Despite the ongoing debate on the risk–benefit ratio of vestibular schwannoma (VS) treatment options, watchful observation and radiation are usually favored in the elderly (>65 years). If surgery is inevitable, a multimodal approach after deliberate subtotal resection has been described as a valid option. The relationship between the extent of resection (EOR) of surgical and functional outcomes and recurrence-free survival (RFS) remains unclear. This present study aims to evaluate the functional outcome and RFS of the elderly in relation to the EOR.This matched cohort study analyzed all consecutive elderly VS patients treated at a tertiary referral center since 2005. A separate cohort (<65 years) served as a matched control group (young). Clinical status was assessed by the Charlson Comorbidity Index (CCI), the Karnofsky Performance (KPS), and the Gardner and Robertson (GR) and House & Brackmann (H&B) scales. RFS was evaluated by Kaplan–Meier analysis using contrast-enhanced magnetic resonance imaging to identify tumor recurrence.surgELDERLY was 67.33 ± 42.02 months and 63.2 ± 70.98 months in the surgCONTROL.Among 2,191 patients, 296 (14%) patients were classified as elderly, of whom 133 (41%) were treated surgically. The elderly were characterized by a higher preoperative morbidity and worse gait uncertainty. Postoperative mortality (0.8% and 1%), morbidity (13% and 14%), and the functional outcome  did not differ between the elderly and the young. There was a significant benefit in regard to the preoperative imbalance. Gross total resection (GTR) was accomplished in 74% of all cases. Lower grades of the EOR  raised the incidence of recurrence significantly. Mean time to recurrence in the Surgical VS treatment aiming for complete tumor resection is feasible and safe, even in advanced age. A higher EOR is not associated with cranial nerve deterioration in the elderly compared to the young. In contrast, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. If surgery is indicated in the elderly, GTR can be intended safely, and if only subtotal resection is achieved, further adjuvant therapy, e.g., radiotherapy, should be discussed in the elderly, as the incidence of recurrence is not significantly lower compared to the young. Among benign nerve sheath tumors, the vast majority are vestibular schwannomas (VSs) with a reported incidence rate of 1.52 per 100,000 , 4. HistIn contrast to other patient cohorts, there seems to be a general agreement that watchful observation and radiation treatment should be favored in the elderly (>65 years of age) assuming a higher operative morbidity and lower life expectancy , 11. Howelderlies (>65 years of age) is of paramount importance, as an incidence peak is described in this specific patient group  the patterns of VS management in a tertiary neurosurgical center, (2) the onco-functional outcome, and (3) the incidence of recurrence in relation to the EOR in a large cohort of elderly patients compared to a matched-control cohort.nonsurgELDERLY) or surgical treatment (surgELDERLY) depending on tumor size, the presence of hydrocephalus, clinical presentation, and a patient’s individual preference. A separate cohort of patients with <65 years of age, who underwent elective VS surgery, served as a matched control group (surgCONTROL) to specifically compare surgical treatment in the elderly and the young , gender, and tumor size (closest match). All patients were treated by the retrosigmoid approach with intraoperative neurophysiological monitoring. Large VS  were generally treated in the semi-sitting position, while small VS  in the prone position  patients (>65 years) with unilateral VS treated at a German academic, tertiary referral center between April 2005 and October 2020. Patients were referred to non-surgical  were retrospectively analyzed to determine the tumor size according to the Koos grading system in a blinded fashion . The EORt-test was used. Recurrence-free and overall survival were estimated using the Kaplan–Meier method and compared between cases and controls using a log-rank test. The length of follow-up for recurrence-free survival was calculated from the date of surgical intervention to the date of either recurrence or the last clinical visit. Significance was defined as the probability of a two-sided type 1 error being <5% (p < 0.05). Data are presented as mean ± standard deviation (SD) if not indicated otherwise. Due to the low incidence of complications and perioperative morbidity, for its analysis and comparison dependent on the EOR, DS and STR were grouped together.Statistical analysis was performed in R Studio (Version 1.2) using descriptive statistics. To compare nonnumeric parameters of both groups, the chi-square test and Fisher’s exact test were applied. For numeric parameters, Welch’s two-sample nonsurgELDERLY) by either SRS  or watchful observation . 133/296 (45%) of elderly patients were treated microsurgically (surgELDERLY) via a retrosigmoid approach. A separate cohort of patients younger than 65 years (N = 133) served as a matched control group (surgCONTROL). The mean age of the surgCONTROL cohort was 46.3 ± 11.9 years  were of >65 years of age at date of diagnosis and classified as elderly Figure 1The most common initial symptom in the elderly was functional hearing loss in 172/296 (58%) cases, followed by vertigo in 117/296 (40%) patients. Tinnitus and gait uncertainty were similarly common with 84/296 (28%) cases and 85/296 (29%) cases, respectively. Facial palsy was a leading initial symptom in only 27/296 (9%) cases in the elderly. Trigeminal affection and swallowing deficits were very rare clinical symptoms with 24/296 (8%) and 5/296 (2%) cases, respectively. No patient presented with double vision Table 1.surgELDERLY with the younger surgCONTROL cohort, they presented with a worse initial KPS  poorer preoperative comorbidity status , yielding in a significantly higher CCI in the surgELDERLY compared to the surgCONTROL group  (surgELDERLY had a higher incidence of pre-operative gait uncertainty (p < 0.001), but complained of less tinnitus than their controlled matches (p = 0.016).When comparing < 0.001) 2. HowevsurgELDERLY and nonsurgELDERLY cohort did not differ in age, gender, the clinical status in KPS. The incidence of cystic morphology and MR-graphic progression was higher in the surgically treated but did not reach statistical significance in this cohort. However, nonsurgELDERLY were characterized by a significant smaller tumor size (p < 0.001). The nonsurgELDERLY cohort had less initial severe CN deficits  than surgELDERLY. The CCI was not significantly different in both cohorts . There were no significant group difference in the initial incidence of facial palsy, functional hearing loss, vertigo, trigeminal affection, swallowing deficit, headache, gustatory deficit and hydrocephalus in a matched control comparison (“surgELDERLY” vs. “surgCONTROL”). Remarkably, surgELDERLY had a higher incidence of gait uncertainty but complained of less tinnitus than their controlled matches. Additionally, surgELDERLY had a poorer preoperative comorbidity status , yielding in a significantly higher CCI in the surgELDERLY compared to the surgCONTROL group  (The eristics Table 1.surgELDERLY and 240.0 ± 82.1 minutes in the surgCONTROL (p = 0.398).Surgery was performed by a retrosigmoid craniotomy in all cases using either a semi-sitting  or prone position  in both surgical study groups. Mean operating time (skin to skin) was noted similarly at 248.0 ± 75.2 minutes in the surgELDERLY  and surgCONTROL group  (p=0.858). Larger tumors (Koos °III and °IV) more often yielded in postoperative complications . Postoperative hemorrhage, venous thrombosis and symptomatic pneumoncephalon occurred more frequently in the surgELDERLY, but this did not reach any statistical significance. In contrast, younger patients were more prone to postoperative CSF leakage. Overall, the complication rate in the surgELDERLY cohort was not significantly raised. One patient suffered a postoperative hemorrhage and treatment was terminated after the patient’s presumed will, yielding in a mortality rate of N = 1 . There was no significant difference in discharge modality (p = 0.377). Impeccable facial function (H&B = 1) was completely unaffected by the surgery in 38/112 (34%) and 53/123 (43%) in surgELDERLY and surgCONTROL, respectively (p = 0.096). After surgery-related deterioration, facial function recovered to a favorable outcome  in 45/75 (60%) and 46/70 (65%) surgELDERLY and surgCONTROL patients, respectively  than in surgCONTROL at 71%  with p = 0.164. New trigeminal deficit was observed in 2%. Of the 20 patients suffering from preoperative trigeminal affection , 17 patients recovered clinically in the surgELDERLY group (85%); the same was observed in 20/22 patients (90%) in the surgCONTROL group (p = 0.277). New postoperative gait uncertainty was observed in N = 4 in the surgELDERLY but none in the younger surgCONTROL group. Postoperative recovery of symptomatic gait uncertainty was observed in 71% (37/52) and 76% (12/16) of the surgELDERLY and surgCONTROL, respectively (p = 0.382). The recovery of vertigo symptoms was observed in N = 40/55 (71%) of all surgELDERLY presenting with preoperative vertigo; this rate was higher in the surgCONTROL cohort with N = 37/40 (90%) (p = 0.013). The incidence of new postoperative vertigo was N = 0 (0%) in surgELDERLY but N = 8/91 (9%) in its control cohort. Considering new postoperative tinnitus, the incidence was higher in the young (N = 1 in surgELDERLY and N = 9 in surgCONTROL), whereas the postoperative improvement of known tinnitus was similar at 14% and 16%, respectively (surgELDERLY and surgCONTROL) (p = 0.585).Postoperative KPS did not differ between ectively Table 5.surgELDERLY cases . When taking the EOR into account, there was no significantly higher postoperative CN affection  in surgELDERLY associated with GTR and STR/DS (surgELDERLY compared to the surgCONTROL (p = 0.035). Additionally, within the surgCONTROL group, STR/DS was associated with a significantly higher incidence of permanent facial deterioration (p = 0.036) compared to GTR.GTR was achieved in the majority of d STR/DS Table 6.surgELDERLY: p = 0.015; surgCONTROL: p = 0.003). The incidence of recurrence was statistically insignificant in surgELDERLY compared to surgCONTROL, when treated with GTR (p = 0.621). Mean time for surveillance was 38 ± 36 months in surgCONTROL (median: 25 months) and 31 ± 37 months (median: 34 months) in surgELDERLY. The overall incidence for recurrence was 5/133 (4%) and 10/133 (8%) after neurosurgical tumor resection in the surgELDERLY and surgCONTROL, respectively, with no statistical significance (p = 0.143). Mean time to recurrence was 67.33 ± 42.02 months in surgELDERLY and 63.2 ± 70.98 months in surgCONTROL. Kaplan–Meier analysis on RFS depending on the EOR is shown in surgELDERLY and surgCONTROL cohorts (p < 0.001). Mean time to recurrence in surgELDERLY was 67 ± 53 months and 79 ± 71 months in surgCONTROL.STR/DS was significantly associated with the incidence of recurrence compared to GTR in both subgroups  in a tertiary neurosurgical center and to assess the oncological and functional outcome of this particular cohort in comparison to matched young controls and in regard to the EOR. The elderly represented approx. 14% of all VS patients in our cohort. The majority was eligible for non-surgical treatment. Patients were allocated for surgical treatment due to large tumor size affecting the brainstem and worse preoperative clinical symptomatology . In comparison to a matched-control cohort, elderly selected for surgery were characterized by a worse preoperative clinical condition (KPS and CCI). Despite this, postoperative mortality, morbidity and functional outcome did not differ between both surgical groups. These data suggest that the retrosigmoid approach for VS resection is safe in the elderly >65 years of age. Patients significantly benefit in regard to preoperative imbalance. GTR was accomplishable in the majority of patients. Notably, the EOR determined RFS.surgELDERLY), preoperative CN deficits  were distinctively more severe than in the conservatively managed (nonsurgELDERLY). Same was described in a nationwide registry study in Sweden with 58 elderly patients and by a series of surgically managed elderly patients by Samii et al. , perioperative complication rates and morbidity are statistically comparable. Perioperative complications in the elderly have been described by current literature from 20% to 57% . The rate of permanent facial deterioration was significantly higher in surgELDERLY compared to surgCONTROL in the GTR group suggesting decreased postoperative rehabilitation potential in facial function with advanced age  comparing the nced age .The explanation for the inversely proportional relationship of permanent facial deterioration and GTR vs. STR/DS in the elderly  and the young  could be attributed to the actual intention-to-treat. In the young, we usually intend GTR unless there is a deterioration of the intraoperative neuromonitoring . This approach explains the GTR rate of 74% in the present study. However, in a larger cohort of the same group, GTR was even higher with approx. 