tbuckley/cabot-search huggingface dataset:
Predicting microRNA targeting efficacy in Drosophila
Authors: Vikram Agarwal, Alexander O. Subtelny, Prathapan Thiru, Igor Ulitsky, David P. Bartel
Journal: Genome biology (2018)

MicroRNAs (miRNAs) are short regulatory RNAs that derive from hairpin precursors. Important for understanding the functional roles of miRNAs is the ability to predict the messenger RNA (mRNA) targets most responsive to each miRNA. Progress towards developing quantitative models of miRNA targeting in Drosophila and other invertebrate species has lagged behind that of mammals due to the paucity of datasets measuring the effects of miRNAs on mRNA levels. We acquired datasets suitable for the quantitative study of miRNA targeting in Drosophila. Analyses of these data expanded the types of regulatory sites known to be effective in flies, expanded the mRNA regions with detectable targeting to include 5′ untranslated regions, and identified features of site context that correlate with targeting efficacy in fly cells. Updated evolutionary analyses evaluated the probability of conserved targeting for each predicted site and indicated that more than a third of the Drosophila genes are preferentially conserved targets of miRNAs. Based on these results, a quantitative model was developed to predict targeting efficacy in insects. This model performed better than existing models, and it drives the most recent version, v7, of TargetScanFly. Our evolutionary and functional analyses expand the known scope of miRNA targeting in flies and other insects. The existence of a quantitative model that has been developed and trained using Drosophila data will provide a valuable resource for placing miRNAs into gene regulatory networks of this important experimental organism.
Hyperpolarized [1,4-13C2]Fumarate Enables Magnetic Resonance-Based Imaging of Myocardial Necrosis
Authors: Jack J. Miller, Angus Z. Lau, Per Mose Nielsen, Giles McMullen-Klein, Andrew J. Lewis, Nichlas Riise Jespersen, Vicky Ball, Ferdia A. Gallagher, Carolyn A. Carr, Christoffer Laustsen, Hans Erik Bøtker, Damian J. Tyler, Marie A. Schroeder
Journal: JACC. Cardiovascular imaging (2017)

The aim of this study was to determine if hyperpolarized [1,4-
Endoscopic ultrasound-guided gastroenterostomy for the treatment of gastroduodenal obstruction in severe chronic pancreatitis
Authors: Emmanuel Coronel, Christopher Chapman, Jeffrey Matthews, Uzma Siddiqui
Journal: Endoscopy (2017)

Endoscopic ultrasound (EUS)-guided gastroenterostomy is a newly described endoscopic technique that can be used to palliate the symptoms of gastroduodenal obstruction due to benign or malignant conditions. Multidisciplinary care, incorporating oncologists, surgeons, radiologists, and gastroenterologists, is strongly encouraged to ensure proper patient selection given the potential for severe adverse events, such as perforation and peritonitis.
Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation
Authors: Ricardo J. Miragaia, Tomás Gomes, Agnieszka Chomka, Laura Jardine, Angela Riedel, Ahmed N. Hegazy, Natasha Whibley, Andrea Tucci, Xi Chen, Ida Lindeman, Guy Emerton, Thomas Krausgruber, Jacqueline Shields, Muzlifah Haniffa, Fiona Powrie, Sarah A. Teichmann
Journal: Immunity (2019)

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation.
Objective response rate and progression-free survival as surrogate endpoints for overall survival and the impact of crossover and unbalanced post-progression treatments: A systematic review and meta-analysis in second- and further-line therapy of advanced non-small cell lung cancer.
Authors: Boris Pfeiffer, Mahmoud Hashim, Robert Bartsch, Maarten Postma, Bart Heeg
Journal: Journal of Clinical Oncology (2017)

