bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy
Authors: Norrish Gabrielle , Topriceanu Cristian , Qu Chen , Field Ella , Walsh Helen , Ziółkowska Lidia , Olivotto Iacopo , Passantino Silvia , Favilli Silvia , Anastasakis Aris , Vlagkouli Vasiliki , Weintraub Robert , King Ingrid , Biagini Elena , Ragni Luca , Prendiville Terrence , Duignan Sophie , McLeod Karen , Ilina Maria , Fernández Adrian , Bökenkamp Regina , Baban Anwar , Drago Fabrizio , Kubuš Peter , Daubeney Piers E F , Chivers Sian , Sarquella-Brugada Georgia , Cesar Sergi , Marrone Chiara , Medrano Constancio , Alvarez Garcia-Roves Reyes , Uzun Orhan , Gran Ferran , Castro Fernandez J , Gimeno Juan R , Barriales-Villa Roberto , Rueda Fernando , Adwani Satish , Searle Jonathan , Bharucha Tara , Siles Ana , Usano Ana , Rasmussen Torsten B , Jones Caroline B , Kubo Toru , Mogensen Jens , Reinhardt Zdenka , Cervi Elena , Elliott Perry M , Omar Rumana Z , Kaski Juan P 
Published: March 2021

Abstract

Aims
The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events.

Methods and results
Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of &gt;5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7%

Conclusion
In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.
Criterion validity of a single-item question for assessment of daily breaks in sedentary time in adults
Authors: Júdice Pedro B , Rosa Gil B , Magalhães João P , Hetherington-Rauth Megan , Correia Inês R , Sardinha Luís B 
Published: March 2021

Abstract

Background
As the implementation of sensor-based assessment for sedentary time (ST) and physical activity (PA) has practical limitations when applied on a large-scale, most studies rely on subjective data. We aimed to examine the criterion validity of a single-item question to assess daily breaks in ST and other PA-related outcomes for the first time using sensor-based data as the criterion.

Methods
In a sample of 858 adults, breaks in ST and other PA-related parameters were assessed through sensor-based accelerometry and subjective data, which included a comprehensive questionnaire with a specific question (‘During the day, do you usually sit for a long time in a row or interrupt frequently?’) with a three-level closed answer. The Spearman’s rank correlation coefficient was used to determine the agreement between the single-item question and sensor-based data.

Results
Positive correlations were found for self-reported breaks in ST with sensor-based breaks in ST in both women (ρ=0.37; 95% CI=0.29–0.44) and men (ρ=0.15; 95% CI=0.04–0.26). Self-reported breaks in ST were inversely correlated with ST in women (ρ =−0.33; 95% CI=−0.40 to 0.25). For both sexes, self-reported breaks in ST showed a positive correlation with light-intensity PA (ρ=0.39; 95% CI=0.31–0.46 women; ρ=0.13; 95% CI=0.02–0.24 men), however, positive correlations between self-reported breaks in ST and moderate-to-vigorous PA (ρ=0.13; 95% CI=0.02–0.24) were found only in men.

Conclusions
Our single-item question can be used as an indication for ranking people’s breaks in ST during the waking day, although acknowledging that some misclassification will occur, especially in men. There must be an effort to include this question in future national and international surveys to replicate these findings.
Rickettsia-host interaction: strategies of intracytosolic host colonization
Authors: Voss Oliver H , Rahman M Sayeedur 
Published: March 2021

ABSTRACTBacterial infection is a highly complex biological process involving a dynamic interaction between the invading microorganism and the host. Specifically, intracellular pathogens seize control over the host cellular processes including membrane dynamics, actin cytoskeleton, phosphoinositide metabolism, intracellular trafficking and immune defense mechanisms to promote their host colonization. To accomplish such challenging tasks, virulent bacteria deploy unique species-specific secreted effectors to evade and/or subvert cellular defense surveillance mechanisms to establish a replication niche. However, despite superficially similar infection strategies, diverse Rickettsia species utilize different effector repertoires to promote host colonization. This review will discuss our current understandings on how different Rickettsia species deploy their effector arsenal to manipulate host cellular processes to promote their intracytosolic life within the mammalian host.
On the relationship between strain rate and seismicity in the India–Asia collision zone: implications for probabilistic seismic hazard
Authors: Stevens V L , Avouac J-P 
Published: March 2021

