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Abstract Spatio-temporal activity patterns have been observed in a variety of brain areas in spontaneous activity, prior to or during action, or in response to stimuli. Biological mechanisms endowing neurons with the ability to distinguish between different sequences remain largely unknown. Learning sequences of spikes raises multiple challenges, such as maintaining in memory spike history and discriminating partially overlapping sequences. Here, we show that anti-Hebbian spike-timing dependent plasticity (STDP), as observed at cortico-striatal synapses, can naturally lead to learning spike sequences. We design a spiking model of the striatal output neuron receiving spike patterns defined as sequential input from a fixed set of cortical neurons. We use a simple synaptic plasticity rule that combines anti-Hebbian STDP and non-associative potentiation for a subset of the presented patterns called rewarded patterns. We study the ability of striatal output neurons to discriminate rewarded from non-rewarded patterns by firing only after the presentation of a rewarded pattern. In particular, we show that two biological properties of striatal networks, spiking latency and collateral inhibition, contribute to an increase in accuracy, by allowing a better discrimination of partially overlapping sequences. These results suggest that anti-Hebbian STDP may serve as a biological substrate for learning sequences of spikes.

Objectives The objectives are to assess smoking abstinence and its effects on vascular risk and to report tobacco-cessation counselling and pharmacotherapy use in patients who had a recent minor stroke or transient ischaemic attack (TIA).Design and setting The TIA registry.org project is a prospective, observational registry of patients with TIA and minor stroke that occurred in the previous 7 days with a 5-year follow-up, involving 61 sites with stroke specialists in 21 countries (Europe, Asia, Latin America and Middle East). Of those, 42 sites had 5-year follow-up data on more than 50% of their patients and were included in the present study.Participants From June 2009 through December 2011, 3847 patients were eligible for the study (80% of the initial cohort).Outcomes Tobacco counselling and smoking-cessation pharmacotherapy use in smoking patients were reported at discharge. Association between 3-month smoking status and risk of a major cardiovascular event (MACE) was analysed with multivariable Cox regression model.Results Among 3801 patients included, 835 (22%) were smokers. At discharge, only 35.2% have been advised to quit and 12.5% had smoking-cessation pharmacotherapy prescription. At 3 months, 383/835 (46.9%) baseline smokers were continuers. Living alone and alcohol abuse were associated with persistent smoking; high level of education, aphasia and dyslipidaemia with quitting. The adjusted HRs for MACE at 5 years were 1.13 (95% CI 0.90 to 1.43) in former smokers, 1.31 (95% CI 0.93 to 1.84) in quitters and 1.31 (95% CI 0.94 to 1.83) in continuers. Using time-varying analysis, current smoking at the time of MACE non-significantly increased the risk of MACE (HR 1.31 (95% CI 0.97 to 1.78); p=0.080).Conclusion In the TIAregistry.org, smoking-cessation intervention was used in a minority of patients. Surprisingly, in this population in which, at 5 years, other vascular risk factors were well controlled and antithrombotic treatment maintained, smoking cessation non-significantly decreased the risk of MACE.

Foodborne diseases are a global burden, are preventable, and young people are a key population for behaviour change as they gain autonomy. This study aimed to explore young people's needs across several European countries in relation to learning about and implementing food hygiene and food safety. Qualitative focus groups and interviews were conducted in rural and city regions across England, France, Hungary and Portugal. Data were collected to attain data saturation, transcribed, thematically analysed, and mapped to the Theoretical Domains Framework. Twenty-five out of 84 schools approached (29.8%) participated, with data collected from 156 11-18-year-old students. Students had good knowledge of personal hygiene but did not always follow hygiene rules due to forgetfulness, lack of facilities or lack of concern for consequences. Students had limited understanding of foodborne microbes, underestimated the risks and consequences of foodborne illness and perceived the "home" environment as the safest. Young people preferred interactive educational methods. Addressing gaps in young people's food safety knowledge is essential to improve their lack of concern towards foodborne illness and motivate them to follow food hygiene and safety behaviours consistently. Findings have been used to develop educational resources to address gaps in knowledge, skills, attitudes and beliefs.

