bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome
Authors: Wang Qing , Leclerc Julie , Bougeard Gaëlle , Olschwang Sylviane , Vasseur Stéphanie , Cassinari Kévin , Boidin Denis , Lefol Cédrick , Naïbo Pierre , Frébourg Thierry , Buisine Marie Pierre , Baert-Desurmont Stéphanie 
Published: January 2020

BackgroundHeterozygous germline PMS2 variants are responsible for about 5% of Lynch syndrome (LS) but their prevalence is most likely underestimated because of complicated routine screening caused by highly homologous pseudogenes. Consequently, there is limited knowledge on the implication of the PMS2 gene in LS.MethodsWe report 200 PMS2 heterozygous variants identified in 195 French patients, including 112 unique variants classified as class-3/4/5.ResultsGenomic rearrangements account for 18% of alterations. The c.137G>T variant was observed in 18% of the patients, but a founder effect could not be clearly identified by haplotype analysis. Among class-4/5 variant carriers, the median age at first tumour onset was 49 years with a predominance of colorectal (80%) and endometrial (8.1%) cancers. Seven patients developed colorectal cancers before the age of 30 with the youngest at the age of 21. Only 6.2% of class-4/5 carriers had a family history fulfilling Amsterdam I/II criteria among patients with available data. Tumours from PMS2 variant carriers exhibited microsatellite instability (96%) and loss of PMS2 expression (76%), confirming the high predictive value of somatic analysis.ConclusionOur results provide further insight into the role of the PMS2 gene in LS. While PMS2 variants are mostly detected in families not fulfilling Amsterdam criteria, which supports their lower penetrance, they can nevertheless cause early-onset cancers, highlighting the variability of their penetrance.
Robust measurement of clinical improvement in patients with cutaneous lupus erythematosus
Authors: Nanes Benjamin A , Zhu Jane L , Chong Benjamin F 
Published: January 2020

ObjectiveThe severity and disease course of cutaneous lupus erythematosus (CLE) are highly variable. Consequently, outcome measures for CLE clinical improvement are heterogeneous, complicating treatment decisions and therapeutic development. This study characterises CLE outcome measures and identifies the influence of clinical improvement thresholds on strengths of associations with patient demographic and clinical factors.MethodsIn this pilot cohort study, multivariable models identified factors associated with CLE activity and skin damage improvement, defined as relative decreases in Cutaneous Lupus Activity and Severity Index (CLASI) activity (CLASI-A) and damage (CLASI-D) scores, over ranges of response thresholds.Results66 patients with 119 visit-pairs were included in the CLASI-A analysis. 74 patients with 177 visit-pairs were included in the CLASI-D analysis. Factors associated with CLE activity and damage improvement depended on the response threshold. Some associations were stronger at more stringent thresholds, including subacute CLE predominance with increased likelihood of CLASI-A improvement (R2=0.73; 50% reduction: OR 1.724 (95% CI 0.537 to 5.536); 75%: 5.67 (95% CI 1.56 to 20.5)) and African-American race with decreased likelihood of CLASI-D improvement (R2=0.80; 20%: 0.40 (95% CI 0.17 to 0.93); 40%: 0.25 (95% CI 0.08 to 0.82)). Other associations were stable across multiple thresholds, including older age of CLE development with increased likelihood of CLASI-A improvement (R2=0.25; 50%: 1.05 (95% CI 1.01 to 1.09]; 75%: 1.05 (95% CI 1.00 to 1.10)) and higher initial disease activity with decreased likelihood of CLASI-D improvement (R2=0.55; 20%: 0.91 (95% CI 0.84 to 0.98); 40%: 0.88 (95% CI 0.79 to 0.97)).ConclusionsExamining a range of CLASI threshold outcomes can comprehensively characterise changes in disease course in patients with CLE. Insufficiently stringent thresholds may fail to distinguish meaningful clinical change from natural fluctuation in disease activity.
Cost-effectiveness of ablation of ventricular tachycardia in ischaemic cardiomyopathy: limitations in the trial evidence base
Authors: Chen Yang , Gomes Manuel , Garcia Jason V , Hunter Ross J , Chow Anthony W , Dhinoja Mehul , Schilling Richard J , Lowe Martin , Lambiase Pier D 
Published: January 2020