SUMMARYThe increasing density of geodetic measurements makes it possible to map surface strain rate in many zones of active tectonics with unprecedented spatial resolution. Here we show that the strain tensor rate calculated from GPS in the India–Asia collision zone represents well the strain released in earthquakes. This means that geodetic data in the India–Asia collision zone region can be extrapolated back in time to estimate strain buildup on active faults, or the kinematics of continental deformation. We infer that the geodetic strain rates can be assumed stationary through time on the timescale needed to build up the elastic strain released by larger earthquakes, and that they can be used to estimate the probability of triggering earthquakes. We show that the background seismicity rate correlates with the geodetic strain rate. A good fit is obtained assuming a linear relationship ($\dot{N} = \lambda \ \cdot \dot{\epsilon }$, where $\dot{N}$ is the density of the rate of Mw ≥ 4 earthquakes, $\dot{\epsilon }$ is strain rate and λ = 2.5 ± 0.1 × 10−3 m−2), as would be expected from a standard Coulomb failure model. However, the fit is significantly better for a non-linear relationship ($\dot{N} = \gamma _1 \cdot \dot{\epsilon }^{\gamma _2}$ with γ1 = 2.5 ± 0.6 m−2 and γ2 = 1.42 ± 0.15). The b-value of the Gutenberg–Richter law, which characterize the magnitude–frequency distribution, is found to be insensitive to the strain rate. In the case of a linear correlation between seismicity and strain rate, the maximum magnitude earthquake, derived from the moment conservation principle, is expected to be independent of the strain rate. By contrast, the non-linear case implies that the maximum magnitude earthquake would be larger in zones of low strain rate. We show that within areas of constant strain rate, earthquakes above Mw 4 follow a Poisson distribution in time and and are uniformly distributed in space. These findings provide a framework to estimate the probability of occurrence and magnitude of earthquakes as a function of the geodetic strain rate. We describe how the seismicity models derived from this approach can be used as an input for probabilistic seismic hazard analysis. This method is easy to automatically update, and can be applied in a consistent manner to any continental zone of active tectonics with sufficient geodetic coverage.
The monks of Rochester and the hospital of St. Mary of Strood: a twelfth-century dispute reassessed
Authors: Barnaby James 
Published: March 2021

Abstract
This article assesses the twelfth-century Rochester dispute concerning St. Mary’s hospital at Strood. Bishop Gilbert Glanville’s plan to endow the hospital with monastic estates was vigorously resisted by the cathedral monks, with Gilbert traditionally being seen as an anti-monastic bishop. This article reassesses the events of the conflict and places it in the context of other twelfth-century disputes. It argues that Gilbert was not trying to supplant his cathedral chapter, but was instead trying to establish a hospital to care for the needs of the sick and poor pilgrims.
Micronations: A lacuna in the law
Authors: Hobbs Harry , Williams George 
Published: March 2021

Abstract
Around 100 active micronations exist across the globe. Led by committed and eccentric individuals, these aspirant or wannabe states assert their claims to sovereignty in myriad ways. In dressing in the language of statehood, they challenge understandings of, and approaches to, international legal personality. In this article we provide the first legal survey of micronations. We develop a conceptual framework to understand what it means to be a micronation, explore their various forms, and analyze key public law issues. Our survey reveals that, although public law has not engaged with this phenomenon, states respond to the assertion of sovereignty by micronations in both benign and violent ways.
Mechanical circulatory support in coronavirus disease-2019-positive patients with severe respiratory failure
Authors: Natanov Ruslan , Wiesner Olaf , Haverich Axel , Kühn Christian 
Published: March 2021

Abstract

OBJECTIVES
Treatment of severe acute respiratory distress syndrome (ARDS) induced by severe acute respiratory syndrome coronavirus 2 has been heavily debated. Our goal was to describe our findings in patients with severe ARDS due to severe coronavirus disease 2019 (sCOVID-19) treated with venovenous extracorporeal membrane oxygenation (vv-ECMO).

