A morphological and molecular study of proposed early forms of the traditional serrated adenoma

AIMS: The traditional serrated adenoma (TSA) is the least common subtype of serrated colorectal polyp. Large protuberant lesions are easily recognized, however, the origins of TSAs are not known and early forms have not been described. Some large TSAs present with a flat "shoulder" component surrounding the central protuberant component. We hypothesized that small polyps with the same histology as these "shoulder" regions may represent early TSAs. METHODS AND RESULTS: We collected 70 small (< 10mm) polyps that may represent early TSAs based on typical TSA cytology covering the luminal surface. We also identified 12 large TSAs with a "shoulder" component resembling these small polyps. The study polyps patients had a mean age of 58 years, 54% were female, had a mean 4.1mm diameter and were predominantly distal (71%). Morphologically, slit-like serration was present in 81%, ectopic crypt formations in 67% and a villous component in 47%. These histological features were similar to the 12 "shoulder" lesions. Immunohistochemical stains showed absence of β-catenin nuclear expression in 96% of the small polyps, retained expression of MLH1 in 100% and Ki-67 positivity restricted to the crypt bases and ectopic crypt formations. BRAF and KRAS mutations were identified in 47% and 31% of the polyps respectively. Compared with KRAS-mutated polyps, BRAF-mutated polyps were more likely to arise in a precursor polyp (82% vs 18%, P < 0.001) and were more likely to have slit-like serrations (100% vs 73%, P = 0.003). CONCLUSIONS: These morphological, immunohistochemical and molecular findings are similar to what has been reported in large TSAs and support the hypothesis that these polyps represent early forms of TSA. This article is protected by copyright. All rights reserved

Injury-related mortality among adolescents: findings from a teaching hospital's post mortem data

<p>Abstract</p> <p>Background</p> <p>Injuries are noted to be an important cause of death among adolescents. There is however limited data on the injury related deaths among adolescents in Ghana.</p> <p>Findings</p> <p>Using data from post-mortem records derived from the Department of Pathology of the Korle-Bu Teaching Hospital (KBTH), Accra Ghana from 2001 to 2003, the causes of injury related deaths among adolescents 10 to 19 years were analyzed by gender and age groups 10 to 14 and 15 to 19 years. There were 151 injury-related deaths constituting 17% of the autopsies performed among adolescents in the study period. The male-to-female ratio was 2.1:1. Drowning was the most common cause of death (37%) in the study population. This was followed by road traffic accidents (RTA) (33%). Over 70% of the RTA victims were pedestrians knocked downed by a vehicle. Deaths from electrocution, poisoning, burns, stab/gunshot, hanging and other miscellaneous causes (example blast injury, traumatic injury from falling debris, fall from height) made up the remaining 30% of the injury related mortality. Among males and in both age categories, drowning was the leading cause of death. In females, the highest mortality was from road traffic accidents accounting for almost half (49%) of the deaths; significantly more than that occurring in males (25%, p = .004).</p> <p>Conclusions</p> <p>Findings from Korle-Bu Teaching Hospital post-mortem data on adolescents show that drowning and road traffic accidents are the leading causes of injury-related mortality. Appropriate injury reducing interventions are needed to facilitate a decrease in these preventable deaths.</p

Copy number profiles of paired primary and metastatic colorectal cancers

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC). In this study, we compared the copy number profiles of paired primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. Paired primary and metastatic tumors from 16 patients and their adjacent normal tissue samples were analyzed using single nucleotide polymorphism arrays. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 188 genes known to be somatically altered in CRC and 24 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. The genomic differences between the tumor and paired metastases revealed an average copy number discordance of 22.0%. The pairs of tumor samples collected prior to treatment revealed significantly higher copy number differences compared to post-therapy liver metastases (P = 0.014). Loss of heterozygosity acquired in liver metastases was significantly higher in previously treated liver metastasis samples compared to treatment naive liver metastasis samples (P = 0.003). Amplification of the clinically actionable genes ERBB2, FGFR1, PIK3CA or CDK8 was observed in the metastatic tissue of 4 patients but not in the paired primary CRC. These examples highlight the intra-patient genomic discrepancies that can occur between metastases and the primary tumors from which they arose. We propose that precision medicine strategies may therefore identify different actionable targets in metastatic tissue, compared to primary tumors, due to substantial genomic differences