93% . This faLong-term results should be chosen to compare functional outcome between such different treatment modalities as radiosurgery and microsurgery, e.g., in hearing outcome. Watchful observation (“WaS”) abandons CN function  to the natural history of VS and tumor dynamic. Thus, it has been shown that 12% lose functional hearing in the course of the VS natural history . In lineIt is not to be forgotten that functional outcome, as physicians and/or treating surgeons may define it, does not necessarily transfer to quality-of-life in the patients’ eyes in a proportional way. Leaving residual tumor behind or treating the tumor by non-invasive treatments such as SRS can impact mental health or illness perception .Due to the study design (matched by tumor size and the EOR), this analysis does not allow any general statement considering the frequency of the achieved EOR in the elderly compared to the young alone. However, when put into context with another series published and treated by the same group and institution with N = 572 primary VS patients, the rate of GTR was significantly higher among a general VS patient cohort of any age. Therefore, we can assume that the management of elderly patients with VS is carried out more conservatively—even in regard to the surgical EOR .Mean time to recurrence was >5 years in both groups, proposing that long-term follow-up in VS patients should be carried out regardless of age. Still, the overall incidence of and mean time to recurrence were statistically insignificant in the elderly compared to the young concordant to previous matched cohort studies with distinctly smaller patient numbers , 10. In The EOR is significantly associated with RFS in both groups independent of age with noted early tumor recurrence in DS compared to STR and GTR. Pre-existing data show that the volume of residual tumor correlates with the incidence of recurrence , 32. GTRA definite statement on surgical treatment of VS is generally very difficult to acquire due to several reasons: (1) the level of evidence: there are no published randomized controlled clinical trials or even prospective studies on surgical resection in the current literature , (2) hetIt is apparent that the retrospective nature of this study bears its limitations and biases. Firstly, this is a single-center study. Therefore, the generalizability and reproducibility of the results may be limited to specialized centers with a comparative caseload in VS. Furthermore, although the number of patients classified as elderly may be regarded as the largest cohort compared to previously published studies , 10, stiThe evidence level of VS management is remarkably low, and the debate on the risk–benefit ratio of surgical treatment is still ongoing, especially in the elderly. The present matched-cohort study shows that the microsurgical tumor resection of VS is safe and does not bear additional perioperative morbidity or worse functional outcome in the elderly as compared to a young control group. The overall incidence and of recurrence was statistically insignificant in the elderly compared to the young. When treating with surgery alone, the EOR determines RFS and the incidence of recurrence/progression in both study cohorts. For maximal tumor control, GTR should be intended. As incidence of recurrence is not significantly lower compared to the young. Postoperative follow-up should be carried out as mean time to recurrence was > 5 years in both groups. If leaving relevant tumor residual is inevitable, adjuvant therapy, e.g. SRS, should be evaluated in the Elderly.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval were not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the participants was not required to participate in this study in accordance with the national legislation and the institutional requirements.SW contributed to the acquisition, analysis, interpretation of data, conception and design, and writing the first draft. KM and FE contributed to interpretation of the data and critical review of the final manuscript. GN contributed to data analysis, interpretation of the data, and reviewing the final manuscript. MT contributed to the interpretation of the data and critical review of the manuscript. All authors contributed to the article and approved the submitted version.


Neurotensin (NTS) is a peptide discovered in 1973, which has been studied in many fields and mainly in oncology for its action in tumor growth and proliferation. In this review of the literature, we wanted to focus on its involvement in reproductive functions. NTS participates in an autocrine manner in the mechanisms of ovulation via NTS receptor 3 (NTSR3), present in granulosa cells. Spermatozoa express only its receptors, whereas in the female reproductive system , we find both NTS secretion and the expression of its receptors. It consistently enhances the acrosome reaction of spermatozoa in mammals in a paracrine manner via its interaction with NTSR1 and NTSR2. Furthermore, previous results on embryonic quality and development are discordant. NTS appears to be involved in the key stages of fertilization and could improve the results of in vitro fertilization, especially through its effect on the acrosomal reaction. Neurotensin (NTS) is a 13 amino acid peptide initially described in 1973 in the bovine hypothalamus , and itsNTS has a physiological role and is implicated in several functions, mainly in digestive and central nervous systems. In the digestive system, NTS acts on intestinal motility  and faciNTS effects are mediated by three receptors (NTSR): NTSR1 and NTSR2 are G-protein-coupled receptors with seven transmembrane-spanning domains, and NTSR3 or sortilin (SORT1) is a Vps10p receptor family member, which is characterized by the presence of an extracellular region containing a cysteine-rich domain and only one transmembrane domain . NTSR1 aThe NTS/NTSR1 complex is involved in the progression of many cancers, such as colic adenocarcinoma , small-cSeveral publications have reported the expressions of NTS and its receptors in reproductive tissues, related to their roles in reproduction functions, particularly in ovulation, sperm capacitation, fertilization, and embryonic development. It has recently been highlighted that NTS receptors are located on male gametes and that NTS is expressed in the uterus. NTS could play a role in reproduction issues by participating in follicular rupture during ovulation ,27 and iSynthesize knowledge regarding the expression and function of the neurotensinergic complex in the different models in which it has been studied;Propose an integrative mechanistic interpretation;Open perspectives for future research.The aim of this review was to synthetize the worldwide knowledge about NTS and its potential role in reproductive functions in order to achieve the following:On the PubMed database, the keywords “fertility”, “fertilization”, “ovulation”, “oocyte”, “embryo”, “endometrium”, “spermatozoa”, “oviduct”, and “reproduction” associated with NTS were tested. After abstract studies, we considered 15 publications of interest ,40,41,42NTS was described in the female tract in the oviduct epithelium using Western Blot, immunohistochemistry, and RT-PCR ,29,33,39Some authors have been interested in the presence of NTS/NTSR1 in the tissues of the human myometrium and leiomyoma and, more particularly, in women having hormonal treatment for in vitro fertilization (IVF) . Rodrigucumulus oophorus and corona radiata granulosa cells do not express NTSR1 and NTSR2; NTSR3 was not studied i levels were increased just after the addition. The calcium intensity when 50 μM of NTS was added was higher than that when 10 μM was added, providing evidence for dose dependency in the [Ca2+]i response. However, the number of sperm cells that immediately increased their calcium levels were low at 50 μM  and 10 μM , whereas almost all the sperm experienced increased calcium mobilization when ionomycin was added  [In human and non-human primates, Campbell et al. studied the NTS effects on the spermatozoa acrosomal reaction using immunofluorescence . They de < 0.05) . They al < 0.05) . Hiradat < 0.05) . When ad < 0.05) . Moreovexamined) .The potential role of NTS in spermatozoa is illustrated in Fertilization was specifically studied in only one publication. The NTS pretreatment of monkey sperm reduced the fertilization rate of monkey MII oocytes in vitro from 72% . Moreovep < 0.05) [p = 0.03). In this treatment group, the hatching rate was 28.1 ± 3.8% versus that of the control group  [Two publications studied the role of NTS in embryo development. The addition of NTS to an IVF medium significantly improved the levels of cleavage in the bovine embryo  . However < 0.05) . The eff < 0.05) . Embryos = 0.08) . No dataThe role of NTS in reproduction was first discussed in 1981 by Clark et al., who analyzed the effect of NTS on blood flow in the uterus of non-pregnant sheep . They coIn 1987, Reinecke et al. showed using an isometric force displacement transducer that NTS enhanced autonomous oviduct contractility up to 55% in vitro and that their amplitude was 9-fold more than that without NTS addition .p < 0.005), while siRNA-NTS induced the apoptosis of EECs (p < 0.005). In addition, NTS may play a role in endometrial receptivity by increasing the levels of certain biochemical markers of the receptive endometrium, such as leukemia inhibitory factor (LIF), COX2, and HOXA10, in EECs in vitro [The effects of NTS on endometrial receptivity appear to be very different depending on the species. In dairy goats, Zhang et al. analyzed the concentrations of NTS mRNA and other molecules in the receptive endometrium and the pre-receptive endometrium . Using iin vitro . Howeverin vitro . Conflicin vitro . The NTS physiological functions in mammalian reproduction are summarized in Data regarding the important role of NTS and its receptors are now well-established. About 15 publications that we reviewed exhaustively show the action of NTS in ovulation and fertilization.The data concerning ovulation are still incomplete. The exponential presence of NTS in granulosa cells, especially after LH, hCG, or eCG triggering, and the co-expression of the specific receptor NTSR3 point us towards an autocrine and/or paracrine mode of action. The limited experimental data support a necessary but not sufficient role in causing ovulation. Mechanistic studies conducting the inhibition testing of signaling pathways confirm a direct action via the MAPK pathway. Likewise, the presence of NTS in the female genital tract, particularly after ovulation, indicates a physiological role. Data concerning the stages of fertilization, as well as the presence of NTSR1 and NTSR2 on the sperm membrane , could suggest a major paracrine effect presiding over capacitation and the acrosomal reaction. However, fertilization rates with NTS-treated sperm were lower than those obtained with untreated sperm. It would be interesting to experiment to determine whether these fertilization rates remain low if NTS is added directly to the fertilization medium rather than to the sperm preparation, as the NTS-induced acrosomal reaction should be performed as close to the oocyte as possible. NTS could potentially play a role in IVF in cases of fertilization failure.The role of NTS in endometrial receptivity is not clear across species, yet implantation failures are a major cause of IVF failure, and its potential mechanisms are still poorly understood. The study of NTS expression at the endometrial level in women could be of interest in patients presenting repeated implantation failures after embryo transfer in this context.


