A negative association between the lower level of psychological resilience (PR) and increased risk of compassion fatigue (CF) and higher Coronavirus disease 2019 (COVID-19) stress has been revealed. However, bibliometric studies have not been performed to comprehensively investigate this topic. This study aimed to identify the status and trends in the CF and PR field from 2008 to 2021 and during the COVID-19 pandemic.® database using “resilience” and “compassion fatigue” on September 30, 2021. All search results were exported in plain text format for collaboration network analysis, reference-based co-citation analysis, analysis of journals, and keywords-based co-occurrence analysis, which were performed using Citespace® 5.8.R1.We identified relevant literature from the Web of Science Core CollectionA total of 388 publications were identified finally, and there has been an increasing trend in the annual number of publications with light fluctuations. The analysis of journals and keywords indicated that nurses and social workers are the main research targets, and their mental problems are the main research topics. The turnover intention of health care providers has been a research focus, particularly during the COVID-19.The results of the present study help us understand the status of the CF and PR field and its recent developments. Currentn = 306) healthcare professionals experienced medium to high CF and BO, especially those who are directly caring for patients with COVID-19 (Coronavirus disease 2019 (COVID-19), an unprecedented global health crisis , has infCOVID-19 . MeanwhiCOVID-19 . ConsequDespite a rich literature on CF in service practitioners, however, very limited information is available on effective initiatives to alleviate it . One potBibliometrics is a scientific approach to analyzing knowledge carriers with mathematical and statistical methods, and it can reveal the trend of a specific research topic . As a poIn the present study, we aimed to identify annual publications and most representative disciplines and journals in the CF and PR field and to unfold which research frontiers could contribute to collaborations between countries, institutions, and authors. Furthermore, we attempted to describe the intellectual landscape of studies and predict future development trending in this field. Finally, we also presented the above content in the view of the COVID-19 pandemic, aiming to analyze and predict trends and hot spots in this special period.This was a descriptive bibliometric analysis and science mappings, which was performed to identify and analyze literature on CF and PR. Meanwhile, we performed a separate analysis to determine the impact of the COVID-19 pandemic on research trends. Certainly, we also made a comparison between the overall findings and the COVID-19 pandemic.® from Clarivate Analytics because it allowed us to perform a precise and specific analysis of publications, authors, citations, and keywords (We retrieved targeted literature from the Web of Science (WOS) Core Collectionkeywords .®, which includes Science Citation Index expanded (SCI-EXPANDED), Social Science Citation Index (SSCI), Arts and Humanities Citation Index (A&HCI), Conference Proceedings Citation Index-Social Sciences & Humanities (CPCI-SSH), and Emerging Science Citation Index (ESCI), to identify relevant literature labeled as article or review. The search was limited from its inception until September 30, 2021. The following search strategy was used to conduct a thorough search: TS (“compassion fatigue” or “vicarious trauma” or “vicarious traumas” or “secondary traumatization” or “secondary trauma” or “secondary traumas” or “secondary traumatization” or “vicarious traumatization”) and TS = (“resilience*”). We did not impose any restrictions on our literature search, such as countries, categories, and language. We show the search strategy in We performed a systematic search in Web of Science Core CollectionNo institutional ethical approval and patient’s informed consent were necessary because the present study did not recruit animal or human subjects.® Excel 2013 . All options in the term source were selected, a node type was selected at a time according to specific conditions, “top 50 levels” as a threshold that are cited or most frequent in the corresponding time slice. For a visualization knowledge figure, node and link were the essential elements. A node represented an element, such as author, keyword, or institution, and the size of a node was proportional to the frequency of appearance or citation, and the color of the node indicated the year. Besides, each node is described with a series of tree rings across the series of time slices. The size of the concentric circles represents the number of publications. Also, the circles of different colors signified the year 2008 to 2021 or 2019 to 2021 from the inside to the outside of the nodes. The link between two nodes represented cooperation or co-occurrence or co-citation relationship. The purple ring represented the betweenness centrality (BC) of literature. If a knowledge map appeared with nodes with high BC value, these nodes were believed to bridge different stages of the development of a scientific field , animal study (n = 1), systematic review (n = 13), perspective (n = 23), interventional study , study protocol (n = 1), survey study (n = 167), and qualitative study (n = 82). As shown in Overall, 391 records published between 2008 and 2021 were analyzed. Among 391 identified studies, a total of 8 categories were determined, including narrative review , Canada (0.36), England (0.22), and Australia (0.17), all of which also entered the top 4 countries with the largest number of articles see . These rDuring the COVID-19 pandemic, as shown in The map of authors was presented to reveal the most prolific authors and co-authors, and intuitively demonstrate the closeness of collaboration among the authors, which could provide information on influential research groups and potential collaborators and help researchers establish cooperative relationships. As described in During the COVID-19, a map of authors was generated including 101 nodes and 64 links shown in . There a® Core Collection showed that the 391 documents included covered 260 different journals over the past 14 years, all of which are widely distributed. We analyzed the top 15 active journals that published articles  . RecentlDuring the COVID-19 pandemic, the largest 5 clusters were discussed in our review see . The silFor health care providers, coping with the COVID-19 emergency can be psychologically stressing/is highly related to stress, and severe stress can accelerate the development of secondary trauma (Cluster 0 and Cluster 3) ,b. PR isThe most cited references are usually viewed as landmarks based on their groundbreaking contributions. By analyzing these articles, the key knowledge foundation of each research field could be identified . Among tDuring the COVID-19, only 3 same publications entered the top 10 landmark articles see  Hegney . The majThere were 348 co-occurrence keywords when we made the keyword co-occurrence analysis of data in set #4 see . We filtDuring the COVID-19 pandemic , there w® Core Collection when retrieving literature. Future studies should retrieve more databases to identify additional papers. Second, only articles and reviews were included in our analysis. Therefore, we have missed related articles in other document types. Third, bibliometrics is a quantitative analysis of academic publications, whereas articles with high citation counts do not necessarily equate to articles with high-quality or high-correlation with the target field. Researchers should use multi-method evaluations to obtain a more in-depth understanding of this research field. Fifth, only Citespace and traditional bibliometric indicators were used in the current study. Using a variety of research methods can make the results of the study more credible, and, therefore, more methods and indicators should be considered in the future.There are several limitations in this study, which should be taken into consideration when interpreting the results. First, we only collected data from the Web of Science® software. Based on publications published from 2008 to 2021, we illustrated the change in this topic as the COVID-19 pandemic. Specifically, the number of publications in the CF and PR field presented an obviously ascending trend during the COVID-19 pandemic, indicating that CF should be especially emphasized for timely and effective delay and even prevent aggravation of psychological status through introducing some positive psychological sources such as PR. Overall, the United States was the most influential country in this research topic, as it not only published the largest number of articles but also had close cooperation with other countries, and therefore, more attention should be paid to enlarge the extrapolation of published findings. Moreover, more studies should also be performed in other countries and fields based on previously published studies. Curtin University in Australia was the most prolific institution, and Frontiers in Psychology was the most productive journal in this field. More researchers and practitioners should be trained under the supervision of specialists in this university, and more journals are also suggested to focus on this topic by launching a special issue. The turnover intention of health care providers has been a research focus in recent years. Nursing practitioners and social workers are currently the key target groups and will likely remain so in the near future. The mental problems of nursing practitioners and social workers are the main research topics. However, it is noted that this field is at an initial stage because limited research focusing on the association of CF with PR has been conducted, which is especially in developing countries. As an emerging research topic, scarce studies have focused on how to effectively prevent and relieve CF. Therefore, further studies and more collaborations among institutions and authors should be encouraged to explore effective interventions for the cultivation of PR and the reduction of CF.This was the first study to analyze the scientific output of research on the association of CF with PR using bibliometric analysis with CiteSpaceThe original contributions presented in the study are included in the article/L-JY, YL, LT, XT, and MJ-H: conception and design. LC, XT, and MJ-H: administrative support. L-JY, YL, LT, and G-HW: collection and assembly of data. L-JY, G-HW, and S-WH: data analysis and interpretation. All authors wrote and approved the final manuscript.The views expressed in this review come from the authors alone.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Amblyomma sculptum is a hard tick that is associated with domestic animals and the transmission of Brazilian spotted fever. This association has motivated several field studies on this ixodid tick within its distribution area in South America. Thorough knowledge of the seasonal dynamics of A. sculptum in different ecological scenarios is required in order to better understand the biological characteristics of this tick and develop techniques for the control and prevention of diseases transmitted by this vector. In this article, we systematically review the seasonal dynamics of A. sculptum and tick collection methodology.A. sculptum. The inclusion criterion was the report of seasonal dynamic studies on A. sculptum through surveys carried out for at least 1 year with, as methodology, tick collection in the environment and/or tick count/collection on A. sculptum primary hosts (horses or capybaras). Studies carried out before the reclassification of Amblyomma cajennense sensu lato in 2014, which referred to Amblyomma cajennense in areas where it is currently known that only A. sculptum occurs, were also included. Articles meeting the inclusion criterion, but not available in online databases, were also added based on the authors’ experience on the subject. Sixteen articles and one thesis were selected for inclusion in this systematic review.A systematic search of the Scopus, Web of Science, PubMed and Scielo databases was carried out for articles (including dissertations and theses) on the population dynamics of 2 traps, dragging, flagging, visual searches and tick counting on animals, used alone or in combination.Most of the studies were carried out in the southeastern region of Brazil, with a few also carried out in the northeast, center-west and south of Brazil and northwest of Argentina. Five techniques/methods were applied across these studies: COA. sculptum was found to