The aim of this study was to investigate employees’ self-reported creativity before and after vacation and to examine the impact of recovery experiences  on changes in creativity. The DRAMMA model of Newman et al. provides the theoretical background of our approach. Longitudinal data was assessed with four repeated measurements. The study encompassed data from 274 white-collar workers. Analyses showed that employees subjectively perceive their creativity to benefit not immediately after their vacation but 2 weeks later. Detachment was significantly related to lower creativity within persons, while mastery experiences explained differences in creativity between persons. This study provides a detailed picture of changes in creativity around vacations. Vacationing has psycho-social benefits similar to, or even exceeding the benefits of leisure time spent over shorter periods, such as evenings or weekends at home . Travel In Western societies, regular time off from work is considered an integral part of working life and vacations are an essential element of quality of life , not leaTwo systematic literature reviews underline the positive impact of vacations on employees’ health and well-being , evidentThe link between vacationing and job performance, however, has received much less research attention. This is surprising, because diary studies on recovery episodes of shorter durations, like evening hours or weekends, indicate that employees who start their workday feeling mentally and physically refreshed report higher task performance . A recenThis study focuses on the impact of vacation, a prolonged episode of recovery from work, as a potential predictor of creativity as a key aspect of employees’ job performance. Researchers see creativity as one of the most complex and advanced achievements of which a person is capable . CreativNumerous theories and studies aim to identify personal and organizational predictors of employees’ creativity at work see . A firstIn the present study, theories and methodological approaches are derived from tourism research, leisure sciences, and psychology aiming to connect research fields and build bridges between hitherto only loosely connected areas of expertise. Our focus is to further our understanding of the link between vacationing and creativity. To scrutinize the relationship between recovery and changes in creativity, we follow Why might vacations be potentially linked to creativity? Unstructured free time is assumed to alleviate people’s sense of urgency and encourage reflective thinking and incubation, which are crucial to creativity . VacatioDetachment focuses on mental unwinding and on gaining inner distance from work, . This study aims to bridge this research gap. More specifically, we hypothesize:H1: Employees’ creativity is higher after vacation than before vacation within persons.H2: Recovery experiences  predict changes in employees’ creativity within and between persons.The participants were 274 German employees working in various industries. Information regarding confidentiality, as well as the voluntary nature of participation, was posted on a website online along with the announcement of the study. Of the 339 employees who had provided their email information, confirmed their interest in participating and reported their individual vacation period, 274 responded to the questionnaires. Two weeks prior to their vacations, we sent all registered employees a link with a baseline survey assessing work and background characteristics. Employees then responded to brief online questionnaires on five measurement points: 2 weeks before vacation, the last day of work before their vacation, during their vacation (=middle of the holiday), on their first day back at work, and 2 weeks after the vacation. While recovery experiences were measured during vacation, self-reported work-related creativity was not measured during vacation. Employees were offered the option of using a smartphone application (that accompanied them) before, during, and after vacation with proposals for tasks to increase recovery.M = 40.20, SD = 10.80). Most employees were married or cohabiting (78%), and 39% had children. Average tenure was 9 years (SD = 8.97), ranging from less than 1–40 years. Most employees worked full time (73%). The majority of participants had a college degree (58%), followed by intermediate level (21%) and high school levels (21%) of education.The data set included 274 employees and 752 measurements, indicating a completion rate of 25% for self-reported work-related creativity. Respondents in the dataset respond to at least three measurement points. Of the sample, 74% were female. Employees were between 18 and 67-year-old  planed wellness activities, 36% going to the beach, 33% reported having planned sporting activities , 31% spending time in natural surroundings, 31% staying at home during their vacation (including day trips), 20% visits to relatives, 10% planned a self-organized round trip, 13% a city trip, 11% cultural activities. Of the sample, 58% planned to travel in Europe (outside Germany), 17% to travel outside Europe, 13% in Germany, and 12% to stay at home.M = 7.19, SD = 1.63 on a scale from 1 = this vacation was a flop to 10 = this vacation was the vacation of my life).Concerning travel companions, 65% reported going on vacation with their partner, 24% with their children, 22% with family, 14% with friends, 3% alone, and 1% with colleagues (multiple answers possible). On their first day back at work, participants on average felt that their vacation was fairly good  for the DRAMMA experiences ranged between 0.19 and 0.42, showing a considerable amount of within-person variance. We modeled time and analyzed linear, quadratic as well as cubic time trends by converting time into power polynomials. The results show that all three time trends  were significant for each DRAMMA dimension, indicating that recovery experiences decreased from 2 weeks prior to the vacation to the last day at work before the vacation, increased during the vacation, and again slightly decreased 2 weeks after the vacation  and 3. Fγ = 0.41, t = 0.53, p = 0.60) was not significant while the quadratic time trend  was significant  for self-reported work-related creativity was 0.42, indicating that almost half of the variance in creativity stemmed from differences between persons, and that there was also substantial variance within persons across time. The linear time trend  predicted self-reported work-related creativity within persons, while mastery  was related to self-reported work-related creativity between persons . The results , while the slope was significant at medium  and enhanced levels of mastery experiences .To examine the changes in creativity over time more closely, we analyzed whether the general level of a DRAMMA experience serves as a potential cross-level moderator. The results indicated that the general level of mastery experiences functions as a cross-level moderator  were not counterbalanced correctly. Accordingly, this measure was not sound.While the DRAMMA model does not specify interdependencies between the six experiences, experiences, such as autonomy, may also represent a moderator variable, influencing the strength of the relationship between the other DRAMMA experiences and creativity. Furthermore, it might be interesting for future research to examine temporal relationships between the DRAMMA experiences to analyze whether, for example, detachment is a necessary precondition and leads to mastery having a higher impact.As all participants of the study had access to our vacation app “Holidaily,” which offers daily ideas on how to recover, we are not certain if the effects we found are attributable solely to the impact of vacation, or to what degree app usage played a role. Thus, recovery during vacation might have been enhanced compared to a vacation without a comparable app. However, we controlled for app usage, which did not influence the pattern of results.The positive correlation between gender and creativity deserves to be mentioned . Earlier research on this relationship often showed no relationship between gender and self-reported creativity or findings consistent with common stereotypes on specific types of creativity and gender , including when work-related thoughts become detrimental .We set out to examine the link between vacations and creativity drawing on research from health psychology, organizational psychology, and leisure sciences. Our analyses provide evidence that (1) employees perceived their creativity to be lower immediately after their vacation but perceived an increase 2 weeks after being back at work, (2) employees’ detachment during leisure time was negatively associated with intraindividual differences in creativity, and (3) mastery experiences were positively related to interindividual differences in creativity.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Leuphana University of Lueneburg (reference number: 201606-EB-Antrag Lehr201606_holidaily). The patients/participants provided their written informed consent to participate in this study.CS, JB, and DL contributed to conception and design of the study. CS performed the statistical analysis and wrote the first draft of the manuscript. JB wrote sections of the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the Academy of Finland (grant number: 308718). The data were collected as part of a larger data collection funded by the German health insurance company Barmer GEK. The funders did not influence in any way the analysis and presentation of the results or drafting of the manuscript.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.