Abstract Eighteen to 35% of adnexal masses remain non-classified following ultrasonography, leading to unnecessary surgeries and inappropriate management. This finding led to the conclusion that ultrasonography was insufficient to accurately assess adnexal masses and that a standardized MRI criteria could improve these patients’ management. The aim of this work is to present the different steps from the identification of the clinical issue to the daily use of a score and its inclusion in the latest international guidelines. The different steps were the following: (1) preliminary work to formalize the issue, (2) physiopathological analysis and finding dynamic parameters relevant to increase MRI performances, (3) construction and internal validation of a score to predict the nature of the lesion, (4) external multicentric validation (the EURAD study) of the score named O-RADS MRI, and (5) communication and education work to spread its use and inclusion in guidelines. Future steps will include studies at patients’ levels and a cost-efficiency analysis. Critical relevance statement We present translating radiological research into a clinical application based on a step-by-step structured and systematic approach methodology to validate MR imaging for the characterization of adnexal mass with the ultimate step of incorporation in the latest worldwide guidelines of the O-RADS MRI reporting system that allows to distinguish benign from malignant ovarian masses with a sensitivity and specificity higher than 90%. Key points • The initial diagnostic test accuracy studies show the limitation of a preoperative assessment of adnexal masses using solely ultrasonography. • The technical developments (DCE/DWI) were investigated with the value of dynamic MRI to accurately predict the nature of benign or malignant lesions to improve management. • The first developing score named ADNEX MR Score was constructed using multiple easily assessed criteria on MRI to classify indeterminate adnexal lesions following ultrasonography. • The multicentric adnexal study externally validated the score creating the O-RADS MR score and leading to its inclusion for daily use in international guidelines.

Abstract Background Primary care is a critical partner for antimicrobial stewardship efforts given its high human antibiotic usage. Peer comparison audit and feedback (A&F) is often used to reduce inappropriate antibiotic prescribing. The design and implementation of A&F may impact its effectiveness. There are no best practice guidelines for peer comparison A&F in antibiotic prescribing in primary care. Objective To develop best practice guidelines for peer comparison A&F for antibiotic prescribing in primary care in high income countries by leveraging international expertise via the Joint Programming Initiative on Antimicrobial Resistance—Primary Care Antibiotic Audit and Feedback Network. Methods We used a modified Delphi process to achieve convergence of expert opinions on best practice statements for peer comparison A&F based on existing evidence and theory. Three rounds were performed, each with online surveys and virtual meetings to enable discussion and rating of each best practice statement. A five-point Likert scale was used to rate consensus with a median threshold score of 4 to indicate a consensus statement. Results The final set of guidelines include 13 best practice statements in four categories: general considerations (n = 3), selecting feedback recipients (n = 1), data and indicator selection (n = 4), and feedback delivery (n = 5). Conclusion We report an expert-derived best practice recommendations for designing and evaluating peer comparison A&F for antibiotic prescribing in primary care. These 13 statements can be used by A&F designers to optimize the impact of their quality improvement interventions, and improve antibiotic prescribing in primary care.

Supercritical Fluid Extraction (SFE) methods dedicated to microorganisms specialized metabolites are very scarce in the literature and limited to liquid cultivation. We proposed here a new sample preparation method to achieve SFE of specialized metabolites from solid-state cultivation. SFE parameters, including CO2 pressure, temperature of extraction cell and percentage of co-solvent, were optimized in the case of solid-state cultures of Penicillium sclerotiorum SNB-CN111, a filamentous fungus producing azaphilone pigments. The metabolic composition of the extracts was then analyzed by reverse-phase liquid chromatography coupled to electrospray ionization and tandem mass spectrometry in data dependent acquisition mode. The resulting molecular networks generated by MetGem software allowed the annotation of the extracted metabolites in the different conditions, confirming the enrichment of fractions according to the polarity of azaphilone subfamilies. First, the 100 % CO2 fraction a yield ten times higher than hexane maceration The optimization of SFE method led to an extraction yield twice as high as ethyl acetate maceration when mixing CO2 with ethanol and, indicating that CO2/ethanol SFE is more environmentally-friendly and efficient than standard maceration methods for the extraction of azaphilones from solid-state fermentation.

Development of cortical regions with precise, sharp, and regular boundaries is essential for physiological function. However, little is known of the mechanisms ensuring these features. Here, we show that determination of the boundary between neocortex and medial entorhinal cortex (MEC), two abutting cortical regions generated from the same progenitor lineage, relies on COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I), a patterning transcription factor with graded expression in cortical progenitors. In contrast with the classical paradigm, we found that increased COUP-TFI expression expands MEC, creating protrusions and disconnected ectopic tissue. We further developed a mathematical model that predicts that neuronal specification and differential cell affinity contribute to the emergence of an instability region and boundary sharpness. Correspondingly, we demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. Thus, we conclude that a sharp boundary requires a subtle interplay between patterning transcription factors and differential cell affinity.

Species in the genus Scymnus Kugelann are common, but there is little information available on their defence compounds. Pupae are covered with setae on tips of which there are small droplets of liquid. This study explored the patterns of the distribution of the droplets and the influence of diet on their production in five species of Scymnus. GC-MS analyses were used to determine the chemical identity of droplets.All these species produced droplets, but the patterns in the distributions varied among species. Preliminary data indicates a de novo synthesis of the droplet compounds by these ladybirds. The results of the GC-MS analyses suggest that Scymnus spp. produce azamacrolides, which are fatty acid-derived alkaloids.