ObjectiveCatheter ablation is an important treatment for ventricular tachycardia (VT) that reduces the frequency of episodes of VT. We sought to evaluate the cost-effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy.MethodsA decision-analytic Markov model was used to calculate the costs and health outcomes of catheter ablation or AAD treatment of VT for a hypothetical cohort of patients with ischaemic cardiomyopathy and an implantable cardioverter-defibrillator. The health states and input parameters of the model were informed by patient-reported health-related quality of life (HRQL) data using randomised clinical trial (RCT)-level evidence wherever possible. Costs were calculated from a 2018 UK perspective.ResultsCatheter ablation versus AAD therapy had an incremental cost-effectiveness ratio (ICER) of £144 150 (€161 448) per quality-adjusted life-year gained, over a 5-year time horizon. This ICER was driven by small differences in patient-reported HRQL between AAD therapy and catheter ablation. However, only three of six RCTs had measured patient-reported HRQL, and when this was done, it was assessed infrequently. Using probabilistic sensitivity analyses, the likelihood of catheter ablation being cost-effective was only 11%, assuming a willingness-to-pay threshold of £30 000 used by the UK’s National Institute for Health and Care Excellence.ConclusionCatheter ablation of VT is unlikely to be cost-effective compared with AAD therapy based on the current randomised trial evidence. However, better designed studies incorporating detailed and more frequent quality of life assessments are needed to provide more robust and informed cost-effectiveness analyses.
Plasmon mediated decomposition of brominated nucleobases on silver nanoparticles – A surface enhanced Raman scattering (SERS) study
Authors: Dutta Anushree , Schürmann Robin , Bald Ilko 
Published: January 2020

Abstract
The localized surface plasmon resonances (LSPRs) of silver nanoparticles (AgNPs) give rise to the generation of so called hot electrons and a high local electric field enhancement, which enable an application of AgNPs in different fields ranging from catalysis to sensing. Hot electrons generated upon the decay of LSPRs are transferred to molecules adsorbed on the surface of the NPs and trigger chemical reactions via dissociative electron attachment (DEA). Herein, we report on the hot electron induced decomposition of the brominated nucleobases – 8-bromoadenine, 8-bromoguanine, 5-bromocytosine and 5-bromouracil on laser illuminated AgNP surfaces. Surface enhanced Raman scattering (SERS) spectra of all canonical nucleobases and their brominated analogues have been recorded at different laser illumination times, and for the very first time we present SERS measurements of 8-bromoguanine and 5-bromocytosine. Reaction products have been identified by their vibrational fingerprint revealing the cleavage of the carbon bromide bond in all cases even under mild illumination conditions. These results indicate that the well-known reactions from DEA experiments in the gas phase (i) are also taking place on nanoparticle surfaces under ambient conditions, (ii) can be monitored by SERS, and (iii) are also of importance in analytical SERS applications involving electrophilic molecules, as the bands originating from reaction products need to be identified.

Graphical abstract
A high resolution multi-turn TOF mass analyzer
Authors: Shchepunov Vyacheslav , Rignall Michael , Giles Roger , Fujita Ryo , Waki Hiroaki , Nakanishi Hiroaki 
Published: January 2020