Women’s diet and nutritional status during pregnancy are important in influencing birth outcomes. We conducted a systematic scoping review of the best available evidence regarding dietary intake of Malaysian pregnant women, and the associations of maternal diet, anthropometry, and nutrition-related co-morbidities with the infant’s birth weight (IBW). The study objectives were to examine: (1) the adequacy of micronutrient intake among pregnant women; and (2) the association of maternal factors  during pregnancy with IBW.Eleven search engines such as Proquest, EbscoHost, Scopus, Cochrane Library, Science Direct, Wiley Online Library, PubMed, Google Scholar, MyJournal, BookSC and Inter Library Loan with Medical Library Group were extensively searched to identify the primary articles. Three reviewers independently screened the abstracts and full articles based on the inclusion and exclusion criteria. Extracted data included details about the population characteristics, study methods and key findings related to the review objectives. Seventeen studies published from 1972 to 2021 were included, following the PRISMA-ScR guideline.Studies showed that maternal micronutrient intakes including calcium, iron, vitamin D, folic acid, and niacin fell short of the national recommendations. Increased maternal fruit intake was also associated with increased birth weight. Factors associated with fetal macrosomia included high pre-pregnancy body mass index (BMI), excess gestational weight gain (GWG) and high blood glucose levels. Low pre-pregnancy BMI, inadequate GWG, intake of confectioneries and condiments, and high blood pressure were associated with low birth weight.This review identified several factors such as the mother’s food habits, comorbidities, BMI and gestational weight gain as the determinants of low birth weight. This implies that emphasis should be given on maternal health and nutrition for the birth outcome. The nutritional status of women prior to conception and during pregnancy is important for fetal growth and development. The first 1000 days of life  emphasize the importance of optimal maternal nutritional status in determining early infant development and risk of nutrition-related chronic diseases in adulthood , 3. On tIn May 2012, the 65th World Health Assembly endorsed the Comprehensive Implementation Plan on Maternal, Infant and Young Child Nutrition (MIYCN). This plan specified a set of six global nutrition targets, including a 30% reduction of LBW. Based on a nationwide survey done among Malaysians, 1 out of 10 livebirth babies were born LBW (NHMS 2016). This is similar to neighboring countries Thailand (9.2%) but lower than Indonesia (20.2%) . While tThe scoping review was conducted to better understand the areas of priority research in maternal diet and nutritional status of the mother and the child in Malaysia. For those research needs, the scoping review was done for the case of Malaysia, because of the unavailability of data on maternal nutritional status with low birth weight in the country. The present review aims to examine the best available evidence regarding dietary intake of Malaysian pregnant women, and the association of diet, anthropometry, and existing co-morbidities during pregnancy with birth outcomes. The objectives are to evaluate: 1) The adequacy of selected dietary micronutrient intake among pregnant women; 2) The association of the following maternal nutritional factors on infant’s birth weight defined in terms of macrosomia and LBW: pre-pregnancy body mass index (BMI), and GWG; 3) Maternal food group intake; and 4) Selected co-morbidities during pregnancy with the infant’s birth weight, such as maternal high blood glucose and high blood pressure.The scoping review framework by Arksey and O’Malley was used as a guide to conduct the review . The PreThe data search strategy comprised of primary studies, grey literature and annual reports published from 1972 to 2021. The following databases were used: Proquest, EbscoHost, Scopus, Cochrane Library, Science Direct, Wiley Online Library, PubMed, Google Scholar, MyJournal , BookSC and Inter Library Loan with Medical Library Group. Search terms used were: Malaysia, maternal nutrition, diet, pregnancy, birth outcome, birth weight, macrosomia, premature, low birth weight, intrauterine growth restriction, gestational diabetes, plasma glucose, blood pressure, obesity, gestational weight gain, anemia, folic acid deficiencies and iron deficiencies. The last search was performed on 25 August 2021. The search strategy is shown in Table The screening process was conducted in accordance with the scoping review framework by Arksey and O’Malley and recommendations made by Levac et al. , 10. ThrData were extracted independently by three reviewers. To map the existing literature on the review objectives, findings were grouped by adequacy of dietary intake, nutritional factors and infant birth weight, maternal anthropometry and birth weight , food group intake and birth weight as well as nutrition-related co-morbidities in pregnancy and birth weight. General and specific information about the studies which included author(s), year of publication, study design, sample characteristics, sample size, exposure and outcomes that were relevant to the objectives of the review were charted in Table Studies were appraised by three researchers for quality –11. ThreOut of the 17 studies that were included in the review, 8 studies investigated infant birth weight while only 4 studies included macrosomia as the outcome variable. There were 4 studies that examined the adequacy of micronutrient intakes and 1 study investigated food group intake among pregnant women. Table Table The results of studies that examined the association of nutritional factors  with infant birth weight were included in Table The studies that examined the association of nutritional factors  with infant birth weight were included in Table High pre-pregnancy body weight and BMI were associated with less LBW deliveries , 20, 30,Excessive GWG was associated with increased frequency of macrosomia , particuOne study showed that low MUAC was associated with increased LBW deliveries in rural, but not in urban women .One study showed that higher fruit intake was associated with greater birth weight, while intakes of confectioneries and condiments were both associated with lower birth weight .The results of studies that examined the effects of co-morbidities (hyperglycemia and hypertension during pregnancy) on infant birth weight were shown in Table Out of the 17 studies, 10 (59%) scored 3, meaning high quality and 6 (35%) scored 2, meaning moderate quality, and only one study  scored 1The research findings were quite consistent with the quality of the studies. A couple of studies that were rated moderate , 20 and Two studies with good quality and four studies with moderate quality showed that factors associated with increased infant’s birth weight (macrosomia) were high pre-pregnancy BMI, excess GWG and high blood glucose levels.2) was associated with higher odds of macrosomic babies.Maternal hyperglycemia, defined as gestational diabetes mellitus (GDM) or high plasma glucose, was associated with increased macrosomic or large-for-gestational-age deliveries in three studies , 18, 23.Dietary iron intake was below the Malaysian recommended iron for pregnant women in a high quality study . SimilarThis review showed that maternal micronutrient intakes were below the recommended levels, specifically vitamin D, calcium and iron, as shown by two high quality studies , 29. TwoIn general, the findings of this review from Malaysia are in line with studies from both Asian and Western settings that report an unfavorable nutritional-related maternal environment during pregnancy including underweight or overweight/obesity, suboptimal GWG, poor dietary intake, hyperglycemia and/or hypertension were associated with abnormal birth weight deliveries –6, 31–35These results are consistent with the emerging evidence showing the associations of pre-pregnancy BMI, GWG, pre-existing diabetes, GDM and maternal dietary factors with adverse birth outcomes including LBW, preterm birth, macrosomia, adiposity, neonatal hypoglycemia and caesarean delivery.Hamid and colleagues reported earlier that among rural pregnant women, 37% displayed serum vitamin D deficiency in their third trimester, potentially resulting in low vitamin D concentrations in breast milk at birth . MeanwhiMultiple reviews have consistently revealed that suboptimal intakes of vitamin D, calcium and iron, are widely prevalent among pregnant women especially in those from low- and middle-income countries –39. MoreThe majority of pregnant women in Malaysia were not able to achieve their recommended intake for iron through the diet , 27, 40,The few studies have shown that maternal pre-pregnancy BMI and GWG are positively associated with birth weight among Malaysian women. An evidence derived from the only prospective cohort study in this review  showed tIndividual nutrients or foods were examined in two studies in Malaysia, whereby more fruit and vegetable intake at late pregnancy were associated with larger birth sizes , 54. ThoMalaysian pregnant women with diabetes, including both pre-existing diabetes and GDM were associated with macrosomia , 18. ProA study by Ismail and co-researchers suggests that higher BMI status in women with diabetes predisposes them to a higher insulin resistance state . Addition = 13,893) further demonstrated that adult offspring of mothers with hypertension in pregnancy had an adverse cardio-metabolic trajectory, including higher risk of hypertension, higher BMI, higher plasma glucose at age of 40 years, compared with offspring of mothers who did not have hypertension in pregnancy [Hypertension in pregnancy includes gestational hypertension, preeclampsia and eclampsia, were associated with LBW deliveries among Malaysian women. This is in agreement with previous reports from both developed and developing countries, showing high rate of LBW or small-for-gestational-age in women developing hypertension in pregnancy –35. Not regnancy . These aOnly a limited number of research related to maternal diet and nutrition were identified over the past decades. Most of the studies in this review focused on iron-deficiency anemia and vitamin D deficiency. There is an urgent need to investigate the role of other dietary patterns and micronutrient deficiencies in determining birth outcomes among Malaysian women. Furthermore, the focus of Malaysian studies was more on certain maternal nutrition-related indicators rather than other aspects of maternal nutrition status, nutrient intake, and dietary pattern. Dietary factors influence towards maternal nutritional status remains understudied in Malaysia with most studies being cross-sectional instead of longitudinal. More attention should be focused on a wider range of micronutrient deficiencies. Importantly, more research is required, particularly prospective cohort study, case-control study, and randomized control trial of maternal nutritional intervention, to explore the maternal dietary practices and to understand the effects of maternal nutritional status on birth outcomes. This is critical in developing targeted interventions for Malaysian women of reproductive age, in order to initiate appropriate health management as early as possible to improve offspring outcomes.Despite the information compiled in this review involves a total of 11,870 sample population, several limitations including the study quality are subjected to bias. The scope of this review was limited to the Malaysian population. The study results must not be generalized to other populations. Secondly, because of the nature of a scoping review, multiple structured searches are required. Even though this review identified articles using 10 or more sources, there is always a possibility that some of the important articles could have been missed. The absence of current studies is a limitation. Another limitation could be the lack of training of the reviewers on quality appraisal prior to the research. We suggest such training of the reviewers should reduce the risk of bias and ensure reliability and consistency in the quality appraisal ratings. The scale that was used to assess risk of bias could be rather insensitive – there were only four items, and the type of the study design  were all weighted equally.Although the findings of maternal nutritional-related indicators such as pre-pregnancy BMI, GWG, glucose and dietary intake in relation to birth outcomes that were covered under this review have been supported by literature, the comparability between the included studies is constrained by a limited number of available reports, along with variations in study design, variable assessment method and period across studies. Dietary factors influence towards maternal nutritional status remains understudied in Malaysia with most studies being cross-sectional instead of longitudinal. More attention should be focused on a wider range of micronutrient deficiencies. Importantly, more research is required, particularly prospective cohort study, case-control study and randomized control trial of maternal nutritional intervention, to explore the maternal dietary practices and to understand the effects of maternal nutritional status on birth outcomes. This is critical in developing targeted interventions for Malaysian women of reproductive age, in order to initiate appropriate health management as early as possible to improve offspring outcomes.This review demonstrated that maternal nutrition status plays a significant role in birth outcomes related to infant birth weight. Reviewed studies consistently showed that increased infant birth weight (macrosomia) was associated with high pre-pregnancy BMI, excess GWG and high blood glucose levels. At the same time, a few studies also demonstrated the association of poor maternal nutritional status (such as low MUAC) with adverse pregnancy outcome of LBW.This review reaffirms the importance of maternal nutrition on maternal and infant outcome but highlights that this area remains understudied in Malaysia. Therefore, there is a need to explore other aspects of maternal nutrition before and during pregnancy. Findings of this review could support the planning or future research and interventions for Malaysian population, both in the rural and urban setting. Meanwhile, the role of dietary factors on maternal health outcomes including maternal nutritional, metabolic, mental and overall wellbeing should be emphasized. This is critical in developing targeted interventions for Malaysian women of reproductive age, in order to initiate appropriate health management as early as possible to improve the outcomes of the offspring.Although the neighboring countries such as Thailand and Indonesia have almost a similar prevalence of LBW as compared with Malaysia, further studies may be undertaken to compare the determinants associated with LBW in the three neighboring countries.


