In mRNA vaccines against COVID-19, a new technology that had never been used for approved drugs was applied and succeeded in rapid clinical use. The development and application of new technologies are critical to solving emerging public health problems therefore it is important to understand which factors enabled the rapid development of the COVID-19 mRNA vaccines. This review discusses administrative and technological aspects of rapid vaccine development. In the technological aspects, I carefully examined the technology and clinical development histories of BioNTech and Moderna by searching their publication, patent application and clinical trials. Compared to the case of Japanese company that has not succeeded in the rapid development of mRNA vaccine, years of in-depth technology research and clinical development experience with other diseases and viruses were found to have enhanced BioNTech and Moderna’s technological readiness and contributed to rapid vaccine development against COVID-19 in addition to government administrative support. An aspect of the investments that supported the long-term research and development of mRNA vaccines is also discussed. The word VUCA stands for volatility, uncertainty, complexity, and ambiguity. Recent years have been called the era of VUCA. The rapid progress of globalization and the information society, as well as various social issues such as global environmental changes and the aging of society, have caused many unexpected events to occur, making it difficult to predict the future. In such an increasingly complex society, countries and companies are required to have strategies and resilience to flexibly respond to changes in political, economic, and social conditions ,2. TheseThe LNP-mRNA technology is an advanced technology that had never before been applied to a marketed drug . This teThis review examines the factors contributing to the rapid development of BioNTech and Moderna’s COVID-19 mRNA vaccines from three aspects. The first is the administrative aspect. New drug development is heavily influenced by government regulations. Clinical development of new drug candidates must strictly adhere to the pharmaceutical regulations set by the regulatory authorities in each country, and a product cannot be released to the market without regulatory approval. The development of a new drug usually takes 10 to 15 years, therefore clinical development of COVID-19 mRNA vaccines in one year is impossible without the strategic initiative of the government. In fact, in the United States, a national project called “operation warp speed” was organized to provide various supports for the rapid development of the COVID-19 vaccine. On the other hand, in Japan, the government has a history of not being proactive in vaccine development due to vaccine-related drug accidents. As such, the impact of government regulations has various effects on the clinical development of vaccines.The second is the technological aspect. No matter how much regulatory and administrative support is provided, clinical development will not be successful unless the technology has reached the specifications for commercial application as a pharmaceutical technology. The profile of a new drug is assessed in non-clinical studies in animals and clinical studies in small groups to confirm whether it can demonstrate sufficient efficacy and safety in humans. In addition, APIs used in clinical trials must be manufactured in accordance with Good Manufacturing Practice (GMP), and in some cases, scale-up may cause the specifications to deviate from the standards, forcing a review of the manufacturing process. In particular, the mRNA vaccine is a new drug modality that had never been applied to a marketed drug before, and it can be inferred that more problem-solving would have been required than with ordinary modalities. Therefore, it is essential to discuss the technological aspects of BioNTech’s and Moderna’s mRNA vaccine research and development in order to examine the factors contributing to the rapid development success of both companies. This paper provides a detailed review of the technological and clinical development efforts undertaken by both companies through a comprehensive survey of published papers, patent applications, and information on clinical trials conducted.The third is the investment aspect. BioNTech and Moderna are bio-ventures founded in 2008 and 2010, respectively. For a bio-venture to be successful in technology development, a lot of investment and the ecosystem to support it are necessary. A long-term investment is required especially in pharmaceutical R&D because new drug development requires a large amount of money and time. In this paper, I examine how BioNTech and Moderna were founded and how they obtained funding, and discuss the implications of the investment in vaccine development for both companies.To accelerate the development and distribution of COVID-19 vaccines and diagnostics, the US government initiated Operation Warp Speed (OWS) as a national project in May 2020 ,11. The In Japan, in order to promote the practical use of the COVID-19 vaccine, the Ministry of Health, Labour and Welfare (MHLW) has allocated a supplementary budget of approximately USD 1 billion and launched an urgent project for the development of a vaccine production system in 2020 . This prThe first successful introduction of mRNA into cells to make proteins was in 1971 . InspireThus, the practical application of mRNA vaccines has faced many challenges from the research to the development stage, and only when the technologies to overcome these challenges are in place can they be applied clinically. Next, I will review how BioNTech and Moderna conducted their research and development and brought the COVID-19 mRNA vaccine to market, focusing on information from papers, patents, and clinical trials. In contrast, the case of Daiichi, which was developing a COVID-19 mRNA vaccine at the same time but has not yet received approval, will also be presented.Ugur Sahin, chief executive officer of BioNTech, and Ozlem Tureci, chief medical officer of BioNTech, started their research on mRNA in the 1990s. They conducted research at universities and published papers and patents. Later, they wanted to apply their research to clinical practice, and in 2001 they founded Ganymed, a company specializing in antibody therapeutics for cancer. Then, they founded BioNTech in 2008.In order to track BioNTech’s R&D, I searched PubMed for articles published by BioNTech on mRNA therapeutics and categorized them according to their contents . The larAlthough papers whose research dates are before the founding of BioNTech were not found in this search because the author affiliations are listed under university names, Sahin and Tureci’s group has been publishing epoch-making research results on the basic technology of mRNA therapeutics since the late 2000s. As mentioned above, the poly(A) tail and 3’UTR regions of mRNA are important for enhancing mRNA translational efficiency and stability. In a 2006 paper, Sahin, Tureci and colleagues identified poly(A) tail and 3’UTR sequences that enhance mRNA stability and translational efficiency . In 2008Weakening the immune response of RNA itself has been a major challenge for the practical application of mRNA vaccines. Dr. Katalin Kariko has been working on mRNA since 1989 and started working on mRNA vaccines with Prof. Weissman in 1997 . In 2005Since mRNA is unstable in vivo in its naked state, it is necessary to encapsulate it in liposomes or other media for delivery to the body. BioNTech has also focused on the research and development of LNPs and conducted the first intravenous nanoparticle delivery of mRNA vaccines in humans in 2014 . After tFor the practical application of mRNA vaccines, it is also important to overcome the manufacturing challenge. In order to distribute the product on the market as an approved drug, it is necessary to establish a mass production method that is different from small-lot production on a lab scale, and a GMP-compliant production method must be established for clinical trials. Sahin recognized the importance of this. BioNTech was able to produce approximately 10,000 doses annually prior to COVID-19, then they refined the process further and could scale it up to more than a billion doses with minor adaptations . BioNTecBioNTech’s technological developments in mRNA structure optimization, delivery, and manufacturing can be seen in their patent applications. Patents filed by BioNTech by the end of the year 2020 were searched on Espacenet where the applicant is BioNTech and all text fields contain mRNA . Althoughttps://clinicaltrials.gov/, accessed on 9 October 2022) for studies with BioNTech as the lead sponsor using advanced search and confirmed from the study details that the study was for mRNA therapeutics. The extracted studies were categorized by disease type (infectious diseases (other than COVID-19), tumor, and COVID-19 vaccine)  . BioNTecAs described, Kariko and colleagues found that modifying the uridine residue of mRNA can significantly suppress the inflammatory response caused by native mRNA while maintaining its ability to be translated into protein . ModernaIn order to track Moderna’s R&D, I searched PubMed for articles published by Moderna on mRNA therapeutics and categorized them according to their contents . Moderna’s paper publications started in 2014, with more than 10 papers published per year starting in 2017. Papers on mRNA therapeutics platform technology were consistently published starting in 2014, with the highest number of papers published through 2019. Moderna’s total publication number was low up to 2016, while patent applications searched on Espacenet peaked in 2013 and then decreased considerably in 2016 . It is phttps://trials.modernatx.com/search-results/?PageIndex=0, accessed on 2 October 2022). Moderna initiated the first clinical trial in 2015 , and the content and start dates of the clinical trials were identified from the press releases. Daiichi initiated two clinical trials of mRNA therapeutics, one in 2021 and one in 2022, both of which were clinical trials of the COVID-19 vaccine. No clinical trials with mRNA therapeutics had been conducted prior to these trials. Unlike BioNTech and Moderna, it was not believed that Daiichi had any experience and accumulation in mRNA vaccine research and development prior to COVID-19 emergence.In order to track Daiichi’s R&D, I searched PubMed for articles published by