Research indicates that sexual violence affects about 30% of women in the general population and between two to three times as much for autistic women.n = 225). We assessed victimization through an open question and through a specific questionnaire, derived from the Sexual Experiences Survey-Short Form Victimization.We investigated prevalence of sexual abuse, autistic traits and a range of symptoms, using an online survey addressed to the women of the French autistic community (n = 12) and/or receive care (n = 13). For the remainder 75%, reporting did not lead to action.Both case identification methods yielded high figures: 68.9% victimization (open question) compared to 88.4% (standardized questionnaire). Two thirds of the victims were very young when they were first assaulted: among 199 victims, 135 were aged 18 or below and 112 participants were aged 15 or below. 75% of participants included in our study reported several aggressions. Analyses indicate that primo-victimization was highly correlated to revictimization and that being young increased that risk. Young victims were also at higher risk of developing post-traumatic stress disorder. A third of the victims reported the assault. 25% of those were able to file a complaint (Those findings indicate a very large proportion of victims of sexual assault among autistic women, consistently with previous research. The World Health Organization states unambiguously that sexual violence is systemic and that vulnerable individuals are preferably targeted by offenders. We therefore postulate that it would be erroneous to consider that victimization of autistic women is mainly due to autism. On the contrary, autism seems to be just a vulnerability factor. Some authors propose that educating potential victims to better protect themselves would help preventing abuse. We reviewed this proposition in the light of our results and found it to be impossible to apply since more than half of the victims were below or at the age of consent. Literature about sexual violence is discussed. Large-scale prevention programs proposed by World Health Organization and the Center for Disease Control aim at cultural changes in order to diminish gender inequality, that they identify as the very root of sexual violence. Whether sexual violence occurs in the context of an intimate partnership, within the larger family or community structure, or during times of conflict, it is a deeply violating and painful experience for the survivor.’’2 Such wide-ranging consequences include long-term depression, post-traumatic stress disorder (PTSD), substance abuse and suicide  states unambiguously that ‘‘Sexual violence is a serious public health and human rights problem with both short- and long-term consequences on women’s suicide . It is w suicide . For exa suicide . By an iSexual victimization is very common in the general population . HoweverThe last decade, however, has seen a steady change taking place: there is a growing movement of victims who have found strength in numbers through social media. They have become able to face social stigma in order to report what happened to them . Such social movements might be beneficial for victims in that they realize that they are not alone and can find support. They might also be beneficial for society in that they help acknowledging the extent of the problem, since the massive amount of testimonies published everywhere demonstrate that sexual abuse victims are much more numerous than previously believed.Statistics on prevalence in the general population indicate elevated rates of victimization all over the world. The recent WHO publication might be the most reliable reference on this topic . It statSexual victimization rates represent about one woman out of three and one child out of ten. Readers may not have expected such elevated figures, especially since many previous studies have reported lower rates  . This isDespite this geographical and methodological variability, the Several researchers have investigated whether autistic women would exhibit higher levels of victimization than women in the general population. Given that being on the autism spectrum condition is characterized by experiencing difficulties in social communication, such as decoding hidden intentions and emotions of others, understanding implicit communication and elements of context, it is expected that women on the spectrum may be at considerable risk for sexual victimization, a hypothesis confirmed by all published studies on this topic. To this end, we have attempted here to conduct an exhaustive review of such research.n = 95) reported experiencing some form of sexual victimization after age 14 and into adulthood. In a study exploring self-reported experiences of many forms of victimization and perpetration, researchers found that adults on the autistic spectrum (n = 45) were more likely to report several forms of victimization, including sexual violence, than control participants (n = 42) , it was found that 10% of the sample had been sexually molested ((n = 42) . In a Da(n = 42) . In a stch abuse . In anotmolested . Interesmolested .n = 7) and/or by strangers (n = 3) (n = 158) were twice as likely to report unwanted sexual contact as compared to students without ASC, but the analysis was limited by the small size of the group of victimized autistic participants (n = 13). Interestingly though, out of those 13 victims, 8 were female and 3 were non-binary, despite the autistic sample including more males (n = 93) than female (n = 44) and non-binary (n = 21) participants  . In a sticipants . Of noteicipants . In a laspectrum , 2020. Tspectrum . In theiual ones . The lasWe tentatively conclude from this short review that being autistic means undergoing a 10–16% risk of enduring sexual molestation as a child and a 62–70% risk of being sexually victimized in adulthood. Most victims are girls and women: autistic female risk of being sexually assaulted is between two and three times as much than non-autistic females and about four times as much than autistic males. Those figures are consistent with the general population rates: around 30% of women and 12% of children are sexually victimized in their lifetime.n = 225) by using standardized assessment. Thereby, we have recruited participants to our survey through the websites of non-profit organizations in order to investigate their lifetime prevalence exposure to sexual aggression and abuse, their autistic traits, as well as comorbid psychiatric disorders for which they were treated  and behaviors that can be connected with childhood or adult sexual abuse  insofar as these behaviors may represent “red flags” that can alert relatives and clinicians. Our study first aim was to confirm previous results using a larger sample. More importantly, our goals were to expand such results by investigating several dimensions of sexual victimization that bear clinical and social significance, such as age at first assault, that we hypothesized to be correlated to levels of revictimization. We also used two modes of inquiry (directed versus open question) because we expected that they would yield different results. Last, we explored other dimensions such as health consequences of aggression, with a focus on post-traumatic stress-disorder, and follow-ups of the aggression such as reports and opinions of victims regarding prevention methods. Importantly, in our study, sexual victimization was defined as one or several of the three following situations: unwanted sexual contact; rape; attempted rape. Our definition was therefore limited and did not include other forms of sexual violence such as sexual harassment, stalking, indecent exposure, revenge porn, etc.In the line of this research, we have conducted an internet-based survey in order to measure the prevalence of sexual victimization in women on the autism spectrum  score less than 14; 4 were aged less than 18).This internet-based study was conducted in France in April and May 2018. A total of 234 participants completed the questionnaire. Our final sample was In order to facilitate results replication and refutation, an extended and detailed version of the statistics section is provided as https://nakala.fr/10.34847/nkl.4021h29a.Repository URL for R code is: https://nakala.fr/10.34847/nkl.d3d35i2o.Repository URL for dataset is: Association Francophone des Femmes Autistes, Asperger Amitié, Asperger Aide, France Asperger…) and asked them for their support by sharing to their community an internet link to a data collection site.Due to social and communication difficulties, many women on the autism spectrum join online autism communities where they can find help and support from peers and where they may feel more comfortable discussing issues of sexual violence that they have experienced. We have contacted several local organizations dedicated to autism . As per French laws regarding data privacy, the questionnaire was declared to CNIL authorities  under identifier # 2172655.4. All questions were multiple choice questions with the exception of questions #8, #13, #33, #36, #37 which were multiple response questions . In addition, questions #8, #9, #13, #33, #34, #36, #37 included an open field question: “Other (please specify).”All participants answered to three questionnaires, for a total of 38 questions, using an online survey system∘Questions #1–6: socio-demographic information.∘Questions #7–9: health level and A.S.D diagnosis.∘Questions #10–12: sexual activity and sexual orientation.∘Question #13: victimization status in an open question form allowing multiple responses. Choices were as follows: (1) I haven’t been sexually assaulted; (2) I have been sexually assaulted; (3) I have been raped; (4) I underwent an attempted rape; (5) I do not know; (6) Other (with open field).∘Questions #14–27: autistic traits  .∘Questions #28–31: victimization level  scale – Short Form Victimization) .∘Questions #32–33: age at first assault and revictimization status.∘Question #34: for victims, did they report the assault (with no specification to whom)? And what were the consequences of reporting ?∘Question #35: for victims, what could have prevented the assault? .∘Question #36–37: presence of psychiatric disorders and assessment of consequences following the assault.∘Question #38: participants’ consent to have their responses used in this study.The RAADS scale is considered to be one of the most reliable self-report screening tools for ASD. In the validation study of the RAADS-14 based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised [RAADS-R ], the meWe calculated the mean, median and standard deviation of the RAADS scores across our sample of participants. We also calculated scores for the three sub-components of RAADS: “social communication” ; “hyper-focalization” (columns 12–14) and “sensory reactivity” (columns 7 and 10).In order to assess victimization status of participants, we used a French translation of items 1, 2, 3, and 5 of the Sexual Experiences Survey Short Form Victimization questionnaire (SES-SFV). The Sexual Experiences Survey (SES) and its recent 10-items update (SES-SFV) are the most widely used measures of unwanted sexual experience . The facOf important note, we did not apply the recommended analysis method for answers to SES-SFV, which distributes them into six situations: non-victim, sexual contact, attempted coercion, coercion, attempted rape and rape. This is due to the fact that the distinction between coercion and assault does not exist in France, where sexual relationships obtained through coercion are legally categorized as rape in France. Therefore, we have used the following categories instead: sexual touching (s1), oral rape (s2), vaginal/anal rape (s3) and attempted rape (s4). In our analyses, (s2) and (s3) were pooled together in a single category titled “rape.”5 : descriptive statistics . We used non-parametric statistical analyses because data was mostly non-continuous. We used Chi square test to assess for significant differences between subgroups. When applicable, we also used McNemar test and conditional probabilities in order to confirm Chi square tests’ results, because differences in sample sizes of our subgroups could increase type 1 and type 2 errors. In order to assess whether some characteristics of our sample increased measured risks , we used three methods: two-sample test for equality of proportions, Wilcoxon test and univariate logistic regression with odds ratio and confidence intervals. Unless otherwise specified, we used Yates continuity correction as post hoc correction in all cases. Bonferroni correction was additionally used when applicable.Statistical analyses were realized with R (R 4.1.1 2021.08.10). We used the following methodsAll participants declared themselves female except one. Participants’ characteristics are reported in In our sample, 60 (26.7%) participants were self-diagnosed, 143 participants (63.6%) declared having received professional diagnosis, and the remainder 22 (9.8%) participants declared situations ranging from early questioning to being currently in the diagnosis process. Hundred and forty-nine participants (66.2%) received IQ testing: 25 (16.7% of those whose IQ was assessed) reported average IQ scores [90–119], 45 (30.2%) reported above average scores [120–129] and 78 (52.3%) reported IQ > 130.Participants reported their state of health as good to excellent for 119 (52.9%) of them, while 67 (29.8%) rated their health as average and 39 (17.3) reported bad health state. Participants also reported existing comorbidities as follows:•Depression: 140 (62.2%)•Anxiety: 127 (56.4%)•Post-traumatic Stress Disorder (PTSD): 60 (26.7%)•ADHD: 25 (11.1%)•Bipolar disorder: 15 (6.7%)•Borderline personality disorder: 12 (5.3%)•Substance abuse: 9 (4.0%)•Alcohol abuse: 8 (3.6%)•Schizophrenia: 2 (<1%)Regarding comorbidities, participants could declare more than one existing comorbidity as shown in SD: 5.24.RAADS total scores: mean = 34.88; median = 36.00; SD = 3.61.RAADS sub scores social communication: mean = 16.06; median = 17.00; SD = 1.64.RAADS sub scores hyper focalization: mean = 8.05, 9, 1.64; median = 9.00; SD = 1.30.RAADS sub scores sensory reactivity: mean = 5.30; median = 6.00; Hundred and fifty-five (68.9%) participants declared being victim of one or another form of sexual violence. 