bluuebunny/crossref_metadata_2025 huggingface dataset:
Hsa_circ_0000520 Promotes Non-Small Cell Lung Cancer Progression through the miR-1258/AKT3 Axis
Authors: Han Lan , Yang Hanxue , Wei Wei , Hu Fen , Yuan Limei
Published: December 2022

Background. There are several previous studies suggesting that circular RNAs (circRNAs) are involved in tumorigenesis of non-small cell lung cancer (NSCLC). Nevertheless, the role of circRNA_0000520 (circ_0000520) in this disease has not yet been studied. Methods. circ_0000520, microRNA (miR)-1258, and AKT serine/threonine kinase 3 (AKT3) mRNA expression levels were detected by qPCR. CCK-8, EdU, and Transwell assays were utilized to detect NSCLC cells’ malignant biological behaviors. The targeted relationship between miR-1258 and AKT3 3′-UTR or circ_0000520 was verified through the dual-luciferase reporter gene assay. Western blotting was utilized to measure the AKT3 expression after circ_0000520 and miR-1258 were selectively regulated. Results. circ_0000520 was upregulated in NSCLC. Highly expressed circ_0000520 is linked to the NSCLC patient’s advanced TNM stage and lymph node metastasis. circ_0000520 overexpression facilitated NSCLC cell growth, migration, and invasion. miR-1258 was identified as the downstream target of circ_0000520. miR-1258 overexpression weakened the effect of circ_0000520 overexpression on NSCLC cells. miR-1258 targeted and inhibited AKT3. circ_0000520 positively regulated the AKT3 expression in NSCLC cells by sponging miR-1258. Conclusion. circ_0000520 upregulates AKT3 by competitively binding with miR-1258 to facilitate NSCLC progression.
Caudatin Inhibits the Proliferation, Invasion, and Glycolysis of Osteosarcoma Cells via the Wnt/β- Catenin Pathway
Authors: Zhang Yan , Sheng Zhizhong , Su Chi , Xia Yuli , Chen Xiangfan , Huang Xiaobo , Li Honglin , Ma Changsheng , Wang Ligang
Published: December 2022

Background. Caudatin is a steroidal glycoside with reported anticancer activity in a variety of studies. Nevertheless, the role and mechanisms of caudatin in osteosarcoma (OS) remain unclear. In this study, we explored the potential anticancer effects of caudatin in OS cells and investigated the underlying mechanisms. Methods. Both the CCK8 proliferation assay and flow cytometry were employed to evaluate cell proliferation and apoptosis. A transwell assay was applied to determine cell invasion ability. Besides, glycolytic capacity was examined by measuring glucose consumption, lactic acid production, as well as ATP production. A western blot was utilized to assess the protein levels of β-catenin, CyclinD 1, C-myc, HK2 (Hexokinase 2), LDHA (lactate dehydrogenase), as well as epithelial-mesenchymal transition (EMT)-related markers. The inhibitory effect of caudatin on tumor growth was investigated using a xenograft tumorigenesis model. Results. Caudatin restrained cellular glycolysis, suppressed cell proliferation and invasion by reducing HK2 and LDHA expression and regulating the Wnt/β-Catenin signaling pathway. Caudatin treatment caused the upregulation of E-cadherin and suppressed N-cadherin expression. Further, caudatin treatment impaired cell viability, invasion ability, and intracellular glycolysis level but induced apoptosis. The administration of BML 284 reversed the inhibitory effects of caudatin. Moreover, caudatin suppressed the tumorigenesis of OS cells in the xenograft model of nude mice. Conclusions. Our study revealed the anticancer effects of caudatin, including proliferation inhibition, cell invasion suppression, and glycolysis impairment. These effects seem to be executed through targeting the Wnt/β-Catenin signaling pathway. These data indicate that caudatin may be formulated as a potential therapeutic for osteosarcoma.
Non-Neurological Complications after Mechanical Thrombectomy for Acute Ischemic Stroke: A Retrospective Single-Center Study
Authors: Goffin Pierre , Thouny Romain , Guntz Julien , Brisbois Denis , Desfontaines Philippe , Demaret Pierre
Published: December 2022

