bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oligogenic Architecture of Rare Noncoding Variants Distinguishes 4 Congenital Heart Disease Phenotypes
Authors: Yu Mengyao , Aguirre Matthew , Jia Meiwen , Gjoni Ketrin , Cordova-Palomera Aldo , Munger Chad , Amgalan Dulguun , Rosa Ma X. , Pereira Alexandre , Tcheandjieu Catherine , Seidman Christine , Seidman Jonathan , Tristani-Firouzi Martin , Chung Wendy , Goldmuntz Elizabeth , Srivastava Deepak , Loos Ruth J.F. , Chami Nathalie , Cordell Heather , Dreßen Martina , Mueller-Myhsok Bertram , Lahm Harald , Krane Markus , Pollard Katherine S. , Engreitz Jesse M. , Gagliano Taliun Sarah A. , Gelb Bruce D. , Priest James R. 
Published: April 2023

Background:
Congenital heart disease (CHD) is highly heritable, but the power to identify inherited risk has been limited to analyses of common variants in small cohorts.

Methods:
We performed reimputation of 4 CHD cohorts (n=55 342) to the TOPMed reference panel (freeze 5), permitting meta-analysis of 14 784 017 variants including 6 035 962 rare variants of high imputation quality as validated by whole genome sequencing.

Results:

Meta-analysis identified 16 novel loci, including 12 rare variants, which displayed moderate or large effect sizes (median odds ratio, 3.02) for 4 separate CHD categories. Analyses of chromatin structure link 13 of the genome-wide significant loci to key genes in cardiac development; rs373447426 (minor allele frequency, 0.003 [odds ratio, 3.37 for Conotruncal heart disease];
P
=1.49×10
−8
) is predicted to disrupt chromatin structure for 2 nearby genes
BDH1
and
DLG1
involved in Conotruncal development. A lead variant rs189203952 (minor allele frequency, 0.01 [odds ratio, 2.4 for left ventricular outflow tract obstruction];
P
=1.46×10
−
8
) is predicted to disrupt the binding sites of 4 transcription factors known to participate in cardiac development in the promoter of
SPAG9
. A tissue-specific model of chromatin conformation suggests that common variant rs78256848 (minor allele frequency, 0.11 [odds ratio, 1.4 for Conotruncal heart disease];
P
=2.6×10
−
8
) physically interacts with
NCAM1
(
P
FDR
=1.86×10
−
27
), a neural adhesion molecule acting in cardiac development. Importantly, while each individual malformation displayed substantial heritability (observed h2 ranging from 0.26 for complex malformations to 0.37 for left ventricular outflow tract obstructive disease) the risk for different CHD malformations appeared to be separate, without genetic correlation measured by linkage disequilibrium score regression or regional colocalization.

Conclusions:
We describe a set of rare noncoding variants conferring significant risk for individual heart malformations which are linked to genes governing cardiac development. These results illustrate that the oligogenic basis of CHD and significant heritability may be linked to rare variants outside protein-coding regions conferring substantial risk for individual categories of cardiac malformation.
Association of Body Mass Index With Clinical Features and Outcomes in Adults With Fontan Palliation
Authors: Yogeswaran Vidhushei , Anigwe Christopher , Salahuddin Ayesha , Aggarwal Anika , Moon Grady Anita J. , Harris Ian S. , Sabanayagam Aarthi , Kouretas Peter C. , Mahadevan Vaikom S. , Agarwal Anushree 
Published: April 2023

Background
With improving survival of patients with single ventricle physiology who underwent Fontan palliation, there is also an increase in the prevalence of overweight and obesity in these patients. This tertiary care single‐center study aims to determine the association of body mass index (BMI) with the clinical characteristics and outcomes in adults with Fontan.