Daiichi and Espacenet for patents applied by Daiichi on mRNA therapeutics. However, I could not find any publication or patent. The only publication identified on the web was a mini-review (not indexed by PubMed). According to the review, Daiichi uses a proprietary technology for the production of LNP used for mRNA vaccines . HoweverNeither BioNTech nor Moderna had any products on the market until the approval of the COVID-19 mRNA vaccine. Both companies were able to spend a large amount of R&D costs for about 10 years since their establishment because they acquired large investments and payments to cover the money spent. In the case of BioNTech, the company received a large investment from the Struengmann brothers, famous investors in Germany, at the time of its founding. In 2008, Thomas Struengmann met Sahin and Toreci, liked their enthusiasm and technology, and decided to invest in them . BioNTecIn the case of Moderna, when Derrick Rossi was convinced of the potential of mRNA therapeutics, he went to Robert Langer of MIT, a well-known chemical engineer and entrepreneur, and Noubar Afeyan, a venture capitalist, and asked for their support. They believed that mRNA therapeutics could be used not only for regenerative medicine but also for the treatment of many diseases, and they joined Moderna’s founding team. Soon after its launch, Moderna’s technology attracted much attention, resulting in large contracts and investments from major pharmaceutical companies. In 2013–2014, Moderna raised USD 1.9 billion from AstraZeneca, Alexion and Merck including payment and investment . In 2013Clinical development and approval of pharmaceutical products are strongly influenced by the regulatory affairs of each country. Therefore, it is important to examine the administrative influence on the rapid development of COVID-19 mRNA vaccines in order to consider the factors that contributed to their success. The reasons for the success of rapid development of Moderna and BioNTech’s mRNA vaccines are often discussed in terms of the accelerated regulatory process and the history of vaccine development. In the United States, the OWS, a public–private partnership program, was promoted under strong national leadership, and this was a major boost to the rapid development of the COVID-19 mRNA vaccines. In Japan, although the government had been reluctant to support vaccine development in the past due to a history of drug-related side effects, the government spent a large amount of money to support the rapid development of vaccines after the COVID-19 outbreak. In addition, some firms succeeded in rapid vaccine development while others did not, even under the same national regulations. These suggest that administrative influences contribute to a certain degree to the success of rapid development, but this alone may not be a sufficient explanation.What I learned from the comparison of the companies that succeeded in the rapid development of mRNA vaccines or did not is that there was an overwhelming difference in technological readiness. A comprehensive review of publications, patents, and clinical trials revealed that BioNTech and Moderna had conducted extensive research and development on mRNA therapeutics prior to the advent of COVID-19. Even before BioNTech was founded, in the late 2000s, Sahin and Tureci had developed a series of technologies that were important for the practical application of mRNA vaccines. The key technologies for optimizing the poly(A) tail and 3’UTR were published in 2006, the discovery of a sequence for enhancing antigen presentation was published in 2008, and the optimization of the cap structure was published in 2010. After BioNTech was established, papers on the basic technology of mRNA therapeutics have been consistently published since 2014, indicating that the company has been working on mRNA structure optimization research for many years. BioNTech has been also working to establish the LNP technology necessary for mRNA delivery. In 2014, they administered mRNA using LNP in a clinical setting for the first time. Establishing a GMP-compliant mass production method is necessary for clinical use, and Sahin recognized the importance of this and had already established a system capable of producing 10,000 doses per year prior to COVID-19. The accumulation of long-term technological development is evident in BioNTech’s patent applications. Already in 2002, patent applications under BioNTech’s name began to be filed, and the number of applications was consistently increasing until 2020. Additionally, they invited Kariko, one of the pioneers in the development of mRNA vaccine technology, to further strengthen the capability. BioNTech has accumulated clinical development experience mainly in the area of oncology vaccines. They began clinical trials of mRNA vaccines in 2012, and by 2019, before the emergence of COVID-19, they had already conducted 13 clinical trials. In parallel, BioNTech has been working on infectious disease vaccines since 2015, proving the efficacy of mRNA vaccines against the Zika virus at the animal level in 2017. Based on these accumulated experiences, at the time of the emergence of COVID-19, BioNTech was ready to develop and commercialize an mRNA vaccine against COVID-19, and they made an immediate decision to work on its development. Tureci said in her interview, “More than two decades of technology development and sound scientific research prepared us for developing the COVID-19 vaccine and enabled us to do it in such a short time” . It is aModerna also possessed much experience in technology development and clinical trials of mRNA vaccines. Their publication revealed that they had been performing research on the sequence optimization of ORF and 5′UTR regarding mRNA structure, LNP optimization regarding delivery, and mRNA manufacturing. Many patents were filed from 2010–2015, prior to the time of publication, and the number of applications peaked in 2013 and declined thereafter, once dropping to zero in 2016. Presumably, Moderna developed the technologies for the clinical application of mRNA vaccines for this time frame and prepared for clinical trials, which began in 2015. Notably, Moderna had conducted many clinical trials in infectious diseases prior to the advent of COVID-19. Among mRNA vaccine trials against viruses other than COVID-19 by 2021, many of them were conducted by Moderna. Moderna published clinical trial results of the mRNA vaccine against the influenza virus in 2017. It is speculated that Moderna had learned a lot of things from their technology development and clinical trials before they developed the COVID-19 vaccine although the first approved mRNA vaccine was for COVID-19.In contrast, I could not identify any accumulation of technology development and clinical trials of mRNA vaccine before the advent of COVID-19 in Daiichi. Although the publication confirmed that an original technology is used for the lipid of LNP, no international patents were filed, and no other publications or patent applications for mRNA vaccines were identified. The clinical trial of the mRNA vaccine was also the first for COVID-19, and the experience of technology and clinical development is significantly less than that of BioNTech and Moderna. It is easy to infer that this overwhelming difference in technology readiness has affected the difference in the speed of development of the COVID-19 vaccine.Having a lot of experience in technology development and clinical trials is especially important in drug development. This is because new drug development using human subjects is conducted under strict regulations, and if a problem arises in clinical trials, such as efficacy, safety, or formulation, the drug candidate compound must be reselected or the manufacturing process changed in the research stage, causing a significant delay of the development period. Without a doubt, BioNTech and Moderna were familiar with mRNA vaccine technology by developing it themselves, and with experience in many clinical trials in viruses and disease areas other than COVID-19, they knew what the problems were and how to overcome them when administered to humans. The impact of investment is important in supporting this long period of R&D. Pharmaceutical R&D typically takes 10–15 years, and new modalities require more time for initial technology development. Neither BioNTech nor Moderna had a product on the market before COVID-19 vaccine approval. During that time, large R&D expenses kept the income statement in the red, with BioNTech’s loss in 2019 amounting to about 180 million euros. However, BioNTech had received substantial investment from business angels since its establishment and had also raised a wealth of venture capital funding. Moderna had the support of a prominent researcher and a venture capitalist with extensive entrepreneurial experience from its establishment. Moderna had also received much joint research funding and investment from several pharmaceutical companies that were interested in their technology and had successfully raised a large amount of money from the market as well. When Rossi founded Moderna, he did not imagine that mRNA drug technology could be used for vaccines against infectious diseases, and BioNTech has been refining its mRNA vaccine technology mainly in the oncology area. As such, innovative technologies often do not have their optimal applications in the early stage. Nevertheless, when there is interest in the innovativeness of a technology, angels and venture capitalists invest heavily from the early stage, creating an ample financial base for deep tech to grow. In the U.S. in particular, there is an abundance of risk money to invest in deep tech, and a culture of investing in and nurturing promising technologies from the early stages and the ecosystem that supports it are well established. In Japan, on the other hand, the amount of risk money used for venture investment is a hundredth of that in the U.S. , and theThe COVID-19 pandemic was a symbolic event in the era of VUCA. The development of a variety of advanced technologies is essential to tackle public health challenges. However, the practical application of such advanced technologies takes a long time and requires a large investment. By comprehensively reviewing the R&D history of BioNTech and Moderna and the policy and investment perspectives surrounding it, this paper describes the importance of technology incubation in the long term and the need for a venture ecosystem to support it.