22 (9.8%) participants declared not having been victimized while 39 (17.3%) declared that they did not know. Declared victims were distributed as follows: assault: 117 (52.0%); rape: 69 (30.7%); attempted rape: 23 (10.2%).Hundred and ninety-nine (88.4%) participants reported being victim of one or another form of sexual violence. Twenty-six (11.6%) participants declared not having been victimized. Reported victims were distributed as follows: sexual touching and/or rape attempt: 196 (87.1%); rape: 155 (68.9%).While some participants reported only one type of aggression, others reported being victims of several types of aggressions, as illustrated in n = 22 (9.8%).Victims of sexual touching only: n = 5 (2.2%).Victims of attempted rape only: n = 3 (1.3%).Victims of rape only: n = 169 (75.1%).Victims of several categories of assaults: n = 26 (11.6%).Non-victims: Age at first aggression was distributed as follows:•Less than 9 years old: 43 (19.1%)•Between age of 10 and 12: 36 (16.0%)•Between age of 13 and 15: 33 (14.7%)•Between age of 16 and 18: 23 (10.2%)•Between age of 19 and 30: 59 (26.2%)•More than 30 years old: 5 (2.2%)•Non-victims: 26 (11.6%)Cases of multiple aggressions were distributed as follows (choices could be cumulative):•There was only one case of aggression: 30 (13.3%)•It happened several times with the same offender: 91 (40.4%)•It happened several times with several offenders: 126 (56.0%)•Non-victims: 26 (11.6%)Participants reported that offenders used different strategies depending on the type of aggression, as illustrated in Participants reported consequences of the aggression during the 6-month period following the assault. As illustrated in •Sleep disorder: 96 (48.2%)•Disgust for sex: 93 (46.7%)•Self-harm: 63 (31.7%)•Weight gain: 45 (22.6%)•Drugs and/or alcohol abuse: 39 (19.6%)•Suicide attempt: 30 (15.1%)•Tattoo/piercing: 19 (9.5%)Among the 199 victims, 111 (55.8%) did not report the assault. Among the 69 who told others about the assault, 18 (26.1%) were not believed. Among the 51 who reported the assault and who were believed , 34 (66.7%) received no care and no complaint was filed, 8 (15.7%) received care and a complaint was filed, 4 (7.8%) did not receive care but a complaint was filed, 5 (9.8%) received care but no complaint was filed. The remainder of victims either answered “other”  or were among the 29 participants (12.9% of the full sample) who answered “not applicable” alongside the non-victims.Participants also chose which of the following sentences best reflected their own opinions regarding prevention methods:•n = 50 (22.2%).Sexual manipulators or predators seem to spot you more easily because of your difficulties in sexual interactions: •n = 39 (17.3%).Knowledge of self-affirmation strategies learned in therapy  could have helped you stay safe better: •n = 37 (16.4%).Your family members should have been more attentive: •n = 23 (10.2%).Female teenagers with Asperger syndrome and their parents should be better informed about the risk of sexual abuse: •n = 24 (10.7%).Nothing could have protected you from this or these assault(s): •n = 18 (8.0%).Health professionals should have given you adapted prevention advice such as better identifying sexually ambiguous situations with men: •n = 8 (3.6%).The officials of the institution  in which you were should have been more watchful: •n = 26 (11.6%).Not applicable (this is not relevant to me): In order to compare answers from the two sexual assault questionnaires, we checked overlaps and incongruencies between Question#13 and SES questionnaire. We looked at how many participants who had chosen at least one of the positive answer columns  in the open question were also victims according to SES, checking the same for participants who hadn’t. We also looked at how many participants who didn’t know or declared being non-victims in the open question were nevertheless victims according to SES, and how many weren’t.While 153 (68%) participants reported victimization in both SES and question#13, there were 46 (20.4%) participants who did not identify as victims in question#13 but nevertheless were classified as victims according to the SES questionnaire. On the other hand, only 2 (<1%) participants reported being victims when answering to question#13 but were not categorized as victims according to SES questionnaire.Also, among the 39 participants who answered “I don’t know” to question#13, 34 of them were actually categorized as victims according to SES questionnaire. More precisely, those 34 victims reported one or more of the following assaults: Sexual touching: 31 (91.2%); rape: 22 (64.7%); rape attempt: 16 (47.1%).Moreover, among the 22 participants who answered being non-victims to question#13, 5 were recategorized as victims according to SES questionnaire, distributed as follows: Sexual touching: 3 (60%); rape 1 (10%); rape attempt: 4 (80%). Those results are illustrated in In order to check consistencies between the two modes of investigation (question#13 and SES), we used two methods: Chi-square tests and Mc Nemar tests were run on the contingency tables.Chi squared tests results were as follows and remain significant after a Bonferroni correction:-p = 2.27e-07*Sexual touching (SES) or assault (open question): -p = 2.01e-08*Rape: -p = 4.61e-05*Rape attempt: McNemar tests results were as follows:-p = 2.05e-15Sexual touching (SES) or assault (open question): -p < 2.2e-16Rape: -p < 2.2e-16Rape attempt: In order to investigate whether being victim of one assault increases the risk of revictimization, we used conditional probabilities within SES questionnaire, with the following results:-P = 96.8%-P = 93.6%-P = 79.4%-P(rape| attempted rape) = 80.0%-P = 54.5%-P(attempted rape| rape) = 56.8%We ran Chi-square tests on the contingency tables within SES questionnaire see , with th-p = 2.27e-07*Sexual touching and rape: -p = 0.0002*Sexual touching and rape attempt: -p = 0.0007*Rape and rape attempt: -p = 1.72e-14*Sexual touching and rape and rape attempt: We also ran McNemar tests on the contingency tables within SES questionnaire, with the following results:-p = 6.53e-07*Sexual touching and rape: -p = 6.05e-16*Sexual touching and rape attempt: -p = 3.10e-06*Rape and rape attempt: We investigated whether the age at first assault is related to the risk of revictimization by another offender, as shown in P-value = 0.0027*; Odds-ratio = 0.75; confidence interval = (0.62–0.90). The influence of age of first assault remained when controlling for PTSD and presence of several assaults by the same offender, with the latter also showing significant correlation with the dependent variable.We did a logistic regression in which having had several abusers was the dependent variable and the age of first assault the independent variable, with the following results: P-value = 0.0513; Odds-ratio = 0.84; confidence interval = (0.70-1.00). The influence of age of first assault increased to the point of becoming significant when controlling for PTSD and presence of several offenders, with the latter also showing significant correlation with the dependent variable.We ran another logistic regression in which being victim of several assaults by the same offender was the dependent variable and the age of first assault the independent variable, with the following results: d = threatening physical harm” was so rare, we had to exclude it from the contingency tables in which it would have been its own category, but kept it when it was a component of a larger category. Of note, we also ran those tests without Yates correction, with comparable results. As a reminder, the remaining strategies are: manipulation/mental ascendency/harassment (“a”), anger/disgust/malicious criticism (“b”), using surprise to take advantage (“c”) and use of force (“e”). The p-values that are significant remain so after a Bonferroni correction.We investigated whether offenders used different aggression strategies depending on the type of assault. Chi-square tests were done on a contingency table within SES of all five strategies and all types of assault see , 6 to sep = 0.016*.Participants could declare one or more existing comorbidities. The mean number of declared comorbidities was different depending on victimization. We also report here the details of comorbidities declared by each group see . In ordep = 0.7707 for depression, p = 0.1817 for anxiety and p = 0.1054 for PTSD. Of note, the same analysis ran without Yates correction led to significant p-value for PTSD only: p = 0.0467*. In order to test if victimization increased the risk of a specific type of comorbidity, we ran two-sample tests of equal proportions within SES, leading to the following p-values: p-value = 0.0760, odds-ratio = 3.08, confidence interval [1.02–13.33]. Using RAADS score, current age and education level as control variables revealed RAADS score to have the strongest correlation. Using the RAADS score as the sole predictor yielded the following results: p-value = 0.0125*, odds-ratio = 1.09, confidence interval [1.02–1.16]. Last, among SES victims, we explored whether age at first aggression was a predictor of PTSD, with the following results: p-value = 0.0162*, odds-ratio = 0.78, confidence interval [0.64–0.95]. Controlling for presence of several assaults from the same assaulter and presence of several assaulters, two other variables correlated with age at first assault, did not significantly change this result.In order to test whether SES victimization increased the risk of PTSD, we ran logistic regressions with the following results: In order to investigate whether multiple assaults perpetrated by one or several offenders made a difference regarding the risk of developing a PTSD, we ran two-sample tests of equal proportions within SES, with the following results:-p = 0.6465.Victims of several assaults from several offenders and victims of only one offender : -p = 1.Victims of several assaults from same offender and other victims : We also ran logistic regressions among victims in order to test if the risk of developing PTSD was increased by multiple victimization by-p-value = 0.948; odds-ratio = 0.98; confidence interval [0.52–1.82]the same offender: -p-value = 0.535; odds-ratio = 1.23; confidence interval [0.65–2.38]several offenders: We investigated whether presentation of autistic traits constituted a risk factor for sexual victimization. In order to compare RAADS scores of victims and non-victims according to SES, we used Wilcoxon tests and logistic regressions. Adding current age and education level as independent variables to the logistic regressions did not significantly change the results. Results are illustrated in n = 225) were of all ages but predominantly in their thirties. A quarter of participants were self-diagnosed.The description of our population sample is revealing of what autism in women looks like and is in line with previous studies . Particin = 123, i.e., more than half of our total sample) obtained a score > 120 and 52.3%  reported IQ > 130. Of course, we can’t extrapolate such numbers to the whole sample, because of a potential clinical bias: it cannot be excluded that IQ testing was more often realized in individuals displaying signs of high IQ, since clinicians may have found that such measures would prove helpful to this subpopulation. Nevertheless, 34.6% of our total sample scored over 130. If true , these results seem to be a rather exceptional situation, and it confirms field observations that report sharp mindedness in the population of ‘‘high-functioning’’6 autistic women. Two thirds of these women graduated university, but only half of them were professionally active (work or studies). Despite demonstrably high cognitive abilities and education levels, participants in our study experienced employment difficulties. This discrepancy illustrates the well-documented employment issues endured by autistic persons.We asked participants if they had received IQ testing. Among the 66.2% who answered yes, 82.5%,  were involved in a relationship and more than half (55.6%) had been sexually active over the last six months . Of important note, more than half of our sample had only experienced heterosexual sex over their lifetime, despite the extremely high percentage