tbuckley/cabot-search huggingface dataset:
The Children’s Oncology Group and QuadW Foundation osteosarcoma banking experience.
Authors: Jason Michael Glover, Richard Greg Gorlick, Chand Khanna, Donald A. Barkauskas
Journal: Journal of Clinical Oncology (2013)

10053 Background: Survival rates of osteosarcoma patients have remained stagnant over the last twenty years. Predictive biomarkers of response to treatment and likelihood of recurrence are yet to be developed. In order to develop new therapeutics and better risk-stratified regimens, a greater understanding of osteosarcoma biology is needed. The Children’s Oncology Group (COG) addressed this need by banking more than 10,000 tumor and tissue samples from over 1500 patients with osteosarcoma, but many samples lacked clinically relevant data. Methods: 1105 eligible patients enrolled on the COG osteosarcoma biology study P9851. Of those, 510 patients were not enrolled on a concurrent therapeutic trial, which limited the clinical annotation of those samples. 589 patients have enrolled on the successor study AOST06B1. The lack of clinical annotation of the P9851 specimens limited their value, and the lack of statistical support slowed the analysis of several biology studies. The QuadW Foundation, CureSearch, and the COG formed the Childhood Sarcoma Biostatistics and Annotation Office (CSBAO) in 2008 to link clinically annotated patient data to the samples and to provide statistical support. Results: In 2008, only 5.3% of samples from the 510 P9851 patients not enrolled on a therapeutic study had full clinical annotation. The efforts of the CSBAO have linked clinical annotation to 90.8% of those specimens and provided statistical analyses. As a result, 18 biology studies in osteosarcoma are completed, with 11 published in peer-reviewed journals. Samples were provided to the TARGET program (for gene expression arrays, copy number analysis, and sequencing data); the resulting data will be available to the scientific community for in silico studies. Conclusions: The efforts of the CSBAO have led to a substantial increase in the value of a large osteosarcoma biospecimen repository by clinically annotating the specimens and providing statistical resources for analyses of planned and completed studies. These samples with annotated patient information are available by request to the research community for basic and translational science projects to improve the biological understanding of, and the treatment of patients with osteosarcoma. Clinical trial information: NCT00899275.
Effects of serelaxin in patients admitted for acute heart failure: a meta‐analysis
Authors: John R. Teerlink, Beth A. Davison, Gad Cotter, Aldo P. Maggioni, Naoki Sato, Ovidiu Chioncel, Georg Ertl, G. Michael Felker, Gerasimos Filippatos, Barry H. Greenberg, Peter S. Pang, Piotr Ponikowski, Christopher Edwards, Stefanie Senger, Sam L. Teichman, Olav Wendelboe Nielsen, Adriaan A. Voors, Marco Metra
Journal: European Journal of Heart Failure (2019)
Clinical validation of a new commercial highly sensitive <i>KIT</i> D816V mutation analysis in mastocytosis
Authors: Thomas Kristensen, Hanne Vestergaard, Carsten Bindslev‐Jensen, Michael Boe Møller, Sigurd Broesby‐Olsen
Journal: Allergy (2019)

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Quality and Safety in Healthcare, Part LVIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2019)

Abstract In the past, many articles focused on one or several interventions to prevent physician burnout, but increasingly, articles now focus on comprehensive programs to not only decrease burnout, but also to promote physician happiness and wellness. These programs include measuring burnout and joy in the workplace, promoting workplace safety and wellness activities, career assistance, optimizing compensation, increasing the respect shown to individuals and their teams, and coordination of the goals between the individual, the teams, and the organization.
CD93 is expressed on chronic myeloid leukemia stem cells and identifies a quiescent population which persists after tyrosine kinase inhibitor therapy
Authors: Ross Kinstrie, Gillian A. Horne, Heather Morrison, David Irvine, Chinmay Munje, Eduardo Gómez Castañeda, Hothri A. Moka, Karen Dunn, Jennifer E. Cassels, Narissa Parry, Cassie J. Clarke, Mary T. Scott, Richard E. Clark, Tessa L. Holyoake, Helen Wheadon, Mhairi Copland
Journal: Leukemia (2020)

