Geyter, Marc Bracke, Christian Vanhove, Sara Neyt, Geert Berx, Bruno G. De Geest, Peter Dubruel, Heidi Declercq, Wim Ceelen, Olivier De Wever
Journal: Biomaterials (2017)
Leptomeningeal gliomatosis: A single institution retrospective study of 31 patients.
Authors: Didier Autran, Emeline Tabouret, Maryline Barrie, Mona Matta, Colette Monserrat, Celine Boucard, Alexia Terciolo, Anderson Loundou, Philippe Metellus, Henry Dufour, Dominique Figarella-Branger, Olivier L. Chinot
Journal: Journal of Clinical Oncology (2014)

e13017 Background: Secondary leptomeningeal gliomatosis (LMG) is a rare and severe progression pattern of glioma. Prognostic factors and therapeutic management of this pattern remains unclear. Our objective was to evaluate characteristics and outcome of LMG patients (pts). Methods: We retrospectively reviewed pts diagnosed with secondary LMG referred to our institution between 2004 and 2013. Diagnosis was obtained by clinical, imaging and cerebrospinal fluid (CSF) data. Results: The identification and diagnosis of 31 pts with LMG was based on CSF cytology (n=12), on MRI data (n=16) with hyperproteinarrachia (>1.2 gr/l) (n=9) or without (n=7), or on meningism with hyperproteinarrachia (n=3). At LMG diagnosis (LMGD), median age was 45 years and Karnofsky Performance Status (KPS) was <70 in 71% of pts; histological grade was IV in 20 pts and II-III in 11 pts. Median interval from initial glioma diagnosis (IGD) to LMGD was 13.5 months (glioblastoma: 8.1; grades II-III: 28.9). As first line therapy for LMG, 22 pts received an oncological treatment: BCNU-temozolomide (TMZ), n=15; other chemotherapy, n=7; craniospinal radiotherapy: n=0; no further trt, n=9. From LMGD, median PFS and median OS were 1.8 months (95% confidence interval [CI]: 0.9–2.7) and 2.1 months (CI95%: 1.3–3) respectively. Clinical improvement was observed in 6/22 treated patients, of which 3 showed concomitant imaging improvement; 13/22 pts exhibit a rapid decline. Univariate analyses showed an improved OS with age < 45 years old (p < 0.001), prolonged interval from IGD to LMGD (p = 0.003) and KPS ≥ 70 (p = 0.012). Remained significant in the multivariate analysis: age (HR: 4.533) and interval since IGD (HR: 4.803). Among the 22 treated patients, median OS was significantly higher with BCNU-TMZ trt: 5.7 months (CI95%: 4.2-7.1) vs 2 months (CI95%: 1.1–2.9) for other trt (p=0.008). Initial proteinorrachia and its changes during LMG treatment were not correlated to response and did not influence outcome. Conclusions: We identify age and time interval from IGD to LMGD as potential prognostic factors for LMGD. BCNU-TMZ combination could be an interesting therapeutic option for these patients.
The BMJ charity appeal Christmas 2017: help Médecins Sans Frontières’ volunteer doctors help the Rohingya people
Authors: Jane Feinmann
Journal: BMJ (2017)

MSF has decades of experience in bringing medical aid to the neediest people worldwide, such as those fleeing violence in Myanmar, as <b>Jane Feinmann</b> writes. This is why <i>The BMJ</i> has chosen MSF for its charity appeal this year. Please give generously
Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy
Authors: Benjamin A Fisher, Colin C Everett, John Rout, John L O’Dwyer, Paul Emery, Costantino Pitzalis, Wan-Fai Ng, Andrew Carr, Colin T Pease, Elizabeth J Price, Nurhan Sutcliffe, Jimmy Makdissi, Anwar R Tappuni, Nagui S T Gendi, Frances C Hall, Sharon P Ruddock, Catherine Fernandez, Claire T Hulme, Kevin A Davies, Christopher John Edwards, Peter C Lanyon, Robert J Moots, Euthalia Roussou, Andrea Richards, Linda D Sharples, Michele Bombardieri, Simon J Bowman
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. Trial registration number 65360827, 2010-021430-64; Results.
Pleiotropic Roles for ZEB1 in Cancer
Authors: Julie Caramel, Maud Ligier, Alain Puisieux
Journal: Cancer Research (2017)

ZEB1 is a prime element of a network of transcription factors that controls epithelial-to-mesenchymal transition (EMT), a reversible embryonic transdifferentiation program that allows partial or complete transition from an epithelial to a mesenchymal state. Aberrant expression of ZEB1 has been reported in a variety of human cancers, where it is generally believed to foster migration, invasion, and metastasis. Over the past few years, in vitro and in vivo observations have highlighted unsuspected intrinsic oncogenic functions of ZEB1 that impact tumorigenesis from its earliest stages. Located downstream of regulatory processes that integrate microenvironmental signals and directly implicated in feedback loops controlled by miRNAs, ZEB1 appears to be a central switch that determines cell fate. Its expression fosters malignant transformation through the mitigation of critical oncosuppressive pathways and through the conferment of stemness properties. ZEB1 is also a key determinant of cell plasticity, endowing cells with the capacity to withstand an aberrant mitogenic activity, with a profound impact on the genetic history of tumorigenesis, and to adapt to the multiple constraints encountered over the course of tumor development. Cancer Res; 78(1); 30-35. ©2017 AACR.
3D Carbon Scaffolds for Neural Stem Cell Culture and Magnetic Resonance Imaging
Authors: Erwin Fuhrer, Anne Bäcker, Stephanie Kraft, Friederike J. Gruhl, Matthias Kirsch, Neil MacKinnon, Jan G. Korvink, Swati Sharma
Journal: Advanced Healthcare Materials (2017)