Methods and Results

Adult patients (aged ≥18 years) with Fontan who were managed at a single tertiary care center between January 1, 2000, and July 1, 2019, and had BMI data available were identified via retrospective review of medical records. Univariate and multivariable (after adjusting for age, sex, functional class, and type of Fontan) linear and logistic regression, as appropriate, were utilized to evaluate associations between BMI and diagnostic testing and clinical outcomes. A total of 163 adult patients with Fontan were included (mean age, 29.9±9.08 years), with a mean BMI of 24.2±5.21 kg/m
2
(37.4% of patients had BMI ≥25 kg/m
2
). Echocardiography data were available for 95.7% of patients, exercise testing for 39.3% of patients, and catheterization for 53.7% of patients. Each SD increase in BMI was significantly associated with decreased peak oxygen consumption (
P
=0.010) on univariate analysis and with increased Fontan pressure (
P
=0.035) and pulmonary capillary wedge pressure (
P
=0.037) on multivariable analysis. In addition, BMI ≥25 kg/m
2
was independently associated with heart failure hospitalization (adjusted odds ratio [AOR], 10.2; 95% CI, 2.79–37.1 [
P
<0.001]) and thromboembolic complications (AOR, 2.79; 95% CI, 1.11–6.97 [
P
=0.029]).

Conclusions
Elevated BMI is associated with poor hemodynamics and worse clinical outcomes in adult patients with Fontan. Whether elevated BMI is the cause or consequence of poor clinical outcomes needs to be further established.
Differences in Adherence to American Heart Association's Life's Essential 8, Diet Quality, and Weight Loss Strategies Between Those With and Without Recent Clinically Significant Weight Loss in a Nationally Representative Sample of US Adults
Authors: Hill Emily B. , Cubellis Lauren T. , Wexler Randell K. , Taylor Christopher A. , Spees Colleen K. 
Published: April 2023

Background
The American Heart Association defines ideal cardiovascular health based on 8 risk factors (Life's Essential 8 [LE8]); a high LE8 score (range 0–100) reflects greater adherence to their recommendations. Weight status influences cardiovascular health, yet individuals may use detrimental diet and weight loss strategies to improve weight status. We assessed differences in LE8 adherence, diet quality, and weight loss strategies between those with and without a recent history of clinically significant weight loss (CSWL).

Methods and Results

Data from 2007 to 2016 National Health and Nutrition Examination Survey questionnaires, clinical measures, and 24‐hour dietary recalls were assessed to determine LE8 adherence, diet quality (Healthy Eating Index), and weight loss strategies between adults with: (1) intentional CSWL ≥5%; and (2) non‐CSWL <5%, weight maintenance, or weight gain over the past 12 months using ANCOVA and chi‐square tests. Those with CSWL demonstrated higher scores for diet quality (
P
=0.014), physical activity (
P
<0.001), and blood lipids (
P
<0.001). Those without CSWL reported lower BMI (
P
<0.001). There were no differences in total LE8 cardiovascular health scores between those with and without CSWL. More individuals with CSWL reported weight loss strategies of exercising (
P
=0.016); those without CSWL reported skipping meals (
P
=0.002) and using prescription diet pills (
P
<0.001).

Conclusions
Greater adherence to the LE8 recommendations was observed among individuals with CSWL, although overall LE8 scores were low. Future research should address the implementation of evidence‐based strategies that improve diet quality while promoting optimal cardiovascular health among those with intent to lose weight.
Mortality and Major Adverse Cardiac Events in Patients With Breast Cancer Receiving Radiotherapy: The First Decade
Authors: Jacobs Johanna E. J. , L'Hoyes Wouter , Lauwens Lieselotte , Yu Yu‐Ling , Brusselmans Marius , Weltens Caroline , Voigt Jens‐Uwe , Wildiers Hans , Neven Patrick , Herrmann Joerg , Thijs Lutgarde , Staessen Jan A. , Janssens Stefan , Van Aelst Lucas N. L. 
Published: April 2023

Background
Treatment for breast cancer (BC) frequently involves radiotherapy. Guidelines recommend screening for cardiac adverse events starting 10 years after radiotherapy. The rationale for this interval is unclear.

