tbuckley/cabot-search huggingface dataset:
<i>Notes From The Field:</i> Mumps Outbreak in a Recently Vaccinated Population — Kosrae, Federated States of Micronesia, August–December, 2017
Authors: Susannah L. McKay, Afeke Kambui, Livinson A. Taulung, Ashley Tippins, Maribeth Eckert, Adam K. Wharton, Rebecca J. McNall, Carole Hickman, W. Thane Hancock, Carter Apaisam, Peter Judicpa, Manisha Patel, Janell Routh
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

On August 6, 2017, the Kosrae Department of Health Services in the Federated States of Micronesia reported a confirmed case of mumps in a resident aged 18 years. The patient had documentation of receipt of 2 doses of measles-mumps-rubella vaccine and had recently traveled to Seattle, Washington, which was experiencing a large mumps outbreak among members of its Pacific Islander population.
Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
Authors: Brian C. Miller, Debattama R. Sen, Rose Al Abosy, Kevin Bi, Yamini V. Virkud, Martin W. LaFleur, Kathleen B. Yates, Ana Lako, Kristen Felt, Girish S. Naik, Michael Manos, Evisa Gjini, Juhi R. Kuchroo, Jeffrey J. Ishizuka, Jenna L. Collier, Gabriel K. Griffin, Seth Maleri, Dawn E. Comstock, Sarah A. Weiss, Flavian D. Brown, Arpit Panda, Margaret D. Zimmer, Robert T. Manguso, F. Stephen Hodi, Scott J. Rodig, Arlene H. Sharpe, W. Nicholas Haining
Journal: Nature Immunology (2019)
Reply
Authors: Siddharth Singh, Rohit Loomba
Journal: Hepatology (2017)

Reply: We appreciate the comments from Safiri and colleagues and Liu and colleagues in response to our article on increasing risk of mortality by fibrosis stage in patients with nonalcoholic fatty liver disease.1 We acknowledge the concern for sparse data bias as highlighted by Safiri and colleagues, especially for liver‐related mortality. As the authors point out, there are several ways to deal with sparse data, with the underlying aim being to minimize bias and yet provide meaningful estimates. Using these principles, we opted to add 0.05 to each cell, instead of adding 0.5 as has been traditionally recommended. As is readily apparent, adding 0.5 to already sparse data would have significantly skewed the results. Even with the approach suggested by Safiri et al., our results would not have been significantly different. We appreciate the detailed reanalyses by Liu and colleagues to evaluate the relationship between fibrosis stage and risk of all‐cause and liver‐related mortality. Our focus was on a simplistic, clinically relevant assessment of this relationship; and as is apparent, the relationship between fibrosis stage and liver‐related mortality was steeper than its association with all‐cause mortality. Hence, based on a logarithmic summary estimate, we believed this relationship to be nearly exponential. We acknowledge that there may be more sophisticated statistical techniques to evaluate this association, as highlighted by Liu and colleagues. Regardless, the underlying message that fibrosis stage is one of the most important prognostic factors in patients with nonalcoholic fatty liver disease is undisputed. More data are needed to improve the precision of these estimates, but summary estimates are unlikely to be too different from currently reported values.
Abstract P065: Exposure to Traffic and Fine Particulate Matter and Aortic Calcium in the Framingham Offspring and Third Generation Cohorts
Authors: Kirsten S Dorans, Elissa H Wilker, Wenyuan Li, Mary B Rice, Petter L Ljungman, Joel Schwartz, Brent A Coull, Julie E Buring, Itai Kloog, Petros Koutrakis, Ralph B D’Agostino, Joseph M Massaro, Udo Hoffmann, Christopher J O’Donnell, Murray A Mittleman
Journal: Circulation (2016)

