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Background: Contrast-enhanced ultrasound (CEUS) technology has been developed for decades, and its application is becoming increasingly more extensive. In this study, bibliometrics was used to characterize the development status of CEUS over the past 20 years and to identify future research hotspots. Methods: We collected data from the Web of Science and analyzed the literature related to CEUS published from 2002 to 2022. We examined 6,382 publications and analyzed the publication year, country of origin, affiliated institutions, authors, journal, categories, keywords, and research frontiers within the relevant literature. Using bibliometric analysis, we aimed to determine the general research direction and current publication trends. This allowed us to identify the most prolific and outstanding authors, institutions, countries, and keywords in CEUS research. For data collection, analysis, and visualization, we employed VOSviewer (Leiden University, Leiden, the Netherlands), Excel (Microsoft Corp., Redmond, WA, USA), CiteSpace, and biblioshiny. These tools helped us gather, analyze, and visualize the data effectively. Results: The analyzed publications indicated a consistent upward trend in the number of works published between 2002 and 2022. Notably, China and Sun Yat-sen University emerged as the most prolific countries and institutions, respectively. China published 391 articles with 5,817 citations and was the leader in terms of international cooperation. Moreover, pediatrics-related keywords have surged in frequency in recent years. Conclusions: The amount of research on CEUS has increased rapidly and continues to grow, with China being at the forefront of this research field. The application of CEUS in some pediatric diseases is a recent research hotspot and perhaps warrants close attention.
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Background: Super-resolution (SR) refers to the use of hardware or software methods to enhance the resolution of low-resolution (LR) images and produce high-resolution (HR) images. SR is applied frequently across a variety of medical imaging contexts, particularly in the enhancement of neuroimaging, with specific techniques including SR microscopy-used for diagnostic biomarkers-and functional magnetic resonance imaging (fMRI)-a neuroimaging method for the measurement and mapping of brain activity. This bibliometric analysis of the literature related to SR in medical imaging was conducted to identify the global trends in this field, and visualization via graphs was completed to offer insights into future research prospects. Methods: In order to perform a bibliometric analysis of the SR literature, this study sourced all publications from the Web of Science Core Collection (WoSCC) database published from January 1, 2000, to October 11, 2023. A total of 3,262 articles on SR in medical imaging were evaluated. VOSviewer was used to perform co-occurrence and co-authorship analysis, and network visualization of the literature data, including author, journal, publication year, institution, and keywords, was completed. Results: From 2000 to 2023, the annual publication volume surged from 13 to 366. The top three journals in this field in terms of publication volume were as follows: (I) Scientific Reports (86 publications), (II) IEEE Transactions on Medical Imaging (74 publications), and (III) IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control (56 publications). The most prolific country, institution, and author were the United States (1,017 publications; 31,301 citations), the Chinese Academy of Sciences (124 publications; 2,758 citations), and Dinggang Shen (20 publications; 671 citations), respectively. A cluster analysis of the top 100 keywords was conducted, which revealed the presence of five co-occurrence clusters: (I) SR and artificial intelligence (AI) for medical image enhancement, (II) SR and inverse problem processing concepts for positron emission tomography (PET) image processing, (III) SR ultrasound through microbubbles, (IV) SR microscopy for Alzheimer and Parkinson diseases, and (V) SR in brain fMRI: rapid acquisition and precise imaging. The most recent high-frequency keywords were deep learning (DL), magnetic resonance imaging (MRI), and convolutional neural networks (CNNs). Conclusions: Over the past two decades, the output of publications by countries, institutions, and authors in the field of SR in medical imaging has steadily increased. Based on bibliometric analysis of international trends, the resurgence of SR in medical imaging has been facilitated by advancements in AI. The increasing need for multi-center and multi-modal medical images has further incentivized global collaboration, leading to the diverse research paths in SR medical imaging among prominent scientists.
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In order to improve and replace the enantiomer method outlined in the olodaterol hydrochloride draft monograph (From the European Pharmacopoeia forum), one new, simple, and fast enantioselective normal phase high-performance liquid chromatography chiral method was developed on polysaccharide-based Chiral MX (2) (4.6 × 250 mm, 5 µm) column. n-Hexane, ethanol, and diethylamine in the ratio of 40:60:0.1 (V/V/V) were selected as mobile phase at a flow rate of 0.8 mL/min, and the detection was performed on a photodiode array detector at 225 nm with 5 µL injection volume. The column temperature was set at 40°C for better peak shape and sensitivity. The analysis time can be shortened to 15 min, whereas the resolution between enantiomer and olodaterol was found to be even more than 10.0, which was far better than that obtained with the reported method in this draft monograph. The developed chiral method was validated in accordance with ICH Q2 (R1), including specificity, LOD&LOQ, precision, linearity, accuracy, and robustness. Thereby, the proposed method was demonstrated to be suitable for the determination of enantiomer in olodaterol hydrochloride bulk drug and drug product. Besides, the thermodynamic parameters were evaluated on the basis of Van't Hoff plots that was used to explain correlative chiral recognition mechanisms with the chiral stationary phase.
