Machine learning models for abstract screening task - A systematic literature review application for health economics and outcome research.

OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.

Real-World Data Quality Framework for Oncology Time to Treatment Discontinuation Use Case: Implementation and Evaluation Study.

BACKGROUND: The importance of real-world evidence is widely recognized in observational oncology studies. However, the lack of interoperable data quality standards in the fragmented health information technology landscape represents an important challenge. Therefore, adopting validated systematic methods for evaluating data quality is important for oncology outcomes research leveraging real-world data (RWD). OBJECTIVE: This study aims to implement real-world time to treatment discontinuation (rwTTD) for a systemic anticancer therapy (SACT) as a new use case for the Use Case Specific Relevance and Quality Assessment, a framework linking data quality and relevance in fit-for-purpose RWD assessment. METHODS: To define the rwTTD use case, we mapped the operational definition of rwTTD to RWD elements commonly available from oncology electronic health record-derived data sets. We identified 20 tasks to check the completeness and plausibility of data elements concerning SACT use, line of therapy (LOT), death date, and length of follow-up. Using descriptive statistics, we illustrated how to implement the Use Case Specific Relevance and Quality Assessment on 2 oncology databases (Data sets A and B) to estimate the rwTTD of an SACT drug (target SACT) for patients with advanced head and neck cancer diagnosed on or after January 1, 2015. RESULTS: A total of 1200 (24.96%) of 4808 patients in Data set A and 237 (5.92%) of 4003 patients in Data set B received the target SACT, suggesting better relevance of the former in estimating the rwTTD of the target SACT. The 2 data sets differed with regard to the terminology used for SACT drugs, LOT format, and target SACT LOT distribution over time. Data set B appeared to have less complete SACT records, longer lags in incorporating the latest data, and incomplete mortality data, suggesting a lack of fitness for estimating rwTTD. CONCLUSIONS: The fit-for-purpose data quality assessment demonstrated substantial variability in the quality of the 2 real-world data sets. The data quality specifications applied for rwTTD estimation can be expanded to support a broad spectrum of oncology use cases.

IGF2BP3 loss inhibits cell progression by upregulating has_circRNA_103820, and hsa_circRNA_103820-encoded peptide inhibits cell progression by inactivating the AKT pathway in lung cancer.

N6-methyladenosine (m6A) modification and m6A-related RNA-binding proteins (RBPs) play vital roles in various aspects of circRNA metabolism. Hsa_circRNA_103820 is implicated in the pathogenesis of multiple cancers, including lung cancer (LC). Moreover, bioinformatics analysis has suggested that hsa_circRNA_103820 possesses potential peptide-coding ability. Thus, we aimed to investigate the function and peptide-coding potential of hsa_circRNA_103820 in this study. Cell viability, apoptosis rate, and migratory and invasive abilities were assessed using CCK-8, flow cytometry, and transwell assays, respectively. Hsa_circRNA_103820 level was measured using RT-qPCR assay, and the interaction between hsa_circRNA_103820 and IGF2BP3 was examined through RIP and RT-qPCR assays. The coding ability of hsa_circRNA_103820 and protein levels were determined through western blot assay. The results showed that hsa_circRNA_103820 reduced cell viability, attenuated cell migratory and invasive abilities, and promoted cell apoptosis in LC. IGF2BP3 negatively regulated hsa_circRNA_103820 expression and interacted with it. Hsa_circRNA_103820 knockdown alleviated si-IGF2BP3-mediated anti-viability, anti-migration, anti-invasion, and pro-apoptosis effects in LC cells. Moreover, a 188-amino acid (aa) peptide encoded by hsa_circRNA_103820 decreased cell viability, facilitated cell apoptosis, and inhibited cell migration and invasion in LC. Collectively, hsa_circRNA_103820, regulated by IGF2BP3, encodes a 188-aa peptide and inhibits the malignant progression of LC cells by inhibiting the AKT pathway.

Phenotype Systemic Lupus Erythematosus Patients from EPIC Cosmos.