The protein p53 is a well-known tumor suppressor that plays a crucial role in preventing cancer development. In Chinese philosophy, the concept of Yin and Yang is used to describe inseparable opposites, where Yin represents the negative or inhibitory force, and Yang represents the positive or promoting force. In this context, the wild type of p53 can be considered Yin, as it acts as a negative regulator of cancer progression, while most p53 mutations can be considered Yang, as they promote cancer progression.Some p53 mutants, such as p53 S46F and S121F, exhibit higher transactivation activity than wild type, which can be considered as a super Yin of p53 . In contIt has been known that some mutated p53 can appear in the cytosol , and cyt


In addition to its role in tumors, p53 has a widespread expression in the brain and participates in most cell processes, such as dendrite formation, oxidative stress, apoptosis, autophagy, DNA repair, and cell cycle arrest. Therefore, abnormalities in p53 and its related signaling pathways play an important role in the diagnosis and treatment of central nervous system diseases. This review mainly discusses the latest findings regarding the role of p53 in some central nervous system diseases, such as brain tumors, Alzheimer disease, Parkinson disease, autism, epilepsy, spinocerebellar ataxia, and so on, to provide a comprehensive interpretation of the treatment of neurological diseases from a new perspective.The transcription factor p53, a widely accepted tumor suppressor, regulates the expression of many oncogenes and their downstream signaling pathways, resulting in a series of biological outcomes. Mutations and deletions of the  Thus, abnormal expression of p53 protein can lead to the occurrence and development of neurological diseases. p53 is an important cancer suppressor factor that has a high mutation frequency in human cancers. Through the pathological analysis of a large number of tumor patients, approximately 50% of the tumor samples had p53 deletion or mutation, including brain tumors  is one of the target genes for p53. A mutation in P53V143A can block the transcription of p21 and its function of inducing cell cycle arrest, leading to cell cycle disorder and promoting the occurrence of malignant glioma  often occur . TherefoAD is a common neurodegenerative disease, and its neuropathological features are the accumulation of amyloid-β (Aβ) and nerve fiber tangles formed by tau hyperphosphorylation, resulting in neuronal dysfunction . A high As mentioned above, p53 is present at a low level in normal cells. In addition to posttranslational modifications, the conformational state of p53 also affects intracellular stability. Unfolded p53 has been detected in early-onset AD patients . UnfoldeTargeting p53 as a therapeutic target to prevent or treat AD remains a great challenge. Although p53 is related to neuronal death and is involved in the pathological processes of AD, only in vitro evidence has been promising, and in vivo studies are needed to support the potential for p53 targeting to be translated into the clinic. As mentioned above, phospho-p53 (Ser15) and phospho-p21 (thr145) are biomarkers for the diagnosis of AD in peripheral blood lymphocytes of patients with AD . In addiDJ-1 is a PD gene that could provide valuable reference ideas for the treatment of PD. In a zebrafish PD model deficient DJ-1, p53 and the proapoptotic factor Bax were overexpressed before toxin exposure, and no significant neuronal cell death was observed, suggesting that subliminal activation of the cell death pathway may have therapeutic effects on PD, such as inhibition of the p53 pathway  is also known as autism. Its clinical manifestations include social interaction difficulties, communication impairment, and stereotyped repetitive behavior patterns, which are the result of a combination of genetics and external environmental factors . HoweverSCA is an autosomal dominant genetic disease that mainly manifests as behavioral movement disorders and speech disorders. There is currently no specific drug treatment, so it is very important to study its pathogenesis and pathways . The patp53 is not only involved in the pathogenesis of brain tumors, AD, and spinocerebellar ataxia, but also in the occurrence and development of other CNS diseases, such as schizophrenia (SCZ), depression, epilepsy, and cerebral ischemia. SCZ and depression are common affective disorders with a high incidence . It has Epilepsy is a common neurological disease with a complex etiology. In addition, p53 is significantly upregulated in both posttraumatic epilepsy and drug-resistant epilepsy rat models, accompanied by increased apoptosis of nerve cells in the mesial temporal lobe and hippocampus . SimilarFigure 2). At present, evidence for the role of p53 in related neurological diseases is still relatively limited and needs more research support. In addition, as people grow older, the risk of co-occurrence tumor and neurodegenerative diseases increases significantly; whether and how p53 is involved in this process should be given more attention. It should be noted that most preclinical models are constructed using adult animals, which ignores the effect of aging and may hinder hypothesis clarification (In this review, we describe the role of the p53 pathway and genetic alterations of p53 in the progression of different CNS diseases (fication . TherefoI/LH have been utilized to reverse the abnormal structure of p53 or downstream signaling pathway changes caused by p53 mutation (Studies have demonstrated a strong correlation between tumors, neurological disorders, and p53. Consequently, antitumor drugs that target p53 may have potential therapeutic benefits for treating AD, PD, autism, and so on. Some of these drugs function by inhibiting the ubiquitination degradation of p53, which is regulated by E3 ligase MDM2 H. . To restmutation . Some coIn addition, when discussing p53, the role and function of its family members p73 and p63 should not be forgotten . Accordi


The COVID-19 pandemic and associated social restrictions had an extensive effect on peoples’ lives. Increased rates of weight gain were widely reported, as were declines in the general populations’ mental health, including increases in perceived stress. This study investigated whether higher perceived levels of stress during the pandemic were associated with greater levels of weight gain, and whether poor prior levels of mental health were a factor in higher levels of both stress and weight gain during the pandemic. Underlying changes in eating behaviours and dietary consumption were also investigated. During January-February 2021, UK adults (n = 179) completed a self-report online questionnaire to measure perceived levels of stress and changes (current versus pre-COVID-19 restrictions) in weight, eating behaviours, dietary consumption, and physical activity. Participants also reported on how COVID-19 had impacted their lives and their level of mental health prior to the pandemic. Participants with higher levels of stress were significantly more likely to report weight gain and twice as likely to report increased food cravings and comfort food consumption . Participants reporting an increase in food cravings were 6–11 times more likely to snack and to have increased consumption of high sugar or processed foods . Females reported a far greater number of COVID-19 enforced lifestyle changes and both being female and having poor mental health prior to the pandemic were significant predictors of higher stress and weight gain during the pandemic. Although COVID-19 and the pandemic restrictions were unprecedented, this study suggests that understanding and addressing the disparity of higher perceived stress in females and individuals’ previous levels of mental health, as well as the key role of food cravings, is key for successfully addressing the continuing societal issue of weight gain and obesity. After the declaration of the SARS-CoV-2 coronavirus COVID-19) pandemic in March 2020 9 pandemi. These iAlthough COVID-19 restrictions were implemented to improve the health outcome of the pandemic, the high level of hospitalisations and deaths in the UK  caused cSince the start of the pandemic there was also an overall reported increase in food intake and weight gain both in the UK and other countries –18. StudPrior to COVID-19, obesity was already considered to be a global epidemic –26. In aPrior to the pandemic, long-term chronic stress already had a significant positive association with weight gain –34. SeveFood cravings are defined an intense desire to consume a particular food or food type, often in the absence of hunger . Higher Some of the main barriers to weight loss and weight maintenance that have been identified in recent studies are mental distress and binge eating (or comfort eating) , negativThe aim of this study was to investigate whether higher levels of stress reported by the general UK population during the pandemic were linked to higher levels of weight gain, and whether these changes were directly associated with increased food cravings and comfort eating. Secondly, we aimed to investigate whether individuals’ level of mental health prior to the pandemic were linked to higher levels of stress and weight gain during the pandemic. In addition, we addressed whether specific lifestyle changes caused by COVID-19 and the UK imposed restrictions were linked to higher levels of stress. We hypothesized that individuals with higher perceived stress would report greater weight gain during the pandemic, with people who had poor mental health before COVID showing the strongest effects. Furthermore, we hypothesized that the weight gain and perceived stress were strongly linked with increased food cravings and comfort food consumption.The study used a convenience sample and the eligibility criteria was that participants were aged 18 or over and had been resident in the UK since the beginning of COVID-19 restrictions in March 2020. Participants were recruited through open adverts on social media and through internal advertising in Bangor University School of Human and Behavioural Sciences. To achieve adequate power for testing a minimum of 92 participants were required, based on a two tailed priori power analysis of 25% effect size, 0.8 power, 0.05 error . Effect size used was based on previously reported increases in food intake and weight gain when under high levels of stress, both prior to and during COVID-19 restrictions , 17. TheData was collected using a bespoke online survey that was administered via Qualtrics . The survey was completed anonymously, with no data collected that could identify participants. The survey was designed to be easy to answer and completed in as short a time as possible, to ensure minimal drop out of participants. To enable this, where appropriate, questions were asked about categorical changes  rather than absolute measures. As well as simplifying the questionnaire, the use of categorical measures, rather than absolute measures, enabled the reporting of overall trends while avoiding inaccuracy problems with self-report measures.At the start of the survey participants were provided with a brief overview of the study aims and the participant inclusion criteria (over 18 and based in the UK since the beginning of COVID-19 restriction). For participants to take part in the study they were required to click on a button of “I meet the inclusion criteria and consent to take part in the study”. After providing informed consent participants reported on the following information:Participants reported on the demographic measures on age, gender, main current occupation, country of the UK based, height and weight . Participants were asked to report how their weight had changed since the beginning of the COVID-19 restrictions within the following categories: lost more than 3kg/6 pounds, lost up to 3kg/6 pounds; weight remained stable, gained up to 3kg/6 pounds, gained between 3kg/6 pounds and 6kg/a stone, gained more than 6kg/a stone.Participants were asked to report whether their general hunger, food cravings, number of meals consumed, snacking in the daytime and snacking in the evening had decreased, increased or stayed the same in the past 3 months, compared to prior to COVID-19 restrictions. Participants also reported if they believed any of the following reasons had increased their dietary consumption: being at home, boredom, stress anxiety or low moods, feeling tired or lacking in energy, The behaviour categories were based on categories reported by other COVID-19 studies , 47.Participants were asked to report if their consumption of any of the following categories had decreased, increased or remained the same in the past 3 months, compared to before the start of the COVID-19 restrictions: fruit and veg; high fibre foods , red or processed meat , dairy products, vegetarian/vegan meat or dairy alternatives, processed foods , home cooked food, tinned or frozen food; high sugar foods , coffee or tea, fruit juices or smoothies, fizzy drinks (including diet drinks), alcohol, water. The range of dietary categories was based on dietary categories reported in other COVID-19 studies –17.To ensure that any reported changes in weight were due to changes in dietary consumption rather than changes in physical activity, participants were asked if their level of vigorous/moderate exercise, walking and sedentary time had decreased, increased or stayed the same in the past 3-months compared to before COVID-19 restrictions.As part of the survey participants completed the Perceived Stress Scale PSS-10  to evaluParticipants were asked to report on ways in which ways COVID-19 and the associated imposed restrictions had impacted their lifestyle and food availability. Participants were asked if the restrictions had impacted them in any of the following ways: continued to work outside the home but had to use personal protective equipment (PPE), moved to work from home, experienced job uncertainly, experienced job loss, had confirmed COVID-19 infection, had to self- isolate due to possible COVID-19 infection, had to self-isolate due to underlying health issues, had additional caring responsibilities including school-aged children or other dependents, had less access to fresh or healthy food, had less money to spend on food, had less time to prepare healthy food.Descriptive statistics (mean ±SD) were used to characterise survey respondents and summarise their changes in weight gain, eating behaviours, dietary consumption and physical activity. Eating behaviours and dietary consumption were re-categorised in to an “increased” or “no increase” categories (which included the “stayed the same” and “decreased” categories). This was as this study was specifically interested in the likelihood of increased food cravings and comfort foods being linked to stress and weight gain.Although the PSS-10 questionnaire gives a continuous score outcome, to enable us to carry out logistic analysis with the categorical variables reported for changes in weight, dietary consumption and exercise, participants were recategorized into a higher or lower stress group, with categorization based on the mean PSS-10 score of trial participants (19.3±6.9). Participants with a PSS score of 19.3 or lower were allocated to the lower stress category and participants with a PSS score of 19.4 or higher were allocated to the higher stress category.p < 0.05 was applied to all statistical analyses.Ordinal regression analyses were used to identify factors linked to a greater likelihood of reporting weight gain. Pearson’s chi-square analyses were used to investigate a significant difference in likelihood in response between the higher and lower stress groups to: weight gain, increases in eating behaviours, increases in dietary consumption, and changes in physical activity. Binary regression analysis was used to identify factors linked to a greater likelihood of belonging to the higher stress group. Odds ratios were also calculated for all chi-square analyses, to allow direct comparison of results with the binary and ordinal regression analyses. All statistical analyses were carried out using the Statistical Package for Social Sciences . A 95% confidence interval (95% CI) was selected, and a significance level of In total, responses were collected from 220 participants between 6th January until 2nd February 2021. After removing duplicates and incomplete questionnaires, 179 participants’ data sets remained. There was no significant demographic difference between survey completers and non-completers. The full survey dataset is available in 2.Most survey respondents were female (75%) and aged between 18–55 (85%). Two thirds of respondents were based in Wales (66%) and a third (34%) in England. The mean BMI of respondents was 26.10(±5.46) kg/mMany respondents reported that their main current occupation involved working from home, with a higher proportion of females being based at home (F = 40%:M = 27%) and more male respondents continuing to work outside the home (F = 15%:M = 27%). As the questionnaire was advertised within the university, unsurprisingly students made up 25% of respondents, although 8% of responders were in the retired category. Notably, only females reported that caring for children or dependents was their main occupation (5%). The overall level of participants unemployed or furloughed was low .When asked about the impact of COVID-19 restrictions on their lifestyle, a comparable number of women and men reported moved to work from home (F = 50%: M = 46%). A higher proportion of women reported worked outside the home using PPE (F = 35%:M = 25%), having to isolate due to potential COVID-19 infection (F = 25%:M = 16%) or having additional caring responsibilities for children or other dependents (F = 39%:M = 9%). Males reported higher levels of job uncertainty (F = 12%:M = 23%), job loss (F = 5%:M = 7%), having had COVID-19 (F = 4%:M = 7%) and self-isolating due to underlying health issues (F = 4%:M = 11%). The difference in the level of impact of COVID-19 restrictions by gender was notable. When comparing the total number of changes that participants were affected by, 53% of females were affected by 2 or more lifestyle changes compared to 39% of males. The impact of COVID-19 restrictions on food availability was also far more likely to impact females. Females were around twice as likely to report less money to spend on food (F = 16%:M = 9%), less access to healthy food (F = 12%:M = 7%) or less time to cook healthy food (F = 11%:M = 5%). Full demographic statistics for survey participants are available in Participants were asked to report their weight change in categories rather than absolute weight changes to avoided inaccuracy problems with self-report measures. There was a notable difference between the genders for reported weight gain, with females almost twice as likely as males to report an overall weight gain since the start of the COVID-19 restrictions (F = 50%: M = 27%). and twice as likely to report the highest level of weight gain of more than 6kg (F = 10%: M = 5%). see 2 = 14.639, p = 0.012, phi = 0.286). This confirmed the study’s main hypothesis that participants reporting a higher level of stress during the pandemic were statistically more likely to report a higher level of weight gain. Although the aim this study was not specifically focus on gender differences, due to the large differences in weight changes reported by males and females a Chi-square tests for independence was carried out, which showed that the association between gender and weight gain was statistically significant, with small to medium effect, χ2 = 11.986, p = 0.035, phi = 0.259).Ordinal regression analysis showed that the likelihood of the higher stress group reporting a greater level of weight gain was statistically significant, with a medium effect size, χIn the survey, participants were asked to report on changes in eating behaviours that are often linked to weight gain, including hunger, number of meals, cravings, and snacking. Overall increases were reported for all eating behaviour categories, apart from number of meals see . Althoug2 = 70.877, p<0.001), with increased food cravings , increased number of meals , increased snacking in the day  and eating due to stress, anxiety or low mood  all significant factors linked to weight gain. Although being at home or boredom were given by the participants for the primary reasons for increased food consumption, there was no statistical significance of these factors and actual weight gain. An ordinal logistic analysis was performed to assess whether increases in the 5 eating behaviours and 4 reasons given for increased eating increased the likelihood of respondents reporting weight gain. The full model was statistically significant, χχ2  = 6.402, p = 0.011, phi = 0.202;) OR = 2.3 and snacking in the day χ2  = 4.192, p = 0.041, phi = 0.165), OR = 1.9. Participants in the higher stress category were also more likely to report increased eating due to stress, anxiety or low mood χ2  = 25.684, p<0.001, phi = 0.390), which is as expected, as both measures are reporting on levels of stress. In comparison, there was no statistical significance for higher stress and increased number of meals. In summary, increased food cravings and snacking in the day were the only behaviours correlated with both higher stress and weight gain.To determine whether these behaviours were more likely in the higher stress group a chi-square test was carried out. This showed that participants who were in the higher stress category were twice as likely to report increased food cravings Like changes in eating behaviours, there was a polarisation of changes dietary consumption. Over half of respondents maintained their pre-COVID-19 consumptions levels of fruit and veg (55%), high fibre (70%), red/processed meats (52%), white meat/fish (60%), dairy products (71%), vegetarian/vegan alternatives (62%) and tinned/frozen foods (68%). A notable change was seen with home cooked food category, where 50% increased their consumption. The other categories which showed the greatest change in consumption were those that can be categorised as comfort foods. There was comparable split between decreased, increased or remained the same for processed foods . Forty percent of participants reported an increase in consumption of high fat/salt foods, and over half (57%) of participants reported an increase in high sugar foods. With the drink categories, the majority respondents reported maintaining their pre-COVID-19 consumption level of fruit juices/smoothies, fizzy drinks and water . In comparison almost half of respondents reported increased consumption of coffee and tea, and alcohol . A full summary of the dietary changes for survey participants is available are available in χ2 = 75.291, p<0.001), although only 4 of the 16 categories made a significant contribution. Increased consumption of high sugar and processed foods were linked to a 2.5–3.2-times likelihood of an increase in weight gain . However, the inverse effect was seen in the categories of high fibre foods  and water , where increased consumption was linked to a greater likelihood of weight loss. To determine which dietary categories were linked to weight gain