Depressive disorder is a chronic mental illness that is vulnerable to relapse, imposes a huge economic burden on society and patients, and is a major global public health problem. Depressive disorders are characterized by depressed mood, decreased energy and interest, and suicidal ideation and behavior in severe cases. They can be treated through pharmacotherapy and psychotherapy or physical treatments such as electroconvulsive therapy (ECT). In patients with suicidal ideation, behavior, or refractory depressive disorder ECT has a faster onset of action and better efficacy than pharmacotherapy. This study used bibliometric and visual analyses to map the current state of global research on ECT for depressive disorder and to predict future research trends in this area.A literature search was performed for studies on ECT and depressive disorder in the Web of Science Core Collection (WoSCC) database. All studies considered for this paper were published between 2012 and 2021. Bibliometric and co-occurrence analyses were performed using the CiteSpace software.The Journal of ECT is not only the most published journal but also the most co-cited journal in the field. Co-occurrence analysis showed that electroconvulsive therapy, treatment-resistant depression, bipolar disorder, hippocampus, efficacy, and electrode placement are current research hotspots. Molecular biomarkers, neuroimaging predictors, and late-life depression will become research hotspots in the future.In total, 2,184 publications were retrieved. The number of publications on ECT and depressive disorder have been increasing since 2012, with China being a emerging hub with a growing influence in the field. Zafiris J. Daskalakis is the top author in terms of number of publications, and Our analysis made it possible to observe an important growth of the field since 2012, to identify key scientific actors in this growth and to predict hot topics for future research. Depressive disorder is a chronic, easily relapsing mental illness with depressed mood, decreased energy, and diminished interest as its core symptoms. It frequently presents, in addition, problems with appetite, sleep, memory, and concentration, or psychotic symptoms, such as hallucinations and delusions. In severe cases, it can also involve suicidal ideation and behavior. The World Health Organization has reported that more than 264 million people worldwide have depressive disorders . EpidemiTreatment for depressive disorders is usually based on medication, psychotherapy, or a combination of both, but approximately 30% of patients with major depressive disorder do not respond well to these treatments . ElectroCurrently, global trends in ECT for depressive disorders are unclear. Bibliometrics is a comprehensive analysis method, which can fill this gap by analyzing publications to qualitatively and quantitatively assess the contributions of countries, institutions, and authors in the field and predict future research trends . This stThe data for this study were retrieved from WoSCC, a wide and high quality database for bibliometric data. We conducted a search of the WoSCC database on 14 June 2022.The search strategy used in our study was TS = electroconvulsive therapy AND (TS = depressive disorder OR depression). The search time ranged from 2012 to 2021. The language used for the search was English. We excluded “meeting abstract“, “editorial material”, “letter”, and “early access”. Given our exclusion criteria, the remaining 2184 paper were mostly composed of original articles and meta-analyses .CiteSpace is a Java program, developed by Professor Chao-Mei Chen at Drexel University, that visualizes literature data from various databases. The software has been used to analyze trends in the evolution of disciplinary research frontiers and internal links between different research frontiers. Collaborative networks can be used to identify core countries/regions, institutions, authors, and their collaborations. Co-occurring keywords can reveal both the starting point of a subfield of research and current research hotspots. In addition, detecting bursts can detect research trends more clearly.In this study, we used WoSCC to analyze publication output, scientific subject category networks, year of publication, and other data such as impact factors. As mentioned earlier, relevant literature was searched using keywords and unqualified literature was filtered. The selected literature information was then saved and imported into CiteSpace v5.8 R3.N = 50; Pruning: MST.The specific parameters were set as follows. Time slice: January 2012–December 2021; term source: title, abstract, author keywords, and keywords; node type: author, institution, country, keyword, and journal; link strength: cosine; selection criteria: Top Centrality is a key indicator of the importance of the keywords analyzed in the CiteSpace output. If the centrality of a node exceeds 0.1, it means that the node is a central node, which is more important and has more influence in the study. In the generated visualization image, the node size represents the frequency of keyword co-occurrences; the larger the node, the higher the frequency. The color of the center of the node represents the time of keyword appearance; the closer the color is, the earlier the keyword first appears. The red areas in the nodes indicate the occurrence of a citation or frequency burst. Burst detection can be used to analyze the current status of research and hotspots, suggesting future research trends in the field.Changes in the quantitative distribution of publications are important indicators that can directly reflect the trends in the field. The annual publications on depressive disorder and ECT in the last 10 years included 2184 relevant articles, and the overall trend showed an increase of publications on depressive disorder and ECT each year. This indicates ECT or depressive disorder as a hot topic of research .r = 0.890, p < 0.001). The comprehensive analysis of publications and centrality shows that the United States made the largest contribution to this field, with 671 publications and a centrality of 0.29, and Canada  also has a large influence on this field. The network map of cooperation between countries/regions is shown in A total of 73 countries/regions have publications in the field of ECT and depressive disorder. The top 10 countries/regions were ranked by publication and centrality . The topr = 0.761, p < 0.001). According to the analysis of publications and centrality, the University of Toronto was overwhelmingly dominant in terms of number of publications, with 104 publications, and its centrality was 0.15. Columbia University  also played a significant role in this area. There were 351 nodes and 1442 linked lines in the collaborative relationships between institutions . Furthermore, The top ten authors are listed in The Journal of ECT, followed by the Journal of Affective Disorders and Biological Psychiatry. The top 10 journals have impact factors above 3.00, with five journals having impact factors above 5.00. Co-cited journals are other journals that are co-cited by researchers. The analysis of journal co-citations shows the contribution of each journal to the field. The top three journals based on co-citation counts were The Journal of ECT (1535), the American Journal of Psychiatry (1480), and the Journal of Affective Disorders (1409).Articles on the application of ECT to depressive disorder have been published in 536 journals. The top 10 journals and co-cited journals were mainly in the fields of psychiatry, brain science, and behavioral medicine . The mosJAMA Psychiatry by CiteSpace can reveal the hot topics of the study by clustering analysis of co-occurring keywords. There were 501 co-occurring keywords in this study: the top ten keywords are listed in The keyword bursts reflect hot topics and trends in the research field within a certain period of time. The blue line represents the last 10 years and the red line represents the duration of keyword bursts, demonstrating the evolution of hot topics. Citation bursts of references can illustrate the evolution of the knowledge domain. This study is the first to apply bibliometric and visual analysis methods to ECT and depressive disorder to visualize global hotspots and trends in ECT for depressive disorder over the past 10 years. The findings of this study may help researchers identify the changes in research hotspots in this field, help them select future research topics, and choose appropriate journals according to recent trends.Our analysis showed that the number of publications in this field has been increasing since 2012. Among the many countries/regions with the highest number of publications, the United States has significantly contributed to the field, and most of the top 10 institutions in terms of number of publications are located in the United States. The University of Toronto, with 104 publications, is the institution with the highest number of publications in the field in the last decade, followed by Duke University and the University of California. Zafiris J. Daskalakis from the University of San Diego is the author with the highest number of publications, contributing to the field and collaborating with other researchers. It is noteworthy that China, as the third most published country, has made increasingly more research in this field in recent years. China also has collaborated with the US, the UK, and Australia. The prediction of research hotspots in the present study is expected to help Chinese researchers in their future research in this field and thus strengthen their international influence. One additional result emerging from the analysis is that Chongqing Medical University has published more papers in this field in the last decade, but has less cooperation with other institutions. International cooperation needs to be strengthened. We also found that the