e20609 Background: Correlations between overall survival (OS) and objective response rate (ORR) or progression-free survival (PFS) are poor. We aimed to evaluate the impact of crossover and unbalanced subsequent treatments on ORR and PFS as surrogate endpoints for OS in patients with advanced NSCLC receiving second- and further-line therapy. Methods: A systematic literature review of randomized clinical trials of systemic treatment for patients with stage IIIB/IV NSCLC receiving second- and further-line therapy was performed. Weighted (by trial size) linear regression models were fitted with the absolute difference in ORR or median PFS as an independent variable and the absolute difference in median OS as a dependent variable. The analysis was repeated in predefined subsets based on crossover and balance of post-progression therapies. Surrogate threshold effect (STE) was estimated using prediction intervals. Results: 146 trials (43,061 patients) fulfilled the eligibility criteria. In all treatment arms, the mean ORR, median PFS, and median OS were 12.2% (standard deviation [SD] 11.2%), 3.2 months (SD 1.3), and 9.6 months (SD 4.1), respectively. ORR and PFS had very weak (R = 0.181; 95% CI: 0.016-0.337) and weak (R = 0.254; 95% CI: 0.074-0.418) relationships, respectively, with OS. However, within trials that did not allow crossover and reported balanced post-progression treatments, ORR and PFS had moderate (R = 0.528; 95% CI: 0.081-0.798) and strong (R = 0.778; 95% CI: 0.475-0.916) relationships, respectively, with OS. STE estimation indicated that trials that show statistically significant treatment effect size of ≥41.0% ORR or ≥4.15 median PFS months can be expected to show significant OS benefit with sufficient certainty. Conclusions: Surrogacy of ORR and PFS for OS might be better estimated in trials that do not allow crossover and report balanced post-progression treatments. Presented STE calculation can be used to estimate the expected effect on OS when either ORR or PFS are used as primary endpoints.
MyPRSR Molecular Subtypes of Multiple Myeloma Represent All High-Risk FISH Translocations Included in the mSMART 2.0 and R-ISS Guidelines
Authors: Ryan K Van Laar, Ivan Borrelo, David Jabalayan, Ruben Niesvizky, Aga Zielinski, Kenton Leigh, Nathan Brown, Richard A Bender
Journal: Blood (2016)
Elements of a comprehensive theory of infant imitation
Authors: Andrew N Meltzoff
Journal: Behavioral and Brain Sciences (2017)

Abstract Imitation is central to human development. Imitation involves mapping between the perception and production of actions. Imitation after delays implicates preverbal memory. Imitation of people informs us about infants' processing of social events. A comprehensive theory needs to account for the origins, mechanisms, and functions of imitation. Neonatal imitation illuminates how the initial state engenders and supports rapid social learning.
Abstract 11329: Risk Factors of Thromboembolism in Patients With Left Ventricular Noncompaction
Authors: Ayumi Eguchi, Shunsuke Eguchi, Hiroki Kamiya, Mamoru Nanasato, Yukihiko Yoshida
Journal: Circulation (2016)