be similar in almost all of the areas studied, with larvae predominating during the autumn, nymphs in the winter and adults in the spring and summer.Seasonal dynamics of The online version contains supplementary material available at 10.1186/s13071-022-05311-w. Amblyomma sculptum Berlese, 1888, is a hard tick belonging to the Amblyomma cajennense species complex, alongside Amblyomma cajennense sensu stricto , Amblyomma interandinum Beati, Nava and Cáceres, 2014, Amblyomma mixtum Koch, 1844, Amblyomma patinoi Labruna, Nava and Beati, 2014 and Amblyomma tonelliae Nava, Beati and Labruna, 2014 [A. sculptum are considered to be aggressive towards humans [Rickettsia rickettsii, the agent of Brazilian spotted fever (BSF), a major tick-borne zoonosis in Brazil [Amblyomma sculptum is distributed over large areas in South America, currently encompassing the entire Cerrado and Pantanal biomes and a large part of the devastated Atlantic forest biome in Brazil [Theileria equi to horses [.s humans , 4 and hn Brazil , 6. AmblA. sculptum in animals and in the environment.Encounters between hosts and ticks, and consequently the transmission of pathogens, is influenced by tick behaviors , 10. TheA. sculptum, the aim of the present study was to assemble all accessible information published on this topic.In the context of the numerous studies that have been conducted on the seasonal dynamics of A. sculptum was conducted, with the Scopus, Web of Science, PubMed and Scielo databases searched for relevant articles (including dissertations and theses). These databases were chosen because they are among the largest and most prominent databases for indexing abstracts of scientific articles and because of the quality of the journals indexed on these platforms. The search of these databases was performed using the following keywords: tick species name (Amblyomma cajennense or Amblyomma sculptum) AND “seasonal dynamics”; articles in Spanish, English and Portuguese were considered.A systematic review of articles on the population dynamics of A. sculptum through surveys carried out for at least 1 year and that had as methodology tick collection in the environment and/or tick count/collection on A. sculptum primary hosts . Studies carried out before the reclassification of Amblyomma cajennense sensu lato in 2014, which referred to A. cajennense in areas where it is currently known that only A. sculptum occurs [The inclusion criterion was articles that reported on seasonal dynamic studies on Data from each article were compiled into an Excel® spreadsheet , in which the following parameters were recorded: authors; year(s) of tick collections; location; state/country and coordinates; biome; duration and frequency of collections; methods used for tick capture; stages collected; months during which each stage was collected; months in which peaks occurred for each stage; animals found at and near each location where collections took place; and whether the study site had any confirmed cases of BSF or any tick-borne rickettsia until the time the study was concluded.A. sculptum distribution and the locations of the seasonal dynamic studies were produced using the QGIS software [A. sculptum distribution had been compiled into the Microsoft Excel® spreadsheet. An image illustrating the ticks’ life-cycle was drawn up using Adobe Illustrator [Maps showing software . These mustrator . Informaustrator  of everyA. sculptum has been confirmed in Bolivia, Brazil, Paraguay and Argentina , capybaras (Hydrochoerus hydrochaeris) and tapirs (Tapirus terrestris) are considered to be the most common primary hosts of all parasitic stages of A. sculptum in Brazil [Pecari tajacu, Tayassu pecari), anteaters , armadillos , feral and domestic pigs (Sus scrofa), carnivores , monkeys (Alouatta guariba), omnivores , rodents , deer , reptiles , birds  and cattle  have been reported to be infested by adults and nymphs [A. sculptum in the environment. Interestingly, although cattle have been considered to be major hosts for members of the A. cajennense species complex  in other South American countries [A. sculptum populations [g humans , 4. Althn Brazil , 4  of the seasonal dynamic studies were near to or in areas with notified or confirmed cases of human rickettsiosis, or with confirmed circulation of p. Table . Moreoveó et al.  and Garcó et al.  publisheó et al.  and betwó et al. .A. sculptum in two biomes that are very widely scattered throughout South America and encompass a large portion of Brazil [Amblyomma sculptum has even been found in degraded areas of the Atlantic Forest biome with abiotic conditions closer to those of the Cerrado (savanna) biome [Of the 17 studies, eight (47.0%) were conducted in areas of tropical and subtropical moist broadleaf forest biome and eight (47.0%) were conducted in areas of tropical and subtropical savanna grassland biome; one (5.9%) was conducted in areas of both biomes Fig. . These cf Brazil . Amblyoma) biome , suggest2) traps, flagging, dragging, tick counting on animals and visual searches, were used separately or simultaneously to determine the seasonal dynamics of A. sculptum.In the 17 studies, various methodologies, including carbon dioxide , as was done in most of the published studies included in this review  can be captured by techniques known as drag or flag sampling using a white cloth [A. sculptum [Free-living active stages of te cloth . Severalsculptum –40, 43  [2 is considered to be a universal attractant for hematophagous insects and is efficient for attracting A. sculptum ticks [Traps using COd traps)  are commum ticks , 35. Whium ticks , 32, 34.um ticks , Szabó eum ticks , Toledo um ticks , Guedes um ticks , Brites-um ticks , Szabó eum ticks , Barbierum ticks   of the studies, the same proportion as cloth dragging. Although highly efficient, CO2 traps have proved to be expensive and troublesome, especially because of lack of availability in smaller cities and rural areas and because of problems regarding their transportation, storage and durability.In comparing visual searches, COs et al.  describeAmblyomma sculptum is a three-host tick . Visual searches are more effective for detecting adult stages, which are easier to notice than the smaller stages. However, the efficacy of visual searches is extremely dependent on the observer’s attention and knowledge of where on the vegetation, and how high, they should inspect.While visual searches are by far the simplest and most inexpensive method for collecting 2 traps (dry ice) for collecting larvae, nymphs and adults of A. sculptum, and concluded that dragging was more efficient for capturing larvae, whereas CO2 traps were more efficient for capturing nymphs and adults. This author argued that these results were related to the limited horizontal active displacement of larvae (i.e. difficult to reach a CO2 trap) while the large size of post-larval stages  accounted for the lower efficiency of dragging. Specifically, many captured specimens were dislodged from the white cloth in contact with vegetation during flagging before the white cloth was checked by the researcher.Oliveira  compared2 traps, dragging and plant litter examination were compared in another study in an area with A. sculptum predominance [2 traps, since 64.7% (11/17) of the studies used cloth dragging.Visual search for ticks on vegetation, COominance , in whicA. sculptum must always consider the environmental preferences of this tick species. Labruna [A. sculptum [A. sculptum found in forest patches than in nearby marshy areas. Barbieri et al. [A. sculptum showed a preference for environments with monthly average temperatures mostly raging between 21 ºC and 27 ºC. Ten (58.8%) of the seasonal dynamic studies were conducted in locations in farm pastures, six (35.3%) in nature reserves and/or nature parks; the authors of one study (5.9%) did not specify the location  of the seasonal dynamic studies. This was probably due to insufficient numbers of horses in other study locations, even though horses were reported in 11 of the 17 (64.7%) studies. Moreover, although tick counting on other hosts is possible, it becomes unfeasible due to the difficulty and costs of capturing, containing and handling wild animals, especially other primary hosts species, such as capybaras and tapirs.A. sculptum completes one generation per year. Although all three parasitic stages are generally found throughout the year, seasonal preferences are demonstrated, depending on the climatic characteristics of each region. Also, despite the similar results that have been found between the southern, southeastern and central-western regions of Brazil and the distinct results from the northeastern region, as discussed below, the seasonal dynamics of this tick species should be related to distinct latitudes (i.e. distinct photoperiod range throughout the year) and differences in seasonal weather patterns. For example, all studies in the southern, southeastern and central-western regions were from areas characterized by a cool and dry winter, and a hot and rainy summer, in contrast to the single study in the northeastern region [Overall, the studies carried out over the last two decades have all reported the conclusion that n region  where thA. sculptum referred to A. cajennense. In addition, since there is no taxonomic key for Brazilian Amblyomma larvae, larvae were identified only to the genus level [A. sculptum only after 2014 [Amblyomma spp. without identification to the species level.It is important to note that up until 2014, published studies on us level . Nymphs us level , 61 and ter 2014 –62. TherA. sculptum, among which a few consisted of tick counting on horses [While different methodologies were applied in these seasonal studies on n horses , 29, 43,It can also be noted that the use of a combination of different sampling methods can potentially increase the number of ticks counted during a study period, as seen in de Paula et al. , who repLarvae are most commonly found in slightly higher quantities between April and November, as shown in Additional file Two types of diapause have been described in ticks: behavioral and morphogenic. The former consists of suppression of host-seeking activity in unfed stages or host feeding on hosts; the latter consists of delayed embryogenesis, metamorphosis of larvae and nymphs, or oogenesis of engorged females .A. sculptum larvae (published as A. cajennense) in Brazil [A. sculptum in southeastern Brazil, as demonstrated by Labruna et al. [Behavioral diapause has been described for n Brazil , 65. In n Brazil . In all The results of one study differed from those of the other studies. Dantas-Torres et al.  showed lHigher numbers of nymphal activity were mostly reported to occur from May to November, only a few weeks after the increase in the quantities of larvae  occurs during the second semester of year, especially during midwinter to spring [A. sculptum is the most important stage for transmitting R. rickettsii to humans, emphasizing the need to expand surveillance measures during the months of nymph abundance. It is noteworthy that in a 2-year study on human parasitism during a survey on ticks in a reserve of the Brazilian savanna [A. sculptum nymphs were the most abundant and the ticks most frequently biting humans.It has been observed for decades that most of the human cases of tick-borne rickettsiosis  [A. mixtum showed a longer period of larval and nymphal activity during the year [A similar seasonal pattern has been described for other onelliae  and A. mennense) . These lthe year .A. sculptum, encompassing various environments where this tick is found, both in preserved areas as well as those anthropized. Thus, much important information on this subject has been surveyed. Despite the differences in rainfall volumes, temperature, seasonal characteristics, distribution and availability of hosts and phytophysiognomy in these studies, A. sculptum always presented a one-generation-per-year cycle. Given this tick’s wide distribution, further studies carried out in unexplored areas is necessary to fully describe its seasonal and ecological profiles, especially in northeastern Brazil, where photoperiod variations are less evident throughout the year.It is evident that several major studies have already been conducted on the populational and seasonal dynamics of Additional file 1: Table S1. Additional data on collection methodology applied by Amblyomma sculptum seasonal dynamic studies between 1990 and 2022.Additional file 2: Table S2. Results from Amblyomma sculptum seasonal dynamic studies between 1990 and 2022 and mean photoperiod (PP: daylight length in hours) at the time of highest availability of each active stage.


Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium were significantly correlated with HAMD and CTQ-SF scores. The mediation analysis showed that childhood maltreatment had a significant direct effect on the patients’ depressive symptoms, and Blautia, Bifidobacterium, Roseburia had a significant mediating effect. The findings of this study suggested that MDD patients with childhood maltreatment experience had different gut microbiota, which might have a mediating effect on the influence of childhood maltreatment on depressive symptoms.Gut microbiota and childhood maltreatment are closely related to depressive symptoms. This study aimed to analyze the characteristics of gut microbiota in major depressive disorder (MDD) patients with childhood maltreatment experience and explore the correlation between gut microbiota, childhood maltreatment, and depressive symptoms. A total of 37 healthy controls (HCs) and 53 patients with MDD were enrolled, including 18 MDD patients without childhood maltreatment experience and 35 MDD patients with childhood maltreatment experience. The Hamilton’s Depression Scale (HAMD-24) and Childhood Trauma Questionnaire-Short Form (CTQ-SF) were used to evaluate their depressive symptoms and childhood maltreatment experience, respectively. The composition of gut microbiota was evaluated using 16S rRNA sequencing. Spearman’s correlation analysis was used to evaluate the correlation between different gut microbiota, depressive symptoms and childhood maltreatment. The mediation analysis was used to evaluate the mediating effect of gut microbiota. In the α-diversity analysis, we found that the Simpson index and Pielou’s Evenness index differed significantly between MDD patients without childhood maltreatment experience and HCs. In the β-diversity analysis, principal coordinate analysis (PCoA) showed significant differences between MDD patients without childhood maltreatment experience, MDD patients with childhood maltreatment experience and HCs. Twenty-seven different bacteria were identified through Linear discriminant analysis effect size (LEfSe) analysis at different levels of classification. The analysis of the correlation showed that  According to recent epidemiological studies, approximately 310 million people worldwide suffered from depression,1 , and mor1 , including 53 first-episode drug-naïve MDD patients and 37 HCs, were recruited from the First Hospital of Shanxi Medical University. The MDD patients who had not experienced child maltreatment were assigned into a group marked as CTQ0, and the MDD patients who had experienced child maltreatment were assigned into a group marked as CTQ1. All the patients met the criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). Hamilton Depression Scale-24 (HAMD-24) was used to measure the severity of depression, and the HAMD score of all MDD patients was greater than 20. The patients also completed the CTQ-SF  to assesThis study was approved by the Ethics Committee of the First Hospital of Shanxi Medical University. All participants provided written consent after provided with detailed information about the study objectives and procedures.Childhood Trauma Questionnaire-Short Form  is an inAfter the completion of the HAMD-24 and CTQ-SF assessments, we collected a total of 90 fecal samples. To ensure that the samples were not contaminated, the stool was collected from the middle using plastic cups. The specimens were sent to the laboratory within 15 min and immediately stored in a refrigerator at −80°C until analysis.Total DNA was extracted from the stool specimens using the Stool Mini Kit . The purity and integrity of DNA were analyzed using 1% agarose gel electrophoresis and the concentration of DNA was quantified. The total DNA was stored in the refrigerator at −20°C until the next analysis.In order to amplify the bacterial 16S rRNA gene, we used 338F universal primer (5′-ACTCCTACGGGAGGCAGCAG-3′) and 806R (5′-GGACTACHVGGGTWTCTAAT-3′) to amplify V3-V4 of the bacterial 16S rRNA hypervariable region. Personal Biotechnology, Co., Ltd. Illumina MiSeq platform was used for PCR amplification, sequencing library preparation and pyrosequencing .QIIME 2 (version: 2019.1) was used for analysis, including repeated sequence removal, clustering, and chimerism removal. The sequences with 100% similarity were clustered into amplicon sequence variants (ASVs). Based on the Greengenes Database, the representative sequences were annotated, and the community composition of each specimen was counted at the classification level. The abundance and classification of all ASVs were recorded for each specimen.P < 0.05.The QIIME 2 (version: 2019.1) and SPSS software (version 23.0) were used for data analyses. The QIIME 2 software was used to calculate α-diversity and β-diversity. The α-diversity analysis included Chao1, Faith’s PD, Good’s coverage, Shannon, Simpson, Pielou’s evenness and Observed species indices, while for the β-diversity analysis, principal coordinate analysis (PCoA) based on bray_curtis was used to reveal the structural differences of bacterial communities between different groups. Linear discriminant analysis effect size (LEfSe) analysis was used to identify marker species between groups. The SPSS software was used to analyze the general demographic information and mediating effects. One-way analysis of variance (ANOVA) was used to compare the age, years of education, and body mass index (BMI) between the three groups, and the χ2 test was used to for the comparison of gender distribution. Correlations between gut microbiota, HAMD-24, and CTQ-SF were calculated using Spearman’s rank-correlation analysis. The mediation effect was analyzed using the Process software. For all analyses, the threshold of statistical significance was set at P = 0.888), gender (P = 0.367), BMI (P = 0.625) and years of education (P = 0.714), and the scores of HAMD-24 and CTQ-SF were significantly higher among patients with MDD as compared to HCs (P < 0.01).The demographic information and clinical characteristics of the patients with MDD and HCs are presented in P < 0.05), while no significant differences were found in other indicators between the three groups  and between HCs and the CTQ1 group (P < 0.001). However, no statistical difference was found between the CTQ0 and CTQ1 groups, as shown in To explore the differences in the comprehensive microbial phenotypes between HCs, the CTQ0 group and the CTQ1 group, we performed β-diversity analysis. Significant differences were found between the HCs and the CTQ0 group  analysis was used to identify differences in species and marker species of the three groups. At the family level, the abundance of the  the HCs .Blautia and Bifidobacterium were significantly positively correlated with HAMD-24 and CTQ-SF, Roseburia, Bacteroides, and Phascolarctobacterium were significantly negatively correlated with HAMD-24 and CTQ-SF , with the value of direct effect being 0.4401 (To further explore the mediating effect of gut microbiota, we constructed a mediation model, with the CTQ-SF score as the independent variable, HAMD-24 scale as the dependent variable, and Blautia, Bifidobacterium, Bacteroides, Roseburia, and Phascolarctobacterium as intermediate variables . The resg 0.4401 . The gutIt is well recognized that the experience of childhood maltreatment is strongly associated with depressive symptoms. However, the specific mechanism through which depression is affected by childhood maltreatment still remains understudied. Through years of in-depth study of gut microbiota, it has been found that the disturbance of gut microbiota is closely related to the pathogenesis of depression. In this study, we explored the relationship between child maltreatment, gut microbiota, and MDD. And the result showed that experience of childhood maltreatment might affect depressive symptoms through gut microbiota.Childhood maltreatment was recognized as a risk factor for the development and maintenance of depression and was associated with increased risk of suicidal behavior . A studyAccording to many previous studies, patients with MDD are highly likely to have gut microbiota disorders. In this study, the α-diversity analysis showed that Simpson index and Pielou’s evenness index of HCs were significantly higher than those of MDD patients without experience of childhood maltreatment, suggesting that patients with MDD might have a lower diversity of gut microbiota than HCs. This finding was inconsistent with the results from the study by The results obtained from animal models of early stress showed a significant difference in fecal microbiota between animals with and without early stress as well as affected homeostasis of gut microbiota in animals that had experienced early stress . In our Actinobacteria and Enterobacteriaceae was higher than that in HCs. This is consistent with the findings of Bifidobacterium was higher than that in HCs and MDD patients without childhood maltreatment experience. Similar to the study of Bifidobacterium accumulated in depressed patients. Although many studies discussed whether probiotics could improve stress and mood, no significant findings have been found (Bifidobacterium might be associated with stress in patients with depression. Therefore, the relationship between Bifidobacterium, depression and childhood maltreatment needs to be further studied.In the present study, we found that, in MDD patients without childhood maltreatment experience, the abundance of the en found . AccordiBacteroidetes, Oscillibacter, and Alistipes were significantly associated with depression. In the present study, we found that Blautia and Bifidobacterium were significantly positively correlated with depressive symptoms, while Roseburia, Bacteroides, and Phascolarctobacterium were significantly negatively correlated with depressive symptoms, indicating that our results are consistent with the findings in the previous study. In addition, we found that Blautia and Bifidobacterium were significantly positively correlated not only with depressive symptoms, but also with child maltreatment, and that Roseburia, Bacteroides, and Phascolarctobacterium were significantly negatively correlated with depressive symptoms and child maltreatment. To our knowledge, these findings in our study have not been reported before.A study  analyzinMany studies have demonstrated the link between intestinal homeostasis and depressive symptoms. Some studies found a causal relationship between disturbance of gut microbiota and depressive symptoms using germ-free animal models, microbiota transplantation  and targBlautia, Bifidobacterium, and Roseburia had significant indirect effect.Some studies used rejection, core self-evaluation and parent-child relationship as mediators to explain the relationship between child maltreatment and depressive symptoms . HoweverBlautia, Bifidobacterium, and Roseburia have potential probiotic properties (Several studies have shown that operties . Howeveroperties , geograpoperties , diet, goperties ; on the Despite the findings and strengths of our study, some limitations should be mentioned. First, the sample size of this study is small, which might have affected the accuracy of the results. Secondly, the data of childhood maltreatment were obtained through patient inquiry, meaning that the subjects needed to recall their memories before the age of 16, which might have introduced memory bias. This, to some extent, could be addressed by recording the subtypes of child maltreatment for patients with MDD. Moreover, we used the 16S RNA sequencing method to assess gut microbiota of participants, which might not be able reach the accuracy level for those species. Finally, certain environmental factors that are difficult to control, such as diet, might have affected the gut microbiota. In future works, inclusion and exclusion criteria can be more strictly controlled to rule out the interference of environmental factors.The present study suggested that the gut microbiota of MDD patients with childhood maltreatment experience is different from that of HCs, and that the effect of childhood maltreatment on depressive symptoms might be exerted through gut microbiota and other pathways, such as genetics, immune, endocrine, etc., which can be investigated in further studies.PRJNA830325.Publicly available datasets were analyzed in this study. This data can be found on NCBI with accession number: The studies involving human participants were reviewed and approved by the Ethics Committee of the First Hospital of Shanxi Medical University. The patients/participants provided their written informed consent to participate in this study.NS and YuZ designed the experiments. NS, RZ, PL, MG, JY, and CY participated in the collection of clinical data and stool samples of all subjects. JW and YaZ processed the stool samples. YaZ analyzed the data and wrote the manuscript. All authors contributed to the clinical data collection and assessment.