Abstract 3D glassy carbon structures with percolated macropores are obtained by pyrolysis of chemically synthesized cryogels featuring tunable porosity. These batch‐fabricated structures are used as scaffolds for culturing neural stem cells (NSCs) and are characterized by magnetic resonance imaging (MRI). With the aid of MRI, the successful cultivation of NSCs on a glassy carbon surface and the precise 3D locations of these cell clusters within the opaque scaffold are demonstrated. MRI also yields pore morphology and porosity analyses, pre‐ and post‐pyrolysis. This integrated approach yields a complete 3D dataset of the NSC network, which enables the visual inspection of the morphological details of individual cell clusters without disturbing them or destroying the scaffold. Reported experimental methodology is expected to have an impact on studies designed to understand the mechanism of neurodegenerative disease (ND) development, and can serve as a protocol for the culture of various other types of cells that display compatibility with glassy carbon surfaces.
Adherence in severe asthma: time to get it right
Authors: Vanessa M. McDonald, Janelle Yorke
Journal: European Respiratory Journal (2017)

How many times have you sat in an asthma consultation and asked a patient "how many doses of your inhaler have you forgotten to take in that last week?" There are times when you may understandably question the person's response, and other times when you will be convinced that they "take their puffers without fail" only to subsequently discover that you have been mistaken. Whilst clinicians want to understand the individual's level of treatment adherence, this approach is clearly flawed and we need to do better. Adherence in severe asthma is suboptimal as are the clinic measures to assess adherence <http://ow.ly/CSZH30gCsBQ>
Change in breast density as a response to adjuvant endocrine treatment: An American cohort.
Authors: Barbara A. Wexelman, Yasuaki Sagara, H E Min, Sughra Raza, Fatih Aydogan, Mehra Golshan
Journal: Journal of Clinical Oncology (2014)

e11523 Background: Anti-estrogen treatment is the cornerstone in adjuvant therapy of estrogen receptor (ER) positive breast cancer. Previous work has demonstrated that endocrine therapy (ET) reduces breast density on subsequent mammograms. Research from Korea and Sweden has shown that decreased mammographic density (MD) after ET is a positive prognostic marker for long-term survival. We seek to validate this finding in a North American cohort. Methods: We identified 102 patients treated at our institution with ER positive breast cancer from 2003-2006, with mammograms available in our system and an intact contralateral breast. MD was measured as percentage volume density using Volpara software (v. 1.2); MD reduction (MDR) was defined as Follow up MD - Baseline MD*100 / Baseline MD. Baseline MD was measured from a preoperative mammogram, and Follow up MD from mammograms taken 1-2 years after start of ET. Logistic regression analysis was performed with endpoint defined as locoregional or distant breast cancer recurrence. Results: There were 9 women (8.8%) with breast cancer recurrence (median follow-up =79 months), while 93/102 (91.2%) remained disease free. MD significantly decreased after ET with mean MDR of -14.2% (-63.2% to 138.7%, p<0.05). Young age (p<0.05) and premenopausal status (p<0.05) correlated significantly with greater MDR. Comparing women with post ET MDR <20% to those with ≥20%, there was no significant difference in recurrence rate (Log-rank test, p=0.86). Conclusions: MDR during short-term use of adjuvant ET led to a decrease in MDR but was not predictive of long-term outcome in this cohort with only 9 cases of recurrence. A larger review is necessary to determine whether decreased breast tissue density correlates with long-term prognosis. Patient demographics. Mean N % Age (yrs) </50 55.0 41 40.2 >50 61 59.8 Postmenopausal 76 74.5 Duration of ET (yrs) 4.91 ET regimen Tamoxifen 43 42.2 Tam to AI 34 33.3 AI 25 24.5 Tumor Size </2 cm 68 66.6 >2cm 15 14.7 DCIS 19 18.6 Lymph Node Status Positive 21 20.6 Negative 74 72.5 Not eval 7 6.9 Stage 0 19 18.6 I 56 54.9 II 20 19.6 III 7 6.9 Operation Breast Conserv 85 83.3 Mastectomy 17 16.6 Recurrence Total 9 8.8 Locoreg 5 4.9 Contralat 2 2.0 Distant Metastasis 2 2.0 Non-Breast Cancer Death 4 3.9
NHS data don’t confirm Labour’s claim of 100 000 vacant posts in England
Authors: Nigel Hawkes
Journal: BMJ (2017)

The NHS in England has more than 100 000 unfilled posts, claims a survey by the Labour Party. But the figures have been difficult to confirm, and the NHS trust with the highest number of vacancies lists a 10th the number of jobs on its website that the survey indicates.

