bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the optimality of score-driven models
Authors: Gorgi P , Lauria C S A , Luati A 
Published: November 2023

Summary
Score-driven models have recently been introduced as a general framework to specify time-varying parameters of conditional densities. The score enjoys stochastic properties that make these models easy to implement and convenient to apply in several contexts, ranging from biostatistics to finance. Score-driven parameter updates have been shown to be optimal in terms of locally reducing a local version of the Kullback–Leibler divergence between the true conditional density and the postulated density of the model. A key limitation of such an optimality property is that it holds only locally both in the parameter space and sample space, yielding to a definition of local Kullback–Leibler divergence that is in fact not a divergence measure. The current paper shows that score-driven updates satisfy stronger optimality properties that are based on a global definition of Kullback–Leibler divergence. In particular, it is shown that score-driven updates reduce the distance between the expected updated parameter and the pseudo-true parameter. Furthermore, depending on the conditional density and the scaling of the score, the optimality result can hold globally over the parameter space, which can be viewed as a generalization of the monotonicity property of the stochastic gradient descent scheme. Several examples illustrate how the results derived in the paper apply to specific models under different easy-to-check assumptions, and provide a formal method to select the link function and the scaling of the score.
Electrical stimulation of the ventromedial prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure
Authors: Braun Joe A , Patel Mariya , Henderson Luke A , Dawood Tye , Macefield Vaughan G 
Published: November 2023

Abstract
We recently showed that transcranial alternating current stimulation of the dorsolateral prefrontal cortex modulates spontaneous bursts of muscle sympathetic nerve activity, heart rate, and blood pressure (Sesa-Ashton G, Wong R, McCarthy B, Datta S, Henderson LA, Dawood T, Macefield VG. Stimulation of the dorsolateral prefrontal cortex modulates muscle sympathetic nerve activity and blood pressure in humans. Cereb Cortex Comm. 2022:3:2tgac017.). Stimulation was delivered between scalp electrodes placed over the nasion and electroencephalogram (EEG) electrode site F3 (left dorsolateral prefrontal cortex) or F4 (right dorsolateral prefrontal cortex), and therefore the current passed within the anatomical locations underlying the left and right ventromedial prefrontal cortices. Accordingly, we tested the hypothesis that stimulation of the left and right ventromedial prefrontal cortices would also modulate muscle sympathetic nerve activity, although we predicted that this would be weaker than that seen during dorsolateral prefrontal cortex stimulation. We further tested whether stimulation of the right ventromedial prefrontal cortices would cause greater modulation of muscle sympathetic nerve activity, than stimulation of the left ventromedial prefrontal cortices. In 11 individuals, muscle sympathetic nerve activity was recorded via microelectrodes inserted into the right common peroneal nerve, together with continuous blood pressure, electrocardiogram, and respiration. Stimulation was achieved using transcranial alternating current stimulation, +2 to −2 mA, 0.08 Hz, 100 cycles, applied between electrodes placed over the nasion, and EEG electrode site FP1, (left ventromedial prefrontal cortices) or FP2 (right ventromedial prefrontal cortices); for comparison, stimulation was also applied over F4 (right dorsolateral prefrontal cortex). Stimulation of all three cortical sites caused partial entrainment of muscle sympathetic nerve activity to the sinusoidal stimulation, together with modulation of blood pressure and heart rate. We found a significant fall in mean blood pressure of ~6 mmHg (P = 0.039) during stimulation of the left ventromedial prefrontal cortices, as compared with stimulation of the right. We have shown, for the first time, that transcranial alternating current stimulation of the ventromedial prefrontal cortices modulates muscle sympathetic nerve activity and blood pressure in awake humans at rest. However, it is unclear if this modulation occurred through the same brain pathways activated during transcranial alternating current stimulation of the dorsolateral prefrontal cortex.
Contemporary Management ofStaphylococcus aureusBacteremia—Controversies in Clinical Practice
Authors: Minter Daniel J , Appa Ayesha , Chambers Henry F , Doernberg Sarah B 
Published: November 2023

AbstractStaphylococcus aureus bacteremia (SAB) carries a high risk for excess morbidity and mortality. Despite its prevalence, significant practice variation continues to permeate clinical management of this syndrome. Since the publication of the 2011 Infectious Diseases Society of America (IDSA) guidelines on management of methicillin-resistant Staphylococcus aureus infections, the field of SAB has evolved with the emergence of newer diagnostic strategies and therapeutic options. In this review, we seek to provide a comprehensive overview of the evaluation and management of SAB, with special focus on areas where the highest level of evidence is lacking to inform best practices.
Review: The Landscape of Antiviral Therapy for COVID-19 in the Era of Widespread Population Immunity and Omicron-Lineage Viruses
Authors: Meyerowitz Eric A , Li Yijia 
Published: November 2023

