tbuckley/cabot-search huggingface dataset:
Long noncoding RNA BLACAT2 promotes bladder cancer–associated lymphangiogenesis and lymphatic metastasis
Authors: Wang He, Guangzheng Zhong, Ning Jiang, Bo Wang, Xinxiang Fan, Changhao Chen, Xu Chen, Jian Huang, Tianxin Lin
Journal: Journal of Clinical Investigation (2018)

The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 may represent a target for clinical intervention in LN-metastatic bladder cancer.
Abstract 17560: Statins Modify the Risk Relationship Between Systolic Blood Pressure Goal and Total Mortality in Chronic Kidney Disease: SPRINT
Authors: Manuel Rivera, Leonardo Tamariz, Maritza Suarez, Gabriel Contreras
Journal: Circulation (2017)

Background:  Ideal management of CKD includes management of hypertension and statin therapy. It however remains unclear if there is a positive interaction between more aggressive blood pressure control and the use of statins.   Methods:  We conducted a post-hoc analysis focusing on patients with CKD from the SPRINT study. These patients had been originally randomized to either an intensive SBP goal  2 . Our goal was to evaluate the added value of statins on the relationship between SBP goal and total mortality using Cox models. Subgroup models were adjusted for age, gender, race, SBP and eGFR at baseline.   Results:  2646 patients with CKD were included in our analysis; of these, 1,354 (51%) were not on statins and 1,273 (49%) patients were on a statins at baseline. CKD patients on statins were predominantly non-Hispanic white (71.6%) men (64.1%), former smokers (51.3%); were often on aspirin (68.8%) and at least one other antihypertensive drug (97%). In a Cox model, the effect of SBP goal on total mortality was modified by the use of statins at baseline (interaction p=0.014). For the CKD subgroup on statins, the total mortality risk was significantly lower in the intensive SBP goal group compared to the standard SBP goal group (1.16 vs. 2.50 deaths/100 patients-years; adjusted hazard ratio (aHR) 0.46 [95% confidence interval [CI] 0.28-0.73]). For the CKD subgroup not on statins, the mortality risk was similar between the two SBP goal groups (2.01 vs. 1.95 deaths/100 patients-years; aHR 1.06 [95% CI 0.69-1.65]) (fig. 1).   Conclusion:  Statin therapy modify the risk relationship between SBP goal and total mortality in the SPRINT trial. Patients randomized to intensive SBP goal using statins at baseline had the lowest mortality rate compared to other groups. Efforts should be directed towards the implementation of statin therapy altogether with optimal blood pressure control in individuals with CKD.
Risk-Adapted Therapy in Adults with Burkitt Lymphoma: Results of NCI 9177, a Multicenter Prospective Phase II Study of DA-EPOCH-R
Authors: Mark Roschewski, Kieron Dunleavy, Jeremy S. Abramson, Brian K Link, Samir Parekh, Deepa Jagadeesh, Philip Bierman, Ronald T. Mitsuyasu, Ramakrishna Battini, Peter R. Watson, David Peace, Wahid Hanna, Bayard L. Powell, Timothy E. O'Brien, David King, Christopher Melani, Andrea Lucas, Seth M. Steinberg, Brad S Kahl, Jonathan W. Friedberg, Richard F. Little, Nancy L. Bartlett, Michelle A. Fanale, Ariela Noy, Wyndham H. Wilson
Journal: Blood (2017)
Global coverage of health information systems for kidney disease: availability, challenges, and opportunities for development
Authors: Emily J. See, Mona Alrukhaimi, Gloria E. Ashuntantang, Aminu K. Bello, Ezequiel Bellorin-Font, Mohammed Benghanem Gharbi, Branko Braam, John Feehally, David C. Harris, Vivekanand Jha, Kailash Jindal, Kamyar Kalantar-Zadeh, Rumeyza Kazancioglu, Adeera Levin, Meaghan Lunney, Ikechi G. Okpechi, Timothy Olusegun Olanrewaju, Mohamed A. Osman, Jeffrey Perl, Bilal Qarni, Harun Ur Rashid, Ahmed Rateb, Eric Rondeau, Arian Samimi, Majid L.N. Sikosana, Laura Sola, Irma Tchokhonelidze, Natasha Wiebe, Chih-Wei Yang, Feng Ye, Alexander Zemchenkov, Ming-hui Zhao, David W. Johnson
Journal: Kidney International Supplements (2018)
Anti-NT5C1A autoantibodies are associated with more severe disease in patients with juvenile myositis
Authors: Richard M Yeker, Iago Pinal-Fernandez, Takayuki Kishi, Katherine Pak, Ira N Targoff, Frederick W Miller, Lisa G Rider, Andrew L Mammen
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Autoantibodies recognising cytosolic 5′-nucleotidase 1A (NT5C1A) are found in adult patients with myositis and other autoimmune diseases. They are especially prevalent in adults with inclusion body myositis (IBM), in which they are associated with more severe weakness and higher mortality. This study was undertaken to define the prevalence and clinical features associated with anti-NT5C1A autoantibodies in juvenile myositis. Methods We screened sera from 380 patients with juvenile myositis, 30 patients with juvenile idiopathic arthritis (JIA) and 92 healthy control children for anti-NT5C1A autoantibodies. Clinical characteristics were compared between patients with myositis with and without anti-NT5C1A autoantibodies. Results Anti-NT5C1A autoantibodies were present in 102 of 380 (27%) patients with juvenile myositis and in 11 of 92 (12%) healthy control children (P=0.002) and 27% of children with JIA (P=0.05 vs controls). Sera of 83 of 307 (27%) patients with juvenile dermatomyositis and 16 of 46 (35%) patients with juvenile overlap myositis were anti-NT5C1A autoantibody-positive (P&lt;0.01 vs healthy controls for each), but sera of only 3 of 27 (11%) patients with juvenile polymyositis were anti-NT5C1A-positive. Patients with juvenile myositis with and without anti-NT5C1A autoantibodies had similar clinical phenotypes. However, patients with anti-NT5C1A autoantibody-positive myositis had greater pulmonary symptoms at diagnosis (P=0.005), more frequent hospitalisations (P=0.01) and required a larger number of medications (P&lt;0.001). Conclusion Anti-NT5C1A autoantibodies are present in more than one-quarter of children with juvenile myositis and JIA compared with only 12% of healthy children, suggesting they are myositis-associated in children. As in adults with IBM, patients with juvenile myositis with anti-NT5C1A autoantibodies have more severe disease.
Loss of KRAS control as consequence of downregulated microRNA-622 in hepatocellular carcinoma and its potential therapeutic implication
Authors: Heike Bantel, Ali Canbay
Journal: Gut (2018)

