bluuebunny/crossref_metadata_2025_split huggingface dataset:
P2876Repeating non-invasive risk stratification tests improves the prediction of outcomes of ICD patients in the EUTrigTreat study
Authors: Vandenberk B , Rover C , Dunnink A , Friede T , Flevari P , Zabel M , Willems R 
Published: October 2019

Abstract

Background
Non-invasive risk stratification of SCD aims to predict the risk by assessing measures of substrate (LVEF), of triggers (PVCs; T-wave alternans, TWA) and of autonomic function (heart rate turbulence, HRT). However, the value of repeating these tests during follow-up is unclear.

Purpose
To study the predictive value of repeated non-invasive risk assessment.

Methods
EUTrigTreat is a prospective trial aimed to improve non-invasive risk stratification in ICD patients. The study protocol included non-invasive testing at baseline and a repeat after 6 to 12 months. The population included ischemic and non-ischemic cardiomyopathies and arrhythmogenic heart disease. Test results were categorized as pathologic (1) versus non-pathologic (0) for LVEF ≤40%, PVCs >400 in 24h, abnormal exercise TWA (Cambridge Heart) and abnormal HRT (TO >0.1% and/or TS ≤2.0ms/RRI). Time dependent Cox regression modelling was performed for mortality, and a Fine-and- Gray competing risk analysis for shocks, including adjustment for independent predictors in the overall study population (mortality: age, LVEF, history of AF, NT-proBNP, NYHA class, eGFR; shocks: LVEF, secondary prevention).

Results
A total of 635 patients were included with a follow-up of 4.3±1.5 years, 96 (15%) received an ICD shock and 108 (17%) died. The table shows the results at baseline and with repeating the tests after 8±1 months.
Worsening of LVEF compared to a stable LVEF >40% and persistent abnormal HRT were independent predictors of mortality. Improvement in HRT was associated with a lower mortality. Worsened results upon TWA testing was associated with a 3 times higher risk of shocks. A persistent low LVEF was an independent predictor of both mortality and ICD shocks.
Baseline 1 (vs. 0) Worsening 0–1 (vs. 0–0) Improvement 1–0 (vs. 1–1) Stable 1–1 (vs. 0–0) HR (CI) HR (CI) HR (CI) HR (CI) Mortality   LVEF (n=315) 1.85 (1.06–3.24) 3.47 (1.13–10.68) 0.88 (0.40–1.94) 2.22 (1.19–4.15)   TWA (n=204) 0.62 (0.28–1.37) 0.80 (0.25–2.59) 0.67 (0.18–2.47) 0.59 (0.20–1.77)   PVC (n=329) 1.26 (0.73–2.16) 0.99 (0.36–2.72) 0.63 (0.26–1.52) 1.38 (0.75–2.55)   HRT (n=163) 2.57 (0.85–7.77) 4.01 (0.39–41.17) 0.10 (0.01–0.81) 8.71 (1.11–68.24) Shocks   LVEF (n=338) 1.73 (0.93–3.22) 0.92 (0.13–6.67) 0.26 (0.06–1.08) 2.02 (1.09–3.76)   TWA (n=256) 0.82 (0.39–1.70) 2.91 (1.04–8.13) 1.31 (0.48–3.59) 1.54 (0.54–4.43)   PVC (n=366) 1.28 (0.70–2.34) 1.48 (0.54–4.09) 0.54 (0.16–1.81) 1.70 (0.86–3.35)   HRT (n=188) 1.12 (0.50–2.50) 0.57 (0.13–2.52) 0.73 (0.20–2.64) 1.06 (0.43–2.61)

Conclusion
Repeating LVEF, TWA and HRT have the potential to improve risk stratification for mortality and shocks in ICD patients.

Acknowledgement/Funding
This research has received funding from European Community's Seventh Framework Program FP7: EUTrigTreat (grant agreement no. HEALTH-F2-2009-241526).
P2880Incidence and clinical relevance of oversensing due to extracardiac signals in subcutaneous implantable cardiac defibrillator (S-ICD)
Authors: Palacios Rubio J , Grande C , Canadas-Godoy V , Perez-Castellano N , Exposito-Pineda C 
Published: October 2019

Abstract

Background
S-ICD is an ICD system completely extrathoracic, composed of a generator in a left infra-axillary position and a parasternal lead. Arrhythmia detection is done by analyzing extracardiac signals registered in a dipole that is several centimeters in length, larger than in a transvenous ICD. Hence, it could potentially be more susceptible to external interference (eg. myopotentials or electromagnetic noise).

Purpose
To assess real-world incidence and clinical relevance of oversensing due to extracardiac signals (OES) in S-ICD.