Introduction. The global burden of stroke is high and mechanical thrombectomy is the cornerstone of the treatment. Incidences of acute non-neurological-complications are poorly described. Improve knowledge about these complications may allow to better prevent, detect and/or manage them. The aim is to identify risk markers of death or poor evolution. Method. We conducted a retrospective single-center study to analyzed the incidence of non-neurologicalcomplications after mechanical thrombectomy in acute ischemic stroke. Patients who had experienced a stroke and undergone thrombectomy were identified using a registry in which we prospectively collected data from each patient admitted to our hospital with a diagnosis of stroke. Quantitative and qualitative variables were analyses. The association between studied variables and hospital death was assessed using simple logistic regression models. Result. 361 patients were reviewed but 16 were excluded due to a lack of medical information. Between 2012 and 2019, 345 patients were included. The median admission NIHSS score was 15. Seven percent of the patients died in the ICU. The following independent risk markers of death in the ICU were identified by logistic regression: respiratory complication, hypotension, infectious complication, and hyperglycemia. Conclusion. In this large retrospective study of stroke, respiratory complications and pulmonary infections represented the most important non-neurological adverse events encountered in the ICU and associated with a risk of death.
Distribution and Characteristics of Bacteria Isolated from Cystic Fibrosis Patients with Pulmonary Exacerbation
Authors: Erfanimanesh Soroor , Emaneini Mohammad , Modaresi Mohammad Reza , Feizabadi Mohammad Mehdi , Halimi Shahnaz , Beigverdi Reza , Nikbin Vajiheh Sadat , Jabalameli Fereshteh
Published: December 2022

Background. Cystic fibrosis (CF) is an inherited recessive disorder characterized by recurrent and persistent pulmonary infections, resulting in lung function deterioration and early mortality. Methods. A cross-sectional study was conducted on the bacterial profile and antibiotic resistance pattern of 103 respiratory specimens from CF patients with signs of pulmonary exacerbation. Antibiotic susceptibility testing and biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa isolates were performed by the Kirby–Bauer disc diffusion method and microtiter plate assay, respectively. Molecular typing of S. aureus and P. aeruginosa isolates was carried out by spa typing and repetitive extragenic palindromic element PCR. Results. In a total of 129 isolates, the most prevalent organisms were S. aureus (55.3%) and P. aeruginosa (41.7%). Other less prevalent bacterial isolates include coagulase-negative staphylococci, Escherichia coli, klebsiella spp., Enterobacter spp., and Achromobacter xylosoxidans. The highest rate of resistance for S. aureus was observed to azithromycin and erythromycin (80%), ciprofloxacin (52.3%), clindamycin (44.6%) and tetracycline (43%). Twenty percent of S. aureus isolates were methicillin-resistant S. aureus (MRSA) and 47.6% were MDR S. aureus. For P. aeruginosa isolates the highest resistance was to cefepime (38.3%) and levofloxacin (33.3%) and 20% showed MDR phenotype. Conclusion. Our study demonstrated a significant decline in the prevalence of P. aeruginosa infections in comparison to previous studies. We found S. aureus to be more prevalent in younger patients, whereas mucoid P. aeruginosa showed a shift in prevalence toward older ages. Molecular typing methods showed great diversity between isolates.
Multirobot Federating Method for Disjoint Segments in Wireless Sensor Network Based on Optimal Anchor Point and Local Priority
Authors: Jing Rong , Chen MingWang , Zhao FengDa , Li XianShan , Kong LingFu
Published: December 2022

In order to solve the connectivity problem between multiple islands in the wireless sensor network (WSN) due to large-scale damage, a multirobot WSN island alliance method based on the local priority of the optimal anchor point is proposed. This method introduces the idea of priority restoration of local connectivity in weighted networks and uses the optimal anchor point election mechanism to construct connectivity paths. Compared with existing methods, LPRMA’s local preferential recovery thinking makes WSN island alliances more adaptable. And LPRMA’s trunk deployment strategy based on optimal anchor can significantly reduce the path length and the number of trunk deployments for connected recovery. Finally, through the comparison and simulation experiments with the existing methods, the results show that the proposed method can effectively improve the efficiency of WSN island alliance while satisfying the constraints of lower network delay and higher robustness.
Yield and Physicochemical Properties of Marula (Sclerocarya birrea) Seed Oils among Nine International Provenances Tested in Malawi
Authors: Kamanula Mussa , Yangontha Munthali Chimuleke , Finias Kamanula John
Published: December 2022

Sclerocarya birrea (Marula) is an indigenous fruit tree that is revered for its numerous socioeconomic contributions to human livelihood. Among others, the species is an important source of seed oil that is utilized in various domestic and industrial applications. This study was carried out to assess the yield and physicochemical properties of seed oils among nine international provenances of Sclerocarya birrea (subspecies caffra and birrea) planted in Malawi. Seed oils were obtained using the Soxhlet extraction method while quality parameters were determined using procedures described by the Malawi Bureau of Standards. Oil yield was highest (52.2%) in subspecies birrea (Missira provenance; Mali). Oil moisture content, free fatty acids, acid value, and peroxide value ranged from 0.06 to 076%, 1.96 to 4.07%, 3.91 to 8.13 mg·KOH/g, and 1.84 to 5.15 meq·KOH/g, respectively. Variations in oil yield and physicochemical properties could be attributed to genetic differences and the origin of genotypes. The selection of Sclerocarya birrea for oil production and use should be based on both provenance and subspecies levels. Further studies should study the heritability of the oil content and its physicochemical properties before conclusive decisions on the use of seed for propagation are carried out.
Adiwiyata Program Innovation through Penta Helix Approach
Authors: Megawati Suci , Yusriadi Yusriadi , Syukran Alfan , Rahaju Tjitjik , Hussen Negash
Published: December 2022

