Dissecting abstract, modality-specific and experience-dependent coding of affect in the human brain.

Emotion and perception are tightly intertwined, as affective experiences often arise from the appraisal of sensory information. Nonetheless, whether the brain encodes emotional instances using a sensory-specific code or in a more abstract manner is unclear. Here, we answer this question by measuring the association between emotion ratings collected during a unisensory or multisensory presentation of a full-length movie and brain activity recorded in typically developed, congenitally blind and congenitally deaf participants. Emotional instances are encoded in a vast network encompassing sensory, prefrontal, and temporal cortices. Within this network, the ventromedial prefrontal cortex stores a categorical representation of emotion independent of modality and previous sensory experience, and the posterior superior temporal cortex maps the valence dimension using an abstract code. Sensory experience more than modality affects how the brain organizes emotional information outside supramodal regions, suggesting the existence of a scaffold for the representation of emotional states where sensory inputs during development shape its functioning.

Balancing the Senses: Electrophysiological Responses Reveal the Interplay between Somatosensory and Visual Processing During Body-Related Multisensory Conflict.

In the study of bodily awareness, the predictive coding theory has revealed that our brain continuously modulates sensory experiences to integrate them into a unitary body representation. Indeed, during multisensory illusions (e.g., the rubber hand illusion, RHI), the synchronous stroking of the participant's concealed hand and a fake visible one creates a visuotactile conflict, generating a prediction error. Within the predictive coding framework, through sensory processing modulation, prediction errors are solved, inducing participants to feel as if touches originated from the fake hand, thus ascribing the fake hand to their own body. Here, we aimed to address sensory processing modulation under multisensory conflict, by disentangling somatosensory and visual stimuli processing that are intrinsically associated during the illusion induction. To this aim, we designed two EEG experiments, in which somatosensory- (SEPs; Experiment 1; N = 18; F = 10) and visual-evoked potentials (VEPs; Experiment 2; N = 18; F = 9) were recorded in human males and females following the RHI. Our results show that, in both experiments, ERP amplitude is significantly modulated in the illusion as compared with both control and baseline conditions, with a modality-dependent diametrical pattern showing decreased SEP amplitude and increased VEP amplitude. Importantly, both somatosensory and visual modulations occur in long-latency time windows previously associated with tactile and visual awareness, thus explaining the illusion of perceiving touch at the sight location. In conclusion, we describe a diametrical modulation of somatosensory and visual processing as the neural mechanism that allows maintaining a stable body representation, by restoring visuotactile congruency under the occurrence of multisensory conflicts.

It is time to implement molecular classification in endometrial cancer.

A huge effort has been done in redefining endometrial cancer (EC) risk classes in the last decade. However, known prognostic factors (FIGO staging and grading, biomolecular classification and ESMO-ESGO-ESTRO risk classes stratification) are not able to predict outcomes and especially recurrences. Biomolecular classification has helped in re-classifying patients for a more appropriate adjuvant treatment and clinical studies suggest that currently used molecular classification improves the risk assessment of women with EC, however, it does not clearly explain differences in recurrence profiles. Furthermore, a lack of evidence appears in EC guidelines. Here, we summarize the main concepts why molecular classification is not enough in the management of endometrial cancer, by highlighting some promising innovative examples in scientific literature studies with a clinical potential significant impact.

The role of L1CAM as predictor of poor prognosis in stage I endometrial cancer: a systematic review and meta-analysis.

INTRODUCTION: Molecular and genomic profiling in endometrial cancer is increasing popularity. L1 cell adhesion molecule (L1CAM) is frequently mutated in endometrial cancer. In this paper, we aim to evaluate the prognostic role of L1CAM in patients with stage I endometrial cancer. METHODS: We performed a systematic review and meta-analysis searching in PubMed (MEDLINE), EMBASE, and Web of Science database to identify studies reporting the expression of L1CAM in endometrial cancer. The primary endpoint measure was to assess and evaluate the impact of L1CAM on survival outcomes. This study was performed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. RESULTS: Five studies were included. The pooled results suggested that L1CAM expression influences survival outcomes in stage I endometrial cancer. High L1CAM expression correlated with worse disease-free survival (HR 4.11, 95% CI 1.02-16.59, p = 0.047) and overall survival (HR 3.62, 95% CI 1.32-9.31, p = 0.012). High L1CAM level was also associated with a more aggressive FIGO grade and with older age. CONCLUSION: This systematic review supported that L1CAM have a prognostic role in stage I endometrial cancer, thus providing a potential useful tool for tailoring the need of adjuvant therapy.

