tbuckley/cabot-search huggingface dataset:
Translational analysis of esophageal adenocarcinoma (EAC) patients treated with oxaliplatin and capecitabine (Xelox) +/- the dual ErbB inhibitor AZD8931 in the DEBIOC study.
Authors: Anita Lavery, Leanne Stevenson, Damian McManus, Gemma E. Logan, Steven M. Walker, Gera L. Jellema, Sandra Van Schaeybroeck, Pradeep Singh Virdee, Leena Elhussein, Julie Turbitt, Diane Colinson, Zofia Miedzybrodzka, Russell D. Petty, Paul D. Harkin, Richard D. Kennedy, Martin McKinlay Eatock, Mark R. Middleton, Anne L. Thomas, Richard C. Turkington
Journal: Journal of Clinical Oncology (2020)

4539 Background: The Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC) trial reported an acceptable safety profile for neoadjuvant Xelox +/- AZD8931 but limited efficacy. We utilized EAC patient samples from DEBIOC to evaluate the impact of neoadjuvant Xelox +/-AZD8931 on biological pathways using a unique software driven solution. Methods: 24 pre-treatment FFPE EAC biopsies and 17 matched surgical resection specimens were transcriptionally profiled using the Almac Diagnostics Xcel Array. Gene expression data was analyzed using the Almac clara T total mRNA report V3.0.0, reporting on 92 gene expression signatures and 7337 single genes associated with 10 key biologies. Paired Wilcoxon tests (5% significance level) were used to evaluate changes in clara T scores pre- and post-treatment. EGFR and Her2 expression were assessed by IHC and FISH. Results: 15 patients received Xelox+AZD8931 and 9 Xelox alone. Hierarchical clustering of biopsies identified 4 major clusters: Inflammation active, Genomic Instability active, EGFR &amp; MAPK active, and EMT &amp; Angiogenesis active. Comparison of signature scores pre- and post- neoadjuvant treatment demonstrated a significant reduction in scores relating to DNA damage repair (DDR) deficiency (Almac DNA Damage assay, p&lt; 0.0001; BRCAness Profile, p= 0.0025; HRD Gene Signature, p&lt; 0.0001; BRCA1ness Signature, p= 0.0004) and a significant increase in angiogenesis signatures (Almac Angiogenesis Assay, p= 0.0002; Angio Predictive G model, p= 0.0228; Angiogenesis Signature A, p= 0.0034) and EMT signatures (EMT Signature, p= 0.0031, EMT Enrichment Score, p= 0.0013, Pan-Can EMT Signature B, p= 0.0001). Comparing pre- and post-treatment signature scores in patients treated with Xelox +/-AZD8931 revealed a significant reduction in EGFR Sensitivity Signature ( p= 0.0088), ERBB2-specific Gene Expression Signature ( p= 0.0127) and Hallmark PI3K-AKT-MTOR Signaling ( p= 0.0195) in those treated with Xelox + AZD8931 in keeping with the mechanism of action of AZD8931. Downregulation of AKT signaling was confirmed in AZD8931 treated and resistant cell lines. Conclusions: We report the use of a novel software tool to apply 92 gene expression signatures to EAC biopsy and resection specimens from the DEBIOC trial to provide insight into mechanisms of action. Neoadjuvant treatment was associated with a reduction in DDR deficiency and an increase in angiogenesis and EMT signatures whilst a reduction in EGFR, Her2 and AKT pathways was noted with AZD8931 treatment.
Exergaming–a physical activity intervention to benefit children with ADHD? (PhD Academy Award)
Authors: Valentin Benzing
Journal: British Journal of Sports Medicine (2020)

I investigated whether exergaming benefits executive functions, motor abilities and symptoms in children with attention-deficit hyperactivity disorder (ADHD).

ADHD is one of the most common neurodevelopmental conditions in childhood. Its symptoms include inattention, hyperactivity and impulsivity, all of which are associated with decreased executive function performance. Executive functions are higher order cognitive functions that are one of the most important predictors of academic achievement.

In school children, physical activity can benefit executive functions, and consequently academic achievement. Children with ADHD, however, are less physically active. They spend more time playing sedentary video games, and frequently drop out of traditional sports. This inactivity contributes to the frequently reported deficits in motor abilities.