The Adiwiyata program is a government program implemented in 2006 due to Indonesia’s declining environmental quality. As a part community, students need to be educated about caring for the environment that can be grown through education. Much research has been described on the Adiwiyata program, but information about the role of Adiwiyata in developing the character of caring for the environment is still limited. This study aims to create the innovation of the Adiwiyata program in developing environmental care characters in elementary schools in Surabaya through the Penta Helix method. The research is located in some elementary schools in Surabaya city, and this study uses a qualitative case study approach. The output of this research is to redesign the Adiwiyata program in the city of Surabaya through the Penta Helix approach. This research method uses qualitative methods. Data are collected through literature studies, semistructured interviews, and surveys and used qualitative data analysis. The results show that the policy’s content and the context of implementing the Adiwiyata program had been going well. Further suggestions researchers suggest continuing to improve the performance of this Adiwiyata properly and providing a reward and punishment system to the implementers involved.
Image Perceptual Hashing for Content Authentication Based on Geometric Invariant Vector Distance
Authors: Xing Huifen , Wang Shuchao , Wu Qilin , Wang Honghai
Published: December 2022

Image perceptual hashing is broadly applied in image content authentication, recognition, retrieval, and social media hotspot event detection. An image authentication algorithm is put forward based on the Itti visual saliency model and geometric invariant vector distance. To begin with, the image is preprocessed and weighted by the Itti model and contourlet transform. After that, the weighted image is randomly divided into blocks, and the image feature vector is constructed by calculating the geometric invariant vector distance on both Hu invariant moment vector and maximum singular value vector of the random blocks. In the end, the feature vector is quantized and encrypted to generate the ultimate hash. Experimental results illustrate that when the threshold T = 70, the true positive rate

P

T
P
R

for duplicate images stands at 0.96574, while the false rate

P

F
P
R

of different images is merely 0.0224, with the total error rate reaching the minimum value (0.0566). Furthermore, the AUC value of the proposed algorithm is 0.9951, which is higher than that of the comparison algorithms, indicating that the algorithm has better performance than other state-of-the-art algorithms in terms of various visual content-preserving attacks.
Screening Patterns of Nonalcoholic Fatty Liver Disease in Children with Obesity in Canadian Primary Care: A Cross-Sectional Study
Authors: Morkem Rachael , Theal Rebecca , Barber David , Flemming Jennifer , Queenan John , Kehar Mohit
Published: December 2022

Background. Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease, and children with a body mass index (BMI) ≥95th percentile are recommended to be screened for NAFLD by liver enzymes. Objectives. This study aimed to determine the frequency and predictors of screening for NAFLD among children with obesity in Canada and to evaluate a sample of children with suspected NAFLD. Methods. This cross-sectional study used data from the Canadian Primary Care Sentinel Surveillance Network, a repository of electronic medical record data from Canadian primary care practices. Results. Of n = 110,827 children aged 9–18 years, 13.9% (n = 9,888) had a BMI ≥95th percentile. Only 8.7% (n = 859) of these patients were screened for NAFLD in the last year, and 23.6% (n = 2336) were ever screened. Using logistic regression, screening in the last year was associated with demographic and clinical characteristics, including previous liver enzyme assessment, prior antidiabetic prescription, and prior anxiolytic prescription. Among children with suspected NAFLD (n = 1,046), 34.7% had a BMI ≥99th percentile and approximately 8% were at increased risk of significant liver disease. Conclusion. The study revealed low screening rates for NAFLD in Canadian primary care and highlighted the important role of primary care providers in identifying and managing pediatric NAFLD.
Associations between Students’ Test Preparation Strategies and Test Anxiety: Gender, Age, and Parents’ Level of Education as Control Variables
Authors: Nwosu Kingsley Chinaza , Wahl WP , Ofojebe Edna Nkechi , Okafor Augustina Ukamaka , Okwuduba Emmanuel Nkemakolam
Published: December 2022