Can the Modified Frailty Index (mFI) Predict Intraoperative and Postoperative Complications in Older Women with Endometrial Cancer Undergoing Laparoscopic or Robotic Surgery? A Multicenter Observational Study.

BACKGROUND: This study aims to evaluate the strength of the association between frailty and intraoperative/postoperative complications in patients undergoing minimally invasive surgery (MIS) for endometrial cancer. METHODS: In this retrospective observational multicenter cohort study, frailty was defined beforehand by a modified frailty index (mFI) score of ≥3. Multiple logistic regressions were performed to investigate possible preoperative predictors-including frailty, age, and body mass index-of intraoperative and early (within 30 days from surgery) or delayed (beyond 30 days from surgery) postoperative complications. RESULTS: The study involved 577 women, of whom 6.9% (n = 40) were frail with an mFI ≥ 3, while 93.1% (n = 537) were non-frail with an mFI of 0-2. Frail women had a significantly higher rate of intraoperative complications (7.5% vs. 1.7%, p = 0.01), with odds 4.54 times greater (95% CI: 1.18-17.60, p = 0.028). There were no differences in the rate of early postoperative complications (15% vs. 6.9%, p = 0.06) and delayed postoperative complications (2.5% vs. 3.9%, p = 0.65) for frail versus non-frail patients. The odds of early postoperative complications increased by 0.7% (95% CI: 1.00-1.15) for every one-unit increase in age (p = 0.032). CONCLUSIONS: Frailty was associated with a significantly higher risk of intraoperative complications in older women undergoing MIS for endometrial cancer. Likewise, increasing age was an independent predictor of early postoperative complications. Our findings support the practice of assessing frailty before surgery to optimize perioperative management in this patient population.

Complement-Mediated Thrombotic Microangiopathy in Pregnancy: An Educational Case Report.

Rationale: Thrombotic microangiopathy (TMA) is a spectrum of rare diseases characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. Differentiating pre-eclampsia, HELLP (Hemolysis, Elevated Liver enzymes, Low Platelets) syndrome and atypical hemolytic uremic syndrome (aHUS) during pregnancy may be diagnostically challenging yet important as the treatment pathways differ. Most cases of aHUS are associated with dysregulation of the complement alternative pathway, for which current guidelines recommend prompt treatment with complement C5 inhibitor to prevent chronic sequelae. Here, we report a case of pregnancy-associated aHUS (p-aHUS) to highlight the challenging aspects of the diagnostic process and the importance of prompt treatment with complement inhibition to reduce the risk of poor outcomes. Presenting concerns: A 28-year-old woman was admitted to a local hospital for induction of vaginal delivery of twins at 34 weeks and 3 days of gestational age, due to intrauterine growth restriction (IUGR). She was previously healthy, and this current pregnancy was uncomplicated, except for the IUGR. Approximately, 10 hours after her induced delivery, she developed vomiting, epigastric pain, and hypertension. Diagnosis: She was initially suspected of having fulminant liver failure in the context of acute fatty liver of pregnancy versus pre-eclampsia/HELLP syndrome, due to evidence of elevated liver enzymes, acute kidney injury (AKI), thrombocytopenia, and hemoglobin levels trending down, for which the patient was initially treated conservatively. On day 2 post-delivery, she was transferred to our hospital for possible liver biopsy and management of liver failure. Upon transfer, dialysis was started due to anuric AKI; at the same time, her liver function spontaneously improved, while platelet count remained very low and hemoglobin levels continued to trend down. A full TMA work-up revealed low C3 levels; secondary causes of TMA were ruled out. The patient received a final diagnosis of p-aHUS. Complement genetic tests were also performed and did not identify any pathogenic variants. Interventions: Given the final diagnosis of p-aHUS, the patient was started on a C5 inhibitor (day 8 post-delivery). Her platelet count quickly normalized 2 days after the first dose, while the hemoglobin levels remained low for a longer period, likely due to retained products of conception. Outcomes: The patient was able to completely discontinue dialysis after approximately 3 months, however, her kidney function did not recover completely, despite all the other TMA markers normalizing (platelets count in range, negative hemolysis markers, and normal hemoglobin levels). Her estimated glomerular filtration rate (eGFR) was 23 mL/min/1.73 m2 at the 6-month follow-up. Teaching points: The diagnosis of p-aHUS can be challenging due to frequent overlapping symptoms and signs with other forms of pregnancy-associated TMA, leading to a delay of the treatment, which can affect the patient's outcome. Failure of TMA to improve in the postpartum period or occurring at this time, with negative ADAMTS13 and antiphospholipid antibody syndrome (APLAS) serologies should favor the diagnosis of p-aHUS. Early treatment with C5 inhibition should be considered in women with a diagnosis of p-aHUS. Patients need multidisciplinary and likely tertiary/quaternary care at centers where clinical experience, access to diagnostics and treatment initiation can begin without delay.