The introduction of BCR-ABL tyrosine kinase inhibitors has revolutionized the treatment of chronic myeloid leukemia (CML). A major clinical aim remains the identification and elimination of low-level disease persistence, termed "minimal residual disease". The phenomenon of disease persistence suggests that despite targeted therapeutic approaches, BCR-ABL-independent mechanisms exist which sustain the survival of leukemic stem cells (LSCs). Although other markers of a primitive CML LSC population have been identified in the preclinical setting, only CD26 appears to offer clinical utility. Here we demonstrate consistent and selective expression of CD93 on a lin-CD34+CD38-CD90+ CML LSC population and show in vitro and in vivo data to suggest increased stem cell characteristics, as well as robust engraftment in patient-derived xenograft models in comparison with a CD93- CML stem/progenitor cell population, which fails to engraft. Through bulk and single-cell analyses of selected stem cell and cell survival-specific genes, we confirmed the quiescent character and demonstrate their persistence in a population of CML patient samples who demonstrate molecular relapse on TKI withdrawal. Taken together, our results identify that CD93 is consistently and selectively expressed on a lin-CD34+CD38-CD90+ CML LSC population with stem cell characteristics and may be an important indicator in determining poor TKI responders.
CIRCexplorer3: A CLEAR Pipeline for Direct Comparison of Circular and Linear RNA Expression
Authors: Xu-Kai Ma, Meng-Ran Wang, Chu-Xiao Liu, Rui Dong, Gordon G. Carmichael, Ling-Ling Chen, Li Yang
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Sequences of circular RNAs (circRNAs) produced from back-splicing of exon(s) completely overlap with those from cognate linear RNAs transcribed from the same gene loci with the exception of their back-splicing junction (BSJ) sites. Therefore, examination of global circRNA expression from RNA-seq datasets generally relies on the detection of RNA-seq fragments spanning BSJ sites, which is different from the quantification of linear RNA expression by normalized RNA-seq fragments mapped to whole gene bodies. Thus, direct comparison of circular and linear RNA expression from the same gene loci in a genome-wide manner has remained challenging. Here, we update the previously-reported CIRCexplorer pipeline to version 3 for circular and linear RNA expression analysis from ribosomal-RNA depleted RNA-seq (CIRCexplorer3-CLEAR). A new quantitation parameter, fragments per billion mapped bases (FPB), is applied to evaluate circular and linear RNA expression individually by fragments mapped to circRNA-specific BSJ sites or to linear RNA-specific splicing junction (SJ) sites. Comparison of circular and linear RNA expression levels is directly achieved by dividing FPBcirc by FPBlinear to generate a CIRCscore, which indicates the relative circRNA expression level using linear RNA expression level as the background. Highly-expressed circRNAs with low cognate linear RNA expression background can be readily identified by CIRCexplorer3-CLEAR for further investigation. CIRCexplorer3-CLEAR is publically available at https://github.com/YangLab/CLEAR.
Abstract 14868: Loss of C-kit Exacerbates Atherosclerosis and Increases Ly-6chi Monocytes Despite Defective Medullary Myelopoiesis
Authors: Lei Song, Juan Camilo Duque Duque, Angela Pena, Keith A Webster, Si M Pham, Roberto Vazquez-Padron
Journal: Circulation (2013)

Introduction: High numbers of pro-inflammatory monocytes have been associated with atherosclerosis in humans and hypercholesterolemic animals. This study assesses how the c-Kit modifies atheroscler...
Protests in India: doctors condemn police violence and restrictions on hospital access
Authors: Anoo Bhuyan
Journal: BMJ (2020)

Doctors in India have condemned police violence towards people protesting against the government’s changes to citizenship laws. The protests have involved thousands of people on the streets of major cities since mid-December.