Methods and Results

We aimed to study cardiovascular event rates in the first decade following curative radiotherapy for BC. We compared mortality and cardiovascular event rates with an age‐ and risk factor‐matched control population. We included 1095 patients with BC (mean age 56±12 years). Two hundred and eighteen (19.9%) women died. Cancer and cardiovascular mortality caused 107 (49.1%) and 22 (10.1%) deaths, respectively. A total of 904 cases were matched to female FLEMENGHO (Flemish Study on Environment, Genes and Health Outcomes) participants. Coronary artery disease incidence was similar (risk ratio [RR], 0.75 [95% CI, 0.48–1.18]), yet heart failure (RR, 1.97 [95% CI, 1.19–3.25]) and atrial fibrillation/flutter (RR, 1.82 [95% CI, 1.07–3.08]) occurred more often in patients with BC. Age (hazard ratio [HR], 1.033 [95% CI, 1.006–1.061],
P
=0.016), tumor grade (HR, 1.739 [95% CI, 1.166–2.591],
P
=0.007), and neoadjuvant treatment setting (HR, 2.782 [95% CI, 1.304–5.936],
P
=0.008) were risk factors for mortality. Risk factors for major adverse cardiac events were age (HR, 1.053 [95% CI, 1.013–1.093];
P
=0.008), mean heart dose (HR, 1.093 [95% CI, 1.025–1.167];
P
=0.007), history of cardiovascular disease (HR, 2.386 [95% CI, 1.096–6.197];
P
=0.029) and Mayo Clinic Cardiotoxicity Risk Score (HR, 2.664 [95% CI, 1.625–4.367];
P
<0.001).

Conclusions
Ten‐year mortality following curative treatment for unilateral BC was mainly cancer related, but heart failure and atrial fibrillation/flutter were already common in the first decade following irradiation. Mean heart dose, pre‐existing cardiovascular diseases, and Mayo Clinic Cardiotoxicity Risk Score were risk factors for cardiac adverse events. These results suggest a need for early dedicated cardio‐oncological follow‐up after radiotherapy.
C-Reactive Protein, Interleukin-6, and Vascular Recurrence After Stroke: An Individual Participant Data Meta-Analysis
Authors: McCabe John J. , Walsh Cathal , Gorey Sarah , Harris Katie , Hervella Pablo , Iglesias-Rey Ramon , Jern Christina , Li Linxin , Miyamoto Nobukazu , Montaner Joan , Pedersen Annie , Purroy Francisco , Rothwell Peter M. , Sudlow Catherine , Ueno Yuji , Vicente-Pascual Mikel , Whiteley William , Woodward Mark , Kelly Peter J. 
Published: April 2023

Background:
Anti-inflammatory therapies reduce recurrent vascular events in coronary disease. Existing studies have reported highly conflicting findings for the association of blood inflammatory markers with vascular recurrence after stroke leading to uncertainty about the potential of anti-inflammatory therapies after stroke and no consensus about the utility of measurement of inflammatory markers in current guidelines.

Methods:
We investigated the association between hsCRP (high-sensitivity C-reactive protein), IL-6 (interluekin-6), and recurrent major adverse cardiovascular events (MACE), and stroke from individual participant data from 8420 patients with ischemic stroke/transient ischemic attack from 10 prospective studies. We did within-study multivariable regression analyses and then combined adjusted risk ratio (RR) by random-effects meta-analysis.

Results:

During 18 920 person-years of follow-up, 1407 (16.7% [95% CI, 15.9–17.5]) patients had MACE and 1191 (14.1% [95% CI, 13.4–14.9]) patients had recurrent stroke. On bivariate analysis, baseline IL-6 was associated with MACE (RR, 1.26 [95% CI, 1.10–1.43]) and recurrent stroke (RR, 1.18 [95% CI, 1.05–1.32]), per unit increase log
e
IL-6. Similar associations were observed for hsCRP (MACE RR, 1.19 [95% CI, 1.09–1.29]; recurrent stroke RR, 1.12 [95% CI, 1.04–1.21], per unit increase log
e
hsCRP). After adjustment for vascular risk factors and treatment, independent associations remained with MACE (IL-6, RR, 1.12 [95% CI, 1.04–1.21]; hsCRP, RR, 1.09 [95% CI, 1.04–1.15]) and recurrent stroke (IL-6, RR, 1.09 [95% CI, 1.00–1.19]; hsCRP, RR, 1.05 [95% CI, 1.00–1.11]). Comparing the top with the bottom quarters (Q4 versus Q1), IL-6 (RR, 1.35 [95% CI, 1.09–1.67]) and hsCRP (RR, 1.31 [95% CI, 1.07–1.61]) were associated with MACE after adjustment. Similar results were observed for recurrent stroke for IL-6 (RR, 1.33 [95% CI, 1.08–1.65]) but not hsCRP (RR, 1.16 [95% CI, 0.93–1.43]).