An ion optical design of a high resolution multi-turn time-of-flight mass analyzer (MT-TOF MA) is presented. The analyzer has rotationally symmetric main electrodes with additional mirror symmetry about a mid-plane orthogonal to the axis of symmetry. Rotational symmetry allows a higher density of turns in the azimuthal (drift) direction compared to MT-TOF MAs that are linearly extended in the drift direction. Mirror symmetry about a mid-plane helps to achieve a high spatial isochronicity of the ions’ motion. The analyzer comprises a pair of polar-toroidal sectors S1 and S3, a pair of polar (trans-axial) lenses, and a pair of conical lenses for longitudinal and lateral focusing. A toroidal sector S2 located at the mid-plane of the analyzer has a set of embedded drift focusing segments providing focusing and spatial isochronicity in the drift direction. The ions’ drift in the azimuthal direction can be reversed by using dedicated reversing deflectors. This gives the possibility of several operational modes with different numbers of turns and passes in the drift direction. According to numerical simulations, the mass resolving power of the analyzer ranges from [Formula: see text]40 k (fwhm) at small (typically below ten) numbers of turns to [Formula: see text]450 k (fwhm) at 96 turns.
Accumulation of Deficits as a Key Risk Factor for Cardiovascular Morbidity and Mortality: A Pooled Analysis of 154 000 Individuals
Authors: Farooqi Mohammed A. M. , Gerstein Hertzel , Yusuf Salim , Leong Darryl P. 
Published: January 2020

Background

Frailty is associated with higher mortality in individuals at high cardiovascular disease (
CVD
) risk. We hypothesize that frailty is a more important prognostic factor than
CVD
risk factors and aim to determine the prognostic value of a cumulative deficit frailty index in patients with or at high risk for
CVD
.

Methods and Results

We conducted an individual‐level pooled analysis of participants with or at risk for
CVD
, recruited in 14 multicenter clinical trials. The cumulative deficit index was calculated as the proportion of 26 deficits exhibited. Individuals were categorized as nonfrail, prefrail, or frail if they had indexes of ≤0.1, >0.1 to 0.21, or >0.21, respectively.
CVD
risk was assessed using the Framingham score. Outcomes included
CVD
event (new or recurrent myocardial infarction, stroke, or heart failure) and mortality. We studied 154 696 patients (mean age, 70.8 years; 63% men) with median follow‐up of 3.2 years. There were 17 535
CVD
events and 15 067 deaths. The frail group (n=13 872) had higher risk of a
CVD
event (incidence rate ratio, 1.97; 95%
CI
, 1.85–2.08), all‐cause mortality (hazard ratio, 1.91; 95%
CI
, 1.79–2.03), and
CVD
mortality (hazard ratio, 1.91; 95%
CI
, 1.77–2.05) than the nonfrail group (n=101 343). Associations remained unchanged after adjusting for
CVD
risk factors. The index statistically outperformed the Framingham score in its ability to discriminate
CVD
events (C‐statistic, 0.60 [95%
CI
, 0.60–0.61] versus 0.58 [95%
CI
, 0.57–0.58], respectively;
P
<0.001).

Conclusions

In individuals with or at high risk of developing
CVD
, the cumulative deficit index is associated with increased
CVD
events and mortality, independent of
CVD
risk factors, and adds incremental prognostic value.
Comparison of Eulerian Bin and Lagrangian Particle-Based Schemes in Simulations of Pi Chamber Dynamics and Microphysics
Authors: Grabowski Wojciech W. 
Published: January 2020

Abstract
This paper presents a comparison of simulations applying either a traditional Eulerian bin microphysics or a novel particle-based Lagrangian approach to represent CCN activation and cloud droplet growth. The Eulerian microphysics solve the evolution equation for the spectral density function, whereas the Lagrangian approach follows computational particles referred to as superdroplets. Each superdroplet represents a multiplicity of natural droplets that makes the Lagrangian approach computationally feasible. The two schemes apply identical representation of CCN activation and use the same droplet growth equation; these make direct comparison between the two schemes practical. The comparison, the first of its kind, applies an idealized simulation setup motivated by laboratory experiments with the Pi Chamber and previous model simulations of the Pi Chamber dynamics and microphysics. The Pi Chamber laboratory apparatus considers interactions between turbulence, CCN activation, and cloud droplet growth in moist Rayleigh–Bénard convection. Simulated steady-state droplet spectra averaged over the entire chamber are similar, with the mean droplet concentration, mean radius, and spectral width close in Eulerian and Lagrangian simulations. Small differences that do exist are explained by the inherent differences between the two schemes and their numerical implementation. The local droplet spectra differ substantially, again in agreement with the inherent limitations of the theoretical foundation behind each approach. There is a general agreement between simulations and Pi Chamber observations, with simplifications of the CCN activation and droplet growth equation used in the simulations likely explaining specific differences.
The Diurnal Cycle of Rainfall and the Convectively Coupled Equatorial Waves over the Maritime Continent
Authors: Sakaeda Naoko , Kiladis George , Dias Juliana 
Published: January 2020