The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into “expected” or “unexpected” groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age , body mass index , antral follicle counting  and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply . The inflection point of BMI was 23.4 kg/m The Patient Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) group proposed a new stratification method for poor ovarian response (POR) patients in 2016 . DiffereAccurate predictive factors of ovarian reserve and pregnancy outcome in infertile women with poor ovarian response (POR) remain unknown and are one of the main puzzles of assisted reproductive technology treatments. Although many studies have been performed to identify predictors of IVF/ICSI outcome, there is still no real consensus , 10. ThiToday, large data and evidence-based medicine have progressively developed as the standard approach for clinical management strategies in the field of reproductive medicine , 14. At This retrospective cohort study evaluated clinical data from 6,580 POR patients classified by the POSEIDON criteria who underwent IVF/ICSI in the reproductive medical center of the First Affiliated Hospital of Zhengzhou University from June 2013 to December 2018. All the included case data were recorded and sorted by dedicated personnel. The quality of data entry is strictly controlled to ensure the completeness and authenticity of the data. This study strictly followed the relevant requirements of the Declaration of Helsinki of the World Medical Association. The study was a retrospective study approved by the Medical Ethics Committee and did not require the informed consent of patients.We compared the experimental data of patients in the “live birth group” and “non-live birth group” and determined the statistically significant influencing factors for the two groups of patients. Based on these results, further single-factor and multifactor logistic regression analysis was performed to screen for independent influencing factors for live birth in POR patients; then, a smooth fitting curve model was constructed based on independent influencing factors, and the linearity between these influencing factors and the occurrence of live birth was observed. The relationship was further analyzed based on the model observation results, and finally, the probability of live birth was explored in detail based on the results before and after the threshold inflection point of each independent influencing factor.There patients were put on either the early-follicular-phase long-acting GnRH-agonist long protocol, Mid-luteal phase short-acting GnRH-a long protocol, GnRH antagonist protocol, GnRH agonist short protocol or natural cycle for IVF/ICSI followed by embryo transfer in the same cycle. The starting dose of gonadotropin  were administrated on the basis of patient`s antral follicle count, age, BMI and previous ovarian response to stimulation. The dosage was also adjusted constantly according to patient`s response. When dominant follicles measuring > 16mm account for 60% or a follicle reached 20mm in mean diameter, trigger was normally performed using 250ug r-hCG  in combination with 2000IU u-HCG . Oocyte retrieval under the guidance of transvaginal ultrasound was performed 37 hours after trigger. The diagnosis of spontaneous abortion is after the pregnancy is confirmed, the clinical history, physical examination, female endocrine and vaginal ultrasound confirm that the embryo stops developing before 20 weeks of pregnancy , 16. LivPOSEIDON “unexpected” group: age < 35 years, AFC ≥ 5, AMH ≥ 1.2 ng/mL and ≤ 9 oocytes retrieved in the first stimulation cycle; age ≥ 35 years, AFC ≥ 5, AMH ≥ 1.2 ng/mL and ≤ 9 oocytes retrieved in the first stimulation cycle; POSEIDON “expected” group: age < 35 years, AFC < 5, AMH < 1.2 ng/mL; age ≥ 35 years, AFC < 5, AMH < 1.2 ng/mL , 17, 18.http://www.r-project.org; version 3.6.1), EmpowerStats (http://www.empowerstats.com) and SPSS 19.0 . The continuous variable data are expressed as the mean ± standard deviation (Mean ± SD) and were compared using Student’s t test or the Wilcoxon rank sum test; categorical variables are expressed as frequencies (percentages) and were compared using the chi-square test. We then applied multiple regression analysis to estimate the independent relationship between live birth and female age, BMI, AFC and COH protocol with an adjustment for potential confounders. P < 0.05 indicated that a difference was statistically significant, to avoid inflating the probability of a Type I error, P-values were adjusted with the Holm-Bonferroni method.All analyses were performed using the statistical packages R  and 95% confidence intervals (Cis) for the threshold turning points of the independent influencing factors. P < 0.05 indicated that a difference was statistically significant.We collected effective experimental data from 6,580 POR patients classified by the POSEIDON criteria, the “unexpected” group (n=3639) and the “expected” group (n=2951), and 1,549 (23.54%) had live births, 5,031 (76.46%) did not have live births, and 1309 of these women (35.97%) succeeded had live births in “unexpected” group, 240 of these women (8.13%) succeeded had live births in “expected” group. There were statistically significant differences in female age, primary infertility, infertility years, BMI, pasal P, AMH, PRL, AFC, number of treatment cycles, initiation dosage of Gn used, duration of Gn used, oocyte number, and use of a controlled ovarian hyperstimulation protocol between the two groups , primary infertility , infertility years , BMI , AMH , PRL , AFC , No. of treatment cycles , initiation dosage of Gn used , duration of Gn used , oocyte number  and COH protocol were factors for predicting live birth in patients with POR. Multivariate logistic regression analysis showed that female age , BMI , AFC  and COH protocol were independent factors for predicting live birth in patients with POR Multivariate logistic regression analysis showed that female age, BMI, and AFC were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The adjusted smooth curve fit showed a nonlinear correlation between them. Age and BMI had a negative correlation with live birth, and AFC had a positive correlation with live birth. However, these influencing factors did not have a simple linear relationship with live birth . When age ≤ 32 years of age, the probability of spontaneous miscarriage and female age were not significantly related . The inflection point of BMI was 23.4 kg/m2; when BMI > 23.4 kg/m2, it had a negative correlation with live birth , but when BMI > 23.4 kg/m2, there was no significant relationship between them . The threshold inflection point of AFC was 8n. However, there was still a roughly linear positive relationship between AFC and live birth before and after the inflection point Our study first analyzed the independent factors predicting the possibility of live birth in POR patients using smooth curve fit and threshold effect analyses. The results confirm that the POSEIDON classification criteria are indeed very accurate in predicting the live birth rate for POR patients, which is very similar to our results, however, it seems that the results indicate that BMI should be considered as well in the POSEIDON criteria, and AFC threshold of 8 instead of 5 may be more relevant. AMH was not an independent factor, as this is also included in the POSEIDON criteria. We all know that various advances in assisted reproductive technologies have led to a significant improvement in the efficacy of treatment for couples who with infertility in recent decades, and various embryo manipulation techniques and controlled ovarian stimulation specifications continue to be improved , 20. HowOur study found that the older the female was, the lower the probability of live birth in POR patients. In fact, some studies have suggested that the blastocyst euploidy rate drops from 60% before 35 years to 30% after 40 years and that the embryo euploidy rate decreases by 2.4% per year with increasing female age. These studies suggest a negative correlation between age and the live birth rate , 22. DifThis study found that AFC and BMI are other important factors for predicting live birth in patients with POR. AFC is a good indicator of reactive ovarian reserve function in infertile patients , 28. BunThe early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols for POR patients. This protocol is designed to suppress the pituitary gland for 28 days, and a standard full dose of GnRH-a before ovarian stimulation in IVF-ET might improve the pregnancy and live birth rates per fresh ET , 32. SomIn summary, our study can more accurately predict the probability of a live birth and provide clinical management strategies for these patients. However, the main limitation of our study is that it is a retrospective study that could not exclude all potential biases, and pregnancy is a process of continuous change, during which there are many confounding factors. For example, maternal infection factors, environmental factors, emotional factors, etc., were not taken into account in this study, and prospective, large-scale and multicenter clinical trials are still needed to confirm our findings in the future.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of The First Affiliated Hospital of Zhengzhou University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.GL and FL conceived of and designed the experiments. GL, TY and LH selected and supervised suitable patients. GL, JL, HJ, and LF obtained basic clinical data including age, body mass index, FSH, LH, estradiol, progesterone and AMH levels, total dosage of gonadotropin used, duration of gonadotropin use, oocyte number, and live birth rate per transfer. GL provided overall supervision. GL, GH and FL drafted the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the National Natural Science Foundation of China (81771534), the Key Science and Technology Foundation of Henan Province (SBGL202002048), the Key Research Projects of Henan Higher Education Institutions (18A320057) and the Medical Science and Technology Project of Henan Province (212102310049).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.


Birth weight has a substantial effect on children’s cognitive development, physical capability, and emotional development, which in turn impact on Health-Related Quality of Life (HRQoL). Generally, evidence indicates that children born with low birth weight tend to have poorer proxy-reported HRQoL, particularly at school age. However, there is limited evidence on whether variation in HRQoL exists across the entire range of possible birth weights. This study aimed to examine the association between birth weight and proxy-reported HRQoL among children aged 5–10 years old.Data from the 1973–78 cohort of the Australian Longitudinal Study on Women’s Health were linked with state-based Perinatal Data Collections and the Mothers and their Children’s Health study for 1,589 mothers and 2,092 children aged 5 − 10 years old. Generalized estimating equations were used to model the association between birth weight and proxy-reported HRQoL measured by the Pediatric Quality of Life Inventory 4.0. Results are presented as odds ratios with 95 % confidence intervals.In this study, 15.61 % of children were at risk of impaired proxy-reported HRQoL. Each 100-gram increase in birth weight was associated with a 3 % reduction in the odds of impaired HRQoL . However, there was only limited evidence of an effect within the normal birth weight range .The findings indicate that increased birth weight was protective against impaired HRQoL, although there was limited evidence of variability within the normal birth weight range. This study contributes to the existing literature by not only emphasizing the impact of low birth weight on children’s health and health-related outcomes but also by focusing on the variability within the normal birth weight range, particularly in a setting where low birth weight is less prevalent. Birth weight is an important marker of the health status of a fetus, and it has a significant impact on children’s outcomes . EvidencHRQoL in children can be defined in different ways. The World Health Organisation defines HRQoL as “a child’s goals, expectations, standards, or concerns about their overall health and health-related domains” , 9. OtheSeveral studies have explored the association between birth weight and HRQoL , 13. In Generally, studies have indicated that children born with a very low or low birth weight have poorer HRQoL and perform worse than their peers on specific domains of HRQoL , 18, altVarious maternal and child-related factors also influence the association between birthweight HRQoL as well as early child development. For example, evidence indicated that poor maternal health and poor parenting practices negatively affected the children’s developmental outcomes around school entry which may, in turn, affect their quality of life , 21. In Few studies have examined the variability of HRQoL  and otheDespite this, the association between the entire birth weight range and HRQoL has not yet been well explored. Therefore, the objective of this study was to comprehensively investigate the association between birth weight and HRQoL by accounting for variability that may exist across the full range of possible birth weights, and also within the normal birth weight range.Data were sourced from the Australian Longitudinal Study of Women’s Health (ALSWH), the Mothers and their Children’s Health study (MatCH), and Australian state-based Perinatal Data Collections (PDCs).The ALSWH is a longitudinal population-based survey that has been conducted since 1996 with three cohorts of women born in 1921-26, 1946-51, and 1973-78. Over 40,000 women responded to the baseline survey [The MatCH study is a sub study of the ALSWH. Women in the 1973-78 cohort who had reported at least one live birth were invited to complete surveys in 2016, either online or on paper, about their biological children aged under 13 years .The PDCs are population-based data collections of pregnancy and birth information for each Australian state and territory. The PDC is also known as the Perinatal Statistics Collection in South Australia  and the The participants of this study were 2092 children aged 5–10 years of 1589 mothers in the 1973-78 cohort of the ALSWH who participated in the MatCH study and who did not opt-out of external data linkage.The variables were organized using the HRQoL theoretical model that was modified for the Pediatric population , from thThe outcome of this study was proxy-reported HRQoL, and it was measured by the Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) in the MatCH study. PedsQL is a 23-item proxy questionnaire for parents of 2–18 years old children . PedsQL The main exposure variable in this study was birth weight. Birth weight was sourced from the PDCs. It was measured to the nearest gram and was used as a continuous predictor.Based on the literature review and theoretical background, the models investigating the association between birth weight and HRQoL were adjusted for the following covariates: parenting practices (measured using the Alabama Parenting Questionnaire Short Form included in the MatCH survey), mother’s physical and mental health (measured using the SF-36 instrument), mother’s area of residence, mother’s age at birth, marital status, child’s mode of birth, child’s average screen time per day, and etc.Descriptive statistics for the maternal and child variables were reported as means and standard deviations for the continuous variables and frequencies and percentages for the categorical variables. Linearity was checked for the continuous predictors and the outcome variable, and multicollinearity was checked for the predictor variables using variance inflation factors (VIF). VIFs greater than 10 were indicative of multicollinearity. Bivariate analyses were performed to select relevant variables for inclusion in the final multivariable model. Variables that were considered clinically important or which displayed a bivariate association with HRQoL with P-values of less than or equal to 0.25 were included in the final models.Generalized estimating equations (GEE)  models wAdjusted odds ratios with 95 % confidence intervals (CI) were presented as estimates of the effect of birth weight on impaired HRQoL after controlling for potential confounders. All analyses were performed in Stata 15.0 .A total of 2,092 children aged 5–10 years were included in the primary analysis that investigated all possible birth weights. The second analysis that focused on variability within the normal birth weight range included 1981 children. The mean age of the children was 6.89 years (SD = 1.36). The overall mean birth weight for the children was 3510.19 g (SD = 515.92) and the mean birth weight for children within the normal birth weight range was 3521.54 g (SD = 412.19).The mean HRQoL score was 87.27 SD = 10.46) and 314 (15.61 %) children were below the 1 SD cut-off and were considered at risk of impaired HRQoL . In the second multivariable model which was restricted to the normal birth weight range, we observed the same effect size  but were not able to conclude that there was evidence of a definite association between birth weight and HRQoL due to the wider confidence interval Table .This study aimed to investigate the association between birth weight and HRQoL by taking account of the variability that may exist within the normal birth weight range. The finding of our study showed that increased birth weight reduced the odds of being at risk of impaired HRQoL after adjusting for the confounding factors. These findings are corroborated with previous studies that examined the associations between birth weight and HRQoL.However, we did not find evidence of an association between birth weight and HRQoL within the normal birth weight range. This finding is in contrast with previous studies that examined the associations between birth weight within the normal range and health-related outcomes in children. For instance, studies reported that within normal birth weight range, birth weight was associated with language abilities , cognitiThe discrepancy between our findings and the previous studies might be attributed to factors such as the population studied and sample size. For example, a previous study reported that the MatCH participants included in this study were more educated, healthier, and more likely to live in major cities  and as aThe mechanisms by which birth weight is linked to different health-related outcomes including HRQoL are not well understood. However, studies have documented a linear relationship between birth weight and language  and execOn the other hand, the paths by which birth weight is linked to various health-related outcomes in normal birth weight children may be different to children of low birth weights . For chiThis study has notable strengths. The study used a nationally representative sample and adjusted for important factors that may confound the association between birth weight and HRQoL. Unlike many other studies that mainly focused on the impact of clinically low birth weight on the HRQoL, this study accounted for the variability that may exist within the normal birth weight range. Furthermore, this study also utilized a standardised and common tool to measure HRQoL in children.This study has also some limitations that must be acknowledged. Both maternal and child data were self-reported by the mother. Importantly, as only a proxy questionnaire for parents was applied to measure HRQoL in the MatCH study, data on self-reported HRQoL were not included, warranting a further study. In addition, while the ALSWH cohorts are representative, mothers participating in the MatCH sub study had better health and health-related characteristics than the general population, which should be considered when evaluating the generalizability of these findings.These findings indicate that increased birth weight was protective against impaired HRQoL, although significant variability within the normal birth weight range was not observed. This study contributes to the existing literature by not only emphasizing the impact of low birth weight on children’s health and health-related outcomes but also by focusing on the variability within the normal birth weight range, particularly in a setting where low birth weight is less prevalent. This is important because a small shift in the distribution of birth size may impact the health and health-related outcomes in children which may also be extended to adulthood and poses additional burdens on the healthcare system.


Sarcoptes scabiei mites from animals are unable to successfully reproduce and persist on human skin; however, several ZS case reports have mentioned the persistence of symptoms and occasionally mites for weeks. The aim of this review was to collect and organize the sparse literature explicitly referring to S. scabiei zoonotic transmission, focusing on the source of the outbreak, the circumstances leading to the transmission of the parasite, the diagnosis including the identification of the Sarcoptes “strain” involved, and the applied treatments. A total of 46 articles, one conference abstract and a book were collected describing ZS cases associated with twenty animal hosts in five continents. Dogs were by far the most common source among pet owners, while diverse livestock and wildlife contributed to the caseload as an occupational disease. Genetic epidemiological studies of ZS outbreaks are still limited in number, but tools are available to fill this knowledge gap in the near future. Further research is also needed to understand the apparent heterogeneity in the morbidity, disease severity and timing of the response to treatment among people infected with different animal-derived strains.Zoonotic scabies (ZS), also referred to as “pseudoscabies”, is considered a self-limiting disease with a short incubation period and transient clinical skin signs. It is commonly thought that  Sarcoptes scabiei  (Sarcoptiformes: Sarcoptidae), affecting more than 150 mammal species worldwide. It has been stated that “no other permanent parasitic mite has such a large variety of hosts as does S. scabiei” [S. scabiei are unable to successfully reproduce and persist on human skin [S. scabiei cross-transmission between different animal species has been reported in more than 50 species [Scabies, also named sarcoptic mange when referring to animals, is a contagious parasitic skin disease caused by the burrowing mite,  DeGeer, 778  published until November 2021 with no time or language limits. The search strategy included different combinations of two or more of the following key words: “te 1800s .On a global scale, ZS episodes are associated with five continents  , with thAccording to the data shown in S. scabiei , dogs are less prone to develop the crusted “Norwegian” form of the disease, which is associated with high mite density and a subsequent greater infectious potential than other sarcoptic mange presentations [Pet owners are an important ZS target. So far, five pet species, namely dogs, cats, miniature pigs, horses and rabbits have been identified as sources for their owners. Dogs arntations . Worthy ntations ,17,18,20ntations .ZS originating from livestock is also a well-known condition, earning appellations such as “goat handler’s itch”, “dairyman’s itch”, “buffaloman’s itch”, “pig handler’s itch” and “cavalryman’s itch” ,38,39,55Panthera leo), a hyena (Hyaena hyaena) and a bear (Ursus arctos) within weeks of importation to France.Wildlife does not appear to be a common source of ZS, as only nine species in different parts of the globe have been found to be responsible for mite transmission to humans , althougOn occasion, people were infected by other people who had acquired scabies from a wild or domestic animal source ,43,44,47n = 21/47 citations) or occurred in the form of small outbreaks, with clinical signs appearing in more members of the same family (n = 20/47 citations) [ZS episodes in this review either involved single patients (tations) ,25,30 ortations) ,43,55 (Tvarietates”) recognized so far within the globally distributed S. scabiei. Consequently, the mite variants involved in ZS episodes have generally been identified on the basis of patient history and epidemiological background. While this is still a primary approach, sharing of similar mite variants can now be demonstrated on the basis of robust molecular evidence. Amongst several genetic markers available, microsatellites were shown to be the most informative and accurate for the purpose of characterizing interspecific cross-transmission of Sarcoptes mites [It is accepted that the study of morphology is of limited, if any, value in characterizing the different host- or host-group-adapted variants , suggesting that Sarcoptes is anything but a panmictic taxon and that Sarcoptes taxonomy is not as simplified as the “traditional” denomination that the clear host-based variants would suggest.Walton et al.  were thetzerland , mites ctzerland  providedtzerland  identifiSarcoptes molecular typing remains challenging for several reasons, including the difficulty of isolating individual mites from skin scrapings or biopsies and the low success rate of DNA extraction and PCR amplification of mite DNA [Despite recent genetic advances, mite DNA ,73.ZS diagnosis is often based on compatible signs coupled with consistent historical features, as the visualization of animal-derived mites on a patient can be challenging but it is still described in the literature ,15,26,43S. scabiei var. hominis [ZS usually manifests as an intensely pruritic papulovesicular rash, affecting areas such as the trunk, abdomen, forearms, thighs and legs, while sparing those parts of the body  that are frequently involved in human scabies by  hominis ,74,75  are sufficient for this purpose. Nonetheless, some dermatologists testify that patients are rarely willing to wait for the disease to run its course .Regarding the benefits of applying an etiological treatment, Smith and Claypoole  reportedThe identification and successful etiological treatment of animal source(s) is crucial not only to establish a correct diagnosis but also to avoid potentially unsafe over-treatment in patients with recurrent symptoms. Effective treatment protocols against sarcoptic mange are available in several domestic and wildlife species, including the new drug class of isoxazolines  ,79,80, aDermanyssus gallinae and Ornithonyssus sylviarum [Trombicula spp., Pyemotes ventricosus [“Pseudoscabies” is a broad definition describing a “skin eruption caused by mites for which humans are not the normal host” ,84. Sincylviarum , or to eDescriptive data on ZS episodes are still limited. The number of events may be greatly underestimated considering that the scientific literature in this review also includes outdated case reports, anecdotal reports and grey literature. Moreover, most of the cases were only reported as a supplement or added details in the frame of another study, and not as a primary description of ZS, which explains why keywords such as “pseudoscabies” or “zoonotic” did not appear in the abstract. This might also be attributed to the fact that ZS originating from numerous sources has already been described, and new reports in the scientific literature would now seem repetitive or obsolete when known animal sources are involved. Yet, ZS remains a neglected zoonosis, with no surveillance nor coordinated reporting system on a regional or global scale. Thus, information on its prevalence and spread can only be extrapolated from the available scientific literature or from anecdotal reports, with implicit inaccuracy.S. scabiei lineages in detail [With the advent of next-generation sequencing such as whole-genome sequencing, new methodologies will be available to explore genomic differences among animal and human n detail . To enhaFinally, we believe that key priorities in understanding ZS are represented by an increased surveillance in high-risk occupations and, on the occasion of outbreaks, improved communication between animal and human health specialists, in line with the One Health approach.