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Benzoxazines , Thermodynamics , Stereoisomerism , Benzoxazines/chemistry , Benzoxazines/analysis , Chromatography, High Pressure Liquid/methods , Reproducibility of Results , Limit of DetectionABSTRACT
[This corrects the article DOI: 10.3389/fnint.2023.1234471.].
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Background: The reporting and data system (RADS) has been researched across the world since it was first developed. This study used bibliometrics to analyze the research trends and current status of this field over the past almost 23 years and explored possible future research hotspots. Methods: We searched the Web of Science (WOS) literature on RADSs from January 1, 2000, to November 1, 2022, and evaluated the findings visually with VOSviewer (1.6.18), CiteSpace (6.1.3), and the "bibliometrix" package in R version 4.2.1. Results: We included 6,239 publications from 88 countries and regions. The number of published has shown an overall growth trend, especially since 2016. The United States was the country with the highest number of publications and citations. The top 10 most productive institutions in RADS research were mainly from South Korea and the United States. Kim EK was the most published author, and Turkbey B had the most cited publication. European Radiology had the most publications on the subject, while Radiology was the most influential journal. Magnetic resonance imaging, carcinoma, ultrasound, RADS, mammography, breast neoplasms, and diagnosis were the most common keywords. Artificial intelligence (AI) appears to be an emerging hotspot in the research of RADS. Conclusions: This study provides an overview of the development status of research into RADSs over the past 23 years. Research into RADSs has included various systems of the body, with the most studied being the breast, prostate, liver, and thyroid. In terms of auxiliary diagnosis, there is an increasing amount of research into the application of AI in RADSs, which along with the interpretability of AI, will be a hotspot of research in the following years.
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Objectives: The purpose of this research is to summarize the structure of radiomics-based knowledge and to explore potential trends and priorities by using bibliometric analysis. Methods: Select radiomics-related publications from 2012 to October 2022 from the Science Core Collection Web site. Use VOSviewer (version 1.6.18), CiteSpace (version 6.1.3), Tableau (version 2022), Microsoft Excel and Rstudio's free online platforms (http://bibliometric.com) for co-writing, co-citing, and co-occurrence analysis of countries, institutions, authors, references, and keywords in the field. The visual analysis is also carried out on it. Results: The study included 6428 articles. Since 2012, there has been an increase in research papers based on radiomics. Judging by publications, China has made the largest contribution in this area. We identify the most productive institutions and authors as Fudan University and Tianjie. The top three magazines with the most publications areãFRONTIERS IN ONCOLOGYã, ãEUROPEAN RADIOLOGYã, and ãCANCERSã. According to the results of reference and keyword analysis, "deep learning, nomogram, ultrasound, f-18-fdg, machine learning, covid-19, radiogenomics" has been determined as the main research direction in the future. Conclusion: Radiomics is in a phase of vigorous development with broad prospects. Cross-border cooperation between countries and institutions should be strengthened in the future. It can be predicted that the development of deep learning-based models and multimodal fusion models will be the focus of future research. Advances in knowledge: This study explores the current state of research and hot spots in the field of radiomics from multiple perspectives, comprehensively, and objectively reflecting the evolving trends in imaging-related research and providing a reference for future research.
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COVID-19 , Radiomics , Humans , Bibliometrics , COVID-19/epidemiology , China , Fluorodeoxyglucose F18ABSTRACT
Background: According to the World Health Organization (WHO), healthy aging is the process of developing and maintaining the functional capacity for health in old age. A rapidly growing number of research studies on healthy aging have been conducted worldwide. The purpose of this research work is to explore global scientific landscape of healthy aging research over the last 22 years. Methods: Scientific publications on healthy aging from January 1, 2000 to October 11, 2022 were retrieved from the Web of Science Core Collection (WoSCC) on October 11, 2022. A total of 6420 publications were included in the scientometric analysis. VOSviewer (1.6.18) was used to conduct scientometric and visualized analysis. Results: The publication growth rate was 35.68 from 2000 to 2021. The United States of America (USA) led in both productivity and citations. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA was prominent in terms of both the highest citation count and the highest average citation count. The National Institute on Aging (NIA) and Evans, Michele K. were the most influential organization and author, respectively. Research hotspots in healthy aging were identified based on the co-occurrence analysis of keywords: (1) physical activity and mental health of older adults; (2) diseases impacting the health and lifespan of older adults; and (3) neuroscience. Our analysis indicates that gut microbiota, loneliness, frailty, mitochondria and resilience were the emerging themes in healthy aging research. Conclusions: The quantity of annual publications on healthy aging has rapidly increased over the past 22 years, especially during 2018-2021. This analysis identified the status, trends, hot topics, and frontiers of healthy aging research. These findings will help researchers quickly understand the global representation of healthy aging research, influence resource dissemination, promote international collaborations, guide policy formulation, and improve health services for older adults.