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Several statistical parameters are also used as metrics to evaluate the performance of implemented models, such as coefficient of determination (R2), mean absolute error (MAE), and mean of squared error (MSE). Among different ML algorithms, convolutional neural network (CNN) with R2 = 0.928, RMSE = 5.043, and MAE = 3.833 shows higher accuracy. On the other hand, K-nearest neighbor (KNN) algorithm with R2 = 0.881, RMSE = 6.477, and MAE = 4.648 results in the weakest performance.Adding hooked industrial steel fibers (ISF) to concrete boosts its tensile and flexural strength. However, the understanding of ISF’s influence on the compressive strength (CS) behavior of concrete is still questioned by the scientific society. The presented paper aims to use machine learning (ML) and deep learning (DL) algorithms to predict the CS of steel fiber reinforced concrete (SFRC) incorporating hooked ISF based on the data collected from the open literature. Accordingly, 176 sets of data are collected from different journals and conference papers. Based upon the initial sensitivity analysis, the most influential parameters like water-to-cement (W/C) ratio and content of fine aggregates (FA) tend to decrease the CS of SFRC. Meanwhile, the CS of SFRC could be enhanced by increasing the amount of superplasticizer (SP), fly ash, and cement (C). The least contributing factors include the maximum size of aggregates (D ML techniques have been effectively implemented in several industries, including medical and biomedical equipment, entertainment, finance, and engineering applications. ML can be used in civil engineering in various fields such as infrastructure development, structural health monitoring, and predicting the mechanical properties of materials. More specifically, numerous studies have been conducted to predict the properties of concrete8. Until now, fibers have been used mainly to improve the behavior of structural elements for serviceability purposes. However, the addition of ISF into the concrete and producing the SFRC may also provide additional strength capacity or act as the primary reinforcement in structural elements. Nowadays, For the production of prefabricated and in-situ concrete structures, SFRC is gaining acceptance such as (a) secondary reinforcement for temporary load scenarios, arresting shrinkage cracks, limiting micro-cracks occurring during transportation or installation of precast members (like tunnel lining segments), (b) partial substitution of the conventional reinforcement, i.e., hybrid reinforcement systems, and (c) total replacement of the typical reinforcement in compression-exposed elements, e.g., thin-shell structures, ground-supported slabs, foundations, and tunnel linings9. Unquestionably, one of the barriers preventing the use of fibers in structural applications has been the difficulty in calculating the FRC properties  that should be included in current design techniques10.One of the drawbacks of concrete as a fragile material is its low tensile strength and strain capacity. Hence, various types of fibers are added to increase the tensile load-bearing capability of concrete. To generate fiber-reinforced concrete (FRC), used fibers are typically short, discontinuous, and randomly dispersed throughout the concrete matrix11 reported that the length of the ISF (LISF) has an insignificant effect on the CS of SFRC. Setti et al.12 also introduced ISF with different volume fractions (VISF) to the concrete and reported the improvement of CS of SFRC by increasing the content of ISF. Zhu et al.13 noticed a linearly increase of CS by increasing VISF from 0 to 2.0%. Despite the enhancement of CS of normal strength concrete incorporating ISF, no significant change of CS is obtained for high-performance concrete mixes by increasing VISF15. This highlights the role of other mix’s components  on CS behavior of SFRC. Therefore, owing to the difficulty of CS prediction through linear or nonlinear regression analysis, data-driven models are put into practice for accurate CS prediction of SFRC.Accordingly, many experimental studies were conducted to investigate the CS of SFRC. Han et al.17 have been conducted for predicting the mechanical properties of normal concrete (NC). Evidently, SFRC comprises a bigger number of components than NC including LISF, L/DISF, fiber type, diameter of ISF (DISF) and the tensile strength of ISFs. In this regard, developing the data-driven models to predict the CS of SFRC is a comparatively novel approach. Kang et al.18 collected a datasets containing 7 features (VISF and L/DISF as the properties of fibers) and developed 11 various ML techniques and observed that the tree-based models had the best performance in predicting the CS of SFRC. Also, it was concluded that the W/C ratio and silica fume content had the most impact on the CS of SFRC. Mahesh et al.19 used ML algorithms on a 140-raw dataset considering 8 different features  and concluded that the artificial neural network (ANN) had the best performance in predicting the CS of SFRC with a regression coefficient of 0.97. Moreover, in a study conducted by Awolusi et al.20 only 3 features (L/DISF as the fiber properties) were considered, and ANN and the genetic algorithm models were implemented to predict the CS of SFRC. It was observed that overall, the ANN model outperformed the genetic algorithm in predicting the CS of SFRC.Recently, ML algorithms have been widely used to predict the CS of concrete. For instance, numerous studiesAccording to the presented literature, the scientific community is still uncertain about the CS behavior of SFRC. In addition, the studies based on ML techniques that have been done to predict the CS of SFRC are limited since it is difficult to collect inclusive experimental data to develop models regarding all contributing features . Hence, the presented study aims to compare various ML algorithms for CS prediction of SFRC based on all the influential parameters. For this purpose, 176 experimental data containing 11 features of SFRC are gathered from different journal papers. The primary sensitivity analysis is conducted to determine the most important features. Therefore, based on expert opinion and primary sensitivity analysis, two features (length and tensile strength of ISF) were omitted and only nine features were left for training the models. Then, nine well received ML algorithms are developed on the data and different metrics were used to evaluate the performance of these algorithms. Also, to prevent overfitting, the leave-one-out cross-validation method (LOOCV) is implemented, and 8 different metrics are used to assess the efficiency of developed models.33. Some of the mixes were eliminated due to comprising recycled steel fibers or the other types of ISFs (such as smooth and wavy). Moreover, some others were omitted because of lacking the information of mixing components . Eventually, 63 mixes were omitted and 176 mixes were selected for training the models in predicting the CS of SFRC. All these mixes had some features such as DMAX, the amount of ISF (ISF), L/DISF, C, W/C ratio, coarse aggregate (CA), FA, SP, and fly ash as input parameters (9 features). Also, the CS of SFRC was considered as the only output parameter.The SFRC mixes containing hooked ISF and their 28-day CS (tested by 150 mm cubic samples) were collected from the literatureThe correlation of all parameters with each other (pairwise correlation) can be seen in Fig. The correlation coefficient . The same results are also reported by Kang et al.18.As can be seen in Fig. Statistical characteristics of input parameters, including the minimum, maximum, average, and standard deviation (SD) values of each parameter, can be observed in Table 34. Normalization is a data preparation technique that converts the values in the dataset into a standard scale. It is essential to note that, normalization generally speeds up learning and leads to faster convergence. consequently, the max–min normalization method is adopted to reshape all datasets to a range from According to Table entclass1pt{minima37, several metrics were used to sufficiently evaluate the performed models and compare their robustness. Accordingly, several statistical parameters such as R2, MSE, mean absolute percentage error (MAPE), root mean squared error (RMSE), average bias error (MBE), t-statistic test (Tstat), and scatter index (SI) were used. R2 is a metric that demonstrates how well a model predicts the value of a dependent variable and how well the model fits the data. Various orders of marked and unmarked errors in predictions are demonstrated by MSE, RMSE, MAE, and MBE6. MAPE is a scale-independent measure that is used to evaluate the accuracy of algorithms. TStat and SI are the non-dimensional measures that capture uncertainty levels in the step of prediction. SI is a standard error measurement, whose smaller values indicate superior model performance. Evaluation metrics can be seen in Table In some studiesTo avoid overfitting, the dataset was split into train and test sets, with 80% of the data used for training the model and 20% for testing. Also, a specific type of cross-validation (CV) algorithm named LOOCV Fig.  was usedAs can be seen in Table 39. MLR predicts the value of the dependent variable  is used. In SVR, 18.SVR model  or classification  problems. In the current research, tree-based models  were used to predict the CS of SFRC. Among these techniques, AdaBoost is the most straightforward boosting algorithm that is based on the idea that a very accurate prediction rule can be made by combining a lot of less accurate regulations45. The brain’s functioning is utilized as a foundation for the development of ANN6. ANN can be used to model complicated patterns and predict problems. ANN model consists of neurons, weights, and activation functions18. the input values are weighted and summed using Eq. . Adam was selected as the optimizer function with a learning rate of 0.01. It is essential to point out that the MSE approach was used as a loss function throughout the optimization process. Table The use of an ANN algorithm Fig.  as a pow49. CNN model is a new architecture for DL which is comprised of several layers that process and transform an input to produce an output. In the current study, the architecture used was made up of a one-dimensional convolutional layer, a one-dimensional maximum pooling layer, a one-dimensional average pooling layer, and a fully-connected layer. Moreover, the ReLU was used as the activation function for each convolutional layer and the Adam function was employed as an optimizer. Table In recent years, CNN algorithm Fig.  has beenTo adjust the validation set’s hyperparameters, random search and grid search algorithms were used. Table The CS of SFRC was predicted through various ML techniques as is described in section "2 of 0.888, RMSE of 6.301, and MAE of 5.317. Al-Abdaly et al.50 reported that MLR algorithm  performed poorly in predicting the CS behavior of SFRC. Khademi et al.51 used MLR to predict the CS of NC and found that it cannot be considered an accurate model (with R2 = 0.518). Moreover, according to the results reported by Kang et al.18, it was shown that using MLR led to a significant difference between actual and predicted values for prediction of SFRC’s CS . Hameed et al.52 developed an MLR model to predict the CS of high-performance concrete (HPC) and noted that MLR had a poor correlation between the actual and predicted CS of HPC . Therefore, based on MLR performance in the prediction CS of SFRC and consistency with previous studies , it was suggested that, due to the complexity of the correlation between the CS and concrete mix properties, linear models (such as MLR) could not explain the complicated relationship among independent variables. So, more complex ML models such as KNN, SVR tree-based models, ANN, and CNN were proposed and implemented to study the CS of SFRC.As the simplest ML technique, MLR was implemented to predict the CS of SFRC and showed R2 = 0.881, RMSE = 6.477, MAE = 4.648) showed lower accuracy compared with MLR in predicting the CS of SFRC. Kang et al.18 observed that KNN predicted the CS of SFRC with a great difference between actual and predicted values. Asadi et al.6 also reported that KNN performed poorly in predicting the CS of concrete containing waste marble powder. Moreover, the CS of rubberized concrete was predicted using KNN algorithm by Hadzima-Nyarko et al.53, and it was reported that KNN might not be appropriate for estimating the CS of concrete containing waste rubber . Therefore, according to the KNN results in predicting the CS of SFRC and compatibility with previous studies (in using the KNN in predicting the CS of various concrete types), it was observed that like MLR, KNN technique could not perform promisingly in predicting the CS of SFRC. This can refer to the fact that KNN considers all characteristics equally, even if they all contribute differently to the CS of concrete6.KNN . Also, a significant difference between actual and predicted values was reported by Kang et al.18 in predicting the CS of SFRC (RMSE = 18.024). For the prediction of CS behavior of NC, Kabirvu et al.5 implemented SVR, and observed that SVR showed high accuracy (with R2 = 0.97). Whereas, Koya et al.39 and Li et al.54 reported that SVR showed a high difference between experimental and anticipated values in predicting the CS of NC. Based on the results obtained from the implementation of SVR in predicting the CS of SFRC and outcomes from previous studies in using the SVR to predict the CS of NC and SFRC, it was concluded that in some research, SVR demonstrated acceptable performance. In contrast, others reported that SVR showed weak performance in predicting the CS of concrete. This can be due to the difference in the number of input parameters.Compared to the previous ML algorithms (MLR and KNN), SVR’s performance was better  and XGB  were the weakest and strongest models in predicting the CS of SFRC, respectively. As is reported by Kang et al.18, among implemented tree-based models, XGB performed superiorly in predicting the CS of SFRC. Al-Abdaly et al.50 also reported that RF  performed better than MLR  in predicting the CS of SFRC. Khan et al.55 also reported that RF  showed more acceptable outcomes than XGB and GB with, an R2 of 0.9 and 0.95 in the prediction CS of SFRC, respectively. Moreover, Nguyen-Sy et al.56 and Rathakrishnan et al.57, after implementing the XGB, noted that the XGB was the best model for predicting the CS of NC. Therefore, based on tree-based technique outcomes in predicting the CS of SFRC and compatibility with previous studies in using tree-based models for predicting the CS of various concrete types (SFRC and NC), it was concluded that tree-based models  showed good performance.Based upon the results in this study, tree-based models performed worse than SVR in predicting the CS of SFRC. However, it is worth noting that their performance in predicting the CS of SFRC was superior to that of KNN and MLR. Among these tree-based models, AdaBoost  performed better than MLR, KNN, and tree-based models (except XGB) in predicting the CS of SFRC, but its accuracy was lower than the SVR and XGB  techniques. Mahesh et al.19 noted that after tuning the model , ANN showed superior performance in predicting the CS of SFRC (R2 = 0.95). Karahan et al.58 implemented ANN with the Levenberg–Marquardt variant as the backpropagation learning algorithm and reported that ANN predicted the CS of SFRC accurately (R2 = 0.96). Asadi et al.6 also used ANN in estimating the CS of NC containing waste marble powder (LOOCV was used to tune the hyperparameters) and reported that in the validation set, ANN was unable to reach an R2 as high as GB and XGB. However, ANN performed accurately in predicting the CS of NC incorporating waste marble powder (R2 = 0.97) in the test set. Finally, it is observed that ANN performs weaker than SVR and XGB in terms of R2 in the validation set due to the non-convexity of the multilayer perceptron's loss surface. Consequently, it is frequently required to locate a local maximum near the global minimum59. Hence, After each model training session, hold-out sample generalization may be poor, which reduces the R2 on the validation set 6. However, it is suggested that ANN can be utilized to predict the CS of SFRC.It was observed that ANN  demonstrated superior performance in predicting the CS of SFRC. In comparison to the other discussed methods, CNN was able to accurately predict the CS of SFRC with a significantly reduced dispersion degree in the figures displaying the relationship between actual and expected CS of SFRC. Using CNN modelling, Chen et al.34 reported that CNN could show excellent performance in predicting the CS of the SFRS and NC. Deng et al.47 also observed that CNN was better at predicting the CS of recycled concrete (average relative error = 3.65) than other methods. Finally, results from the CNN technique were consistent with the previous studies, and CNN performed efficiently in predicting the CS of SFRC.Eventually, among all developed ML algorithms, CNN  have a minor effect on the CS of SFRC. Li et al.54 noted that the CS of SFRC increased with increasing amounts of C and silica fume, and decreased with increasing amounts of water and SP. Therefore, based on the sensitivity analysis, the ML algorithms for predicting the CS of SFRC can be deemed reasonable.The sensitivity analysis investigates the importance's magnitude of input parameters regarding the output parameter. The feature importance of the ML algorithms was compared in Fig. 60 did. The result of this analysis can be seen in Fig. A parametric analysis was carried out to determine how well the developed ML algorithms can predict the effect of various input parameters on the CS behavior of SFRC. To perform the parametric analysis to analyze the influence of one specific parameter  on the predicted CS of SFRC, the actual values of that parameter (W/C ratio) were considered, while the mean values for all the other input parameters values were introduced. The implemented procedure was repeated for other parameters as well, considering the three best-performed algorithms, which are SVR, XGB, and ANN. This method has also been used in other research works like the one Khan et al.As shown in Fig. In addition, Fig. However, it is depicted that the weak correlation between the amount of ISF in the SFRC mix and the predicted CS. This indicates that the CS of SFRC cannot be predicted by only the amount of ISF in the mix. In other words, in CS prediction of SFRC, all the mixes’ components must be presented .The impact of the fly-ash on the predicted CS of SFRC can be seen in Fig. MAX, L/DISF, and CA have relatively little effect on the CS. Moreover, the results show that increasing the amount of FA causes a decrease in the CS of SFRC , followed by SVR . In contrast, KNN  showed the weakest performance in predicting the CS of SFRC.Among the several ML techniques used in this research, CNN attained superior performance . Also, C, DAccording to the results obtained from parametric analysis, among the developed models, SVR can accurately predict the impact of W/C ratio, SP, and fly-ash on the CS of SFRC, followed by CNN.This study modeled and predicted the CS of SFRC using several ML algorithms such as MLR, tree-based models, SVR, KNN, ANN, and CNN. From the open literature, a dataset was collected that included 176 different concrete compressive test sets. This research leads to the following conclusions:


Plasmodium falciparum -infected mosquitoes with a present scale of symptoms ranging from moderate fever to neurological disorders. P. falciparum is the most lethal of the five strains of malaria, and is a major case of morbidity and mortality in endemic regions. Recent advancements in malaria diagnostic tools and prevention strategies have improved conjugation antimalarial therapies using fumigation and long-lasting insecticidal sprays, thus lowering malarial infections. Declines in the total number of infected individuals have been correlated with antimalarial drugs. Despite this, malaria remains a major health threat, affecting more than 30 million men, women, and children around the globe, and 20 percent of all children around the globe have malaria parasites in their blood. To overcome this life-threatening condition, novel therapeutic strategies, including immunization, are urgently needed to tackle this infection around the world. In line with this, the development of the RTS, S vaccine was a significant step forward in the fight against malaria. RTS, S is a vaccine for P. falciparum in which R specifies central repeat units, T the T-cell epitopes, and S indicates surface antigen. The RTS, S/AS01 malarial vaccine was synthesized and screened in several clinical trials between 2009 and 2014, involving thousands of young children in seven African countries, showing that children who received the vaccine did not suffer from severe malaria. Mosquirix™ was approved by the World Health Organization in 2021, indicating it to be safe and advocating its integration into routine immunization programs and existing malaria control measures. This paper examines the various stages of the vaccine’s development, including the evaluation of its immunogenicity and efficacy on the basis of a total of 2.3 million administered doses through a routine immunization program. The protection and effectiveness provided by the vaccine are strong, and evidence shows that it can be effectively delivered through the routine child immunization platform. The economic cost of the vaccine remains to be considered.Malaria is a parasitic infection caused by bites from  P. falciparum remains the most lethal of all species infecting the population, and presents a huge health concern in malaria-endemic regions [Malaria is a parasitic illness mostly found in tropical and subtropical regions, and is transmitted to humans by mosquitoes. The signs and symptoms of malaria include fever, shivers, stomach pain, nausea, muscle aches, tiredness, and lethargy. The incubation period of malarial infection is 7–14 days.  regions .P. falciparum, 87% of infected individuals remain asymptomatic, and are considered to be reservoirs for infection transition as a result of the shortage of efficient diagnostic routes for malaria in endemic countries [In outbreaks of ountries . People ountries .P.falciparum; (2) specification of objectives for the study of a wide scale of strains; (3) specification of an appropriate adjuvant to stimulate immunogenicity in terms of both quantity and quality against the antigen, regardless of the effect of age [Patients suffering from acute malarial infection who do not receive proper medication and treatment have a 90% mortality rate, whereas those who receive proper treatment have a 20% mortality rate . The rist of age . In essestrains;  specificIn the world malarial report 2018, produced by WHO, it was revealed that the numbers of people affected by malaria were plateauing in 2017; there were an estimated 219 million cases of malaria, compared to 217 million in 2016 . AccordiChildren under the age of five continue to be the most vulnerable. Malaria is the leading cause of mortality in children, accounting for 61% of all malaria-related fatalities in 2017. Even though post-2010 mortality rates decreased, no serious steps have been taken to improve techniques and technologies with the aim of eradicating this disease . MalariaP. falciparum. P. vivax is a major source of illness and fatality in many parts of the globe. Malarial parasites are single-celled eukaryotes that infect a variety of insect and vertebrate taxa, including mammals and birds. The life cycle of malarial parasites begins with the growth of plasmodium in an insect species that relies on a host’s body and inserts harmful parasites into the bloodstream. Diagnostic indications of malaria develop when it causes the lysis of RBCs in the host.Of the 100 species of plasmodium, five common species are responsible for causing malarial transmission in human beings, the most prevalent and fatal of which is Plasmodium spp. is a diagnostic antigen tool used as a biomarker to control seasonal alterations in malarial infection. By applying P. vivax CSP antibody using the ELISA method, epidemiological features were studied within the populations of many affected countries during the period 2017–2018. PvCSP is a helpful antigen to detect the extant of spread of malarial infection. Since the antibody is relatively transient, it can act as sero-epidemiological factor for estimating the extent of malaria transmission in the present year [The circumsporozoite protein (CSP) extracted from ent year .P. falciparum sporozoite-stage parasites to the host. Venous circulation of blood helps them reach the host’s liver, which is where offspring are produced [Female anopheline mosquitoes transmit produced . The numproduced ,15.Pyrexia, nausea, tiredness, and lethargy are signs of the rise in cytokine levels due to the bursting of infected red blood cells (RBCs), which leads to severe malarial infection causing renal disease, jaundice, hypoglycemia, coma, and death ,17.The initial phases of malarial illness are characterized by recurrent infections and pyrexia, with a periodicity that is unique to different malarial species. The newly produced merozoites are discharged in the bloodstream throughout these periods. In addition to this, RBC infection can be of two different types: it can be an erythrocytic invasion by asexual merozoites, or an infections by male or female gametocytes that can be consumed by a mosquito during blood-feeding, which then mix in the insect’s midgut, generating diploid recombinant progeny ,19. FiguThe transmission of malarial infection is a major cause of illness and fatality, and a variety of different methods have been used for its prevention and control. Until 1600, the exact cause of malaria was not known, and “medicine men” suggested quinine as the only treatment for malaria . It was A successful malaria vaccine would be the most significant weapon in countering the disease’s massive impact on socio-economic domains. Vaccines are one of the most effective public health interventions, since they benefit everyone ,25. CompThe United Nations’ (UN) sustainable development goal #3 aims to reduce deaths and infections caused by malaria in acknowledgment of the worldwide relevance of malarial infection . AnotherAntimalarials are given to susceptible people on an intermittent basis to remove malaria-causing parasites and avoid illness. Certain other projects in the works involve mass medication distribution and bioengineered mosquitoes. The most significant task that has been performed in this regard is the research carried out on the execution of the first malarial vaccine directed by the WHO ,29,30. TP. falciparum to different species of malaria, this field of study requires further intensive research. Gene diversity is the main reason for the evasion and resistance of vaccines against diverse strains, and this was recently indicated in a study in which reduced effectiveness was demonstrated in those variants possessing heterologous sequences when compared with the pattern of the RTS, S vaccine [P. falciparum parasites and destroys them before they enter the liver, where they could develop.People, including those who have been immunized with shots of the RTS, S/AS01 vaccine, are vulnerable to repeated attacks of malarial infection due to site-specific genetic diversity. Although there is no documented immune responsiveness that linking  vaccine . The catThe first and foremost vaccine for malarial infection, which was evaluated up to phase III clinical trials to check its efficacy and efficiency, was RTS, S/AS01. The RTS, S/AS01 vaccine was also among the first to be evaluated in endemic zones in regular vaccination drives. A study, conducted upon 8922 patients with malaria, showed that administration of vaccines to children between the ages of 5 and 7 years produced a rate of 36% effective immunization against malaria. All of these children received four shots of the RTS, S/AS01 vaccine at months 0, 1, 2, and the booster shot was administrated at the age of 20 months. They were followed up for a period of four years. The registered number for this clinical trial is NCT00866619.Clinical trials upon newborns between the ages of 6 and 14 weeks showed that the vaccine’s effectiveness was even lower than the efficiency attained in children of 5–7 years. Low efficiency of RTS, S/AS01 vaccine in infants was reportedly due to the immature immune system and the intervention of maternal antibodies in neonates .In places with high endemic rates, RTS, S/AS01 was the most promising vaccine. The vaccine helps to drastically decrease the incidence of malaria, hospitalization rates, and other requirements in the treatment of infection.The RTS, S/AS01 vaccine was acknowledged by the WHO, and received a grant for further assessment and appraisal to ensure its effectiveness before including it in mass immunization. An immunization drive to evaluate the effectiveness of the vaccine was undertaken in different endemic regions within Malawi, Ghana, and Kenya ,33.The Walter Reed Army Institute of Research (WRAIR) and GlaxoSmithKline (GSK), in 1987, developed the RTS, S malarial vaccine. The National Institute of Health and WRAIR had found that sporozoites that had been exposed to radiation elicited an immune response, hence producing a response for which the target was the CSP (circumsporozoite) antigen. Furthermore, they had determined the genetic pattern of the CSP antigen, sequenced it, and produced the genetic clone ,35,36,37P. falciparum, the researchers utilized the surface antigen of Hepatitis B as a CSP carrier matrix and inserted CSP’s C terminals, which carry epitopes for both B and T cells [Following the production of Energix- B™, a vaccine used to immunize against the Hepatitis B virus, a research team from GSK created the RTS, S vaccine for malarial infection. For the NF54 strain of  T cells . The “R” T cells ,40,41.Saccharomyces cerevisiae, along with the fusion of the N terminus surface antigen of Hepatitis B, resulted in the production of entities analogous to the virus, possessing surface CSP and S. The additional “S” component is the Hepatitis B surface antigen, which is combined with the RTS component. The RTS, S antigen has a highly recurrent structure, which is why immunization is believed to aid in the defense mechanism by producing anti-CSP antibodies and T cells [Coexpression of RT peptides in  T cells .The RTS, S vaccine was exposed to a wide range of adjuvants by GSK researchers, almost all of which were found to be effective. ASO4 is the combination of an adjuvant—alum versus alum + 3-O-desacyl-4′- monophosphoryl lipid A (MPL)—and RTS, S. The first clinical trial of the RTS, S vaccine was conducted using this combination. It was found that, as compared to CHMI, AS04 showed enhanced efficacy and safety .On the basis of studies performed in rhesus monkeys, it was found that six competing adjuvants tested with the RTS, S vaccine abolished ASO2A, which is a combination of oil-in-water emulsion, monophosphoryl lipid A, and the extract from Quillaja saponaria. The RTS, S vaccine provided extraordinary immunization and CMI reactivity . When CHFollowing that, further improvements in the immune response of the RTS, S vaccine were made using a novel adjuvant approach called AS01, which is the combination of QS-21, liposomes, and MPL. The clinical study of young people in Kenya validated that ASO1 had a better immune response than ASO2. ASO1 produces enhanced response in anti-CSP antibody and CD4+ T cells . These vBetween 2009 and 2014, the malarial vaccine RTS, S/AS01 was tested in seven African regions, involving 15,459 individuals, under the registration number NCT00866619 . Among tThe trial was split into two parts: a double-blind phase that lasted from 0 to 32 months, and an extension phase that lasted from 33 months to the end of the trial. The average estimated observational period for children aged 5–17 months was 48 months, whereas newborns aged 6–12 weeks had an observation period of 38 months. The immunization shots were administered intramuscularly. As part of the long-term vaccination program, infant immunizations were paired with administration of oral polio and parenteral DTP-containing vaccines.This Phase III vaccine study aimed to evaluate RTS, S/AS01 effectiveness in two age groups, the effectiveness of a booster dose, and to analyze its long-term efficiency after the termination of the extension phase. P. falciparum asexual parasitemia strain, including active infection markers or indicators with no treated diseases over the time duration of one year. A sickness with an elevated fever of at least 37.5 °C and the existence of P. falciparum asexual parasitemia was classified as severe malarial infection [The main outcome was the identification of clinical symptoms of malaria by passive approaches and nfection ,55.In an analysis after subjecting patients to the third dose of the vaccine, it was found that the coprimary endpoints of efficacy to clinical malaria were 55.8% (97.5% CI 50.6–60.4) in children aged 5–17 months and 31.3% (23.6–38.3) in infants aged 6–12 weeks. This analysis took a total time of four years from March 2009 to January 2011. These analytical data were obtained using the passive case finding method [The protocol was later amended to extend the follow-up period to 31 December 2013 (median follow-up 48 months for children and 38 months for young infants). Four shots of RTS, S/AS01 vaccine showed 25.9% effectiveness against malarial infection in newborns aged 6–12 weeks and 36.3% in children aged 5–17 months. The vaccine’s effectiveness for malarial infection declined with time for both categories and programs, although the drop-off in efficiency with four dosages is comparatively slow. The effectiveness of the