Neuronavigation greatly improves the surgeons ability to approach, assess and operate on brain tumors, but tends to lose its accuracy as the surgery progresses and substantial brain shift and deformation occurs. Intraoperative MRI (iMRI) can partially address this problem but is resource intensive and workflow disruptive. Intraoperative ultrasound (iUS) provides real-time information that can be used to update neuronavigation and provide real-time information regarding the resection progress. We describe the intraoperative use of 3D iUS in relation to iMRI, and discuss the challenges and opportunities in its use in neurosurgical practice.We performed a retrospective evaluation of patients who underwent image-guided brain tumor resection in which both 3D iUS and iMRI were used. The study was conducted between June 2020 and December 2020 when an extension of a commercially available navigation software was introduced in our practice enabling 3D iUS volumes to be reconstructed from tracked 2D iUS images. For each patient, three or more 3D iUS images were acquired during the procedure, and one iMRI was acquired towards the end. The iUS images included an extradural ultrasound sweep acquired before dural incision (iUS-1), a post-dural opening iUS (iUS-2), and a third iUS acquired immediately before the iMRI acquisition (iUS-3). iUS-1 and preoperative MRI were compared to evaluate the ability of iUS to visualize tumor boundaries and critical anatomic landmarks; iUS-3 and iMRI were compared to evaluate the ability of iUS for predicting residual tumor.Twenty-three patients were included in this study. Fifteen patients had tumors located in eloquent or near eloquent brain regions, the majority of patients had low grade gliomas (11), gross total resection was achieved in 12 patients, postoperative temporary deficits were observed in five patients. In twenty-two iUS was able to define tumor location, tumor margins, and was able to indicate relevant landmarks for orientation and guidance. In sixteen cases, white matter fiber tracts computed from preoperative dMRI were overlaid on the iUS images. In nineteen patients, the EOR (GTR or STR) was predicted by iUS and confirmed by iMRI. The remaining four patients where iUS was not able to evaluate the presence or absence of residual tumor were recurrent cases with a previous surgical cavity that hindered good contact between the US probe and the brainsurface.This recent experience at our institution illustrates the practical benefits, challenges, and opportunities of 3D iUS in relation to iMRI. Maximal safe resection of high-grade and low-grade gliomas has been established as an important prognostic factor with a strong correlation to survival 4. Image-5The first iMRI system, developed in the 1990s by General Electric in collaboration with physicians at Brigham and Womens Hospital, was designed as a double donut configuration with the surgeon standing in the aperture between the two halves of the magnet. This provided the surgeon full access to the head without the need to move the patient in and out of the bore of the scanner . This syIntraoperative ultrasound (iUS) is a powerful alternative to iMRI for monitoring brain shift and updating neuronavigation during surgery. The main advantage of iUS is that it causes minimal disruption to the surgical workflow while providing real-time information to the surgeon and is much less expensive and resource intensive than iMRI . 2D iUS 1316In this report, we present the challenges and opportunities in the use of 3D iUS during brain tumor resection in an advanced image-guided operating environment with multimodal preoperative MRI, neuronavigation and iMRI. We describe how we use preoperative MRI, iMRI, and 3D iUS intraoperatively and discuss the current and future impact of these imaging modalities on neurosurgical practice.We retrospectively evaluated patients who underwent image-guided brain tumor resection in the Advanced Multi-modal Image-Guided Operating (AMIGO) Suite , 20 at B21The study was conducted between June 2020 and December 2020 when an extension of a commercially available navigation software was introduced in our practice enabling 3D iUS volumes to be reconstructed from tracked 2D iUS images. During this period, a total of 23 cases were performed in the AMIGO suite by the study surgeons. Preoperatively, MR images were acquired using a 3T MRI scanner  and a 20-channel Siemens head-coil. Structural MR imaging included a 3D T1-weighted post-contrast sequence, a 2D T2-weighted sequence, a 3D MP2RAGE sequence, and a 3D T2-weighted FLAIR sequence. Patients with lesions in or near eloquent areas underwent blood oxygen level-dependent (BOLD) fMRI with a single-shot 2D echo-planar imaging (EPI) sequence with the appropriate tasks paradigms for language and motor mapping, according to our institutional protocol . PreoperiUS was performed using a 2D neuro-cranial curvilinear transducer on a cart-based ultrasound system . This sterilizable transducer has a contact surface area of 29x10 mm and frequency range of 13-5 MHz. The ultrasound probe was tracked with the Brainlab Curve navigation system . Similar to optical tracking of other surgical instruments, a fiducial array was attached to the ultrasound transducer and tracked relative to a reference array attached to the head fixation device . This allowed the navigation software to localize the acquired 2D iUS slices and orient them at the transducer tip. During image acquisition, the imaging plane of the transducer was oriented as close as possible to one of the three cardinal axes of the head, determined by the size and shape of the craniotomy . The 2D probe was slowly swept across the craniotomy to acquire a sequence of tracked 2D images. A 3D iUS volume was created from the tracked images at a resolution of 0.2mm x 0.2mm x 0.2mm using an automated ultrasound reconstruction extension at the backend of the navigation software . The 3D iUS volume was overlaid on preoperative imaging, providing insight into brain shift and possible registration errors. For each patient, three or more 3D iUS volumes were acquired during the procedure, and one iMRI was acquired after significant resection towards the end of the procedure. The iUS images included: an extradural image acquired immediately after the craniotomy and before dural incision (iUS-1); an intradural image acquired immediately after the dural opening (iUS-2); and a third image acquired immediately before the iMRI acquisition (iUS-3) S. .iMRI was performed using a 3T wide-bore (70cm) MRI scanner  after significant resection to evaluate the presence of any residual tumor. A temporary closure was performed prior to the iMRI acquisition. The total time required to obtain iMRI including preparation for scanning, MR safety check, image acquisition, and repreparing for surgery t was 1-1.5 hours per session. In some of the surgeries, clinical needs necessitated imaging sessions at 2 distinct surgical timepoints. The Brainlab registration module was used to automatically register iMRI to preoperative MRI (rigid registration). This allows us to compare iMRI in the same coordinate space as iUS.iUS-1 and iUS-2 were used to provide a real-time assessment of the lesion extension, location and local anatomy and to confirm navigation accuracy. iUS-3 was qualitatively compared to iMRI to evaluate how well the iUS could image residual tumor and predict the extent of the resection. The presence or absence of residual tumor on iUS-3, as per the attending neurosurgeon, was recorded prior to the acquisition of the iMRI. The assessment of the residual tumor in iMRI was also made by the attending neurosurgeon in consultation with a neuroradiologist.IDH1-mutant grade 3 gliomas, three patients had an integrated histological and molecular diagnosis of glioblastoma multiforme, ten had grade 2 gliomas, one had brain metastases from a non-small cell lung carcinoma, one had a diagnosis of radiation necrosis and one had a central nervous system lymphoma. GTR was achieved in twelve patients . Temporary postoperative deficits were observed in five patients, all of whom had tumors in eloquent or near-eloquent regions. We compared the clinical utility of iUS with preoperative MRI and iMRI in twenty-three patients  who underwent image-guided brain tumor resection in the AMIGO suite Table 1.In all cases, iUS images acquired at two time points were visually compared with either preoperative MRI or iMRI. In nineteen patients, the iUS and iMRI findings regarding the status of the resection (GTR or STR) were concordant. In all these patients, iUS was able to define tumor location, tumor margins and was able to indicate relevant landmarks for orientation and guidance. The remaining four patients where iUS was not able to evaluate the presence or absence of residual tumor were recurrent cases with a previous surgical cavity that hindered good contact between the US probe and the brain surface. In sixteen cases, white matter fiber tracts computed from preoperative dMRI were overlaid on the iUS images. A 61-year-old right-handed man presented with new onset focal seizures, manifesting as dysarthria, and left-sided facial twitching. Brain MRI revealed a non-enhancing mass in the right frontal lobe anterior to the precentral gyrus Figure 1A right frontotemporal craniotomy with transcranial and direct cortical motor mapping was performed. After the craniotomy, an extradural ultrasound (iUS-1) confirmed a homogeneously hyperechoic mass, expanding the gyrus anterior to the prefrontal gyrus 3A. OverA 28-year-old right-handed man presented with episodes of anxiety and fear lasting 20-30 seconds, with an initial diagnosis of post-traumatic stress disorder. Escalating frequency of these episodes prompted imaging evaluation, which revealed a large left non-enhancing mass in the mid- and posterior medial temporal lobe. Preoperative language fMRI showed BOLD activations in the putative receptive language areas of the left superior temporal gyrus, within 1cm of the T2-hyperintense lesion. Visual tasks were used to map the primary visual cortex using fMRI. The AF, IOFF/IFOF, ILF, FAT and Optic Radiations (OR) were created on the tractography software using fMRI BOLD activation areas as seed ROIs, consistent with their expected anatomical locations. An