of declared queer orientations (71.6%). This gap between aspiration and experience might be partly explained by social factors that are non-specific to autistic women , but could also be linked to autistic characteristics, such as camouflaging and social imitation strategies that have been previously described in autistic women . AnotherInterrogated about their health, while only 17% of participants reported poor health status, more than 75% reported at least one psychiatric comorbidity, as if mental health disorders comorbidities were not health issues. Depression and anxiety were by far the most prevalent comorbidities (62.2 and 56.4% respectively). PTSD came in third place (26.7%). These results should however be interpreted cautiously because of the absence of structured clinical interviews for psychiatric diagnosis in this study. Considering that all these findings are in agreement with reports and studies on the topic of autism in adult women, it is reasonable to see our sample as reliably representative .In order to confirm autism diagnosis reported by participants, we collected their RAADS scores. We only included in the analyses participants who obtained RAADS score > 14 (merely two participants were excluded solely on that criterion). Mean RAADS in our sample was equal to 34.9 ± 5.2 and median was equal to 36, well above the median = 32 reported in the validation study of that scale . Moreoven = 135 victims) where aged 18 or below when the first aggression took place; more than half  being at or below age of consent (15 in France).We assessed victimization status twice: through an open question (Question#13) and through a specific questionnaire (SES-SVF). Both methods yielded extremely high figures: open question resulted in 68.9% victimization, compared to 88.4% with SES-SFV questions. Those results are very high but nonetheless extremely consistent with the findings that we have reviewed earlier: a rate of almost 30% victimization in non-autistic women and a 2 to 3-fold increased victimization of autistic women . MoreoveRegarding ascertainment procedure, we used two methods of case identification. As expected, the SES-SVF questions revealed a significantly higher level of victimization than the open question. This confirms that it is necessary to ask questions about specific situations, rather than using open questions, in order to identify all victims, since some victims may need many years of processing memories about the assault before realizing that the non-consensual sex that happened to them qualifies as a legal offense/crime. One participant wrote this “It happened many times over my lifetime . It is only 5 years ago, at the age of 50, that I understood that I had been victim of sexual violence.” Another participant wrote “This event remained out of my consciousness’ access for many years.” We indeed found several instances of such confusion in our sample: 34 out of 39 participants who answered “I don’t know” to the open question were nevertheless identified as victims through SES. Furthermore, 5 out 22 participants who responded “non-victim” to the open question were actually victims according to SES. Last, Chi-squared test results indicated that participants were consistent: all but two of those who declared being victim in the open question declared the same thing in SES-SFV questions.n = 169 out of 199). In other words, 75.1% of all participants reported several aggressions. By contrast, only 13.3% (n = 30) were assaulted just once over their lifetime – with the assault consisting of unwanted sexual touching for most of them (n = 22).Sexual revictimization among our participants was very important: 84.9% of victims were revictimized  and a confidence interval starting above 1. This is obviously a strong limitation for between-groups comparison. Notwithstanding, in accordance with As mentioned in the introduction to this text, sexual violence has a very negative impact on health. In our sample, participants who had endured sexual violence exhibited significantly more comorbidities than participants who hadn’t. Further testing suggested that, among all comorbidities, it is specifically PTSD that is increased after the aggression, in accordance with a recent meta-analysis . Given tBesides PTSD, victims also reported consequences that occurred within the 6 months following the assault. Half of them suffered from sleep disorder (48.2%) and disgust for sex (46.7%) and third of them attempted self-harm (31.7%). It is specifically rape that induces such deleterious effects, as opposed to victims of attempted rape only or unwanted sexual touching only. Of course, this is to be interpreted with caution because there is a discrepancy in sample sizes: 44 victims did not endure rape while 155 did.Other major vulnerability factors associated with autism and with mental health issues such as social isolation, social stigma and social rejection should be further studied in order to better describe the mechanisms of abuse .n = 69). For the vast majority of those victims , such accusation had strictly no effect . Even worse, 18 out of 52 were not even believed. A lot has been written about the devastating effects of denunciating sexual violence only to be ignored or even be considered a liar, adding insult to the injury. This is not at all specific to autism: an abundant literature indicates that victims of sexual violence, whatever their gender, age and social status, often experience similar skepticism and indifference to their suffering (n = 17) whose testimony was acted upon, only 13 received care and only 12 filed a complaint. How many of those 12 complaints resulted in the perpetrators being actually condemned is here a matter of imagination as such a question was not part of the questionnaire.In our study, only a third of the victims reported the assault  and that may help sexual predators to spot them. However, it could be the opposite: victims could display heightened reactivity due to trauma (a PTSD symptom). And last, it could be two effects of a common cause: for example, the trauma of being severely bullied at school could increase such sensitivity while at the same time making the victims more vulnerable to sexual violence.However, a true effect of autism cannot be excluded of course. We did find a significant correlation between PTSD and total RAADS score after all, and PTSD was significantly correlated with victimization. But that could be interpreted both ways: (i) high autism traits lead to more victimization, leading to more PTSD, or (ii) PTSD might be the confound mentioned above, with PTSD being at the same time a consequence of sexual violence and the cause of heightened sensitivity in adulthood. In any case, it must be reminded here that the very small number of non-victims, the statistical negative results of our between group comparison are not very reliable. The absence of proof is not proof of absence and further research is needed here.7. However, in the case our sample, such a solution would not be deontologically applicable since half of the victims were below the age of consent, and therefore out of the scope of applied sex education. Even for victims who were aged between 15 and 18, this is not applicable: expecting minors with a disability to protect themselves thanks to education can be equated to another form of victim-blaming. Suggesting to a victim that she should have learned how to better state her personal limits is not fundamentally different than telling her that her skirt was too short. Be it in a more benevolent and well-intended way, it is as hurtful and unfair.At that point, it seems important to ponder about the fact that several of the publications that we have cited above mention sexual education as the primary prevention method against sexual violence. 8. Regrettably, the opposite proposition is not as often suggested. Educating potential offenders instead of educating potential victims would be more ethical and might prove a more efficient method, although it would be of limited efficiency since offenders are usually not enamored youngsters unable to control their sexual urges, thereby becoming unintentional sex offenders. That is simply another rape myth  and using surprise to take advantage (“c”). Strategy “c” was the first choice for imposing unwanted sexual contact, while strategy “a” was preferably used for rape attempt and rape. This might prove crucial for understanding why and how sexual violence happens so often in this population. As we have seen, one out of three non-autistic women is a victim of sexual violence. How could autistic women who, by very definition, are ingenuous and cannot guess hidden motives, defend themselves better than non-autistic persons against deviousness, treachery and deception? As Interrogated about prevention methods, one victim out of ten answered that nothing could have protected them. One out of four considered that their autistic traits made them easy to spot by sexual predators. Four out of ten thought that knowledge about risk and self-affirmation strategies could have prevented the assault. However, as we asserted, the high proportion of underage victims renders such a method irrelevant since it would mean putting the responsibility of avoiding victimization on the shoulders of the minor victims.In addition, it is very important to remember that, contrary to widespread myths regarding rape, offense is almost always perpetrated by a close person, exploiting ascendancy or hierarchical power over the victim. What could education do against situations such as the ones reported by our participants: “I was repeatedly raped by a relative during infancy and childhood”; “the first time, I was 6 years old”; “someone who had authority over me (father)”? On the contrary, as mentioned by one out of five participants, the most efficient protection, especially in the case of vulnerable individuals, is the presence of a vigilant caregiver. Educating families and professional about the risk of sexual victimization of girls on the autism spectrum should therefore be a priority.Our research indicates that almost 9 autistic women out of 10 are sexually victimized, at huge costs for their mental and physical health. Of course, one major limitation of our study is that it is based on voluntary participation and that represents a bias since concerned individuals, i.e., victims, may be more willing to contribute to such research than non-victims. However, this bias might not impact results a lot, since our findings are very consistent with literature about sexual violence against autistic women and against women in general. So, what could be done to prevent such generalized issue? The WHO study  shows unPrevention is absolutely necessary, certainly not in the sole form of sex education but rather by promoting profound cultural changes such as recommended by the Center for Disease Control (CDC) and World Health Organization (WHO): both organizations indeed strongly affirm that the very root of sexual violence is gender inequality. As Jessica Leight formulates it , “the li•Social Norms that Protect Against ViolenceS: Promote •Teach Skills to Prevent Sexual ViolenceT: •Opportunities to Empower and Support Girls and WomenO: Provide •Protective EnvironmentsP: Create •Support Victims/Survivors to Lessen HarmsSV: The WHO has published a framework, very consistent with the above model, titled the RESPECT framework .•Relationship skills strengthened. This refers to strategies to improve skills in interpersonal communication, conflict management and shared decision-making.R – •Empowerment of women. This refers to economic and social empowerment strategies including those that build skills in self-efficacy, assertiveness, negotiation, and self-confidence.E – •Services ensured. This refers to a range of services including health, police, legal, and social services for survivors of violence.S – •Poverty reduced. This refers to strategies targeted to women or the household, whose primary aim is to alleviate poverty.P – •Environments made safe. This refers to efforts to create safe schools, public spaces and work environments, among others.E – •Child and adolescent abuse prevented. This includes strategies that establish nurturing family relationships.C – •Transformed attitudes, beliefs and norms. This refers to strategies that challenge harmful gender attitudes, beliefs, norms and stereotypes.T – In her seminal article, “Cultural myths and supports for rape,” Martha R. Burt wrote that “the task of preventing rape is tantamount to revamping a significant proportion of our societal values” . The CDChttps://nakala.fr/10.34847/nkl.d3d35i2o; Repository URL for R code is: https://nakala.fr/10.34847/nkl.4021h29a.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: Repository URL for dataset is: Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.FC: writing and supervising statistical analyses. ER: statistical analyses and proofreading. SL: co-initiator of the study and experimental design. DG: initiator of the study, experimental design, data collection, and preliminary analyses. All authors contributed to the article and approved the submitted version.ER was employed by Auticonsult. The remaining 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.


Salvia abrotanoides under multiple irrigation regimes (30% (severe), 50% (medium) and 100% (control) field capacity).The use of organic nanoparticles to improve drought resistance and water demand characteristics in plants seems to be a promising eco-friendly strategy for water resource management in arid and semi-arid areas. This study aimed to investigate the effect of chitosan nanoparticles (CNPs)  on some physiological, biochemical, and anatomical responses of S. abrotanoides plants compared to the control (CNPs = 0). Furthermore, the activity of antioxidant enzymes superoxide dismutase (86%), polyphenol oxidase (72.8%), and guaiacol peroxidase (75.7%) were enhanced after CNPs treatment to reduce the effects of water deficit. Also, the CNPs led to an increase in stomatal density (5.2 and 6.6%) while decreasing stomatal aperture size (50 and 25%) and semi-closed stomata (26 and 53%) in leaves.The results showed that drought stress decreases almost all biochemical parameters. However, foliar application of CNPs mitigated the effects caused by drought stress. This elicitor decreased electrolyte conductivity (35%), but improved relative water content (12.65%), total chlorophyll (63%), carotenoids (68%), phenol (23.1%), flavonoid (36.4%), soluble sugar (58%), proline (49%), protein (45.2%) in S. abrotanoides but also are able to enhance the drought tolerance ability of this plant particularly in drought-prone areas.The findings show that CNPs not only can considerably reduce water requirement of The online version contains supplementary material available at 10.1186/s12870-022-03689-4. • Foliar application of CNPs can improves drought tolerance.• Leaves showed a high antioxidant enzyme activity under drought stress using CNPs.• Biochemicals varied by drought stress levels and CNPs concentrations.• The highest and the lowest stomatal density and aperture size, respectively were observed in the plants treated with CNPs under drought stress.The online version contains supplementary material available at 10.1186/s12870-022-03689-4. As one of many adverse effects of climate change, prolonged droughts are a significant challenge in the twenty-first century. Forecasts show that many countries will be affected by more droughts and water scarcity issues in the coming years . DroughtChitosan is a non-toxic, non-allergenic, cost-effective, biodegradable, and eco-friendly biopolymer that serves various purposes in the agricultural, biomedical, and feed industries , 9. ThisTriticum aestivum [Catharanthus roseus [Zea mays L. [Saccharum spp. mitigated adverse effects of drought through the increase of the chlorophyll concentration, photosynthesis rate, and activity of antioxidant enzymes, relative water content (RWC), yield, and biomass.Some studies showed that exogenous treatment of CNPs caused a significant improvement in the plant’s innate immune response through induction of the defense enzyme activity , an incraestivum , Catharas roseus , Zea may mays L. , and SacSalvia abrotanoides (Kar.), also known as Proveskia abrotanoides, is a species of the family Lamiaceae native to the arid and semi-arid regions of Central and South Asia, including parts of Iran. Various phytochemical compounds include rosmarinic acid, tanshinones, and monoterpenes in the essential oils, have been identified in this species [S. abrotanoides also has significant aesthetic value due to its long flowering period, attractive flowers, unique colors, and pleasant scent. It is one of the most popular widespread species in xeriscaping and is used as an ornamental plant in the landscape of arid and semi-arid regions due to its good resistance to DS. Recently, S. abrotanoides has been propagated by seeds and planted in botanic gardens and green spaces in some areas [ species . This pl species –24. S. ame areas –27.S. abrotanoides, we hypothesize that this species is an ornamental-medicinal plant with relatively good tolerance to environmental stresses, especially drought. There have been some reports about this plant’s ability to withstand water shortages and hard climate [S. abrotanoides. For this purpose, physiological and biochemical parameters such as RWC, electrolyte conductivity (EC), total chlorophyll, carotenoid, phenol, flavonoid, proline, sugar, protein, and antioxidant enzymes activity, and stomatal morphology were quantified.Given the climatic and ecological conditions of the natural habitats of  climate , 28. Up P ≤ 0.05) but not by CNPs or the interaction of DS and CNPs (P ≥ 0.05)  Table , Fig. 1.Data presented in Fig. P ≥ 0.05). As can be seen in Table According to the analysis of variance, irrigation stress and CNPs treatment significantly influenced photosynthetic pigments  than the well-watered plants (control). Foliar application of CNPs in any three concentrations significantly increased TPC levels under all three irrigation regimes Table . The higP ≤ 0.05). Data presented in Table The results of ANOVA showed that the interaction effect of nanoparticle concentration and irrigation regime on sugar and proline content was significant (P ≤ 0.05). The highest protein levels were observed in the plants treated with 60 ppm and 90 ppm of CNPs under 50% DS   Table , Fig. 4.− 1 protein) was observed in the plants under 50% DS treated with 90 ppm of CNPs. However, data in Table − 1 protein, respectively) were in the plants under 70% DS that received the 90 ppm treatment.The plants exposed to DS showed significantly higher SOD, PPO, and GPO activity than those under normal irrigation conditions Table , Fig. 5.Scanning electron microscopy (SEM) images of the stomatal morphology of the plants treated with 90 ppm of CNPs under two different irrigation levels (100 and 30% FC) are displayed in Fig. 2) and those of well-watered plants (37 n/mm2). Under normal irrigation conditions, the plants that received the CNPs treatment showed higher stomatal density (42 n/mm2) than untreated plants. The highest stomatal density (45 n/mm2) was observed in the plants treated with CNPs under DS. The plants under severe stress conditions showed a more significant stomatal aperture reduction (6 μm) than the well-watered plants (12 μm). In addition, applying the CNPs treatment under normal irrigation conditions led to a reduced stomatal aperture size (8 μm) compared to the untreated control plants. The lowest stomatal aperture size (3 μm) was measured in the plants treated with CNPs under DS. The results showed that stomatal closures were significantly higher in the water-stressed plants (19 n/mm2) than in the control plants (10 n/mm2).The results showed a notable difference in stomatal density between the leaves of the plants subjected to severe stress (40 n/mm2) than the control plants under normal irrigation conditions. The CNPs treatment reduced the number of open stomata in water-stressed plants to such an extent that the leaves of these plants had the maximum number of stomatal closures (30 n/mm2).The plants treated with CNPs also showed higher stomatal closures .It was found low concentrations of nanomaterials (under 100 ppm) improved plant resistance to abiotic stress through mechanisms such as (1) triggering plant cell signals due to high production of ROS and/or reactive nitrogen species (RNS) and (2) stimulating the plant protection mechanism, which includes enzymatic and non-enzymatic antioxidants –35. SomeHowever, nanoparticle application at higher concentrations has toxic effects on cellular processes and plant metabolism even under normal conditions –41. For S. abrotanoides stressed- plants. Other experiments have also reported a significant reduction in RWC under DS in S. nemorosa [S. sinaloensis [S. miltiorrhiza [S. abrotanoides may be attributed to less access to water, decreased relative water absorption, or lower water retention in the leaves of these plants [In our study, DS decreased the RWC of leaves up to 20%) in 0% in S. nemorosa , S. sinaaloensis , and S. iorrhiza . The rede plants .Hordeum vulgare with 90 ppm of CNPs increased RWC by 1.57 times compared to the control sample. Other investigators have also shown the positive effect of CNPs on improving RWC in Trifolium repens [Z. mays [Treatment with CNPs, especially at 60 ppm, improved the RWC of the stressed plants, especially at the 70% stress level. Similarly, Behboudi et al.  reportedm repens  and Z. m[Z. mays  under DSChitosan nanoparticles help improves water retention and RWC of stressed plants by reducing their transpiration rate, promoting water absorption and essential elements from roots, and regulating the cell osmotic pressure. Also, CNPs benefit from stomatal conductance and photosynthetic rate, then maintain water balance in cells by stomatal adjustment , 47.S. abrotanoides leaf cells suffering from DS by preserving plasma membrane structure, increasing RWC, regulating water pressure, and reducing oxidative stress [Contrary to the results obtained for RWC, the EC of the plants subjected to severe DS was 2.33 times higher than the plants with the regular irrigation regime. The results of this investigation revealed that plants treated with 90 ppm CNPs had a 35% lower EC than untreated plants under severe DS. These findings are consistent with the results reported by other authors –50. There stress .Salvia species under drought conditions [The chlorophyll content is one of the most important factors in maintaining photosynthetic capacity and determining the rate of photosynthesis in plants , 52. Dronditions , 53, 54.nditions , 55.T. aestivum has also been found by Behboudi et al. [T. aestivum up to 33% compared with untreated plants. Ghasemi Pirbalouti et al. [Ocimum basilicum under water limitation conditions (30% FC). There are also some reports of the positive effect of chitosan and its oligomers on the carotenoid content of Coffea canephora [Fragaria × annanasa [In the present study, exogenous CNPs increased chlorophyll and carotenoid concentrations during DS and had a dose-dependent effect on these photosynthesis pigments. After using 90 ppm CNPs under 50% DS, the total chlorophyll and carotenoid levels were enhanced up to 63 and 68% compared to untreated plants, respectively. Similarly, increased chlorophyll content following 90 ppm CNPs treatment under DS in i et al. . In a sti et al. , CNPs ini et al.  reportedanephora  and Fragannanasa .It appears that CNPs stimulate the expression of genes involved in the chlorophyll synthesis by increasing the internal cytokinin level and enhancing the availability of free amino compounds released from chitosan . Also, cS. abrotanoides leaves by 29 and 13%, respectively. These results were in agreement with some scientists who founded that water deficit improved the TPC and TFC of plants, including S. officinalis [S. sinaloensis [S. nemorosa [S. dolomitica. Another study also stated that DS inhibited the synthesis of flavonoid compounds in the leaves and stems of Thymus daenensis [Phenolic compounds, including flavonoids, can scavenge ROS and prevent cellular oxidation under water deficiency , 61. In aloensis  and S. nnemorosa  reportedaenensis . As a reCamellia sinensis leaves with CNPs led to a 24% higher concentration of phenolic compounds than the untreated control group [S. officinalis was observed after applying 500 ppm of chitosan. There are also similar reports of the effect of chitosan and its derivatives on the concentration of phenolic compounds in other plants [This investigation showed an increase in TPC and TFC of the plants treated with CNPs in well-watered and water-stressed groups. The highest TPC (1.3-fold of control) and TFC (1.57-fold of control) were observed when 60 ppm of CNPs was applied to the plants under 50 and 70% stress levels, respectively. Similarly, a study described that the treatment of ol group . In a stol group , the higr plants –66. It ir plants , 67, 68.r plants .T. aestivum sprayed with 90 ppm CNPs under DS, which was 1.13 times greater than control plants. In another study, CNPs treatment led to higher proline concentration in the leaves of C. roseus under 50% DS [Z. mays plants treated with chitosan and exposed to 50% DS. There are also some reports of the interaction effect of chitosan and DS on proline and soluble sugar content in the other plants [This study indicated that soluble sugar and proline concentrations were higher in drought-stressed plants than in control. The interaction of CNPs with DS caused a significant increase in these osmoprotectants levels. At 60 ppm of CNPs and 50% DS conditions, the sugar and proline content increased 58 and 49% compared with untreated control plants, respectively. Consistent with this study, Behboudi et al.  demonstrr 50% DS  found thr 50% DS  observedr plants , 30, 48.T. repens leaves under DS [Under DS, the external application of chitosan and its derivatives leads to a higher accumulation of soluble sugars, proline, starch, and flavonoids in plant cells which are osmotic adjustments . The higunder DS . As a reunder DS .S. abrotanoides. This result agrees with the findings of Behboudi et al. [H. vulgare and T. aestivum. Li et al. [T. aestivum seedlings. In another study, 100 ppm of chitosan improved the protein content of potato plant leaves by up to 100% under DS [In this work, severe drought decreased total proteins by 36.5% compared to well-watered plants. There are similar reports of reduced protein content in other plants under DS , 71. Duri et al. , 20, whoi et al.  suggesteunder DS  . This iunder DS , 73.S. abrotanoides in response to DS. In accordance with our data, different plant species have observed enhancing antioxidant enzyme activity for DS-resistant [S. abrotanoides leaves in a dose-dependent manner (except for SOD at 60 ppm CNPs in 50% DS). Foliar application of 90 ppm of CNPs to the plants under severe DS increased the SOD, GPO, and PPO activity levels by 86, 75.8, and 72.8%, respectively (compared to untreated plants). However, the highest SOD activity was observed in the plant treated with 90 ppm of CNPs subjected to 50% FC (2.38-fold of control). Several studies support our findings that chitosan and its nanoparticles have a favorable effect on antioxidant system gene expression and activation under DS [Camellia. sinensis leaves with 10 ppm CNPs, POX, SOD and PPO activity levels of these plants were 4, 1.7 and 3.5 times than untreated control plants. In the same way, Abdel-Aziz [Vicia faba. Similar results showed that chitosan increases the activity of antioxidant enzymes, including SOD, POX and GPO, in other plants [Rosa damascena Mill. flowers treated with CNPs, suggesting that CNPs may play a role in floral quality maintenance.The activity of SOD, PPO, and GPO enzymes in the current study increased in leaves of esistant –78. Undeunder DS , 47, 59.under DS  observedunder DS  found thdel-Aziz  reportedr plants , 69, 80.r plants  discoverThe positively charged chitosan binds to a negatively charged phospholipid or protein receptor in the cell membrane, inducing oxidative burst and cascade reactions. ROS act as signaling molecules, which activate the antioxidant enzyme systems , 29. CNPGrammatophyllum scriptum after applying chitosan. Our finding is also consistent with Lee et al. [2O2 in stomatal guard cells, making the plant respond by reducing the stomatal aperture size [Coffea canephora, which stated that CNPs might increase the stomatal aperture size [In this examination, the plants subjected to severe DS showed 1.08-fold higher stomatal density and 2-fold smaller stomatal aperture size than well-watered plants. There are similar reports of reduced aperture size due to DS in other plants , 83. Sime et al.  results,ure size . Howeverure size .S. abrotanoides increased stomatal density about 12% in both water regimes, compared to untreated plants. Similarly, a study by Hasanah and Sembiring [2 required for photosynthesis in DS conditions [Our findings revealed that foliar application of CNPs to embiring  reportednditions .2 absorption. However, having a greater number of closed stomata and lower aperture size decreases the plant’s water requirement and makes it more tolerant to water stress [This survey found that, the number of stomatal closures in stressed plants was as much as 57% higher than the corresponding number in the control plants, consistent with the results reported for other plants , 82. Stor stress .2) was observed in the CNPs treated plant subjected to drought conditions. Likewise, foliar treatment of chitosan nanoemulsion on water-stressed pearl millet plants induced more stomata to close down than untreated plants [Capsicum annuum resulted in less open stomata than plants not treated with this elicitor in DS conditions [This research indicated that CNPs increased the number of stomatal closures under both regular irrigation and severe drought conditions. The highest number of stomatal closures  in stomatal guard cells and up-regulating ABA synthesis , 11. FurS. abrotanoides tolerance mechanisms induced by CNPs under moderate and severe DS. CNPs (particularly at 60 and 90 ppm) improved drought resistance in S. abrotanoides, as evidenced by considerable increases in biochemical and physiological responses under DS. Due to the environmental benefits of CNPs , they can be an excellent alternative for agrochemicals to mitigate DS. Future investigations should evaluate the molecular mechanisms and expression pattern of related genes induced in this ornamental-medicinal plant after using CNPs for water deficit tolerance.For the first time, this study revealed information related to the Chitosan nanoparticles were commercially purchased from Iranian Nanomaterials Pioneers Company, NANOSANY . The characteristics of CNPs were 50 nm in size, with a molecular weight of 161 g/mol and 99% purity  .S. abrotanoides were collected from its natural habitat in Kalat Naderi County  at the longitude of 59° 9′ 40“ E, latitude of 36° 24’ 20” N, and altitude of 2100 m above sea level. Seeds were grown in growing trays containing cocopeat (80%) and perlite (20%). The four-leaf stage seedlings were transferred to plastic pots, filled with sand and clay loam soil . Plants was fertilized after seeding with a NPK fertilizer . The average temperature of the greenhouse was 18–24 °C (night-day), the photoperiod was 14–16 h, and the humidity was 50–60%.Seeds of mature Chitosan nanoparticles were prepared at four concentrations  , 37, 38,At the end of the experiment (1 month following the initiation of DS at full flowering stage), a SEM  was used to examine the leaf structure and the number and function of stomata. The samples used for this purpose were stabilized with glutaraldehyde .The chlorophyll content of the samples was measured using the method of Lichtenthaler . For thiTo measure the RWC of leaves as instructed by Ritchie et al. , fully mOne gram of leaf tissue was added to 20 ml of distilled water and maintained at room temperature (24 °C) for 24 h to determine the EC of leaves. After 24 h, the electrical conductivity of the mixture was measured by an EC meter to determine the initial EC (EC1). The Secondary EC (EC2) was determined by repeating the measurement after placing the sample in an autoclave (120 °C) for 15 min. With this data, the electrolyte conductivity of the leaves was calculated using the formula below .\documenThe chlorophyll content of the samples was measured using the method of Lichtenthaler . For thiFresh leaves 0.1 g) were thoroughly homogenized in 1 ml methanol and stored at 4 °C for 24 h to create the sample extract. The supernatant was removed for use in phenol and flavonoid assays after centrifugation at 6000 rpm for 15 min. The total phenol content (TPC) was determined using the method of Wojdyło et al.  with a s g were tFor this measurement, 0.01 g of fresh leaves were homogenized with 1 ml of ethanol (70%) and kept at 4 °C for 1 week. The extract was centrifuged at 6000 rpm for 15 min and the supernatant was separated for measuring the concentration of soluble sugar. This measurement was performed using the phenol-sulfuric acid method. This method is based on the acid hydrolysis of soluble sugars and the formation of furfural, which produces a color complex with phenol. For this purpose, 100 ml of the extract was combined with 300 ml of distilled water and 1 ml of phenol (5%) and vortexed before adding 1 ml of concentrated sulfuric acid. After 30 min, the absorbance of the sample at 485 nm was read against a blank sample. The sugar contents were determined using a standard curve in mg/g FW. To determine the concentration of soluble sugar, first, a standard curve with different glucose concentrations was prepared  were weighed and completely powdered with liquid nitrogen to make the enzyme extract. Then 1 ml of the phosphate-buffered saline (PBS)  and ethylene diamine tetra acetic acid (EDTA) with a concentration of 0.1 mM were added, and the mixture was thoroughly homogenized. The product was centrifuged at 12000 g and 4 °C for 15 min. The supernatant was separated and stored in a freezer at − 80 °C to measure protein and enzyme activity. To determine the amount of protein in the extract, 2.5 ml of Bradford solution was added to 50 μl of the separated supernatant, and the absorbance was read at 595 nm after 5 min to determine the amount of protein in the extract. Specific concentrations of standard bovine serum albumin (BSA) were prepared in the extraction buffer to create a protein calibration curve , 103 (Su− 1 protein).Superoxide dismutase (SOD) activity was assayed by measuring the inhibition of photochemical reduction of nitroblutetrazolium (NBT) in the reaction mixture according to Giannopolitis and Ries  with sli− 1 protein.Polyphenol oxidase (PPO) activity was measured using the method of Raymond et al.  with som2O2 (1 mM), and 50 μL of the enzyme extract. Enzyme activity was determined by measuring the increase in absorbance at 470 nm due to guaiacol oxidation. The change in absorption was measured every 5 sec for 1 min and the result was expressed in U mg− 1 protein.The guaiacol peroxidase (GPO) activity was measured by the method of Hemeda and Klein  with somThe research was conducted according to a factorial experiment (4 × 3) based on completely randomized design with four replications. Factors including nanoparticle concentration  and DS . For data analysis, the analysis of variance (ANOVA) was performed using the software SPSS version 21, and the comparison of means for the measured traits was performed using the Duncan’s test at test at a significance level of 5%. The graphs were drawn with the software Excel.Additional file 1. Report of analysis of variance and mean comparisons using Minitab.Additional file 2. Some photos of Salvia abrotanoides in the green house and field in Iran.Additional file 3: Figure 1. Standard curve of gallic acid. Figure 2. Standard curve of quercetin. Figure 3. Standard curve of glucose. Figure 4. Standard curve of proline. Figure 5. Standard curve of bovine serum albumin (BSA).Additional file 4.Additional file 5.Additional file 6.Additional file 7.Additional file 8.Additional file 9.Additional file 10.Additional file 11.Additional file 12.Additional file 13.Additional file 14.Additional file 15.


Bioprosthetic valve fracture allows for placement of a larger transcatheter valve, as well as a fully expanded transcatheter valve, decreasing postoperative gradients and the risk of PPM.The use of bioprosthetic prostheses during surgical aortic valve replacements has increased dramatically over the last two decades, accounting for over 85% of surgical implantations. Given limited long-term durability, there has been an increase in aortic valve reoperations and reinterventions. With the advent of new technologies, multiple treatment strategies are available to treat bioprosthetic valve failure, including valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR). However, ViV TAVR has an increased risk of higher gradients and patient prosthesis mismatch (PPM) secondary to placing the new valve within the rigid frame of the prior valve, especially in patients with a small surgical bioprosthesis  Treatment of aortic valve pathology has evolved over the past decade with the advent of transcatheter aortic valve replacement (TAVR). In Europe, TAVR first received Conformitè Europèenne (CE) Mark approval in 2007, and the number of patients undergoing TAVR grew exponentially. In the United States (US), clinical trials began in 2007 and TAVR gained Food and Drug Administration (FDA) approval in 2011 for inoperable patients with severe aortic stenosis. Since then, surgical aortic valve replacements (SAVR) have decreased slightly as TAVR approval expanded to patients of all surgical risk profiles in 2019 [More than 85% of SAVRs are with bioprosthetic valves , but oneThe 2021 Valve Academic Research Consortium 3 (VARC-3) guidelines define bioprosthetic valve failure in three stages: (1) any bioprosthetic valve dysfunction with clinically expressive criteria , (2) aortic valve intervention, and (3) valve-related death  Figure . With thp < 0.0001), increased body surface area , smoking , and PPM  as the four significant determinants for SVD [Given the increase in bioprosthetic AVR utilization, the identification of predictors of valve failure and the recognition of opportunities to reduce the incidence of SVD are imperative. A variety of factors contribute to valve failure, including patient characteristics and comorbidities, type of implanted valve, and size of implanted valve. In a recent systematic review and meta-analysis, Ochi et al. identified multiple risk factors for BVD including younger age, sex, prosthesis brand, prosthesis size , PPM, absence of anticalcification preparation, concomitant coronary artery bypass graft surgery, subcoronary implantation technique, postoperative pressure gradient, dyslipidemia, smoking, metabolic syndrome, use of lipid lowering medication, elevated body mass index and body surface area, and renal disease. Meta-analysis identified younger age , moderate (0.85 to 0.65 cm2/m2), and severe (≤0.65 cm2/m2). Fallon et al. reported that 65% of patients ≥65 years old with severe aortic stenosis who underwent SAVR had moderate or severe PPM [p < 0.001), especially among patients receiving a valve size ≤23 mm  [Patient-prosthesis mismatch occurs when the effective orifice area (EOA) of the implanted prosthetic valve is too small for the patient's body size . PPM is vere PPM . Those pvere PPM , 10. Oldvere PPM , 12. TAVp=0.048) . The aveWhen selecting a valve, the internal orifice diameter (ID) of the proposed implant should be identified, as the ID differs amongst valve models and manufacturers for the same labeled valve size. The largest valve that can be safely implanted is recommended, but strategies for selecting valve size differ in SAVR vs. TAVR. For SAVR, the valve size is selected by the surgeon at the time of implant based on manufacturer-specific annular valve sizers, while TAVR sizing relies entirely on preoperative computed tomography angiography (CTA). This difference in measurement results in valves with smaller ID being implanted during SAVR . Preoper2/m2 and may be considered when the EOA index is ≤0.85 cm2/m2 [Especially in young patients with small annuli, an aortic root enlargement or replacement should be performed when the EOA index is ≤0.65 cm5 cm2/m2 . Aortic 5 cm2/m2 , 16. Tec5 cm2/m2 , Manougu5 cm2/m2 , Konno e5 cm2/m2 , and the5 cm2/m2 . Both th5 cm2/m2 , 18. The5 cm2/m2 . A Konno5 cm2/m2 . The Y-i5 cm2/m2 , 22, 23.5 cm2/m2 .p = 0.001) [p = 0.02) and stenosis as the primary mechanism of failure , p = 0.008) were significant risk factors for one-year mortality [Once clinically significant BVD occurs, intervention is indicated. Redo-SAVR may not be appropriate for all patients and a full imaging assessment with CTA and heart team discussion is necessary to determine the best strategy. In Europe, ViV TAVR was first CE Mark approved in 2013 and FDA approved for inoperable and high-risk patients  with the balloon expandable valves  and subs= 0.001) . Surgicaortality . To imprThe bioprosthetic valve fracture was first described by Nielsen-Kudsk et al. in 2015. In small mitroflow bioprostheses, a high-pressure balloon predilatation with an ATLAS Gold balloon fractured the annular stent ring of the SAVR valves and a 20 mm SAPIEN XT was placed in the 19 mm Mitroflow and a SAPIEN 3 23 mm TAVR valve was placed in a 21 mm mitroflow without any complications . The BVFFor BVF/BVR, the implanted surgical valve is first identified to determine if it can be fractured or remodeled. Valve fracture is an option for some bioprosthetic valves including Magna, Magna Ease, Perimount 2800, Mitroflow, Mosaic, and Bicor Epic  while vaThe BVF fractures the internal annular ring within the sewing cuff of the surgical valve to allow for maximal expansion of the new valve and results in improved hemodynamics post-ViV TAVR deployment. Following initiation of rapid ventricular pacing, a noncompliant balloon is rapidly filled with dilute contrast and pressurized using an indeflator until fracture occurs . Specifiin-situ valve, particularly the ID, determines the largest transcatheter valve that can be implanted. In both cases, a degree of oversizing is chosen to ensure secure fixation. The ID of the in-situ surgical valve can be obtained from the manufacturer; however, the true internal diameter is affected by how the leaflets are secured ; internally mounted leaflets can reduce the true ID by at least 2 mm [https://apps.apple.com/us/app/valve-in-valve/id655683780) [In a native aortic valve, the ID is measured at the level of the aortic annulus and used to determine the size of the transcatheter valve to be implanted. For ViV TAVR, the size of the ast 2 mm . The Val5683780)  is a usein-situ surgical valves compared to those with native valves. Therefore, in ViV TAVR planning, the coronary height should be measured from the sewing ring of the basal plane of the prosthesis and not the true native annular plane [p < 0.0001) [Cardiac gated multidetector computed tomography (MDCT) is used to determine the inner diameter and area of the failed valve for selection of the appropriate TAVR. Under-sizing can result in paravalvular regurgitation and embolization, but oversizing may result in incomplete expansion, increased gradients, and coronary obstruction , 33. Durar plane . On preo 0.0001) . When BV 0.0001) . Additio 0.0001) .BVF results in an increase in the ID of the surgical valve of 3-4 mm and the selection of transcatheter valve size should be based on this anticipated increased ID. BVF can be performed before or after ViV TAVR. When performed before ViV TAVR, it effectively fractures the surgical valve but does not ensure adequate expansion of the subsequent TAVR. If BVF is performed after ViV TAVR, it fractures the surgical valve and fully expands the transcatheter valve. BVF has been shown as a beneficial strategy to prevent PPM, in particular for small surgical prostheses. Despite patients with larger surgical valves having a lower risk of PPM and high gradients, BVF can still be utilized to promote full transcatheter valve expansion. However, BVF remains understudied in patients with larger surgical valve sizes . BVF resDuring SAVR, commissure-to-commissure alignment is maintained, while in TAVR the orientation of the commissures is often random and not consistently achievable. Tang et al. found that the Evolut “hat” marker and the ACURATE-neo commissural post facilitated improved commissural alignment and reduced coronary artery overlap . The criV shaped opening (leaflet splay) to increase blood flow and access to the coronary artery at risk. In a series of 30 patients in the initial BASILICA feasibility study, freedom from coronary obstruction was 95% and no patient required reintervention [Bioprosthetic or native Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery Obstruction (BASILICA) is an electrosurgical leaflet modification technique which is effective in preventing coronary obstruction in native and bioprosthetic valves. In patients at high risk of coronary obstruction due to a VTC distance <4 mm, or at risk of sinus sequestration due to a narrow SOV, short STJ height, and/or long bioprosthetic valve leaflets, using an electrified wire, the nadir of the bioprosthetic leaflet is crossed and leaflet lacerated to create a rvention . Patientrvention .In addition to ViV TAVR, redo-SAVR is another option. Although redo-SAVR has traditionally been considered a higher-risk operation compared to primary AVR, the mortality of redo SAVR is 1–5% with appropriate patient selection , 44. ComDue to the increase in bioprosthetic valve utilization for the treatment of aortic valve disease and patients with longer life expectancy, bioprosthetic valve failure is becoming a significant problem requiring innovative treatment strategies. Redo-SAVR has traditionally been the only treatment modality for failed biologic valves, but many elderly patients are not candidates for a second operation or do not wish to undergo a redo-sternotomy. Valve fracture provides one strategy to achieve optimal hemodynamics by increasing the size of the annulus for ViV TAVR. BVF is especially useful in patients with small surgical valves to decrease the risk of PPM by removing the constraints of placing a transcatheter valve within a rigid surgical bioprostheses and when performed after ViV-TAVR facilitates expansion of the transcatheter valve. Although in the US ViV TAVR is reserved for high-risk patients, risk drift is expected with this technology. Not only do we need to provide a solution to the initial failed surgical valve, but planning for a third valve when the VIV TAVR fails must be considered in the lifetime management of aortic valve disease. It may be that all patients, not just those with small annuli, benefit long-term from valve fracture and additional study is needed.


