bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Aggregation Is an Early Manifestation of Phospholamban p.(Arg14del)–Related Cardiomyopathy: Development of PLN-R14del–Related Cardiomyopathy
Authors: Eijgenraam Tim R. , Boogerd Cornelis J. , Stege Nienke M. , Oliveira Nunes Teixeira Vivian , Dokter Martin M. , Schmidt Lukas E. , Yin Xiaoke , Theofilatos Konstantinos , Mayr Manuel , van der Meer Peter , van Rooij Eva , van der Velden Jolanda , Silljé Herman H.W. , de Boer Rudolf A. 
Published: September 2021

Background:

The p.(Arg14del) pathogenic variant (R14del) of the
PLN
(phospholamban) gene is a prevalent cause of cardiomyopathy with heart failure. The exact underlying pathophysiology is unknown, and a suitable therapy is unavailable. We aim to identify molecular perturbations underlying this cardiomyopathy in a clinically relevant PLN-R14del mouse model.

Methods:

We investigated the progression of cardiomyopathy in PLN-R14
Δ/Δ
mice using echocardiography, ECG, and histological tissue analysis. RNA sequencing and mass spectrometry were performed on cardiac tissues at 3 (before the onset of disease), 5 (mild cardiomyopathy), and 8 (end stage) weeks of age. Data were compared with cardiac expression levels of mice that underwent myocardial ischemia-reperfusion or myocardial infarction surgery, in an effort to identify alterations that are specific to PLN-R14del–related cardiomyopathy.

Results:

At 3 weeks of age, PLN-R14
Δ/Δ
mice had normal cardiac function, but from the age of 4 weeks, we observed increased myocardial fibrosis and impaired global longitudinal strain. From 5 weeks onward, ventricular dilatation, decreased contractility, and diminished ECG voltages were observed. PLN protein aggregation was present before onset of functional deficits. Transcriptomics and proteomics revealed differential regulation of processes involved in remodeling, inflammation, and metabolic dysfunction, in part, similar to ischemic heart disease. Altered protein homeostasis pathways were identified exclusively in PLN-R14
Δ/Δ
mice, even before disease onset, in concert with aggregate formation.

Conclusions:
We mapped the development of PLN-R14del–related cardiomyopathy and identified alterations in proteostasis and PLN protein aggregation among the first manifestations of this disease, which could possibly be a novel target for therapy.
Associations of Medicaid Expansion With Access to Care, Severity, and Outcomes for Acute Ischemic Stroke
Authors: McGee Blake T. , Seagraves Karen B. , Smith Eric E. , Xian Ying , Zhang Shuaiqi , Alhanti Brooke , Matsouaka Roland A. , Reeves Mathew , Schwamm Lee H. , Fonarow Gregg C. 
Published: September 2021

Background:
Multiple states have not expanded Medicaid under the Affordable Care Act, resulting in higher uninsured rates in states with high stroke burdens. This study aimed to evaluate the association of Medicaid expansion with changes in health insurance coverage, severity of presentation, access to care, and outcomes among patients with acute ischemic stroke.

Methods:
A retrospective, difference-in-differences analysis of Get With The Guidelines–Stroke registry data. The study population comprised first-time ischemic stroke admissions from 2012 to 2018 for patients aged 19 to 64 in 45 states (27 that expanded Medicaid and 18 that did not). A probable low-income cohort was defined based on having Medicaid, no insurance/self-pay, or undocumented insurance. Outcomes analyzed were indicators of health insurance status, stroke severity, use of emergency services, time to acute care, in-hospital mortality, receipt of rehabilitation, discharge disposition, and level of disability.

Results:
In the starting population (N=342 765), Medicaid-covered stroke admissions rose from 12.2% to 18.1% in expansion states and from 10.0% to only 10.6% in nonexpansion states, while uninsured admissions declined from 15.0% to 6.7% in expansion states and from 24.0% to 19.2% in nonexpansion states. In the low-income cohort (N=95 086; 28% of starting population), Medicaid expansion was associated with increased odds of discharge to a skilled nursing facility (adjusted odds ratio, 1.33 [95% CI, 1.12–1.59]) and transfer to any rehabilitation facility among those eligible (adjusted odds ratio, 1.24 [95% CI, 1.08–1.41]) and lower odds of discharge home (adjusted odds ratio, 0.89 [95% CI, 0.80–0.98]). Expansion was not associated with any other outcomes.