I contended that innovative physical activity interventions to improve executive functions, motor abilities and symptoms were needed. Exergaming (ie, active video gaming) might serve as a home-based intervention …
Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds
Authors: Susan Mayor
Journal: BMJ (2020)

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Abstract 11591: Health-related Quality of Life in Patients With Adult Congenital Heart Disease - A Nation-wide Cross-sectional Questionnaire Survey -
Authors: Ryo Konno, Shunsuke Tatebe, Yasuhiko Sakata, Koichiro Sugimura, Kimio Satoh, Takashi Shiroto, Satoshi Miyata, Osamu Adachi, Masato Kimura, Yoshiko Mizuno, Junko Enomoto, Shigeru Tateno, Hiromichi Nakajima, Kotaro Oyama, Yoshikatsu Saiki, Hiroaki Shimokawa
Journal: Circulation (2019)

Background: With the progress of surgical treatment, the number of patients with adult congenital heart disease (ACHD) has been increasing worldwide. However, epidemiological evidence showed that t...
Abstract 14287: Predicting Disposition Decision, Mortality, and Readmission for Acute Heart Failure Patients in the Emergency Department Using Vital Sign, Laboratory, Echocardiographic, and Other Clinical Data
Authors: Claire Y Zhao, Minnan Xu-Wilson, Sandeep R Gangireddy, Steven Horng
Journal: Circulation (2018)

Introduction: The emergency department (ED) is often the first point of contact for Acute Heart Failure (AHF) patients where time-critical decisions are made with often limited information. Automat...
Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility ― Four U.S. Metropolitan Areas, February 26–April 1, 2020
Authors: Arielle Lasry, Daniel Kidder, Marisa Hast, Jason Poovey, Gregory Sunshine, Kathryn Winglee, Nicole Zviedrite, Faruque Ahmed, Kathleen A. Ethier, Catherine Clodfelter, Mara Howard-Williams, Rachel Hulkower, Gi Jeong, Lisa Landsman, Russell McCord, Amanda Moreland, Julia Shelburne, Alexander Billioux, Julie Hand, Joseph Kanter, Andrew Smith, Theresa Sokol, Jeffrey S. Duchin, Meaghan S. Fagalde, Sargis Pogosjans, Robert Brown, Sandra Huang, Nicholas Moss, Erica Pan, Munira Shemsu, Emily Yette, Carly Bock, Rachel Curtis-Robles, Cassius Lockett, Scott Morrow, Catherine Sallenave, Lisa Santora, Matthew Willis
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

During February 26–April 1, 2020, community mobility (a proxy measure for social distancing) in the metropolitan areas of San Francisco, Seattle, New Orleans, and New York City declined, decreasing ..
The Effects of Mercaptopurine on Pulmonary Vascular Resistance and BMPR2 Expression in Pulmonary Arterial Hypertension
Authors: Liza Botros, Robert Szulcek, Samara M. A. Jansen, Kondababu Kurakula, Marie-José T. H. Goumans, André B. P. van Kuilenburg, Anton Vonk Noordegraaf, Frances S. de Man, Jurjan Aman, Harm Jan Bogaard
Journal: American Journal of Respiratory and Critical Care Medicine (2020)
Outcomes and Mortality of Grade 1 Ascites and Recurrent Ascites in Patients With Cirrhosis
Authors: Marta Tonon, Salvatore Piano, Carmine G. Gambino, Antonietta Romano, Chiara Pilutti, Simone Incicco, Alessandra Brocca, Antonietta Sticca, Massimo Bolognesi, Paolo Angeli
Journal: Clinical Gastroenterology and Hepatology (2020)
Trends in prevalence of comorbidities in heart failure clinical trials
Authors: Muhammad Shahzeb Khan, Ayman Samman Tahhan, Muthiah Vaduganathan, Stephen J. Greene, Alaaeddin Alrohaibani, Stefan D. Anker, Orly Vardeny, Gregg C. Fonarow, Javed Butler
Journal: European Journal of Heart Failure (2020)
Metacarpal bone mineral density by radiographic absorptiometry predicts fracture risk in patients undergoing maintenance hemodialysis
Authors: Yosuke Nakagawa, Hirotaka Komaba, Naoto Hamano, Takehiko Wada, Miho Hida, Takao Suga, Takatoshi Kakuta, Masafumi Fukagawa
Journal: Kidney International (2020)
Combined deletion of <i>Bap1</i>, <i>Nf2</i>, and <i>Cdkn2ab</i> causes rapid onset of malignant mesothelioma in mice
Authors: Jitendra Badhai, Gaurav Kumar Pandey, Ji-Ying Song, Oscar Krijgsman, Rajith Bhaskaran, Gayathri Chandrasekaran, Min-chul Kwon, Lorenzo Bombardelli, Kim Monkhorst, Cristoforo Grasso, John Zevenhoven, Jan van der Vliet, Miranda Cozijnsen, Paul Krimpenfort, Daniel Peeper, Maarten van Lohuizen, Anton Berns
Journal: The Journal of Experimental Medicine (2020)