Plant Science Decadal Vision 2020–2030: Reimagining the Potential of Plants for a Healthy and Sustainable Future

Plants, and the biological systems around them, are key to the future health of the planet and its inhabitants. The Plant Science Decadal Vision 2020–2030 frames our ability to perform vital and far‐reaching research in plant systems sciences, essential to how we value participants and apply emerging technologies. We outline a comprehensive vision for addressing some of our most pressing global problems through discovery, practical applications, and education. The Decadal Vision was developed by the participants at the Plant Summit 2019, a community event organized by the Plant Science Research Network. The Decadal Vision describes a holistic vision for the next decade of plant science that blends recommendations for research, people, and technology. Going beyond discoveries and applications, we, the plant science community, must implement bold, innovative changes to research cultures and training paradigms in this era of automation, virtualization, and the looming shadow of climate change. Our vision and hopes for the next decade are encapsulated in the phrase reimagining the potential of plants for a healthy and sustainable future. The Decadal Vision recognizes the vital intersection of human and scientific elements and demands an integrated implementation of strategies for research (Goals 1–4), people (Goals 5 and 6), and technology (Goals 7 and 8). This report is intended to help inspire and guide the research community, scientific societies, federal funding agencies, private philanthropies, corporations, educators, entrepreneurs, and early career researchers over the next 10 years. The research encompass experimental and computational approaches to understanding and predicting ecosystem behavior; novel production systems for food, feed, and fiber with greater crop diversity, efficiency, productivity, and resilience that improve ecosystem health; approaches to realize the potential for advances in nutrition, discovery and engineering of plant‐based medicines, and green infrastructure. Launching the Transparent Plant will use experimental and computational approaches to break down the phytobiome into a parts store that supports tinkering and supports query, prediction, and rapid‐response problem solving. Equity, diversity, and inclusion are indispensable cornerstones of realizing our vision. We make recommendations around funding and systems that support customized professional development. Plant systems are frequently taken for granted therefore we make recommendations to improve plant awareness and community science programs to increase understanding of scientific research. We prioritize emerging technologies, focusing on non‐invasive imaging, sensors, and plug‐and‐play portable lab technologies, coupled with enabling computational advances. Plant systems science will benefit from data management and future advances in automation, machine learning, natural language processing, and artificial intelligence‐assisted data integration, pattern identification, and decision making. Implementation of this vision will transform plant systems science and ripple outwards through society and across the globe. Beyond deepening our biological understanding, we envision entirely new applications. We further anticipate a wave of diversification of plant systems practitioners while stimulating community engagement, underpinning increasing entrepreneurship. This surge of engagement and knowledge will help satisfy and stoke people\u27s natural curiosity about the future, and their desire to prepare for it, as they seek fuller information about food, health, climate and ecological systems

Risk Factors for Colorectal Cancer in Patients with Multiple Serrated Polyps: A Cross-Sectional Case Series from Genetics Clinics

Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps. Methods and Findings We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes. Conclusion A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.Daniel D. Buchanan, Kevin Sweet, Musa Drini, Mark A. Jenkins, Aung Ko Win, Dallas R. English, Michael D. Walsh, Mark Clendenning, Diane M. McKeone, Rhiannon J. Walters, Aedan Roberts, Sally-Ann Pearson, Erika Pavluk, John L. Hopper, Michael R. Gattas, Jack Goldblatt, Jill George, Graeme K. Suthers, Kerry D. Phillips, Sonja Woodal, Julie Arnold, Kathy Tucker, Amanda Muir, Michael Field, Sian Greening, Steven Gallinger, Renee Perrier, John A. Baron, John D. Potter, Robert Haile, Wendy Franke, Albert de la Chapelle, Finlay Macrae, Christophe Rosty, Neal I. Walker, Susan Parry and Joanne P. Youn

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist