bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylation-Based Biological Age and Hypertension Prevalence and Incidence
Authors: Kresovich Jacob K. , Sandler Dale P. , Taylor Jack A. 
Published: March 2023

Background:
Hypertension is common in older individuals and is a major risk factor for cardiovascular disease. Blood DNA methylation profiles have been used to derive metrics of biological age that capture age-related physiological change, disease risk, and mortality. The relationships between hypertension and DNA methylation-based biological age metrics have yet to be carefully described.

Methods:
Among 4419 women enrolled in the prospective Sister Study cohort, DNA methylation data generated from whole blood samples collected at baseline were used to calculate 3 biological age metrics (PhenoAgeAccel, GrimAgeAccel, DunedinPACE). Women were classified as hypertensive at baseline if they had high blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) or reported current use of antihypertensive medication. New incident cases of hypertension during follow-up were identified via self-report on annual health questionnaires.

Results:
All 3 DNA methylation metrics of biological age were positively associated with prevalent hypertension at baseline (per 1-SD increase; PhenoAgeAccel, adjusted odds ratio, 1.16 [95% CI, 1.05–1.28]; GrimAgeAccel, adjusted odds ratio, 1.28 [95% CI, 1.14–1.45]; DunedinPACE, adjusted odds ratio, 1.16 [95% CI, 1.03–1.30]). Among 2610 women who were normotensive at baseline, women with higher biological age were more likely to be diagnosed with incident hypertension (per 1-SD increase; PhenoAgeAccel, adjusted hazard ratio, 1.09 [95% CI, 0.97–1.23]; GrimAgeAccel, adjusted hazard ratio, 1.16 [95% CI, 0.99–1.36]; DunedinPACE, adjusted hazard ratio, 1.16 [95% CI, 1.01–1.33]).

Conclusions:
Methylation-based biological age metrics increase before a hypertension diagnosis and appear to remain elevated in the years after clinical diagnosis and treatment.
Carotid Artery Stiffness Mechanisms Are Associated With End Organ Damage and All‐Cause Mortality: MESA (Multi‐Ethnic Study of Atherosclerosis)
Authors: Pewowaruk Ryan , Korcarz Claudia , De Boer Ian , Kestenbaum Bryan , Heckbert Susan R. , Tedla Yacob G. , Gepner Adam D. 
Published: March 2023

Background
Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown.

Methods and Results

MESA (Multi‐Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant‐specific models. Load‐dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow‐up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01–1.08],
P
=0.02) and dementia (HR, 1.06 [95% CI, 1.01–1.12],
P
=0.03) but not CKD (HR, 1.03 [95% CI, 0.98–1.08],
P
=0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00–1.08],
P
=0.04) but not CKD (HR, 1.00 [95% CI, 0.94–1.05],
P
=0.86) or dementia (HR, 1.06 [95% CI, 0.99–1.13],
P
=0.06). Load‐dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17–1.63],
P
<0.001) but not mortality (HR, 1.11 [95% CI, 0.99–1.25],
P
=0.07) or dementia (HR, 1.14 [95% CI, 0.94–1.38],
P
=0.19).

Conclusions
The mechanisms of arterial stiffness were associated with all‐cause mortality and CKD. Structural stiffness was associated with all‐cause mortality, and load‐dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load‐dependent and structural stiffness were not.
Stage 1 Hypertension and the 10‐Year and Lifetime Risk of Cardiovascular Disease: A Prospective Real‐World Study
Authors: Peng Xinyi , Jin Cheng , Song Qirui , Wu Shouling , Cai Jun 
Published: March 2023

Background
The 10‐year and lifetime cardiovascular disease risk in the population with stage 1 hypertension and the effects of recovery from and progression of stage 1 hypertension remain undetermined.

Methods and Results
This prospective cohort study included 96 268 individuals with blood pressure measurements obtained in 2006 and again in 2010. The 10‐year cardiovascular disease risk was estimated using the multivariable Cox proportional hazards model, and the lifetime risk was calculated using a modified survival analysis that accounted for the competing risk of death. Stage 1 hypertension was detected in 30.83% of the cohort. The 10‐year cardiovascular disease risk was 2.80%, and the lifetime risk was 16.61%. Compared with the normal blood pressure group, the stage 1 hypertension group had a 35% higher 10‐year risk (hazard ratio [HR], 1.35 [95% CI, 1.19–1.52]) and a 36% higher lifetime risk (HR, 1.36 [95% CI, 1.25–1.49]). By 2010, 12.57% of the participants with stage 1 hypertension had progressed to stage 2, with a significant 156% increase in 10‐year risk (HR, 2.56 [95% CI, 2.11–3.11]) and an increased lifetime risk of 129% (HR, 2.29 [95% CI, 1.89–2.77]). There was no appreciable change in risk in those with stage 1 hypertension whose blood pressure returned to the normal‐elevated range.