We have generated mouse models of malignant mesothelioma (MM) based upon disruption of the Bap1, Nf2, and Cdkn2ab tumor suppressor loci in various combinations as also frequently observed in human MM. Inactivation of all three loci in the mesothelial lining of the thoracic cavity leads to a highly aggressive MM that recapitulates the histological features and gene expression profile observed in human patients. The tumors also show a similar inflammatory phenotype. Bap1 deletion alone does not cause MM but dramatically accelerates MM development when combined with Nf2 and Cdkn2ab (hereafter BNC) disruption. The accelerated tumor development is accompanied by increased Polycomb repression and EZH2-mediated redistribution of H3K27me3 toward promoter sites with concomitant activation of PI3K and MAPK pathways. Treatment of BNC tumor–bearing mice with cisplatin and pemetrexed, the current frontline treatment, prolongs survival. This makes the autochthonous mouse model described here very well suited to explore the pathogenesis of MM and validate new treatment regimens for MM, including immunotherapy.
Effects of Telephone and Short Message Service Support on Infant Feeding Practices, “Tummy Time,” and Screen Time at 6 and 12 Months of Child Age
Authors: Li Ming Wen, Chris Rissel, Huilan Xu, Sarah Taki, Limin Buchanan, Karen Bedford, Philayrath Phongsavan, Louise A. Baur
Journal: JAMA Pediatrics (2020)

There is limited information as to whether telephone or short message service (SMS) support is effective in improving infant feeding practices and tummy time and reducing screen time.
National Evaluation of Racial/Ethnic Discrimination in US Surgical Residency Programs
Authors: Tarik K. Yuce, Patricia L. Turner, Charity Glass, David B. Hoyt, Thomas Nasca, Karl Y. Bilimoria, Yue-Yung Hu
Journal: JAMA Surgery (2020)

surgical training, discrimination is common 2 but has not been comprehensively evaluated among racial/ethnic minorities.The objectives of this study were to (1) determine the national prevalence and sources of discrimination based on race/ ethnicity in US general surgery programs, (2) identify factors associated with discrimination, and (3) assess its association with resident wellness.
Covid-19: Black people and other minorities are hardest hit in US
Authors: Owen Dyer
Journal: BMJ (2020)

In the United States, black people are being admitted to hospital and dying in disproportionate numbers from the covid-19 pandemic. The Trump administration acknowledged the issue after a Washington Post analysis found that black majority counties had three times the coronavirus infection rate and almost six times the death rate of white majority counties.1

The excess deaths among African-Americans “are shining a very bright light on some of the real weaknesses and foibles in our society,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, adding that at least part of the problem was due to a higher burden of underlying medical conditions such as diabetes, hypertension, obesity, and asthma among African-Americans. “There’s nothing we can do about it right now except to try and give them the best possible care to avoid complications,” he said.

The true scale of the disparity is unknown because so few states and counties include racial data in their …
Resequencing of the Vascular Endothelial Growth Factor Promoter Reveals Haplotype Structure and Functional Diversity.
Authors: B. Hancock, M. Radovich, N. Kassem, D. Mi, T. Skaar, B. Schneider
Journal: Cancer Research (2009)