Twenty five people have died and scores have been injured.

The Indian Medical Association has called for hospitals to remain safe zones after an incident on 19 December in which police allegedly fired at protesters in the southern state of Karnataka. Two people died from bullet injuries and were taken to hospital, after which police entered the hospital and used tear gas to try to find protesters. Reports also alleged that police broke down doors and assaulted hospital staff. Some of the violence …
Three-Dimensional Histologic, Immunohistochemical, and Multiplex Immunofluorescence Analyses of Dynamic Vessel Co-Option of Spread Through Air Spaces in Lung Adenocarcinoma
Authors: Yukako Yagi, Rania G. Aly, Kazuhiro Tabata, Afsar Barlas, Natasha Rekhtman, Takashi Eguchi, Joeseph Montecalvo, Meera Hameed, Katia Manova-Todorova, Prasad S. Adusumilli, William D. Travis
Journal: Journal of Thoracic Oncology (2019)
Interactive effects of vitamin A, and folate intakes and ATM polymorphisms for breast cancer risk
Authors: Sang-Ah Lee, Kyoung-Mu Lee, Hye-Won Chung, Keun-Young Yoo, Dong-Young Noh, Sei-Hyun Ahn, Daehee Kang
Journal: Cancer Research (2004)

4496  To evaluate the interactive effect of vitamins intake and ATM genetic polymorphisms on the development of breast cancer, a hospital-based case-control study was conducted in Korea. Histologically confirmed breast cancer cases (n=836) and controls (n=826) with no present or previous history of cancer were recruited from several teaching hospitals in Seoul during 2001-2003. Information on demographic characteristics and other information were collected by interviewed questionnaire. Dietary information was collected by trained interviewer with semi-quantitative food frequency questionnaire, which was validated by comparing the results with those obtained from three day 24-hour recall method. Vitamin intakes, estimated from dietary information, included vitamin A, retinol, beta carotene, vitamin B1, vitaminB2, vitamin B6, niacin, vitamin C, vitamin E, and folate. Genetic polymorphisms of ATM (-5144A>T (rs228589), 3393T>G (rs4585), IVS21+1049T>C (rs664677), IVS33-55T>C (rs664982), IVS34+60G>A (rs664143)) were determined by 5’-nuclease assay (TaqMan). To evaluate the interactive effects with dietary factors, combined genotypes of the five polymorphisms were divided into two groups (-5144 AA, 3393 TT, IVS21+1049 TT, IVS33-55 TT, and IVS34+60 GG; the others). Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression model adjusting for age, education, family history of breast cancer, lifetime estrogen exposure, alcohol consumption, smoking, and energy intake. The vitamin A (
Adhesion-related readmissions after open and laparoscopic surgery: a retrospective cohort study (SCAR update)
Authors: Pepijn Krielen, Martijn W J Stommel, Pille Pargmae, Nicole D Bouvy, Erica A Bakkum, Harold Ellis, Michael C Parker, Ewen A Griffiths, Harry van Goor, Richard P G ten Broek
Journal: The Lancet (2020)
Patient Views on Religious Institutional Health Care
Authors: Maryam Guiahi, Patricia E. Helbin, Stephanie B. Teal, Debra Stulberg, Jeanelle Sheeder
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Federal protections allow health facilities to limit options to patients on the basis of religious values. Little is known about whether US adults consider religious affiliation when selecting facilities and whether they agree with such limitations. <h3>Objective</h3> To understand patient views on religious institutional care. <h3>Design, Setting, and Participants</h3> This is a population-based, cross-sectional survey study of US adults recruited from the probability-based AmeriSpeak Omnibus panel available from NORC (formerly the National Opinion Research Center) at the University of Chicago. Surveys were administered via internet or telephone during a 3-day fielding period in November 2017. Data analysis was performed from January 2018 to October 2019. <h3>Exposures</h3> Participant characteristics, including religiosity measures. <h3>Main Outcomes and Measures</h3> Whether patients consider religious affiliation when selecting a health care facility and their views on whether an institution's religious values should take precedence over their health choices. Responses were compared by gender. When gender differences existed, regression models were