an ordinal logistic regression was carried out. The full model, containing all 16 food and drinks categories, was statistically significant, χ2 = 4.001, p = 0.045, phi = 0.161), OR = 1.9 and processed foods χ2  = 6.310, p = 0.012, phi = 0.201), OR = 2.5. In comparison, there was no statistical significance for changes in the consumption of high fibre food or water and higher levels of stress. In summary, increases in high sugar and processed food consumption were the only dietary categories linked both to a higher level of stress and weight gain.A chi-square analysis was carried out to determine whether the dietary categories linked to weight change were also linked to higher levels of stress. This showed that participants in the higher stress group were twice as likely to have increased their consumption of both high sugar foods χ2(1) = 48.008, p<0.001, phi = 0.534; OR = 11.2), and over 6 times more likely to report increased consumption of processed foods, χ2 (1) = 22.920, p<0.001, phi = 0.374, OR = 6.3), although there was no significant link with high fat/salt foods. There was also a statistically significant link between increased cravings and increased snacking in the day (but not snacking in the evening), with participants reporting increased food cravings 6 times more likely to report an increase in snacking during the day, χ2 (1) = 29.181, p<0.001, phi = 0.419; OR = 6.0).To investigate further the relationship between increased food cravings and increased comfort food consumption , a chi-square analysis was performed. We also investigated if an increase in food cravings was linked to an increase in snacking, as comfort food is often consumed outside mealtimes . Particiχ2 = 25.354, p = 0.005, phi = 0.271), but not for changes in level of walking or sedentary time. Chi-squared tests of level of activity versus stress levels were non-significant χ2 = 1.40, p = 0.50, phi = 0.088). Consequently, although a reduction of moderate/strenuous activity increased the likelihood of weight gain, it was not a mediator of the effect of stress on weight gain. A full summary of the physical activity changes for survey participants is available in To discount the role of physical activity in the effect of stress on weight gain, participants were also asked to report in their changes in physical activity. Almost half of respondents (47%) reported a reduction in their level of moderate or strenuous activity compared to their pre-COVID-19 levels of activity. In comparison, almost half (43%) of participants reported that they had increased their level of walking compared to pre-COVID-19 level. However, the category with the greatest reported difference, was sedentary behaviour, with 78% or respondents reporting an increase in sedentary compared to their pre-COVID-19 levels. Chi-squared tests for level of activity versus weight change did show a statistical significance for a reduction in moderate/strenuous activity and weight gain, Participants were asked to report both their current levels of perceived stress, using the PSS-10 questionnaire, and their mental health prior to the start of the pandemic. With both categories a higher level of stress was reported by women. The overall PSS-10 score for trial participants was (19.3±6.9). However, the average score for women was 20.4±6.6, compared to an average score of 15.7±6.7 for men. Half of participants (54%) reported that prior to COVID-19 they had generally coped well with stress. 25% reported that they had some level of stress, anxiety or depression prior to COVID-19 restrictions, but had not received a formal diagnosis and 17% reported that they had previously been diagnosed with stress, anxiety or depression. Again, women were far more likely than men to report having been diagnosed with stress, anxiety or depression prior to COVID-19 (F = 19%:M14%) or have had some level of stress anxiety or depression but had not been diagnosed (F = 26%:M = 20%).p = 0.014, OR = 3.6), which was independent of their levels of stress prior to COVID-19. As the pandemic caused so many enforced changes to peoples’ everyday life, one of the aims of this study was to see if any of these changes directly increased participants level of perceived stress. As reported in the descriptive statistics, moving to work from home was the highest reported change and was comparable for women and men. There were also notable differences between the genders in the numbers of changes they were affected by and some key categories such as caring from children and other dependents. A binary regression analysis was carried out which included all lifestyle changes, and gender, age and mental health prior to COVID-19. Surprisingly, the analysis did not show a significant link between any of the lifestyle changes and higher levels of perceived stress. However, gender and mental health prior to COVID-19 were both significantly linked to perceived stress during the pandemic χ2 = 58.95, p<0.001). Participants who had a prior diagnosis of stress, anxiety or depression were almost six times more likely to be in the higher stress category , confirming our hypothesis, with participants who had not been officially diagnosed, but reported some levels of stress, anxiety, or depression over three times more likely to be in the higher stress category . Females were around 4 times more likely to be in the higher stress category than males  diagnosis prior to the pandemic were almost six times more likely to be in the higher stress category (OR = 5.7). In addition, participants who had not been officially diagnosed, but reported some prior levels of stress, anxiety, or depression were also three times more likely to be in the higher stress category (OR = 3.6). Other studies have also reported prior mental health, stress and weight gain. Participants with a diagnosis of psychiatric illness or obesity prior to the pandemic were more likely to report declines in weight gain protective behaviours . Having R = 3.6), which was independent of their levels of mental health prior to COVID-19. Other published studies have also highlighted higher stress levels during COVID-19 in women than in men [Whilst this study was not specifically designed to investigate differences by gender, our results reported significant differences between women and men. Women reported higher levels of weight gain (F = 50%: M = 27%) and were twice as likely to have reported the highest weight gain category F = 10%: M = 5%). Women were more likely to have a mental health diagnosis prior to COVID-19  or have low mental health but not diagnosed . In addition, during the study they were also over 3 times more likely to be in the higher stress category than males  being within in the 18–55 age range. We believe, however, that the study results are valid, as the survey achieved adequate power . In addition, the results are in line with other similar larger published studies cited in this paper. With respondents being mainly young-middle aged adults, we recognise that this population is not fully representative of the UK adult population. However, as many of the COVID-19 imposed restrictions  were more likely to impact the working age population, we believe that with this study sample enabled a realistic evaluation the impact of the pandemic restrictions on people’s lives.The primary aim of this study was to investigate the relationship between higher stress and weight gain for a wide range of factors. To enable us to do this using logistic analyses we categorised all factors. However, it is accepted that by using categorical rather than continuous measures for perceived stress scores we may have limited the ability to track smaller changes in lifestyle factors on stress levels, particularly as former studies indicate that females routinely report higher levels of stress –12. We aPerhaps the most important limitation of this work that it is a correlational study, so although we are proposing that higher stress leads to weight gain, it needs to be considered that weight gain could also be the driver of stress. We acknowledge that there are complex interactions between stress and weight gain, with different responses shown in females and males . HoweverIn summary, the results from this study corroborate previous research, that higher levels of stress are significantly linked to increased weight gain. The study also highlights significant differences in perceived stress and weight gain during the pandemic by gender and the role in mental health prior to the pandemic in weight gain. Further work is necessary to understand how stress reduction strategies could be incorporated into weight loss/maintenance approaches, including a greater awareness of individuals’ stress levels and history of mental health when developing weight loss and maintenance strategies. A more gendered approach to weight loss may also be required, either to take into consideration differences in perceived stress levels between females and males or to determine if the role of stress in weight gain is a gendered factor.The study also reiterates the key role of food cravings in the link between stress and weight gain. Food cravings were linked to a 3 times increased likelihood of reporting weight gain, and to 6–11 times increased likelihood of snacking and consumption of high sugar and-processed foods. This strongly suggests that re-focusing weight loss methods on the ability to control cravings, possibly by using stress reduction techniques, will be a more effective approach to than the current focus on reduction of the downstream behaviours of increased snacking, and consumption of processed and high sugar foods.S1 Dataset(ZIP)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Due to physical differences between the genders, it is hard to study whether women also vary from men in their competitive drive in sports. The Olympic committee instituted major rule changes in the sport of shooting in the Tokyo Olympic Games (2021), leveling the playing field. We explored performance in a myriad of competitions including newly established mixed-gender doubles events in this unique sport of very limited physical input. Men performed better than women in events which required “dynamic” qualities (following moving targets) but when the competitions were held most constant (rifle shooting with stationary targets indoors) and regardless of distance or posture, women performed equally to men exhibiting seemingly similar competitive drive. The last finding should propel the Olympic committee to fully integrate rifle events. In the broader sense, we find that when the playing field is even, the genders, at least among highly trained selective competitors compete equally. Sometime in the early 2000’s Uri Gneezy and Aldo Rustichini conducted a very intriguing field study in an elementary school in Israel . The parNotwithstanding experimental concerns in regards to the criterion of who was assigned to the control vs. the experimental condition, time measurement , possiblAbundant of research in this field is still in agreement with the results of the original running study, arguing that when the stakes are especially high males show greater competitive tendencies, which lead them to superior performance over females. Three main categories of research make this claim. Laboratory experiments ,7, archiDue to the limiting circumstances of gender separation, which preclude direct comparisons, researchers need to show ingenuity in exploring gender differences in sport. Also of note is the type of sports studied whereupon some competitions are characterized as closed skill  ,16 such In tennis, an interactive sport, Paserman  