Introduction: Left ventricular noncompaction (LVNC) is a newly recognized cardiomyopathy characterized by a pattern of prominent trabeculation and deep recesses. LVNC can lead to progressive left ventricular (LV) dysfunction and thromboembolism. However, there are few reports that the factors develop thromboembolism in patients with LVNC. Purpose: This study was sought to investigate a difference of characteristics in patients with LVNC developing thromboembolism. Methods: We retrospectively studied 43 patients (age 61 ± 17 years, 32 male) fulfilling the diagnostic criteria of LVNC out of 7842 adults patients (ejection fraction (EF)≦60%) undergoing echocardiography in our hospital between 2012 and 2015. A thickness of the noncompacted endocardial and the compacted epicardial layers was measured at the site of maximal thickness to calculate the ratio of noncompacted to compacted layer (NC/C). The LV wall was divided into five segments (apical, inferior, lateral, anterior and septal) to describe the location of the noncompacted segments. We defined the diagnostic criteria of LVNC as a presence of prominent trabeculation and deep recesses of LV on more than one segment and a maximal end systolic ratio of NC/C≧2.0. Results: LVEF was 38.0 ± 13.0%, LV end-diastolic diameter was 60.0 ± 9.5mm and left atrial diameter (LAD) was 43.8 ± 8.8 mm, respectively. Eight patients (18.6%) were complicated with thromboembolism. There were no significant difference between the patients with thromboembolism and without them on atrial fibrillation, EF and the dilation LAD. The multivariate analysis showed that the patients with thromboembolism had a significantly larger prevalence of patients with a pattern of prominent trabeculation and deep recesses of LV on more than two segments (Odds ratio 6.964, P=0.050) and the height of noncompacted layer ≧ 15 mm (Odds ratio 4.879, P=0.049). Conclusions: The findings such as more than two segments with a pattern of prominent trabeculation and deep recesses of LV and the height of noncompacted layer ≧ 15mm on echocardiography were associated with thromboembolism in patients with LVNC. Anticoagulants should be considered to prevent the patients from thromboembolism regardless of LV function and arrhythmia.
Prevalence of Physical Problems Detected by the Distress Thermometer and Problem List in Patients With Myeloproliferative Disorders
Authors: Daniel C. McFarland, Kelly M. Shaffer, Heather Polizzi, John Mascarenhas, Marina Kremyanskaya, Jimmie Holland, Ronald Hoffman
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Patients with myeloproliferative neoplasms (MPNs) can have a severe physical symptom burden over an extended disease trajectory that contributes to decreased quality of life. Few studies, however, have characterized which patients most frequently consider physical symptoms a problem. This study describes the physical symptoms of patients with MPNs and the relationship of these symptoms to patient characteristics. Methods: Patients with MPNs (N=117) completed questionnaires in a dedicated academic medical center MPN clinic. Patients reported demographics (age, race/ethnicity, sex, marital status, employment status), disease characteristics (MPN type, time with MPN), and whether they were bothered by any of 22 variables in the "Physical Problems" list in the Distress Thermometer and Problem List (DT&PL). Results: The median number of physical problems endorsed by patients was 2 (median, 2.26; SD, 3.18), with a range from 0 to 20. Two-fifths endorsed no physical problems, one-fifth endorsed 1 problem, and two-fifths endorsed ≥2 problems, with fatigue (35.5%), sleep (27.1%), pain (21.5%), dry skin/pruritus (18.7%), and memory/concentration (16.8%) being the most commonly reported. Non-Caucasian participants reported more problems with sleep (P=.050), pain (P=.016), and tingling (P=.026). Patients with polycythemia vera (PV) reported more issues with tingling (P=.046) and sexual problems (P=.032). Conclusions: Patients with MPNs are more likely to report physical symptom bother than to report no bother with multiple physical problems on the DT&PL. Patients of minority race/ethnicity and those with PV, however, showed heightened prevalence of physical problems—characteristics which may be used to triage patients for more intensive symptom management.
Abstract 12077: Stroke as the First Manifestation of Atrial Fibrillation
Authors: Jussi Jaakkola, Pirjo Mustonen, Tuomas Kiviniemi, Juha E Hartikainen, Antti Palomäki, Päivi Hartikainen, Ilpo Nuotio, Antti Ylitalo, K.E. J Airaksinen
Journal: Circulation (2016)

Introduction: Atrial fibrillation (AF) may remain undiagnosed until an ischemic stroke occurs. In this retrospective cohort study we assessed the prevalence of ischemic stroke or transient ischemic attack (TIA) as the first manifestation of AF in a cohort of patients with AF-associated stroke or TIA. Methods: Altogether 3,623 patients treated for their first ever ischemic stroke or TIA during 2003-2012 were identified from the electronic patient records of four clinical centers. Two groups were formed: patients with a history of AF and patients with new AF diagnosed during hospitalization for stroke or TIA. A control group of 781 patients with intracranial hemorrhage was compiled similarly to explore the direction of causality between new AF and stroke. Results: The median age of the patients was 78.3 [13.0] years and 2,009 (55.5%) were women. New AF was diagnosed in 753 (20.8%) patients with stroke or TIA, compared to 15 (1.9%) with intracranial hemorrhage. Younger age (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.02; p=0.014) and no history of coronary artery disease (OR: 1.45; 95% CI: 1.16-1.82; p=0.001) or other vascular diseases (OR: 1.75, 95% CI: 1.09-2.79. p=0.020), heart failure (OR: 2.62; 95% CI: 1.94-3.54, p&lt;0.001), or hypertension (OR: 1.22; 95% CI:1.01-1.47; p=0.041) were the independent predictors of new AF detected concomitantly with an ischemic event. Thus, ischemic stroke was the first clinical manifestation of AF in 37% of younger (&lt;75 years) patients with no history of cardiovascular diseases (Figure). Conclusions: In conclusion, AF is too often diagnosed only after an ischemic stroke has occurred, especially in middle-aged healthy individuals. New AF seems to be predominantly the cause of the ischemic stroke and not triggered by the acute cerebrovascular event.
Abstract IA28: Deciphering immune regulation and recognition at the tumour site
Authors: Sergio A. Quezada
Journal: Cancer Research (2017)