Abstract Our group has previously reported that SNPs in the VEGF promoter are strongly associated with efficacy and toxicity to the anti-VEGF antibody bevacizumab in metastatic breast cancer. In order to better understand the biologic mechanism for our previously reported biomarkers, we embarked on a comprehensive evaluation of the genetic variation in the VEGF promoter coupled with a study of its intrinsic function. By resequencing 96 DNA samples (48 Caucasians, 48 African-Americans) for the VEGF promoter, we elucidated its complete haplotype structure and identified SNPs that were not previously reported in prior resequencing efforts. SNPs that were identified included twenty previously reported SNPs/insertions/deletions, one novel SNP, and one novel deletion. Among these variants, we identified five SNPs (VEGF-3818G/T, -2305G/T, -1210C/A, -1154G/A, &amp; -7C/T) that tag six haplotypes capturing 74% of the genetic variation of the VEGF promoter. Subsequently, we cloned the six major haplotypes into reporter constructs in order to determine the effect of genetic variation on function. The reporter assays were performed in 5 breast cancer cell lines representing all ER and HER-2 statuses along with an inflammatory breast cancer cell line. We demonstrate that there is significant variation in promoter-induced expression among the haplotypes. More importantly, we show that the haplotypes containing the SNPs previously reported to be associated with increased survival with the use of bevacizumab are high-expressing haplotypes, thus lending putative functional evidence to the prior clinical finding. Further, we also report the presence of a low-expressing haplotype predominantly in African-Americans. Altogether, these results set the foundation for future studies elucidating the role of VEGF genetic variation with response to anti-angiogenic therapy and associations with angiogenesis-related diseases. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2122.
Assessment of an Unplanned Extubation Bundle to Reduce Unplanned Extubations in Critically Ill Neonates, Infants, and Children
Authors: Darren Klugman, Kristin Melton, Patrick O’Neal Maynord, Aaron Dawson, Gowri Madhavan, Vicki Lee Montgomery, Mary Nock, Anthony Lee, Anne Lyren
Journal: JAMA Pediatrics (2020)

Unplanned extubations (UEs) in children contribute to significant morbidity and mortality, with an arbitrary benchmark target of less than 1 UE per 100 ventilator days. However, there have been no multicenter initiatives to reduce these events.To determine if a multicenter quality improvement initiative targeting all intubated neonatal and pediatric patients is associated with a reduction in UEs and morbidity associated with UE events.This multicenter quality improvement initiative enrolled patients from pediatric, neonatal, and cardiac intensive care units (ICUs) in 43 participating children's hospitals from March 2016 to December 2018. All patients with an endotracheal tube requiring mechanical ventilation were included in the study.Participating hospitals implemented a quality improvement bundle to reduce UEs, which included standardized anatomic reference points and securement methods, protocol for high-risk situations, and multidisciplinary apparent cause analyses.The main outcome measures for this study included bundle compliance with each factor tested and UE rates on the center level and on the cohort level.Among the 43 children's hospitals, the quality improvement initiative was associated with an aggregate 24.1% reduction in UE events, from a baseline rate of 1.135 UEs per 100 ventilator days to 0.862 UEs per 100 ventilator days. Across ICU settings studied, the pediatric ICU and neonatal ICU demonstrated centerline shifts, with an absolute reduction in events of 20.6% (from a baseline rate of 0.729 UEs per 100 ventilator days to 0.579 UEs per 100 ventilator days) and 17.6% (from a baseline rate of 1.555 UEs per 100 ventilator days to 1.282 UEs per 100 ventilator days), respectively. Most UEs required reintubation within 1 hour (mean of 120 of 206 events per month [58.3%]), followed by UEs that did not require reintubation (mean of 78 of 206 events per month [37.9%]) and UEs that resulted in cardiovascular collapse (mean of 8 of 206 events per month [3.9%]). Cardiovascular collapse events represented the most significant consequence of UE studied, and the collaborative reduced these UE events by 36.6%, from a study baseline rate of 0.041 UEs per 100 ventilator days to 0.026 UEs per 100 ventilator days.This multicenter quality improvement initiative was associated with a reduction in UEs across different pediatric populations in diverse settings. A significant reduction in event rate and rate of harm (cardiovascular collapse) was observed, which was sustained over the time course of the intervention. This quality improvement process and UE bundle may be considered standard of care for pediatric hospitals in the future.
Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China
Authors: Wen-hua Liang, Wei-jie Guan, Cai-chen Li, Yi-min Li, Heng-rui Liang, Yi Zhao, Xiao-qing Liu, Ling Sang, Ru-chong Chen, Chun-li Tang, Tao Wang, Wei Wang, Qi-hua He, Zi-sheng Chen, Sook-San Wong, Mark Zanin, Jun Liu, Xin Xu, Jun Huang, Jian-fu Li, Li-min Ou, Bo Cheng, Shan Xiong, Zhan-hong Xie, Zheng-yi Ni, Yu Hu, Lei Liu, Hong Shan, Chun-liang Lei, Yi-xiang Peng, Li Wei, Yong Liu, Ya-hua Hu, Peng Peng, Jian-ming Wang, Ji-yang Liu, Zhong Chen, Gang Li, Zhi-jian Zheng, Shao-qin Qiu, Jie Luo, Chang-jiang Ye, Shao-yong Zhu, Lin-ling Cheng, Feng Ye, Shi-yue Li, Jin-ping Zheng, Nuo-fu Zhang, Nan-shan Zhong, Jian-xing He
Journal: European Respiratory Journal (2020)