studied Shifting to more closed and continuous type of sport, performance in New York City Marathon (2007–2014) was studied where female runners start the race 30 minutes earlier than their male runners, which leads some elite women to be eventually passed by the fastest men . It was Other research in gender differences in professional sports focused on financial rewards and their impact on performance –23. For Most closely approximating the sport of shooting, Duffy  in quasiSpecifically in rifle shooting, the focus of the current investigation, competitors perform in a highly controlled environment. The sport is characterized as closed in terms of skill execution where the environment is mostly predictable and static , with fiIn the same sport, an important rule change in 2018 was examined when the Olympic shooting protocols increased the number of women’s shots from 40 to 60, making them equal to men . This stIn the current investigation, we endeavored to test this conclusion when the stakes are highest during the Olympics where contestants can win substantial sums of money  and sponIn the way of specific directional hypotheses, we predicted based on past research ,30 that This study was approved by the Ethics Committee of the Polytechnical University of Madrid. The participants of the study were 357 shooters of 101 countries. Of the total participants’ number, two shooters were excluded because one was disqualified, and the other did not start the competition. The final sample was composed of 355 shooters with an average age of 29.9 ±7.65 years . The gender distribution was 178 women and 177 men.The qualification system for the mixed team events according to the ISSF rules is as follows: “Mixed Team entries may come from athletes entered in Mixed Team quota places obtained at the 2018 WCH Changwon, KOR and from double starters who are also entered in individual events.” . In consequence, those athletes qualified in the mixed events during the world Championship in 2018 were directly classified for the Olympics in the mixed events. In addition, those shooters who qualified in the individual’s events with an opposite gender mate who qualified independently in the same event, were able to join forces in the mixed event. For example, a male air pistol shooter and a female air pistol shooter who has qualified in the individual event could participate in the mixed event together. Lastly, it is important to note that the individual events were finished before the mixed events had commenced as to not undermine performance in the individual modalities. Shooters who qualified for the team competition hence increased their chances of winning a medal without jeopardizing their focal individual pursuit.See The participants took part in a total of 15 shooting modalities, five modalities for each weapon: pistol, rifle, and shotgun. Additionally, six shooting modalities were for men, six for women and three for mixed team modalities. Among the competitors, 95 men and 125 women were double starters, competing in two events. nd to August 2nd. The results were tabulated from the International Shooting Sport Federation (ISSF) webpage once the results became official .The data of the present study were collected during the Olympic Games Tokyo 2021 from July 22According to the new International Olympic Committee competition protocol, the number of shots allotted were matched and to balance the competition by gender. In addition, prone rifle, free pistol and double trap modalities were replaced by three mixed team modalities in the Tokyo 2021 schedule , in which both men and women competed together and simultaneously .As inclusion criteria, only those modalities in which men and women fired the same number of shots and under the same conditions, both individually and in mixed teams, were selected to be analyzed. Consequently, the modalities of rapid-fire pistol (only men) and sport pistol (only women) were excluded from the study.Additionally, the final rounds were excluded from the analysis due to the specificity of these stages’ rules and the low number of participants , as they could entail insufficient statistical power.Regarding the qualification round structure, athletes fired 60 shots in sets of 10 shots for individual events of air pistol and air rifle (both men and women) while mixed events of air pistol and air rifle have a total 60 shots per team in sets of 10 shots, (each gender shot 30 shots). Additionally, 3x40 rifle event consist in 120 shots in sets of 10 shots divided 40 shots by position . On the other hand, clay target individual modalities of trap and skeet consist of 125 targets in sets of 25 shots (both men and women) while, in the mixed trap team event, each gender shot 75 targets for maximum score of 150 hits. See Performance were measured using the total points in the precision events and total number of hits in trap and skeet events according to the ISSF rules and regulations . Furthermore, to make possible the performance comparison between modalities with the same weapon but with different number of shots (for example: air pistol vs. air pistol mixed team and air rifle vs. air rifle mixed team) the average points per shot was calculated .Performance outcomes were measured using the total points (continuous score) in the precision events. More specifically, points with decimals in 10m Air Rifle and 10m Air Rifle Mixed Team and points without decimals in the rest of events. The total number of hits (a fraction score) was computed for the trap and skeet events and trap mixed team events according to the ISSF rules and regulations  see .M) and standard deviation (SD). The normal distribution of the variables was checked using the Kolmogorov–Smirnov and Shapiro–Wilk tests.The data are described by arithmetic mean (T tests used to contrast gender and competition type). In our main analysis, we utilized A two-way mixed ANOVA to analyze the differences between gender , the shooting event , and the interaction between them. Effect size with a 95% interval confidence was calculated using Cohen’s d and partial eta squared. Three benchmark points were defined to indicate the effect size,  and partial η2 = 0.01 small; η2 = 0.06 medium; η2 = 0.14 large. . All statistical analysis was conducted with SPSS version 28.For descriptive purposes, the cells means by gender and type of competition are presented in (t(87) = -3.1; p = 003; d = 0.60, IC95% ); skeet (t(56) = -2.89; p = 005; d = 0.76, IC95% (0.23–1.30)); trap (t(38.61) = -5.04; p < 001; d = -1.38, IC95% (0.80–1.98)). Contrary, no differences by gender were found in 10m air rifle nor 50m rifle 3 positions (p > .05). In order to increase confidence in the overall reliability of the results we also conducted a repeated bootstrapping procedure. The results remained the same for the t-tests with a simulation of 2000 samples and a 95% confidence interval.The comparisons between gender in the individual competitions showed that men shot better than women in 10m air pistol t(38) = -2.97; p = .005; d = 0.94 IC95% (0.29–1.59). No differences by gender were found in trap nor 10m air rifle (p > .05). Also, no differences were found between the individual and mixed competitions in any event by gender (p > 0.05). See In addition, the comparisons between gender in the mixed competitions showed that men perform better than women in10m air pistol  as the repeated measure was carried out. See F = 8.33; p = .007; partial η2 = .19) with men (M = 9.59) performing better than women (M = 9.48). There was no main effect of type of event on shooting performance  = 1.32; p = .260; partial η2 = .04), nor was there an interaction  = .73; p = .400; partial η2 = .02), showing that women did not deteriorate further in the mixed events beyond their individual performance level.For the 10-meters pistol shooting events  gender has a main effect  = 6.29; p = .018; partial η2 = .19) with men (M = 0.96) performing marginally better than women (M = 0.94). There was no main effect of type of event on shooting performance  = .007, p = .940, partial η2 = .00), nor was there an interaction  = .21; p = .65; partial η2 = .008), showing that women did not deteriorate further in the mixed events beyond their individual performance level.In the trap shooting events  a significant gender effect was found  = 1.06; p = .308; partial η2 = .02). There was no main effect of type of event on shooting performance  = 1.36; p = .250; partial η2 = .03), nor was there an interaction  = .17; p = .680; partial η2 = .003), showing that women did not deteriorate in the mixed events in comparison to their individual performance level.Regarding the 10-meters air-rifle shooting events  our results showed no main effect for gender . The latter competitions are unique as they afford the most control (initiation of trigger pull and stationary targets indoors) as well as physical support (the rifle is held close to the trunk of the body and a support vest is sustaining the weight of the rifle). These findings lead us to the conclusion that when movement is kept minimal and regardless of distance or posture, women are not less competitive than men are, and they perform equally. This was true both when they compete in gender segregated events as well as in the mixed-team competition. It is important to note that by no means do we deem rifle events to be “easier” or less demanding in comparison to other shooting events. Rifle elite shooting requires intense focus and sustained effort  as well However, the results should be also analyzed through a much broader lens extending beyond Olympic shooting competitions. They show that under unique and probably not easy to attain set of circumstances, highly trained experts of both genders compete equally. Still it seems that even minor barriers may cause uneven competitive environment. Coming full circle to Gneezy and Rustichini’s  contemplA psychological analysis contrasting the “mixed-double” events with the individual competitions highlights several important dimensions . In the We choose to pursue our gender exploration based on average performance analysis since this approach was most robust and valid statistically allowing maximum power to test the hypotheses under the current sample size limitations. However, Olympic medal winning competitions (and other sports) are a case of outlier performance . In otheAlthough this is the first study that have analyzed gender performance differences comprehensively in all shooting modalities, general limitations should be pointed out such as the Covid 19 pandemic timing which disrupted practice and competition routines  as well More specifically, it is important to note that the number of shooters who participated in both, the mixed and in the individual competition were smaller than those who competed only in the individual or the mixed competitions, a dimension that could reduce our statistical power. Nevertheless, the results of this study corroborate earlier findings from the world championship event  and collTwo major consequences arise if indeed in a direct competition scenario, the genders perform equally. First, recent years highlighted the controversy around the participation of trans competitors in sports . This coWomen and men shooters performed separately but equally in the 2021 Tokyo Olympics in “static” rifle shooting modalities. Men were superior in “dynamic”  shooting events. In the newly formed “mixed” team events  these performance patterns were maintained and the mixed gender competitive environment did not impede women’s performance beyond. Supported by earlier research ,30 we enS1 File(SAV)Click here for additional data file.