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During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.
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Chromatography, High Pressure Liquid , Chromatography, High Pressure Liquid/methods , Rosuvastatin Calcium , Gas Chromatography-Mass Spectrometry , Limit of Detection , SolventsABSTRACT
Introduction: Candida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients' skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results. Method: A bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva's articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for 'drug resistance,' 'antifungal susceptibility test,' 'infection,' 'Candida auris,' and 'identification.' The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris. Conclusion: The bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris.
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Objective: Acupuncture has certain effects to improve myopia visual function, but its neural mechanism is unclear. In this study, we acupunctured at the right Taiyang acupoint of myopic patients to analyze the effects of acupuncture on visual function and electroencephalographic activity and to investigate the correlation between improvements in visual function and changes in the brain. Methods: In this study, a total of 21 myopic patients were recruited. The contrast sensitivity (CS) of the subjects was examined before and after acupuncture, and electroencephalography (EEG) data of the entire acupuncture process were recorded. Results: The study found that compared with before acupuncture, the CS of both eyes in myopic patients at each spatial frequency was increased after acupuncture; compared with the resting state, the contribution of microstate C was decreased during the post-acupuncture state, and the transition probability between microstate A and microstate C was reduced; in addition, the contribution of microstate C was negatively correlated with CS at both 12 and 18 cpd. Conclusion: The contrast sensitivity of myopic patients was improved after acupuncture at the Taiyang acupoint (20 min), which may be related to microstate C.
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BACKGROUND: The application of the suprapatellar (SP) approach has challenged the traditional infrapatellar (IP) approach in the surgery treatment of tibial shaft fractures, yet the advantages and disadvantages still remain controversial. We included more high-quality studies for this meta-analysis and systematic review to evaluate the clinical outcomes and prognosis of both approaches and thus to provide new ideas for surgeons. METHOD: We searched literatures from PubMed, Cochrane Library, Web of Science, and EMBASE databases from January 2000 to December 2022. We extracted general information including sample size, gender, proportion of open fracture, follow-up time, and outcome indicators including entrance accuracy, fluoroscopy time, operation time, intraoperative blood loss, Lysholm score, VAS pain score, range of motion (ROM) function score, reposition accuracy, and revision cases. Cochrane Collaboration's tool and the Newcastle-Ottawa Scale were used to evaluate literature qualities. Meta-analysis was performed using RevMan 5.4 software. RESULTS: A total of 23 studies were generated that qualified for inclusion, 17 of which were used for meta-analysis. This study found statistically significant differences in coronal plane entrance accuracy, fluoroscopy time, Lysholm score, and VAS pain score. CONCLUSION: The results of our meta-analysis showed that the SP approach was significantly better than the IP approach in angle and distance entrance accuracy of coronal plane, angle entrance accuracy of sagittal plane, fluoroscopy time, Lysholm score, and VAS pain score. There were no significant differences in sagittal angle accuracy, operative time, intraoperative blood loss, and ROM score.