performed, and thematic content analysis was applied to open-ended responses. <h3>Results</h3> There were 1446 participants (745 [51.5%] male; mean [SD] age, 46 [17] years), for a survey completion rate of 24.5% and weighted cumulative response weight of 7.3%. Most respondents (62.6%) were white, and the most common religion was Protestant (28.2%). When specifically asked, only 6.4% reported that they considered religious affiliation when selecting a health care facility; most participants (71.3%) reported when selecting a health care facility that they did not care whether it is religiously affiliated, 13.4% preferred a religious affiliation, and 15.3% preferred no religious affiliation. There were no gender differences. Most participants (71.4%) believed that their health choices should take priority over an institution's religious affiliation in services offered, and this was more common for women than for men (74.9% vs 68.1%; difference, 6.8%; 95% CI, 5.6%-8.2%;<i>P</i> = .005), who more commonly endorsed concerns for personal choice and autonomy over one's own body. <h3>Conclusions and Relevance</h3> This study suggests that most patients value their personal choices, yet do not consider an institution's religious affiliation when choosing their source of health care. Women placed greater emphasis on their autonomy in comparison with an institution's right to invoke religious restrictions to care. Given the growth in ownership of health care facilities by religious entities in the United States and increasing attention to conscientious objections, these findings point to a need for advocacy and legislation that effectively balances protections for religious institutions with protections for patients.
Towards a New Generation of Trait-Flexible Vegetation Models
Authors: Fabio Berzaghi, Ian J. Wright, Koen Kramer, Sylvie Oddou-Muratorio, Friedrich J. Bohn, Christopher P.O. Reyer, Santiago Sabaté, Tanja G.M. Sanders, Florian Hartig
Journal: Trends in Ecology & Evolution (2019)
Long circulating photoactivable nanomicelles with tumor localized activation and ROS triggered self-accelerating drug release for enhanced locoregional chemo-photodynamic therapy
Authors: Saji Uthaman, Shameer Pillarisetti, Ansuja Pulickal Mathew, Yugyeong Kim, Woo Kyun Bae, Kang Moo Huh, In-Kyu Park
Journal: Biomaterials (2019)
An LTR Retrotransposon-Derived Long Noncoding RNA lncMER52A Promotes Hepatocellular Carcinoma Progression by Binding p120-Catenin
Authors: Yangjun Wu, Yiming Zhao, Lin Huan, Jingjing Zhao, Yuqiang Zhou, Linguo Xu, Zhixiang Hu, Yizhe Liu, Zhiao Chen, Lu Wang, Shenglin Huang, Xianghuo He, Linhui Liang
Journal: Cancer Research (2019)

Long terminal repeat (LTR) retrotransposons are a major class of transposable elements, accounting for 8.67% of the human genome. LTRs can serve as regulatory sequences and drive transcription of tissue or cancer-specific transcripts. However, the role of these LTR-activated transcripts, especially long non-coding RNAs (lncRNA), in cancer development remains largely unexplored. Here, we identified a novel lncRNA derived from MER52A retrotransposons (lncMER52A) that was exclusively expressed in hepatocellular carcinoma (HCC). HCC patients with higher lncMER52A had advanced TNM stage, less differentiated tumors, and shorter overall survival. LncMER52A promoted invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, lncMER52A stabilized p120-catenin and triggered the activation of Rho GTPase downstream of p120-catenin. Furthermore, we found that chromatin accessibility was crucial for the expression of lncMER52A. In addition, YY1 transcription factor bound to the cryptic MER52A LTR promoter and drove lncMER52A transcription in HCC. In conclusion, we identified an LTR-activated lncMER52A, which promoted the progression of HCC cells via stabilizing p120-catenin and activating p120-ctn/Rac1/Cdc42 axis. LncMER52A could serve as biomarker and therapeutic target for patients with HCC. SIGNIFICANCE: A novel long noncoding RNA lncMER52 modulates cell migration and invasion via posttranslational control of p120-catenin protein stability. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/5/976/F1.large.jpg.
Dysphagia in a young female patient: it’s not always that simple
Authors: Joana Carvão, Armando Peixoto, Elisabete Rios, Guilherme Macedo
Journal: Gut (2019)