Methods
Retrospective review of medical reports and remote monitoring system in two Spanish hospitals. Events were assessed by EHRA-certified specialists in cardiac devices. Differences in patients with OES were sought by univariate analysis using parametric or non-parametric methods according to sample characteristics.

Results
117 patients since October 2014 were analyzed. 88 (75,2%) men, age at implant 49,1±13,8 years. Implants were indicated mainly in primary prevention (72; 61,5%), due to ischemic cardiomyopathy (52; 44,4%), NYHA functional class I-II (107; 91,5%). 24 (20,5%) had intraventricular conduction disorders (9 right bundle branch, 2 left, 13 delayed intraventricular conduction). Electrodes implanted mostly left parasternal (107; 91,5%). On implant, gain ×1 in 90 (96,7% cases with data registered; 24 cases not registered), SmartPass activated in every device with such tool available.
Patients were followed-up for 1,9±1,2 years (maximum 4,2). 4 (3,4%) received appropriate shocks, 10 (8,5%) inappropriate: 3 OES, 3 T-wave oversensing, 3 voltage decrease (leading to SmartPass deactivation), 1 lead dysfunction. In 8 cases OES was identified (incidence 3,7 /100 patients/year): in 3 (37,5%) cases inappropriate shocks were delivered. OES occurred 1,9 (interquartile range, IQR, 0,9–2,9) years after implant. No differences in OES were found depending on sex, indication, S-ICD or lead model, lead position, intraventricular conduction disorders, detection vector at implant, number of suitable vectors at screening, tachycardia detection rate or SmartPass automatic deactivation during follow-up
In 5 cases, a cause for OES was identified: 4 myopotentials, 1 interference from electric engine. Cases were managed by changing sensing vector (3), increasing tachycardia detection rate (2), watchful waiting (2, OES source unidentified) or providing instructions to the patient (1). No OES recurrence after 0,8 years (IQR 0,6–1,1).
Example of OES

Conclusions
S-ICD has an incidence of OES of 3,7 cases /100 patients/year. OES can be successfully managed with a conservative approach.
P2881Eligibility for a subcutaneous defibrillator based on standard 12-lead electrocardiogram
Authors: Sakhi R , Theuns D A M J , Cosgun D , Michels M , Schinkel A F L , Kauling R M , Roos-Hesselink J W , Yap S C 
Published: October 2019

Abstract

Background
Currently, the eligibility for a subcutaneous implantable defibrillator (S-ICD) system relies on a pre-implant vector screening based on the automated screening tool (AST).

Objective
To determine 12-lead ECG characteristics associated with eligibility for an S-ICD in a heterogeneous population at risk for sudden cardiac death (SCD). The goal is to determine patient eligibility for S-ICD using the standard 12-lead ECG, thereby avoiding additional AST screening.

Methods
We prospectively evaluated the eligibility for an S-ICD in 254 consecutive patients at risk for SCD. We identified 12-lead ECG parameters which were independently associated with AST passing (≥1 vector) using multivariable logistical regression analysis in our derivation cohort. The final model was tested in a separate validation cohort.

Results
The overall passing rate was 92% in our derivation cohort. Independent 12-lead ECG characteristics associated with AST passing were QRS≤130 ms, absence of QRS/T discordance in lead II and R/T-ratio ≥3.5 in lead II (Table). Eighty-three of 254 patients (33%) fulfilled these three criteria and had a passing rate of 100%. Of the validation cohort, 37 of 60 patients (62%) fulfilled all three criteria and also had a passing rate of 100%. The interobserver agreement for applying the ECG model was 90% (Cohen's Kappa=0.80).
Table 1 Variables Univariable Multivariable OR (95% CI) P-value OR (95% CI) P-value QRS ≤130 ms 9.65 (3.66–25.43) <0.01 8.09 (2.88–22.77) <0.01 QTc ≤450 ms 3.33 (1.18–9.54) 0.02 Absence of T-wave inversion in lead I 2.74 (1.03–7.25) 0.04 Absence of T-wave inversion in lead II 3.65 (1.29–10.33) 0.02 Absence of QRS/T-wave discordance in lead II 5.05 (1.98–12.92) <0.01 4.19 (1.49–11.74) <0.01 Absence of QRS/T-wave discordance in lead aVF 3.95 (1.53–10.19) <0.01 R/T-ratio ≥3.5 in lead II 3.58 (1.27–10.01) 0.02 4.21 (1.27–13.95) 0.02 R/T-ratio ≥3.5 in lead aVF 3.16 (1.18–8.42) 0.02 OR = odds ratio; CI = confidence interval.
Figure 1

