tbuckley/cabot-search huggingface dataset:
The Challenges of Sharing Data in an Era of Politicized Science
Authors: Howard Bauchner, Phil B. Fontanarosa
Journal: JAMA (2019)

The goal of making science more transparent-sharing data, posting results on trial registries, use of preprint servers, and open access publishing-may enhance scientific discovery and improve individual and population health, but it also comes with substantial challenges in an era of politicized science, enhanced skepticism, and the ubiquitous world of social media.The recent announcement by the Trump administration of plans to proceed with an updated version of the proposed rule "Strengthening Transparency in Regulatory Science," 1 stipulating that all underlying data from studies that underpin public health regulations from the US Environmental Protection Agency (EPA) must be made publicly available so that those data can be independently validated, epitomizes some of these challenges. 2,3According to EPA Administrator Andrew Wheeler: "Good science is science that can be replicated and independently validated, science that can hold up to scrutiny.That is why we're moving forward to ensure that the science supporting agency decisions is transparent and available for evaluation by the public and stakeholders." 3irtually every time JAMA publishes an article on the effects of pollution or climate change on health, the journal immediately receives demands from critics to retract the article for various reasons.Some individuals and groups simply do not believe that pollution or climate change affects human health.Research on climate change, and the effects of climate change on the health of the planet and human beings, if made available to anyone for reanalysis could be manipulated to find a different outcome than initially reported.In an age of skepticism about many issues, including science, with the ability to use social media to disseminate unfounded and at times potentially harmful ideas, it is challenging to balance the potential benefits of sharing data with the harms that could be done by reanalysis.Can the experience of sharing data derived from randomized clinical trials (RCTs)-either as mandated by some funders and journals or as supported by individual investigatorsserve as examples as a way to safeguard "truth" in science.Over the past 3 years, the International Committee of Medical Journal Editors (ICMJE) has issued 2 statements regarding the sharing of data that underpin RCTs.The first statement, published in January 2016, was a proposal for the research community to consider. 4There was criticism of the proposal: some investigators thought the ICMJE was not moving fast enough to insist on immediate availability of all data that underpin the publication of RCTs, whereas others felt that the ICMJE was moving too quickly and had not considered all of the methodologic, statistical, ethical, administrative, and cost issues related to sharing data.
Multi-Center Phase 2 Study of Pembroluzimab (Pembro) and Azacitidine (AZA) in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML) and in Newly Diagnosed (≥65 Years) AML Patients
Authors: Ivana Gojo, Robert K. Stuart, Jonathan Webster, Amanda Blackford, Juan Carlos Varela, Jillian Morrow, Amy E. DeZern, Matthew C Foster, Mark J. Levis, Catherine C. Coombs, Gabrielle T. Prince, B. Douglas Smith, Hendrik W. Van Deventer, Katarzyna Jamieson, Ravi Varadhan, Benjamin G. Vincent, Jonathan S Serody, Leo Luznik, Joshua F Zeidner
Journal: Blood (2019)
Prospective virome analyses in young children at increased genetic risk for type 1 diabetes
Authors: Kendra Vehik, Kristian F. Lynch, Matthew C. Wong, Xiangjun Tian, Matthew C. Ross, Richard A. Gibbs, Nadim J. Ajami, Joseph F. Petrosino, Marian Rewers, Jorma Toppari, Anette G. Ziegler, Jin-Xiong She, Ake Lernmark, Beena Akolkar, William A. Hagopian, Desmond A. Schatz, Jeffrey P. Krischer, Heikki Hyöty, Richard E. Lloyd
Journal: Nature Medicine (2019)
Early Results from a Biomarker-Directed Phase 2 Trial of Sy-1425 in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Demonstrate DHRS3 Induction and Myeloid Differentiation Following Sy-1425 Treatment
Authors: Joseph G. Jurcic, Azra Raza, George Vlad, Eytan M. Stein, Mikhail Roshal, Dale L. Bixby, Daniel F. Boyer, Carlos Enrique Vigil, Sergei Syrbu, Mikkael A. Sekeres, Heesun J. Rogers, David A. Rizzieri, Anand Shreeram Lagoo, Gail J. Roboz, Robert L. Redner, David P. Steensma, Rachel J. Cook, Tamara Moyo, Michael McKeown, Nigel J. Waters, Kristin Stephens, Angela Volkert, Emmanuelle Di Tomaso, David A. Roth, Jorge E. Cortes
Journal: Blood (2017)
Bernard J Tyson: chief executive of US non-profit healthcare provider Kaiser Permanente
Authors: Bob Roehr
Journal: BMJ (2019)

