tbuckley/cabot-search huggingface dataset:
Molecular switch from MYC to MYCN expression in MYC protein negative Burkitt lymphoma cases
Authors: Lucia Mundo, Maria Raffaella Ambrosio, Francesco Raimondi, Leonardo Del Porro, Raffaella Guazzo, Virginia Mancini, Massimo Granai, Bruno Jim Rocca, Cristina Lopez, Susanne Bens, Noel Onyango, Joshua Nyagol, Nicholas Abinya, Mohsen Navari, Isaac Ndede, Kirkita Patel, Pier Paolo Piccaluga, Roshanak Bob, Maria Margherita de Santi, Robert B. Russell, Stefano Lazzi, Reiner Siebert, Harald Stein, Lorenzo Leoncini
Journal: Blood Cancer Journal (2019)

Abstract MYC is the most altered oncogene in human cancer, and belongs to a large family of genes, including MYCN and MYCL . Recently, while assessing the degree of correlation between MYC gene rearrangement and MYC protein expression in aggressive B-cell lymphomas, we observed few Burkitt lymphoma (BL) cases lacking MYC protein expression despite the translocation involving the MYC gene. Therefore, in the present study we aimed to better characterize such cases. Our results identified two sub-groups of MYC protein negative BL: one lacking detectable MYC protein expression but presenting MYCN mRNA and protein expression; the second characterized by the lack of both MYC and MYCN proteins but showing MYC mRNA. Interestingly, the two sub-groups presented a different pattern of SNVs affecting MYC gene family members that may induce the switch from MYC to MYCN . Particulary, MYCN-expressing cases show MYCN SNVs at interaction interface that stabilize the protein associated with loss-of-function of MYC. This finding highlights MYCN as a reliable diagnostic marker in such cases. Nevertheless, due to the overlapping clinic, morphology and immunohistochemistry (apart for MYC versus MYCN protein expression) of both sub-groups, the described cases represent bona fide BL according to the current criteria of the World Health Organization.
Single Cell DNA Sequencing Identifies Combinatorial Mutation Patterns and Clonal Architecture in Myeloid Malignancies
Authors: Linde A Miles, Robert L Bowman, Tiffany R Merlinsky, Aik Ooi, Pedro Mendez, Christopher Famulare, Minal A Patel, Kelly Bolton, Neil Palmisiano, Martin P. Carroll, Elli Papaemmanuil, Ahmet Zehir, Sara E. Meyer, Aaron D Viny, Ross L. Levine
Journal: Blood (2019)
Association between the arrested decline in cardiovascular disease and health and social-care costs: a modelling study
Authors: Brendan Collins, Piotr Bandosz, Maria Guzman-Castillo, Jonathan Pearson-Stuttard, George Stoye, Jeremy McCauley, Sara Ahmadi-Abhari, Martin J Shipley, Marzieh Araghi, Simon Capewell, Eric French, Eric J Brunner, Martin O’Flaherty
Journal: The Lancet (2019)
Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study
Authors: Alexander Röth, Wilma Barcellini, Shirley D'Sa, Yoshitaka Miyakawa, Catherine M Broome, Marc Michel, David J. Kuter, Bernd Jilma, Tor Henrik Anderson Tvedt, Stella Lin, Xiaoyu Jiang, Caroline Reuter, William Hobbs, Sigbjørn Berentsen
Journal: Blood (2019)
The anti-IgE mAb omalizumab induces adverse reactions by engaging Fcγ receptors
Authors: Bianca Balbino, Pauline Herviou, Ophélie Godon, Julien Stackowicz, Odile Richard-Le Goff, Bruno Iannascoli, Delphine Sterlin, Sébastien Brûlé, Gael A. Millot, Faith M. Harris, Vera A. Voronina, Kari C. Nadeau, Lynn E. Macdonald, Andrew J. Murphy, Pierre Bruhns, Laurent L. Reber
Journal: Journal of Clinical Investigation (2019)

Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of severe asthma and chronic spontaneous urticaria. Use of omalizumab is associated with reported side effects ranging from local skin inflammation at the injection site to systemic anaphylaxis. To date, the mechanisms through which omalizumab induces adverse reactions are still unknown. Here, we demonstrated that immune complexes formed between omalizumab and IgE can induce both skin inflammation and anaphylaxis through engagement of IgG receptors (FcγRs) in FcγR-humanized mice. We further developed an Fc-engineered mutant version of omalizumab, and demonstrated that this mAb is equally potent as omalizumab at blocking IgE-mediated allergic reactions, but does not induce FcγR-dependent adverse reactions. Overall, our data indicate that omalizumab can induce skin inflammation and anaphylaxis by engaging FcγRs, and demonstrate that Fc-engineered versions of the mAb could be used to reduce such adverse reactions.
Long-term Functional, Psychological, Emotional, and Social Outcomes in Survivors of Firearm Injuries
Authors: Michael A. Vella, Alexander Warshauer, Gabriella Tortorello, Joseph Fernandez-Moure, Joseph Giacolone, Bofeng Chen, Alexander Cabulong, Kristen Chreiman, Carrie Sims, C. William Schwab, Patrick M. Reilly, Meghan Lane-Fall, Mark J. Seamon
Journal: JAMA Surgery (2019)

The outcomes of firearm injuries in the United States are devastating. Although firearm mortality and costs have been investigated, the long-term outcomes after surviving a gunshot wound (GSW) remain unstudied.
What motivated the Industrial Revolution: England's libertarian culture or affluence<i>per se</i>?
Authors: Scott Atran
Journal: Behavioral and Brain Sciences (2019)

Abstract What impelled the Industrial Revolution's spectacular economic growth? Life History Theory, Baumard argues, explains how England's world-supreme affluence psychologically fostered innovation; moreover, wherever similar affluence abounds, a “civilizing process” bringing enlightenment and democracy is apt to evolve. Baumard insightfully analyzes a “constellation of affluence” but proffers somewhat whiggish history given England's prior and unique proto-capitalist culture of economic liberty and individualism.
SAT0711-HPR ADDING INFORMATION ON WIDESPREAD PAIN TO THE START BACK SCREENING TOOL WHEN IDENTIFYING LOW BACK PAIN PATIENTSAT INCREASED RISK FOR POOR PROGNOSIS
Authors: Katarina Aili, Stefan Bergman, Emma Haglund
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Early identification of those with the highest risk of developing chronic low back pain (CLBP) is important but difficult. STarT Back Screening Tool (SBST) is reported to capture patients at high risk of developing CLBP, but does not include concurrent pain from other locations, which is a known risk factor for worse outcome. <h3>Objectives:</h3> To study differences in self-reported health between patients with low, medium and high risk of developing CLBP identified by the combination of SBST and information on widespread pain. <h3>Methods:</h3> Adults aged 18-67 seeking primary care for LBP in the southwest of Sweden were included. The STSB was used to differentiate between three risk levels; low, medium and high risk. When patients were classified as medium risk, information from a pain mannequin on widespread pain and multisite pain were added to further distinguish between high and medium risk. If widespread pain and pain from more than seven locations (multisite pain) were reported, patient was transformed from the medium risk to the high risk group. Differences between the three risk groups with regard to physical function (Roland Morrison Disability Questionnaire (RMDQ), 0-24 best-worst), mental health (Hospital Anxiety and Depression scale (HADa and HADd) 0-21 no distress-maximum distress), health related quality of life (EuroQol-5D (EQ5D), 0-1 worst-best), fear avoidance for physical activity (PA) and work (Fear-Avoidance Beliefs Questionnaire (FABQ) PA, 0-24, and work, 0-42 best-worst) were analyzed in an ANOVA. <h3>Results:</h3> Ninety-five patients (61% women), mean (SD) age 42 years (14) seeking health-care for their LBP were included in the study. Of those scoring low risk on SBST (n=19), 3 also reported multisite CWP. Of those who scored medium risk on SBST (n=48), 8 reported multisite CWP and were moved to the high risk group. Of 17 scoring high risk on SBST, 4 simultaneously reported multisite CWP. After constructing three risk groups combining SBST and multisite CWP, there were 19 in the low risk group, 40 in the medium risk group, and 25 in the high-risk group. The low, medium, high risk groups identified by the combined method, differed statistically significant in reported RMDQ (low, medium, high mean respectively 7.0, 12.2, 13.4, p&lt;0.001), HADa (3.7, 6.4, 10.1, p&lt;0.001), HADd (2.9, 4.0, 8.4, p&lt;0.001), FABQ PA (9.1, 12.7, 14.4, p=0.005), FABQ work (9.9, 16.7, 23.1 p=0.001), EQ5D (0.72, 0.53, 0.38, p=0.001). <h3>Conclusion:</h3> Adding information on multisite widespread pain to the SBST resulted in classifying more patients in the high risk group as compared to using only SBST. The three groups identified by combing the screening tools differed significantly on all investigated health variables, indicating the combination may be capturing more patients at risk for CLBP. <h3> Disclosure of Interests:</h3> None declared
Racial and Socioeconomic Disparities in the Utilization of Autologous Stem Cell Transplant for Treatment of Multiple Myeloma in the Era of Novel Agents
Authors: Victoria A. Vardell, Daniel Ermann, Maryam Gbadamosi-Akindele, Funmi Badejo, Peter T. Silberstein, Srinivas K. Tantravahi
Journal: Blood (2019)
A pH/Ultrasound dual-response biomimetic nanoplatform for nitric oxide gas-sonodynamic combined therapy and repeated ultrasound for relieving hypoxia
Authors: Jie An, Yong-Guo Hu, Cheng Li, Xiao-Lin Hou, Kai Cheng, Bin Zhang, Ruo-Yun Zhang, Dong-Yu Li, Shao-Jun Liu, Bo Liu, Dan Zhu, Yuan-Di Zhao
Journal: Biomaterials (2019)
Impact of newborn screening on outcomes and social inequalities in cystic fibrosis: a UK CF registry-based study
Authors: Daniela K Schlüter, Kevin W Southern, Carol Dryden, Peter Diggle, David Taylor-Robinson
Journal: Thorax (2019)