Conclusion
Using the standard 12-lead ECG, we developed a simple screening model with a high specificity for S-ICD eligibility. Our results suggest that patients who fulfill the three ECG criteria do not need additional AST-screening. Therefore, we developed a simple flowchart to determine eligibility for an S-ICD that can be easily implemented in daily clinical practice (Figure).
Acuity Is Seasonal in a Tertiary Care Burn Center
Authors: Williams Felicia N , Sljivic Sanja , Chrisco Lori , Nizamani Rabia , Cairns Bruce A , Jones Samuel W 
Published: October 2019

AbstractSupply and demand dictate resource allocation in large academic institutions. Classic teaching is that burns is a seasonal specialty with winter being the “busiest” time of year. Resident allocation during the winter and summer months, however, is traditionally low due to the holidays and travel peaks. Our objective was to evaluate our acuity—defined as patient complexity—based on seasons, in order to petition for appropriate mid-level provider allocation. We performed a retrospective review of all admissions to an accredited, large academic burn center. All patients admitted between January 1, 2009 and December 31, 2018 were eligible for inclusion. Demographics, length of stay, injury characteristics, and mortality were evaluated. Thirteen thousand four hundred fifty-eight patients were admitted during this study period. Most patients were admitted during the summer. Patients admitted to the intensive care unit were more likely to be admitted in the winter, although this was not statistically significant. Winter admissions had the longest lengths of stay, and the highest incidence of inhalation injury. Female and elderly patients were more likely admitted during the winter. There was a significant difference in mortality between summer and winter seasons. Acuity is seasonal in our large academic burn center and resource allocation should align with the needs of the patients. This data may help large centers petition their institutions for more consistent experienced mid-level providers, specifically during critical seasons.
Everyday Security, Feminism, and the Continuum of Violence
Authors: Wibben Annick T R 
Published: October 2019

AbstractThis article returns to the original forum question “What is Global Security Studies?,” looking at it in relation to the theme of inclusion and exclusion to point out that security studies scholars exclude feminist scholarship on (everyday) security at their own peril. Showcasing the increasing body of feminist security studies scholarship, the article then highlights not only what scholarship might be included in a truly global security studies, but also the important insights (e.g., about the continuum of violence that spans peace- and wartime) that are missed without it. The article ends with a reflection on the need to also include a wider range of approaches as eminently valuable to global security studies.
The First Darwinian: Alfred Russel Wallace and the Meaning of Darwinism
Authors: Hesketh Ian 
Published: October 2019

Abstract
This essay is an initial study of a larger project that seeks to produce a history of the term ‘Darwinism’. While it is generally well-known that Darwinism could refer to a variety of different things in the Victorian period, from a general evolutionary naturalism to the particular theory of natural selection, very little has been written about the history of the term or how it was contested at given times and places. Building on James Moore’s 1991 sketch of the history of Darwinism in the 1860s, this paper specifically seeks to situate Alfred Russel Wallace’s 1889 book Darwinism in the context of a larger struggle over Darwin’s legacy in the 1880s. It is argued that Wallace used his authority as one of the founders of evolution by natural selection to reimagine what he called ‘pure Darwinism’ as a teleological evolutionism, one that integrated the theory of natural selection with an interpretation of spirit phenomena thereby producing a more agreeable and holistic account of life than was previously associated with Darwinian evolution. By considering the reception of Wallace’s Darwinism in the periodical press it will be argued further that Wallace’s interpretation of Darwinism was generally well received, which suggests that our understanding of what Darwinism meant in the late Victorian period needs to be revisited.
History-Dependent Risk Preferences: Evidence from Individual Choices and Implications for the Disposition Effect
Authors: Andrikogiannopoulou Angie , Papakonstantinou Filippos 
Published: October 2019

AbstractUsing trading data from a sports wagering market, we estimate individuals’ dynamic risk preferences within a prospect theory paradigm. This market’s experimental-like features facilitate preference estimation, and our long panel enables us to study whether preferences vary across individuals and depend on earlier outcomes. Our estimates extend support for experimental findings—mild utility curvature, moderate loss aversion, and probability overweighting of extreme outcomes—to a market setting and reveal that preferences are heterogeneous and history dependent. Applying our estimates to a portfolio choice problem, we show prospect theory can better explain the prevalence of the disposition effect than previously thought.Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Wikidata as a FAIR knowledge graph for the life sciences
Authors: Waagmeester Andra , Stupp Gregory , Burgstaller-Muehlbacher Sebastian , Good Benjamin M. , Griffith Malachi , Griffith Obi , Hanspers Kristina , Hermjakob Henning , Hudson Toby S. , Hybiske Kevin , Keating Sarah M. , Manske Magnus , Mayers Michael , Mietchen Daniel , Mitraka Elvira , Pico Alexander R. , Putman Timothy , Riutta Anders , Queralt-Rosinach Núria , Schriml Lynn M. , Shafee Thomas , Slenter Denise , Stephan Ralf , Thornton Katherine , Tsueng Ginger , Tu Roger , Ul-Hasan Sabah , Willighagen Egon , Wu Chunlei , Su Andrew I. 
Published: October 2019