Although students’ test preparation tendencies are related to their test-taking confidence, empirical evidence on how students’ test preparation strategies relate to their test anxiety is still lacking. Framed within the skills deficit model, we examined the associations between students’ test preparation strategies (cognitive, metacognitive, and social preparation strategies) and their test anxiety (worry, cognitive, tension, and physiological test anxiety). Students’ gender, age, and parents’ level of education served as control variables. Participants were 248 students in two randomly selected secondary schools in Awka, Anambra state, Nigeria. Survey questionnaires were used for data collection. Major findings revealed that cognitive and metacognitive test preparation strategies significantly predicted worry and physiological indicators components of test anxiety, respectively. When the sociodemographic variables were controlled, the ΔR2 was significant only in the worry and physiological subscale. We concluded that test preparation strategies could be more associated with the worry subscale than the affective-physiological subscale. Furthermore, test preparation strategies involving monitoring and regulation could be associated to physiological indicators of test anxiety.
Dynamic Analysis of Construction and Demolition Waste Management System (A Case Study of Tehran, Iran)
Authors: Ghanbari Milad
Published: December 2022

Increasing construction and demolition (C&D) waste generation has faced serious challenges in the metropolitan areas of Iran. The objective of this research is to present a system dynamics model for C&D waste management of Tehran. In particular, variables such as energy consumption and carbon dioxide (CO2) emissions for the city of Tehran to the horizon of 2041 are studied and predicted. Increasing the rate of construction of housing and urban infrastructure will increase C&D waste and, on the other hand, increase the demand for raw materials, which is contrary to the principles of sustainable development. The increase in quarries exploitation and the increase in C&D waste generation can reduce the buildable area of the city. The impacts of such factors are in a cyclic and systemic approach that either reinforces a destructive factor or balances the existing solution. In general, the assessment of the implementation or nonimplementation of C&D waste recycling in each city requires a system insight that examines the aspects of the subject with a systemic perspective over time. To this end, the system dynamic approach, along with the environmental and economic approach of the life cycle, can clarify the hidden dimensions of the problem. One of the important limitations of the research is the large number of variables in the model and finding reliable historical information for these variables.
A Network Pharmacology‐Based Study on the Mechanism of Dibutyl Phthalate of Ocimum basilicum L. against Alzheimer’s Disease through the AKT/GSK‐3β Pathway
Authors: Simayi Jimilihan , Bayinsang  , Nuermaimaiti Maimaitiming , Hailati Sendaer , Han Mengyuan , Reheman Zulihuma , Wumaier Ainiwaer , Zhou Wenting
Published: December 2022

Background. Ocimum basilicum L. (OBL) is mainly used to treat neurological diseases in China. The preliminary work of this group showed that OBL improves cognitive impairment in Alzheimer’s disease (AD). However, the underlying pharmacological mechanism remains unclear. Methods. The components of OBL were compiled by literature search, and their active ingredients were screened by online database. The drug targets of OBL in the treatment of AD were predicted and analyzed using information derived from sources such as the SwissTargetPrediction tool. And through the network visual analysis function of Cytoscape software and protein‐protein interaction analysis (PPI), the core targets of OBL treatment of AD are predicted. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by OBL. Moreover, AutoDock software was used to assess the potential binding affinity between the core targets and the active compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. Results. A total of 35 active compounds and 188 targets of OBL were screened, of which 43 common targets were related to AD. The active compounds of 35 OBLs induced 118 GO and 78 KEGG. The results of PPI and network topology parameter analysis show that targets such as MAPK1, GSK3B, NR3C2, ESR1, and EGFR are known as the core targets for the treatment of AD by OBL and are docked with the active ingredients of OBL. Molecular docking results suggest that diterbutyl phthalate (DBP) may be the main active component of OBL for the treatment of AD. Flow cytometry analysis results showed that apoptosis decreased with increasing DBP dose. In addition, DBP significantly decreased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in the supernatant of Aβ25-35‐induced injury HT22 cell cultures, and it can be speculated that DBP has the ability to protect the stability of injured neuronal cells and improve the permeability of cell membranes, thus stabilizing the intracellular environment. Mechanistically, DBP may increase the mRNA levels of AKT, GSK‐3β, etc. in AD cell models and regulate the phosphorylation of AKT/GSK‐3β pathway‐related. Conclusions. Conclusively, our study suggests that DBP, the main active component of OBL, has potential in the prevention or treatment of AD.
HSBM-Produced Zinc Oxide Nanoparticles: Physical Properties and Evaluation of Their Antimicrobial Activity against Human Pathogens
Authors: Massoudi Imen , Hamdi Ridha , Ababutain Ibtisam , Alhussain Ethar , Kharma Aya
Published: December 2022

This work examines the antibacterial and anticandidal activities of zinc oxide nanoparticles (ZNPs) synthesized by high-speed ball milling (HSBM), for short milling times: 0.5, 1, 1.5, and 2 h. First, ZNPs have been characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and the Zetasizer analyzer. The HSBM results in semispherical ZNPs with some local agglomeration. We found that nanoparticles decrease in size continuously with milling time until they reach about 84% of their original size after only two hours; at 1000 rpm, HSBM reduces ZNP’s average size by 6 nm/min. As particle size decreases, the X-ray diffracted patterns become broader and less intense while confirming that no phase transformation has occurred, proving HSBM’s effectiveness in synthesizing nanoparticles on a large scale within a short period of time. According to FT-IR analysis, as material sizes change, the polarization charge of the ZNP surface changes as well, creating discrepancies in vibrational frequency, as demonstrated by the shifting of the IR spectra in the 300–600 cm−1 frequency band. Raman responses have also been proven to depend on the particle size. Using the Agar well diffusion method, eleven microorganisms have been tested for the antimicrobial activity of ZNPs. Among the six Gram-negative tested bacteria, S. sonnei showed the largest inhibition zone of about 11.3 ± 0.6 mm with ZNPs measuring 148 nm in size (milled for 2 h), followed by E. coli ATCC 25922. Accordingly, S. aureus was the most susceptible Gram-positive bacteria, with inhibition zone size gradually increasing from 11.8 ± 0.3 mm to 13.5 ± 0.5 mm with decreasing nanoparticle size from 767 to 148 nm, while S. aureus ATCC 25923 was resistant to both milled and unmilled samples. Similar results were seen with candida, all milled ZNPs inhibited C. albicans, followed by C. tropicalis, whereas C. knisei was resistant to all ZNP sizes. In light of microorganism-ZNP interaction mechanisms, the obtained results have been discussed in depth.
RETRACTION NOTICE TO "Aplikasi Model Diffence in Difference Pada Regresi Binomial Logistik"
Authors: Sihombing Pardomuan Robinson , Pratiko Wisnu
Published: December 2022

This article entitled “Aplikasi Model Diffence in Difference Pada Regresi Binomial Logistik (Studi Kasus: Implementasi Program Indonesia Pintar Terhadap Status Sekolah Anak)” (2022), authored by  Pardomuan Robinson Sihombing and Wisnu Pratiko, published in Vol. 2, No. 3 of Jurnal Ekonomi dan Statistik Indonesia. 2(3), 244 – 249 has been retracted as requested by the authors.
Dampak Pandemi Covid-19 terhadap Tenaga Kerja di Indonesia
Authors: Friska Maya
Published: December 2022

The case of the Covid-19 pandemic was first detected in Indonesia on March 2, 2020 and is still ongoing. The COVID-19 pandemic has had many social and economic impacts. The impact will be very widespread, starting from politics, economy, social, culture, defense, and security, as well as community welfare. This unstable economy also has an effect on labor conditions in Indonesia, such as the rising unemployment rate. This study aims to determine the effect of the pandemic on unemployed or temporarily unemployed workers based on the classification of place of residence, gender, age, last completed education, expertise, and business field. This study uses the August 2021 National Manpower Survey (SAKERNAS) dataset with the enter method binary logistic regression method. The results showed that the classification of residence. Age, last education completed, expertise, and business field affect the temporary unemployed condition due to COVID-19, while the classification of residence, gender, age, and the last education completed affect the unemployment condition due to COVID-19.
Modelling the Impact of a Rise in Global Equity Risk Premium: The G-Cubed Simulation
Authors: Eschachasthi Realita
Published: December 2022

The global disruptions—the Covid-19 pandemic, financial crisis, trade tension, and geopolitical issues—led to uncertainty across the world economies. The impact either on individual emerging or advanced countries, however, remains unclear. To this end, this study is simulating a shock of a one percent increase in equity risk premium permanently in all sectors in all countries, and focusing on exploring its impact on the United States (US), the United Kingdom (UK), Australia, China, Indonesia, and India. The results reveal that no countries are immune from the short-lived synchronised nuisance. Investment plummeted massively following the profound drop in interest rate, while unemployment suddenly soars, and Gross Domestic Product (GDP) contracted dramatically. In the long run, all economies reverse and converge to the initial condition. Nevertheless, there would be persistent GDP loss and sluggish investment in all economies. Therefore, policy responses should be designed based on strong international cooperation, focusing on fiscal policy to limit the impact of global losing confidence.
Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach
Authors: Ruthirakuhan Myuri , Cogo‐Moreira Hugo , Swardfager Walter , Herrmann Nathan , Lanctot Krista L. , Black Sandra E.
Published: December 2022

Background

Cardiovascular risk factors co‐occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between‐group differences in incident AD and death.