Labour sent freedom of information requests to 82 trusts—just over a third of all hospital and community service trusts—asking for the number of vacancies on 31 March 2017, which totalled 35 993 unfilled full-time equivalent posts.

Extrapolated to the whole NHS in England, this implied a figure of more than 100 000, a 9% vacancy rate. A typical UK business has a vacancy rate of …
Contralateral prophylactic mastectomy decision-making in the population-based iCanCare study of early-stage breast cancer patients: Knowledge and physician influence.
Authors: Reshma Jagsi, Sarah T. Hawley, Kent A. Griffith, Nancy K. Janz, Allison W. Kurian, Kevin C. Ward, Ann S. Hamilton, Steven J. Katz, Monica Morrow
Journal: Journal of Clinical Oncology (2015)

1011 Background: Contralateral prophylactic mastectomy (CPM) use is increasing in women who are not at increased risk of contralateral cancer development and will experience no survival benefit from the more morbid procedure. Little is known about treatment decision-making or provider interactions. Methods: We surveyed patients newly diagnosed with breast cancer in 2013-14, identified through the population-based SEER registries of Los Angeles and Georgia, about 6 months after diagnosis, to determine receipt of diagnostic tests and factors related to the decision about surgery (including knowledge and perceived physician recommendation). Survey return is ongoing with an expected final response rate > 70%; current response rate 68%. Results: Nearly half of 1949 respondents with unilateral cancer considered CPM (20% very strongly, 6% strongly, 9% moderately, 10% weakly). Only 37% of those who considered CPM knew that it does not improve survival for all women with breast cancer (23% believed it does, 49% didn’t know). Among women receiving CPM, 36% believed it generally improves survival. Ultimately, 1138 (58%) received BCS and 811 (42%) mastectomy (387, or 20% overall, with CPM). On multivariable analysis, pts who received CPM were younger, more likely to be white, and more likely to have a family history, private rather than Medicaid insurance, and received MRI. Even among pts without a deleterious genetic mutation or family history in multiple relatives (1,849), 354 (19%) received CPM; CPM was uncommon among pts who reported that their surgeons recommended against it (3.7% [13/649]) but much higher (22.7% [197/869]) among those who reported no surgeon recommendation regarding CPM and (58.7% [138/235]) among those who perceived their surgeons to have recommended it. Conclusions: Many patients consider CPM, but knowledge is low and discussions with surgeons appear incomplete. Use of CPM is substantial among patients without clinical indications but is low when patients report their surgeon recommended against it. More effective discussion and navigation about CPM is needed to reduce potential overtreatment. Funding: P01-CA-163233.
Erratum: The role of PAX5 and C/EBP α/β in atypical non-Langerhans cell histiocytic tumor post acute lymphoblastic leukemia
Authors: F Pagni, G Fazio, S Zannella, M Spinelli, C De Angelis, C Cusi, F Crosti, L Corral, C Bugarin, A Biondi, G Cazzaniga, G Isimbaldi, G Cattoretti
Journal: Leukemia (2014)
Using Clinical Registries to Enhance Implementation Research
Authors: Scott E. Regenbogen, Justin B. Dimick
Journal: JAMA Surgery (2017)

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Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection
Authors: Antonio F. Pardiñas, Peter Holmans, Andrew J. Pocklington, Valentina Escott-Price, Stephan Ripke, Noa Carrera, Sophie E. Legge, Sophie Bishop, Darren Cameron, Marian L. Hamshere, Jun Han, Leon Hubbard, Amy Lynham, Kiran Mantripragada, Elliott Rees, James H. MacCabe, Steven A. McCarroll, Bernhard T. Baune, Gerome Breen, Enda M. Byrne, Udo Dannlowski, Thalia C. Eley, Caroline Hayward, Nicholas G. Martin, Andrew M. McIntosh, Robert Plomin, David J. Porteous, Naomi R. Wray, Armando Caballero, Daniel H. Geschwind, Laura M. Huckins, Douglas M. Ruderfer, Enrique Santiago, Pamela Sklar, Eli A. Stahl, Hyejung Won, Esben Agerbo, Thomas D. Als, Ole A. Andreassen, Marie Bækvad-Hansen, Preben Bo Mortensen, Carsten Bøcker Pedersen, Anders D. Børglum, Jonas Bybjerg-Grauholm, Srdjan Djurovic, Naser Durmishi, Marianne Giørtz Pedersen, Vera Golimbet, Jakob Grove, David M. Hougaard, Manuel Mattheisen, Espen Molden, Ole Mors, Merete Nordentoft, Milica Pejovic-Milovancevic, Engilbert Sigurdsson, Teimuraz Silagadze, Christine Søholm Hansen, Kari Stefansson, Hreinn Stefansson, Stacy Steinberg, Sarah Tosato, Thomas Werge, David A. Collier, Dan Rujescu, George Kirov, Michael J. Owen, Michael C. O’Donovan, James T. R. Walters
Journal: Nature Genetics (2018)