AbstractWikidata is a community-maintained knowledge base that epitomizes the FAIR principles of Findability, Accessibility, Interoperability, and Reusability. Here, we describe the breadth and depth of biomedical knowledge contained within Wikidata, assembled from primary knowledge repositories on genomics, proteomics, genetic variants, pathways, chemical compounds, and diseases. We built a collection of open-source tools that simplify the addition and synchronization of Wikidata with source databases. We furthermore demonstrate several use cases of how the continuously updated, crowd-contributed knowledge in Wikidata can be mined. These use cases cover a diverse cross section of biomedical analyses, from crowdsourced curation of biomedical ontologies, to phenotype-based diagnosis of disease, to drug repurposing.
Connectivity characterization of the mouse basolateral amygdalar complex
Authors: Hintiryan Houri , Bowman Ian , Johnson David L. , Korobkova Laura , Zhu Muye , Khanjani Neda , Gou Lin , Gao Lei , Yamashita Seita , Bienkowski Michael S. , Garcia Luis , Foster Nicholas N. , Benavidez Nora L. , Song Monica Y. , Lo Darrick , Cotter Kaelan , Becerra Marlene , Aquino Sarvia , Cao Chunru , Cabeen Ryan , Stanis Jim , Fayzullina Marina , Ustrell Sarah , Boesen Tyler , Zhang Zheng-Gang , Fanselow Michael S. , Golshani Peyman , Hahn Joel D. , Wickersham Ian R. , Ascoli Giorgio A. , Zhang Li I. , Dong Hong-Wei 
Published: October 2019

ABSTRACTThe basolateral amygdalar complex (BLA) is implicated in behavioral processing ranging from fear acquisition to addiction. Newer methods like optogenetics have enabled the association of circuit-specific functionality to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. In this work, we applied computational analysis techniques to the results of our circuit-tracing experiments to create a foundational, comprehensive, multiscale connectivity atlas of the mouse BLA. The analyses identified three domains within the classically defined anterior BLA (BLAa) that house target-specific projection neurons with distinguishable cell body and dendritic morphologies. Further, we identify brain-wide targets of projection neurons located in the three BLAa domains as well as in the posterior BLA (BLAp), ventral BLA (BLAv), lateral (LA), and posterior basomedial (BMAp) nuclei. Projection neurons that provide input to each nucleus are also identifed. Functional characterization of some projection-defined BLA neurons were demonstrated via optogenetic and recording experiments. Hypotheses relating function to connection-defined BLA cell types are proposed.
Unifying single-cell annotations based on the Cell Ontology
Authors: Wang Sheng , Pisco Angela Oliveira , McGeever Aaron , Brbic Maria , Zitnik Marinka , Darmanis Spyros , Leskovec Jure , Karkanias Jim , Altman Russ B. 
Published: October 2019

AbstractSingle cell technologies have rapidly generated an unprecedented amount of data that enables us to understand biological systems at single-cell resolution. However, joint analysis of datasets generated by independent labs remains challenging due to a lack of consistent terminology to describe cell types. Here, we present OnClass, an algorithm and accompanying software for automatically classifying cells into cell types part of the controlled vocabulary that forms the Cell Ontology. A key advantage of OnClass is its capability to classify cells into cell types not present in the training data because it uses the Cell Ontology graph to infer cell type relationships. Furthermore, OnClass can be used to identify marker genes for all the cell ontology categories, independently of whether the cells types are present or absent in the training data, suggesting that OnClass can be used not only as an annotation tool for single cell datasets but also as an algorithm to identify marker genes specific to each term of the Cell Ontology, offering the possibility of refining the Cell Ontology using a data-centric approach.
Mapping the brain-wide network effects by optogenetic activation of the corpus callosum
Authors: Chen Yi , Sobczak Filip , Pais-Roldán Patricia , Schwarz Cornelius , Koretsky Alan P. , Yu Xin 
Published: October 2019