Systemic Lupus Erythematosus (SLE) is a widespread autoimmune disease for which early diagnosis is paramount in improving clinical outcomes. In this project, we used the de-identified patients from Epic Cosmos to retrieve the ICD code for SLE, checked data quality based on the EULAR/ACR classification systems, created an approach to determine the SLE patients, and performed statistical analyses on lab tests and clinical characteristics. Our preliminary results showed that clinical notes must be reviewed to improve the completeness, as structured EHR data fields provide limited information in determining if a patient meets the established classification criteria.

An Essential Role of c-Fos in Notch1-mediated Promotion of Proliferation of KSHV-Infected SH-SY5Y Cells.

BACKGROUND: This study aimed to investigate the influence of Notch1 on c-Fos and the effect of c-Fos on the proliferation of Kaposi's sarcoma-associated herpesvirus (KSHV)-infected neuronal cells. METHODS: Real-time PCR and western blotting were used to determine c-Fos expression levels in KSHV-infected (SK-RG) and uninfected SH-SY5Y cells. C-Fos levels were measured again in SK-RG cells with or without Notch1 knockdown. Next, we measured c-Fos and p-c-Fos concentrations after treatment with the Notch1 γ-secretase inhibitor LY-411575 and the Notch1 activator Jagged-1. MTT and Ki-67 staining were used to evaluate the proliferation ability of cells after c-Fos levels downregulation. CyclinD1, CDK6, and CDK4 expression levels and cell cycle were analyzed by western blotting and flow cytometry, respectively. After the c-Fos intervention, the KSHV copy number and gene expression of RTA, LANA and K8.1 were analyzed by real-time TaqMan PCR. RESULTS: C-Fos was up-regulated in KSHV-infected SK-RG cells. However, the siRNA-mediated knockdown of Notch1 resulted in a significant decrease in the levels of c-Fos and p-c-Fos (P <0.01, P <0.001). Additionally, a decrease in Cyclin D1, CDK6, and CDK4 was also detected. The Notch1 inhibitor LY-411575 showed the potential to down-regulate the levels of c-Fos and p-c-Fos, which was consistent with Notch1 knockdown group (P <0.01), whereas the expression and phosphorylation of c-Fos were remarkably up-regulated by treatment of Notch1 activator Jagged-1 (P <0.05). In addition, our data obtained by MTT and Ki-67 staining revealed that the c-Fos down-regulation led to a significant reduction in cell viability and proliferation of the SK-RG cells (P <0.001). Moreover, FACS analysis showed that the cell cycle was arrested in the G0/G1 stage, and the expressions of Cyclin D1, CDK6, and CDK4 were down-regulated in the c-Fos-knockdown SK-RG cells (P <0.05). Reduction in total KSHV copy number and expressions of viral genes (RTA, LANA and K8.1) were also detected in c-Fos down-regulated SK-RG cells (P <0.05). CONCLUSION: Our findings strongly indicate that c-Fos plays a crucial role in the promotion of cell proliferation through Notch1 signaling in KSHV-infected cells. Furthermore, our results suggest that the inhibition of expression of key viral pathogenic proteins is likely involved in this process.

Atorvastatin Calcium Ameliorates Cognitive Deficits Through the AMPK/Mtor Pathway in Rats with Vascular Dementia.

AIM: In this study, the protective effects of atorvastatin calcium (AC) on nerve cells and cognitive improvement in vivo and in vitro were investigated by establishing cell models and vascular dementia (VD) rat models. BACKGROUND: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear. OBJECTIVE: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD. METHODS: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student's t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05. RESULTS: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway. CONCLUSION: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.

Eukaryotic translation initiation factor 4A1 in the pathogenesis and treatment of cancers.

Abnormal translate regulation is an important phenomenon in cancer initiation and progression. Eukaryotic translation initiation factor 4A1 (eIF4A1) protein is an ATP-dependent Ribonucleic Acid (RNA) helicase, which is essential for translation and has bidirectional RNA unwinders function. In this review, we discuss the levels of expression, regulatory mechanisms and protein functions of eIF4A1 in different human tumors. eIF4A1 is often involved as a target of microRNAs or long non-coding RNAs during the epithelial-mesenchymal transition, associating with the proliferation and metastasis of tumor cells. eIF4A1 protein exhibits the promising biomarker for rapid diagnosis of pre-cancer lesions, histological phenotypes, clinical staging diagnosis and outcome prediction, which provides a novel strategy for precise medical care and target therapy for patients with tumors at the same time, relevant small molecule inhibitors have also been applied in clinical practice, providing reliable theoretical support and clinical basis for the development of this gene target.

Changes in vaccine administration trends across the life-course during the COVID-19 pandemic in the United States: a claims database study.

BACKGROUND: This study provides an updated and expanded analysis of the impact of the COVID-19 pandemic on routine vaccinations across the life-course in the United States. RESEARCH DESIGN AND METHODS: Routine wellness visits and vaccination rates were calculated using structured claims data for each month during the impact period (January 2020 to August 2022) and compared to the respective baseline period (January 2018 to December 2019). Monthly rates were aggregated as annual accumulated and cumulative percent changes. RESULTS: The complete monthly rate interactive dataset can be viewed at https://vaccinationtrends.com. The greatest decrease in annual accumulated administration rates in the 0-2 and 4-6 years age groups was for the measles, mumps, and rubella vaccine; for adolescents and older adults, it was for human papillomavirus and pneumococcal vaccines, respectively. Routine in-person wellness visit rates recovered faster and more completely than vaccination rates in all age groups, indicating potential missed opportunities to administer vaccines during visits. CONCLUSIONS: This updated analysis reveals that the negative impact of the COVID-19 pandemic on routine vaccination continued through 2021 and into 2022. Proactive efforts to reverse this decline are needed to increase individual- and population-level vaccination coverage and avoid the associated preventable morbidity, mortality, and health care costs.

Investigating the Effects and Mechanism of Rhodiola Rosea Injection on Cardiac Function in Rats with Chronic Heart Failure.

AIM: To study the effect of Rhodiola Rosea injection on cardiac function and the reninangiotensin- aldosterone system (RASS) in rats with chronic heart failure. BACKGROUND: Rhodiola Rosea injection, a traditional Chinese medication for relieving blood stasis and improving blood circulation, is an excellent therapeutic for treating coronary heart disease-angina pectoris. Rhodiola Rosea injection's major component, salidroside, protects the cardiovascular system. But there isn't much first-hand evidence about how injectable Rhodiola Rosea affects heart failure. OBJECTIVES: In this study, a rat model of heart failure was established, and the effect of Rhodiola rosea injection on myocardial cell morphology, cardiac function, and ventricular remodelling in rats with heart failure was investigated. METHODS: 66 SD male rats were selected; 10 were randomly selected as a blank control group, and 56 were treated intraperitoneally with doxorubicin (4 g/g). After 6 weeks, all animals had LVEF 60%. Established a heart failure model. Each group had 14 rats: model control, low-dose, mediumdose, and high-dose Rhodiola Rosea injection. The 2 mL/kg of Rhodiola Rosea injection was injected into the tail vein once a day for 2 weeks. Both the blank and control groups received normal daily saline. After 2 weeks, the echocardiographic index, RASS-related index, and serum BNP level were assessed in all rats, and myocardial tissue morphology was observed. MiRNA423-5p, miRNA499-5p, and miRNA210-3p were extracted from peripheral blood. Rhodiola rosea injection on its expression was compared to healthy control rats. RESULTS: 6 mL/kg Rhodiola Rosea injection lowered LVEDV and LVESV while increasing LVEF and LVFS. Injections of 6 mL/kg Rhodiola Rosea reduce plasma levels of miR-210-3p, miR-423- 5p, miRNA-499, and BNP in heart failure model rats. The 6 mL/kg Rhodiola Rosea injection can restore the RASS indexes of heart failure rats to the level of the normal group. CONCLUSION: The present study offers preliminary evidence supporting the use of Rhodiola Rosea injection in the treatment of heart failure and offers a solid foundation for clinical off-label medication use.

Early Initiation of HPV Vaccination and Series Completion in Early and Mid-Adolescence.