countries/regions or institutions that have contributed more to this field are located in Europe and the United States, while Southeast Asian or African countries have contributed less. We speculate that this may be related to the level of development and economic development of the country, which also indicates that the economic status of the country has an important influence on research development.The Journal of ECT is the most published and most cited journal, and reports on clinical research and related projects related to ECT worldwide, covering all aspects of contemporary ECT and making a significant contribution to the field.This study found that most of the articles in this field were published in journals related to psychiatry, neurology, and behavioral medicine, and that the impact factors of the journals were high, which indicates that the distribution of articles was concentrated and of high quality. In addition, the top ten journals and the most cited journals are consistent, including many top journals, which also indicates the high quality of research and reliability of research results in this field. Biological Psychiatry, who found that hippocampal volume was smaller in patients with depressive disorder (p < 0.04) and predicted clinical response after ECT (p < 0.05) by comparing hippocampal volume in patients with depressive disorder with controls at baseline. They also performed a longitudinal comparison of hippocampal and amygdala volumes in patients with depressive disorder before ECT, after two ECT sessions, and 1 week after completion of ECT and found significant increases in the volumes of the anterior hippocampus, basolateral, and centromedial amygdala. This suggests that ECT-induced neuroplasticity is associated with an elevated response and that these structural alterations may be related to neurotrophic processes. The results of some studies suggest an increase in brain-derived neurotrophic factor (BDNF) and other trophic factors after ECT, which is considered to be an important marker of cellular plasticity and these microscopic level changes may correspond to structural changes in imaging. JAMA Psychiatry predicted the ECT treatment response of individuals based on pretreatment gray matter volume through machine learning. The prediction was 78.3% accurate (18/23) and 100% sensitive (13/13). The study also found that patients with depression with less damage to the structure of the subgenual cingulate cortex before ECT responded better to ECT. The results of this study serve as a catalyst for subsequent studies, providing a possible biological marker for individual responsiveness to ECT. The most recent and co-cited article is a meta-analysis by British Journal of Psychiatry, which is also a reference with the strongest citation burst lasting until 2021. This article provides a separate analysis of response and remission after ECT, and the results show that presence of psychotic features and older age can predict ECT remission and response, while severity of depression can only predict ECT response but not remission.Among the ten most co-cited publications, seven were published in journals with impact factors higher than 10, and five were about changes in hippocampal volume after ECT. The most co-cited literature was published by The above study explored the predictors of treatment response after ECT. The results suggest that both clinical features and neuroimaging findings are predictive of treatment response to ECT. In clinical practice, if we can identify patients with lower responsiveness to ECT early, we can choose other treatment options in the first place.We combined the cluster analysis of co-occurring words and bursts in terms of keywords and citations to predict future research hotspots in this field. In what follows, we examine the hotspots that emerged from our analysis, one by one.The search for biological markers that can predict the response to treatment after ECT remains an important goal in the treatment of patients with depressive disorders. It has been shown that ECT has a neurotrophic effect, and it is likely that this effect is achieved by increasing the concentration of BDNF and vascular endothelial growth factor (VEGF) in the brain .Brain-derived neuro trophic factor is an indispensable neurotrophin in the development of the central nervous system, which not only promotes axonal growth and synaptic connections but also plays an important role in the mechanism of neuroplasticity . It has Vascular endothelial growth factor is a highly specific provascular endothelial growth factor that increases vascular endothelial permeability and is associated with processes such as neuronal growth and regeneration . Animal There is growing evidence that changes in hippocampal structure not only reflect the clinical state of major depressive disorder, but also correlate with treatment response. On the one hand, patients with depressive disorders have increased hippocampal apoptosis and reduced glial cell numbers ; on the Lancet subjournal suggested that ECT was not associated with the risk of incident dementia in patients with affective disorders (With the advent of China’s aging society , an incrisorders , which pisorders . A largeisorders  from theAdolescent suicide is one of the major mental health concerns at present. Some studies have shown that adolescent patients with major depressive disorder are prone to suicidal ideation as well as suicidal behavior . EpidemiThis study has some limitations. First, our study only searched the WoSCC database. We believe this database is rich enough to provide an adequate base for the analysis, but conducting the same search on a different database might provide different results. Second, we only analyzed the results visually; therefore, it is possible that some publications were overlooked. Third, we only searched the literature in English and ignored publications in other languages. This approach may lead to overlook useful publications in languages other than English.The Journal of ECT is not only the most published journal, but also the most co-cited journal, and we predict that molecular biomarkers, neuroimaging predictors, and late-life depression will be relevant research hotspots in the future. The results of the present analysis of the literature suggest that more high-quality studies should be conducted to identify markers that can effectively predict ECT responsiveness. This would also help clinicians choose appropriate individualized treatment plans.This study is the first to apply bibliometric and visual analyses to an article on ECT for depressive disorder. We explored the current state of global research in the field and predicted future research trends. Since 2012, the number of publications has been increasing, with the United States and the University of Toronto being the most influential country and institution, respectively, and China as a relevant latecomer to the field. Daskalakis made a large contribution to the field as the author with the highest number of publications. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.HC and RD were responsible for study design and statistical analysis. ZW and KY were responsible for manuscript preparation. HC, RD, and WL were involved in evolving the ideas and edited the manuscript. All authors contributed to the article and approved the submitted version.


Central auditory processing screening in schoolchildren has led to debates in literature, both regarding the protocol to be used and the importance of actions aimed at prevention and promotion of auditory health. Defining effective screening procedures for central auditory processing is a challenge in Audiology.This study aimed to analyze the scientific research on central auditory processing screening and discuss the effectiveness of the procedures utilized.A search was performed in the SciELO and PUBMed databases by two researchers. The descriptors used in Portuguese and English were: auditory processing, screening, hearing, auditory perception, children, auditory tests and their respective terms in Portuguese. Inclusion criteria: original articles involving schoolchildren, auditory screening of central auditory skills and articles in Portuguese or English. Exclusion criteria: studies with adult and/or neonatal populations, peripheral auditory screening only, and duplicate articles. After applying the described criteria, 11 articles were included.At the international level, central auditory processing screening methods used were: screening test for auditory processing disorder and its revised version, screening test for auditory processing, scale of auditory behaviors, children's auditory performance scale and Feather Squadron. In the Brazilian scenario, the procedures used were the simplified auditory processing assessment and Zaidan's battery of tests.At the international level, the screening test for auditory processing and Feather Squadron batteries stand out as the most comprehensive evaluation of hearing skills. At the national level, there is a paucity of studies that use methods evaluating more than four skills, and are normalized by age group. The use of simplified auditory processing assessment and questionnaires can be complementary in the search for an easy access and low-cost alternative in the auditory screening of Brazilian schoolchildren. Interactive tools should be proposed, that allow the selection of as many hearing skills as possible, validated by comparison with the battery of tests used in the diagnosis. Auditory screening in school-aged children has been extensively studied in the literature, both regarding the protocol to be used and the importance of actions aimed at prevention and promotion of auditory health, since this age group is undergoing oral and written language development and auditory changes may interfere with the learning process. Recent studies indicate that the incidence of