Background: Exposure to traffic and ambient air pollution is associated with an increased risk of cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium (TAC) or abdominal aortic calcium (AAC), which are correlates of atherosclerosis. Objective: We assessed whether living close to a major road and residential exposure to fine particulate matter (PM 2.5 ) were associated with TAC and AAC in a community-based Northeastern U.S. cohort. Methods: TAC was measured from 2002[[Unable to Display Character: &amp;#8211;]]2005 and AAC up to two times (2002[[Unable to Display Character: &amp;#8211;]]2005; 2008[[Unable to Display Character: &amp;#8211;]]2011) among participants from the Framingham Offspring or Third Generation Cohorts. We first assessed associations of residential distance to a major road and PM 2.5 exposure (2003 annual average from a spatiotemporal model) with detectable aortic calcium. We used logistic regression for TAC and generalized estimating equations (logit link) for AAC. As aortic calcium scores were right-skewed, we next used linear regression models and mixed effects models to assess associations with log-transformed TAC and AAC, respectively, among participants with aortic calcium scores &gt; 0 (95% CIs bootstrapped). We also assessed associations with AAC progression. Models were adjusted for demographic variables, individual and area-level markers of socioeconomic position and time. Results: Among 3518 participants with TAC or AAC measured, 52% had AAC measured twice. Mean age was 55.8 years; 50% female. There were no associations of distance to a major road or PM 2.5 with detectable TAC or AAC, though some estimates were in the opposite direction than expected ( Table ). There were no associations with extent of TAC or AAC ( Table ), or with AAC progression. Conclusions: Proximity to a major road and PM 2.5 were not associated with the presence or extent of aortic calcium, or with AAC progression in this cohort from a region with relatively low PM 2.5 levels. Future work should explore these associations in other populations.
Immunophenotypic Assessment of Minimal Residual Disease in Younger Acute Myeloid Leukemia Patients Is Highly Predictive of Outcome
Authors: Papagudi Ganesan Subramanian, Chinmayee Kakirde, Rohan Kodgule, Goutham Raval, Sanjay Talole, Shraddha Kadechkar, Nikhil Rabade, Yajamanam Badrinath, Sitaram Ghogale, Nilesh Deshpande, Shruti Chaudhary, Swapnali Joshi, Russel Mascarenhas, Dhanlaxmi Shetty, Hari Menon, Manju Sengar, Hasmukh Jain, Bhausaheb Bagal, Anant Gokarn, Sachin Punatar, Avinash Bonda, Lingaraj Nayak, Prashant Tembhare, Sumeet Gujral, Nikhil Patkar, Navin Khattry
Journal: Blood (2018)
Cardioprotective effects of inhaled corticosteroid-containing combination therapy in COPD
Authors: Brian J. Lipworth, Chris R.W. Kuo
Journal: European Respiratory Journal (2019)

The pooled post hoc analysis of three randomised controlled trials by Vestbo et al. [1] found that combinations containing inhaled corticosteroid (ICS) significantly reduced non-respiratory-related mortality in chronic obstructive pulmonary disease (COPD) compared to long-acting bronchodilator therapies alone, the difference amounting to −35% (95% CI −57% to −3%). These studies did not adjudicate on cause of death and only followed patients for up to 1 year. In the IMPACT trial, all-cause mortality was 42% lower and cardiovascular attributed deaths were 52% lower when comparing triple therapy to combined long-acting bronchodilators over 1 year [2]. We propose that combination therapy containing inhaled corticosteroids may confer cardioprotective effects in patients with COPD <http://ow.ly/AwQG30nmGa9>
Abstract P138: The Association of a Greater Step Count with Body Composition in Young Adults
Authors: Madison M DeMello, Clemens Drenowatz, Gregory A Hand, Steven N Blair
Journal: Circulation (2016)