unexpected fiber bundle running through the middle of the posterior aspect of the lesion was suspected to be related to the visual pathway Figure 4IDH1-mutant anaplastic astrocytoma.A left temporal craniotomy was performed, with subsequent extradural ultrasound (iUS-1) which confirmed presence of a heterogeneous hyperechoic mass within the exposed area 5. When A 53-year-old woman presented with a partial motor seizure, with postictal transient right-sided hemiparesis. Brain MRI showed a non-enhancing deep-seated lesion in the left cingulate gyrus, extending to the mid-/posterior corpus callosum inferiorly and to the paracentral gyrus superiorly. Preoperative fMRI of hand clenching, finger tapping, and toe wiggling tasks showed BOLD activations in the anatomically expected M1 location and more anteriorly in the superior frontal gyrus. DTI tractography using fMRI BOLD activation areas as seed ROIs was used to generate the left CST and the left FAT. A 3D rendering of preoperative T1 post-contrast MRI reconstruction highlighted two prominent cortical veins entering the superior sagittal sinus in the planned craniotomy. Taken together, preoperative imaging suggested a narrow window for a safe operative corridor to the tumor.A left frontal craniotomy with transcranial and direct cortical motor evoked potentials as well as subcortical motor mapping was planned. The patient was positioned supine with head neutral and 30 neck flexion. Via a linear incision a craniotomy was performed to expose the superior sagittal sinus and coronal suture. iUS-1 confirmed adequate exposure of the tumor Figure 6In the present paper, the locations and margins of the tumors as shown by iUS were in agreement with preoperative MRI. This is consistent with findings in the literature of significant correlation between 2D US and preoperative MRI , 29. WhiNavigated 3D iUS was able to provide real-time information regarding brain shift, possible problems with registration and to identify potential surgical entry points in all cases. Since we used iUS-1 and iUS-2 to validate neuronavigation on preoperative MRI, we were able to recognize rigid mismatches and avoid errors such as incision of the incorrect gyrus that could have happened if we had navigated solely on the preoperative MRI (Case 1). iUS allowed us to enhance neuronavigation by providing important information regarding the best window between two functional areas to proceed with a corticectomy (Case 3). A recent study of 210 glioma patients reported that serially acquired navigated iUS played an important role in assessing resection progress .An important advantage of iUS is its ability to monitor brain shift over the course of surgical resection and to provide real-time anatomical information that reflects the current intraoperative state. In our cohort, we observed minimal brain shift between iUS-1 and iUS-2, but as the surgical resection progressed, the mismatch between the preoperative MRI on the navigation system and the iUS became evident, rendering neuronavigation suboptimal for clinical decision-making. Therefore, the only true, real-time image-guidance available to us was from iUS. While we have not employed any non-rigid registration methods in this study, we and others have developed several that have continued to move the field forward for registration of MRI-MRI and MRI-iUS volumes , 3337.33Our study showed a concordance rate of 100% between iUS and iMRI findings in predicting the EOR in patients where good contact between the US probe and the brain surface was possible; on iUS-3 four patients showed no residual tumor and fifteen patients showed residual tumor, all confirmed by iMRI. These results are similar to the earliest study that revealed a 100% concordance rate between the two imaging modalities . 38) sh sh38) shIn patients with large resection cavities, either new or previous, contact between iUS probe and the brain surface can be difficult or impossible to achieve, particularly in cases where the head position does not favor retention of fluid in the cavity. In such cases we were unable to obtain 2D and hence 3D iUS.Although 3D iUS provides us with a powerful surgical tool, creating these volumes poses some challenges. It is difficult to maintain a uniform speed of probe translation while collecting 2D images for a volume. This task becomes more difficult later in the surgery when the resection cavity is filled with fluid and subtle variations in the steadiness of the transducer leads to artifacts in the resultant 3D volume.The impact of iUS on neurosurgical practice continues to evolve in the face of improved transducers, neuronavigation systems, and surgical technique. This review of the recent experience at our institution illustrates the practical benefits of iUS in relation to iMRI, and the challenges encountered in a range of tumor resection cases.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Mass General Brigham Institutional Review Board. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.Data collection: DB, PJ. Data interpretation: DB, PJ, AG, WB, TK, SF. Manuscript: DB, PJ, AG, WB, TK, SF, SP. Manuscript editing: DB, PJ, AG, WB, TK, SF, YT, SP, WW. Bibliography editor: DB, NJ, TK. Images editor: DB, PJ. All authors contributed to the article and approved the submitted version.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.


The development of hydatid cysts in the muscle is rare, and it is even rarer in children. We report the case of a 9-year-old child treated in pediatric orthopedics department at the University Hospital of Marrakech for a hydatid cyst psoas muscle revealed by lameness.  The child was consulted for painless and afebrile lameness of the left hip evolving since 3 months. The clinical examination finds a mass of the left flank. Investigations based on the abdominal ultrasound in first intention showed a hydatid cyst depending on the left psoas muscle. Pelvic CT and abdominal MRI were able to confirm the diagnosis and allowed a better study of the cyst neighboring elements. The drainage of the cyst followed by pericystectomy after evacuation of the vesicles contained in the cyst was done as radical treatment.  The hydatid cyst of the psoas is a rare entity in the child requiring a good radiological study of the cyst as well as its neighboring elements to propose the most adapted surgery. Taenia Echinococcus granulosus responsible for cystic formation called hydatid disease or echinococciasis. Hydatid cyst is still a public health problem in several countries where it is endemic. The muscle is an uncommon location for hydatid cyst, accounting for only 2 to 3% of cases [Human is an accidental host in the parasitic cycle of of cases . We repoWe report the case of a 9-year-old boy admitted to the pediatric emergency unit for painless limp without fever since 3 months. He had no alterations in his objective examination upon admission. He had no significant previous medical events, but alluded to having regular contact with dogs and sheep in Douar where he lived in the rural zone of Kalaa Sraghna city in Morocco. The physical examination noted a painless wheelbase of the left iliac fossa and a perfectly free and painless left hip joint. Workup findings included inflammatory biological markers with moderate elevation of C-reactive protein at 75 mg/L and erythrocyte sedimentation rate of 44 mm at the 1st hour. Hypereosinophilia was noted at 1.6% of the leucocytes formula. The hydatic serology was negative in the case of our patient. The abdominopelvic ultrasound revealed a cyst of the left psoas muscle looking like a hydatid cyst measuring 11.8 cm × 5.85 cm without other lesions particularly in the liver. An abdominopelvic CT was ordered to better characterize the mass and relations with its neighboring structures ; it showDiagnosis is confirmed, and cyst limits and relations are well defined; the patient was proposed for surgery. We used the left pararectal approach with retro-peritoneal passage. The puncture of the contents of the cyst brought back a purulent liquid (infected hydatid cyst) which was completely sucked up and then extraction of the proliferous membrane with realization of a pericystectomy and abundant washing of the residual cavity with physiological saline. Antimicrobial therapy with ceftriaxone and flagyl was started perioperative.th day after surgery. The patient was seen monthly in consultation during three months and then every six months during two years without noticing any abnormalities on clinical examination and ultrasound control.We followed up the patient for 34 months. Immediate postoperative follow-up was simple, and the patient was discharged in the 4Echinococcus granulosus) in the host's organism. The definitive host of this tenia is dog, whereas the development in humen is accidental by consumption of parasitized viscera, particularly the liver and lungs of the intermediate host (sheep). Hydatic cyst is endemic in the rural and poor population [Hydatidosis is a zoonotic condition caused by the development of the larval form of canine tenia (pulation . The patpulation , 3, 4, epulation , renitenpulation , 7. Somepulation , 7. Radipulation . Ultrasopulation , 10. It pulation , 10. EosAccording to the latest recommendations published by the WHO-IWGE about the treatment of liver hydatid disease, the choice of treatment should be based on the characteristics of the cyst, the experience of the medical staff and the availability of drug therapy/surgery, and the possibility of following the patients in the long term; however, no ideal treatment was defined in the recommendations .Surgery remains the first-line treatment for psoas hydatid cyst. Medical treatment based on albendazole or mebendazole remains an alternative for inoperable cases or in massive recurrence in addition to surgery , 11, 12 The psoas hydatid cyst remains a very rare entity, especially in children, and can simulate a tumor mass. Hence, the interest of an adequate diagnostic procedure based on ultrasound and CT is usually sufficient to make the diagnosis and specify relations with neighboring organs, thus conditioning the therapeutic approach where surgery remains the only radical treatment. However, we recommend association of antiparasitic treatment to avoid dissemination or recurrence of cyst.