AbstractPrecipitation variability over the Maritime Continent is predominantly explained by its diurnal cycle and large-scale disturbances such as the Madden–Julian oscillation (MJO) and convectively coupled equatorial waves (CCEWs). To advance our understanding of their interactions and physical processes, this study uses satellite data to examine changes in the diurnal cycle of rainfall associated with the MJO and CCEWs over the Maritime Continent. We find that diurnal cycle modulations associated with the passage of any type of large-scale disturbance are closely tied to changes in rain types and land–sea diurnal propagation of rainfall. When the amplitude of the diurnal cycle increases over the islands, the phase of the diurnal cycle is delayed by a few hours as clouds are more organized and rainfall from stratiform-anvil clouds increases. Enhanced amplitude of the diurnal cycle can alter the speed of land–sea diurnal propagation of rainfall, which then influences the timing of diurnal rainfall over coastal regions. These changes in the diurnal cycle occur asymmetrically across the island terrain associated with the MJO and equatorial Rossby waves, while such asymmetric modulations are not observed for other waves. Geographical and wave dependencies of the diurnal cycle are linked to differences in large-scale lower tropospheric wind, vertical motion, and moisture profile perturbations, which are in turn tied to differences in cloud population evolution. The results of this study highlight the importance of further improving our understanding of the sensitivity of cloud populations to varying large-scale phenomena.
Southeastern U.S. Tornado Outbreak Likelihood Using Daily Climate Indices
Authors: Brown Matthew C. , Nowotarski Christopher J. 
Published: January 2020

AbstractThis study investigates relationships between climate-scale patterns and seasonal tornado outbreaks across the southeastern United States. Time series of several daily climate indices—including Arctic Oscillation (AO), North Atlantic Oscillation (NAO), Pacific–North American (PNA) pattern, east/west Pacific Oscillation (EPO/WPO), and both raw and detrended Gulf of Mexico SST anomalies (SSTA/SSTAD)—are collected in advance of Southeast severe convective days and grouped using self-organizing maps (SOMs). Spatiotemporal distributions of storm reports within nodes are compared to seasonal climatology, and the evolution of the regional environment for nodes associated with outbreaks is analyzed to provide physical justification for such associations. This study confirms findings from several tornado-related climate studies in the literature, while also identifying a number of new patterns associated with Southeast tornado outbreaks. Both the AO and NAO are relevant across all seasons, especially on lead time scales of 1–2 months, while SSTA/SSTADs are relevant on smaller time scales. The physical connection between these patterns and the regional storm environment is largely related to alterations of upper-level circulation and jet stream patterns, which in turn influence deep- and low-level shear, inland transport of moisture and instability, and other regional characteristics pertinent to tornado outbreaks. These results suggest that climate-scale variability can modulate and potentially be used to predict regional storm environments and their likelihood to produce tornado outbreaks across the Southeast.
Image quality in abdominal CT using an iodine contrast reduction algorithm employing patient size and weight and low kV CT technique
Authors: Iyer Veena R , Ehman Eric C , Khandelwal Ashish , Wells Michael L , Lee Yong S , Weber Nikkole M , Johnson Matthew P , Yu Lifeng , McCollough Cynthia H , Fletcher Joel G 
Published: January 2020