peripheral auditory alterations varies from 14% to 63.4%, depending on the evaluation procedure used.2It is known that peripheral auditory dysfunction and/or a history of secretory otitis media in the first five years of life can result in immaturity in the development of auditory pathways and central auditory abilities.8Listening to and understanding auditory information involves greater complexity central to the auditory periphery, since it involves the appropriate transmission of nerve impulses to the cochlear nuclei the, thalamus and auditory cortex. These auditory stations are responsible for sound localization and lateralization, auditory discrimination, auditory recognition, temporal aspects of hearing, auditory performance with competing acoustic signals, and auditory performance in unfavorable acoustic situations.The literature contains relevant discussions about the nature of the CAPD and its direct or indirect association with higher cognitive functions, such as attention, memory and language.The similarity of signs and behaviors in CAPD with other conditions such as Attention Deficit Hyperactivity Disorder (ADHD) and Attention Deficit Disorder (ADD) are confounding factors for the diagnosis and generate questions. However, although some symptoms are common in different clinical pictures, CAPD has signs and symptoms that are specifically related to auditory deficit, such as difficulty in understanding language spoken in noisy environments, when speech is quickly presented; difficulty with words of similar sounds and difficulty following complex auditory commands. Although these characteristic signs can be detected from the clinical history and symptom assessment through validated questionnaires,With schoolchildren, care always must be taken to obtain a global speech-language assessment of the child and, whenever possible, a multiprofessional one, since CAPD might be an associated comorbidity with other clinical alterations, increasing diagnostic difficulties especially with respect to reading and writing performance.Defining effective screening procedures to assess central auditory processing is a challenge for the field of Audiology. Since 1986, researchers have been searching for screening techniques, either through batteries of tests and/or questionnaires; however, there is no consensus regarding the most efficient protocol to be used for central auditory processing screening. Auditory screening should be a simple and rapid procedure that can be applied to many individuals, aiming at the early identification of those with a high probability of having a specific problem and, based on that identification, mandate a full evaluation.Studies have shown that children with academic difficulties had worse speech perception in silence and in noiseprocessamento auditivo (auditory processing), triagem (screening), audição (hearing), percepção auditiva (auditory perception), crianças (children) and testes auditivos (hearing tests). All identified articles were included, according to the inclusion and exclusion criteria, regardless of the year of publication. The titles of the articles found in both databases were transported into an Excel spreadsheet for the exclusion of articles in duplicate during the matches made during the search.A review of the literature independently was performed by two researchers through an electronic search in the SciELO and PUBMed databases in the month of May of 2017. The research was carried out by crossing the following descriptors and their corresponding terms in English: Inclusion criteria: original articles involving schoolchildren, auditory screening with procedures focused on the evaluation of central auditory skills and articles in Portuguese and/or English languages.Exclusion criteria: studies carried out with adult and/or neonatal populations, peripheral auditory screening only and duplicated articles.A total of 197 articles were identified, 50 in the SciELO database and 147 in the PUBMed database. After applying the exclusion criteria, 11 articles met the criteria and were included in the review. The articles found in the SciELO and PUBMed databases, according to the criteria described in this review, were published between 1998 and 2016, as shown in The basis of the discussion of the study carried out by Amos and HumesThe battery was revised and expanded by adding competing sentences and modifying instructions to make it more understandable to younger children. The Competing Words test was reviewed and revised for children aged 5–11 years.In 2012, Yathiraj and Maggu developed the Screening Test for Auditory Processing (STAP) and in 2013, they applied this screening battery to 400 schoolchildren aged 8–13 years.17The questionnaires, or the so-called “checklists”, have been important internationally as a means of screening central auditory processing.In 2016, Ahmmed and AhmmedThe use of questionnaires is a simple and inexpensive procedure that can add information to the screening of at-risk children. Studies suggest that when the checklist procedures and auditory tests are applied in a complementary way, there is a correlation with the diagnostic tests.The use of interactive and easy-access tools has gained importance as a screening method.In Brazil, the CAP screening procedure most commonly used with schoolchildren is the Simplified Auditory Processing Assessment (ASPA),Colella-Santos and collaboratorsToscano and Anastasio evaluated schoolchildren aged 4–6 years using ASPA and 24.6% showed at least one altered skill. The authors also found that younger children had a higher rate of abnormalities in auditory skill tests and acoustic immittance measures.The prevalence of hearing skill alterations found in another studyFor younger children, the ASPA has widespread applicability because it requires only a brief administration time and requires readily accessible materials,. However, performance on the test improves with advancing age until pre-adolescence. Since the battery does not evaluate auditory mechanisms, it is unable to identify schoolchildren with other auditory mechanism impairments. However, the ASPA can be a sensitive predictor of CAPDs, because when the assessed auditory mechanisms have matured, and when the skills are altered, the behavioral tests are very likely to be altered, since they include more complex tasks.n = 11) and the great variation in age in the group.Another CAP screening method used in Brazil is the Zaidan battery, which consists in the SCAN adapted to Portuguese.In 2006, researchers applied the SCAN to 57 children aged 8–10 years using a portable stereo disk-player and two headphones.In 2007, the battery was applied to 40 children aged 7 and 8 years in the municipality of Bauru, state of São Paulo, using an audiometer coupled to the Compact Disc Player (CD) to establish a standard of normal for the SCAN test in central auditory processing evaluation, and to be able to compare the findings with those in Zaidan's study. However, differences in scores were observed. According to the researchers, it is necessary to execute a study with larger numbers of children and children from different geographic regions.In 2008, the Zaidan battery was again applied to schoolchildren aged 7 and 8 years old in the municipality of Cuiabá, state of Mato Grosso.These studiesWith the advances in technology, the utilization of Telehealth in audiology has become prominent as a means to improve access to auditory health services and quality of care.The central auditory processing screening initiatives reviewed in this study are satisfactory with respect to being easy to apply and short duration. However, it is necessary to consider the reality of each geographic region with respect to feasibility; the use of audiometers, IPADs and/or computers may not be possible in some school environments.The use of only one tool such as the ASPA or the questionnaire also does not address the complexity of CAP screening, since none of the methods can address, in a single battery, all the auditory mechanisms underlying the hearing skills recommended by ASHA.Based on the analyzed studies, there is a need for technological resources that identify evaluation procedures that include the auditory skills in the audiological evaluation. The STAP and Feather Squadron have a more complete battery for CAP screening. The Feather Squadron was applied in the age group of 5–14 years, and divided the battery in two versions, for children aged 5–7 years and those older than 8 years. The STAP battery was applied only in schoolchildren older than 8 years, reflecting the maturation of CAP skills by that age. Considering the analyzed studies, it is clear that central auditory processing screening is an area yet to be explored.New studies should be carried out that aim to identify a battery of procedures that screen as many auditory skills as possible, that can evaluate different age groups, and then be validated by comparison with the battery of tests used in the CAPD diagnosis.At the international level, two screening batteries can be highlighted for their most comprehensive assessment of hearing skills – STAP and Feather Squadron. At the national level, there is a shortage of studies that use central auditory processing screening methods that evaluate more than four central auditory processing skills. The association of questionnaires in schoolchildren screening practices, the use of ASPA for pre-school children and the development and study of new auditory screening proposals for older children are suggested, including procedures aimed at the evaluation of central auditory skills that can be applied in the school environment. Such procedures should be validated based on studies that confirm the schoolchildren's performance in central auditory processing screening by comparing it with the performance in the CAP behavioral assessment battery tests.The authors declare no conflicts of interest.


