bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two‐Year Outcomes With a Next‐Generation Left Atrial Appendage Device: Final Results of the PINNACLE FLX Trial
Authors: Doshi Shephal K. , Kar Saibal , Sadhu Ashish , Horton Rodney , Osorio Jose , Ellis Christopher , Stone James , Shah Manish , Dukkipati Srinivas R. , Adler Stuart , Nair Devi G. , Kim Jamie , Wazni Oussama , Price Matthew J. , Holmes David R. , Shipley Robert , Christen Thomas , Allocco Dominic J. , Reddy Vivek Y. , Adler Stuart , Buchbinder Maurice , Chinitz Larry , Delurgio David , Desai Amish , Center Health , Doshi Shephal , Dukkipatti Srinivas R. , Ellis Christopher , Gibson Douglas , Holmes David , Horton Rodney , Huber Kenneth , Kar Saibal , Khairallah Farhat , Kim Jamie , Koneru Jayanthi , Mahoney Paul , Mansour Moussa , Mark George , Nair Devi , O’Neill William , Nicholson William , Osorio Jose , Price Matthew J. , Reddy Vivek Y. , Reiss James , Sadhu Ashish , Saliba Walid , Shah Manish , Shehata Michael , Stone James , Swarup Vijendra 
Published: February 2023

Background
The PINNACLE FLX (Protection Against Embolism for Non‐valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next‐generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2‐year outcomes with this next‐generation left atrial appendage closure device.

Methods and Results

Patients with nonvalvular atrial fibrillation with CHA
2
DS
2
‐VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA
2
DS
2
‐VASc, 4.2±1.5), the secondary efficacy end point of 2‐year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1‐sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two‐year rates of adverse events were as follows: 9.3% all‐cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device‐related thrombi after 1 year.

Conclusions
The secondary end point of 2‐year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next‐generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.
Sleep Irregularity and Subclinical Markers of Cardiovascular Disease: The Multi‐Ethnic Study of Atherosclerosis
Authors: Full Kelsie M. , Huang Tianyi , Shah Neomi A. , Allison Matthew A. , Michos Erin D. , Duprez Daniel A. , Redline Susan , Lutsey Pamela L. 
Published: February 2023

Background
Sleep irregularity has been linked to incident cardiovascular disease. Less is known about associations of sleep regularity with atherosclerosis. We examined cross‐sectional associations of actigraphy‐assessed sleep duration and sleep timing regularity with subclinical atherosclerosis in the community‐based MESA (Multi‐Ethnic Study of Atherosclerosis).

Methods and Results
MESA Sleep Ancillary Study participants (N=2032; mean age, 68.6±9.2 years; 37.9% White) completed 7‐day wrist actigraphy. Participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima‐media thickness, and the ankle‐brachial index. Sleep regularity was quantified by the 7‐day with‐in person SD of sleep duration and sleep onset timing. Relative risk regression models were used to calculate prevalence ratios and 95% CIs. Models are adjusted for demographics, cardiovascular disease risk factors, and other objectively assessed sleep characteristics including obstructive sleep apnea, sleep duration, and sleep fragmentation. After adjustment, compared with participants with more regular sleep durations (SD ≤60 minutes), participants with greater sleep duration irregularity (SD >120 minutes) were more likely to have high coronary artery calcium burden (>300; prevalence ratio, 1.33 [95% CI, 1.03–1.71]) and abnormal ankle‐brachial index (<0.9; prevalence ratio, 1.75 [95% CI, 1.03–2.95]). Compared with participants with more regular sleep timing (SD ≤30 minutes), participants with irregular sleep timing (SD >90 minutes) were more likely to have high coronary artery calcium burden (prevalence ratio, 1.39 [95% CI, 1.07–1.82]). Associations persisted after adjustment for cardiovascular disease risk factors and average sleep duration, obstructive sleep apnea, and sleep fragmentation.