METHODS
We retrospectively examined all patients treated with vv-ECMO for severe ARDS due to acute respiratory syndrome coronavirus 2.

RESULTS
In total, 13 patients were treated with vv-ECMO in our medical centre. The mean patient age was 48.1 years. Most patients were obese (69%) and male (85%). All patients were mechanically ventilated before ECMO. The mean time from intubation to proning was 16.6 h; the time from start of prone therapy to vv-ECMO implantation was 155.1 h. The mean total ECMO run time was 358 h. Significant reduction of positive end-expiratory pressure (P = 0.02), peak pressure (P = 0.001) and minute volume (P = 0.03) could be achieved after implantation of vv-ECMO. All patients showed an inflammatory response. Overall mortality was 30.7%: 1 patient died of mesenteric ischaemia; 3 patients died of multiple organ failure. A worse prognosis was seen in patients with highly elevated concentrations of interleukin-6.

CONCLUSIONS
The use of vv-ECMO in patients with sCOVID-19-induced ARDS is safe and associated with improved respiratory ventilation settings. The rate of immune system involvement plays a pivotal role in the development and outcome of sCOVID-19.
Accuracy and reliability of injury coding in the national Dutch Trauma Registry
Authors: Twiss Eric , Krijnen Pieta , Schipper Inger 
Published: March 2021

Abstract

Objective
Injury coding is well known for lack of completeness and accuracy. The objective of this study was to perform a nationwide assessment of accuracy and reliability on Abbreviated Injury Scale (AIS) coding by Dutch Trauma Registry (DTR) coders and to determine the effect on Injury Severity Score (ISS). Additionally, the coders’ characteristics were surveyed.

Methods
Three fictional trauma cases were presented to all Dutch trauma coders in a nationwide survey (response rate 69%). The coders were asked to extract and code the cases’ injuries according to the AIS manual (version 2005, update 2008). Reference standard was set by three highly experienced coders. Summary statistics were used to describe the registered AIS codes and ISS distribution. The primary outcome measures were accuracy of injury coding and inter-rater agreement on AIS codes. Secondary outcome measures were characteristics of coders: profession, work setting, experience in injury coding and training level in injury coding.

Results
The total number of different AIS codes used to describe 14 separate injuries in the three cases was 89. Mean accuracy per AIS code was 42.2% (range 2.4–92.7%). Mean accuracy on number of AIS codes was 23%. Overall inter-rater agreement per AIS code was 49.1% (range 2.4–92.7%). The number of assigned AIS codes varied between 0 and 18 per injury. Twenty-seven percentage of injuries were overlooked. ISS was correctly scored in 42.4%. In 31.7%, the AIS coding of the two more complex cases led to incorrect classification of the patient as ISS &lt; 16 or ISS ≥ 16. Half (47%) of the coders had no (para)medical degree, 26% were working in level I trauma centers, 37% had less than 2 years of experience and 40% had no training in AIS coding.

Conclusions
Accuracy of and inter-rater agreement on AIS injury scoring by DTR coders is limited. This may in part be due to the heterogeneous backgrounds and training levels of the coders. As a result of the inconsistent coding, the number of major trauma patients in the DTR may be over- or underestimated. Conclusions based on DTR data should therefore be drawn with caution.
Antibiotics and healthcare facility-associatedClostridioides difficileinfection: systematic review and meta-analysis 2020 update
Authors: Slimings Claudia , Riley Thomas V 
Published: March 2021