Abstract Introduction Keratoconus has a significant impact on patients’ quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. Methods Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide’s main themes. Results Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: “psychological”, “social life”, “professional life”, “financial costs” and “student life”. All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary’s model for patient outcomes common to all patients. This conceptual model describes the relationship between patients’ characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. Conclusions These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients’ QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

As a result of screening a panel of marine organisms to identify lead molecules for the stimulation of endochondral bone formation, the calcareous sponge Pericharax heteroraphis was identified to exhibit significant activity during endochondral differentiation. On further molecular networking analysis, dereplication and chemical fractionation yielded the known clathridine A-related metabolites 3–6 and the homodimeric complex (clathridine A)2 Zn2+ (9), together with the new unstable heterodimeric complex (clathridine A–clathridimine)Zn2+ (10). With the presence of the zinc complexes annotated through the LC-MS analysis of the crude extract changing due to the instability of some metabolites and complexes constituting the mixture, we combined the isolation of the predicted molecules with their synthesis in order to confirm their structure and to understand their reactivity. Interestingly, we also found a large quantity of the contaminant benzotriazoles BTZ (7) and its semi-dimer (BTZ)2CH2 (8), which are known to form complexes with transition metals and are used for preventing corrosion in water. All isolated 2-aminoimidazole derivatives and complexes were synthesized not only for structural confirmation and chemical understanding but to further study their bioactivity during endochondral differentiation, particularly the positively screened imidazolone derivatives. Compounds leucettamine B, clathridine A and clathridimine were found to increase type X collagen transcription and stimulate endochondral ossification in the ATDC5 micromass model.

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The segmental organization of the vertebral column is established early in embryogenesis, when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock1,2. Although this oscillator has been well-characterized in model organisms1,2, whether a similar oscillator exists in humans remains unknown. Genetic analyses of patients with severe spine segmentation defects have implicated several human orthologues of cyclic genes that are associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans3. Here we show that human PSM cells derived in vitro-as well as those of the mouse4-recapitulate the oscillations of the segmentation clock. Human PSM cells oscillate with a period two times longer than that of mouse cells (5 h versus 2.5 h), but are similarly regulated by FGF, WNT, Notch and YAP signalling5. Single-cell RNA sequencing reveals that mouse and human PSM cells in vitro follow a developmental trajectory similar to that of mouse PSM in vivo. Furthermore, we demonstrate that FGF signalling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in 'clock and wavefront' models1. Our work identifying the human segmentation clock represents an important milestone in understanding human developmental biology.

Abstract Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious and rare diseases, most often drug-induced, and their incidence has been estimated at 6 cases/million/year in France. SJS and TEN belong to the same spectrum of disease known as epidermal necrolysis (EN). They are characterized by more or less extensive epidermal detachment, associated with mucous membrane involvement, and may be complicated during the acute phase by fatal multiorgan failure. SJS and TEN can lead to severe ophthalmologic sequelae. There are no recommendations for ocular management during the chronic phase. We conducted a national audit of current practice in the 11 sites of the French reference center for toxic bullous dermatoses and a review of the literature to establish therapeutic consensus guidelines. Ophthalmologists and dermatologists from the French reference center for epidermal necrolysis were asked to complete a questionnaire on management practices in the chronic phase of SJS/TEN. The survey focused on the presence of a referent ophthalmologist at the center, the use of local treatments (artificial tears, corticosteroid eye drops, antibiotic-corticosteroids, antiseptics, vitamin A ointment (VA), cyclosporine, tacrolimus), the management of trichiatic eyelashes, meibomian dysfunction, symblepharons, and corneal neovascularization, as well as the contactologic solutions implemented. Eleven ophthalmologists and 9 dermatologists from 9 of the 11 centers responded to the questionnaire. Based on questionnaire results, 10/11 ophthalmologists systematically prescribed preservative-free artificial tears, and 11/11 administered VA. Antiseptic or antibiotic eye drops or antibiotic-corticosteroid eye drops were recommended as needed by 8/11 and 7/11 ophthalmologists, respectively. In case of chronic inflammation, topical cyclosporine was consistently proposed by 11/11 ophthalmologists. The removal of trichiatic eyelashes was mainly performed by 10/11 ophthalmologists. Patients were referred to a reference center for fitting of scleral lenses (10/10,100%). Based on this practice audit and literature review, we propose an evaluation form to facilitate ophthalmic data collection in the chronic phase of EN and we also propose an algorithm for the ophthalmologic management of ocular sequelae.