Credit: Kaiser Permanente

Bernard J Tyson had a leading role in making Kaiser Permanente the largest and one of the most innovative healthcare providers in the US before he became chairman and chief executive of the non-profit organisation. His death shocked the company, depriving it of a charismatic leader.

One of seven children, Tyson was born in Vallejo, California, a “hardscrabble” city at the north east end of San Francisco Bay. His father was a carpenter and part time preacher. His mother had diabetes, and the time young Bernard spent with her in hospitals for that condition led him to a career in hospital administration.

Kaiser Permanente (KP) grew out of efforts by industrialist Henry J Kaiser to create affordable, accessible healthcare for his workers—first in isolated locations, where he was building large dams and smelting aluminium, and later in the shipyards that quickly and inexpensively cranked out hundreds of Liberty ships and other cargo vessels for the war effort. Later it would become an independent non-profit health maintenance organisation that collects insurance premiums and provides a full range of medical care.

Tyson joined KP soon after college and spent 35 years rising …
Therapeutic effect of inhibiting nonsense mediated decay in human cancers with TP53 premature termination codons
Authors: Mingde Luo, Baojin Fu, Antonio Jimeno, Manuel Hidalgo, Christine A Iacobuzio-Donahue
Journal: Cancer Research (2006)

2211  Purpose: Nonsense-mediated mRNA decay (NMD) is one of several post-transcriptional mechanisms that are used by eukaryotic cells to detect and degrade mRNAs with nonsense mutations (a.k.a. premature termination codons, or PTCs), and thus control the quality of mRNA function. Aminoglycoside antibiotics and small interfering RNAs (siRNAs) to RENT1, a component of the NMD surveillance complex, have been shown to inhibit NMD with resultant changes in gene expression. Our present study was designed to determine the feasibility of NMD inhibition as a novel chemotherapeutic modality for human cancers with TP53 PTCs. Methods: Twelve cancer cell lines derived from a variety of organ sites were used for which the genetic status of the TP53 tumor suppressor gene was known. For in vitro studies, each cell line was incubated with 20-200 ug/ml emetine or PBS for 4∼18 hours, and viability determined by MTT assay. Alternatively, incubations were followed immediately by harvesting of mRNA and protein for determinations of TP53 mRNA by real-time quantitative PCR and protein expression by Western Blot using clone Ab-6 at 1:200 (specific Anti-p53, for Human/Mouse, EMD Biosciences, Inc, San Diego, USA). Small interfering RNAs (siRNAs) to RENT1 or mock oligonucleotides were used in place of emetine to confirm the specificity of observed effects. For in vivo studies, cell lines with wild type or nonsense mutant TP53 genes were xenografted into nude mice and allowed to grow in the presence or absence of gentamicin or RENT1 siRNA for 5 days, during which the tumors were monitored for overall growth and harvested for measurement of TP53 mRNA and protein levels. These experiments are currently ongoing and will be reported in detail when complete. Results: Viability of all cancer cells reduced significantly after 18-hour incubation with emetine, varying from 80% to 5%. Incubation of cell lines with known TP53 PTCs with emetine in vitro resulted in as much as an 8∼28-fold increase in TP53 mRNA levels, whereas no effect was observed in cell lines with wild type or missense mutant TP53 genes. The specificity of this effect was confirmed in three different cell lines with known TP53 PTCs by transfection with RENT1 siRNA for 96 hours, after which RENT1 protein expression were blocked >95% and TP53 mRNA levels raised from 7.5 to 23.5-fold as compared to controls. Conclusion: Robust increases in TP53 expression in cancer cells with known TP53 PTCs can be induced by NMD inhibition. The potential benefits of NMD as a therapeutic option for pancreatic cancer are profound, as up to 20% of all human cancers contain at least one PTC in one or more tumor suppressor genes.
Research is like a bad game of ‘telephone’: mitigating the information breakdown from clinicians and researchers to the general public
Authors: Zachary Y Kerr, Avinash Chandran, Scott L Zuckerman, Lee Stoner, Gary S Solomon
Journal: British Journal of Sports Medicine (2019)