OBJECTIVES: Routine human papillomavirus (HPV) vaccination has been recommended in the United States since 2006 but rates remain suboptimal. State-based studies suggest that initiation in late childhood at ages 9 to 10 years compared with the recommended early adolescent ages of 11 to 12 years improves series completion. No study with national scope has explored the early initiation-HPV series completion relationship. This study addresses this knowledge gap and explores whether early initiation might improve series completion by increasing time to target completion age (time pathway) or by moving initiation to an earlier developmental stage (development pathway). METHODS: Using data from the National Immunization Survey-Teen 2017-2020, a retrospective cohort of 19 575 15 to 17 year olds who initiated HPV vaccination between ages 9 and 12 years was assembled. Time pathway endpoints were series completion by ages 13 and 15 years. The development pathway endpoint was completion within 3 years of initiation. RESULTS: Early initiators were more likely to complete by ages 13 (74.0% vs 31.1%, P < .001) and 15 (91.7% vs 82.7%, P < .001) years but less likely to complete within 3 years (82.3% vs 84.9%, P = .007). The association of early initiation to completion was maintained in multivariable analyses for time pathway endpoints (age 13 years adjusted odds ratios [AOR] = 6.16; 95% confidence interval [CI], 5.45-6.96, age 15 years = AOR 2.56; 95% CI, 2.14-3.14) but not the development pathway endpoint (AOR = 0.93; 95% CI, 0.80-1.07). CONCLUSIONS: Moving routine HPV vaccination to ages 9 to 10 may improve vaccination coverage rates in early and mid-adolescence. Providers should be vigilant to patient interactions after HPV series initiation to optimize public health benefits of vaccination.

HPV vaccine initiation at 9 or 10 years of age and better series completion by age 13 among privately and publicly insured children in the US.

The US Advisory Committee on Immunization Practice recommends routine human papillomavirus (HPV) vaccination at 11-12 years of age, but states that vaccination may be initiated as early as 9 years. Our primary goal was to assess whether initiating HPV vaccination at 9-10 years of age, compared to 11-12, was associated with a higher rate of series completion by 13 years of age, and to identify factors associated with series completion by age 13. The study used vaccine claims and other data from the IBM MarketScan Commercial Claims and Encounters (privately insured) and IBM MarketScan Multi-State Medicaid (publicly insured) databases. Participants were 9-12 years of age and initiated HPV vaccination between January 2006 and December 2018 (publicly insured) or February 2019 (privately insured). Among 100,117 privately insured individuals, those initiating the HPV vaccination series at 9-10 years of age had a significantly higher series completion rate by 13 years of age than did those initiating at 11-12 years of age (76.2% versus 48.1%; p < .001). The same pattern was observed for 115,863 publicly insured individuals (70.4% versus 40.0%; p < .001). Provider and health care plan type, female sex, race/ethnicity, and wellness checks or non-HPV vaccinations during the baseline period were significantly associated with series completion by 13 years of age. Proactive initiation of HPV vaccination at 9-10 years of age was associated with higher rates of series completion by 13 years of age. These findings can inform provider education and other interventions to encourage timely HPV vaccination series completion.

Targeted delivery of miR-34a-5p by phenylborate-coupled polyethylenimide nanocarriers for anti-KSHV treatment.

Kaposi's sarcoma-associated herpesvirus (KSHV) can infect a variety of cells and cause malignant tumors. At present, the use of microRNA (miRNA) for anti-KSHV is a promising treatment strategy, but the instability and non-specific uptake of miRNA still limit its use in the treatment of KSHV. In the present study, we constructed a nano-drug delivery system employing chemical grafting and electrostatic adsorption to solve the problems of easy degradation and low cell uptake of miRNA during direct administration. This nano-drug delivery system is to graft 4-carboxyphenylboric acid (PBA) and lauric acid (LA) onto polyethylenimine (PEI) through amidation reaction, and then prepare cationic copolymer nanocarriers (LA-PEI-PBA). The drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p was formed after further electrostatic adsorption of miR-34a-5p on the carrier and could protect miR-34a-5p from nuclease and serum degradation. Modification of the drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p by targeted molecule PBA showed effective uptake, increase in the level of miR-34a-5p, and inhibition of cell proliferation and migration in KSHV-infected cells. In addition, the drug-carrying nanocomplex could also significantly reduce the expression of KSHV lytic and latent genes, achieving the purpose of anti-KSHV treatment. In conclusion, these cationic copolymer nanocarriers with PBA targeting possess potential applications in nucleic acid delivery and anti-KSHV therapy.