Background Newborn bloodspot screening (NBS) for cystic fibrosis (CF) was introduced across the UK in 2007 but the impact on clinical outcomes and health inequalities for children with CF is unclear. Methods We undertook longitudinal analyses of UK CF registry data on over 3000 children with CF born between 2000 and 2015. Clinical outcomes were the trajectories of percent predicted forced expiratory volume in one second (%FEV 1 ) from age 5, weight for age and body mass index (BMI) SD-scores from age one, and time to chronic Pseudomonas aeruginosa (cPA) infection. Using mixed effects and time-to-event models we assessed the association of NBS with outcomes and potential interactions with childhood socioeconomic conditions, while adjusting for confounders. Results NBS was associated with higher average lung function trajectory (+1.56 FEV 1 percentage points 95% CI 0.1 to 3.02, n=2216), delayed onset of cPA, and higher average weight trajectory intercept at age one (+0.16 SD; 95% CI 0.07 to 0.26, n=3267) but negative rate of weight change thereafter (−0.02 SD per year; 95% CI −0.03 to −0.00). We found no significant association of NBS with BMI or rate of change of lung function. There was no clear evidence of an impact of NBS on health inequalities early in life. Conclusions Children diagnosed with CF by NBS in the UK have better lung function and increased early weight but NBS does not appear to have narrowed early health inequalities.
Low levels of total and high-molecular-weight adiponectin may predict non-alcoholic fatty liver in Korean adults
Authors: Young-Sang Kim, Soo-Hyun Lee, Seung Geon Park, Bo Youn Won, Hyejin Chun, Doo-Yeoun Cho, Moon-Jong Kim, Ji Eun Lee, Ji-Hee Haam, Kunhee Han
Journal: Metabolism (2019)
Current Approaches to Germline Cancer Genetic Testing
Authors: Elena M. Stoffel, John M. Carethers
Journal: Annual Review of Medicine (2019)

The prevalence of genetic predisposition to cancer is greater than initially appreciated, yet most affected individuals remain undiagnosed. Deleterious germline variants in cancer predisposition genes are implicated in 1 in 10 cases of advanced cancer. Next-generation sequencing technologies have made germline and tumor DNA sequencing more accessible and less expensive. Expanded access to clinical genetic testing will improve identification of individuals with genetic predisposition to cancer and provide opportunities to effectively reduce morbidity through precision cancer therapies and surveillance. Cross-disciplinary clinical education in genomic medicine is needed to translate advances in genomic medicine into improved health outcomes.
Presence of Bisphenol A and Parabens in a Neonatal Intensive Care Unit: An Exploratory Study of Potential Sources of Exposure
Authors: Luz M. Iribarne-Durán, Francisco Artacho-Cordón, Manuela Peña-Caballero, José M. Molina-Molina, Inmaculada Jiménez-Díaz, Fernando Vela-Soria, Laura Serrano, José A. Hurtado, Mariana F. Fernández, Carmen Freire, Nicolás Olea
Journal: Environmental Health Perspectives (2019)