Justification: La microangiopathie thrombotique (MAT) est un spectre de maladies rares caractérisées par une thrombocytopénie, une anémie hémolytique microangiopathique et des lésions à différents organes. Pendant la grossesse, il peut être difficile de différencier la prééclampsie, le syndrome HELLP (Haemolysis, Elevated Liver enzymes, Low Platelets) et le syndrome hémolytique et urémique atypique (SHUa) d'un point de vue diagnostique, mais il est important de le faire, car les avenues de traitement diffèrent. La plupart des cas de SHUa sont associés à un dérèglement de la voie alterne du complément, pour lequel la recommandation actuelle est de privilégier un traitement rapide avec un inhibiteur de la fraction C5 du complément afin de prévenir les séquelles chroniques. Dans le présent article, nous présentons un cas de SHUa associé à une grossesse (SHUa-g) afin de mettre en évidence les difficultés associées au diagnostic et l'importance de traiter rapidement par inhibition du complément afin de réduire le risque de résultats défavorables. Présentation du cas: Une femme de 28 ans admise dans un hôpital local pour l'induction d'un accouchement vaginal de jumeaux à 34 semaines et 3 jours, en raison d'un retard de croissance intra-utérin (RCIU). La patiente était en bonne santé et la grossesse, à l'exception du RCIU, était sans complications. Environ dix heures après l'accouchement, la patiente a développé des vomissements, des douleurs épigastriques et de l'hypertension. Diagnostic: On a d'abord soupçonné une insuffisance hépatique fulminante liée soit à une stéatose hépatique aiguë de la grossesse ou encore à une prééclampsie/syndrome HELLP, en raison d'une élévation des enzymes hépatiques, d'une insuffisance rénale aiguë, d'une thrombocytopénie et d'une baisse de l'hémoglobine, pour lesquelles la patiente a initialement été traitée de façon conservatrice. Deux jours après l'accouchement, la patiente a été transférée à notre hôpital pour une possible biopsie du foie et la prise en charge d'une insuffisance hépatique. Après le transfert, une IRA anurique a justifié l'initiation de la dialyse. Au même moment, la fonction hépatique s'est améliorée spontanément, tandis que la numération plaquettaire est demeurée très faible et que les taux d'hémoglobine ont continué à baisser. Un bilan MAT complet a révélé de faibles taux de C3; les causes secondaires de MAT ont été écartées. La patiente a reçu un diagnostic final de SHUa-g. Des tests génétiques complémentaires n'ont pas permis d'identifier de variants pathogènes. Intervention: Compte tenu du diagnostic final de SHUa-g, un traitement avec un inhibiteur de C5 a été amorcé (au huitième jour après l'accouchement). La numération plaquettaire s'est rapidement normalisée deux jours après la première dose, mais les taux d'hémoglobine sont demeurés bas sur une plus longue période, probablement en raison de la rétention de produits de la conception. Résultats: La patiente a pu cesser complètement la dialyse environ trois mois plus tard, mais sa fonction rénale ne s'est pas complètement rétablie, malgré la normalisation de tous les autres marqueurs de MAT (numération plaquettaire dans les normales, marqueurs d'hémolyse négatifs, taux d'hémoglobine normaux). Son débit de filtration glomérulaire estimé (DFGe) s'établissait à 23 ml/min/1.73 m2 lors du suivi à six mois. Enseignements tirés: Le chevauchement fréquent des symptômes et signes cliniques des autres formes de MAT associées à la grossesse rend parfois difficile le diagnostic du SHUa-g, ce qui peut retarder le traitement et affecter l'évolution clinique. L'absence d'amélioration d'une MAT dans la période postpartum, ou sa survenue à ce moment, couplée à des sérologies négatives pour ADAMTS13 et pour le syndrome des anticorps antiphospholipides (SAPL) devrait plaider en faveur d'un diagnostic de SHUa-g. Un traitement précoce par inhibition de C5 doit être envisagé chez les femmes qui reçoivent un diagnostic de SHUa-g. Ces patientes requièrent des soins multidisciplinaires, et probablement tertiaires/quaternaires, dans des centres où l'expérience clinique, l'accès au diagnostic et l'initiation du traitement sont rapidement accessibles.