Abstract My laboratory is interested in defining and targeting the key pathways regulating immune recognition and destruction of cancerous cells within tumours. In recent years, a number of publications have demonstrated the essential role of the tumour microenvironment in the in vivo activity of checkpoint targeting antibodies. In this talk I will discuss novel developments in this area relating to the mechanism of action and the development of immune modulatory antibodies that promote maximal modulatory activity in different tumour microenvironments. In addition to immune regulation, another key area of research in the field of cancer immunology relates to the recognition of tumour cells by T lymphocytes. Whilst recent studies highlight the potential importance of T cell reactivity towards patient-specific mutant epitopes in the successful outcome of immune modulatory therapies, little is known about the impact of intra-tumour heterogeneity (ITH) on this relation. In the second part of this talk I will describe recent data using multi tumour region sampling to characterise the interplay between ITH, immune-reactivity and immune-regulation in non-small cell lung cancer patients. Citation Format: Sergio A. Quezada. Deciphering immune regulation and recognition at the tumour site [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA28.
An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report
Authors: Daniel E Spratt, Whitney H Beeler, Fabio Y de Moraes, Laurence D Rhines, Joseph J Gemmete, Neeraj Chaudhary, David B Shultz, Sean R Smith, Alejandro Berlin, Max Dahele, Ben J Slotman, Kelly C Younge, Mark Bilsky, Paul Park, Nicholas J Szerlip
Journal: The Lancet Oncology (2017)
Focal 18F-DOPA Uptake in Brain Parenchyma Surrounding Developmental Venous Anomalies
Authors: Lee Condon, John Blazak
Journal: Clinical Nuclear Medicine (2017)

We report the finding of increased F-DOPA uptake within parenchyma surrounding a developmental venous anomaly, found incidentally in a 64-year-old woman undergoing PET scan to assess for Parkinson's disease. Not identified on previous T1/T2 MRI, susceptibility-weighted imaging MRI performed post-PET scan demonstrated the presence of developmental venous anomaly within the left cerebellar hemisphere. Focal uptake of F-DOPA may suggest the presence of a brain tumor and prompt invasive diagnostic investigations. Nuclear medicine physicians should be aware of this finding when interpreting F-DOPA PET and consider appropriate imaging to identify venous anomalies prior to more invasive investigations for possible brain tumors.
Abstract 5933: Reduced Number of Gap Junctions at the Intercalated Disc in the Ventricles of Boxer Dogs Afflicted with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
Authors: Eva M Oxford, Karen Maass, N. Sydney Moise, Mario Delmar
Journal: Circulation (2008)

ARVC is an inherited myocardial disease associated with sustained monomorphic ventricular tachycardia, sudden cardiac death, and replacement of RV myocardium with fatty or fibro-fatty tissue. Lethal arrhythmias often occur in young patients, before apparent structural damage. It has been hypothesized that loss of Cx43 gap junctions (GJ) may act as a substrate for ventricular arrhythmias in these patients. An inherited form of ARVC is present in the boxer, with clinical symptoms and pathological features similar to those of humans. Here, we used transmission electron microscopy (TEM) to assess the ultrastructure of the intercalated disc (ID) in ARVC-afflicted boxers. Samples from the right and left ventricles (RV and LV) of 1 unafflicted beagle, and 3 ARVC afflicted boxers were examined by TEM. Samples from beagle tissue showed normal morphology, good alignment of the sarcomeres and myofibrils, and attachment of myofibrils to the ID. Samples from the ARVC-afflicted boxer lacked myofibril organization, with few attachments to the ID. Within RV and LV longitudinal sections from one afflicted and one control animal, three parameters were measured: ID length, individual GJ length, and number of GJ per ID. No significant differences were found in the length of IDs or of GJs from RV or LV samples of ARVC vs. control. ID length (μm) was 26.8 +/− 5.4 and 44.9+/− 10.6 in control RV and LV, respectively. ID length in afflicted samples was 31.2+/− 5.0 and 52.3+/−13.5 (pNS). GJ length (μm) was .5+/−.03 and .5+/.05 for RV and LV of the control group, and .4+/−.07 and .6+/−,13 in samples obtained from RV and LV of ARVC afflicted animals (pNS). However, our data indicated a significant (p&lt;.01) decrease in the number of GJ per ID in the ARVC sample by over 80% (5.7+/−.4 RV, 5.8+/− 1.4 LV in control; 1.1+/−.16 RV, 1.5+/−.2 LV in ARVC). Our results suggest that ARVC, both in humans and in boxer dogs, associates with a loss of GJ, which may act as a substrate for lethal arrhythmias. In contrast to human ARVC, no desmosomal protein mutations have been linked to boxer ARVC. This suggests a different genetic basis and yet, a common molecular pathway for ARVC in both species. As such, boxers represent a valuable model to understand the mechanisms leading to malignant ventricular arrhythmias in ARVC patients. This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Why attempt en bloc resection of non-pedunculated colorectal adenomas? A systematic review of the prevalence of superficial submucosal invasive cancer after endoscopic submucosal dissection
Authors: Lorenzo Fuccio, Alessandro Repici, Cesare Hassan, Thierry Ponchon, Pradeep Bhandari, Rodrigo Jover, Konstantinos Triantafyllou, Daniele Mandolesi, Leonardo Frazzoni, Cristina Bellisario, Franco Bazzoli, Prateek Sharma, Thomas Rösch, Douglas K Rex
Journal: Gut (2017)