BACKGROUND: Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic chemicals with hormonal activity.OBJECTIVES: Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical products commonly used in NICUs in prolonged intimate contact with NICU newborns.METHODS: Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl-(MeP), ethyl-(EtP), propyl-(PrP), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in vitro (anti-)estrogenic and (anti-)androgenic activity, respectively, of the extracts.Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leaching methodologies.RESULTS: BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and ∼ 25% and ∼ 10% of extracts evidenced estrogenic and anti-androgenic activity, respectively.The highest BPA content was found in the three-way stopcock (>7:000 ng=g), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to 700 ng=g BPA).A total PB concentration ( P PBs) >100 ng=g was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape.The highest estrogenic activity [>450 pM estradiol equivalent (E 2 eq)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [>5 mM procymidone equivalent units per gram (Proceq=g)] in small dummy nipples and three-way stopcocks.DISCUSSION: According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes.There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency.
The interplay between m6A RNA methylation and noncoding RNA in cancer
Authors: Shuai Ma, Chen Chen, Xiang Ji, Jinbo Liu, Quanbo Zhou, Guixian Wang, Weitang Yuan, Quancheng Kan, Zhenqiang Sun
Journal: Journal of Hematology & Oncology (2019)

Abstract N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.
A Novel Assay of Neutrophil Extracellular Traps (NETs) Formation Independently Predicts DIC and Identifies the Rationale for Anti-IL-8 Therapies
Authors: Simon Timothy Abrams, Ben Morton, Yasir Alhamdi, Mohmad Alsabani, Zhenxing Cheng, Steven Lane, Ingeborg Welters, Guozheng Wang, Cheng-Hock Toh
Journal: Blood (2019)
Systemic Autoimmune Disease Among Adults Exposed to the September 11, 2001 Terrorist Attack
Authors: Sara A. Miller‐Archie, Peter M. Izmirly, Jessica R. Berman, Jennifer Brite, Deborah J. Walker, Renato C. Dasilva, Lysa J. Petrsoric, James E. Cone
Journal: Arthritis & Rheumatology (2019)

Autoimmune disease is an emerging condition among persons exposed to the September 11, 2001 attack on the World Trade Center (WTC). Components of the dust cloud resulting from the collapse of the WTC have been associated with development of a systemic autoimmune disease, as has posttraumatic stress disorder (PTSD). We undertook this study to determine whether dust exposure and PTSD were associated with an increased risk of systemic autoimmune disease in a 9/11-exposed cohort.Among 43,133 WTC Health Registry enrollees, 2,786 self-reported having a post-9/11 systemic autoimmune disease. We obtained informed consent to review medical records to validate systemic autoimmune disease diagnoses for 1,041 enrollees. Diagnoses of systemic autoimmune diseases were confirmed by classification criteria, rheumatologist diagnosis, or having been prescribed systemic autoimmune disease medication. Controls were enrollees who denied having an autoimmune disease diagnosis (n = 37,017). We used multivariable log-binomial regression to examine the association between multiple 9/11 exposures and risk of post-9/11 systemic autoimmune disease, stratifying by responders (rescue, recovery, and clean-up workers) and community members (e.g., residents, area workers).We identified 118 persons with systemic autoimmune disease. Rheumatoid arthritis was most frequent (n = 71), followed by Sjӧgren's syndrome (n = 22), systemic lupus erythematosus (n = 20), myositis (n = 9), mixed connective tissue disease (n = 7), and scleroderma (n = 4). Among 9/11 responders, those with intense dust cloud exposure had almost twice the risk of systemic autoimmune disease (adjusted risk ratio 1.86 [95% confidence interval 1.02-3.40]). Community members with PTSD had a nearly 3-fold increased risk of systemic autoimmune disease.Intense dust cloud exposure among responders and PTSD among community members were associated with a statistically significant increased risk of new-onset systemic autoimmune disease. Clinicians treating 9/11 survivors should be aware of the potential increased risk of systemic autoimmune disease in this population.
Atezolizumab for children and young adults with previously treated solid tumours, non-Hodgkin lymphoma, and Hodgkin lymphoma (iMATRIX): a multicentre phase 1–2 study
Authors: Birgit Geoerger, C Michel Zwaan, Lynley V Marshall, Jean Michon, Franck Bourdeaut, Michela Casanova, Nadège Corradini, Gianluca Rossato, Mufiza Farid-Kapadia, Colby S Shemesh, Katherine E Hutchinson, Francis Donaldson, Minlei Liao, Hubert Caron, Tanya Trippett
Journal: The Lancet Oncology (2019)
TACC3 is a novel target of paclitaxel: its implication in paclitaxel-mediated tumor therapy
Authors: Eun-Kyoung Yim, Keun-Ho Lee, Hee-Jung Lee, Chan-Joo Kim, Tae-Chul Park, Soo-Jong Um, Jong-Sup Park
Journal: Cancer Research (2006)