Abstract
The goals of coronavirus disease 2019 (COVID-19) antiviral therapy early in the pandemic were to prevent severe disease, hospitalization, and death. As these outcomes have become infrequent in the age of widespread population immunity, the objectives have shifted. For the general population, COVID-19–directed antiviral therapy should decrease symptom severity and duration and minimize infectiousness, and for immunocompromised individuals, antiviral therapy should reduce severe outcomes and persistent infection. The increased recognition of virologic rebound following ritonavir-boosted nirmatrelvir (NMV/r) and the lack of randomized controlled trial data showing benefit of antiviral therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for standard-risk, vaccinated individuals remain major knowledge gaps. Here, we review data for selected antiviral agents and immunomodulators currently available or in late-stage clinical trials for use in outpatients. We do not review antibody products, convalescent plasma, systemic corticosteroids, IL-6 inhibitors, Janus kinase inhibitors, or agents that lack Food and Drug Administration approval or emergency use authorization or are not appropriate for outpatients.
Neutrophil counts and cardiovascular disease
Authors: Luo Jiao , Thomassen Jesper Qvist , Nordestgaard Børge G , Tybjærg-Hansen Anne , Frikke-Schmidt Ruth 
Published: November 2023

Abstract

Background and Aims
Anti-inflammatory trials have shown considerable benefits for cardiovascular disease. High neutrophil counts, an easily accessible inflammation biomarker, are associated with atherosclerosis in experimental studies. This study aimed to investigate the associations between neutrophil counts and risk of nine cardiovascular endpoints using observational and genetic approaches.

Methods
Observational studies were conducted in the Copenhagen General Population Study (n = 101 730). Genetic studies were firstly performed using one-sample Mendelian randomization (MR) with individual-level data from the UK Biobank (n = 365 913); secondly, two-sample MR analyses were performed using summary-level data from the Blood Cell Consortium (n = 563 085). Outcomes included ischaemic heart disease, myocardial infarction, peripheral arterial disease, ischaemic cerebrovascular disease, ischaemic stroke, vascular-related dementia, vascular dementia, heart failure, and atrial fibrillation.

Results
Observational analyses showed associations between high neutrophil counts with high risks of all outcomes. In the UK Biobank, odds ratios (95% confidence intervals) per 1-SD higher genetically predicted neutrophil counts were 1.15 (1.08, 1.21) for ischaemic heart disease, 1.22 (1.12, 1.34) for myocardial infarction, and 1.19 (1.04, 1.36) for peripheral arterial disease; similar results were observed in men and women separately. In two-sample MR, corresponding estimates were 1.14 (1.05, 1.23) for ischaemic heart disease and 1.11 (1.02, 1.20) for myocardial infarction; multiple sensitivity analyses showed consistent results. No robust associations in two-sample MR analyses were found for other types of leucocytes.

Conclusions
Observational and genetically determined high neutrophil counts were associated with atherosclerotic cardiovascular disease, supporting that high blood neutrophil counts is a causal risk factor for atherosclerotic cardiovascular disease.
Cardiovascular magnetic resonance rest and exercise-stress left atrioventricular coupling index to detect diastolic dysfunction
Authors: Backhaus S J , Lange T , Schulz A , Evertz R , Frey S M , Hasenfus G , Schuster A 
Published: November 2023

Abstract

Background
Left atrial and ventricular (LA/LV) dysfunction are inter-linked in heart failure with preserved ejection fraction (HFpEF), however little is known about their inter-play and relation to cardiac decompensation. We hypothesized that cardiovascular magnetic resonance (CMR) left atrioventricular coupling index (LACI) would identify pathophysiological alterations in HFpEF and be amenable to rest and ergometer-stress CMR.

Methods
Patient with exertional dyspnoea, signs of diastolic dysfunction (E/e’ ≥8) and preserved EF (≥50%) on echocardiography were prospectively recruited and classified as HFpEF (n=34) or non-cardiac dyspnoea (NCD, n=34) according to pulmonary capillary wedge pressure (PCWP) on right heart catheterisation (rest/stress: ≥15/25 mmHg). LA and LV volumes were assessed on short-axis real-time cine sequences at rest and during exercise-stress. LACI was defined as the ratio of the LA/LV end-diastolic volume. Cardiovascular hospitalisation (CVH) was assessed after 24 months.

Results
Volume-derived LA (p≥0.008) but not LV (p≥0.347) morphology and function at rest and during exercise-stress detected significant differences comparing HFpEF and NCD. There was impaired atrio-ventricular coupling in HFpEF at rest (LACI 45.7 vs 31.6 %, p&lt;0.001) and during exercise-stress (45.7 vs 27.9 %, p&lt;0.001). LACI correlated with PCWP at rest (r=0.48, p&lt;0.001) and during exercise-stress (r=0.55, p&lt;0.001). At rest, LACI was the only volumetry derived parameter to differentiate NCD and HFpEF patients which were identified using exercise-stress thresholds (p=0.001). Resting and exercise-stress LACI dichotomised at their medians were associated CVH (p≤0.005).

Conclusions
Assessment of LACI is a simple approach for LA/LV coupling quantification and allows easy and fast identification of heart failure with preserved ejection fraction (HFpEF).
Quantification of aortic valve fibrosis and calcification by computed tomography angiography: a prospective head-to-head comparison with histology
Authors: Grodecki K , Olasinska-Wisniewska A , Cyran A , Urbanowicz T , Kwiecinski J , Gocol R , Nawara-Skipirzepa J , Wilimski R , Perek B , Jemielity M , Wojakowski W , Gornicka B , Huczek Z , Dey D 
Published: November 2023

Abstract

Background
Calcific aortic stenosis (AS) is characterized by leaflet degeneration involving fibrocalcific alterations which limit leaflet mobility and eventually lead to obstruction of flow across the aortic valve. While cardiac computed tomography (CT) has been routinely used for quantification of aortic valve calcium in individuals in whom echocardiography is inconclusive, recent studies on quantification of aortic valve fibrosis are lacking histological validation. [1,2]

Purpose
We, thus, aimed to validate a non-invasive CTA-derived quantitative characterization of aortic valve tissue against histologic examination of excised aortic valve leaflets.

Methods
In this prospective study, patients underwent CTA within a month before surgical aortic valve replacement for aortic stenosis. Tomographic valve tissue components were identified by Gaussian mixture modeling applied to CTA, by automatically fitting Gaussian functions to the Hounsfield Unit (HU) histograms for blood pool, non-calcific, and calcific aortic valve tissue. Tissue composition, expressed as % [(tissue component volume / total tissue volume) × 100%], was automatically calculated. For histologic evaluation, explanted valve leaflets were stained with Movat's Pentachrome. For every leaflet, three non-consecutive 5-µm sections were obtained. Further, an automatic algorithm detecting pixel intensities was applied for color differentiation and quantification of tissue components (Figure 1). Separate measurements from all the sections of the single valve were finally averaged and compared with CTA-derived calculations.

Results
A total of nineteen patients (63% men, 67±8 years old) undergoing isolated surgical aortic valve replacement for severe aortic stenosis with preoperative CTA were evaluated. The mean proportion of non-calcific aortic valve tissue was 68±16% in CTA and 75±3% on Movat’s Pentachrome staining (p=0.004, paired samples comparison). There was a strong correlation between the two modalities (r=0.856, p&lt;0.001; Figure 2A). Intermodal repeatability between CTA and histology for non-calcific tissue quantification was excellent with an interclass correlation coefficient of 0.855 (95% CI 0.663 – 0.942, p&lt;0.001), coefficient of repeatability of 16.8% and bias of -6.7% (p=0.234, Figure 2B).

Conclusions
CTA-derived characterization of aortic valve tissue provides an accurate quantification of non-calcific tissue as compared with gold-standard histologic examinations of explanted stenotic valves.Figure 1Figure 2
Structural and functional abnormalities of cardiac chambers in Barlow disease without significant mitral regurgitation
Authors: Meucci M C , Mantegazza V , Wu H , Garlasche A , Tamborini G , Pepi M , Bax J J , Ajmone Marsan N 
Published: November 2023

Abstract

Background
Limited and conflicting data have been reported on the existence of an early chamber remodelling in patients with Barlow disease (BD) without significant mitral regurgitation (MR).

Purpose
To explore the presence of left ventricular (LV) and left atrial (LA) morphological and functional abnormalities, evaluated by conventional and speckle-tracking echocardiography, in patients with BD and without significant MR; in addition, potential determinants of MR progression in these patients have been investigated.