Introduction: Walking has been associated with a reduction of cardiovascular disease risk, but there remains limited information on the association between volume of steps and body composition. Therefore, the purpose of this study is to examine the association between the number of steps per day and percent body fat in young, generally healthy adults. Hypothesis: It is hypothesized that those with a greater number of steps per day will have a decreased percent body fat, compared to those who spend more time in sedentary behavior. Methods: A sample of 418 young adults (49% male), between the ages of 21 and 35 and a body mass index (BMI) between 20 and 35 kg/m2 provided valid objective activity data. Participants were given a SenseWear mini armband to wear for ten days with compliance set at 7 days of wear time, including 2 weekend days, with at least 21 hours of verifiable time per day. Step count was averaged per day based off the total days of armband wear. In addition, participants completed a dual x-ray absorptiometry scan to measure fat mass and fat free mass, percent body fat (BF) was then calculated. Results: The average BMI of the sample was 25.3 kg/m2 with a percent body fat of 22.5% and 34.1% for males and females, respectively. Males had higher step counts than females (p=.005). Quintiles were created based off average steps per day (±SD) (mean values for least steps to most steps: 4051 ± 336; 4503 ± 800; 7286 ± 360; 8544 ± 436; 12,011 ± 2,140). There was a linear trend across quintiles (p for trend &lt; .01) of decreasing percent body fat with increased steps, after adjusting for age and sex. No significant difference between step quintiles was observed for BMI (p for trend = .06) after adjusting for the same covariates. Results were similar when analyzing males and females separately. Conclusion: In conclusion, these results indicate that a higher step count is associated with lower BF. Given that percent body fat is associated with various health outcomes and the fact that walking is an inexpensive and feasible activity for most populations, further efforts are needed to increase steps/day in US adults.
Glucose Measurements at Various Time Points During the OGTT and Their Role in Capturing Glucose Response Patterns
Authors: Adam Hulman, Róbert Wagner, Dorte Vistisen, Kristine Færch, Beverley Balkau, Melania Manco, Alain Golay, Hans-Ulrich Häring, Martin Heni, Andreas Fritsche, Daniel R. Witte
Journal: Diabetes Care (2019)

Intermediate time points during the oral glucose tolerance test (OGTT) have received more attention recently (1), with some researchers even suggesting to use 1-h glucose when screening for prediabetes (2). We demonstrated that characterization of glucose response patterns from OGTTs with five time points provides useful insights into the heterogeneity of type 2 diabetes development (3). Although such analyses are feasible in small pathophysiological investigations, they are not common in large epidemiological studies where the number of glucose measurements during an OGTT is often limited. Therefore, we aimed to study how well different combinations of fewer than five time points during an OGTT approximate glucose response patterns based on five time points.

We analyzed data from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study, which we previously used to develop a glucose pattern classification model (3). The Tubingen Family Study (TUEF) cohort was used for external validation (4). Both studies included five-point OGTTs with glucose measurements at 0, 30, 60, 90, and 120 min. We excluded participants with self-reported diabetes or screen-detected diabetes (fasting plasma glucose ≥7.0 mmol/L or 2-h postload plasma glucose ≥11.1 mmol/L), participants taking glucose-lowering medication, and those with missing measurements at any of the five time points.

We previously identified four glucose …
Blinatumomab Administered Concurrently with Oral Tyrosine Kinase Inhibitor Therapy Is a Well-Tolerated Consolidation Strategy and Eradicates Measurable Residual Disease in Adults with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Authors: Amber C. King, Jeremy Pappacena, Martin S. Tallman, Jae H. Park, Mark Blaine Geyer
Journal: Blood (2018)
iGUIDE: an improved pipeline for analyzing CRISPR cleavage specificity
Authors: Christopher L. Nobles, Shantan Reddy, January Salas-McKee, Xiaojun Liu, Carl H. June, J. Joseph Melenhorst, Megan M. Davis, Yangbing Zhao, Frederic D. Bushman
Journal: Genome biology (2019)