During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences.
Covid-19: Death rate in England and Wales reaches record high because of covid-19
Authors: Jacqui Wise
Journal: BMJ (2020)

Covid-19: Death rate in England and Wales reaches record high because of covid-19Jacqui Wise LondonThe death toll in England and Wales is at its highest since weekly statistics began 15 years ago, with 16 387 deaths registered in the week ending 3 April-37% more than expected.This is 5246 deaths more (14%) than the previous week and 6082 more (59%) than the five year average for this week in the year, the Office for National Statistics (ONS) has reported. 1 The ONS said that 3475 of these registered deaths mentioned "novel coronavirus (covid-19)," which was 21.2% of all deaths.In London, nearly half (46.6%) of deaths in the week ending 3 April involved covid-19.The West Midlands also had a high proportion of covid-19 deaths, accounting for 22.1% of deaths registered in the region.
Abstract 15273: Genetic Variant Burden and Outcomes in Pediatric Cardiomyopathy
Authors: Danielle Burstein, James W Gaynor, Heather Griffis, Alyssa Ritter, Matthew J O’Connor, Joseph W Rossano, Kimberly Y Lin, Rebecca C Ahrens-Nicklas
Journal: Circulation (2019)

Introduction: Previous research in pediatric cardiomyopathy (CM) focusing on causative pathogenic variants has not demonstrated consistent genotype-outcome findings. Variants of unknown significant...
PRMT5-dependent transcriptional repression of c-Myc target genes promotes gastric cancer progression
Authors: Ming Liu, Bing Yao, Tao Gui, Chan Guo, Xiaobin Wu, Jiahuang Li, Lingling Ma, Yexuan Deng, Peipei Xu, Ying Wang, Dongjun Yang, Qixiang Li, Xiangwei Zeng, Xinyu Li, Ruifeng Hu, Jingru Ge, Zenong Yu, Yugen Chen, Bing Chen, Junyi Ju, Quan Zhao
Journal: Theranostics (2020)

The proto-oncogene c-Myc regulates multiple biological processes mainly through selectively activating gene expression. However, the mechanisms underlying c-Myc-mediated gene repression in the context of cancer remain less clear. This study aimed to clarify the role of PRMT5 in the transcriptional repression of c-Myc target genes in gastric cancer. Methods: Immunohistochemistry was used to evaluate the expression of PRMT5, c-Myc and target genes in gastric cancer patients. PRMT5 and c-Myc interaction was assessed by immunofluorescence, co-immunoprecipitation and GST pull-down assays. Bioinformatics analysis, immunoblotting, real-time PCR, chromatin immunoprecipitation, and rescue experiments were used to evaluate the mechanism. Results: We found that c-Myc directly interacts with protein arginine methyltransferase 5 (PRMT5) to transcriptionally repress the expression of a cohort of genes, including PTEN, CDKN2C (p18INK4C), CDKN1A (p21CIP1/WAF1), CDKN1C (p57KIP2) and p63, to promote gastric cancer cell growth. Specifically, we found that PRMT5 was required to promote gastric cancer cell growth in vitro and in vivo, and for transcriptional repression of this cohort of genes, which was dependent on its methyltransferase activity. Consistently, the promoters of this gene cohort were enriched for both PRMT5-mediated symmetric di-methylation of histone H4 on Arg 3 (H4R3me2s) and c-Myc, and c-Myc depletion also upregulated their expression. H4R3me2s also colocalized with the c-Myc-binding E-box motif (CANNTG) on these genes. We show that PRMT5 directly binds to c-Myc, and this binding is required for transcriptional repression of the target genes. Both c-Myc and PRMT5 expression levels were upregulated in primary human gastric cancer tissues, and their expression levels inversely correlated with clinical outcomes. Conclusions: Taken together, our study reveals a novel mechanism by which PRMT5-dependent transcriptional repression of c-Myc target genes is required for gastric cancer progression, and provides a potential new strategy for therapeutic targeting of gastric cancer.