Machine learning endometrial cancer risk prediction model: integrating guidelines of European Society for Medical Oncology with the tumor immune framework.

OBJECTIVE: Current prognostic factors for endometrial cancer are not sufficient to predict recurrence in early stages. Treatment choices are based on the prognostic factors included in the risk classes defined by the ESMO-ESGO-ESTRO (European Society for Medical Oncology-European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology) consensus conference with the new biomolecular classification based on POLE, TP53, and microsatellite instability status. However, a minority of early stage cases relapse regardless of their low risk profiles. Integration of the immune context status to existing molecular based models has not been fully evaluated. This study aims to investigate whether the integration of the immune landscape in the tumor microenvironment could improve clinical risk prediction models and allow better profiling of early stages. METHODS: Leveraging the potential of in silico deconvolution tools, we estimated the relative abundances of immune populations in public data and then applied feature selection methods to generate a machine learning based model for disease free survival probability prediction. RESULTS: We included information on International Federation of Gynecology and Obstetrics (FIGO) stage, tumor mutational burden, microsatellite instability, POLEmut status, interferon γ signature, and relative abundances of monocytes, natural killer cells, and CD4+T cells to build a relapse prediction model and obtained a balanced accuracy of 69%. We further identified two novel early stage profiles that undergo different pathways of recurrence. CONCLUSION: This study presents an extension of current prognostic factors for endometrial cancer by exploiting machine learning models and deconvolution techniques on available public biomolecular data. Prospective clinical trials are advisable to validate the early stage stratification.

Shiga toxin targets the podocyte causing hemolytic uremic syndrome through endothelial complement activation.

BACKGROUND: Shiga toxin (Stx)-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) is the leading cause of acute kidney injury in children, with an associated mortality of up to 5%. The mechanisms underlying STEC-HUS and why the glomerular microvasculature is so susceptible to injury following systemic Stx infection are unclear. METHODS: Transgenic mice were engineered to express the Stx receptor (Gb3) exclusively in their kidney podocytes (Pod-Gb3) and challenged with systemic Stx. Human glomerular cell models and kidney biopsies from patients with STEC-HUS were also studied. FINDINGS: Stx-challenged Pod-Gb3 mice developed STEC-HUS. This was mediated by a reduction in podocyte vascular endothelial growth factor A (VEGF-A), which led to loss of glomerular endothelial cell (GEnC) glycocalyx, a reduction in GEnC inhibitory complement factor H binding, and local activation of the complement pathway. Early therapeutic inhibition of the terminal complement pathway with a C5 inhibitor rescued this podocyte-driven, Stx-induced HUS phenotype. CONCLUSIONS: This study potentially explains why systemic Stx exposure targets the glomerulus and supports the early use of terminal complement pathway inhibition in this devastating disease. FUNDING: This work was supported by the UK Medical Research Council (MRC) (grant nos. G0901987 and MR/K010492/1) and Kidney Research UK (grant nos. TF_007_20151127, RP42/2012, and SP/FSGS1/2013). The Mary Lyon Center is part of the MRC Harwell Institute and is funded by the MRC (A410).

Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial.

BACKGROUND: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial. METHODS: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included. RESULTS: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers. CONCLUSIONS: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.

Evaluation of eating habits by 7-day food record: web-PC vs. traditional paper format.