Conclusions
Sleep irregularity, particularly sleep duration irregularity, was associated with several measures of subclinical atherosclerosis. Sleep regularity may be a modifiable target for reducing atherosclerosis risk. Future investigation into cardiovascular risk reduction interventions targeting sleep irregularity may be warranted.
SARC Gene Mutation Is Associated With Myocardial Fibrosis Measured by Histopathology and Cardiac Magnetic Resonance in Patients With Hypertrophic Cardiomyopathy
Authors: Huang Manyun , Zhang Jian , Song Changpeng , Wang Shuiyun , Zhou Zhou , Wang Hongyue , Zhao Shihua , Yin Kunlun , Li Li , Yang Shujuan , Zheng Xinxin , Lu Jie , Huang Xiaohong 
Published: February 2023

Background
Sarcomere gene mutation and myocardial fibrosis are both associated with poorer clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to determine the relationship between sarcomere gene mutation and myocardial fibrosis measured by both histopathology and cardiac magnetic resonance (CMR).

Methods and Results

Two hundred twenty‐seven patients with HCM who underwent surgical treatment, genetic testing, and CMR were enrolled. We retrospectively analyzed basic characteristics, sarcomere gene mutation, and myocardial fibrosis measured by CMR and histopathology. In our study, the mean age was 43 years, and 152 patients (67.0%) were men. A total of 107 patients (47.1%) carried a positive sarcomere gene mutation. The myocardial fibrosis ratio was significantly higher in the late gadolinium enhancement (LGE)+ group (LGE+ 14.3±7.5% versus LGE− 9.0±4.3%;
P
=0.001). Patients with HCM with SARC+ showed a high probability of fibrosis both in histopathology (myocardial fibrosis ratio 15.3±8.0% versus 12.4±6.5%;
P
=0.003) and CMR examination (LGE+ 98.1% versus 84.2%;
P
<0.001; LGE quantification 8.3% versus 5.8%;
P
<0.001). Linear regression analysis showed that sarcomere gene mutation (B=2.661;
P
=0.005) and left atrial diameter (B=0.240;
P
=0.001) were related factors for histopathological myocardial fibrosis. Also, the myocardial fibrosis ratio was significantly higher in the
MYH7
(myosin heavy chain) group (
MYH7
18.1±9.6% versus
MYBPC3
[myosin binding protein C] 13.1±5.2%;
P
=0.019).

Conclusions

Patients with HCM with positive sarcomere gene mutation had a higher myocardial fibrosis extent than patients without mutation, and a significant difference in myocardial fibrosis was also observed between the
MYBPC3
and
MYH7
groups. In addition, a high consistency was found between CMR–LGE and histopathological myocardial fibrosis in patients with HCM.
Isolation and characterization of the actinomycete, Nocardiopsis, from Haizhou Bay, and its application as a probiotic for Exopalaemon carinicauda (Holthuis, 1950) (Caridea, Palaemonidae)
Authors: Shen Shanrui , Mi Xiaoyan , Shen Qin , Chen Jing , Gao Huan , Lai Xiaofang 
Published: February 2023

Abstract
Actinomycetes, as the main producers of a variety of active metabolites and enzymes, have received extensive attention in aquaculture. An actinomycete had been isolated from Haizhou Bay and been identified by morphological analysis and 16S rRNA sequencing. Results showed that the actinomycete had the highest similarity (99.65%) with Nocardiopsis sp. and was named strain E10. Strain E10 produced an exo-enzyme with proteinase effect that showed strong antibacterial activity against Vibrio anguillarum. This strain E10 was tested as a probiotic for the culture of Exopalaemon carinicauda. After having been fed with a diet supplemented with strain E10 for 30 days, the final body weight (Wt), weight gain rate (WGR), special growth rate (SGR), survival rate (SR) and digestive enzymes (chymotrypsin, α-amylase and lipase) of E. carinicauda in all experimental groups showed no significant differences (). However, the antioxidant enzymes (total superoxide dismutase, catalase and peroxidase) and the non-specific immune-related enzymes (acid phosphatase, alkaline phosphatase and lysozyme) in the treatment groups increased significantly () compared with the control group. The cumulative mortality of the treatment groups (35.56% in 5 × 109 CFU/100 g) was significantly lower than that of the control treatment (73.33%) () post challenge with V. anguillarum for 14 days. The results indicated that strain E10 had no significant effect on the growth, but a significant improvement on the immunity of E. carinicauda. This study provides the data for ecological aquaculture of E. carinicauda.
Gene expression profiling and FDG-PET radiomics uncover radiometabolic signatures associated with outcome in DLBCL
Authors: Mazzara Saveria , Travaini Laura , Botta Francesca , Granata Chiara , Motta Giovanna , Melle Federica , Fiori Stefano , Tabanelli Valentina , Vanazzi Anna , Ramadan Safaa , Radice Tommaso , Raimondi Sara , Lo Presti Giuliana , Ferrari Mahila E. , Jereczek-Fossa Barbara Alicja , Tarella Corrado , Ceci Francesco , Pileri Stefano , Derenzini Enrico 
Published: February 2023

Abstract
Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)– and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP–based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP–based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL.
Defining a cohort of anemia-activated cis elements reveals a mechanism promoting erythroid precursor function
Authors: Zhou Yichao , Dogiparthi Venkatasai Rahul , Ray Suhita , Schaefer Meg A. , Harris Hannah L. , Rowley M. Jordan , Hewitt Kyle J. 
Published: February 2023

Abstract
Acute anemia elicits broad transcriptional changes in erythroid progenitors and precursors. We previously discovered a cis-regulatory transcriptional enhancer at the sterile alpha motif domain-14 enhancer locus (S14E), defined by a CANNTG-spacer-AGATAA composite motif and occupied by GATA1 and TAL1 transcription factors, is required for survival in severe anemia. However, S14E is only 1 of dozens of anemia-activated genes containing similar motifs. In a mouse model of acute anemia, we identified populations of expanding erythroid precursors, which increased expression of genes that contain S14E-like cis elements. We reveal that several S14E-like cis elements provide important transcriptional control of newly identified anemia-inducing genes, including the Ssx-2 interacting protein (Ssx2ip). Ssx2ip expression was determined to play an important role in erythroid progenitor/precursor cell activities, cell cycle regulation, and cell proliferation. Over a weeklong course of acute anemia recovery, we observed that erythroid gene activation mediated by S14E-like cis elements occurs during a phase coincident with low hematocrit and high progenitor activities, with distinct transcriptional programs activated at earlier and later time points. Our results define a genome-wide mechanism in which S14E-like enhancers control transcriptional responses during erythroid regeneration. These findings provide a framework to understand anemia-specific transcriptional mechanisms, ineffective erythropoiesis, anemia recovery, and phenotypic variability within human populations.
Ultrasound and microbubble-mediated delivery of miR-424-5p has a therapeutic effect in preeclampsia
Authors: Wang Xudong , Wu Yan , Sun Qinliang , Jiang Zhonghui , Che Guoying , Tao Yangyang , Tian Jiawei 
Published: February 2023

Abstract
Objective
To determine the influence of ultrasound/microbubble-mediated miR-424-5p delivery on trophoblast cells and the underlying mechanism.

Methods
Blood pressure and 24-h proteinuria of patients with preeclampsia (PE) were measured as well as the levels of miR-424-5p and amine oxidase copper containing 1 (AOC1) in placental tissues. HTR-8/Svneo and TEV-1 cells were subjected to cell transfection or ultrasonic microbubble transfection for determination of the expression of miR-424-5p, AOC1, β-catenin and c-Myc as well as cell proliferation, apoptosis, migration and invasiveness. The concentrations of placental growth factor (PLGF), human chorionic gonadotropin (β-hCG) and tumor necrosis factor-α (TNF-α) were measured in HTR-8/Svneo and TEV-1 cells. RNA immunoprecipitation (RIP) and dual luciferase reporter assay detected the binding of miR-424-5p to AOC1. A PE mouse model was induced by subcutaneous injection of L-NAME, where the influence of ultrasound/microbubble-mediated miR-424-5p delivery was evaluated.