Conclusions
Stage 1 hypertension was associated with a significant increase in 10‐year and lifetime cardiovascular disease risk. Progression to stage 2 hypertension was associated with a marked increase in lifetime risk. The current guidelines require revision to promote early detection and appropriate management of blood pressure.
Racial and Ethnic Disparities in the Use and Outcomes of Transcatheter Mitral Valve Replacement: Analysis From the National Inpatient Sample Database
Authors: Ismayl Mahmoud , Abbasi Muhannad Aboud , Al‐Abcha Abdullah , El‐Am Edward , Walters Ryan W. , Goldsweig Andrew M. , Alkhouli Mohamad , Guerrero Mayra , Anavekar Nandan S. 
Published: March 2023

Background
Racial and ethnic disparities in outcomes exist following many cardiac procedures. Transcatheter mitral valve replacement (TMVR) has grown as an alternative to mitral valve surgery for patients at high surgical risk. The outcomes of TMVR by race and ethnicity are unknown. We aimed to evaluate racial and ethnic disparities in the outcomes of TMVR.

Methods and Results

We analyzed the National Inpatient Sample database from 2016 to 2020 to identify hospitalizations for TMVR. Racial and ethnic disparities in TMVR outcomes were determined using logistic regression models. Between 2016 and 2020, 5005 hospitalizations for TMVR were identified, composed of 3840 (76.7%) White race, 505 (10.1%) Black race, 315 (6.3%) Hispanic ethnicity, and 345 (6.9%) from other races (Asian, Pacific Islander, American Indian or Alaska Native, Other). Compared with other racial and ethnic groups, Black patients were significantly younger and more likely to be women (both
P
<0.01). There were no significant differences between White, Black, and Hispanic patients in in‐hospital mortality (5.2% versus 5.0% versus <3.5%;
P
=0.89) and procedural complications, including heart block (
P
=0.91), permanent pacemaker (
P
=0.49), prosthetic valve dysfunction (
P
=0.45), stroke (
P
=0.37), acute kidney injury (
P
=0.32), major bleeding (
P
=0.23), and blood transfusion (
P
=0.92), even after adjustment for baseline characteristics. Adjusted vascular complications were higher in Black compared with White patients (
P
=0.03). Trend analysis revealed a significant increase in TMVR in all racial and ethnic groups from 2016 to 2020 (
P
trend
<0.05).

Conclusions
Between 2016 and 2020, Black and Hispanic patients undergoing TMVR had similar in‐hospital outcomes compared with White patients, except for higher vascular complications in Black patients. Further comparative studies of TMVR in clinically similar White patients and other racial and ethnic groups are warranted to confirm our findings.
Monitoring of Hemodynamics With Right Heart Catheterization in Children With Pulmonary Arterial Hypertension
Authors: Grynblat Julien , Malekzadeh‐Milani Sophie‐Guiti , Meot Mathilde , Perros Frédéric , Szezepanski Isabelle , Morisset Stéphane , Ovaert Caroline , Bonnet Caroline , Maragnes Pascale , Ranchoup Julien , Humbert Marc , Montani I. David , Levy Marilyne , Bonnet Damien 
Published: March 2023

Background
Right heart catheterization (RHC) is a high‐risk procedure in children with pulmonary arterial hypertension without clear guidelines for the indications and targets of invasive reassessment. Our objectives are to define the aims of repeated RHC and evaluate the correlation between noninvasive criteria and hemodynamic parameters.