The treatment effects on hospitalization for heart failure (hHF) from sodium-glucose cotransporter 2 (SGLT2) inhibitors may vary among type 2 diabetes (T2D) patients depending on whether or not they have established atherosclerotic cardiovascular diseases (ASCVD). We aimed to examine differences in hHF outcomes after dapagliflozin or empagliflozin use between T2D patients with and without a history of established ASCVD.We conducted a retrospective multi-institutional cohort study in Taiwan. We included T2D patients newly receiving dapagliflozin or empagliflozin during 2016–2019, and followed them up until December 31, 2020. We implemented 1:1 propensity score matching to create homogenous groups for comparisons. We generated Cox proportional hazard models to compare the risk of hHF between dapagliflozin and empagliflozin (reference group). We included interaction terms of SGLT2 inhibitor and ASCVD history in the regression models to examine effect modification by ASCVD.We included a total cohort of 9,586 dapagliflozin new users and 9,586 matched empagliflozin new users. The overall hHF risks were similar for dapagliflozin and empagliflozin . However, differential hHF risks between dapagliflozin and empagliflozin were observed only in the subgroup without ASCVD , while not in the subgroup with ASCVD , and the p-value for examining interaction was 0.0097.In this study, history of established ASCVD was associated with different hHF risks among SGLT2 inhibitors. For T2D patients without ASCVD, dapagliflozin may offer a more favorable hHF reduction effect, compared to empagliflozin, in clinical practice. Future prospective studies should be conducted to validate our findings.The online version contains supplementary material available at 10.1186/s12933-021-01406-3. Sodium glucose co-transporter 2 (SGLT2) inhibitors, the second-line treatment for type 2 diabetes (T2D) with their pleiotropic metabolic effects –5, offerRecently, Shao et al. analyzing Taiwan’s multi-institutional electronic medical records (EMR) database found that the use of dapagliflozin may have more favorable outcomes on heart failure, compared to the use of empagliflozin . HoweverThis retrospective cohort study is based on Taiwan’s extensive, multi-institutional Chang Gung Research Database (CGRD). CGRD comprises seven Chang Gung Memorial Hospitals located throughout Northern and Southern Taiwan, and contains the EMR of 1.3 million patients (6% of Taiwan’s population). Disease identification in the CGRD follows the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) prior to 2016, and ICD-10-CM thereafter. For the purpose of assuring patients’ baseline status in regard to cardio-metabolic and cardiovascular conditions, the database also includes laboratory examination data. Details of data structures and representativeness of the CGRD are described elsewhere , and man2 because, following the drug label information, SGLT2 inhibitor use was not suggested for them [For the analysis we adopted a new-user design with an active-comparator to minimize potential selection bias and other unmeasured confounding factors . We inclfor them .The study outcome was hHF, as determined by the clinical diagnosis (ICD-10-CM codes: I50) at any point in the hospital discharge records. The diagnosis codes for heart failure in CGRD have been validated by previous study with positive predictive value of 89.8% . We follWe determined potential confounding covariates on the basis of expert opinion and previous studies , 28–31. To afford more homogeneous comparisons, we used the propensity score method to generate comparable groups , 35. We We conducted several sensitivity analyses to examine the robustness of our results. First, to ensure the outcome validity, we re-defined hHF to include only diagnosis from specialized cardiologists at discharge. Second, we used heart failure diagnosis codes at discharge plus the serum B-type Natriuretic Peptide (BNP) levels at two cutoffs of 100 pg/ml and 400 pg/ml during hospitalization to redefine heart failure. BNP levels appear useful for the detection of heart failure, with a cutoff < 100 pg/ml excluding heart failure and > 400 pg/ml a possible diagnosis of heart failure . Third, We calculated E-value on the basis of our study outcomes. E-value was developed by Vanderweele et al. to estimate the minimum strength of association that an unmeasured confounder, conditional on the measured covariates, would require to fully explain away the observed associations . For exa2, respectively. This was similar to empagliflozin new users with a mean age of 60.0 (SD 12.0) years, HbA1c of 8.7 (SD 1.7) % and eGFR of 92.3 (SD 31.6) ml/min/1.73 m2, respectively. At baseline, 25.1% of dapagliflozin new users and 25.4% of empagliflozin new users had a history of ASCVD. The mean follow-up periods were similar for dapagliflozin (2.7 years) and empagliflozin (2.7 years) new users. Without stratification by history of ASCVD, there was no significant difference in hHF incidence between dapagliflozin (7.56/1000 person-years) and empagliflozin new users (8.39/1000 person-years) , lower hHF risks were observed, compared to those receiving empagliflozin (5.42/1000 person-years), with an HR of 0.67  . Table S4. Results from the Cox regression model after 1:1 propensity score matching Table S5. The number of patients at risk, patients with hHF outcomes, and patients censored.


Although they are comparable, our study shows that NDVI and EVI2 differ in their ability to track the phenological cycle of bracken fern. Overall, EVI2 performed better in estimating bracken fern phenological metrics as it related more to ground observed phenological events compared to NDVI. The key phenological metrics extracted in this study are critical for improving the precision in the controlling of the spread of bracken fern as well as in implementing active protection strategies against the invasion of highly susceptible rangelands.Bracken fern is an invasive plant that has caused serious disturbances in many ecosystems due to its ability to encroach into new areas swiftly. Adequate knowledge of the phenological cycle of bracken fern is required to serve as an important tool in formulating management plans to control the spread of the fern. This study aimed to characterize the phenological cycle of bracken fern using NDVI and EVI2 time series data derived from Sentinel-2 sensor. The TIMESAT program was used for removing low quality data values, model fitting and for extracting bracken fern phenological metrics. The Sentinel-2 satellite-derived phenological metrics were compared with the corresponding bracken fern phenological events observed on the ground. Findings from our study revealed that bracken fern phenological metrics estimated from satellite data were in close agreement with ground observed phenological events with R Pteridium Aqulinimun) is one of the most problematic alien invasive ferns that encroaches into new landscapes [The encroachment of invasive species in productive rangelands influences changes in nutrient cycles , fire inndscapes . In Soutndscapes  noted thndscapes , animal ndscapes , forestrndscapes , leadingndscapes –11, whilndscapes . Furtherndscapes .Understanding the biological structure and timing of bracken fern phenology improves rangeland management’s knowledge and ability to choose the suitable treatment method in areas infested by the fern . The pheEarlier works on bracken fern phenology have used field-based studies , 25 and LSP scientists have utilized numerous spectral vegetation indices derived from satellite data to estimate the phenological cycles of vegetation at various scales –38. OverThe characterization of the phenological profile of specific vegetation species using satellite data has mainly been done for crops –48, whil3 and C4 grass species such as Festuca and Themeda respectively [The Cathedral Peak area is a World Heritage Site which falls within South Africa’s summer rainfall region. The Drakensberg climate is a result of a combination of factors such as altitude, topography as well as the Agulhas current in conjunction with atmospheric pressure system patterns over and adjacent to South Africa . The meaectively . The Catectively . Bracken2) for them to match the Sentinel-2-pixel size as well as to account for geolocation errors of the GPS and the Sentinel-2 imagery. Purposive sampling was used to select bracken fern patches with more than 75% bracken percentage cover. The bracken fern phenological developments were recorded weekly from 1 January 2016 to 31 December 2018. Ferns like bracken develop fronds instead of leaves, for ground phenology observations in this study, the term ’fronds’ was used instead of leaves. Specifically, we recorded the dates of bracken fern frond emergence, expanded frond growth, withering and frond drying and considered them as green up, maturity, senescence and dormancy respectively. The recording of bracken phenological events on the ground was done with the assistance of the Department of Invasive Species for the Ezemvelo KwaZulu-Natal (KZN) Wildlife under the project lisence number 144/2017b. There were no plants and animals that were destroyed or killed during then data collection process. The ground phenology recordings included the collection of bracken fern patches locations using a portable Leica GS20 Global Positioning System. A total of 60 bracken fern patches were collected. The bracken fern patches that were recorded were larger than 10 by 10 m (100mhttps://earthexplorer.usgs.gov/). Sentinel-2A and 2B satellite images were included in the time series data for bracken fern phenological analysis. The satellite images were acquired at the processing level 1C. The images were atmospherically and geometrically corrected by ESA. A total of 108 images from January 2016 to December 2018 were acquired. Sentinel-2 images with less than 20% cloud cover were selected and included in the phenological analysis. The Function of mask (Fmask) 4.0 algorithm was used for detecting and removing clouds and shadows in the satellite images. For more details about the Fmask 4.0 algorithm procedure, see Qiu, Zhu [Sentinel-2 Multispectral Instrument (MSI) satellite images were obtained from the European Space Agency (ESA) online platform   and the e sensor , 2.5 is The current study used TIMESAT 3.3 program for processing vegetation indices time series data and estimating bracken fern phenological metrics. The TIMESAT program provides an understandable Matlab based user interface which facilitates the manipulation of data into vegetation phenological parameters. Specifically, three main processing stages were executed in TIMESAT: (1) preprocessing of NDVI and EVI2 time series data by detecting and removing outliers, (2) data smoothing and gap filling using the SG, DL and AG models based on the procedures which are described in detail by Eklundha and Jönsson  and (3) In the current study, the bracken fern