The aim of this study was to evaluate the validity of a web-based 7-day food-record using METADIETA-web link (Meteda s.r.l.) - a professional software used in nutritional practice and research - compared with the traditional paper format. Twenty-six healthy adults of both sexes were recruited in this cross-over study based on the number coming from the sample size calculation, and randomly assigned to start with METADIETA-web or traditional 7-Day Food-Diary. All the 7-day food-diaries were recorded in the Metadieta-software. The System Usability Scale (SUS) questionnaire was administered to evaluate the participants' preferences in terms of usability, acceptability, and feasibility. Differences in energy intake, nutrient composition, and SUS between the digital and traditional modalities were evaluated. Energy and nutrients were not significantly different between the two methods with a variation <15%, with alcohol intake showing the strongest relation (0.1% variation). The Interclass Correlation Coefficient showed a grade of consistency between the two methods excellent for alcohol, good for proteins, carbohydrates, and fibre, moderate for energy and saturated fat, and poor for total fat and cholesterol. SUS suggested that the web-based platform was in general well accepted, but highlighted some inconsistencies and complexity compared to the written food diary. The web-based 7-day food-record may allow an accurate and quicker analysis of food timing than conventional approaches, seeming reliable for energy and macronutrient composition, making it a potentially attractive tool for nutritional research. However, the reported inconsistencies and complexity must be considered and addressed.

Sexual dysfunctions in breast cancer patients: evidence in context.

INTRODUCTION: In breast cancer patients, endocrine therapy may exert a negative impact on sexual functioning in both genders, with potentially relevant consequences concerning quality of life and treatment adherence. The availability of effective interventions to maintain and/or restore sexual health in breast cancer patients is a key issue to a research agenda. OBJECTIVES: To summarize and critically discuss the most updated and qualitatively relevant literature on the therapeutic approach to sexual impairment in breast cancer patients, with a focus on patients treated with endocrine therapy. METHODS: We searched PubMed from its inception to February 2022 for observational and intervention trials including participants with sexual dysfunctions. We were particularly interested in studies of breast cancer patients with sexual dysfunctions while undergoing endocrine therapy. We developed a search strategy with the aim of maximizing the number of articles considered for screening and potential inclusion. RESULTS: Forty-five studies were selected: 3 observational and 42 intervention studies. Thirty-five studies were exclusively focused on female breast cancer populations. We could not identify studies exclusively focused on or also including male breast cancer patients. Overall, in female patients, the available armamentarium encompasses vaginal lubricants, moisturizers, estrogens, dehydroepiandrosterone, CO2 laser, ospemifene, and counseling. None of these interventions has been demonstrated to completely solve sexual dysfunctions when singularly considered. More favorable outcomes have come from the combination of different therapies. CONCLUSION: In female breast cancer, future research is oriented toward the gain of evidence on combined therapies and long-term data on safety issues on the most promising interventions. The lack of evidence on sexual disturbances in male breast cancer patients remains a major concern.

New insights into the immune functions of podocytes: the role of complement.

Podocytes are differentiated epithelial cells which play an essential role to ensure a normal function of the glomerular filtration barrier (GFB). In addition to their adhesive properties in maintaining the integrity of the filtration barrier, they have other functions, such as synthesis of components of the glomerular basement membrane (GBM), production of vascular endothelial growth factor (VEGF), release of inflammatory proteins, and expression of complement components. They also participate in the glomerular crosstalk through multiple signalling pathways, including endothelin-1, VEGF, transforming growth factor ß (TGFß), bone morphogenetic protein 7 (BMP-7), latent transforming growth factor ß-binding protein 1 (LTBP1), and extracellular vesicles.Growing literature suggests that podocytes share many properties of innate and adaptive immunity, supporting a multifunctional role ensuring a healthy glomerulus. As consequence, the "immune podocyte" dysfunction is thought to be involved in the pathogenesis of several glomerular diseases, referred to as "podocytopathies." Multiple factors like mechanical, oxidative, and/or immunologic stressors can induce cell injury. The complement system, as part of both innate and adaptive immunity, can also define podocyte damage by several mechanisms, such as reactive oxygen species (ROS) generation, cytokine production, and endoplasmic reticulum stress, ultimately affecting the integrity of the cytoskeleton, with subsequent podocyte detachment from the GBM and onset of proteinuria.Interestingly, podocytes are found to be both source and target of complement-mediated injury. Podocytes express complement proteins which contribute to local complement activation. At the same time, they rely on several protective mechanisms to escape this damage. Podocytes express complement factor H (CFH), one of the main regulators of the complement cascade, as well as membrane-bound complement regulators like CD46 or membrane cofactor protein (MCP), CD55 or decay-accelerating factor (DAF), and CD59 or defensin. Further mechanisms, like autophagy or actin-based endocytosis, are also involved to ensure podocyte homeostasis and protection against injury.This review will provide an overview of the immune functions of podocytes and their response to immune-mediated injury, focusing on the pathogenic link between complement and podocyte damage.