Methods and Results

Clinical and hemodynamic characteristics from 71 incident treatment‐naïve children (median age 6.2 years) with pulmonary arterial hypertension who had a baseline and reevaluation RHC were analyzed. Correlations between noninvasive predictors and hemodynamic parameters were tested. Adverse outcomes were defined as death, lung transplantation, or Potts shunt. At baseline, pulmonary vascular resistance index (hazard ratio [HR] 1.07 per 1 WU·m
2
increase [95% CI, 1.02–1.12],
P
=0.002), stroke volume index (HR 0.95 per 1 L·min
−1
·m
−2
increase [95% CI, 0.91–0.99],
P
=0.012), pulmonary artery compliance index (HR 0.16 per 1 mL·mm Hg
−1·
m
−2
increase [95% CI, 0.051–0.52],
P
=0.002), and right atrial pressure (HR, 1.31 per 1 mm Hg increase [95% CI, 1.01–1.71],
P
=0.043) were associated with adverse outcomes. Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure were still associated with a worse outcome at second RHC. Noninvasive criteria accurately predicted hemodynamic evolution; however, 70% of the patients who had improved based on noninvasive criteria still presented at least 1 “at risk” hemodynamics at second RHC.

Conclusions
Pulmonary vascular resistance index, pulmonary artery compliance index, and right atrial pressure are solid predictors of adverse outcomes in pediatric pulmonary arterial hypertension and potential therapeutic targets. Noninvasive criteria accurately predict the evolution of hemodynamic parameters, but insufficiently. Repeated RHC are helpful to identify children with persistent higher risk after treatment introduction.
Introduction. Space Diplomacy: The Final Frontier of Theory and Practice
Authors: Cross Mai’a K. Davis , Pekkanen Saadia M. 
Published: March 2023

Summary
A quantum leap is under way in space as a domain of human activity. The global space economy has rapidly reached almost USD450 billion in size and is projected to grow to over USD1 trillion by the 2040s. There are hundreds of actors involved, from space agencies to private companies to start-ups. Over 70 countries have space programmes and 14 have launch capabilities. These developments have involved intense transnational and international co-operation and competition, across both the public and private sectors. With such rapid changes underway, this article takes stock of how these developments impact international relations. Overall, this is the first special issue in the field of international relations to use theories of diplomacy to bring to light the various ways in which experts, scientists, astronauts, space enthusiasts and professional diplomats, among others, have shaped the formal and informal interactions among states in this key area of foreign policy.
The promotion action of AURKA on post-ischemic angiogenesis in diabetes-related limb ischemia
Authors: Bai Tao , Li Mingxing , Liu Yuanfeng , Qiao Zhentao , Zhang Xusheng , Wang Yafeng , Wang Zhiwei 
Published: March 2023

Abstract
Background
Diabetes-related limb ischemia is a challenge for lower extremity amputation. Aurora Kinase A (AURKA) is an essential serine/threonine kinase for mitosis, while its role in limb ischemia remains unclear.

Method
Human microvascular endothelial cells (HMEC-1) were cultured in high glucose (HG, 25 mmol/L d-glucose) and no additional growth factors (ND) medium to mimic diabetes and low growth factors deprivation as in vitro model. Diabetic C57BL/6 mice were induced by streptozotocin (STZ) administration. After seven days, ischemia was surgically performed by left unilateral femoral artery ligation on diabetic mice. The vector of adenovirus was utilized to overexpress AURKA in vitro and in vivo.

Results
In our study, HG and ND-mediated downregulation of AURKA impaired the cell cycle progression, proliferation, migration, and tube formation ability of HMEC-1, which were rescued by overexpressed AURKA. Increased expression of vascular endothelial growth factor A (VEGFA) induced by overexpressed AURKA were likely regulatory molecules that coordinate these events. Mice with AURKA overexpression exhibited improved angiogenesis in response to VEGF in Matrigel plug assay, with increased capillary density and hemoglobin content. In diabetic limb ischemia mice, AURKA overexpression rescued blood perfusion and motor deficits, accompanied by the recovery of gastrocnemius muscles observed by H&E staining and positive Desmin staining. Moreover, AURKA overexpression rescued diabetes-related impairment of angiogenesis, arteriogenesis, and functional recovery in the ischemic limb. Signal pathway results revealed that VEGFR2/PI3K/AKT pathway might be involved in AURKA triggered angiogenesis procedure. In addition, AURKA overexpression impeded oxidative stress and subsequent following lipid peroxidation both in vitro and in vivo, indicating another protective mechanism of AURKA function in diabetic limb ischemia. The changes in lipid peroxidation biomarkers (lipid ROS, GPX4, SLC7A11, ALOX5, and ASLC4) in in vitro and in vivo were suggestive of the possible involvement of ferroptosis and interaction between AUKRA and ferroptosis in diabetic limb ischemia, which need further investigation.