Analysis of plasma and serum provides valuable information on the amounts of polar phenols’ circulating after ingestion. In the present study, protein precipitation (PPT), liquid–liquid extraction (LLE), solid phase extraction (SPE), enzymatic hydrolysis and their combinations were meticulously evaluated for the extraction of a variety of polar phenolic moieties from plasma and serum. The recovery values of the above methods were compared; satisfactory recoveries (>60%) were attained for most analytes. Polar phenol aglycones undergo degradation with enzymatic hydrolysis; however, their extended phase II metabolism makes enzymatic hydrolysis a mandated process for their analysis in such biofluids. Hence, enzymatic hydrolysis followed by LLE was used for the identification of polar phenols in rats’ serum, after the long-term oral consumption of Corinthian Currant. Corinthian Currant is a Greek dried vine product rich in bioactive polar phenolics. Flavonoids and phenolic acids, detected as aglycones, ranged from 0.57 ± 0.08 to 181.66 ± 48.95 and 3.45 ± 1.20 to 897.81 ± 173.96 ng/mL, respectively. The majority of polar phenolics were present as phase II metabolites, representing their fasting state in the blood stream. This is the first study evaluating the presence of polar phenolics in the serum of rats following a long-term diet supplemented with Corinthian Currant as a whole food. Vitis vinifera L., var. Apyrena, which is almost exclusively cultivated in Southern Greece. One of the three commercial sub-varieties of Corinthian Currants, namely Vostizza, falls under the high-quality category and has a protected designation of origin (PDO) name. Corinthian Currants have been found to contain a plethora of polar phenolic components, including benzoic and phenyl acetic acid derivatives, hydroxy-cinnamic acids, anthocyanins and flavonoids  .Intra- and inter-day precision (% RSD) and accuracy (% RE) were assessed by analyzing quality control (QC) samples at various levels (0.5–160 ng/mL depending on the compound) prepared in five replicates. Precision and accuracy values within ± 15% (± 20% for LLOQ) were considered acceptable .QC samples were analyzed after preparation and after the applied storage conditions that were to be evaluated. The QC samples were also analyzed against a calibration curve and the obtained concentrations were compared to the nominal concentrations. The mean concentration at each assayed level was set within ± 15% of the nominal concentration .The extraction recovery was evaluated by calculating the peak responses of spiked matrix samples and comparing them with those obtained from the matrix-matched samples at the corresponding amounts.® HLB cartridges, as described by Vasilakopoulou et al. [Polar phenols were extracted from Corinthian Currants and rat chow with MeOH as described by Chiou et al. . Brieflyu et al. . ®: WIST rats (350–400 g bw) were randomized into two groups  according to their dietary regimen, i.e., healthy animals that received the control diet, i.e., rat chow (C) or control diet supplemented with 10% w/w Corinthian Currant (CC) for 4 weeks. At the end of the intervention, animals were sacrificed and blood samples were collected by cardiac puncture; serum samples were isolated and stored at −80 °C until analysis. Animal experimentation was reviewed and approved by the Veterinary Directorate of the Athens Prefecture (Ref. Number 453264/07-08-2019), and conducted in compliance with the European Directive 2010/63. Animal housing took place in the Centre of Experimental Surgery of the Biomedical Research Foundation of the Academy of Athens (BRFAA). The animals were housed in accordance with the European legal framework and the international guidelines existing for the protection of animals used for scientific purposes.Twelve male RccHanp < 0.05.All statistical analyses were performed using IBM SPSS Statistics for Windows, version 26 . For multiple comparisons among samples subjected to different sample treatment procedures, one-way analysis of variance (ANOVA) was used. Tukey’s multiple range tests were performed post hoc to evaluate differences among groups. Comparisons for the detected levels of polar phenolics were conducted with dependent samples T-test for the comparisons within the control (C vs. Cenz) and the dietary intervention group (CC vs. CCenz), whereas independent samples T-tests were applied for the comparisons among the control and dietary intervention group . Data are presented as mean ± standard deviation (SD). The level of statistical significance was set at In the present study, in order to assess the extraction performance of polar phenolics from both plasma and serum, ten sample preparation procedures were compared in each case; PPT with organic solvents with or without the addition of acid; hybrid methods combining the aforementioned PPT conditions and SPE; LLE with ethyl acetate with or without the addition of acid prior extraction. The % extraction recoveries (% R), which served as the main evaluation index, were obtained by comparing spiked versus matrix-matched plasma and serum samples, at a concentration level of 100 ng/mL for all studied compounds .The most generic method to prepare plasma and serum samples in large scale studies is protein precipitation (PPT), by adding 3–5 times the sample’s volume of organic solvents such as acetonitrile, methanol, ethanol or mixtures of the aforementioned, and/or acidified solutions depending on the stability of analytes in low pH . Even thIn contrast, the hybrid methods combining PPT and SPE seemed to improve the extraction recoveries for most of the analytes from both studied biofluids; the extraction recoveries of most polar phenolics ranged from 40–80%, with a fewer being > 80% . This isLiquid–liquid extraction (LLE) with ethyl acetate (EtOAc) in non-acidified plasma and serum samples yielded rather high extraction recoveries for the majority of polar phenolics; almost all had extraction recoveries > 60%, of which most varied from 70–105%. The extraction recoveries from LLE were similar to the PPT + SPE treated samples for most analytes, especially for flavonols, flavones, isoflavones and most phenolic acids in the case of serum samples. Acidification of plasma and serum samples prior to LLE did not seem to improve analyte extraction; on the contrary, this method led to extraction recoveries < 60%. Overall, our results indicate that LLE with EtOAc and no prior sample acidification led to somewhat satisfactory recoveries, consumed less time for sample preparation and is a more affordable alternative than PPT + SPE. Hence, LLE with EtOAc and no acidification was chosen for the ensuing analyses for both plasma and serum samples.Prior to liquid–liquid extraction with EtOAc, serum and plasma samples underwent enzymatic hydrolysis treatment. The hydrolysis protocol performed was based on previously published studies ,31. In tp < 0.05), with the glycosides in particular suffering a notable reduction of almost 100% in both plasma and serum samples. Some flavonoids, namely epigallocatechin, epigallocatechin gallate, naringenin, kaempferol, isorhamnetin and quercetin also experienced a significant reduction of up to 85% under these conditions. These findings are in line with [According to our results , the temine with , who alsine with   of rat serum is given in w/w) Corinthian Currant as a whole food .By adopting a simple serum treatment method that included the enzymatic hydrolysis of samples followed by liquid–liquid extraction (LLE) with EtOAc, we were able to detect and quantify polar phenolics that were present in the rats’ serum as a result of their diet. In our study, we evaluated the content of free and conjugated forms of various flavonoids and phenolic acids in both intervention groups (C and CC); β-Glucuronidase/sulfatase from p = 0.006), 4.35 ± 1.62 (p = 0.039) and 1.85 ± 0.54 (p = 0.005) ng/mL, respectively. Luteolin was detected and quantified in both groups (C & CC); however, with no statistically significant differences (p = 0.297). Phenolic acids were also detected at quantifiable amounts in both serum samples of the control (C) and dietary intervention group (CC); vanillic acid was detected at statistically significantly higher amounts in the CC group compared to the C group (p = 0.017). Analysis with independent T-tests revealed statistically significant differences among the detected levels of free polar phenolics among the two intervention groups; the Corinthian Currant supplemented group showed a tendency towards higher levels of the detected free polar phenolics when compared to the non-supplemented group . When cop = 0.046), 2.54 ± 1.06 (p = 0.005), 113.74 ± 66.08 (p < 0.000), 5.93 ± 2.22 (p = 0.016), 8.54 ± 4.83 (p = 0.004), 9.80 ± 3.82 (p = 0.036) and 40.40 ± 16.28 (p = 0.049) ng/mL, respectively. In the study of Yanni et al. [When comparing the enzymatically treated serum samples of the control and dietary intervention group , the flavonoids apigenin, chrysin, luteolin, isorhamnetin, quercetin, hesperetin and genistein were found at statistically significantly higher amounts in the CCenz group; their detected levels were 181.66 ± 48.95  of rats’ serum, representing their fasting state in the blood stream. The majority of detected flavonoids and phenolic acids were present as phase II metabolites, given that after the implementation of enzymatic hydrolysis their aglycones were found at quantifiable amounts. Our findings may shed light on the amounts of polar phenolics in circulation, which in return indicate that the observed increase of some polar phenolics may be linked to the regular consumption of Corinthian Currant as a whole food over an extended period of time.