Methods
We retrospectively identified consecutive patients with BD evaluated in two tertiary centers between 2010 and 2021. Only patients with MR graded from trivial to mild-to-moderate, as defined by an integrated multiparametric echocardiographic assessment, were selected. BD patients were matched with healthy controls with similar demographic characteristics and prevalence of cardiovascular risk factors, in a 1:1 ratio. A comprehensive echocardiographic evaluation, including LV and LA strain assessment by speckle-tracking analysis, was performed in all patients. Follow-up echocardiograms, when available, were reviewed in BD patients to evaluate the MR progression.

Results
A total of 231 patients with BD were included, of which 109 (56%) had trivial or mild MR and the remaining 122 (44%) had mild-to-moderate MR. As showed in Figure 1, patients with BD showed increased LV dimensions and indexed LV mass (LVMi), as compared with controls (all p&lt;0.001); LV remodelling worsened with higher degree of MR (trivial-mild vs mild-to-moderate) and was accompanied by an increased prevalence of eccentric LV hypertrophy (eLVH). Conversely, parameters of LV systolic performance, including LV strain, were similar to controls and between the two groups. In addition, BD patients had larger LA volumes and more impaired LA reservoir strain than controls (p&lt;0.001), without differences in the latter according to MR severity. Multivariable linear regression analyses in the overall population identified BD and MR grade as independent predictors of remodelling markers (LV dimensions, LVMi and LA volumes), and BD as independent correlate of LA reservoir strain.
Progression to moderate-to-severe or greater MR was observed in 51 subjects (on 172 with available follow-up) after a median time of 38 (range: 24-68) months. On multivariable Cox regression analysis, LVMi (or alternatively eLVH), together with age, MR grade and the presence of mitral annular disjunction emerged as independent predictors of MR progression (Figure 2).

Conclusions
Patients with BD and no significant MR show an early LV and LA remodeling, together with a mild impairment of LA reservoir strain, but not of LV function. LV remodelling, and the presence of eLVH in particular, portends a higher risk of MR progression.Comparative echocardiographic analysisMultivariable Cox regression analyses
Progression of different echocardiographic parameters of aortic stenosis have different clinical associations
Authors: Sen J , Wahi S , Marwick T 
Published: November 2023

Abstract

Background
Previous reports have described the risk factors for progression of aortic stenosis (AS). However, AS is recognized as a condition of the aortic valve and ventricle, and the AS marker chosen for the assessment of progression may influence the determinants of progression.

Purpose
To assess whether different clinical and demographic characteristics have a different impact on the progression of echocardiographic parameters on which stroke volume has a lesser (aortic valvular area [AVA], dimensionless severity index [DSI]) or greater influence (mean pressure gradient [MPG], or peak velocity [Vmax]).

Methods
Patients diagnosed with at least mild AS without an aortic valvular intervention identified from an echocardiographic database from January 1, 2009, to July 26, 2022, from a tertiary level hospital were included. AS progression models were evaluated using univariable and multivariable linear regression or mixed effects. AS severity was defined based on international guidelines.

Results
A total of 8,720 patients with at least mild AS were included and followed for up to 13.7 years. Multivariable mixed effects models identified important clinical predictors in understanding AS progression. After adjustment for relevant covariates, AVA decreased by 0.02 cm per year (95% CI: -0.025, -0.016, p&lt;0.001), DSI decreased by 0.006 per year (95% CI: -0.008, -0.005), MPG increased by 0.962 mmHg per year (95% CI: 0.818, 1.107, p&lt;0.001), Vmax increased by 6.742 cm/s per year (95% CI: 5.934, 7.549, p&lt;0.001). Age, calcification, revascularisation, ejection fraction below 50%, and rheumatic heart disease, were the most consistent associations of progression of all echocardiographic parameters (Figure 1). Sex was associated with progression of AVA and DSI but not gradients. Changes in gradients (but not AVA and DSI) were associated with ischemic heart disease, chronic kidney disease, and atrial fibrillation or atrial flutter.