In the contemporary media environment, it is impossible for researchers to control how their research is disseminated and interpreted. Researchers’ findings can become lost in translation, particularly when deemed ‘newsworthy’. This information breakdown reminds us of the children’s game, ‘telephone’. In telephone, an individual whispers a message to another individual, which is repeated to another and so on. When the final individual receives the message, it has likely changed substantially.

Our model of the information breakdown within the research telephone focuses on two factors—the messenger and the receiver (figure 1). The messenger is the researcher who conducts the study, submits the manuscript for review and disseminates the findings through traditional and social media. The receivers of messaging may further propagate the findings, while making their own inferences, thereby crafting slightly revised messages. Unlike the game of telephone, the research telephone does not follow a single path; intermediate pathways can be bypassed (eg, disseminating findings prior to publication). When the scientific method is misrepresented or not comprehensively disclosed, subtle yet important misinterpretations occur, or the research message may be deliberately skewed to maximise ‘clicks’. When scientific writers fail to …
A Fast and Accurate Diagnostic Method for Ph-like ALL Using the Ncounter System
Authors: Kensuke Sasaki, Kohta Miyawaki, Yuichiro Semba, Koji Kato, Jumpei Nogami, Takeshi Sugio, Toshihiro Miyamoto, Yoshikiyo Ito, Koji Nagafuji, Takahiro Maeda, Koichi Akashi
Journal: Blood (2019)
Triclocarban exposure exaggerates colitis and colon tumorigenesis: roles of gut microbiota involved
Authors: Haixia Yang, Katherine Z. Sanidad, Weicang Wang, Minhao Xie, Min Gu, Xiaoqiong Cao, Hang Xiao, Guodong Zhang
Journal: Gut Microbes (2019)

Triclocarban (TCC) is a widely used antimicrobial ingredient in consumer products and is a ubiquitous contaminant in the environment. In 2016, the FDA removed TCC from over-the-counter handwashing products, but this compound is still approved for use in many other personal care products. A better understanding of its impact on human health could lead to significant impact for public health and regulatory policies. Here we show that exposure to low-dose TCC exaggerated the severity of colitis and exacerbated the development of colitis-associated colon tumorigenesis, via gut microbiota-dependent mechanisms. Exposure to TCC increased dextran sodium sulfate (DSS)- and interleukin 10 (IL-10) knockout-induced colitis, and exaggerated azoxymethane (AOM)/DSS-induced colon tumorigenesis in mice. Regarding the mechanisms, TCC exposure reduced the diversity and altered the composition of gut microbiota and failed to promote DSS-induced colitis in mice lacking the microbiota, supporting that the presence of the microbiota is critical for the pro-colitis effects of TCC. Together, these results support TCC could be a novel risk factor for colitis and colitis-associated colon cancer, and further regulatory policies on this compound could be needed.
Woman who was brain damaged after Achilles tendon operation is awarded £11m
Authors: Clare Dyer
Journal: BMJ (2019)

A woman who had a cardiac arrest and sustained brain damage after a simple operation to repair a torn Achilles tendon has won a settlement of over £11m (€12.9m; $14.2m) from the NHS.

The unnamed woman, who was in her early 40s, went to the emergency department at North Middlesex University Hospital in 2010 after rupturing her Achilles tendon while playing sport. She had the operation the following day.