Objective Endoscopic submucosal dissection (ESD) aims to achieve en bloc resection of non-pedunculated colorectal adenomas which might be indicated in cases with superficial submucosal invasive cancers (SMIC), but the procedure is time consuming and complex. The prevalence of such cancers is not known but may determine the clinical necessity for ESD as opposed to the commonly used piecemeal mucosal resection (endoscopic mucosal resection) of colorectal adenomas. The main aim was to assess the prevalence of SMIC SM1 (ie, invasion ≤1000 µm or less than one-third of the submucosa) on colorectal lesions removed by ESD. Design A literature review was conducted using electronic databases (up to March 2017) for colorectal ESD series reporting the histology of the dissected lesions. Results 51 studies with data on 11 260 colorectal dissected lesions were included. Most resected lesions (82.2%; 95% CI 78.8% to 85.3%) were adenomas (low- and high-grade dysplasia, 26.8% and 55.4%, respectively). Overall, 15.7% were submucosal cancers, but only slightly more than half (8.0%; 95% CI 6.1% to 10.3%) had an infiltration depth of ≤1000 µm, providing a number needed to treat (NNT) to avoid one surgery of 12.5. Estimating an oncologically curative (R0; G1/2; L0/V0) resection rate of 75.3% (95% CI 52.2% to 89.4%) for malignant lesions, the prevalence of curative resection lowered to 6% (95% CI 4.2% to 7.2%) with an NNT of 16.7. Conclusion The low prevalence of SMIC SM1 in lesions selected for ESD as well as the even lower rate of curative resection limits the clinical applicability of endoscopic en bloc resection. This calls for caution over an indiscriminate use of this technique in the resection of colorectal neoplasia.
Bedroom allergen exposures in US households
Authors: Päivi M. Salo, Jesse Wilkerson, Kathryn M. Rose, Richard D. Cohn, Agustin Calatroni, Herman E. Mitchell, Michelle L. Sever, Peter J. Gergen, Peter S. Thorne, Darryl C. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2017)
Molecular predictors of post-transplant survival in acute myeloid leukemia
Authors: Tong Qin, Sun Wu, Hongmian Zhao, Keman Xu, Huaping Fu, Zhiheng Cheng, Yifan Pang, Yu Han, Li Chen, Chao Wang, Yijie Zhang, Xiaoyan Ke, Kailin Xu, Jinlong Shi, Lin Fu
Journal: Blood Cancer Journal (2017)

Acute myeloid leukemia (AML) is a heterogeneous disease.Based on risk stratification at diagnosis, patients with AML either receive consolidation chemotherapy or undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) after attaining initial remission.It has been shown that cytogenetic abnormalities at diagnosis are associated with outcome after post remission therapy, including allo-HSCT 1 .Based on cytogenetic risk stratification, Koreth et al. 2 undertook a systematic review and meta-analysis of prospective trials, and concluded that allo-HSCT had significant relapse-free survival and overall survival (OS) benefit for intermediate-and for poor-risk AML, but not for good-risk AML in first complete remission.A growing number of recurrent genetic abnormalities have been recognized in the revised 2016 World Health Organization (WHO) classification of AML 3 .Acquired recurrent genetic abnormalities at diagnosis are among the most important independent factors used for diagnosis and prognostic stratification, and deepens our understanding of the disease pathogenesis 4 .Whether recurrent genetic abnormalities are also important markers that imply response to allo-HSCT is unknown.To address this question, we examined samples from patients with AML who had undergone allo-HSCT to determine whether recurrent genetic abnormalities were associated with long-term outcome after transplantation.This is a retrospective study.A total of 78 patients who received allo-HSCT for AML (derived from The Cancer Genome Atlas (TCGA) database (https://cancergenome.