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Background: Nrf2 plays a pivotal role in governing the antioxidant defense system, triggering the transcription of diverse genes involved in cellular protection. Its role in mitigating oxidative damage and modulating inflammatory processes has made Nrf2 an attractive target for therapeutic interventions. Despite the growing interest in Nrf2 research, a bibliometric analysis is relatively rare. This study aimed to clarify Nrf2's role in multiple diseases, identify emerging trends and hotspots using bibliometric analysis, and provide valuable insights and potential directions for future therapeutic interventions. Methods: The Science Citation Index of Web of Science Core library from 2000 to 2022 was searched on 22 October 2022. Use Microsoft Excel, CiteSpace, Bibliometrix, and VOS viewers for data collection and visualization of research focus and trends. Results: A vast collection of 22,040 research studies on Nrf2 published between 2000 and 2022 were identified. Nrf2 research has seen significant growth globally from 2000 to 2022. China leaded in publication numbers (9,623, 43.66%), while the United States dominated in citation frequency with 261,776 citations. China Medical University was the most productive institutions (459, 2.08%). Masayuki Yamamoto topped in publications (307), while Itoh K. ranked first in citations with 3669. Free Radical Biology and Medicine was the journal with the most studies and citations on Nrf2 (613, 29,687 citations). The analysis of keyword clustering enhanced the categorization of topics and can be summarized as oxidative stress, cancer, disorders in glycolipid metabolism, inflammation, and neurological conditions. Conclusion: China and the United States are the pioneers in Nrf2 research. Recently, there has been a comprehensive exploration of Nrf2 involving both experimental and clinical aspects, as well as mechanisms and therapeutic applications. Investigating novel molecular mechanisms, including NF-κB, Ho1, and Keap1, and developing enhanced, targeted Nrf2 activators or inhibitors to uncover the interplay among cancer, glycolipid metabolic disorder, inflammation, and neurological disorders will be upcoming trends and hotspots.
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Tumor dormancy continues to be a research hotspot with numerous pressing problems that need to be solved. The goal of this study is to perform a bibliometric analysis of pertinent articles published in the twenty-first century. We concentrate on significant keywords, nations, authors, affiliations, journals, and literature in the field of tumor dormancy, which will help researchers to review the results that have been achieved and better understand the directions of future research. We retrieved research articles on tumor dormancy from the Web of Science Core Collection. This study made use of the visualization tools VOSviewer, CiteSpace, and Scimago Graphica, as visualization helps us to uncover the intrinsic connections between information. Research on tumor dormancy has been growing in the 21st century, especially from 2015 to the present. The United States is a leader in many aspects of this research area, such as in the number of publications, the number of partners, the most productive institutions, and the authors working in this field. Harvard University is the institution with the highest number of publications, and Aguirre-Ghiso, Julio A. is the author with the highest number of publications and citations. The keywords that emerged after 2017 were "early dissemination", "inhibition", "mechanism", "bone metastasis", and "promotion". We believe that research on tumor dormancy mechanisms and therapy has been, and will continue to be, a major area of interest. The exploration of the tumor dormancy microenvironment and immunotherapeutic treatments for tumor dormancy is likely to represent the most popular future research topics.
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Although numerous spatiotemporal approaches have been presented to address the problem of missing spatiotemporal data, there are still limitations in concurrently capturing the underlying spatiotemporal dependence of spatiotemporal graph data. Furthermore, most imputation methods miss the hidden dynamic connection associations that exist between graph nodes over time. To address the aforementioned spatiotemporal data imputation challenge, we present an attention-based message passing and dynamic graph convolution network (ADGCN). Specifically, this paper uses attention mechanisms to unify temporal and spatial continuity and aggregate node neighbor information in multiple directions. Furthermore, a dynamic graph convolution module is designed to capture constantly changing spatial correlations in sensors utilizing a new dynamic graph generation method with gating to transmit node information. Extensive imputation tests in the air quality and traffic flow domains were carried out on four real missing data sets. Experiments show that the ADGCN outperforms the state-of-the-art baseline.
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ABSTRACT: Instruments evaluating HIV-related psychological distress (HRPD) in people living with HIV may lack sensitivity to capture patients' psychological burden. We developed a comprehensive scale measuring HRPD and evaluated its psychometric properties. A mixed-method study was conducted from July 2021 to April 2022; it involved a literature review, semistructured interviews ( n = 15), three rounds of panel discussions, two rounds of Delphi studies ( n = 20), a pilot test ( n = 20) to generate new scale items, and a cross-sectional survey ( n = 659) to evaluate the psychometric properties of the HIV-related psychological distress scale. The scale contains 22 items across 4 subscales (i.e., disease-related distress, treatment adherence distress, identity distress, and disclosure distress). The confirmatory factor analysis revealed high goodness of fit (χ 2 /df = 2.412, comparative fit index = 0.916, incremental fit index = 0.917, and TuckerâLewis index = 0.902), showing that the HIV-related psychological distress scale is a reliable (Cronbach's α = 0.871 overall) and valid scale for evaluating HRPD in China and can be used to dynamically evaluate and monitor HRPD levels during patient follow-up.