Conclusions
These results implicated a potent role of AURKA in diabetes-related impairment of ischemia-mediated angiogenesis and implied a potential therapeutic target for ischemic diseases of diabetes.
p20BAP31 induces cell apoptosis via both AIF caspase-independent and the ROS/JNK mitochondrial pathway in colorectal cancer
Authors: Jiang Xiaohan , Li Guoxun , Zhu Benzhi , Zang Jingnan , Lan Tian , Jiang Rui , Wang Bing 
Published: March 2023

Abstract
Background
During cell apoptosis, the C-terminus of BAP31 is cleaved by caspase-8 and generates p20BAP31, which has been shown to induce an apoptotic pathway between the endoplasmic reticulum (ER) and mitochondria. However, the underlying mechanisms of p20BAP31 in cell apoptosis remains unclear.

Methods
We compared the effects of p20BAP31 on cell apoptosis in six cell lines and selected the most sensitive cells. Functional experiments were conducted, including Cell Counting Kit 8 (CCK-8), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) assay. Then, cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. Next, NOX inhibitors (ML171 and apocynin), ROS scavenger (NAC), JNK inhibitor (SP600125), and caspase inhibitor (Z-VAD-FMK) were used to further investigate the underlying mechanisms of p20BAP31 on cell apoptosis. Finally, apoptosis-inducing factor (AIF) translocation from the mitochondria to the nuclei was verified by immunoblotting and immunofluorescence assay.

Results
We found that overexpression of p20BAP31 indeed induced apoptosis and had a much greater sensitivity in HCT116 cells. Furthermore, the overexpression of p20BAP31 inhibited cell proliferation by causing S phase arrest. Further study revealed that p20BAP31 reduced MMP, with a significant increase in ROS levels, accompanied by the activation of the MAPK signaling pathway. Importantly, the mechanistic investigation indicated that p20BAP31 induces mitochondrial-dependent apoptosis by activating the ROS/JNK signaling pathway and induces caspase-independent apoptosis by promoting the nuclear translocation of AIF.

Conclusions
p20BAP31 induced cell apoptosis via both the ROS/JNK mitochondrial pathway and AIF caspase-independent pathway. Compared with antitumor drugs that are susceptible to drug resistance, p20BAP31 has unique advantages for tumor therapy.
Novel bispecific aptamer targeting PD-1 and nucleolin for cancer immunotherapy
Authors: Fu Junjun , Yao Fengjiao , An Yacong , Li Xundou , Wang Wenya , Yang Xian-Da 
Published: March 2023

Abstract
Background
Immune checkpoint blockade (ICB) is a promising strategy for cancer treatment and has achieved remarkable clinical results. Further improvement of ICB efficacy may advance cancer immunotherapy and has evident medical importance. Here in this study, a PD-1 aptamer was functionalized with a tumor-homing nucleolin aptamer (AS1411) to build a novel bispecific agent (BiApt) for boosting the efficacy of ICB therapy.

Results
The two aptamers were coupled together via sticky ends to form BiApt, which had an average size of 11.70 nm. Flow cytometry revealed that BiApt could bind with both the activated T cells and the nucleolin-expressing tumor cells. In addition, BiApt could recruit more T cells to the vicinity of nucleolin-positive tumor cells. Functionally, BiApt enhanced the PBMC-mediated anticancer cytotoxicity in vitro compared with free PD-1 aptamer. Moreover, in an animal model of CT26 colon cancer, BiApt significantly boosted the antitumor efficacy vs. free PD-1 aptamer.

Conclusion
The results suggest that bispecific agent combining ICB and tumor-homing functions has potential to improve the efficacy of ICB immunotherapy.
GVC: efficient random access compression for gene sequence variations
Authors: Adhisantoso Yeremia Gunawan , Voges Jan , Rohlfing Christian , Tunev Viktor , Ohm Jens-Rainer , Ostermann Jörn 
Published: March 2023

Abstract
Background
In recent years, advances in high-throughput sequencing technologies have enabled the use of genomic information in many fields, such as precision medicine, oncology, and food quality control. The amount of genomic data being generated is growing rapidly and is expected to soon surpass the amount of video data. The majority of sequencing experiments, such as genome-wide association studies, have the goal of identifying variations in the gene sequence to better understand phenotypic variations. We present a novel approach for compressing gene sequence variations with random access capability: the Genomic Variant Codec (GVC). We use techniques such as binarization, joint row- and column-wise sorting of blocks of variations, as well as the image compression standard JBIG for efficient entropy coding.