Hepatocellular carcinoma (HCC) represents a serious and urgent global health problem because of its increasing incidence and the limited therapeutic options.1 2 The standard treatment for patients with advanced HCC is the multikinase inhibitor sorafenib, which shows only modest survival improvement of approximately 2–3 months and remains associated with disease progression in a large number of patients.3 4 Therefore, to improve the survival of patients with advanced HCC, it is fundamental to understand the mechanisms of sorafenib resistance.

The antitumour efficacy of sorafenib is mainly based on the inhibition of the proliferative RAF/mitogen-activated protein kinase (MAPK) pathway, which is regulated by upstream RAS proteins.5 6 The majority of human HCCs shows an activation of this pathway, which is associated with shorter survival.6–9 In contrast to other human tumours, RAS activation in HCC occurs in the absence of RAS mutation, which is rare in this tumour entity.6 10 The pathomechanisms of enhanced activation of RAS and in particular of KRAS, the most important RAS isoform for carcinogenesis, in HCC as well as its implication for sorafenib resistance remain largely unclear.

There is increasing evidence that microRNAs …
Persistence of schistosomal transmission linked to the Cavu river in southern Corsica since 2013
Authors: Lauriane Ramalli, Stephen Mulero, Harold Noël, Jean-Dominique Chiappini, Josselin Vincent, Hélène Barré-Cardi, Philippe Malfait, Guillaume Normand, Florian Busato, Vincent Gendrin, Jean-François Allienne, Judith Fillaux, Jérôme Boissier, Antoine Berry
Journal: Eurosurveillance (2018)

Seven cases of urogenital schistosomiasis occurred in Corsica in 2015 and 2016. The episodes were related to exposure to the same river and involved the same parasite strain as an outbreak with 106 cases in summer 2013. The connection calls for further investigations on the presence of an animal reservoir and the survival of infested snails during winter. However, recontamination of the river from previously infected bathers remains the most likely hypothesis.
The inflammatory cell landscape in the lungs of patients with idiopathic pulmonary arterial hypertension
Authors: Leigh M. Marsh, Katharina Jandl, Gabriele Grünig, Vasile Foris, Mina Bashir, Bahil Ghanim, Walter Klepetko, Horst Olschewski, Andrea Olschewski, Grazyna Kwapiszewska
Journal: European Respiratory Journal (2018)