Methods and Results

Cognitively normal individuals were recruited from the National Alzheimer's Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between‐group differences in the incidence of AD, mortality, and mortality‐adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow‐up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular‐dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular‐metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all
P
<0.05). However, only the vascular‐metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years,
P
<0.001). Only the vascular‐dominant group had a greater incidence of AD (odds ratio [OR], 1.30;
P
<0.001) compared with the reference group. Mortality was greater in the vascular‐dominant (OR, 3.26;
P
<0.001) and vascular‐metabolic groups (OR, 1.84;
P
=0.02). Mortality‐adjusted AD was greater in the vascular‐dominant (OR, 1.54;
P
=0.02) and vascular‐metabolic groups (OR, 1.46;
P
=0.04).

Conclusions

Three distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular‐dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular‐metabolic group and incident AD.
Long‐Term Clinical Outcomes in Patients With Severe Tricuspid Regurgitation
Authors: Nishiura Naoki , Kitai Takeshi , Okada Taiji , Sano Madoka , Miyawaki Norihisa , Kim Kitae , Murai Ryosuke , Toyota Toshiaki , Sasaki Yasuhiro , Ehara Natsuhiko , Kobori Atsushi , Kinoshita Makoto , Koyama Tadaaki , Furukawa Yutaka
Published: December 2022

Background

The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long‐term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR.

Methods and Results

Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left‐sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all‐cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow‐up period of 26.5 (interquartile range, 6.0–57.9) months. The 5‐year event‐free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01–1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01–1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002–1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36–0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m
2
) revealed a graded increase in the risk of adverse events (
P
<0.001).

Conclusions

The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.
Occult Diastolic Dysfunction and Adverse Clinical Outcomes in Adolescents and Young Adults With Fontan Circulation
Authors: Peck Daniel , Averin Konstantin , Khoury Philip , Veldhuis Grant , Alsaied Tarek , Lubert Adam M. , Hirsch Russel , Whiteside Wendy M. , Veldtman Gruschen , Goldstein Bryan H.
Published: December 2022

Background

In Fontan circulation, diastolic dysfunction portends a worse clinical outcome but may be concealed during routine assessment. Invasive evaluation with rapid volume expansion (RVE) can identify patients with occult diastolic dysfunction (ODD). We sought to evaluate the association between ODD and adverse clinical outcomes at medium‐term follow‐up.

Methods and Results

We conducted a single‐center observational study of patients with Fontan circulation who underwent clinical catheterization with RVE from 2012 to 2017. ODD was defined as post‐RVE end‐diastolic pressure ≥15 mm Hg. A composite adverse clinical outcome included mortality, cardiac transplant, ventricular assist device, plastic bronchitis, protein‐losing enteropathy, arrhythmia, stroke/thrombus, or cardiac‐related hospital admission. Proportional hazards regression was used to compare the ODD‐positive and ODD‐negative groups for risk of the composite adverse clinical outcome. Eighty‐nine patients with Fontan circulation (47% female patients) were included at a median age of 14 years. ODD was identified in 31%. Fontan duration was longer in the ODD group (
P
=0.001). The composite adverse clinical outcome occurred more frequently in the ODD group (52 versus 26%,
P
=0.03) during a median follow‐up duration of 2.9 years after catheterization. ODD (hazard ratio [HR], 2.68 [95% CI, 1.28–5.66];
P
=0.02) and Fontan duration (HR, 1.07 [95% CI, 1.02–1.12];
P
=0.003) were associated with the composite adverse clinical outcome. When stratified by Fontan duration, ODD remained significantly associated with the hazard of adverse clinical outcomes in patients with a Fontan duration ≥10 years (HR, 2.57 [95% CI, 1.03–6.57];
P
=0.04).

Conclusions

Cardiac catheterization with rapid volume expansion reveals a significant incidence of ODD, which relates to Fontan duration. ODD is associated with an increased hazard of adverse clinical outcomes during medium‐term follow‐up, especially in patients with longer Fontan duration. ODD may portend a worse prognosis in Fontan circulation.
Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria
Authors: Aeschbacher‐Germann Martina , Kaiser Nathalie , Speierer Alexandre , Blum Manuel R. , Bauer Douglas C. , Del Giovane Cinzia , Aujesky Drahomir , Gencer Baris , Rodondi Nicolas , Moutzouri Elisavet
Published: December 2022

Background

Randomized clinical trials (RCTs) might not be representative of the real‐world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid‐lowering therapy.