Results
Our results show that GVC provides the best trade-off between compression and random access compared to the state of the art: it reduces the genotype information size from 758 GiB down to 890 MiB on the publicly available 1000 Genomes Project (phase 3) data, which is 21% less than the state of the art in random-access capable methods.

Conclusions
By providing the best results in terms of combined random access and compression, GVC facilitates the efficient storage of large collections of gene sequence variations. In particular, the random access capability of GVC enables seamless remote data access and application integration. The software is open source and available at https://github.com/sXperfect/gvc/.
Integrated transcriptomics contrasts fatty acid metabolism with hypoxia response in β-cell subpopulations associated with glycemic control
Authors: Miranda Mario A , Macias-Velasco Juan F , Schmidt Heather , Lawson Heather A 
Published: March 2023

Abstract
Background
Understanding how heterogeneous β-cell function impacts diabetes is imperative for therapy development. Standard single-cell RNA sequencing analysis illuminates some factors driving heterogeneity, but new strategies are required to enhance information capture.

Results
We integrate pancreatic islet single-cell and bulk RNA sequencing data to identify β-cell subpopulations based on gene expression and characterize genetic networks associated with β-cell function in obese SM/J mice. We identify β-cell subpopulations associated with basal insulin secretion, hypoxia response, cell polarity, and stress response. Network analysis associates fatty acid metabolism and basal insulin secretion with hyperglycemic-obesity, while expression of Pdyn and hypoxia response is associated with normoglycemic-obesity.

Conclusions
By integrating single-cell and bulk islet transcriptomes, our study explores β-cell heterogeneity and identifies novel subpopulations and genetic pathways associated with β-cell function in obesity.
Cardiac magnetic resonance feature tracking myocardial strain analysis in suspected acute myocarditis: diagnostic value and association with severity of myocardial injury
Authors: Gao Qian , Yi Wenfang , Gao Chao , Qi Tianfu , Li Lili , Xie Kaipeng , Zhao Wei , Chen Wei 
Published: March 2023

Abstract
Background
Albeit that cardiac magnetic resonance feature tracking (CMR-FT) has enabled quantitative assessment of global myocardial strain in the diagnosis of suspected acute myocarditis, the cardiac segmental dysfunction remains understudied. The aim of the present study was using CMR-FT to assess the global and segmental dysfunction of the myocardium for diagnosis of suspected acute myocarditis.

Methods
Forty-seven patients with suspected acute myocarditis (divided into impaired and preserved left ventricular ejection fraction [LVEF] groups) and 39 healthy controls (HCs) were studied. A total of 752 segments were divided into three subgroups, including segments with non-involvement (SNi), segments with edema (SE), and segments with both edema and late gadolinium enhancement (SE+LGE). 272 healthy segments served as the control group (SHCs).

Results
Compared with HCs, patients with preserved LVEF showed impaired global circumferential strain (GCS) and global longitudinal strain (GLS). Segmental strain analysis showed that the peak radial strain (PRS), peak circumferential strain (PCS), and peak longitudinal strain (PLS) values significantly reduced in SE+LGE compared with SHCs, SNi, SE. PCS significantly reduced in SNi (-15.3 ± 5.8% vs. -20.3 ± 6.4%, p < 0.001) and SE (-15.2 ± 5.6% vs. -20.3 ± 6.4%, p < 0.001), compared with SHCs. The area under the curve (AUC) values of GLS (0.723) and GCS (0.710) were higher than that of global peak radial strain (0.657) in the diagnosis of acute myocarditis, but the difference was not statistically significant. Adding the Lake Louise Criteria to the model resulted in a further increase in diagnostic performance.

Conclusions
Global and segmental myocardial strain were impaired in patients with suspected acute myocarditis, even in the edema or relatively non-involved regions. CMR-FT may serve as an incremental tool for assessment of cardiac dysfunction and provide important additional imaging-evidence for distinguishing the different severity of myocardial injury in myocarditis.