Increasing evidence points towards an inflammatory component underlying pulmonary hypertension. However, the conclusive characterisation of multiple inflammatory cell populations in the lung is challenging due to the complexity of marker specificity and tissue inaccessibility. We used an unbiased computational flow cytometry approach to delineate the inflammatory landscape of idiopathic pulmonary arterial hypertension (IPAH) and healthy donor lungs. Donor and IPAH samples were discriminated clearly using principal component analysis to reduce the multidimensional data obtained from single-cell flow cytometry analysis. In IPAH lungs, the predominant CD45 + cell type switched from neutrophils to CD3 + T-cells, with increases in CD4 + , CD8 + and γδT-cell subsets. Additionally, diversely activated classical myeloid-derived dendritic cells (CD14 − HLA-DR + CD11c + CD1a +/− ) and nonclassical plasmacytoid dendritic cells (pDCs; CD14 − CD11c − CD123 + HLA-DR + ), together with mast cells and basophils, were more abundant in IPAH samples. We describe, for the first time, the presence and regulation of two cell types in IPAH, γδT-cells and pDCs, which link innate and adaptive immunity. With our high-throughput flow cytometry with multidimensional dataset analysis, we have revealed the interactive interplay between multiple inflammatory cells is a crucial part of their integrative network. The identification of γδT-cells and pDCs in this disease potentially provides a missing link between IPAH, autoimmunity and inflammation.
Personalized Chemosensitivity Assays for Mesothelioma: Are They Worth the Effort?
Authors: Thomas John, Puey Ling Chia
Journal: Clinical Cancer Research (2018)

Cell lines formed from an individual's tumor can be used to predict response to specific therapies and determine genomic predictors. For mesothelioma, where chemotherapy remains the backbone of current therapeutic paradigms, such assays could be used to treat patients with the most effective agents specific to their "chemical profile." Clin Cancer Res; 24(7); 1513-5. ©2018 AACRSee related article by Schunselaar et al., p. 1761.
Hamstring injuries are increasing in men’s professional football: every cloud has a silver lining?
Authors: Cristiano Eirale
Journal: British Journal of Sports Medicine (2018)

Ekstrand et al recently showed that since 2001 hamstring injuries have increased by 4% annually in men’s professional football.1 A reason could be that evidence-based preventive measures are only partially implemented at the elite level,2 despite that they have been proven to be effective in the reduction of hamstring injuries in football in professional and amateur Danish footballers.3 However, while the rate of hamstring injuries increased during training sessions (4%/year), there was not a significant increase of these injuries during matches.1 The authors speculate that this may be due to the fact that the training sessions are more intense with the aim to better prepare the players to the match. They also hypothesise that this new training approach may be protective during matches and therefore the hamstring injury rate during match play has not …
Abstract 11446: Systemic Administration of Mitochondria Alleviates 100% Oxygen-Induced Acute Respiratory Distress Syndrome in Rats
Authors: Hon Kan Yip, Tzu -Hsien Tsai, Steve Leu, Sarah Chua
Journal: Circulation (2014)