Background Low tube potential-high tube current computed tomography (CT) imaging allows reduction in iodine-based contrast dose and may extend the benefit of routine contrast-enhanced CT exams to patients at risk of nephrotoxicity. Purpose To determine the ability of an iodine contrast reduction algorithm to maintain diagnostic image quality for contrast-enhanced abdominal CT. Material and Methods CT exams with iodine contrast reduction were prescribed for patients at risk for renal dysfunction. The iodine contrast reduction algorithm combines weight-based contrast volume reduction with patient width-based low tube potential selection and bolus-tracking. Control exams with routine iodine dose were selected based on weight, width, and scan protocol. Three radiologists evaluated image quality and diagnostic confidence using a 4-point scale (<2 acceptable). Another radiologist assessed contrast reduction indications and measured portal vein and liver contrast-to-noise ratios. Results Forty-six contrast reduction algorithm and control exams were compared (mean creatinine 1.6 vs. 1.2 mg/dL, P ≤  0.0001). Thirty-nine contrast reduction patients had an eGFR <60 mL/min/1.73m2 and 15 had single or transplanted kidney. Mean iodine contrast dose was lower in the contrast reduction group (20.9 vs. 39.4 g/mL, P <  0.0001). Diagnostic confidence was rated as acceptable in 95% (131/138) of contrast reduction and 100% of control exams (1.18–1.28 vs. 1.02–1.13, respectively; P >  0.06). Liver attenuation and contrast-to-noise ratio (CNR) were similar ( P =  0.08), but portal vein attenuation and CNR were lower with contrast-reduction (mean 176 vs. 198 HU, P =  0.02; 13 vs. 16, P =  0.0002). Conclusion This size-based contrast reduction algorithm using low kV and bolus tracking reduced iodine contrast dose by 50%, while achieving acceptable image quality in 95% of exams.
Comparing face-to-face with online training for occupational therapists in advising on fitness for work: Protocol for the CREATE study
Authors: Coole Carol , Konstantinidis Stathis T , Ablewhite Joanne , Radford Kate , Thomson Louise , Khan Sayeed , Drummond Avril 
Published: January 2020

Introduction Occupational therapists play a key role in advising on fitness for work; however, there is a concern that they lack knowledge and confidence in using the Allied Health Professions health and work report (formerly the Allied Health Professions advisory fitness for work report), developed in the United Kingdom. Comparing a reusable learning object with face-to-face training for occupational therapists in advising on fitness for work (CREATE) compares face-to-face training with online training for occupational therapists in completing the Allied Health Professions health and work report. Method A mixed methods study. Phase 1, occupational therapists will co-design an online training resource. A standardised face-to-face group-based training session will also be developed based on the same content. Phase 2, a feasibility study will be conducted. Thirty occupational therapists will either attend face-to-face group training or access the online resource. Data on self-reported knowledge and confidence in using the Allied Health Professions health and work report will be collected at baseline, 1 week and 8 weeks post-training. Feedback on the training will be collected by interview and, for the online resource, using an online tool. Results Quantitative results will be predominantly analysed descriptively. If appropriate, between-group responses will be compared using the Mann–Whitney test. Qualitative findings will be analysed thematically. Conclusion CREATE will have made a significant contribution to the debate around appropriate training methods in advising on fitness for work.
Following severe childhood stroke, specialised residential rehabilitation improves self-care independence but there are ongoing needs at discharge
Authors: Wales Lorna , Dunford Carolyn , Davis Kathy 
Published: January 2020

Introduction Stroke is a major cause of mortality and disability in childhood. There is a false belief that children will recover better than adults and recent research confirms that younger age at injury can have a negative impact on rehabilitation outcomes, resulting in lifelong disability. Self-care is a key rehabilitation outcome for children and young people. Methods This service evaluation reviews routinely collected clinical self-care data from one specialised residential rehabilitation centre in the United Kingdom. Admission and discharge scores from the United Kingdom Functional Independence Measure +Functional Assessment Measure, Rehabilitation Complexity Scale – E and Northwick Park Nursing Dependency Scale were analysed. Results Twenty-six children and young people age 8 years and over with severe stroke were included. Mean scores of independence increased and mean scores of complexity and dependency decreased. A proportion of the sample had ongoing self-care needs in relation to support needed in washing, dressing and bathing. A small number remained highly dependent, requiring assistance from two carers. Conclusion Children and young people make significant gains in self-care independence during specialised rehabilitation. However, a proportion return to the community with high self-care needs. Occupational therapists and the wider care team should address ongoing self-care needs in this population.