ABSTRACTThe optogenetically driven manipulation of circuit-specific activity enabled functional causality studies in animals, but its global effect on the brain is rarely reported. Here, we applied simultaneous fMRI with calcium recording to map brain-wide activity by optogenetic activation of fibers running in one orientation along the corpus callosum(CC) connecting the barrel cortex(BC). Robust positive BOLD signals were detected in the ipsilateral BC due to antidromic activity, which spread to ipsilateral motor cortex(MC) and posterior thalamus(PO). In the orthodromic target (contralateral barrel cortex), positive BOLD signals were reliably evoked by 2Hz light pulses, whereas 40Hz light pulses led to a reversed sign of BOLD - indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light with peripheral whisker stimulation at varied inter-stimulus intervals. Whisker induced positive BOLD, and calcium signals were reduced at inter-stimulus intervals of 50/100ms. The calcium-amplitude modulation (AM)-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC as well as ipsilateral MC and PO. This work raises the need of fMRI to elucidate the brain-wide network activation in response to projection-specific optogenetic stimulation.
EGFR Oncogenes Expressed In Glioblastoma Are Activated As Covalent Dimers And Paradoxically Stimulated By Erlotinib
Authors: O’Connor Matthew , Zhang Jie , Markovic Sandra , Romashko Darlene , Salomatov Andrei , Ishiyama Noboru , Iacone Roberto , Flohr Alexander , Nicolaides Theodore , Mayweg Alexander , Epstein David , Buck Elizabeth 
Published: October 2019

AbstractMutation of both the intracellular catalytic domain and the extracellular domain of the receptor for epidermal growth factor (EGFR) can drive oncogenicity. Despite clinical success with targeting EGFR catalytic site mutations, no drugs have proven effective in patients expressing allosteric extracellular domain EGFR mutations, including glioblastomas (GBM) where these mutations are highly expressed. We define the molecular mechanism for oncogenic activation of families of extracellular EGFR mutations and reveal how this mechanism renders current generation small molecule ATP-site inhibitors ineffective. We demonstrate that a group of commonly expressed extracellular domain EGFR mutants expressed in GBM is activated by disulfide-bond mediated covalent dimerization, collectively referred to as locked dimerization (LoDi) EGFR oncogenes. Strikingly, small molecules binding to the active kinase conformation (Type I), but not those binding to the inactive kinase conformation (Type II), potently inhibit catalytic site mutants, but induce covalent dimerization and activate LoDi-EGFR oncogenes, manifesting in paradoxical acceleration of proliferation.SignificanceOur data demonstrate how the locked-dimer mechanism of EGFR oncogenesis has a profound impact on the activity of small molecule inhibitors. This provides a mechanistic understanding for the failure of current generation EGFR inhibitors to effectively treat LoDi-EGFR mutants in GBM, and sets guidelines for discovery of selective LoDi-EGFR inhibitors.
Same father, same face: deep-learning reveals paternally-derived signalling of kinship in a wild primate
Authors: Charpentier Marie JE , Harté Mélanie , Poirotte Clémence , Bellefon Jade Meric de , Laubi Benjamin , Kappeler Peter M , Renoult Julien P 
Published: October 2019

ABSTRACTAnimal faces convey important information such as individual health status1 or identity2,3. Human and nonhuman primates rely on highly heritable facial traits4,5 to recognize their kin6–8. However, whether these facial traits have evolved for this specific function of kin recognition remains unknown. We present the first unambiguous evidence that inter-individual facial similarity has been selected to signal kinship using a state-of-the-art artificial intelligence approach based on deep neural networks and long-term data on a natural population of nonhuman primates. The typical matrilineal society of mandrills, is characterized by an extreme male’s reproductive skew with one male generally siring the large majority of offspring born into the different matrilines each year9. Philopatric females are raised and live throughout their lives with familiar maternal half-sisters (MHS) but because of male’s reproductive monopolization, they also live with unfamiliar paternal half-sisters (PHS). Because kin selection predicts differentiated interactions with kin rather than nonkin10 and that PHS largely outnumber MHS in a mandrills’ social group, natural selection should favour mechanisms to recognize PHS. Here, we first show that PHS socially interact with each other as much as MHS do, both more than nonkin. Second, using artificial intelligence trained to recognize individual mandrills from a database of 16k portrait pictures, we demonstrate that facial similarity increases with genetic relatedness. However, PHS resemble more to each other than MHS do, despite both kin categories sharing similar degrees of genetic relatedness. We propose genomic imprinting as a plausible genetic mechanism to explain paternally-derived facial similarity among PHS selected to improve kin recognition. This study further highlights the potential of artificial intelligence to study evolutionary mechanisms driving variation between phenotypes.