Conclusions:
Medicaid expansion is associated with fewer uninsured hospitalizations for acute ischemic stroke and increased rehabilitation at skilled nursing facilities. More targeted interventions may be needed to improve other stroke outcomes in the low-income US population. Future research should evaluate the impact of health care reform on primary stroke prevention.
Cerebral Small Vessel Disease and Depression Among Intracerebral Hemorrhage Survivors
Authors: Castello Juan Pablo , Pasi Marco , Kubiszewski Patryk , Abramson Jessica R. , Charidimou Andreas , Kourkoulis Christina , DiPucchio Zora , Schwab Kristin , Anderson Christopher D. , Gurol M. Edip , Greenberg Steven M. , Rosand Jonathan , Viswanathan Anand , Biffi Alessandro 
Published: September 2021

Background and Purpose:
Intracerebral hemorrhage (ICH) is an acute manifestation of cerebral small vessel disease (CSVD), usually cerebral amyloid angiopathy or hypertensive arteriopathy. CSVD-related imaging findings are associated with increased depression incidence in the general population. Neuroimaging may, therefore, provide insight on depression risk among ICH survivors. We sought to determine whether CSVD CT and magnetic resonance imaging markers are associated with depression risk (before and after ICH), depression remission, and effectiveness of antidepressant treatment.

Methods:
We analyzed data from the single-center longitudinal ICH study conducted at Massachusetts General Hospital. Participants underwent CT and magnetic resonance imaging imaging and were followed longitudinally. We extracted information for neuroimaging markers of CSVD subtype and severity. Outcomes of interest included pre-ICH depression, new-onset depression after ICH, resolution of depressive symptoms, and response to antidepressant treatment.

Results:

We followed 612 ICH survivors for a median of 47.2 months. Multiple CSVD-related markers were associated with depression risk. Survivors of cerebral amyloid angiopathy-related lobar ICH were more likely to be diagnosed with depression before ICH (odds ratio, 1.68 [95% CI, 1.14–2.48]) and after ICH (sub-hazard ratio, 1.52 [95% CI, 1.12–2.07]), less likely to achieve remission of depressive symptoms (sub-hazard ratio, 0.69 [95% CI, 0.51–0.94]), and to benefit from antidepressant therapy (
P
=0.041). Cerebral amyloid angiopathy disease burden on magnetic resonance imaging was associated with depression incidence and treatment resistance (interaction
P
=0.037), whereas hypertensive arteriopathy disease burden was only associated with depression incidence after ICH.

Conclusions:
CSVD severity is associated with depression diagnosis, both before and after ICH. Cerebral amyloid angiopathy-related ICH survivors are more likely to experience depression (both before and after ICH) than patients diagnosed with hypertensive arteriopathy-related ICH, and more likely to report persistent depressive symptoms and display resistance to antidepressant treatment.
Let's Tweet Again? Social Networks and Literature Achievement in High School Students
Authors: Barbetta Gian Paolo , Canino Paolo , Cima Stefano 
Published: September 2021

Abstract
The availability of cheap Wi-Fi Internet connections has encouraged schools to adopt Web 2.0 platforms for teaching, with the intention of stimulating students’ academic achievement and participation in school. Moreover, during the recent explosion of the COVID-19 crisis that forced many countries to close schools (as well as offices and factories), the widespread diffusion of these applications kept school systems going. Despite their widespread use as teaching tools, the effect of adopting Web 2.0 platforms on student performance has never been rigorously tested. We fill this gap in the literature by analyzing the impact of using Twitter as a teaching tool on high school students’ literature skills. Based on a large-scale, randomized controlled trial that involved seventy schools and about 1,500 students, we find that using Twitter to teach literature has an overall negative effect on students’ average achievement, reducing standardized test scores by about 25 percent of a standard deviation. The negative effect is stronger on students who usually perform better.
Top-of-Atmosphere Albedo Bias from Neglecting Three-Dimensional Cloud Radiative Effects
Authors: Singer Clare E. , Lopez-Gomez Ignacio , Zhang Xiyue , Schneider Tapio 
Published: September 2021