A 42-year-old female patient was referred to our gastroenterology department with a 4-month history of weekly symptoms of dysphagia for solids and liquids. The patient also reported occasional symptoms of food impaction and heartburn. She denied nausea, vomiting, weight loss or a recent change in bowel habits. The patient was not under any medication. Medical or surgical history was unremarkable. There was no family history of gastrointestinal cancer. Physical examination was normal, and laboratory tests did not reveal anaemia or other abnormalities. She underwent an oesophagogastroduodenoscopy, and the oesophagus is shown in figure 1. Biopsies were performed in the upper and lower parts of the oesophagus and …
RADAR: differential analysis of MeRIP-seq data with a random effect model
Authors: Zijie Zhang, Qi Zhan, Mark Eckert, Allen Zhu, Agnieszka Chryplewicz, Dario F. De Jesus, Decheng Ren, Rohit N. Kulkarni, Ernst Lengyel, Chuan He, Mengjie Chen
Journal: Genome biology (2019)

Epitranscriptome profiling using MeRIP-seq is a powerful technique for in vivo functional studies of reversible RNA modifications. We develop RADAR, a comprehensive analytical tool for detecting differentially methylated loci in MeRIP-seq data. RADAR enables accurate identification of altered methylation sites by accommodating variability of pre-immunoprecipitation expression level and post-immunoprecipitation count using different strategies. In addition, it is compatible with complex study design when covariates need to be incorporated in the analysis. Through simulation and real dataset analyses, we show that RADAR leads to more accurate and reproducible differential methylation analysis results than alternatives, which is available at https://github.com/scottzijiezhang/RADAR.
Suppression of the SLC7A11/glutathione axis causes synthetic lethality in KRAS-mutant lung adenocarcinoma
Authors: Kewen Hu, Kun Li, Jing Lv, Jie Feng, Jing Chen, Haigang Wu, Feixiong Cheng, Wenhao Jiang, Jieqiong Wang, Haixiang Pei, Paul J. Chiao, Zhenyu Cai, Yihua Chen, Mingyao Liu, Xiufeng Pang
Journal: Journal of Clinical Investigation (2019)