Genome engineering methods have advanced greatly with the development of programmable nucleases, but methods for quantifying on- and off-target cleavage sites and associated deletions remain nascent. Here, we report an improvement of the GUIDE-seq method, iGUIDE, which allows filtering of mispriming events to clarify the true cleavage signal. Using iGUIDE, we specify the locations of Cas9-guided cleavage for four guide RNAs, characterize associated deletions, and show that naturally occurring background DNA double-strand breaks are associated with open chromatin, gene dense regions, and chromosomal fragile sites. iGUIDE is available from https://github.com/cnobles/iGUIDE .
<i>KRAS</i> and <i>TP53</i> status as a predictor of survival in patients with resected pancreatic ductal adenocarcinoma.
Authors: Caitlin A McIntyre, Sharon Anita Lawrence, Winston Wong, Joanne F. Chou, Marinela Capanu, Michael F. Berger, Peter Allen, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2019)

276 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. KRAS, TP53, CDKN2A and SMAD4 are established driver genes in PDAC. We aimed to determine if the mutational status of these 4 driver genes, and other frequently altered genes, are predictive of clinical outcomes in patients who undergo resection. Methods: Patients who underwent resection of PDAC and consented to targeted sequencing of their primary tumor using MSK-IMPACT, were included. Genomic alterations were determined based on MSK-IMPACT sequencing results of formalin-fixed, paraffin-embedded tumor. A prospectively maintained database and electronic medical record were queried for clinical and pathologic variables. Gene mutation status was compared with overall survival (OS) and recurrence free survival (RFS) using the log-rank test, and with pathologic variables using Wilcoxon rank-sum and Fishers exact tests. Results: Targeted genomic sequencing was performed on N = 285 primary tumors resected between 2004-2017. N = 55 (19%) patients received neoadjuvant therapy prior to sequencing and N = 220 (77%) received adjuvant therapy. Median OS was 39 months with a median follow up of 22 months. Frequency of genomic alterations and their association with OS and RFS are shown in Table 1. Alterations in both KRAS and TP53 were associated with worse OS, but not RFS, as compared to wildtype. Mutant KRAS was also associated with larger tumor size (median, 3.0 vs 2.2cm, p = 0.009). Conclusions: Alterations in KRAS and TP53 were associated with worse OS in patients with resected PDAC. Further analysis will include the association of driver gene variants, as well as other gene alterations, with clinical and pathologic outcomes. [Table: see text]
Genetic variants in the lipopolysaccharide (LPS) receptor complex and TLR4 expression levels to predict efficacy of cetuximab (cet) in patients (pts) with metastatic colorectal cancer (mCRC): Data from the FIRE-3 phase III trial.
Authors: Francesca Battaglin, Alberto Puccini, Shu Cao, Joshua Millstein, Ryuma Tokunaga, Madiha Naseem, Shivani Soni, Jae Ho Lo, Tricia Ning, Hiroyuki Arai, Martin D. Berger, Afsaneh Barzi, Wu Zhang, Volker Heinemann, Sebastian Stintzing, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