vaccine was reduced in 6–12-week-old newborns compared to in 5–17-month-old children. Children between the ages of 5 to 17 months were prone to develop a febrile seizure seven days, when they were administrated with their third shot of vaccine. This was a temporary impact, and all the afflicted children healed within seven days. It was suggested that the fourth shot, which was a booster shot, enhanced the vaccine’s efficacy. The efficacy of the vaccine was determined using negative binominal regression in the case of clinical malaria .Saccharomyces cerevisiae, RIX4397, which is collected from a two-tier cell bank by a variety of different processing steps such as cell collection, disruption, separation, and filtration.In 2001, GSK and the Program for Appropriate Technology in Health collaborated to produce the malarial vaccine RTS, S with the goal of combating malaria in Sub-Saharan Africa. Industrial manufacturing of pure mass antigen RTS, S consists of a few stages, including feed-batch fermentation of the modified yeast variant Various kinds of chromatography apparatuses, ultracentrifuges, and filters are used in the purification process. The maintenance and storage temperature of RTS, S is −70 °C. In the formation process, standard control conditions are implemented to ensure product preservation, output, and quality during the production process. For a minimum of three consecutive sets, the procedure must be consistent to ensure the validity of the factor used during manufacturing of the vaccine .The production of GSK biologicals’ AS01 conformation involves the following steps: a combination of liposome with PO4/NaCl buffer solution is incorporated into QS-21 liquid substance; then, the pH of the formulation is assessed; and after sterile filtering, it is poured into the containers.The rebuilt RTS, S/AS01 adjuvant framework is an opalescent, translucent-to-pastel brown injectable solution devoid of contaminants. RTS, S is available in pellet or powder form, preserved in a glass tube of nearly 3 mL stopped with a rubber cork and capped with an aluminum lid. The other is two dosages containing the AS01 liquid formulation, stored in a glass tube of 3 mL, stopped with a rubber cork, and capped with an aluminum lid. The two shots are injected intramuscularly, one from each glass tube .The genetic variation in the two protein components of yeast cells, i.e., RTS and S, and their autonomous merging produces entities that resemble the virus with CSP and S patterns . For furThe advantages may be highly relevant for youngsters in endemic malarial regions, according to the CHMP. The WHO Strategic Advisory Group of Experts on Immunization (SAGE) and the Malaria Policy Advisory Group (MPAC) evaluated Phase III clinical results for the RTS, S malarial vaccine in October 2015. The WHO has suggested preliminary investigations with the RTS, S/AS01 vaccine utilizing a four-dosage schedule in three to five malaria-endemic areas of Sub-Saharan Africa with moderate to high rates of malarial infection.The vaccine is presently being tested in different malaria-endemic regions in children between 5 and 17 months of age under the clinical trial number NCT00866619. The findings of these studies should help decision makers, regulators, and sovereign states make decisions regarding the licensing of RTS, S/AS01. Children who were administrated only three shots of RTS, S/AS01 vaccine are prone to higher malarial risk in later stages. This was validated by research conducted for seven years, which concluded that vaccine effectiveness decreased with time in newborns, with an age limit between 5 and 17 months .Gavi’s objective was to save lives and safeguard public health by promoting equal vaccination among underdeveloped countries . The RTSAlthough the RTS, S/AS01 vaccine has low efficacy, it nevertheless has considerable advantages regarding people’s general health. Among every 1000 children who were given four vaccination shots, a total of 1744 cases of malarial infection were avoided. Furthermore, according to data from phase III clinical trials conducted under the direction of the WHO, it was found that four doses of the vaccine would avoid 116,480 instances of malarial infection and 484 fatalities per 100,000 immunized children.In the malaria-endemic regions where the infection rate is 10%, RTS, S/AS01 immunization is considered one of the most practical measures, compared to other measures to save children from getting malarial infection such as nets treated with insecticide and temporary malaria chemoprophylaxis .The majority of the participants in the study were willing to pay for malaria vaccinations for children at significantly less than the profile cost. Therefore, it helps policy makers to be aware of the price issue before specifying the price of the vaccine RTS, S/AS01 is administered via intramuscular injection as a lyophilized suspension. Children are currently prescribed four shots of vaccine. According to the administration schedule of the vaccine, the first shot should be given to the infant at the age of five months, and the rest should be given with one-month gaps until the age of 9 months. After that, children aged 15–18 months should be given a fourth shot of vaccination.The immunogenicity of RTS, S has been intensively studied, and successful attempts were made to link immunological behavior to the vaccination in order to safeguard public health ,62,63,64Immunological studies in susceptible groups such as HIV-positive children have also been performed to evaluate the responses. Clinical investigations have been performed on children living in Kenya suffering from first- or second-stage HIV, declared by the WHO to have higher antibody (anti-CSP) counts when compared with control groups. Compared to infants, older children showed higher immune response generation via vaccine induction in Phase III testing. Anti-CSP antibody levels increased post receipt of the booster shot of the vaccine. The study showed that antibody count decreased from 318.2 EU/mL to 34.2 EU/mL in children between the ages of 5 and 17 months who were not administered the booster shot . The antP. falciparum vaccines. This is further validated by a study showing that variations in the sequence of CSPs decreases the effectiveness of vaccines [These CSPs efficacy in providing protection against some malarial strains is similar to the RTS, S, and vaccines .Malarial immunizations with an adjuvanticity profile comparable to that of regular vaccinations are more appropriate to be chosen by parents of children residing in areas with higher rates of malarial infection. The advantages and disadvantages require detailed descriptions, as well as community education drives to enlighten people about the dangers and advantages of immunization. All other preventive measures, such as bed nets, health care, and encouragement of treatment-seeking behavior, have been shown to lessen the likelihood of malarial infection and fatality, but they cannot be used in lieu of vaccination. Critical appraisal of behavioral interventions following immunization is part of the ongoing RTS, S/AS01 execution research efforts.P. falciparum, and has progressed to Phase III clinical testing.The first malarial vaccine to have received positive approval from the European Medicines Agency’s CHMP is RTS, S/AS01. It specifically targets the malarial strain P. falciparum strain of malaria. To determine their effectiveness, these medications are still being evaluated in people suffering from malaria in comparison with those not suffering from malaria [PfSPZ Vaccine and R21 are two more potential immunizations against the  malaria ,67. HoweP. falciparum NF54 strain. It is a complete sporozoite vaccine that is active and enervated by rays [P. falciparum strain in people of Africa who were suffering from malaria when they were administered five shots of 2.7 × 105 vaccines in 6 months [The PfSPZ Vaccine works against the  by rays ,69,70. T6 months .P. falciparum is PfSPZ. Bioko Island in Equatorial Guinea conducted major phase III clinical investigation studies for the further analysis of the vaccine. It protects against the infection of hepatocytes in the liver by producing immune response in CD8+ T cells [The vaccine aims to deter malarial illness by inhibiting the pre-erythrocytic sporozoite stage of  T cells .In comparison with RTS, S/AS01, the R21 vaccination elicits a higher anti-CSP immune reaction and a lower anti-HBsAg antibody activity. In addition, the R21 vaccine is made up of a protein with a single CSP-antigen against Hepatitis B on the protein surface, resulting in a considerably greater percentage of CSP antigen.R21 has higher effectiveness than RTS, S/AS01, and PfSPZ because of a higher concentration of CSP for each HBsAg antibody, which may lead to improved effectiveness and defense in opposition to the CHMI parasite . PrelimiThe introduction of the RTS, S/AS01 vaccine to combat malaria in areas where the rate of malarial infection is high is a quite hopeful prospect. The WHO has started critical research to see if giving 4.486 M. B. LAURENS dosages of vaccination to children is feasible.When people who had not encountered malaria were inoculated with the one-fifth portion of RTS, S/AS01 after the delayed third shot, they showed enhanced defense against the CHMI antigen. On the basis of this study, children were inoculated with alternate shots of RTS, S/AS01 . The fouAnother way of counteracting the fast degradation of antibodies induced by the vaccine in susceptible populations is periodic booster shots of the RTS, S vaccine. Immunity can also be improved by using complementary adjuvants for RTS, S, because of the strong reliance of the antigen on the adjuvant. Further improvements are also possible based on the consideration of possible side effects; for example, it would be advantageous to have an adjuvant that did not raise the probability of the threat of febrile seizures in children.GSK, a pharmaceutical firm, is still producing a vaccine for the present deployment trials. Therefore, the availability of vaccines in the long term is still unclear. Additional vaccine manufacturing and delivery delays are possible, since vaccine producers must prepare ahead of time to fulfill demand, and as the WHO has now approved the RTS, S vaccine for use, now is the time for estimating what kind of quantities will be required. Shipping and stockpiling of vaccines will also require consideration at the global, provincial, and state levels. Awareness and collaborations will undoubtedly help to solve these constraints.The most suitable approach, which is an interesting substitute for conventional vaccination techniques, is represented by current developments in mRNA technology, enabling stable and tailored antigen production. The mRNA technology-based manufacturing of COVID vaccines opened paths toward the development of messenger RNA vaccines against malaria, which could enhance the immune response through the formation of malarial pathogenic proteins ,76. ThisThe first malarial vaccine approved by the WHO after evaluation of phase III clinical testing is the RTS, S/AS01 vaccine. This represents a significant landmark, after decades of testing, evaluation, research, and clinical trials. When the WHO, Gavi, and other organizations examine the vulnerability, expenditure, and operational issues while addressing the execution drive of vaccines, they should also address the possible effects on people residing in malaria-endemic zones with health issues, low income, and socio-economic barriers. In addition, future advancements, such as improved defense utilizing a staggered, segmented dosage regimen, and other alternative adjuvants, must be developed with the aim of attaining the final goal.