Oncogenic KRAS is a major driver in lung adenocarcinoma (LUAD) that has yet to be therapeutically conquered. Here we report that the SLC7A11/glutathione axis displays metabolic synthetic lethality with oncogenic KRAS. Through metabolomics approaches, we found that mutationally activated KRAS strikingly increased intracellular cystine levels and glutathione biosynthesis. SLC7A11, a cystine/glutamate antiporter conferring specificity for cystine uptake, was overexpressed in patients with KRAS-mutant LUAD and showed positive association with tumor progression. Furthermore, SLC7A11 inhibition by either genetic depletion or pharmacological inhibition with sulfasalazine resulted in selective killing across a panel of KRAS-mutant cancer cells in vitro and tumor growth inhibition in vivo, suggesting the functionality and specificity of SLC7A11 as a therapeutic target. Importantly, we further identified a potent SLC7A11 inhibitor, HG106, that markedly decreased cystine uptake and intracellular glutathione biosynthesis. Furthermore, HG106 exhibited selective cytotoxicity toward KRAS-mutant cells by increasing oxidative stress- and ER stress-mediated cell apoptosis. Of note, treatment of KRAS-mutant LUAD with HG106 in several preclinical lung cancer mouse models led to marked tumor suppression and prolonged survival. Overall, our findings reveal that KRAS-mutant LUAD cells are vulnerable to SLC7A11 inhibition, offering potential therapeutic approaches for this currently incurable disease.
Erratum: A clinical trial for patients with acute myeloid leukemia or myelodysplastic syndromes not eligible for standard clinical trials
Authors: G Montalban-Bravo, X Huang, K Naqvi, E Jabbour, G Borthakur, C D DiNardo, N Pemmaraju, J Cortes, S Verstovsek, T Kadia, N Daver, W Wierda, Y Alvarado, M Konopleva, F Ravandi, Z Estrov, N Jain, A Alfonso, M Brandt, T Sneed, H C Chen, H Yang, C Bueso-Ramos, S Pierce, E Estey, Z Bohannan, H M Kantarjian, G Garcia-Manero
Journal: Leukemia (2017)
24-Month Phase I/II Clinical Trial of Bimatoprost Sustained-Release Implant (Bimatoprost SR) in Glaucoma Patients
Authors: E. Randy Craven, Thomas Walters, William C. Christie, Douglas G. Day, Richard A. Lewis, Margot L. Goodkin, Michelle Chen, Veronica Wangsadipura, Michael R. Robinson, Marina Bejanian, Tin Aung, Allen D. Beck, James D. Branch, William C. Christie, Michael Coote, Charles J. Crane, E. Randy Craven, Andrew Crichton, Douglas G. Day, Steven Day, F. Jane Durcan, Richard M. Evans, William J. Flynn, Sébastien Gagné, Damien F. Goldberg, Jack V. Greiner, Paul Jeppsen, Delan Jinapriya, C. Starck Johnson, Shimon Kurtz, Richard A. Lewis, Steven L. Mansberger, Joseph R. Martel, Shamira A. Perera, Michael H. Rotberg, Robert M. Saltzmann, Howard I. Schenker, Michael E. Tepedino, Maria Imelda R. Yap-Veloso, Harvey S. Uy, Thomas R. Walters
Journal: Drugs (2019)

The objective of this study was to evaluate the safety and intraocular pressure (IOP)-lowering effects over 24 months of biodegradable bimatoprost sustained-release implant (Bimatoprost SR) administration versus topical bimatoprost 0.03% in patients with open-angle glaucoma (OAG).This was a phase I/II, prospective, 24-month, dose-ranging, paired-eye controlled clinical trial. At baseline following washout, adult patients with OAG (N = 75) received Bimatoprost SR (6, 10, 15, or 20 µg) intracamerally in the study eye; the fellow eye received topical bimatoprost 0.03% once daily. Rescue topical IOP-lowering medication or single repeat administration with implant was permitted. The primary endpoint was IOP change from baseline. Safety measures included adverse events (AEs).At month 24, mean IOP reduction from baseline was 7.5, 7.3, 7.3, and 8.9 mmHg in eyes treated with Bimatoprost SR 6, 10, 15, and 20 µg, respectively, versus 8.2 mmHg in pooled fellow eyes; 68, 40, and 28% of pooled study eyes had not been rescued/retreated at months 6, 12, and 24, respectively. AEs in study eyes that occurred ≤ 2 days post-procedure typically were transient. After 2 days post-procedure, overall AE incidence was similar between study and fellow eyes, with some events typically associated with topical prostaglandin analogs having lower incidence in study eyes.Bimatoprost SR showed favorable efficacy and safety profiles up to 24 months, with all evaluated dose strengths demonstrating overall IOP-reducing effects comparable to those of topical bimatoprost. Targeted and sustained delivery of bimatoprost resulted in protracted IOP lowering, suggesting that Bimatoprost SR may represent a transformational new approach to glaucoma therapy. Clinicaltrials.gov identifier: NCT01157364.