growth cycle was characterized by four main transition dates which are; 1) green up: indicating the date of onset of vegetation indices increase, 2) maturity: the date indicating the onset of vegetation indices maximum, 3) senescence: the date of onset of vegetation indices decrease and 4) dormancy: the date of onset of vegetation minimum. The TIMESAT program relies on the assumption that the growing seasons begin and end at a similar time annually. In principle, the start and end of the season for the targeted year is identified in the same time period as the first and third years . The sea2) [To assess the statistical relationships between satellite-derived phenological metrics and ground observed bracken fern phenological events, the coefficient of determination (R2) , the Roo2)  and the 2)  were comp < 0.05) for all the bracken fern phenological stages based on both NDVI and EVI2 time series. Results obtained using NDVI phenological retrievals shows that the mean bracken fern green up onset dates for the AG, SG and the DL were approximately around day 298, 296 and 294 while EVI2 dates were estimated to be around day 280, 288 and 284 respectively. Using the calendar dates, the average timing of bracken fern green up onset dates was towards the end of October 2016. The EVI2 green up onset dates were generally earlier than NDVI dates by an average of 11 days across the three models. For all the models, the standard deviations for the green up onset retrievals were consistent with a range of 2 to 5 days. Based on the NDVI phenological estimations, the DL model recorded the lowest deviation of 2.96 days while the SG NDVI model reported the highest deviation of 5.3 days.The NDVI maturity onset dates for the AG, SG and the DL were estimated to have occurred around day 54, 57 and 56 while the EVI2 dates were predicted to be around day 44, 53 and 54 respectively. Using the calendar dates, the estimated bracken fern maturity dates were towards the end of February 2017. The NDVI maturity onset dates were later than EVI2 dates by an average of 8 days across the three models. Compared to the green up the phenological stage, the maturity standard deviations were higher across all the models ranging from 2 to 7 days. The bracken fern green decrease was associated with the plummet in the vegetation index signal which signified the onset of the senescence phenological stage. Based on the AG, DL and SG the NDVI estimated date of senescence onset was around day 96, 99 and 101 while EVI2 retrievals estimated day 88, 90 and 81 respectively. The standard deviations ranged from 2 to 5 days across all models. The NDVI retrievals predicted the onset of dormancy stage to be around day 181, 177 and 176 for AG, DL and SG, while EVI2 retrievals were estimated to be around day 190, 184 and 196 respectively. For both NDVI and EVI2 phenological retrievals, the DL dormancy dates were earlier when compared to the other two models by an average of 16 days. The SG model had the lowest standard deviations (NDVI = 2.03 and EVI2 = 2.52), while the DL recorded the highest deviations (NDVI = 6.23 and EVI2 = 3.42).p < 0.05) although the correlation coefficients were weak for some of the phenological stages with R2 values ranging from 0.49–0.61. For the green up onset stage, the coefficient of determination (R2 = 0.58) indicated a good correlation between NDVI and EVI2 phenological retrievals. The EVI2 phenological dates for green up onset were earlier than NDVI retrievals for most of the pixels across the study site. The green up onset RMSD was 8.2 days while a bias of 4.9 days was recorded.To compare bracken fern phenological metrics retrieved using NDVI and EVI2 time series, we averaged the dates of the four metrics estimated using the three models embedded in TIMESAT. Findings from our study demonstrated that the phenological metrics estimated using NDVI and EVI2 across the four major bracken fern phenological stages were comparable. The statistical analysis on 2 = 0.49), the highest RMSD (9.8 days) as well as the highest bias of 5.6 days. Like the green up onset dates, the EVI2 retrievals recorded earlier green up onset dates compared to the NDVI retrievals. The senescence stage recorded a good correlation (R2 = 0.61) for the phenological retrievals between the two vegetation indices and a relatively moderate RMSD of 4.3 days and a bias of 3.4 days. The highest correlation between NDVI and EVI2 phenological retrievals was reported in the dormancy phenological stage (R2 = 0.57) while the RMSD recorded 5.8 days and bias was 3.7 days. Generally, the agreement was moderate, and bias was low between phenological metrics estimated using the two vegetation indices across the four bracken fern phenological stages. The EVI2 phenological retrievals were mostly earlier than NDVI retrievals across the four bracken fern phenological stages.The maturity stage recorded the lowest correlation between NDVI and EVI2 phenological retrievals (Rp < 0.05) with bracken fern ground observed phenological events with varrying correlations across all phenological stages. To provide a more comprehensive and quantitative assessment, 2 values ranging from 0.53–0.85. The dormancyEVI2 phenological retrievals recorded the highest correlation (R2 = 0.85) with the ground observed frond drying and falling dates. The relationship between EVI2 retrieved dormancy onset dates and the ground observed bracken fern frond drying and falling showed a very strong correspondence for more than 75% of the pixels across the study site. The maturity EVI2 also reported a strong correspondence (R2 = 0. 72) with ground observed bracken fern expanded frond growth.Bracken fern phenological metrics estimated using NDVI and EVI2 generally showed a good agreement with phenological dates from ground observations. Both EVI2 and NDVI phenological metrics show significant linear relationships  was reported between maturity EVI2 and bracken fern frond emergence. Generally, the EVI2 phenological retrievals corresponded more with bracken fern ground observed phenological events compared to NDVI phenological retrievals as shown by higher EVI2 correlation coefficients and lower RMSDs and Biases. Overall, the satellite-based bracken fern phenological estimates matched moderately well with the ground observed phenological events.The RMSDs statistical values between satellite-based phenological retrievals and ground observed phenological transitional dates ranged from 2.5 to 6.4 days across the four bracken fern phenological stages. The RMSDs between NDVI and corresponding ground transitional dates were modestly higher (approximately one week) for senescence and dormancy phenological stages, while the EVI2 maturity and dormancy had the lowest RMSDs of 3.1 and 2.4 days respectively. The RMSDs between NDVI and ground recorded phenological dates were also higher (approximately one week) for maturity, senescence and dormancy while the green up phenological stage showed the lowest RMSD value of 4.6 days. The bias between satellite-based phenological retrievals and ground observed phenological events appeared to be very low as they ranged from 2.2 to 5.3 days. The largest bias (5.3 days) was recorded between green up The current study characterized the phenological cycle of bracken fern invasive species using NDVI and EVI2 time series data derived from the Sentinel-2 MSI sensor. The satellite-based phenological retrievals were compared with bracken fern ground observed phenological events. The Sentinel-2 sensor proved to be a reliable data source that could assist in improving the understanding of bracken fern phenological cycles, an aspect that could lead to better management of rangelands that are infected by the fern. Corresponding to our findings in this study, a plethora of scientific studies have also reported the capability of Sentinel-2 data 0.in extracting the phenological cycles of vegetation at various scales , 69–71. The bracken fern phenological metrics estimated using the three models in the TIMESAT program were comparable across the four bracken fern phenological stages. The shape of the fitted NDVI and EVI2 curves in The validation of phenology metrics is essential for the evaluation of satellite sensors’ performance in estimating LSP. However, previous research studies have shown that the validation of remote sensing products is a huge challenge in LSP investigations –79. OverThe NDVI showed poor correlation with ground observation during the maturity phenological stage, while the EVI2 retrievals performed well during the maturity stage. As the bracken fern fronds increased in size and the canopy expanded, NDVI tends to saturate and become less efficient in extracting phenological metrics during the maturity period. The differences in phenological retrievals between NDVI and EVI2 probably originated from various resistance levels to noise and sensitivities to spectral signal at different bracken fern stage of the growing season. The NDVI’s poor performance in estimating the bracken fern maturity could probably be related to its loss of sensitivity when vegetation canopy’s leaf area index reaches a maximum as reported by Davi, Soudani  and SoudChallenges in controlling the encroachment of bracken fern into areas of ecological importance due to inappropriate timing, have been widely reported in literature , 88, 89.The debate with regards to the most suitable methods of controlling the spread of bracken fern has received much attention in the literature , 91, 92.The current study focused on characterizing the phenological cycle of bracken fern using NDVI and EVI2 time series data derived from the Sentinel-2 sensor. The satellite-based phenological retrievals showed a good correlation with bracken fern ground observed phenological events, making remote sensing technology a potential tool for effective bracken fern management. Inter-comparisons between NDVI and EVI2 based phenological metrics revealed that the two vegetation indices differ in their ability to track the phenological developments of bracken fern during its growing season. EVI2 is more suitable for retrieving LSP metrics than NDVI as it produced phenological metrics that were more related to bracken fern ground phenological events. The AG and DL models produced the best fits that optimally described the phenological profile of bracken fern. Through this study, remote sensing has been demonstrated to be an invaluable data source that can be used by conservationists, ecologists and rangeland managers in controlling and managing bracken-infested rangelands. The key phenology dates derived from the Sentinel-2 time series are relevant in informing stakeholders and policymakers on designing effective management strategies for controlling bracken fern invasion. After the successful characterization of bracken fern phenological cycle in the Drakensberg, the bracken fern phenological data may be used to improve the management of rangelands.