Abstract
Clouds cover on average nearly 70% of Earth’s surface and regulate the global albedo. The magnitude of the shortwave reflection by clouds depends on their location, optical properties, and three-dimensional (3D) structure. Due to computational limitations, Earth system models are unable to perform 3D radiative transfer calculations. Instead they make assumptions, including the independent column approximation (ICA), that neglect effects of 3D cloud morphology on albedo. We show how the resulting radiative flux bias (ICA-3D) depends on cloud morphology and solar zenith angle. We use high-resolution (20–100-m horizontal resolution) large-eddy simulations to produce realistic 3D cloud fields covering three dominant regimes of low-latitude clouds: shallow cumulus, marine stratocumulus, and deep convective cumulonimbus. A Monte Carlo code is used to run 3D and ICA broadband radiative transfer calculations; we calculate the top-of-atmosphere (TOA) reflected flux and surface irradiance biases as functions of solar zenith angle for these three cloud regimes. Finally, we use satellite observations of cloud water path (CWP) climatology, and the robust correlation between CWP and TOA flux bias in our LES sample, to roughly estimate the impact of neglecting 3D cloud radiative effects on a global scale. We find that the flux bias is largest at small zenith angles and for deeper clouds, while the albedo bias is most prominent for large zenith angles. In the tropics, the annual-mean shortwave radiative flux bias is estimated to be 3.1 ± 1.6 W m−2, reaching as much as 6.5 W m−2 locally.
Vertical Divergence of the Atmospheric Momentum Flux near the Sea Surface at a Coastal Site
Authors: Mahrt L. , Nilsson Erik , Rutgersson Anna , Pettersson Heidi 
Published: September 2021

AbstractMotivated by previous studies, we examine the underestimation of the sea surface stress due to the stress divergence between the surface and the atmospheric observational level. We analyze flux measurements collected over a 6-yr period at a coastal tower in the Baltic Sea encompassing a wide range of fetch values. Results are posed in terms of the vertical divergence of the stress scaled by the stress at the lowest observational level. The magnitude of this relative stress divergence increases with increasing stability and decreases with increasing instability, possibly partly due to the impact of stability on the boundary layer depth. The magnitude of the relative stress divergence increases modestly with decreasing wave age. The divergence of the heat flux is not well correlated with the divergence of the momentum flux evidently due to the greater influence of advection on the temperature. Needed improvement of the conceptual framework and needed additional measurements are noted.
Pediatric Tracheostomy Outcomes After Development of a Multidisciplinary Airway Team: A Quality Improvement Initiative
Authors: Chorney Stephen R. , Brown Ashley F. , Brooks Rebecca L. , Bailey Candace , Whitney Cindy , Sewell Ashley , Johnson Romaine F. 
Published: September 2021

ObjectivesTo analyze a multidisciplinary tracheostomy team’s effect on length of stay and cost.MethodsAn airway management program using a balanced scorecard was created to track key performance measures. Interventions included weekly rounding, standardized placement, postoperative care, and caregiver education. Process measures included time to first education, speech‐language pathology consultation rates, and pretracheostomy consultations. Outcome measures focused on the total length of stay, 30‐day revisit rates after discharge, accidental decannulation rate, and standardized cost. Regression analysis was used to predict the program’s effect on length of stay and total cost.ResultsIn total, 239 children met inclusion. The mean time to first education class was reduced from 13.7 to 1.9 days (P <. 001). The speech‐language pathology consultation rate increased from 68% to 95% (P <. 001), and the presurgical consultation rate with the tracheostomy team increased from 14% to 93% (P <. 001). The length of stay decreased from 133 to 96 days (P =. 006). Total costs were lower for short admissions but higher for prolonged admissions. Revisits within 30 days remained stable over time (18%).DiscussionEstablishing a multidisciplinary tracheostomy team results in improvements in quality metrics when caring for children with tracheostomies. Controlling for associated factors showed the mean length of stay decreased significantly in the first full year of program implementation. Cost analysis estimated significant reductions for tracheostomy patients spending less time in the hospital.Implications for PracticeA airway management program can positively affect tracheostomy processes and outcomes.
Weakly-Supervised Single-view Dense 3D Point Cloud Reconstruction via Differentiable Renderer
Authors: Jin Peng , Liu Shaoli , Liu Jianhua , Huang Hao , Yang Linlin , Weinmann Michael , Klein Reinhard 
Published: September 2021