AbstractBackgroundAntibiotic use is the most important modifiable risk factor for healthcare facility-associated Clostridioides difficile infection (HCFA-CDI). Previous systematic reviews cover studies published until 31 December 2012.ObjectivesTo update the evidence for associations between antibiotic classes and HCFA-CDI to 31 December 2020.MethodsPubMed, Scopus, Web of Science Core Collection, WorldCat and Proquest Dissertations & Theses were searched for studies published since 1 January 2013. Eligible studies were those conducted among adult hospital inpatients, measured exposure to individual antibiotics or antibiotic classes, included a comparison group and measured the occurrence of HCFA-CDI as an outcome. The Newcastle–Ottawa Scale was used to appraise study quality. To assess the association between each antibiotic class and HCFA-CDI, a pooled random-effects meta-analysis was undertaken. Meta-regression and subgroup analysis was used to investigate study characteristics identified a priori as potential sources of heterogeneity.ResultsCarbapenems and third- and fourth-generation cephalosporin antibiotics remain the most strongly associated with HCFA-CDI, with cases more than twice as likely to have recent exposure to these antibiotics prior to developing HCFA-CDI. Modest associations were observed for fluoroquinolones, clindamycin and β-lactamase inhibitor combination penicillin antibiotics. Individual study effect sizes were variable and heterogeneity was observed for most antibiotic classes.ConclusionsThis review provides the most up-to-date synthesis of evidence in relation to the risk of HCFA-CDI associated with exposure to specific antibiotic classes. Studies were predominantly conducted in North America or Europe and more studies outside of these settings are needed.
Goals, life events, and transitions: examining fertility apps for holistic health tracking
Authors: Costa Figueiredo Mayara , Huynh Thu , Takei Anna , Epstein Daniel A , Chen Yunan 
Published: March 2021

Abstract

Objective
Fertility is becoming increasingly supported by consumer health technologies, especially mobile apps that support self-tracking activities. However, it is not clear whether the apps support the variety of goals and life events of those who menstruate, especially during transitions between them.

Methods
Thirty-one of the most popular fertility apps were evaluated, analyzing data from three sources: the content of app store pages, app features, and user reviews.

Findings
Results suggest that fertility apps are designed to support specific life goals of people who menstruate, offering several data collection features and limited feedback options. However, users often desire holistic tracking that encompasses a variety of goals, life events, and the transitions among them.

Discussion
These findings suggest fertility patients can benefit more from holistic self-tracking and provide insights for future design of consumer health technologies that better support holistic fertility tracking.

Conclusion
Fertility apps have the potential to support varied experiences of people who menstruate. But to achieve that, apps need to expand their support by offering ways for more users to perform holistic, personalized, and personally meaningful tracking, so they can derive long-term benefit from the data they collect.
A12 PRE-TREATMENT HLADQA1-HLADRB1 TESTING FOR THE PREVENTION OF AZATHIOPRINE-INDUCED PANCREATITIS IN INFLAMMATORY BOWEL DISEASE: A PROSPECTIVE COHORT STUDY
Authors: Wilson A , Wang M , Ponich T , Gregor J C , Chande N , Yan B , Sey M , Beaton M D , Kim R 
Published: March 2021

Abstract

Background
Azathioprine (AZA) therapy has a long history of use in IBD. The need to promote its safe use in this population is ensured by governmental health policy requiring IBD patients to fail low cost drugs, such as AZA, prior to approving funding for more potent biologic therapies. AZA-induced pancreatitis is an idiosyncratic and unpredictable response, occurring in up to 7% of AZA-exposed patients that can lead to patient morbidity, hospitalization, delay in effective IBD management, as well as result in substantial additional health-related costs. There are no tools in clinical practice to identify individuals at risk of AZA-induced pancreatitis. Genetic variation in the HLADQA1-HLADRB1*07:01 haplotype is strongly associated with azathioprine (AZA)-induced pancreatitis in inflammatory bowel disease (IBD).

Aims
To evaluate whether HLA DQA1-HLADRB1*07:01A&gt;C pre-treatment genotype testing in an adult IBD population prior to AZA therapy to guide AZA selection would result in a lower incidence of AZA-induced pancreatitis.

Methods
Participants with IBD (n=599) were screened for HLADQA1-HLADRB1*07:01A&gt;C and participants with a variant genotype were excluded from azathioprine treatment (n=271). Wildtype participants (n=328) were started on azathioprine and followed for 3 months. The incidence of pancreatitis was compared to unscreened historical controls (n=373).

Results
The minor allele frequency of HLADQA1-HLADRB1*07:01 was 30.4% and 30.0% in the screened and unscreened populations respectively. Up to 45.2% of participants were excluded from AZA therapy based on genotype in the HLADQA1-HLADRB1*07:01A&gt;C screened cohort. HLADQA1-HLADRB1*07:01A&gt;C screening resulted in an 11-fold reduction in the odds of azathioprine-induced pancreatitis (0.30% versus 3.4%, OR=0.085, 95%CI=0.011–0.651, p=0.002).