Conclusions:
Blood markers of inflammation were independently associated with vascular recurrence after stroke, strengthening the rationale for randomized trials of anti-inflammatory therapies for secondary prevention after ischemic stroke/TIA.
Description length guided nonlinear unified Granger causality analysis
Authors: Li Fei , Lin Qiang , Zhao Xiaohu , Hu Zhenghui 
Published: April 2023

Abstract
Most Granger causality analysis (GCA) methods still remain a two-stage scheme guided by different mathematical theories; both can actually be viewed as the same generalized model selection issues. Adhering to Occam’s razor, we present a unified GCA (uGCA) based on the minimum description length principle. In this research, considering the common existence of nonlinearity in functional brain networks, we incorporated the nonlinear modeling procedure into the proposed uGCA method, in which an approximate representation of Taylor’s expansion was adopted. Through synthetic data experiments, we revealed that nonlinear uGCA was obviously superior to its linear representation and the conventional GCA. Meanwhile, the nonlinear characteristics of high-order terms and cross-terms would be successively drowned out as noise levels increased. Then, in real fMRI data involving mental arithmetic tasks, we further illustrated that these nonlinear characteristics in fMRI data may indeed be drowned out at a high noise level, and hence a linear causal analysis procedure may be sufficient. Next, involving autism spectrum disorder patients data, compared with conventional GCA, the network property of causal connections obtained by uGCA methods appeared to be more consistent with clinical symptoms.
Resting State Network Segregation Modulates Age-Related Differences in Language Production
Authors: Zhang Haoyun , Diaz Michele T. 
Published: April 2023

Abstract
Older adults typically exhibit decline in language production. However, how the brain supports or fails to support these processes is unclear. Moreover, there are competing hypotheses about the nature of age-related neural changes and whether age-related increases in neural activity reflect compensation or a decline in neural efficiency. In the current study, we investigated the neural bases of language production focusing on resting state functional connectivity. We hypothesized that language production performance, functional connectivity, and their relationship would differ as a function of age. Consistent with prior work, older age was associated with worse language production performance. Functional connectivity analyses showed that network segregation within the left hemisphere language network was maintained across adulthood. However, increased age was associated with lower whole brain network segregation. Moreover, network segregation was related to language production ability. In both network analyses, there were significant interactions with age—higher network segregation was associated with better language production abilities for younger and middle-aged adults, but not for older adults. Interestingly, there was a stronger relationship between language production and the whole brain network segregation than between production and the language network. These results highlight the utility of network segregation measures as an index of brain function, with higher network segregation associated with better language production ability. Moreover, these results are consistent with stability in the left hemisphere language network across adulthood and suggest that dedifferentiation among brain networks, outside of the language network, is a hallmark of aging and may contribute to age-related language production difficulties.
The Role of the North Atlantic Blocking High during Large-Scale Heavy Rainfall Events over Central India
Authors: Nikumbh Akshaya C. , Thakur A. B. S. , Chakraborty Arindam , Bhat G. S. , Sukhatme Jai 
Published: April 2023

Abstract
Large-scale extreme rainfall events (LEREs) over central India are produced by monsoon low pressure systems (LPSs) when assisted by a secondary cyclonic vortex (SCV). Both the LPS and the SCV are embedded in a monsoon trough and form mainly during the positive phase of the boreal summer intraseasonal oscillation. Here, we observe that tropical–extratropical interactions exist during LEREs. Using ray tracing, we show that extratropical Rossby waves propagate to the Indian subcontinent during the summer monsoon season. Stationary Rossby wave rays originating over the North Atlantic Ocean reach India following approximately a great circle path at midtropospheric levels. This pathway appears to play an important role in tropical–extratropical interactions during LEREs. Seventy-seven percent of LEREs are preceded by a North Atlantic blocking high and 90% by a quasi-stationary central Asian high. The Atlantic blocking high triggers a quasi-stationary Rossby wave response and strengthens the downstream central Asian high. In turn, the quasi-stationary central Asian high facilitates Rossby wave breaking, transporting high-PV streamers and cutoffs equatorward. The central Asian high is in close proximity to the monsoon trough in the mid- and lower troposphere. It interacts with the monsoon trough over the northwest Indian subcontinent. The equatorial monsoon trough is strengthened due to the supply of dynamic forcing and static instabilities from the extratropics. This additional forcing from the extratropics creates an environment that is conducive for LEREs.
A Deep-Learning Reconstruction of Tropical Cyclone Size Metrics 1981–2017: Examining Trends
Authors: Zhuo Jing-Yi , Tan Zhe-Min 
Published: April 2023