AbstractIn recent years, addressing ill-posed problems by leveraging prior knowledge contained in databases on learning techniques has gained much attention. In this paper, we focus on complete three-dimensional (3D) point cloud reconstruction based on a single red-green-blue (RGB) image, a task that cannot be approached using classical reconstruction techniques. For this purpose, we used an encoder-decoder framework to encode the RGB information in latent space, and to predict the 3D structure of the considered object from different viewpoints. The individual predictions are combined to yield a common representation that is used in a module combining camera pose estimation and rendering, thereby achieving differentiability with respect to imaging process and the camera pose, and optimization of the two-dimensional prediction error of novel viewpoints. Thus, our method allows end-to-end training and does not require supervision based on additional ground-truth (GT) mask annotations or ground-truth camera pose annotations. Our evaluation of synthetic and real-world data demonstrates the robustness of our approach to appearance changes and self-occlusions, through outperformance of current state-of-the-art methods in terms of accuracy, density, and model completeness.
Pooling Nasopharyngeal Swab Specimens to Improve Testing Capacity for SARS-CoV-2 by Real-Time RT-PCR
Authors: Handous Imene , Hannachi Naila , Marzouk Manel , Hazgui Olfa , Bouafif Ep Ben Alaya Nissaf , Boukadida Jalel 
Published: September 2021

Abstract
Background
The detection of SARS-CoV-2 using qRT-PCR with the pooling of samples can reduce workload and costs especially when the prevalence rate of COVID-19 in a population is low.
To analyse the effect of pooling samples on the sensitivity of RT-qPCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection, we compared the cycle threshold (Ct) values of pools of 5 and 10 that tested positive with Ct values of individual samples that tested positive in that pool. Twenty positive nasopharyngeal (NP) specimens with low to high viral load were selected and pooled individually with four and nine negative NP.

Results
In NP specimens, the sensitivity of pools of 5 and 10 were 90 and 85%, compared to individual sample testing, respectively. The RT-qPCR sensitivity of pools of 5 and 10 against individual testing were not significantly different (p > 0.05). Detection of positive samples with low Ct values (< 36) was consistently achieved in pools of 5 and 10. However, there were higher false negatives when samples with high ct values (> 36) were pooled and tested. The mean Ct values obtained with the 5-sample pooled testing exceeded individual sample testing by 1.85 ± 1.09 cycles, while Ct values obtained with the 10-sample pooling exceeded individual sample testing by 3.4 ± 1.65 cycles.

Conclusions
In a low prevalence setting, testing capacity can be increased by pooling 5 or 10 samples, but the risk of additional false negatives needs to be considered
Using BioPAX-Parser (BiP) to enrich lists of genes or proteins with pathway data
Authors: Agapito Giuseppe , Cannataro Mario 
Published: September 2021

Abstract
Background
Pathway enrichment analysis (PEA) is a well-established methodology for interpreting a list of genes and proteins of interest related to a condition under investigation. This paper aims to extend our previous work in which we introduced a preliminary comparative analysis of pathway enrichment analysis tools. We extended the earlier work by providing more case studies, comparing BiP enrichment performance with other well-known PEA software tools.

Methods
PEA uses pathway information to discover connections between a list of genes and proteins as well as biological mechanisms, helping researchers to overcome the problem of explaining biological entity lists of interest disconnected from the biological context.

Results
We compared the results of BiP with some existing pathway enrichment analysis tools comprising Centrality-based Pathway Enrichment, pathDIP, and Signaling Pathway Impact Analysis, considering three cancer types (colorectal, endometrial, and thyroid), for a total of six datasets (that is, two datasets per cancer type) obtained from the The Cancer Genome Atlas and Gene Expression Omnibus databases. We measured the similarities between the overlap of the enrichment results obtained using each couple of cancer datasets related to the same cancer.