Conclusions
HLA DQA1-HLADRB1*07:01A&gt;C screening substantially reduced the risk of pancreatitis during AZA treatment in patients with IBD. However, using this strategy as a tool for guiding the use of AZA therapy in IBD may eliminate a large proportion of patients from being eligible for treatment with AZA. In regions, where there is access to other IBD therapies, and given the short and long term toxicities associated with AZA, HLA DQA1-HLADRB1*07:01A&gt;C screening may be a clinically-relevant strategy for enhancing the safe use of AZA in IBD. Additionally, cost-effectiveness analyses are needed to further solidify the utility of HLA DQA1-HLADRB1*07:01A&gt;C-screening in IBD populations.

Funding Agencies
Academic Medical Organization of Southwestern Ontario Innovation Fund
A16 FIBER SUPPLEMENTATION DIFFERENTIALLY MODULATES RESPONSES TO FECAL MICROBIAL TRANSPLANTATION IN PATIENTS WITH METABOLIC SYNDROME AND SEVERE OBESITY: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT TRIAL
Authors: Mocanu V , Zhang Z , Deehan E , Samarasinghe K , Hotte N , Kao D H , Karmali S , Birch D W , Walter J , Madsen K 
Published: March 2021

Abstract

Background
Fecal microbial transplantation (FMT) from lean donors to obese patients with metabolic syndrome (MS) has been associated with promising yet short-term metabolic improvements. The concept of using dietary or fiber supplementation to enhance effects induced by FMT has been much discussed in the literature, but to date no human trials have examined this concept.

Aims
The aim of this study was to determine if fiber supplementation following FMT was able to enhance or sustain FMT-mediated metabolic benefits.

Methods
We performed a 12-wk double-blind randomized placebo-controlled trial in patients with severe obesity and MS recruited from Edmonton’s Bariatric Clinic from 2018 to 2019. Patients were stratified by sex and block randomized 1:1:1:1 amongst one of four groups: (1) Placebo FMT and a non-fermentable fiber (NF) (2) Placebo FMT and fermentable fiber (FF); (3) FMT and non-fermentable fiber (FMT-NF); and (4) FMT and fermentable fiber (FMT-FF). Patients received a single dose of FMT (50g donor stool) with 20 oral capsules followed by a 6-wk period of daily fiber. The primary outcome was evaluating mean differences (MD) in insulin sensitivity from baseline to 6-wks using the homeostatic model assessment of insulin resistance (HOMA2-IR).

Results
Sixty-eight patients were randomized with 61 completing the primary outcome (NF = 17; FF = 15; FMT-NF = 14; FMT-FF = 15) and evaluated using a modified intent-to-treat analysis. Baseline characteristics were similar with a mean BMI 45 ± 7 kg/m2, a female predominance (83.6%), and a HOMA2-IR of 3.43 ± 2.2. There were no baseline differences in clinical characteristics, metabolic parameters, medications, or dietary intake. FMT-NF had improvements in HOMA2-IR (MD -24.0% ± 12.0%; p=0.02), insulin sensitivity (MD 27.6% ± 12.3%; p=0.02), and insulinemia (MD -25.4% ± 12.3%; p=0.02) from baseline to 6-wks (Figure 1). These benefits were associated with increased microbial richness and improvements in GLP-1 metabolism. Linear mixed model regression revealed that select bacterial taxa including Phascolarctobacterium, Ruminococcaeceae, and B. stercoris correlated with increased insulin sensitivity. Findings occurred in the absence of changes in anthropometric parameters, dietary intake, medication regimen and were not observed in groups receiving fermentable fiber or in any group following cessation of fiber.

Conclusions
This proof-of-concept trial provides evidence that a single FMT dose combined with daily non-fermentable fiber supplementation can successfully improve insulin resistance in patients with metabolic syndrome and severe obesity on optimized medical therapy.

Funding Agencies
W. Garfield Weston Foundation