Early menarche is associated with obesity, and metabolic and mental health risks, among other diseases. Thus, it is relevant to identify modifiable risk factors of early menarche. Some nutrients and foods have been linked to pubertal timing, but how menarche relates to overall dietary patterns is unclear.The aim of this study was to analyze the association between dietary patterns and age at menarche in a prospective cohort of Chilean girls from low and middle-income families. We conducted a survival analysis of 215 girls  from the Growth and Obesity Cohort Study (GOCS) who had been followed prospectively since 4 years of age (2006). Age at menarche and anthropometric measurements were recorded every 6 months since 7 years of age while diet  was collected for 11 years. Dietary patterns were obtained from exploratory factor analysis. Accelerated Failure Time models adjusted for potential confounding variables were used to study the association between dietary patterns and age at menarche.Girls' median age at menarche was 12.7 years. Three dietary patterns were identified: “Breakfast/Light Dinner,” “Prudent” and “Snacking” which explained 19.5% of the diet variation. Girls in the lowest tertile of the “Prudent” pattern had menarche 3 months earlier than girls in the highest tertile . “Breakfast/Light Dinner” and “Snacking” patterns were not associated with age at menarche.Our results suggest that healthier dietary patterns during puberty might be associated with menarche timing. Nevertheless, further studies are required to confirm this result and to clarify the association between diet and puberty. Puberty is a critical period for growth and development. Age at menarche, a later marker of puberty, is one important reproductive event related to women's health in later stages . Early mSome nutritional factors have been linked with the timing of puberty , 9. RapiDietary pattern analysis, rather than individual nutrients or foods intake, allow capturing food interactions under real-life conditions, to increase understanding on the effects of diet in health , 19. NonIn Latin American countries, rapid changes in socioeconomic conditions, urbanization, retail foods, and public transportation have contributed to the emergence of an epidemic of childhood obesity. The nutrition transition has caused a dietary change reflecting increased consumption of animal products, ultra-processed foods, and SSBs. In contrast, the intake of vegetables, fruit, and legumes has decreased in the past decades in several countries in the region . The rolIn Chile, the first study on menarche's age was published in 1886 and reported a mean age of 16 . In 2004Growth and Obesity Chilean Cohort Study is a population-based ambispective cohort of 1,195 children of middle-low-income families from public nursery schools, who were born in 2002–2003 in six counties from the Southeast area of Santiago, Chile. Participants were singletons who were born at term, had a birth weight ≥2,500 and < 4,500 g, and were free from conditions that could affect growth. The details of the study design, protocol, and baseline were described elsewhere . From thn = 238), and girls who had not experienced menarche at the time of the present analysis (n = 5) were excluded. Therefore, a final sample size of 215 girls was considered for the study  and anthropometric measurements. However, for the primary purpose of this prospective analysis, girls who completed 24HR after their first menses  were also inserted into the program.The Nutrition Data System for Research (NDSR) software  was used to type each food and beverage of the 24HR. This program uses the United States Department of Agriculture (USDA) database as the main food composition table. For this reason, all foods and beverages reported on the 24HR were matched in the NDS-R database through the general description . Energy and macronutrient values available in Chilean food composition tables , local fA total of 771 different food items were reported in each 24HR and 732 were consumed by at least 5% of the sample. These food items were classified into 30 food categories based on their nutritional value, the correlation coefficient between groups, communalities values, food preparation, and Chilean dietary behaviors. In addition, evidence of potentially relevant food groups for pubertal development  were considered for the study .Starting at 7 years old, a single pediatric endocrinologist assessed pubertal development in girls based on the Tanner scale . Age at 2) and BMI z-scores were calculated based on the age of the participants according to the World Health Organization Growth Reference . Thvia a structured questionnaire. A trained dietitian also measured the mother's current height and weight to calculate BMI according to WHO cutoffs for adults (Participants' mothers self-reported information on education level (dichotomized as ≥12 or < 12 years) and age at menarche were collected r adults . Time spWe estimate the usual energy intake, adjusting for intra-individual variance according to the Multiple Source Method . In addiThe dietary patterns of the GOCS participants have already been reported elsewhere . BecauseInitially, statistical modeling techniques incorporated into the Multiple Source Method, an online platform, were used to estimate the usual intake of each food group in grams . Explorap-value < 0.10 in the univariate analysis.Cox regression models were used to evaluate the relationship between the exposure variables and the age at menarche. However, these models violated the proportional hazards assumption, which was tested graphically using a plot of the log cumulative hazard using ln{–ln[S(t)]}. Consequently, Accelerated Failure Time models (AFT) were used to evaluate the relationship between dietary patterns and age at menarche. The exponential AFT model, the Weibull AFT model, the log-logistic AFT model, and the log-normal AFT model were fitted to the data set. The Bayesian Information Criterion, Akaike Information Criterion, and Cox-Snell residuals were used to evaluate the performance of each model. Finally, the log-logistic AFT model was chosen as the best fitted model. The Multivariate AFT model was estimated using the backward stepwise procedure including those variables with p-value < 0.05 was considered statistically significant. All the analyses were made using Stata 16® .For sensitivity analysis, the multivariate model was adjusted by usual energy intake  and misThe estimated median age at menarche was 12.7 years old (IQR = 12.2–13.2). Almost half of the participants (43.2%) presented excess weight (overweight and obesity). One out of three mothers reported < 12 years of education, about one-third had obesity and at least one out of three self-reported age at menarche < 12 years old .Exploratory factor analysis allowed the identification of three dietary patterns: (i) “Breakfast/Light Dinner” consisting of tea, sugar, bread, margarine/butter, and cold cuts (positive loadings) and flavored milk (negative loading); (ii) “Prudent” consisting of white meats (poultry and fish), fruits, vegetables, homemade salad dressing  (positive loadings) and processed meats (negative loadings); (iii) “Snacking” consisting of soft drinks, junk food, cookies and cakes, and soups (positive loadings) and yogurt, and ready-to-eat cereal (negative loadings). These patterns explained variance in total intake of 7%, 6.4%, and 6% .p < 0.04). In addition, girls grouped in the second and third tertile of the prudent pattern had a later age of menarche compared to those classified in the first tertile  after adjusting for BMI-for-age z scores and mothers' age at menarche, usual total energy intake .In this prospective study of Chilean adolescents, we found that girls with lower adherence to the “Prudent” dietary pattern during adolescence had slightly earlier age at menarche (three months), compared to those with higher adherence, independently of their nutritional status.The associations described for the “Prudent” pattern are consistent with the literature that has examined individual foods and/or nutrients. Our “Prudent” dietary pattern had a higher and positive factor loading to vegetables, fruits, homemade salad dressing, and lean meats  groups and negative factor loading to processed meat. Girls with lower adherence to this pattern might suggest that they have a lower intake of vegetal protein, fiber, and phytoestrogens. Although there is some consistency in studies that the intake of vegetal proteins during middle childhood has been related to later menarche, the causal mechanisms are unknown or have other components that confound your relation , 11, 48.z-score and total energy intake, and interestingly, we found that the association between the “Prudent” dietary pattern and age at menarche remained significant showing that not only the caloric content of the diet but the nature and quality of the foods are relevant at least in terms of developmental milestones. In this same cohort, we have previously described that the consumption of yogurt (>125 g/d) was associated with older age at menarche (4.6 months), however, milk or yogurt did not have positive factor loadings in the most prevalent dietary patterns that we identified, and thus, we were unable to corroborate these findings  . HoweverThis study also has several strengths. First, given the prospective design, we could estimate the temporality of the studied associations between peripubertal diet and age at menarche, excluding the possibility of reverse causality. Diets were recorded using a robust method of estimation that allows decreasing errors inherent to a measurement based on the respondent's memory. The “Multiple-Pass Method” was applied to certify that all foods were listed properly by the adolescents and there was no missing information. In addition, the usual intake adjusted for intra-individual variance according to the “Multiple Source Method” was estimated to increase the reliability of the results . Also, wIn conclusion, in this prospective study of Chilean adolescents, we found that girls with lower adherence to the “Prudent” dietary pattern during adolescence had slightly earlier age at menarche (3 months), compared to those with higher adherence. Although our result of age at menarche could seem irrelevant from a clinical perspective, these changes are in the range of the results described in other population studies, both descriptive and in association with different health outcomes , 58–62. The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of the Institute of Nutrition and Food Technology, University of Chile. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.CC, AM-A, and RMF contributed to the study's conception and design. CC provided essential materials. AM-A wrote the first draft of the manuscript. EC and AM-A are involved in data analysis. AM-A, RMF, CC, and EC contributed to the interpretation of the results. All authors contributed to the manuscript writing and read and approved the final manuscript.