1284  Paclitaxel is currently used in the treatment of various solid cancers. Initial studies have demonstrated the mechanism of action of paclitaxel that alters microtubule dynamics. Although treatment of various tumor cells with paclitaxel in vivo and in vitro induces apoptosis, but early paclitaxel-targeted proteins is not yet known. We identified TACC3 as a novel protein that is down-regulated with paclitaxel treatment by proteome analysis including 2-DE and MALDI-TOF-MS in cervical cancer cell line. Our current studies aim to show TACC3 functions through in vitro treatment of paclitaxel or TACC3 siRNA by RNAi (RNA interference). Paclitaxel-treated cells are unable to proceed normally through the cell cycle and are arrested in G2/M phase and reveal apoptotic morphology including chromatin condensation, apoptotic body formation and nuclear fragmentation. Also, TACC3 levels after paclitaxel treatment decreased as a time- and dose-dependent manner both mRNA and protein levels. These results indicate paclitaxel suppress TACC3 expression in transcription level. After treatment of paclitaxel or TACC3 RNAi, there were significant G2/M phase arrest (>4 fold), TACC3 down-regulation and apoptosis in cervical carcinoma HeLa cell lines. Also, we confirmed that the role of TACC3 siRNA for microtubule stabilization is similar to that of paclitaxel. This finding indicates that an important mechanism of TACC3 expression exits within the process of the G2/M phase. TACC3 down-regulations had an effect on increase of α- and γ-tubulin polymerization. Although the primary target of paclitaxel is microtubules, its efficacy exceeds that of conventional microtubule-disrupting agents, suggesting that it may have another action mechanism through TACC3 down-regulation. mTACC3-overexpressing cells showed cell overgrowth and S-phase delay on cell cycle progression as compared with control cells. Paclitaxel treatments in mTACC3-overexpressing cells were unable to suppress exogenous TACC3 expression and induce cell growth inhibition, G2/M phase arrest, apoptosis and microtubule disintegration. In addition to, TACC3 is expressed at high levels in various cancer cells and tumor tissues. We suggest TACC3 overexpression might imply that it has a role in tumor progression. TACC3 levels decreased in paclitaxel-sensitive cells, but had no changes in paclitaxel-resistant cells by paclitaxel treatment (IC50 concentration).This study is proposed that the TACC3 protein may be participated in microtubule formation as an oncoprotein during mitosis and be regulated by paclitaxel as a novel target. In conclusion, TACC3 may involve the mechanisms of tumorigenesis and may be a target protein for cancer therapy.
Application of the Lung Immune Prognostic Index From Research to Clinical Practice
Authors: Junyu Long, Jianzhen Lin, Haitao Zhao
Journal: JAMA Oncology (2019)

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Plasma protein patterns as comprehensive indicators of health
Authors: Stephen A. Williams, Mika Kivimaki, Claudia Langenberg, Aroon D. Hingorani, J. P. Casas, Claude Bouchard, Christian Jonasson, Mark A. Sarzynski, Martin J. Shipley, Leigh Alexander, Jessica Ash, Tim Bauer, Jessica Chadwick, Gargi Datta, Robert Kirk DeLisle, Yolanda Hagar, Michael Hinterberg, Rachel Ostroff, Sophie Weiss, Peter Ganz, Nicholas J. Wareham
Journal: Nature Medicine (2019)