Conclusion
This longitudinal data analysis demonstrates differences in impact of baseline risk factors on AS progression on different echocardiographic parameters.Figure 1.Colour map of clinical predictors
Myocardial edema measured by T2 mapping is an independent predictor of ventricular arrhythmias in hypertrophic cardiomyopathy
Authors: Kirshenboim Z K , Fardman A F , Shagraui R S , Sabbag A S , Konen E K , Beytelman A B , Arad M A , Wassershtrum Y W , Goitein O G , Brodov Y , Kirshenbaum Z K 
Published: November 2023

Abstract

Introduction
Clinical outcome of patients with hypertrophic cardiomyopathy (HCM) largely depends on ventricular arrhythmias. Parametric T2 mapping from Cardiac MRI (CMR) was found to be a measure of myocardial edema. We sought to study whether elevated T2 values on CMR in patients with hypertrophic cardiomyopathy (HCM) might predict ventricular arrhythmias (VA) and adverse clinical outcome.

Methods
Consecutive patients with HCM (n = 59) and healthy volunteers (n = 21) underwent 3 Tesla CMR. T2 mapping values were independently analyzed by 2 independent readers and presented using a 16-segment AHA model. VA was recorded by 24-hour Holter monitoring and/or during exercise stress test. Composite outcome was defined as ventricular tachycardia (VT) per Holter and/or ergometry, admission due to arrhythmias, ICD insertion and all-cause mortality. Statistical analysis was a t-test for VA and multi-variant logistic regression model adjusted for age and gender.

Results
Septal and apical variants of HCM were found in 42 and 17 patients, respectively. We found good interobserver agreement in T2 values (ICC=0.92, 95% CI 0.86 - 0.96, p value &lt;0.001). The 3rd tertile of T2 values (48 ± 8 msec) was significantly associated with VA 92% vs. 57 and 40% in lower tertiles, p = 0.02. Logistic regression analysis showed the 3rd tertile was an independent predictor of composite outcome (VT per Holter and/or ergometry, admission due to arrhythmias, ICD and all-cause mortality) OR 95% CI = 22.8 (1.4 - 361.6), p = 0.026. ROC analysis to find best cut-off of T2 for prediction of outcome showed AUC 0.7 (Figure 1).

Conclusion
Elevated T2 is an independent predictor of VA and adverse outcome in HMC patients. These results suggest the impact of myocardial edema in myocardial disease activity in HCM.ROC analysis to find best cut-off of T2
Effects of treatment response on echocardiographic features among patients with light-chain cardiac amyloidosis
Authors: Briasoulis A , Rempakos A , Petropoulos I , Bampatsias D , Theodorakakou F , Dimopoulos M A , Stamatelopoulos K , Kastritis E 
Published: November 2023

Abstract

Background
Complete response to treatment for light chain cardiac amyloidosis (AL-CA) may lead to improvement of myocardial function. The aim of this study was to evaluate the effect of treatment for AL-CA on echocardiographic characteristics of patients, and the prognostic impact of changes in longitudinal strain and myocardial work.

Methods
The study population comprised of sixty-one patients treated for AL between 2020 and 2022. All patients underwent comprehensive echocardiographic assessment including longitudinal strain and myocardial work imaging at baseline and at 1-year follow-up. Patients were stratified according to the depth of hematologic response to treatment for AL-CA as complete or not complete responders. The relationship between echocardiographic parameters and all-cause mortality was assessed by Kaplan Meir curves and cut-off points were selected using ROC analysis.

Results
A significant reduction in median NT-proBNP (from 2,771 to 1,486 pg/mL; p&lt;0.001), posterior wall thickness (PWT) (from 13 to 12mm; p=0.002), and an increase in global work index (GWI) (from 1,115 to 1,356 mmHg%; p=0.018) was observed in all patients at 1-year follow up. After stratifying patients based on hematologic response to treatment, patients with complete response (CR) had a more pronounced decrease in intraventricular septum thickness (14.2 to 12.0mm; p=0.006), a trend towards improved global longitudinal strain (GLS) (-11.6 to -13.1%; p=0.064) and increased global constructive work (1,245 to 1,436 mmHg%; p=0.008), in addition to significant improvements in NT-proBNP, posterior wall thickness and global work index. Furthermore, the delta GLS (ρspearman=0.35; p&lt;0.001) and delta GWI (ρspearman=-0.32; p=0.02) significantly correlated with delta NT-proBNP. Patients with GWI response, either any response or ROC-curve derived cut-off, had a better prognosis compared with patients without GWI response (log-rank p=0.043 and log-rank p=0.035, respectively).

Conclusions
Among patients treated for AL-CA, those with hematologic CR exhibited significant improvement in GWI and GWW. Additionally, our results indicate that GLS and GWI may have prognostic value in predicting survival among AL-CA patients and their changes correlate to NTproBNP decrease.