Abstract
Observed climate records of length, homogeneity, and reliability are the basis of climatological studies on tropical cyclones (TCs). However, such data are scarce for TC size in terms of wind field, particularly over the western North Pacific (WNP). This study demonstrates that deep learning can practically bridge this data gap when applied to satellite data. Using transfer learning, deep learning algorithms were developed to estimate reliable TC sizes from infrared imagery for the WNP TCs. The algorithms were then applied to a homogeneous satellite database to reconstruct a new historical dataset of TC sizes, named DeepTCSize, which covers 37 years (1981–2017) over the WNP. DeepTCSize includes multiple TC size quantities, such as wind radii of 17, 26, and 33 m s−1 and maximum winds (i.e., R17, R26, R33, and RMW), which have high correlations (R = 0.85, 0.84, 0.79, and 0.76, respectively) with postseason quality-controlled best track data. Comparisons with ocean wind observations were made and this further revealed that DeepTCSize has good quality and is free from spurious error trends, providing an advantage over the historical “best estimates” of TC sizes currently available in the best track archives for the WNP. The new reconstructed TC sizes dataset for the WNP TCs shows significant expanding trends in the annual-mean outer circulations (at a rate of 2% decade−1 for R17 and a rate of 2% decade−1 for R26), which are mainly associated with weaker storms, as well as a weak contracting trend in the annual-mean inner-core size (RMW).

Significance Statement
Tropical cyclone (TC) size largely controls the TC-induced hazard and risk. If the size of TC can be determined more efficiently in observations spanning a long-enough period, the climatology and changes in TC can be better modeled and understood. This study applies deep learning methods to reconstruct a new dataset of multiple inner- to outer-core TC size metrics from infrared imagery of satellites for the western North Pacific TCs. The dataset spans 37 years. It is homogenous and has comparable accuracy with the existing “best estimates.” Using the dataset, a significant expanding trend was identified in the outer-core size, while the inner-core size exhibits a weak contracting trend. The dataset can be employed in several applications.
Interannual Variations in the Intraseasonal Variability of Spring Precipitation over Southern China and the Possible Mechanisms
Authors: Zeng Zixuan , Sun Jianqi 
Published: April 2023

Abstract
This study first investigates the interannual variations in spring precipitation intraseasonal variability over southern China (SC). The results show that SC spring precipitation exhibits distinct intraseasonal variations with a period of 7–25 days. The first mode of 7–25-day precipitation intraseasonal variability (PIV) displays a monopole pattern over SC, and the PIV magnitude is largely determined by the upward motion intensity during intraseasonal precipitation events. Further analysis suggests that two atmospheric wave trains are observed during intraseasonal precipitation events, which propagate eastward from the North Atlantic along the northern and southern paths. In strong PIV years, the two wave trains can propagate to East Asia and show coordinated influences. The resultant low pressure to the west of SC causes strong upward motion and PIV over SC by bringing strong zonal vorticity and meridional temperature advection. In weak PIV years, the southern wave train can only propagate to the Bay of Bengal; therefore, the northern wave train plays a major role. The resultant low pressure is now over the upper to middle reaches of the Yangtze River, which causes relatively weak upward motion and PIV over SC by bringing weak meridional vorticity and temperature advection. Further analysis indicates that the sea surface temperature (SST) condition over the tropical Indian Ocean and the South China Sea is essential for southern wave train propagation. The warming SST over the regions can intensify westerlies to its north and consequently favors the propagation of the southern wave train to SC, eventually contributing to strong PIV over SC.