She was slow to wake up after the procedure, so the anaesthetist gave her doxapram, a respiratory stimulant. The drug is effective for only a short period, …
Effect of Dasatinib Vs Imatinib in the Treatment of Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized, Open-Label, Multicenter Study of the Chinese Children's Cancer Group
Authors: Shuhong Shen, Xiaojuan Chen, Jiaoyang Cai, Yu Jie, Ju Gao, Shaoyan HU, Xiaowen Zhai, Changda Liang, Xiuli Ju, Hua Jiang, Runming Jin, Xuedong Wu, Ningling Wang, Xin Tian, Kaili Pan, Hui Jiang, Lirong SUN, Yongjun Fang, Chi Kong Li, Qun Hu, Minghua Yang, Yiping Zhu, Chunfu Li, Jun J. Yang, Hui Zhang, Jing-Yan Tang, Xiaofan Zhu, Ching-Hon Pui
Journal: Blood (2019)
Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet
Authors: Ville Wallenius, Erik Elias, Erik Elebring, Bauke Haisma, Anna Casselbrant, Pierre Larraufie, Emma Spak, Frank Reimann, Carel W le Roux, Neil G Docherty, Fiona M Gribble, Lars Fändriks
Journal: Gut (2019)

Objective Food intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms. Design Jejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures. Results The most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline. Conclusion Intestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.
Oncologists’ perspectives on medical marijuana for the elderly.
Authors: Desiree Rachel Azizoddin, Andrea Catherine Enzinger, Alexi A. Wright, Miryam Yusufov, Fangxin Hong, James A. Tulsky, Eric G Campbell, William F. Pirl, Manan Nayak, Ilana Braun
Journal: Journal of Clinical Oncology (2019)

78 Background: Cancer patients are increasingly using medical marijuana (MM) to manage symptoms and treatment side effects. Although cancer disproportionately affects the elderly, little is known about oncologists’ attitudes toward MM in this population. We surveyed US oncologists’ beliefs about the benefits of MM for older adults, and examined their associations with oncologists’ perceptions of MM efficacy and safety. Methods: 232 out of 400 randomly selected U.S. oncologists (63% response rate) completed a cross-sectional survey about their beliefs and recommendations regarding MM for cancer patients. Using Chi-square tests, we examined associations between oncologists’ demographics, their perceptions of geriatric MM use, as well as beliefs about comparative effectiveness of MM for cancer related symptoms, and comparative risks of MM to prescription opioids. Results: Among 232 oncologists included in this cohort, 109 (47.0%) reported that MM had at least some benefit for elderly cancer patients, 66 (28.4%) responded it was rarely or never beneficial, and 57 (24.6%) reported not knowing. There were no significant associations between oncologists’ beliefs about MM’s benefit for older adults and their sociodemographic characteristics. Those who believed MM was beneficial for the elderly were significantly more likely to report that MM was at least as effective as standard treatments for the following indications: coping (58.3% vs. 26.6%), appetite (83.3% vs 58.5%), depression (46.3% vs 25.0%), and nausea (66.7% vs 33.9%), respectively ( p &lt; 0.001). In contrast, oncologists’ beliefs about MM for the elderly were not significantly associated with perceptions of the comparative risks of MM ( p &gt; 0.05). Conclusions: In this nationally-representative sample of US oncologists, about half thought MM was beneficial for older adults with cancer. Oncologists’ support of MM for older adults was associated with perceptions of MM’s efficacy but was not associated with perceptions of MM’s risks. More research is needed regarding the safety and efficacy of MM to guide oncologists’ recommendations about its use in older adults.
ARGININOSUCCINATE SYNTHASE 1 IMMUNOMARKER IDENTIFIES SONIC HEDGEHOG HEPATOCELLULAR ADENOMAS:ITS USE IN CLINICAL PRACTICE
Authors: Margaux Sala, Dephine Gonzales, Thierry Teste-Lassere, Nathalie Dugot-Senant, Valerie Paradis, Sylvaine Di-Tommaso, Jean William Dupuy, Vincent Pitard, Cyril Dourthe, Christine Sempoux, Annette Gouw, Linda Ferrell, Andrew D. Clouston, Gregory Miller, Yasuni Nakanuma, Amedeo Sciarra, Matthew M. Yeh, Swan N. Thung, Alberto Quaglia, Jing Han, Ji Yuan, Cathy Fan, James M. Crawford, Laurent Possenti, Charles Balabaud, Paulette Bioulac-Sage, Anne Aurelie Raymond, Frederic Saltel
Journal: Hepatology (2019)
Antibody Cloning Identifies Pathogenic and Non-Pathogenic Antibodies in Heparin-Induced Thrombocytopenia and Defines the Molecular Signatures That Differentiate the Two Types of Antibodies
Authors: Wen Zhu, Yongwei Zheng, Mei Yu, Yaling Wu, Jianhui Wei, Nicholas Schneider, Anand Padmanabhan, Richard H. Aster, Demin Wang, Renren Wen
Journal: Blood (2019)
Third-Generation CAR T Cells Targeting CD19 Are Associated with an Excellent Safety Profile and Might Improve Persistence of CAR T Cells in Treated Patients
Authors: Maria-Luisa Schubert, Anita Schmitt, Brigitte Neuber, Angela Hückelhoven-Krauss, Alexander Kunz, Lei Wang, Ulrike Gern, Birgit Michels, Leopold Sellner, Susanne Hofmann, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt
Journal: Blood (2019)
A clinical model to predict one-year mortality for patients with advanced cancer.
Authors: Catherine Owusuaa, Annemieke Van Der Padt - Pruijsten, Daan Nieboer, Agnes van der Heide, Carin C. D. Van Der Rijt
Journal: Journal of Clinical Oncology (2019)