Conclusion
As a result, BiP identified some well-known pathways related to the investigated cancer type, validated by the available literature. We also used the Jaccard and meet-min indices to evaluate the stability and the similarity between the enrichment results obtained from each couple of cancer datasets. The obtained results show that BiP provides more stable enrichment results than other tools.
Association between anxiety symptoms and atrial fibrillation in a community cohort of Chinese older adults: a case-control study
Authors: Shen Zhu-Xia , Sun Yu-Min , Gu Hui-Hui , Zhang Yan , Shen Zhi-Wen , Liang Xiao-Niu , Ding Ding , Wang Jun 
Published: September 2021

Abstract
Background
The association between anxiety and atrial fibrillation (AF) remains unclear. Moreover, this association has rarely been studied in Chinese individuals aged 60 years or older. This study investigated the association between anxiety and AF in a community-based case-control study of older adult residents in urban China.

Methods
The cases and controls were from a community-based study conducted in the Jingansi community in Shanghai, China, between January 2010 and December 2012. A total of 3622 residents aged 60 years or older without severe vision, hearing, or speaking impairments were eligible to participate in the physical examinations and questionnaire survey. AF was assessed based on a previous physician’s diagnosis, electrocardiogram, ambulatory electrocardiogram, or echocardiogram. Anxiety was evaluated using the Zung Self-Rating Anxiety Scale (ZSAS). Using the AF group as a reference, the control group consisted of randomly selected age- and sex-matched individuals in a 1:5 ratio (case:control = 1:5). The association between anxiety and AF in the AF group and the multifactor-matched control group was explored using logistic regression.

Results
In the AF and control groups, after adjusting for a history of coronary heart disease, valvular heart disease, hypertension, stroke, hyperlipidemia, and diabetes, as well as depression score, ZSAS scores (odds ratio 1.07; 95% confidence interval 1.02–1.12; p = 0.003), and anxiety symptoms (odds ratio 3.94; 95% confidence interval 1.06–14.70; p = 0.041) were associated with AF.

Conclusions
Anxiety symptoms were associated with AF in a Chinese older population. This suggests that older adults who have anxiety symptoms may need psychological intervention or treatment in daily life and care.
Sequential Multiple Assignment Randomized Trial (SMART) to identify optimal sequences of telemedicine interventions for improving initiation of insulin therapy: A simulation study
Authors: Yan Xiaoxi , Matchar David B. , Sivapragasam Nirmali , Ansah John P. , Goel Aastha , Chakraborty Bibhas 
Published: September 2021

Abstract
Background
To examine the value of a Sequential Multiple Assignment Randomized Trial (SMART) design compared to a conventional randomized control trial (RCT) for telemedicine strategies to support titration of insulin therapy for Type 2 Diabetes Mellitus (T2DM) patients new to insulin.

Methods
Microsimulation models were created in R using a synthetic sample based on primary data from 63 subjects enrolled in a pilot study of a smartphone application (App), Diabetes Pal compared to a nurse-based telemedicine strategy (Nurse). For comparability, the SMART and an RCT design were constructed to allow comparison of four (embedded) adaptive interventions (AIs).

Results
In the base case scenario, the SMART has similar overall mean expected HbA1c and cost per subject compared with RCT, for sample size of n = 100 over 10,000 simulations. SMART has lower (better) standard deviations of the mean expected HbA1c per AI, and higher efficiency of choosing the correct AI across various sample sizes. The differences between SMART and RCT become apparent as sample size decreases. For both trial designs, the threshold value at which a subject was deemed to have been responsive at an intermediate point in the trial had an optimal choice (i.e., the sensitivity curve had a U-shape). SMART design dominates the RCT, in the overall mean HbA1c (lower value) when the threshold value is close to optimal.

Conclusions
SMART is suited to evaluating the efficacy of different sequences of treatment options, in addition to the advantage of providing information on optimal treatment sequences.