O. ficus-indica (prickly pear cactus) is an important forage and food source in arid and semiarid ecosystems and is the most important cactus species in cultivation globally. The high degree of apomixis in the species is a hindrance in plant breeding programs where genetic segregation is sought for the selection of superior genotypes. To understand if in ovulo embryo rescue could increase the proportion of zygotic seedlings, we compared the mature seed-derived seedlings with those regenerated from in vitro embryo rescue at 20, 25, 30, 35, and 40 post-anthesis days (PADs) in four Italian cultivars. The seedlings were classified as apomictic or zygotic based on molecular marker analysis using inter-sequence single repeat (ISSR) primers. Multiple embryos were recovered from all the cultured immature ovules, and plantlets were regenerated and acclimatized to the field post hardening, with success rates ranging from 62% (‘Senza spine’) to 83% . The level of polyembryony differed among cultivars and recovery dates, with the highest being ‘Rossa’, producing 4.8 embryos/ovule at 35 PADs, and ‘Gialla’, the lowest, with 2.7 at 40 PADs. The maximum number of embryos observed within a single ovule was 14 in ‘Trunzara bianca’. ISSR analysis revealed that ovule culture at 35 PADs produced the highest percentage of zygotic seedlings in all the cultivars, from 51% (‘Rossa’) to 98% , with a high genotype effect as well. Mature seeds produced much fewer seedlings per seed, ranging from 1.2 in ‘Trunzara bianca’ to 2.0 in ‘Rossa’ and a lower percentage of zygotic seedlings . Our research opens a pathway to increase the availability of zygotic seedlings in O. ficus-indica breeding programs through in ovulo embryo culture. Opuntia ficus-indica (L.) Mill.), also called cactus pear, Barbary fig, or nopal cactus, is a member of the Cactaceae family; it originated in central Mexico and is considered the most important cactus species in horticulture worldwide, with a global distribution , (AC)8YT (Ta 50.3 °C), (AG)8YT (Ta 50.3 °C), (GT)8YG (Ta 52.1 °C), and (CA)8RG (Ta 51 °C). To distinguish apomictic from zygotic seedlings, a genetic analysis based on ISSR analysis was performed, as previously described in detail  (145 DAP) [We attempted embryo rescue over five PADs periods from 20 to 40 days in four Italian cultivars with contrasting morphologies, and in all the cultivars, 35 PADs embryo rescue was the most successful in terms of the percentage of responsive ovules (80–95%) and the mean number of responsive embryos per ovule (4.4–5.3) in all four cultivars. In contrast, mature seeds produced very low numbers of seedlings per seed . Our method of acclimation and hardening of immature embryo-derived seedlings was efficient, and the success rate was from 62% (‘Senza spine’) to 83% . The next step in our research was to identify the origins of the seedlings, and we used ISSR markers, which are highly efficient and reliable ,50,51. A145 DAP) .in vitro development of the zygotic and apomictic embryos present in the immature ovules. Interestingly, we observed that in some combinations, PGR stimulated callus formation and the production of adventitious embryos from the different tissues of immature ovules. On the contrary, the PGR-free medium allowed the regular development of the zygotic and apomictic embryos already present in the immature ovules without the production of callus and adventitious embryos. Therefore, the immature ovules used in the present study were incubated on PGR-free medium to facilitate the recovery of zygotic embryos. The in vitro protocol used in our research is simple, as it consists of only MS media supplemented with malt extract and sucrose. For in ovulo embryo rescue of Hylocereus interspecific hybrids, another cactus of horticultural significance, Cisneros and Tel-Zur [in vitro ovule culture, casein hydrolysate seems to be an essential ingredient. Thus, a reduced form of organic nitrogen seems to be essential for embryo growth in vitro, as also suggested by Sahijram et al. [In preliminary experiments (data not presented), different combinations of plant growth regulators (PGR) were added to the culture medium to stimulate the  Tel-Zur  used a c Tel-Zur  and gent Tel-Zur  in vitrom et al. .Opuntia spp., apomixis can occur mainly through sporophytic agamospermy [Opuntia [in vivo during the seed maturation processes is not known, and we are focusing on this aspect in our current research. Our hypothesis is that the numerous embryos of apomictic origin that are contained in the ovule  compete with the zygotic embryo by using the resources necessary for its development, causing its abortion. This hypothesis is substantiated by the increase in the proportion and number of zygotic embryos when the immature ovules are incubated on a culture medium providing sufficient nutrients, which enhances the chances of survival of zygotic embryos.It is known that in mospermy ,22,23, w[Opuntia . Howeverin ovulo embryo culture can increase the number of zygotic seedlings and their ratio to apomictic seedlings; therefore, this can play a significant role in crop improvement programs of apomictic O. ficus-indica involving hybridisation and selection in segregating populations.In conclusion, it can be stated that


Endometrial cancers with p53 mutations tend to recur and develop metastases more frequently. From this point of view, the detection of new potential therapeutic targets such as HER2 is particularly interesting. In this study, we demonstrated that overexpression of HER2 (++ or +++) was present in 31.4% of p53-mutated endometrial carcinomas and that among these, 36.3% showed amplification of the HER2 gene by CISH (Chromogenic In Situ Hybridization). These results suggest that various anti-HER2 agents could constitute interesting future treatments in this type of cancer.p53-mutated endometrial carcinomas tend to recur and develop distant metastases. Therefore, the detection of new potential therapeutic targets such as HER2 is particularly interesting. In this retrospective study, which considered over 118 endometrial carcinomas, the p53 mutation was detected in 29.6% of cases. In these cases, the HER2 protein profile was studied via immunohistochemistry, and an overexpression of HER2 protein (++ or +++) was noted in 31.4%. The CISH technique was used in these cases to determine if gene amplification was present. In 18% of cases, the technique was not conclusive. Amplification of the HER2 gene was observed in 36.3% of cases and 36.3% of cases showed a polysomal-like aneusomy for centromere 17. Amplification was found in serous carcinomas, clear cell carcinomas and carcinosarcomas, highlighting the future potentiality of HER2-targeted therapies in these variants of aggressive carcinomas. More than 400,000 women worldwide were affected by endometrial cancer in 2020. The mortality rate of endometrial cancer is estimated to increase by 1.9% per year. The morbidity rate is higher in North America and Western Europe, which could be explained by a lifestyle marked by risk factors for endometrial cancer such as obesity [In 2020, endometrial cancer was the fourth most common tumor in Europe with an incidence of 12.9 to 20.2 per 100,000 women. It is the most frequent gynecologic cancer in Europe [It is established that a high body mass index (BMI) is a modifiable risk factor for endometrial cancer, and it is a more important risk factor for endometrial cancer than for any other cancer .Obesity is a risk factor for endometrial cancer because adipocytes convert androgens into estrogens and estrogens stimulate endometrial proliferation and therefore potentially the development of hyperplasia and cancer. In addition, hyperglycemia and insulin resistance, which are associated with obesity, promote IGF-1 signaling abnormalities, leading to increased cell proliferation [Initially, endometrial cancers were classified into two categories: type I, which represents approximately 80% of cases with a hormone-dependent profile, and type II for the remaining 20% of cases presenting a hormone-independent profile and a poor prognosis .The Cancer Genome Atlas of molecular analyses for different histologic types of endometrial cancers reveled four tumoral subtypes, each associated with a different survival profile and of great interest for prognosis, namely: POLE -mutated tumors; MMR (Mismatch Repair)-stable tumors; MMR-instable tumors; and p53-mutated tumors .This new classification, according to the ESGO , ESTRO (European Society for Radiotherapy and Oncology) and ESP (European Society of Pathology) 2020 recommendations, allows some modulations of the therapeutic schemes, adding to its therapeutic prognosis value . TherefoP53-mutated tumors are classically associated with more aggressive tumor histological types and a pejorative prognosis, such as high-grade endometrioid carcinomas, serous carcinomas and carcinosarcomas .The p53 protein is normally involved in the preservation of the cellular genome by blocking the replication of cells containing genomic alterations. It is a beneficial element at the cellular level; therefore, one can understand how important it is for this element to stay active. If a mutation occurs, efficiency decreases or is totally annihilated according to the mutation type. This protein is found to be mutated in 2/3 of cancers, preventing apoptosis when genetic abnormalities are present and thus encouraging cancer survival. On the endometrial cancers’ side, this mutated protein is found in 20 to 40% of cases. One of the characteristics of the mutated p53 protein is that its half-life is increased, and therefore it can be detected by immunohistochemistry .The p53 protein “wild type” has a short half-life and is rapidly degraded after activation; thus, it is kept at low levels in the cell. This mechanism is mainly due to MDM2 and MDM4, which decrease the transcriptional activity of the p53 protein, in particular by making it the target of degradation by proteasomes. When the p53 protein is mutated, this cascade is broken either because the mutated p53 protein does not have the ability to activate MDM2 or because MDM2 becomes a stimulator of p53 protein transcription.In both cases, the p53 protein accumulates in the cell and thus becomes detectable via immunohistochemistry .(a)“Nul type”: complete absence of immunohistochemical detection of the protein in tumor cells .(b)“Wild type”: nuclear immunohistochemical reactivity of low and/or moderate and/or diffuse intensity detected in less than 80% of tumor cells.(c)“Mutant”: strong and diffuse immunohistochemical reactivity detected in 80 to 100% of cells.