Results
miR-424-5p was downregulated while AOC1 was upregulated in the placental tissues from PE patients. Overexpression of miR-424-5p activated Wnt/β-catenin signaling pathway and promoted the proliferation of HTR-8/Svneo and TEV-1 cells as well as enhanced the migratory and invasive behaviors. AOC1 overexpression partly eliminated the effects of miR-424-5p on HTR-8/Svneo and TEV-1 cells. Ultrasound and microbubble mediated gene delivery enhanced the transfection efficiency of miR-424-5p and further promoted the effects of miR-424-5p in trophoblast cells. Ultrasound/microbubble-mediated miR-424-5p delivery alleviated experimental PE in mice.

Conclusion
Ultrasound and microbubble-mediated miR-424-5p delivery targets AOC1 and activates Wnt/β-catenin signaling pathway, thus promoting the aggressive phenotype of trophoblast cells, which indicating that miR-424-5p/AOC1 axis might be involved with PE pathogenesis.
Absence of fluctuation and inverted circadian rhythm of blood pressure increase the risk of cognitive dysfunction in cerebral small vessel disease patients
Authors: Xu Yiwen , Gong Chen , Liao Jingxian , Ge Zhonglin , Tan Yu , Jiang Yi , Liu Mengqian , Zhong Wen , Zhang Xianxian , Dong Nan , Shen Xiaozhu 
Published: February 2023

Abstract
Background and purpose
Cerebral small vessel disease (CSVD) is a common cause of stroke and senile vascular cognitive impairment, imposing a heavy burden on public health care systems worldwide. Hypertension and 24-hour blood pressure variability (BPV), known to be significant risk factors for cognitive dysfunction, have been found to be associated with cognitive function in CSVD patients in previous studies. However, as a derived part of BPV, there are few studies on the relationship between circadian rhythm of blood pressure and cognitive dysfunction in CSVD patients, and the relationship between them is still unclear. Thus, this study aimed to investigate whether the disturbance of circadian rhythm of blood pressure can affect the cognitive function of patients with CSVD.

Methods
A total of 383 CSVD patients hospitalized in the Geriatrics Department of the Lianyungang Second People’s Hospital between May 2018 and June 2022 were enrolled in this study. The clinical information and parameters of 24-hour ambulatory blood pressure monitoring were compared between the cognitive dysfunction group (n = 224) and the normal group (n = 159). Finally, a binary logistic regression model was used to assess the relationship between circadian rhythm of blood pressure and cognitive dysfunction in patients with CSVD.

Results
(1) Patients in the cognitive dysfunction group were older, had lower blood pressure on admission, and had a greater number of previous cardiovascular and cerebrovascular diseases (P < 0.05). (2) More patients in the cognitive dysfunction group had circadian rhythm abnormalities in blood pressure, especially the non-dipper and reverse-dipper types (P < 0.001). (3) In the elderly, there was a statistical difference in the circadian rhythm of blood pressure between the cognitive dysfunction group and the normal group, but this phenomenon did not exist in the middle-aged. (4) Binary logistic regression analysis showed that after adjusting for confounding factors, the risk of cognitive dysfunction in CSVD patients with non-dipper type was 4.052 times higher than that of dipper type (95% CI, 1.782–9.211; P = 0.001), and reverse-dipper type was 8.002 times higher than those with dipper type (95% CI, 3.367–19.017; P<0.001).

Conclusions
The disturbance of circadian rhythm of blood pressure may affect the cognitive function of patients with CSVD, and the risk of cognitive dysfunction in non-dipper and reverse-dipper types are higher.
Prevalence and correlates of modifiable risk factors for cervical cancer and HPV infection among senior high school students in Ghana: a latent class analysis
Authors: Ampofo Ama Gyamfua , Boyes Allison W. , Asibey Shadrack Osei , Oldmeadow Christopher , Mackenzie Lisa J. 
Published: February 2023

Abstract
Background
While health risk behaviours are likely to co-occur, there is dearth of studies exploring the clustering of cervical cancer and HPV infection risk factors among adolescents. This study aimed to determine: 1) the prevalence of modifiable risk factors for cervical cancer and HPV infection, 2) the clustering of modifiable risk factors for cervical cancer and HPV infection, and 3) factors associated with the identified clusters.