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HIV Infections , HIV , Humans , HIV Infections/psychology , Surveys and Questionnaires , Cross-Sectional Studies , Reproducibility of Results , China , Psychometrics/methods , Factor Analysis, StatisticalABSTRACT
Aims: To use visual mapping and bibliometrics to analyze and summarize the valuable information on laparoscopic surgery for gastric cancer (GC) obtained in the last 20 years, so as to determine the research hotspots and trends in this field. Methods: We screened all literature on laparoscopic surgery for GC in the Web of Science published from 2000 to 2022 and analyzed the research hotspots and trends in this field using VOSviewer. Results: A total of 2796 reports from 61 countries and regions were selected. Japanese researchers published the most papers (n=946), followed by those from China (n=747) and South Korea (n=557). Papers from Japan also had the most citations (n=21,836). Surgical Endoscopy and Other Interventional Techniques published the most reports on laparoscopic surgery for GC (n=386) and also had the highest total number of citations (n=11,076), making this journal the most authoritative in this field. Among the institutions, researchers from Seoul National University in South Korea had the highest numbers of published papers and citations. The keywords of the articles could be divided into five categories: surgical methods for GC, short-term and long-term efficacy of laparoscopic surgery, guiding role of laparoscopy in the treatment of advanced GC, diagnosis and treatment of early gastric cancer (EGC), and lymph node dissection. Keywords such as "laparoscopic proximal gastrectomy", "surgical outcomes", and "esophagogastric junction" have emerged recently, and relevant studies on laparoscopic surgery for adenocarcinoma of esophagogastric junction(AEG)have gradually become a hot topic and trend. Conclusion: This study adopted bibliometric analysis to identify the current research hotspots and research trends in the field of laparoscopic surgery for GC. Five main research hotspots of laparoscopic surgery for GC were also identified. Laparoscopic surgery for AEG may become an important research focus in the future.
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A simple and stability-indicating reverse phase high-performance liquid chromatographic (RP-HPLC) method for the determination of rivaroxaban (RIX) and its related substances was developed. Fifteen impurities of RIX, including three unreported isomers, were identified, synthesized, purified, and confirmed using MS, 1H NMR, 13C NMR, and HSQC spectral methods. This new method offered baseline separation for all monitored impurities, and was fast and reliable when compared to the European Pharmacopoeia method. Optimum separation for RIX and its related impurities was achieved on an octyldecyl silica column (YMC Core C18, 4.6 ×100 mm, 2.7 µm) by using a gradient HPLC method in 38 min. The final method was validated with respect to precision, LOD and LOQ, linearity, accuracy, and robustness. This developed method was suitable for routine quality control and drug analysis of RIX active substance.
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Drug Contamination , Rivaroxaban , Chromatography, High Pressure Liquid/methods , Drug Contamination/prevention & control , Quality Control , Magnetic Resonance Spectroscopy , Reproducibility of Results , Drug StabilityABSTRACT
Diet has been recognized as a vital risk factor for non-communicable diseases (NCDs), climate changes, and increasing population, which has been reflected by a rapidly growing body of the literature related to healthy eating. To reveal a panorama of the topics related to healthy eating, this study aimed to characterize and visualize the knowledge structure, hotspots, and trends in this field over the past two decades through bibliometric analyses. Publications related to healthy eating between 1 January 2002 and 31 December 2021 were retrieved and extracted from the Web of Science database. The characteristics of articles including publication years, journals, authors, institutions, countries/regions, references, and keywords were assessed. The analyses on co-authorship, co-occurrence, and co-citation were performed and network visualization maps were constructed by VOSviewer. Major subdomains identified by bibliometrics were further discussed and analyzed. A total of 12,442 articles on healthy eating were identified. Over the past two decades, the annual global publications increased from 71 to 1764, showing a nearly 25-fold growth. The journal Nutrients published the most articles and The American Journal of Clinical Nutrition possessed the highest citations. The United States, Harvard University, and Hu, Frank B. were identified as the most productive and influential country, institution, and author, respectively. The co-occurrence cluster analysis of the top 100 keywords formed four clusters: (1) the food insecurity environment for youths highlighting the necessity and significance of implementing healthy eating in early life; (2) sustainable advantages of the Mediterranean diet; (3) the importance of an overall healthy lifestyle optimization leveraged by eHealth; (4) the challenges during the course of healthy eating against obesity, which are prominent in reflecting the knowledge structure, hotspots, and trends. Moreover, COVID-19, orthorexia nervosa, sustainability, microbiota, food insecurity, and e-health are identified keywords that represented the latest high-frequency keywords and indicated the emerging frontiers of healthy eating. This study indicates that the number of publications on healthy eating will increase in the future and that healthy dietary patterns and clinical applications of healthy eating will be the next hotspots in this research field.
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COVID-19 , Diet, Healthy , Adolescent , Humans , Bibliometrics , Orthorexia Nervosa , Healthy LifestyleABSTRACT
OBJECTIVE: To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated. METHODS: A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay. RESULTS: Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05). CONCLUSIONS: ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).