Methods and Results

We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid‐lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non‐Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta‐analyzed the prevalence of included patients to obtain pooled estimates with a random‐effects model. We included 42 RCTs (298 605 patients). Eighty‐one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy‐one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%–49%), 11% (3%–18%) for >75 years of age, and 51% (38%–63%) for multimorbidity.

Conclusions

The majority of lipid‐lowering therapy trials excluded patients with common diseases, such as moderate‐to‐severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side‐effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research.

Registration

URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.
Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population
Authors: Zhou Tan Lai , Schütten Monica T. J. , Kroon Abraham A. , Henry Ronald M. A. , Houben Alfonsius J. H. M. , van der Kallen Carla J. H. , van Greevenbroek Marleen M. J. , de Leeuw Peter W. , Stehouwer Coen D. A.
Published: December 2022

Background

Salt restriction may lower blood pressure variability (BPV), but previous studies have shown inconsistent results. Therefore, we investigated in an observational study and intervention trial whether urinary sodium excretion and salt intake are associated with 24‐hour BPV.

Methods and Results

We used data from the cross‐sectional population‐based Maastricht Study (n=2652; 60±8 years; 52% men) and from a randomized crossover trial (n=40; 49±11 years; 33% men). In the observational study, we measured 24‐hour urinary sodium excretion and 24‐hour BPV and performed linear regression adjusted for age, sex, mean blood pressure, lifestyle, and cardiovascular risk factors. In the intervention study, participants adhered to a 7‐day low‐ and high‐salt diet (50 and 250 mmol NaCl/24 h) with a washout period of 14 days, 24‐hour BPV was measured during each diet. We used linear mixed models adjusted for order of diet, mean blood pressure, and body mass index. In the observational study, 24‐hour urinary sodium excretion was not associated with 24‐hour systolic or diastolic BPV (β, per 1 g/24 h urinary sodium excretion: 0.05 mm Hg [95% CI, −0.02 to 0.11] and 0.04 mm Hg [95% CI, −0.01 to 0.09], respectively). In the intervention trial, mean difference in 24‐hour systolic and diastolic BPV between the low‐ and high‐salt diet was not statistically significantly different (0.62 mm Hg [95% CI, −0.10 to 1.35] and 0.04 mm Hg [95% CI, −0.54 to 0.63], respectively).

Conclusions

Urinary sodium excretion and salt intake are not independently associated with 24‐hour BPV. These findings suggest that salt restriction is not an effective strategy to lower BPV in the White general population.

Registration

URL:
https://clinicaltrials.gov/ct2/show/NCT02068781
Impact of Race and Ethnicity on Use and Outcomes of Septal Reduction Therapies for Obstructive Hypertrophic Cardiomyopathy
Authors: Patlolla Sri Harsha , Schaff Hartzell V. , Nishimura Rick A. , Eleid Mackram F. , Geske Jeffrey B. , Ommen Steve R.
Published: December 2022

Background

Information on impact of race and ethnicity on use and early outcomes of septal reduction therapies (SRTs) for obstructive hypertrophic obstructive cardiomyopathy are limited.

Methods and Results

Using the National Inpatient Sample from January 2012 through December 2019, we identified all adult admissions with a primary diagnosis of obstructive hypertrophic cardiomyopathy and those undergoing SRT. Predictors of receiving SRT and outcomes including in‐hospital mortality, complications, and resource use were evaluated in racial and ethnic groups. Among a total of 18 895 adult admissions with obstructive hypertrophic cardiomyopathy, SRT was performed in 7255 (38.4%) admissions. Septal myectomy was performed in 4930 (26.1%), while alcohol septal ablation was performed in 2325 (12.3%). In adjusted analysis, Black patient (versus White patient adjusted odds ratio, 0.65 [95% CI, 0.57–0.73];
P
<0.001) and Hispanic patient admissions (versus White adjusted odds ratio, 0.78 [95% CI, 0.66–0.92];
P
=0.003) were less likely to receive SRT. Among admissions undergoing SRT, in‐hospital mortality was significantly higher for Hispanic (adjusted odds ratio, 3.38 [95% CI, 1.81–6.30],
P
<0.001) and other racial and ethnic groups (adjusted odds ratio 2.02 [95% CI, 1.00–4.11];
P
=0.05) compared with White patient admissions, whereas Black patient admissions had comparable mortality. Black, Hispanic, and other ethnic group patients had higher rates of SRT complications and more frequent dismissals to acute care facilities.