The loss of glycocalyx integrity impairs complement factor H binding and contributes to cyclosporine-induced endothelial cell injury.

Background: Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown. Methods: Using blood outgrowth endothelial cells (BOECs) from healthy donors, we evaluated the effects of cyclosporine on endothelial cell integrity. Specifically, we determined complement activation (C3c and C9) and regulation (CD46, CD55, CD59, and complement factor H [CFH] deposition) as these occurred on the endothelial cell surface membrane and glycocalyx. Results: We found that exposing the endothelium to cyclosporine resulted in a dose- and time-dependent enhancement of complement deposition and cytotoxicity. We, therefore, employed flow cytometry, Western blotting/CFH cofactor assays, and immunofluorescence imaging to determine the expression of complement regulators and the functional activity and localization of CFH. Notably, while cyclosporine led to the upregulation of complement regulators CD46, CD55, and CD59 on the endothelial cell surface, it also diminished the endothelial cell glycocalyx through the shedding of heparan sulfate side chains. The weakened endothelial cell glycocalyx resulted in decreased CFH surface binding and surface cofactor activity. Conclusion: Our findings confirm a role for complement in cyclosporine-induced endothelial injury and suggest that decreased glycocalyx density, induced by cyclosporine, is a mechanism that leads to complement alternative pathway dysregulation via decreased CFH surface binding and cofactor activity. This mechanism may apply to other secondary TMAs-in which a role for complement has so far not been recognized-and provide a potential therapeutic target and an important marker for patients on calcineurin inhibitors.

Towards reproducible research in recurrent pregnancy loss immunology: Learning from cancer microenvironment deconvolution.

The most recent international guidelines regarding recurrent pregnancy loss (RPL) exclude most of the immunological tests recommended for RPL since they do not reach an evidence-based level. Comparisons for metanalysis and systematic reviews are limited by the ambiguity in terms of RPL definition, etiological and risk factors, diagnostic work-up, and treatments applied. Therefore, cohort heterogeneity, the inadequacy of numerosity, and the quality of data confirm a not standardized research quality in the RPL field, especially for immunological background, for which potential research application remains confined in a separate single biological layer. Innovative sequencing technologies and databases have proved to play a significant role in the exploration and validation of cancer research in the context of dataset quality and bioinformatics tools. In this article, we will investigate how bioinformatics tools born for large-scale cancer immunological research could revolutionize RPL immunological research but are limited by the nature of current RPL datasets.

Potential Protective Role of Pregnancy and Breastfeeding in Delaying Onset Symptoms Related to Multiple Sclerosis.

The impact of pregnancy and breastfeeding on the development and outcomes of Multiple sclerosis (MS) has been debated for decades. Since several factors can influence the evolution of the disease, the protective role of multiparity and breastfeeding remains uncertain, as well the role of hormone replacement therapy in the perimenopausal period. We report two cases of relatively late-onset MS in two parous women, who developed their first neurological symptoms after six and nine pregnancies, respectively. Both women breastfed each of their children for 3 to 12 months. One of them underwent surgical menopause and received hormone replacement therapy for 7 years before MS onset. We performed a systematic literature review to highlight the characteristics shared by women who develop the disease in similar conditions, after unique hormonal imbalances, and to collect promising evidence on this controversial issue. Several studies suggest that the beneficial effects of pregnancy and breastfeeding on MS onset and disability accumulation may only be realized when several pregnancies occur. However, these data on pregnancy and breastfeeding and their long-term benefits on MS outcomes suffer from the possibility of reverse causality, as women with milder impairment might choose to become pregnant more readily than those with a higher level of disability. Thus, the hypothesis that multiparity might have a protective role on MS outcomes needs to be tested in larger prospective cohort studies of neo-diagnosed women, evaluating both clinical and radiological features at presentation.

Outpatient Hysteroscopic Polypectomy-A Retrospective Study Comparing Rigid and Semirigid Office Hysteroscopes.