564 Background: Large metagenomic studies associate disrupted gut microbiome signatures, comprising more prevalently gram-negative bacteria, with CRC carcinogenesis. TLR4, the LPS receptor, has been involved in microbiota-mediated tumorigenesis. High TLR4 expression is associated with poor prognosis in CRC and TLR4 can activate EGFR through ligands epiregulin and amphiregulin. Hence, we hypothesized that genetic variants in the LPS receptor complex and TLR4 expression levels may predict cetuximab efficacy in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in the randomized FIRE-3 trial was genotyped through the OncoArray, a custom array manufactured by Illumina. The impact on outcome of 5 functional SNPs within TLR4, MD2 and CD14 was analyzed in 129 pts treated with first-line FOLFIRI/cet (discovery, mPFS/OS: 12.8/49.8 mo) and 107 pts treated with FOLFIRI/bevacizumab (bev) (mPFS/OS: 11.5/31.4 mo). Gene expression levels were measured from 102 tumor samples of pts in the cet arm by HTG EdgeSeq Oncology Biomarker Panel. Results: In the discovery cohort, pts carrying the C/T variant of TLR4 rs4986791 had significantly shorter mPFS and OS compared to the C/C genotype in both uni- and multivariable analysis (PFS: 5.4 vs 13.3 mo, adjusted P[ P adj ] = .01; OS: 21.7 vs 40.7 mo, P adj = .03). Conversely, C/C carriers of rs12377632 had a longer mPFS compared to any T in uni- and multivariable analysis (15.8 vs 12.2 mo, P adj &lt; .001). Any A allele carriers of MD2 rs12546552 and any G allele carriers of CD14 rs2569190 showed shorter mPFS in multivariable analyses. These associations were not observed in bev arm. Significant interaction was found between TLR4 rs12377632 and RAS status ( P= .015). High TLR4 expression (log2 &gt; 10.93) was associated with worse mPFS (7.2 vs 11 mo, P= .003) and OS (19.1 vs 29.8 mo, P&lt; .001) in FIRE-3 cet arm. Conclusions: Our results provide the first evidence that polymorphisms in the LPS receptor complex and TLR4 expression levels may have a predictive value in mCRC pts receiving first-line cetuximab-based treatment and, overall, contribute to resistance to anti-EGFRs.
Identification of Heterotopic Ossification Using 18F-NaF PET/CT
Authors: Siavash Mehdizadeh Seraj, Abdullah Al-Zaghal, Brian Østergaard, Poul F. Høilund-Carlsen, Abass Alavi
Journal: Clinical Nuclear Medicine (2019)

Abstract Heterotopic ossification (HO) is a benign condition characterized by the abnormal formation of mature lamellar bone in extraskeletal soft tissues. Most frequently, HO is observed around the hip joint after fractures or surgical procedures such as open reduction internal fixation or total hip arthroplasties. We are presenting a case of HO as detected by 18 F-NaF PET/CT in a 68-year-old woman with multiple myeloma and a history of internal fixation of the right hip. Many previous publications have reported 18 F-NaF uptake portraying calcification in soft tissue; the present report demonstrates the feasibility of 18 F-NaF PET/CT to assess extraosseous calcification.
Abstract 20229: Comparative Methods to Estimate the Relationship Between LDL Cholesterol Reduction and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis
Authors: Eliano Navarese, Mariusz Kowalewski, Michalina Kolodziejczak, Kevin Bliden, Udaya Tantry, Jacek Kubica, Paul A Gurbel
Journal: Circulation (2017)

Background: Patients achieving low plasma levels of low density lipoprotein-cholesterol (LDL-C) are at reduced cardiovascular risk. We aimed to evaluate in a comprehensive manner whether reduction of LDL-C levels beyond currently recommended goals produce a corresponding reduction in cardiovascular events. Methods: We performed a meta-analysis to investigate the association between chosen descriptors of LDL-C reduction and related cardiovascular risk across randomized controlled lipid-lowering trials. Electronic databases (the Cochrane Collaboration, MEDLINE, and Embase) were searched systematically up to 18th March 2017 comparing more intensive vs less intensive lipid lowering strategies. The primary endpoint was all-cause mortality; secondary endpoints were cardiovascular mortality, myocardial infarction, cerebrovascular events, revascularizations and the composite of major cardiovascular events. Rate ratios (RR) and 95% confidence intervals (CIs) were used as summary statistics to better appreciate sin...
Structural rearrangements generate cell-specific, gene-independent CRISPR-Cas9 loss of fitness effects
Authors: Emanuel Gonçalves, Fiona M. Behan, Sandra Louzada, Damien Arnol, Euan A. Stronach, Fengtang Yang, Kosuke Yusa, Oliver Stegle, Francesco Iorio, Mathew J. Garnett
Journal: Genome biology (2019)