(d)“Cytoplasmic”: significant cytoplasmic reactivity that is associated with variable nuclear reactivity but does not reach the high and diffuse detection threshold.The immunohistochemical profile of the p53 protein in endometrial carcinomas has been classified into four patterns :(a)“Nul The histochemistry of the p53-mutated protein is of interest, but we will refrain from going too much in depth on the subject since it is not the aim of this study.As p53 mutations in tumors tend to recur more frequently and develop distant metastases within five years in 50% of cases, it is of great interest to determine the presence of potential targets for future targeted therapies, which be of some benefit in the treatment of these varieties of endometrial cancer, whether or not they are targeted in conventional radio/chemotherapy .In particular, it has recently been suggested that overexpression of the HER2 protein may be observed in approximately 25–30% of endometrial serous carcinomas, which are typically p53-mutated and therefore could constitute a potential therapeutic target  ,11.HER2 is a transmembrane receptor involved in cell proliferation. When the HER2 receptor is activated, it stimulates signaling pathways that lead to oncogenic transformation through cell survival, proliferation, angiogenesis and metastasis. HER2 has no known ligand and can therefore be constitutionally activated. In addition, when HER2 is overexpressed, it forms heterodimers with other members of the HER family, inducing particularly important downstream oncogenic signaling. HER2 overexpression is used in breast cancer to select patients who may potentially respond to targeted therapy with an anti-HER2 agent; this concerns 15 to 30% of breast cancers. Targeted anti-HER2 therapies have significantly improved the prognosis of breast cancer patients .The aim of this study was to assess HER2 protein overexpression and the secondary gene’s amplification using CISH (Chromogenic In Situ Hybridization)-improved NGS (Next-Generation Sequencing) p53-mutated endometrial carcinomas to determine if this could be a good approach for future studies on new targeted therapies to add to the therapeutical panel of endometrial cancer.-The MMR and the p53 proteins analyzed by immunohistochemistry: MLH1 (MutL Homolog 1) ; MSH2 (MutS Homolog 2) ; MSH6 (MutS Homolog 6) ; and PMS2 (Postmeiotic Segregation 2)  and p53  .-Immunostaining was performed using a fully automated immunohistochemical system .-® Fluorometer in combination with the Qubit® dsDNA HS Assay Kit . NGS was then performed in order to sequence hotspot mutations in the following panel of genes , the database of the Department of Pathology was studied. This database lists every gynecological case analyzed by the Department of Pathology. The cases concerning breast pathologies, ovarian pathologies, vulvar pathologies and cervix pathologies were not retained. Every endometrial case between 2019 and 2022 was analyzed to finally extract endometrial cancers meeting the following criteria:Once this selection was achieved, 118 cases between 2019 and 2022 were included in this series.First, the proportions of histological types in the series were determined according to the WHO 2020 classification: low-grade endometrioid carcinomas, high-grade endometrioid carcinomas, serous carcinomas, clear cell carcinomas and carcinosarcomas; finally, other extremely rare histological types, such as neuroendocrine tumors, were excluded.Next, the molecular profile protocoled via NGS was analyzed. The cases were classified according to the 4 tumoral subtypes identified by The Cancer Genome Atlas: pole-mutated; MMR-stable; MMR-instable; and p53-mutated.The pole-mutated and MMR-instable tumors were excluded. Indeed, 8% of endometrial carcinomas with microsatellite instability and a third of Pole-mutated carcinomas are also carriers of a mutation in the TP53 gene .However, it seems that these mutations are events encouraged by this initially present microsatellite instability and therefore do not affect the molecular profile or phenotype of these tumors because these mutations affect sequences of the TP53 gene that do not impact the function or expression of the p53 protein. These cases of unstable MMR tumors with a mutation of the added TP53 gene also have a better prognosis than tumors with a mutated P53 profile .For the remaining cases with a TP53 mutation detected via NGS, the HER2 protein profile was studied.The slides were again reviewed by two experienced pathologists in order to classify the cases according to their immunohistochemical classification, as seen in  and FiguTo finalize our description, in the cases with an immunohistochemistry “++” or “+++”, to determine if a gene was amplified, CISH (Chromogenic In Situ Hybridization) was performed . The VenA total of 68.64% of cases were low-grade endometrioid cancers; 10.17% were high-grade endometrioid cancers; 214.41% were serous cancers; 4.24% were clear cells cancers; and 2.54% were carcinosarcomas .Concerning the 118 cases included in the study , they weA total of 5.93% of cases had a Pole-mutated profile; 40.68% had an MMR-stable profile; 23.73% had an MMR-instable profile; and 29.66% had a p53-mutated profile .The 35 cases with a p53 protein mutation were classified according to their histological type. Altogether, 22.86% were low-grade endometrioid cancers; 11.43% were high-grade endometrioid cancers; 48.57% were serous cancers; 14.28% were clear cells cancers; 8.57% were carcinosarcomas .Concerning the 81 low-grade endometrioid cancers in our series, 9.88% were p53-mutated; of the 12 high-grade endometrioid carcinomas, 33.33% were p53-mutated; of the 17 serous cancers, 88.24% were mutated; of the 3 clear cell cancers, 66% were mutated; and of the 3 carcinosarcomas, 100% were mutated .A total of 88.24% of the 17 serous endometrial cancers of this series were mutated for the p53 protein; 5.88% were MMR-stable and 5.88% were MMR-instable .Concerning the cases in this study that had a TP53 gene mutation detected using NGS, 1 of them was unavailable and the other 34 were analyzed by two experienced pathologists. Using the criteria previously described, 38.24% had a “0” profile for HER2 protein immunohistochemistry expression; 29.41% had a “+” profile; 23.53% had a “++” profile; and 8.82% had a “+++” profile .For the 11 cases in the series that had an immunohistochemistry profile corresponding to “++” or “+++” for the HER2 protein, 9 were analyzable. Four of them presented an amplification for the HER2 gene; four others presented an aneusomy, which looked like a CEP17 polysomy; and one case was not amplified.With regard to the four cases presenting an amplification of the HER2 gene, 50% were clear cell carcinomas; 25% were carcinosarcomas and 25% were serous cancers . The ampOf the four other cases presenting an aneusomy for CEP17 (polysomy-like), 75% were serous cancers and 25% were carcinosarcomas . The p53We first aimed to answer: Is this series sufficiently representative of the distributions found in other series in order to be able to draw conclusions?Regarding the proportions of histological types and molecular profiles, they followed the trends published in the literature; the endometrioid type affected 80% of patients while the others types of non-endometrioid carcinomas corresponded to 20% of tumors, with this group presenting mainly serous carcinomas . A literThe second question is as follows: Is HER2 amplification worth studying in the future to add some new targeted therapies to the therapeutical panel of the p53-mutated endometrial cancer?A randomized clinical trial that began in 2011 and is currently in phase II (NCT01367002) is investigating the therapeutic response of stage III or IV or recurrent serous carcinomas to carboplatin/paclitaxel compared to carboplatin/paclitaxel to which trastuzumab, an anti-HER2 agent, is added . The firCurrently, it is recommended HER2 gene amplification be tested for only in serous histological types of endometrial cancer, which is considered the most aggressive histological type of endometrial cancer. However, Ross et al., in their retrospective study in 2021, report that in 94% of cases of endometrial cancers with amplification for the HER2 gene, there is a mutation of the TP53 gene as well . This TPMoreover, Ross et al. have observed at least one case of amplification of the HER2 gene in all histological types of endometrial cancer . InsteadRegarding the 21.57% of cases of mutated P53 tumors presenting a polysomal-like aneusomy for centromere 17, this is a phenomenon already described in breast cancers for which the clinical impact and effects on the expression of the HER2 protein are still uncertain .A recent study showed that polysomy of centromere 17, without amplification of the HER2 gene, would be associated with a higher immunohistochemical expression of the HER2 protein, corresponding to “++”/”+++” scores . TherefoAgain, the data reported in the literature diverge. However, Hofmann et al., in 2008, had already described two cases of breast cancers overexpressing the HER2 protein in the presence of polysomy of centromere 17 and which presented a therapeutic response to trastuzumab . MoreoveOf course, all these data concerning HER2 expression and/or amplification in endometrial cancers must be tempered, firstly, because endometrial tumors are often large (>30 mm) and HER2 expression/amplification may be heterogeneous. However, it has been shown that in other cancers , this heterogeneity can affect not only the prognosis of these carcinomas but also their response to the various HER2 therapies. In addition, most of the clinical studies that tested the different anti-HER2 therapies are only based on the immunohistochemical score and do not consider HER2 amplification. Finally, in breast cancer, tumors considered HER2-negative (+ or ++ without HER2 gene amplification) may still respond to new HER2 therapies. Finally, in breast cancer, tumors that are considered HER2-negative may still respond to new HER2 therapies .In this study, we have demonstrated that overexpression of HER 2 (++ or +++) was present in 31.4% of p53-mutated endometrial carcinomas and that among these, 36.3% showed HER2 gene amplification by CISH. This overexpression and gene amplification are not restricted to serous carcinomas but were also found in clear cell carcinomas and carcinosarcomas. These results suggest that various anti-HER2 agents could constitute interesting future treatments in this type of cancer. Naturally, our findings should be confirmed by larger studies in the future. Furthermore, in the era of personalized medicine, we advocate for the continuation of studies on targeted anti-HER2 therapies for cases with HER2 amplification. In addition, their extension to endometrial carcinomas with polysomal aneusomy for centromere 17 could be proposed, following studies already initiated for breast cancers.