The health and safety of the miners in the South African mining industry are guided by the regulations and standards applied to promote a healthy work environment. The miners must comply with these regulations/standards to protect themselves from potential occupational health and safety risks, accidents, and fatalities. The status of compliance to safety regulations and standards in the mining industry of Limpopo Province has received little attention from scholars. This study explores the practices related to occupational health and safety standards compliance in the mining industry. A total of 277 miners were randomly selected from 1300 respondents in the mining industry. Data were collected using a 31-item survey questionnaire, administered to miners to explore occupational health and safety standards compliance from December 2019 to May 2020. Principal Component Analysis (PCA) extracted key attributes of occupational health and safety standards compliance in the mining industry and uncovered relationships between different dimensions. The study revealed that seven factors could measure occupational health and safety standards practices. It was observed that Factor 1  is correlated with Factor 2 (measures to reduce risk of injuries/accidents). Additionally, Factor 2 (measures to minimise the risk of injuries/accidents) is correlated with Factor 4 (impact of the environment and production). There is a correlation between non-compliance with the safety regulations and the occurrence of injuries and accidents. Occupational health and safety standards play an essential role in guiding all miners on health and safety-related issues, focusing more on prevention. There is evidence of models, legislation, standards, and theories to mitigate the high incidences of accidents and fatalities in the mining industries ,2. Most In Africa, there are comprehensive laws regarding health and safety standards and systems to ensure compliance; however, adherence to them is generally weak and under-resourced in many organisations ,6. The mPromoting occupational health and safety in the workplace has several benefits for society; the mining organisations; the miners and their families; and South Africa’s (SA) socio-economic growth. Previous studies have reported that poor enforcement and implementation of health and safety measures negatively affect social and economic growth ,11. SeveA quantitative, descriptive, cross-sectional design was used to obtain data from the miners regarding compliance with health and safety standards . The stuA total of 297 miners were conveniently sampled from 1300 miners. The sample constituted of miners, artisans, mining engineers, operators, electricians, shift bosses, team leaders, winch operators, health and safety personnel, mining managers, engineering managers, and mine surveyors in the mining industry. Exactly 277 miners returned the signed consent form, giving a 93% response rate from the initial sampled group of miners. The respondents who consented to participate were asked to complete the self-administered questionnaire written in English and three indigenous languages: Sepedi, Xitsonga, and Tshivenda. Data were collected for six months from December 2019 to May 2020, using a self-administered questionnaire with closed-ended questions Refer to . The queData were entered into Microsoft Excel and then exported to Statistical Package for the Social Sciences (SPSS) version 26 . Demographic characteristics of the participants were presented as frequencies and percentages. Principal Component Analysis (PCA) was used to extract key attributes from 29 items related to occupational health and safety standards practices in the mining industry, and to uncover relationships between the different dimensions. A Kaiser–Meyer–Olkin measure of >0.5 means that the sample size was appropriate to run an Exploratory Factor Analysis (EFA) . Only itA literature review on health and safety compliance in the mining industry was conducted to ensure validity. Face validity was ensured through consultation with the health and safety practitioners to confirm that the questionnaire was, indeed, measuring what it was designed to measure . CronbacThe total variance explained by the five factors was 71.4%, suggesting a satisfactory factor solution. The PCA revealed that seven factors could measure occupational health and safety standards practices, as shown in Factor 1: Occupational health practice related to regulations; Factor 2: Measures to reduce risk of injuries/accidents; Factor 3: Role of safety culture and resources; Factor 4: Impact of the environment and production; Factor 5: Attitude and behaviour; Factor 6: The role of mine management; andFactor 7: Use and quality of equipment see .The Cronbach’s alpha for the 29 items was 0.911 see . The comThis study sought to explore practices of the occupational health and safety legislation/standards compliance in the South African mining industry, Limpopo Province. The study revealed that most respondents were male, at 74%, with only 26% being female. The issue of gender inequality has been under discussion in the SA mining industry, with provisions in place for the inclusion of women in core mining activities. Though some progress has been made in employing more women, with the requirement of 10% of positions to be occupied by women, mining has always been considered a very masculine industry due to its heavily male-dominated workforce and the physicality of mining work . In SA, The miners who were considered to be more experienced 18%) had more than 10 years of working experience compared to those with 1 to 5 years (36%) experience. Haas, Eiter, Hoebbel, and Ryan  conducte% had morFactor 1 included items that addressed the importance of, and practices related to, the occupational health legislation and standards, and their relation to health and safety compliance within the mining industry. By looking at the items within this factor, it is clear that knowledge, availability, implementation, and training on health and safety regulations are viewed as important in ensuring health and safety compliance. The results of this study are similar to previous studies, which revealed that knowledge and the accessibility of occupational health and safety legislation impact implementation and compliance amongst miners . More imFactor 2 included all items related to the existing measures available to reduce the mine’s risks of injuries and accidents. It is also recognised that the mine has developed specific health and safety standards related to miners’ duties. It was observed that most accidents in the mining industry are caused by non-compliance with health and safety standards. In agreement with the study findings, the existing literature reveals that most accidents and injuries are caused by non-compliance with the available regulations and standards and the organisation’s established health and safety management system . TherefoFactor 3 included all items describing the role of a safety culture and resources in ensuring safety compliance. According to Widajati, Ernawati, and Martiana (2017) , the safFactor 4 highlights elements describing the impact of the environment and production on compliance with the health and safety standards. The physical environment is a poorly designed item that recorded the highest loading under this dimension, suggesting that this item contributes the most to the impact of the environment and production. Non-compliance with safety standards could, thus, result from a poorly designed physical environment. Qasim et al.  conducteThe literature revealed production pressure as the miners’ fundamental cause of poor compliance, especially for those who intend to meet the production targets, which results in “doing things faster” while compromising their health and safety . This liFactor 5 included the attitude and behaviour items associated with safety compliance. According to Li et al. , a safetFactor 6 included all items indicating the mine management’s significance in influencing miners’ health and safety compliance. The aspect that stands out is that violation/non-compliance of health and safety regulations causes accidents. This item recorded the highest loading under this dimension. This suggests that mine management plays a significant role in promoting compliance, including monitoring and supervising miners during production activities. The current study’s findings are echoed in scholarly work wherein the role of leaders in supervision affects the safety practices in the workplace and provides an opportunity to influence positive outcomes for workers, managers, and the organisation . PractisFactor 7 included all items on the use and quality of the equipment that influences health and safety compliance. The item with the highest loading was “equipment provided is good quality”. The current study findings are in contrast to that of Shaw, Verna Blewett, and Schutte , who outThe Pearson correlation test suggests a positive correlation between the occupational health practice regulations and measures to reduce the risk of injuries/accidents. Our study findings are related to those reported by the WHO Healthy Framework, which states that each mining organisation must strive to achieve compliance and create a healthy work environment. This could be achieved by involving the miners in focus groups so that they can identify and implement the solutions in unity . Our finMeasures to reduce the risk of injuries/accidents, and the impact of the environment and production on safety compliance, had the strongest correlation. This implies that the impact of an environment, such as the elimination of the risk factors for injuries within the mining environment, could result in a better presentation of the mining industry. The current study findings are similar to those reported in the existing literature. For example, Michell  reportedThe COVID-19 pandemic affected the data collection process, making it difficult for the researchers to access the respondents, which affected the study’s sample size.This study contributes to the body of knowledge about the practices of occupational health and safety legislation/standards compliance. The study results indicate that the mining environment’s activities and production pressure may affect and compromise miners’ safety and, subsequently, result in non-compliance to safety guidelines. Therefore, a safety awareness/behaviour awareness programme is recommended to encourage the miners’ behaviour in promoting safety in the working environment and during production, which will be healthy and safer for everyone. The study also revealed that training and the availability of policies/standards and procedures has a greater impact on how the miners perceive compliance with the health and safety standards. Strengthening the training and education system by adopting new education methods using information and communication technologies, sharing information through social networks, using websites, and e-learning will be beneficial in creating a platform for miners to quickly discuss the issue of health and safety at work. It is also recommended that the mining organisations must develop and implement an effective health and safety management system that contributes to building a positive health and safety culture at work. Moreover, understanding the health and safety practices of miners might assist the mine in developing on-site interventions to improve the state of health and safety.