Towards quality improvement of vaccine concept mappings in the OMOP vocabulary with a semi-automated method.

The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) provides a unified model to integrate disparate real-world data (RWD) sources. An integral part of the OMOP CDM is the Standardized Vocabularies (henceforth referred to as the OMOP vocabulary), which enables organization and standardization of medical concepts across various clinical domains of the OMOP CDM. For concepts with the same meaning from different source vocabularies, one is designated as the standard concept, while the others are specified as non-standard or source concepts and mapped to the standard one. However, due to the heterogeneity of source vocabularies, there may exist mapping issues such as erroneous mappings and missing mappings in the OMOP vocabulary, which could affect the results of downstream analyses with RWD. In this paper, we focus on quality assurance of vaccine concept mappings in the OMOP vocabulary, which is necessary to accurately harness the power of RWD on vaccines. We introduce a semi-automated lexical approach to audit vaccine mappings in the OMOP vocabulary. We generated two types of vaccine-pairs: mapped and unmapped, where mapped vaccine-pairs are pairs of vaccine concepts with a "Maps to" relationship, while unmapped vaccine-pairs are those without a "Maps to" relationship. We represented each vaccine concept name as a set of words, and derived term-difference pairs (i.e., name differences) for mapped and unmapped vaccine-pairs. If the same term-difference pair can be obtained by both mapped and unmapped vaccine-pairs, then this is considered as a potential mapping inconsistency. Applying this approach to the vaccine mappings in OMOP, a total of 2087 potentially mapping inconsistencies were obtained. A randomly selected 200 samples were evaluated by domain experts to identify, validate, and categorize the inconsistencies. Experts identified 95 cases revealing valid mapping issues. The remaining 105 cases were found to be invalid due to the external and/or contextual information used in the mappings that were not reflected in the concept names of vaccines. This indicates that our semi-automated approach shows promise in identifying mapping inconsistencies among vaccine concepts in the OMOP vocabulary.

Introns in the Naa50 gene act as strong enhancers of tissue-specific expression in Arabidopsis.

Naa50 is the catalytic subunit of N-terminal acetyltransferase complex E, which plays an important role in regulating plant development, endoplasmic reticulum stress and immune responses in Arabidopsis. In this study, the complete genomic sequence (but not the coding sequence) of Naa50 rescued the phenotype of Naa50 deletion mutants. Naa50 expression was noted in whole roots except for central root cap cells. The deletion of intron 1 resulted in a loss of Naa50 expression in the root meristem zone and in the epidermis, cortex and endodermis of the elongation zone and mature zone, while the deletion of intron 2 decreased Naa50 expression in the epidermis, cortex and endodermis of the root elongation zone and mature zone. The native Naa50 promoter together with introns 1 and 2 promotes the expression of Naa50 in sepal vascular bundles, filaments, pollen and stigmas; however, neither intron has positive effect on Naa50 expression in mature rosette leaves. The results of this study show that introns 1 and 2 in the Naa50 gene function as enhancers to promote the tissue-specific expression of Naa50.

HistoML, a markup language for representation and exchange of histopathological features in pathology images.

The study of histopathological phenotypes is vital for cancer research and medicine as it links molecular mechanisms to disease prognosis. It typically involves integration of heterogenous histopathological features in whole-slide images (WSI) to objectively characterize a histopathological phenotype. However, the large-scale implementation of phenotype characterization has been hindered by the fragmentation of histopathological features, resulting from the lack of a standardized format and a controlled vocabulary for structured and unambiguous representation of semantics in WSIs. To fill this gap, we propose the Histopathology Markup Language (HistoML), a representation language along with a controlled vocabulary (Histopathology Ontology) based on Semantic Web technologies. Multiscale features within a WSI, from single-cell features to mesoscopic features, could be represented using HistoML which is a crucial step towards the goal of making WSIs findable, accessible, interoperable and reusable (FAIR). We pilot HistoML in representing WSIs of kidney cancer as well as thyroid carcinoma and exemplify the uses of HistoML representations in semantic queries to demonstrate the potential of HistoML-powered applications for phenotype characterization.