CRISPR-Cas9 genome editing is widely used to study gene function, from basic biology to biomedical research. Structural rearrangements are a ubiquitous feature of cancer cells and their impact on the functional consequences of CRISPR-Cas9 gene-editing has not yet been assessed. Utilizing CRISPR-Cas9 knockout screens for 250 cancer cell lines, we demonstrate that targeting structurally rearranged regions, in particular tandem or interspersed amplifications, is highly detrimental to cellular fitness in a gene-independent manner. In contrast, amplifications caused by whole chromosomal duplication have little to no impact on fitness. This effect is cell line specific and dependent on the ploidy status. We devise a copy-number ratio metric that substantially improves the detection of gene-independent cell fitness effects in CRISPR-Cas9 screens. Furthermore, we develop a computational tool, called Crispy, to account for these effects on a single sample basis and provide corrected gene fitness effects. Our analysis demonstrates the importance of structural rearrangements in mediating the effect of CRISPR-Cas9-induced DNA damage, with implications for the use of CRISPR-Cas9 gene-editing in cancer cells.
Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) for Children and Young Adults with T-Cell Acute Lymphoblastic Leukemia (T-ALL) Treated at Investigator Discretion: A Report from Children's Oncology Group (COG) AALL0434
Authors: Stuart S. Winter, Meenakshi Devidas, Brent Wood, Zhiguo Chen, Natia Esiashvili, Barbara L Asselin, Mignon L. Loh, Karen R. Rabin, Elizabeth A. Raetz, Patrick A. Zweidler-McKay, Kirk R. Schultz, Naomi Winick, William L. Carroll, Stephen P. Hunger, Kimberly P. Dunsmore
Journal: Blood (2018)
Development and surveillance of hepatocellular carcinoma in patients with sustained virologic response after antiviral therapy for chronic hepatitis C
Authors: Seong Kyun Na, Byung-Cheol Song
Journal: Clinical and Molecular Hepatology (2019)

Hepatitis C virus (HCV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC), and is a leading cause of liver-related deaths worldwide. Recently available direct-acting antiviral agent is very safe and highly effective (>95% sustained virologic response, SVR) against all genotypes of HCV. Achievement of SVR has been associated with a significant reduction of hepatic decompensation, development of HCC, and liver-related mortality. However, HCC risk is not eliminated even after SVR. The annual incidences of HCC in advanced fibrosis or cirrhosis have been estimated to be up to 2.5-4.5% even in patients with SVR. Therefore, surveillance for HCC is recommended in this high-risk patients. In this review, we will describe the clinical outcomes and the risk of HCC in patients with SVR and suggest who should receive surveillance for HCC.
Genetic Characterization of B-Cell Prolymphocytic Leukemia (B-PLL): A Hierarchical Prognostic Model Involving MYC and TP53 Abnormalities. on Behalf of the Groupe Francophone De Cytogenetique Hematologique (GFCH) and the French Innovative Leukemia Organization (FILO) Group
Authors: Elise Chapiro, Damien Roos-Weil, Nadia Bougacha, Clementine Gabillaud, Clémentine Dillard, Elodie Pramil, Melanie Yon, Karim Maloum, Catherine Settegrana, Lucile Baseggio, Claude Lesty, Frederic Davi, Magali Le Garff-Tavernier, M'boyba Khadija Diop, Nathalie M Droin, Philippe Dessen, Veronique Leblond, Caroline Algrin, Simon Bouzy, Virginie Eclache, Baptiste Gaillard, Evelyne Callet-Bauchu, Marc Muller, Christine Lefebvre, Nathalie Nadal, Antoine Ittel, Stéphanie Struski, Marie-Agnes Collonge-Rame, Benoit Quilichini, Sandra Fert-Ferrer, Nathalie Auger, Isabelle Radford-Weiss, Lena Wagner, Sebastian Scheinost, Thorsten Zenz, Santos Susin, Olivier Bernard, Florence Nguyen-Khac
Journal: Blood (2018)