The systemic immune-inflammation index (SII) is a novel biomarker to predict the prognosis of some malignant tumors based on neutrophil, platelet, and lymphocyte counts. Evidence is scarce about the prognostic value of SII for prostate cancer patients. This systematic review and meta-analysis was conducted to explore the prognostic value of the SII in prostate cancer.The PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases were searched to determine eligible studies from inception to August 15, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to pool the results. Statistical analyses were conducted by using Stata 17.0 software.p < 0.001). Furthermore, a subgroup analysis showed that a high SII was associated with poor OS in the groups of any ethnicity, tumor type, and cutoff value. An increased SII was also associated with inferior progression-free survival (PFS) . In the subgroup analysis, a high SII value was related to poor PFS in Asian patients  and a cutoff value > 580 .A total of 12 studies with 8083 patients were included. The quantitative synthesis showed that a high SII was related to poor overall survival (OS) (HR = 1.44, 95% CI 1.23–1.69, Based on the current evidence, a high pretreatment SII may be associated with poor OS and PFS. The SII may serve as an important prognostic indicator in patients with prostate cancer. More rigorously designed studies are needed to explore the SII and the prognosis of prostate cancer. Prostate cancer (PCa) is one of the most common cancers in the urinary system, with an estimated 1,414,259 new cases and 375,304 deaths worldwide in 2020 –8. AndroTumor-associated immune reactions in the tumor microenvironment (TME) act as immunological surveillance and antitumor immune responses, which are closely related to the prognosis of patients . Thus, sAlthough SII integrated three types of hematology indicators, the results for the prognostic value of SII in PCa patients were not robust. Rajwa et al.  exploredWe performed this systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines . This stWe searched the PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases to identify eligible studies up to August 15, 2022. We applied the following terms: (prostatic neoplasm* OR prostate neoplasm* OR prostate cancer* OR prostatic cancer* OR PCa) AND (systemic immune-inflammation index OR SII). MeSH and free text terms were used to identify the eligible literature. We manually screened the references of the included studies to identify potentially eligible studies.The included studies met the following criteria: (1) randomized controlled trials or observational studies; (2) patients were pathologically diagnosed with PCa; (3) studies exploring the relationship between pretreatment SII and prognosis in PCa patients; (4) studies reporting the cutoff value of SII; (5) studies providing hazard ratios (HRs) with 95% confidence intervals (CIs); and (6) studies reporting survival outcomes, including OS, progression-free survival (PFS), or cancer-specific survival (CSS).The following studies were excluded: (1) non-English language; (2) duplicate articles; (3) reviews, letters, case reports, protocols, conference abstracts, and any article without full text; (4) in vitro or animal experiments; and (5) studies that did not provide sufficient data.Two authors (LM and YY) independently extracted the data from the included studies. Disagreements were resolved by discussion with a third reviewer (XL). The following data were extracted: first author, publication year, country or region, study design, sample size, age of patients, tumor type, treatment methods, cutoff value of SII, analysis methods, follow-up period, survival outcomes, HRs, and 95% CIs. The Newcastle‒Ottawa quality assessment scale (NOS) was used to assess the risk of bias . The NOS2 tests were used to assess the heterogeneity of the studies. When I2 > 50% or p < 0.10, we considered significant heterogeneity, and therefore, a random-effects model was used. We conducted a subgroup analysis to explore the potential sources of heterogeneity. Ethnicity, tumor type, treatment method, sample size, and cut-off value were considered to execute the subgroup analysis in order to explore the influence of confounding factors. Begg’s test and Egger’s test were performed to assess publication bias. If there were potential publication bias from the included studies, Duval and Tweedie nonparametric trim and fill procedure would be used to explore the effect of missing studies. Concrete details and interpretation were available in the reference [P < 0.05 (two-tailed) was considered statistically significant.We synthesized the HRs and CIs to determine the prognostic value of SII in PCa patients. Pooled HR > 1 without 95% CI overlapping 1 suggested that a high SII was associated with poor prognosis of PCa patients. Cochran’s Q and Higgin’s Ieference . We alsoThe detailed flowchart of the study search and selection process is shown in Fig. All of the included studies were retrospective and published between 2016 and 2022. Three studies were conducted in China , 37, 41,p < 0.001). Significant heterogeneity was detected in the included studies  . We performed subgroup analysis based on ethnicity, tumor type, treatment method, sample size, and cutoff value of SII. A high SII was significantly associated with worse OS in the subgroups of any ethnicity, tumor type, and cutoff value. A high SII was associated with worse OS in patients treated with chemotherapy + androgen receptor targeting agents (ARTA)  and in studies with a sample size > 200 . The details are available in Table Ten studies including 1753 patients focused on the association between SII and OS in patients with PCa , 32–39. p = 0.001. A random-effects model was used because of the significant heterogeneity . In the subgroup analysis, a high SII value was significantly associated with poor PFS in Asian patients and a cutoff value > 580, with HR = 4.03, 95% CI 1.07–15.17, p = 0.04 and HR = 1.19, 95% CI 1.04–1.36, p = 0.01, respectively .Six studies comprising 6978 patients focused on the relationship between SII and PFS in patients with PCa , 40, 41.p = 0.074; PFS: p = 0.133). However, Egger’s test showed significant publication bias , and the asymmetric funnel plot showed the potential publication bias of the meta-analysis . Therefore, we conducted the Duval and Tweedie nonparametric trim and fill procedure to evaluate the effect of the potential missing studies [.We used Begg’s test and Egger’s test to analyze the publication bias of OS and PFS of the included studies. The results of Begg’s test showed no significant publication bias in the meta-analysis .Sensitivity analysis was used to assess the robustness of the meta-analysis. The leave-one-out test showed that no single study influenced the results, indicating that the results of the meta-analysis were stable and reliable Fig. .Presently, the surveillance of progression and estimation of prognosis in patients with PCa mainly rely on conventional clinicopathological variables, such as Gleason scores and PSA, which could partly reflect cancer behavior in biology but may not represent the actual status of PCa. In recent years, SII, an index based on blood tests, has shown great potential as a complementary item for the prediction of survival in patients with malignancies. The impact of SII on the prognosis of solid tumors, including breast cancer , pancrea9/l), neutrophils  and lymphocytes  in peripheral blood using the following formula: SII = P × N/L [SII is based on the quantity of platelets  SII partly represents the actual status of immune system in PCa patients. (2) SII includes more items of immune cells than NLR and PLR which had been already researched in survival outcomes of PCa. (3) All the data used for calculation of SII could be acquired from routine blood tests, which means that investigators could collect and analyze SII data without any difficulty. (4) SII may have the potential of being a decisive factor for immunotherapy. Limitations of this meta-analysis are as follows: (1) The cutoff values of SII are variable across the studies included in the analysis, which may cause substantial heterogeneity between the studies included. The heterogeneity might confine its application in clinical practice; hence, more credible evidence is needed to identify the optimal cutoff values of SII. (2) All the studies in this meta-analysis were retrospective, which may cause selection bias. Evaluation of the effect of the potential missing studies through the Duval and Tweedie nonparametric trim and fill procedure indicated that publication bias may exist in studies included in this meta-analysis. (3) This meta-analysis only included 12 studies and 8083 patients. Sample size of studies included in this meta-analysis is of great discrepancy. The comparatively small sample size caused relatively insufficient reliability of this study. Population-based studies are necessary in the future to provide profound and accurate evidence for this subject.This systematic review and meta-analysis suggested that a high SII value was significantly associated with poor OS and PFS in patients with PCa. The SII may serve as an independent effective prognostic indicator for PCa. Furthermore, more rigorously designed studies should be conducted for use in clinical practice.