A social and news media benchmark dataset for topic modeling.

Topic modeling is an active research area with several unanswered questions. The focus of recent research in this area is on the use of a vector embedding representation of the input text with both generative and evolutionary topic modeling techniques. Unfortunately, it is hard to compare different techniques when the underlying data and preprocessing steps that were used to develop the models are not available. This paper presents two secondary datasets that can help address this gap. These datasets are derived from two primary datasets. The first consists of 8145 posts from the r/Cancer health forum and the second consists of 18,294 messages submitted to 20 different news groups. The same preprocessing procedure is applied to both datasets by removing punctuation, stop words and high frequency words. Each dataset is then clustered using three different topic modeling techniques: pPSO, ETM and NVDM and three topic numbers: 10, 20, 30. In addition, for pPSO two text embeddings representation are considered: sBERT and Skipgram. The secondary datasets were originally developed in support of a comparative analysis of the aforementioned topic modeling techniques in a study titled "Comparing PSO-based Clustering over Contextual Vector Embeddings to Modern Topic Modeling" submitted to the Journal of Information Processing and Management. The present paper provides a detailed description of the two secondary datasets including the unique identifier that can be used to retrieve the original documents, the pre-processing scripts, the topic keywords generated by the three topic modeling techniques with varying topic numbers and embedding representations. As such, the datasets allow direct comparison with other topic modeling techniques. To further facilitate this process, the algorithm underlying the evolutionary topic modeling technique, pPSO, proposed by the authors is also provided.

Effect of radiofrequency catheter ablation on left atrial structure and function in patients with different types of atrial fibrillation.

Radiofrequency catheter ablation (RFCA) is widely used to treat atrial fibrillation (AF), but its effect on left atrial (LA) remodeling in patients with AF is not completely clarified. Few studies have reported the changes in structure and function of the left atrium in patients with different types of AF after RFCA. To analyze the effect of RFCA on the LA structure and function in patients with nonvalvular paroxysmal AF, persistent AF and long-standing persistent AF (LSPAF). RFCA was performed in 180 patients with paroxysmal AF, persistent AF and LSPAF. The changes of LA structure and function in echocardiogram and speckle-tracking echocardiography findings were compared before the procedure, and at 1, 2, 3, 4 weeks, and 2, 3, 6, and 9-12 months after the procedure. There were 60 patients in the paroxysmal AF group, 60 in the persistent AF group and 60 patients in LSPAF group. The pre-procedure LA diameter and volume were smaller in the paroxysmal AF group than persistent AF and LSPAF group. There was no significant change of in the LA structure and function in the paroxysmal AF group within 1 year. In the persistent AF and LSPAF groups, LA structure (anteroposterior diameter, LA volume) significantly decreased, but remained larger than that in paroxysmal AF group. In persistent and LSPAF, function (LA ejection fraction, strain, strain rate) increased significantly within 1 week, then gradually increased. RFCA improved the LA structure and function and resulted in heart reverse remodeling, especially for persistent AF and LSPAF.

Recover From Failure: Examining the Impact of Service Recovery Stages on Relationship Marketing Strategies.