Anthropogenic habitat changes are disrupting the mate choice process in a range of organisms, with consequences for populations and communities. Research has so far focused on male sexually selected traits and female mate choice, given their conspicuousness, whereas effects on female ornaments and male mate choice have been largely overlooked. Yet, females of many species develop ornaments that males use in mate choice. These ornaments can be costly and reduce female fecundity and viability and, hence, influence population growth rate. Thus, attention should be paid to changes in female ornaments and the consequences the changes have for populations. Here, we show that declining visibility in aquatic ecosystems reduces the investment of female three-spined stickleback in a melanin-based ornament in favor of increased mate search activity. The adjustment appears adaptive as males pay less attention to the ornament under poor visibility, and as melanin-based ornaments are generally physiologically costly. It is likely that past fluctuations in visibility have promoted the evolution of environment-dependent plasticity in female ornamentation. More attention should be paid to changes in female ornaments and their adaptive value, across taxa, given the impact that female investment in ornaments can have on fecundity and population growth rate. Environments are changing at an accelerating rate because of human activities and knowledge of the responses of both males and females is needed to evaluate and predict the ultimate impact on populations and biodiversity. Females often use costly ornaments to attract males. Yet, how these are influenced by human-induced environmental change is unknown, although information on changes in both male and female traits are needed to determine the impact of environmental change on populations. We show that declining visibility reduces the efficiency of a female ornament in the threespine stickleback, and interestingly, that females show adaptive adjustments of the ornament to its reduced efficiency. Habitats are changing across the world because of human activities. In many aquatic ecosystems, visibility is deteriorating because of anthropogenic eutrophication and enhanced growth of algae . Blooms The mechanism behind altered mating success under poor visibility is often found to be reduced efficiency of male sexually selected visual signals . Poor viGasterosteus aculeatus). Males build a tunnel-shaped nest and attract females to spawn by combining nuptial coloration with courtship, and then singly care for the eggs. The number of females that can spawn into a nest is restricted by the size of the nest and the ability of the male to care for the eggs by fanning fresh water into the nest  the signal value of the ornament in reflecting female fecundity and inclination to spawn, and 3) the efficiency of the ornament in attracting males and, hence, the adaptive value of adjusting ornament expression to visibility. We performed two experiments that assessed the impact of altered habitat conditions and visibility on 1) the expression of the female ornament and its value as an indicator of female fecundity and interest in spawning, and 2) the efficiency of the ornament in attracting males.In the Baltic Sea, the breeding habitat of the three-spined stickleback is changing because of anthropogenic eutrophication . ExcessiWe caught adult three-spined sticklebacks from shores close to Tvärminne Zoological Station in the Northern Baltic Proper , Finland, at the start of the breeding season, using Plexiglas traps . We housIndividuals that came into reproductive condition – indicated by blue eyes in males and the swelling of the abdomen in females – were moved to separate tanks; females to large holding tanks and males to individual 10-L tanks. The male tanks contained a dish (15 cm in diameter) filled with sand and filamentous green algae for nest building and an artificial plant for shelter . To stimTo investigate if reduced visibility because of the growth of algae influences the expression of the female ornament, we moved females to individual tanks  with either an open or a vegetated habitat structure. In the open habitat, the bottom of the tank was covered by sand, whereas the vegetated habitat contained four bunches of artificial filamentous algae in addition to the sand. The artificial algae consisted of a cement clump to which 15 cm long polypropylene strings had been attached . The vegWe used recently spawned females, who had released their first egg clutch within the last 12 h, to ensure that the whole egg maturation and ornament development period was spent under the experimental conditions. Females release their ovulated eggs spontaneously if no nest is available . RecentlTo determine if ornamentation correlates with female investment in mate searching and fecundity, we allowed the females to search for and spawn with a nesting male. One hour after the photographing, we moved the female into an experimental arena . She was first enclosed in a transparent, perforated cylinder (diameter 20 cm) for 15 min to allow her to acclimatize to the new conditions, and then released by gently removing the cylinder, which lacked a bottom. At the opposite corner of the tank  was a male in breeding condition, enclosed within a transparent, perforated cylinder (diameter 20 cm). He had been placed into the tank the day before, together with the dish containing his nest. The female could not see the male from where she was released, as visibility was restricted by four bunches of artificial algae that covered about 50% of the area, and by two clay pots (diameter 10 cm) that imitated larger rocks.3. Two hours after spawning, when the eggs in the nest had hardened, we recorded the amount of eggs spawned by gently removing the clutch of eggs from the nest and weighing it to the nearest 0.01 g , body mass without eggs , or mass of eggs . We tested 30 females from each habitat treatment, 60 females in total.We recorded the latency of the female to approach the nesting male, within 5 cm of the cylinder, as this has been found to reflect investment in mate searching; females who invest less take longer to find a nesting male . We allot 0.01 g . Femaleshttps://imagej.nih.gov/ij). We converted the images to grayscale and selected a constant sized area on the darkest bar and on the area to the right of the selected bar, and recorded the difference in darkness between these two areas. In addition, one of us (SB) used the images to visually rank females based on the conspicuousness of the ornament. The two methods correlated strongly  and we used the software-based measure in the statistical analyses.We placed the female into a small glass box containing a black sponge that restricted her movements, and photographed her under standardized light conditions . On the To investigate if reduced visibility influences the preference of males for ornamented females, we allowed males to choose between two dummy females differing in ornamentation, under three visual conditions: clear water, poor visibility , and visual background noise . Thus, the treatments separated between the effects of altered visibility and altered background.To initiate a trial, we moved a male with his nest (on the nesting dish) to an experimental tank  in the evening before experimentation. The experimental tank had been divided into a male and a female section (both 35 × 40 cm) using a clear Plexiglas sheet. The backside of the female section was uniformly grey-green to mimic the natural background. In the poor visibility treatment, the Plexiglas sheet was covered with a green plastic film that made the environment on the other side look green while allowing the male to see through the sheet, imitating an algal bloom. In the visual background noise treatment, we added two bunches of artificial algae to the backside of the female compartment .The following morning, we placed two dummy females into the female section, one ornamented and one plain. We used several ornamented and plain dummies that slightly differed in form to separate out the influence of other characteristics than the ornament on male preferences. The dummies were about 7 cm long and realistically painted. The ornamented dummy had darker bars painted on both lateral sides, imitating an ornamented female. The two dummies hang from a transparent rod to which they were attached with transparent threads. The dummies were 23 cm from each other and 12 cm from the Plexiglas divider, and in front of the artificial vegetation in the background noise treatment. They were kept in a head-up posture that indicates readiness to spawn; a 45 degrees angle from the bottom . We presWe exposed each male to the three treatments sequentially, during three days, altering the order of the treatments among males. Environmental conditions were changed in the evening before the next day’s trial. Visibility in the spawning habitat of the stickleback can quickly change through the inflow of algal blooms and unattached filamentous algae. Thus, the treatments mimicked changes occurring in the natural habitat. We altered the position of the two dummies between treatments and replicates, and randomized the use of the individual dummies. We tested 37 males. No males or females were reused within or among experiments.In experiment 1, we analyzed the effect of habitat on the expression of the ornament using a linear model (LM) with ornament contrast as response variable and habitat as fixed effect. To analyze the effect of habitat and ornamentation on latency to approach the nesting male, we used a LM with latency as response variable, habitat as fixed effect, and ornament as covariate. In order to assess if the expression of the ornament changed from maturation to the courtship stage, and then from courtship to the spawning stage , we used linear mixed models (LMMs) with ornament contrast at each stage as response variable, female identity as random effect, and habitat and stage as fixed effects. To assess if the ornament correlated with female traits , we used LMs with ornament as response variable and female trait as covariate.In experiment 2, we assessed the influence of habitat on which dummy female the male first visited (plain or ornamented) using a generalized linear mixed model (GLMM) with binomial distribution and male identity as random effect and habitat as fixed effect. To analyze the effect of habitat on the number of visits to each dummy female, we used a GLMM with Poisson distribution and log link, with number of visits to each female as response variable, male identity as random effect, and habitat and ornamentation as fixed effects. To assess the effect of habitat on the time spent by each dummy female, we used a LMM with time by each female as response variable, male identity as random effect, and habitat and ornamentation as fixed effects. We tested the assumptions of the models before analyses. All analyses were performed using the software IBM SPSS Statistics 26. The models and full estimates are given in the Supplementary Materials.N = 30 females per habitat, F1,58 = 42.93, P < 0.001, Stage 