Methods
Female students (aged 16–24 years, N = 2400) recruited from 17 randomly selected senior high schools in the Ashanti Region, Ghana completed a questionnaire assessing modifiable risk factors for cervical cancer and HPV infection including sexual experience, early sexual intercourse (< 18 years), unprotected sex, smoking, sexually transmitted infections (STIs); multiple sexual partners (MSP) and smoking. Latent class analysis explored separate classes of students according to their risk factor profiles for cervical cancer and HPV infection. Latent class regression analysis explored factors associated with latent class memberships.

Results
Approximately one in three students (34%, 95%CI: 32%-36%) reported exposure to at least one risk factor. Two separate classes emerged: high-risk and low-risk (cervical cancer: 24% and 76% of students, respectively; HPV infection: 26% and 74% of students, respectively). Compared to participants in the low-risk classes i) the cervical cancer high-risk class were more likely to report exposure to oral contraceptives; early sexual intercourse (< 18 years); STIs; MSP and smoking; and ii) the HPV infection high risk class were more likely to report exposure to sexual intercourse; unprotected sex and MSP. Participants with higher risk factor knowledge had significantly higher odds of belonging to cervical cancer and HPV infection high-risk classes. Participants with greater perceived susceptibility to cervical cancer and HPV infection were more likely to belong to the high-risk HPV infection class. Sociodemographic characteristics and greater perceived seriousness about cervical cancer and HPV infection had significantly lower odds of belonging to both high-risk classes.

Conclusions
The co-occurrence of cervical cancer and HPV infection risk factors suggests that a single school-based multi-component risk reduction intervention could concurrently target multiple risk behaviours. However, students in the high risk class may benefit from more complex risk reduction interventions.
Predictors of national health insurance membership among the poor with different education levels in Indonesia
Authors: Putri Nuzulul Kusuma , Laksono Agung Dwi , Rohmah Nikmatur 
Published: February 2023

Abstract
Background
Indonesia has made significant progress in expanding universal health coverage (UHC) through its National Health Insurance (NHI) mechanism. However, in the context of NHI implementation in Indonesia, socioeconomic disparities caused its subpopulations to have different literacy of NHI concepts and procedures, increasing the risk of healthcare access inequities. Hence, the study aimed to analyse the predictors of NHI membership among the poor with different education levels in Indonesia.

Methods
This study used the secondary dataset of the nationwide survey “Abilities and Willingness to Pay, Fee, and Participant Satisfaction in implementing National Health Insurance in Indonesia in 2019” by The Ministry of Health of the Republic of Indonesia. The study population was the poor population in Indonesia and included a weighted sample of 18,514 poor people. The study used NHI membership as a dependent variable. Meanwhile, the study analysed seven independent variables: wealth, residence, age, gender, education, employment, and marital status. In the final step of the analysis, the study used binary logistic regression.

Results
The results show that the NHI membership among the poor population tends to be higher among those who have higher education, live in urban areas, are older than 17 years old, are married and are wealthier. The poor population with higher education levels is more likely to become NHI members than those with lower education. Their residence, age, gender, employment, marital status, and wealth also predicted their NHI membership. Poor people with primary education are 1.454 times more likely to be NHI members than those without education (AOR 1.454; 95% CI 1.331–1.588). Meanwhile, those with secondary education are 1.478 times more likely to be NHI members than those with no education (AOR 1.478; 95% CI 1.309–1.668). Moreover, higher education is 1.724 times more likely to result in being an NHI member than no education (AOR 1.724; 95% CI 1.356–2.192).

Conclusion
Education level, residence, age, gender, employment, marital status, and wealth predict NHI membership among the poor population. Since significant differences exist in all of those predictors among the poor population with different education levels, our findings highlighted the importance of government investment in NHI, which must be supported with investment in the poor population’s education.