Background: We tested the hypothesis that mitochondria-replacement therapy ameliorated 100% oxygen-induced rat acute respiratory distress syndrome (ARDS). Methods and Results: Adult-Male SD rats (n=24) were equally categorized into group 1 (controls, room air inhalation), group 2 (ARDS: induced by inhalation of 100% oxygen for 48 hrs), and group 3 [ARDS + mitochondrial transfusion (1400 μg/each rat) from intra-venous administration 6 h after ARDS induction]. By 72 h after ARDS induction, the oxygen saturation (O 2 -Sat) was significantly lower in group 3 and more significantly lower in group 2 than in group 1, whereas pulmonary artery systolic-blood pressure showed a reversed pattern of O 2 -Sat among three groups (all p&lt;0.001). H&amp;E stain for lung crowded score showed an identical pattern of O 2 -Sat and number of alveolar sacs and lung weight exhibited an opposite pattern of O 2 -Sat among the three groups. The protein expressions of apoptotic (mitochondrial Bax, cleaved caspase 3 &amp; PARP), fibrotic (Smad5, TGF-β), ROS (NOX-1, NOX-2, NOX-4), oxidative stress (oxidized protein), DNA- &amp; mitochondrial-damaged (γ-H2AX, Ki-67; cytosolic cytochrome-c) and inflammatory (TNF-α, MMP-9, NF-κB) biomarkers, and IHC/IF microscopic findings of inflammatory (CD14+, CD68+), DNA-damaged (γ-H2AX+, Ki-67+) cells exhibited an opposite pattern, whereas the protein expressions of anti-apoptotic (Smad1/3, BMP-2) markers exhibited an identical pattern of O 2 -Sat among three groups (all p&lt;0.001). The anti-oxidant (HO-2, NQO-1), mitochondrial-preserved (mitochondrial cytochrome-c) biomarkers, and cellular levels of anti-oxidants (HO-1, NQO-1, GR, GPx) were significantly higher in group 2 and more significantly higher in group 3 than in group 1 (all p&lt;0.0001). Conclusions: Mitochondria therapy protects against 100% oxygen-induced ARDS. Key words: mitochondrial replacement, acute lung injury, inflammation, oxidative stress, DNA and mitochondrial damage
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management
Authors: David J Birnkrant, Katharine Bushby, Carla M Bann, Susan D Apkon, Angela Blackwell, David Brumbaugh, Laura E Case, Paula R Clemens, Stasia Hadjiyannakis, Shree Pandya, Natalie Street, Jean Tomezsko, Kathryn R Wagner, Leanne M Ward, David R Weber
Journal: The Lancet Neurology (2018)
Multi-Functional Genetic Engineering of Pluripotent Cell Lines for Universal Off-the-Shelf Natural Killer Cell Cancer Immunotherapy
Authors: Ryan Bjordahl, Raedun Clarke, Svetlana Gaidarova, Matthieu Bauer, Jeff Sasaki, Brian Groff, Tom Lee, Weijie Lan, Ramzey Abujarour, Greg Bonello, Megan Robinson, Ian Hardy, Daniel Shoemaker, Bahram Valamehr
Journal: Blood (2017)
Tumor-infiltrating BRAFV600E-specific CD4+ T cells correlated with complete clinical response in melanoma
Authors: Joshua R. Veatch, Sylvia M. Lee, Matthew Fitzgibbon, I-Ting Chow, Brenda Jesernig, Tom Schmitt, Ying Ying Kong, Julia Kargl, A. McGarry Houghton, John A. Thompson, Martin McIntosh, William W. Kwok, Stanley R. Riddell
Journal: Journal of Clinical Investigation (2018)

T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who achieved a complete response following adoptive transfer of tumor-infiltrating lymphocytes (TILs). Tumor exome sequencing surprisingly revealed fewer than 30 nonsynonymous somatic mutations, including oncogenic BRAFV600E. Analysis of the specificity of TILs identified rare CD4+ T cells specific for BRAFV600E and diverse CD8+ T cells reactive to nonmutated self-antigens. These specificities increased in blood after TIL transfer and persisted long-term, suggesting they contributed to the effective antitumor immune response. Gene transfer of the BRAFV600E-specific T cell receptor (TCR) conferred recognition of class II MHC-positive cells expressing the BRAF mutation. Therapy with TCR-engineered BRAFV600E-specific CD4+ T cells may have direct antitumor effects and augment CD8+ T cell responses to self- and/or mutated tumor antigens in patients with BRAF-mutated cancers.
What Does AL Amyloidosis Look like in the Era of Mass Spectrometry Typing
Authors: Eli Muchtar, Morie A. Gertz, Robert A Kyle, Martha Q Lacy, David Dingli, Nelson Leung, Francis K Buadi, Suzanne R. Hayman, Prashant Kapoor, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Wilson I Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Stephen J. Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven Zeldenrust, S. Vincent Rajkumar, Shaji K Kumar, Angela Dispenzieri
Journal: Blood (2017)
Acquired Somatic Mutations in T Cells in Patients with Aplastic Anemia and Hypoplastic Myelodysplastic Syndromes
Authors: Sofie Lundgren, Mikko Keränen, Kari Nousiainen, Samuli Eldfors, Sari Hannula, Tiina Hannunen, Pekka Ellonen, Gunilla Walldin, Michael Clemente, Freja Ebeling, Hanna Rajala, Jaroslaw P. Maciejewski, Harri Lähdesmäki, Eva Hellstrom-Lindberg, Satu Mustjoki
Journal: Blood (2017)
Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017
Authors: Marjolein J. Poen, Theo M. Bestebroer, Oanh Vuong, Rachel D. Scheuer, Henk P. van der Jeugd, Erik Kleyheeg, Dirk Eggink, Pascal Lexmond, Judith M.A. van den Brand, Lineke Begeman, Stefan van der Vliet, Gerhard J.D.M. Müskens, Frank A. Majoor, Marion P.G. Koopmans, Thijs Kuiken, Ron A.M. Fouchier
Journal: Eurosurveillance (2018)