132 Background: Advance care planning is necessary for cancer patients who are in their last year of life. We developed a clinical model to predict 1-year mortality for patients with advanced cancer. Methods: Patients with advanced cancer and no curatively aimed treatment options were included in a prospective multicenter observational study involving six hospitals in the Netherlands (June-November 2017). Using cox regression, a model was developed with candidate predictors as identified in literature: surprise question (SQ), clinical characteristics (age, sex, primary tumor, metastases, WHO performance status, food intake, weight loss, pain, comorbidity, dyspnea, and fatigue), and laboratory values (serum albumin, hemoglobin, and C-reactive protein). The primary outcome was all-cause 1-year mortality. Discriminative ability was measured using the c-statistic and assessed using internal-external validation by study hospital. Results: Of 867 patients (median age 66 years, male 47%), 362 (42%) died within 1-year follow-up. Three models were developed: model 1: SQ; model 2: SQ + clinical characteristics; model 3: SQ + clinical characteristics + laboratory values. Predictors included in the most expansive model 3 were: SQ ‘no’ (ref: ‘yes’; HR 3.43, 95% CI 2.57-4.58), age per 10 years (HR 1.07, 95% CI 0.97-1.18), primary tumor-site (ref: prostate, breast, or thyroid; HR 1.35, 95% CI 1.01-1.82), visceral metastases (HR 1.32, 95% CI 1.05-1.65), brain metastases (HR 1.54, 95% CI 1.07-2.22), WHO performance status 1 (ref: 0; HR 1.03, 95% CI 0.76-1.41), WHO performance status 2+ (ref: 0; HR 1.50, 95% CI 1.04-2.15), any weight loss (ref: none; HR 1.09, 95% CI 0.86-1.38), pain score (HR 1.03, 95% CI 0.98-1.09); dyspnea grade 1 (ref: 0; HR 1.20, 95% CI 0.94-1.54), dyspnea grade 2+ (ref: 0; HR 1.33, 95% CI 0.93-1.91), C-reactive protein (HR 1.15, 95% CI 1.04-1.27), and serum albumin (HR 0.97, 95% CI 0.95-1.00). The pooled c-statistic at internal-external validation was 0.69 for model 1, 0.76 for model 2, and 0.78 for model 3. Conclusions: A model that combines the SQ with easily available clinical characteristics (with or without laboratory values) is more accurate in predicting 1-year mortality in patients with advanced cancer than the SQ alone.
US Narrowly Preserves Measles Elimination Status
Authors: Bridget Kuehn
Journal: JAMA (2019)

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Selective Dependency of MLL-Rearranged Leukemia on Immunoproteasome Function
Authors: Nuria Tubío Santamaría, Jonas Tönsing, Tina M. Schnoeder, Ulrike Seifert, Clemens Cammann, Juliane Mohr, Aniruddha J. Deshpande, Joanna Kirkpatrick, Alessandro Ori, Florian Perner, Florian H. Heidel
Journal: Blood (2019)