Endometrial polyps are one of the most common pathological conditions in gynecology. Hysteroscopy is the gold standard for the diagnosis and treatment of endometrial polyps. The purpose of this multicenter, retrospective study was to compare patients' pain perception during an operative hysteroscopic endometrial polypectomy in an outpatient setting with two different hysteroscopes (rigid and semirigid) and to identify some clinical and intraoperative characteristics that are related to worsening pain during the procedure. We included women that underwent, at the same time as an diagnostic hysteroscopy, the complete removal of an endometrial polyp (using the see-and-treat strategy) without any kind of analgesia. A total of 166 patients were enrolled, of which 102 patients underwent a polypectomy with a semirigid hysteroscope and 64 patients underwent the procedure with a rigid hysteroscope. No differences were found during the diagnostic step; on the contrary, after the operative procedure, a statistically significant greater degree of pain was reported when the semirigid hysteroscope was used. Cervical stenosis and menopausal status were risk factors for pain both in the diagnostic step and in the operative one. Our results confirm that operative hysteroscopic endometrial polypectomy in an outpatient setting is an effective, safe, and well-tolerated procedure and indicate that it might be better tolerated if a rigid rather than semirigid instrument is used.

Beyond Sentinel Lymph Node: Outcomes of Indocyanine Green-Guided Pelvic Lymphadenectomy in Endometrial and Cervical Cancer.

BACKGROUND: The aim of our study was to compare the number of lymph nodes removed during indocyanine green (ICG)-guided laparoscopic/robotic pelvic lymphadenectomy with standard systematic lymphadenectomy in endometrial cancer (EC) and cervical cancer (CC). METHODS: This is a multicenter retrospective comparative study (Clinical Trial ID: NCT04246580; updated on 31 January 2023). Women affected by EC and CC who underwent laparoscopic/robotic systematic pelvic lymphadenectomy, with (cases) or without (controls) the use of ICG tracer injection within the uterine cervix, were included in the study. RESULTS: The two groups were homogeneous for age (p = 0.08), Body Mass Index, International Federation of Gynaecology and Obstetrics (FIGO) stages (p = 0.41 for EC; p = 0.17 for CC), median estimated blood loss (p = 0.76), median operative time (p = 0.59), and perioperative complications (p = 0.66). Nevertheless, the number of lymph nodes retrieved during surgery was significantly higher (p = 0.005) in the ICG group (n = 18) compared with controls (n = 16). CONCLUSIONS: The accurate and precise dissection achieved with the use of the ICG-guided procedure was associated with a higher number of lymph nodes removed in the case of systematic pelvic lymphadenectomy for EC and CC.

Spatial proximity to others induces plastic changes in the neural representation of the peripersonal space.

Peripersonal space (PPS) is a highly plastic "invisible bubble" surrounding the body whose boundaries are mapped through multisensory integration. Yet, it is unclear how the spatial proximity to others alters PPS boundaries. Across five experiments (N = 80), by recording behavioral and electrophysiological responses to visuo-tactile stimuli, we demonstrate that the proximity to others induces plastic changes in the neural PPS representation. The spatial proximity to someone else's hand shrinks the portion of space within which multisensory responses occur, thus reducing the PPS boundaries. This suggests that PPS representation, built from bodily and multisensory signals, plastically adapts to the presence of conspecifics to define the self-other boundaries, so that what is usually coded as "my space" is recoded as "your space". When the space is shared with conspecifics, it seems adaptive to move the other-space away from the self-space to discriminate whether external events pertain to the self-body or to other-bodies.

A modality-independent proto-organization of human multisensory areas.

The processing of multisensory information is based upon the capacity of brain regions, such as the superior temporal cortex, to combine information across modalities. However, it is still unclear whether the representation of coherent auditory and visual events requires any prior audiovisual experience to develop and function. Here we measured brain synchronization during the presentation of an audiovisual, audio-only or video-only version of the same narrative in distinct groups of sensory-deprived (congenitally blind and deaf) and typically developed individuals. Intersubject correlation analysis revealed that the superior temporal cortex was synchronized across auditory and visual conditions, even in sensory-deprived individuals who lack any audiovisual experience. This synchronization was primarily mediated by low-level perceptual features, and relied on a similar modality-independent topographical organization of slow temporal dynamics. The human superior temporal cortex is naturally endowed with a functional scaffolding to yield a common representation across multisensory events.