1, “Maturity”, in Females in the vegetated habitat developed less conspicuous ornaments than females in the open habitat , at any of the investigated stages  and in the background noise treatment , but not in the poor visibility treatment . Males spent more time by the ornamented dummy female in clear water , but not in the background noise  or the poor visibility  treatments.The interest of the male in the two dummy females depended on habitat treatment. Males visited the ornamented dummy female before the plain one in clear water, but not in the two other habitats (GLMM with binomial distribution, differences among habitats: P < 0.001, see t216 = 5.04, P < 0.001, and to background noise: t216 = 3.64, P < 0.001, t216 = 1.40, P = 0.16, The total number of visits to the two dummy females  and the The results show that females develop less conspicuous ornaments when visibility is poor and instead increase their investment in mate searching. The switch in investment appears adaptive as the ornament is less efficient in attracting males under poor visibility, and as increased search activity is needed to find nesting males when visibility is poor .The cause of the expression of weaker ornaments in the vegetated habitat with poor visibility could be higher costs than benefits of developing and expressing the ornament. Males paid less attention to the ornament when visibility was poor, which reduced its benefit. The perceived cost could again be higher as parasite abundance is greater in vegetated than in open habitats  and as mThe negative correlation between ornamentation and mate search activity, which occurred independent of the habitat the females had experienced during ornament development, suggests a trade-off in investment between the two traits; females that developed less visible ornaments invested instead in searching for males, and vice versa. An increased investment in search activity may be needed when the ornament is weak and less likely to attract males, while the costs of both traits may cause females to balance the traits against each other. Although we did not find the ornament to correlate with current female fecundity or body condition, it could influence future fecundity and body condition, as females in the present population can produce up to 7 egg clutches during one breeding season and as melanin-based colors generally incur both energetic and viability costs . The whoThe efficiency of the ornament in attracting males depended on the habitat. The ornament attracted males in clear water, with males approaching the ornamented dummy female before the plain one, and visiting and spending more time with her, while poor visibility reduced ornament efficiency, as did visual background noise, although to a lesser degree. Males were also less attracted to the two dummies in the altered habitats, and especially under poor visibility. It is likely that males received less stimuli from the females when visibility was poor. Thus, reduced visibility influences male mate choice not only by hampering the ability of males to evaluate females, but also by reducing their interest in them. Similar results have been gained for female interest in ornamented males and the assessment of their qualities . Thus, rWe did not find the ornament to indicate female current fecundity or body condition, independent of habitat structure during egg maturation. The possibility still remains that the ornament indicates other qualities of females, such as the nutrient content of the eggs, or the genetic quality and viability of the expected offspring, as found for male ornaments . MelaninThe reduced efficiency of the ornament under poor visibility suggests that the recorded adjustment of the ornament to visibility is adaptive. It is likely that past selection has favored the evolution of plastic adjustment of the ornament to local conditions, as visibility naturally fluctuates in the breeding habitats of the investigated population, depending on spatial and temporal changes in algal blooms and the abundance of filamentous algae. Plasticity in relation to environmental conditions has been recorded also for sexually selected traits of male stickleback , and forTo conclude, an increasing number of studies show that females use ornaments to attract males, yet the sensitivity of the ornaments to habitat changes has remained unexplored . Considearac080_suppl_Supplementary_MaterialsClick here for additional data file.


To evaluate the bibliometric profile of the national academic production of public and private medical schools in Scopus after the publication of a new university law (2015–2020).  A descriptive bibliometric study was conducted. The secondary data corresponding to the 42 Peruvian medical schools that had scientific publications in Scopus from 2015 to 2020 were evaluated, and the Affiliation ID of each Peruvian institution was considered. Data were analysed using SciVal. Peruvian Journal of Experimental Medicine and Public Health had published the highest number of manuscripts (500 articles), with an approximate publication citation of two.  The total production of the Peruvian medical schools was 5406 manuscripts (100%), of which 3018 (56%) were included in the ‘clinical medicine' category. The total production of publications in Peru from 2015 to 2020 was 21597 manuscripts, of which medical publications accounted for 7950, with only 5406 manuscripts belonging to the Faculties of Medicine of Peru. The  There was a constant increase in the scientific production of Peruvian medical schools from 2015 to 2020. Additionally, it was found that medical publications contribute the most to the total scientific production of Peru. Scientometrics consists of the application of different statistical methods to analyse results of scientific research indexed in databases such as Embase, Scopus, Medline, and Web of Science. This area measures the scientific productivity of institutions, especially in the field of medicine .Bibliometric studies generally analyse the quantitative characteristics of scientific publications to obtain findings in relation to scientific communication. This type of research enables drawing contrasts between countries, affiliations, and/or authors. Consequently, bibliometrics is the numerical analysis of scientific publications in a certain period, field, or institution, and the collaborations between them .Scientometrics analyses study the impact of scientific production in an area of knowledge, such as collaborative networks that help identify dynamics between authors, countries, and institutions , 4. In tHowever, a lack of methodological uniformity can be observed in the evaluation of scientific production by medical schools, which may directly impact their reputation. For example, when evaluating the scientific production of medical schools in Europe, different bibliometric data have been used to track the amount of international collaboration, volume, and increases in research production, integrating different bibliometric techniques that could provide a more nuanced and accurate interpretation of the research output of medical schools .Thus, this research was aimed at determining the scientometric profile of the national academic production of all Peruvian medical schools in Scopus.This scientometric study was of retrospective, descriptive, and observational design. All medical schools in Peru that had a Scopus ID were evaluated, which corresponded to 42 faculties. The scientific production of these faculties was evaluated between 2015 and 2020 The search strategy was developed based on the institutional profiles (Affiliation ID) of Peruvian universities that had a school of human medicine. Afterwards, the profiles found in the Scopus database were exported to a CSV file, which was then imported into the SciVal tool to proceed with the bibliometric analysis. This analysis included indicators such as scientific production by sub-subject area, total scientific production, type of collaboration, scientific production by university, and indexed journals with the highest publication of Peruvian medical manuscripts.All Peruvian colleges were evaluated according to the licensing pattern issued by the regulatory entity SUNEDU . The following selection criteria were applied:public Peruvian medicine schoolsprivate Peruvian medicine schoolspublic and private Peruvian medicine schools with institutional licensing by SUNEDUInclusion criteria are as follows:Peruvian medicine schools that do not have Scopus registrationExclusion criteria are as follows:A descriptive statistic of the scientific production of all the evaluated medical schools was obtained and tabulated in Excel. Bibliometric analysis was performed using the SciVal tool from Scopus.The total production of the Peruvian medical schools was 5406 manuscripts (100%), of which 3018 (56%) were included in the “clinical medicine” category. In contrast, the “basic medicine” and “health sciences” categories were represented by 36% and 34%, respectively. Finally, only 1% of the investigations were in the “medical biotechnology” category .Of the 42 Peruvian universities with a faculty of medicine, the leading institutions were Universidad Peruana Cayetano Heredia, Universidad Nacional Mayor de San Marcos, and Universidad Peruana de Ciencias Aplicadas, with 2172, 975, and 705 manuscripts, respectively. In relation to other institutions, a progressive increase was observed from 2015 to 2020 .The American Journal of Tropical Medicine and Hygiene was in the second place with a total of 130 published manuscripts and a higher average publication citation of 7.2. The Revista de Gastroenterología del Peru was in the third place with 115 published manuscripts, although its average publication citation (0.7) was one of the lowest  had published at least one article in Scopus. Therefore, the scientific production of the research vice-rectors of the universities that were evaluated was deficient. This can be identified using bibliometrics . TherefoThe main limitation to the present study was that it was only possible to show the scholarly output of the Peruvian medical schools in the Scopus database, although future studies could be carried out to evaluate other databases such as Web of Science, Medline, and Embase. Another limitation was that only a specific period (2015–2020) was evaluated, although it is predicted that the highest production peak is expected in the years following 2020.This research will help determine the scientometric profile of the academic production of all Peruvian medical schools in Scopus. It will also help in the choice of journals, research fields, and topics. Because the main strength of a scientometric study is to provide a statistical analysis of the scientific publications of the Peruvian medical schools.There has been a notable and constant increase in the scholarly output of the Peruvian medical schools from 2015 to 2020. Additionally, it was found that medical publications contribute the most to the total scientific production of Peru. This coincides with the enactment of a new university law that, among other aspects, encourages research in Peru.