Purpose: Given the digital transformation of service businesses by providing online food services and the influence of online reviews on consumers' purchasing decisions, this study examines how service recovery attributes in different stages influence relationship marketing strategies, i.e., relationship quality and customer loyalty after service failure. This study is built upon a revised service recovery cycle model by accounting for three stages and their corresponding attributes; whereon a conceptual stage model of service recovery is proposed. This conceptual stage model incorporates stages of service recovery, their respective attributes, and how they influence relationship marketing strategies. Design/methodology/approach: An online marketing company was employed for data collection in 2019, which resulted in 301 valid responses. A Structural Equation Model (SEM) was conducted with all the data to test the relationships between the constructs. The individual measurement model was tested using the Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). A structural model was estimated using AMOS to test all the hypotheses. Findings: The findings demonstrate that the attributes (i.e., response speed, compensation) paired with the first two stages of service recovery can significantly influence consumer loyalty in a positive state. The findings also manifest the intermediary role that relationship quality has played in the association of service recovery and consumer loyalty, which implies that the food delivery businesses could attain a more comprehended relationship quality with consumers through active and timely compensatory service recovery consumer loyalty to the food businesses. Originality/value: This study examines how these different stages of the service recovery cycle influence the decision-making of relationship marketing strategies (i.e., relationship quality, customer loyalty) on the prerequisite of service failure. This study aspires to expand the service recovery research by objectifying a conceptual stage model of service recovery, incorporating stages' recovery attributes and how these recovery attributes reciprocally influence relationship quality and customer loyalty.

miRNA-29a inhibits atherosclerotic plaque formation by mediating macrophage autophagy via PI3K/AKT/mTOR pathway.

BACKGROUND: miR-29a plays a vital role in AS, but the relationship between the miR-29a-targeted PI3K signaling pathway and AS remains unclear. Therefore, this study was carried out. METHODS: Gene expression profiles from the GEO database containing AS samples were analyzed. ApoE-/- mice and RAW264.7 cells were treated with miR-29a negative control (NC), miR-29a mimic and miR-29a inhibitor to establish the AS model. Then MOVAT staining, TEM, Western blotting, and immunofluorescence staining were adopted for testing target proteins. RESULTS: DEGs were identified from GSE137578, GSE132651, GSE113969, GSE43292, and GSE97210 datasets. It was found that there were targeted binding sites between miR-29a and PIK3CA. Besides, GO and KEGG analysis demonstrated that autophagy was an enriched pathway in AS. Later, PPI network was depicted, and hub genes were then determined. The results revealed that miR-29a suppressed the areas of plaques and lesional macrophages, but had no impact on VSMCs. TEM results showed the organelles pyknosis of lesional macrophages damaged morphological changes. Furthermore, miR-29a amplified the M2-like macrophages but suppressed the polarization of M1-like macrophages in atherosclerotic plaques. According to mouse and RAW 264.7 cell experiments, miR-29a significantly inhibited the protein expressions of PI3K, p-PI3K, p-AKT, and p-mTOR, which were consistent with the increased expressions of autophagy-related proteins, Beclin 1 and LC3II. However, the miR-29a suppression exhibited the contrary results. CONCLUSION: MiR-29a elevation induces the increase of autophagy by down-regulating the PI3K/AKT/mTOR pathway in the progression of AS, indicating that miR-29a is a novel therapeutic strategy for AS.

The N-terminal acetyltransferase Naa50 regulates tapetum degradation and pollen development in Arabidopsis.

The N-terminal acetylation of proteins is a key modification in eukaryotes. However, knowledge of the biological function of N-terminal acetylation modification of proteins in plants is limited. Naa50 is the catalytic subunit of the N-terminal acetyltransferase NatE complex. We previously demonstrated that the absence of Naa50 leads to sterility in Arabidopsis thaliana. In the present study, the lack of Naa50 resulted in collapsed and sterile pollen in Arabidopsis. Further experiments showed that the mutation in Naa50 accelerated programmed cell death in the tapetum. Expression pattern analysis revealed the specific expression of Naa50 in the tapetum cells of anthers at 9-11 stages during pollen development, when tapetal programmed cell death occurred. Reciprocal cross analyses indicated that male sterility in naa50 is caused by sporophytic effects. mRNA sequencing and quantitative PCR of the closed buds showed that the deletion of Naa50 resulted in the upregulation of the cysteine protease coding gene CEP1 and impaired the expression of several genes involved in pollen wall deposition and pollen mitotic division. The collective data suggest that Naa50 balances the degradation of tapetum cells during anther development and plays an important role in pollen development by affecting several pathways.