Introduction Highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in south-east Asia and Russia. This second H5N8 wave resulted in a large number of outbreaks in poultry farms and the deaths of large numbers of wild birds in multiple European countries. Methods : Here we report on the detection of HPAI H5N8 virus in 57 wild birds of 12 species sampled during active (32/5,167) and passive (25/36) surveillance activities, i.e. in healthy and dead animals respectively, in the Netherlands between 8 November 2016 and 31 March 2017. Moreover, we further investigate the experimental approach of wild bird serology as a contributing tool in HPAI outbreak investigations. Results : In contrast to the first H5N8 wave, local virus amplification with associated wild bird mortality has occurred in the Netherlands in 2016/17, with evidence for occasional gene exchange with low pathogenic avian influenza (LPAI) viruses. Discussion : These apparent differences between outbreaks and the continuing detections of HPAI viruses in Europe are a cause of concern. With the current circulation of zoonotic HPAI and LPAI virus strains in Asia, increased understanding of the drivers responsible for the global spread of Asian poultry viruses via wild birds is needed.
Commentary: Heterogeneity of respiratory disease in children and young adults with sickle cell disease
Authors: Robyn T Cohen, Elizabeth S Klings
Journal: Thorax (2018)

Sickle cell disease (SCD) affects 300 000 children born worldwide annually. While classically thought of as a genetic haemoglobinopathy, complications impact nearly every vascular bed leading to progressive organ damage and accelerated mortality. Pulmonary complications of SCD are among the most common causes of morbidity and mortality and affect every structure of the lungs. Abnormal pulmonary function is often one of the earliest indicators of lung disease, yet our understanding of the clinical significance of this finding is poor. 

Prior studies suggest several consistent themes: (1) while most children with SCD have lung function within the normal range,1 2 spirometry is, on average, reduced compared with healthy …
A prospective clinical utility study of the impact of the 21-gene recurrence score assay (Onco<i>type</i> DX) in estrogen receptor positive (ER+) node negative (pN0) breast cancer in academic Canadian centers.
Authors: James Ashley Davidson, Ian Cromwell, Susan Ellard, Caroline A. Lohrisch, Karen A. Gelmon, Tamara Nina Shenkier, Diego Villa, Howard John Lim, Sophie Sun, Sara Kristina Taylor, Marianne Taylor, Barbara Czerkawski, Malcolm Hayes, Diana Ionescu, Janice Pope, Jayne Berube, Carl N. Yoshizawa, Calvin Chao, Stuart Peacock, Stephen K. L. Chia
Journal: Journal of Clinical Oncology (2012)

549^ Background: The Oncotype DX 21-gene Recurrence Score assay (RS) can potentially predict the magnitude of chemotherapy benefit in patients with stage I-II, node-negative, ER+ disease who will be treated with tamoxifen for 5 years. While use in the United States has grown significantly since its introduction, it is not yet routinely ordered by oncologists in most parts of Canada. The primary purpose of this study was to measure the impact of the Oncotype DX test on the physician’s treatment recommendation in ER+ pN0 breast cancer in British Columbia. Methods: After providing informed consent, patients and medical oncologists completed respective pre-RS questionnaires indicating their treatment preferences and level of confidence and a decisional conflict scale (patients only). At a subsequent visit, after the RS result was known and discussed, the patient and oncologist completed a second set of questionnaires. The proportion of physician treatment recommendations that changed from baseline to follow-up (post RS) were calculated with 95% confidence interval (CI). A prospective health economic (HE) analysis was also performed. Results: From May 2010 to July 2011, two participating BCCA centres enrolled 156 patients. Of the 150 for whom successful RS assay results were obtained, physicians changed their chemotherapy recommendation in 45 cases (30%; 95% CI 22.8-38.0%); either to add (10%; 95% CI 5.7-16.0%) or omit (20%; 95% CI 13.9-27.3%) adjuvant chemotherapy. As a secondary end-point, in 84 cases (56%; 95% CI 47.7-64.1%) there was a change in either the planned chemo and/or endocrine therapy recommendation. There was an overall significant improvement in physician confidence post RS (p &lt; 0.001). Patient decisional conflict also significantly decreased following the RS assay (p &lt; 0.001). The HE analysis is ongoing and will be presented separately. Conclusions: Within the context of a publicly funded health care system, the RS assay significantly affects adjuvant treatment recommendations in ER+ node negative breast cancer, in addition to reducing patient decisional conflict.