Conclusions

Among obstructive hypertrophic cardiomyopathy hospitalizations, minoritized racial groups were less likely to receive SRT. Importantly, hospitalizations of Hispanic and other ethnic patients undergoing SRT had significantly higher in‐hospital mortality and complication rates. Further studies with granular echocardiographic information to assess indications for SRT are needed to better understand these differences.
Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries: Results From the PLATO Trial
Authors: Hjort Marcus , Eggers Kai M. , Lakic Tatevik Ghukasyan , Lindbäck Johan , Budaj Andrzej , Cornel Jan H. , Giannitsis Evangelos , Katus Hugo A. , Siegbahn Agneta , Storey Robert F. , Becker Richard C. , Wallentin Lars , Lindahl Bertil ,   the PLATO trial investigators*
Published: December 2022

Background

The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights.

Methods and Results

In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI.

Conclusions

Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery.

Registration

URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT00391872.
Lifetime Burden of Morbidity in Patients With Isolated Congenital Ventricular Septal Defect
Authors: Eckerström Filip , Nyboe Camilla , Redington Andrew , Hjortdal Vibeke Elisabeth
Published: December 2022

Background

The lifetime burden of morbidity in patients with isolated congenital ventricular septal defect (VSD) is not completely described.

Methods and Results

In a population‐based cohort study in Denmark using nationwide medical registries, we included 8006 patients diagnosed with a congenital VSD before 2018 along with 79 568 randomly selected controls from the general Danish population matched by birth year and sex. Concomitant congenital cardiac malformations and chromosomal abnormalities were excluded. Cox proportional hazard regression, Fine and Gray competing risk regression, and Kaplan‐Meier survival function were used to estimate burden of morbidity, compared with matched controls. Median follow‐up was 23 years (interquartile range, 11–37 years). The hazard ratio (HR) of heart failure was high in both patients with unrepaired and surgically closed VSD when compared with their corresponding matched controls (5.4 [95% CI, 4.6–6.3] and 30.5 [95% CI, 21.8–42.7], respectively). Truncated analyses with time from birth until 1 year after VSD diagnosis (unrepaired) or surgery (surgically closed) censored revealed reduced but persisting late hazard of heart failure. Similarly, the late hazard of arrhythmias and pulmonary arterial hypertension was high irrespective of defect closure. The HR of endocarditis was 28.0 (95% CI, 19.2–40.9) in patients with unrepaired defect and 82.7 (95% CI, 37.5–183.2) in patients with surgically closed defect. The increased HR diminished after VSD surgery. In general, the incidence of morbidity among patients with unrepaired VSD accelerated after the age of 40 years.

Conclusions

Patients with isolated congenital VSD carry a substantial burden of cardiovascular morbidity throughout life, irrespective of defect closure.
Association of Cardiovascular Health Score With Early‐ and Later‐Onset Diabetes and With Subsequent Vascular Complications of Diabetes
Authors: Choi Yuni , Jacobs David R. , Bancks Michael Patrick , Lewis Cora E. , Cha EunSeok , Yan Fengxia , Carnethon Mercedes R. , Schreiner Pamela J. , Duprez Daniel A.
Published: December 2022

BACKGROUND

Little attention has been paid to how well the American Heart Association's cardiovascular health (CVH) score predicts early‐onset diabetes in young adults. We investigated the association of CVH score with early‐ and later‐onset diabetes and with subsequent complications of diabetes.

METHODS AND RESULTS

Our sample included 4547 Black and White adults in the CARDIA (Coronary Artery Risk Development in Young Adults) study without diabetes at baseline (1985–1986; aged 18–30 years) with complete data on the CVH score at baseline, including smoking, body mass index, physical activity, diet quality, total cholesterol, blood pressure, and fasting blood glucose. Incident diabetes was determined based on fasting glucose, 2‐hour postload glucose, hemoglobin A1c, or self‐reported medication use throughout 8 visits for 30 years. Multinomial logistic regression was used to assess the association between CVH score and diabetes onset at age <40 years (early onset) versus age ≥40 years (later onset). Secondary analyses assessed the association between CVH score and risk of complications (coronary artery calcium, clinical cardiovascular disease, kidney function markers, diabetic retinopathy, and diabetic neuropathy) among a subsample with diabetes. We identified 116 early‐ and 502 later‐onset incident diabetes cases. Each 1‐point higher CVH score was associated with lower odds of developing early‐onset (odds ratio [OR], 0.64 [95% CI, 0.58–0.71]) and later‐onset diabetes (OR, 0.78 [95% CI, 0.74–0.83]). Lower estimates of diabetic complications were observed per 1‐point higher CVH score: 19% for coronary artery calcification≥100, 18% for cardiovascular disease, and 14% for diabetic neuropathy.

CONCLUSIONS

Higher CVH score in young adulthood was associated with lower early‐ and later‐onset diabetes as well as diabetic complications.