Abstract Background Several changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development. Methods Narrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation. Results General practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented. Conclusions Independent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

Abstract Aims Atrial fibrillation (AF)/atrial flutter is common during cardiac amyloidosis (CA). Electrical cardioversion (EC) is a strategy to restore sinus rhythm (SR). However, left atrial thrombus (LAT) represents a contraindication for EC. CA patients with AF/atrial flutter have a high prevalence of LAT. We aimed to evaluate EC characteristics, LAT prevalence and risk factors, and AF/atrial flutter outcome in CA patients undergoing EC, predominantly treated with direct oral anticoagulants (DOACs). Methods and results All patients with CA and AF/atrial flutter referred for the first time to our national referral centre of amyloidosis for EC from June 2017 to February 2021 were included in this study. In total, 66 patients (median age 74.5 [70;80.75] years, 67% male) were included with anticoagulation consisted of DOAC in 74% of cases. All patients underwent cardiac imaging before EC to rule out LAT. EC was cancelled due to LAT in 14% of cases. Complete thrombus resolution was observed in only 17% of cases. The two independent parameters associated with LAT were creatinine [hazard ratio (HR) = 1.01; confidence interval (CI) = 1.00–1.03, P = 0.036] and the use of antiplatelet agents (HR = 13.47; CI = 1.85–98.02). EC acute success rate was 88%, and we observed no complication after EC. With 64% of patients under amiodarone, AF/atrial flutter recurrence rate following EC was 51% after a mean follow‐up of 30 ± 27 months. Conclusions Left atrial thrombus was observed in 14% of CA patients listed for EC and mainly treated with DOAC. The acute EC success rate was high with no complication. The long‐term EC success rate was acceptable (49%).

Abstract We gathered a collection of termite mutualistic strains from French Guiana to explore the metabolites of symbiotic microorganisms. Molecular networks reconstructed from a metabolomic analysis using LC–ESI–MS/MS methodology led us to identify two families of chlorinated polyketides, i.e., azaphilones from Penicillium sclerotiorum and ilicicolins from Neonectria discophora. To define the biosynthetic pathways related to these two types of scaffolds, we used a whole genome sequencing approach followed by hybrid assembly from short and long reads. We found two biosynthetic gene clusters, including two FAD-dependent halogenases. To exploit the enzymatic promiscuity of the two identified FAD halogenases, we sought to biosynthesize novel halogenated metabolites. An OSMAC strategy was used and resulted in the production of brominated analogs of ilicicolins and azaphilones as well as iodinated analogs of azaphilones.

The wave–current–seabed interaction problem is studied by using a coupled-mode system developed for modeling wave scattering by non-homogeneous, sheared currents in variable bathymetry regions. The model is based on a modal series expansion of wave velocity based on vertical eigenfunctions, dependent on local depth and flow parameters, including propagating and evanescent modes. The latter representation is able to accurately satisfy the wave flow continuity condition and the no-entrance boundary condition on the sloping parts of the seabed. A new derivation of a simplified nonlinear system is introduced using decomposition to a mean flow and a perturbative wave field. To force the system to consider incoming waves at the inlet, boundary knowledge of periodic, travelling nonlinear water waves over a flat bottom is required. For this purpose, specific solutions are derived using the semi-analytical method based on the stream function formulation, for cases of water waves propagating above linearly and exponentially sheared currents. Results obtained by the application of the CMS concerning the propagation of waves and currents—in particular, examples characterized by depth inhomogeneities—are presented and discussed, illustrating the applicability and performance of the method.

The homogenization of microstructured interfaces requires solving specific problems posed on semi-infinite bands. To tackle these problems with existing FFT-based algorithms, a reformulation of these band problems into fully periodic cell problems, posed on bounded domains, is established. This is performed thanks to a Dirichlet-to-Neumann operator and a decomposition of the solution involving a boundary corrector, in a Fourier framework. A fixed-point algorithm and an example choice of corrector are proposed. Comparisons with other computational methods support this proposition.

Cervical cancer (CC) is the fourth cancer in women and is the leading cause of cancer death in 42 countries. Lymph node metastasis is a determinant prognostic factor, as underlined in the latest FIGO classification. However, assessment of lymph node status remains difficult, despite the progress of imaging such as PET-CT and MRI. In the specific setting of CC, all data underlined the need for new biomarkers easily available to assess lymph node status. Previous studies have underlined the potential value of ncRNA expression in gynecological cancers. In this review, we aimed to evaluate the contribution of ncRNAs in tissue and biofluid samples to determine lymph node status in CC with potential impact on both surgical and adjuvant therapies. In tissue samples, our analysis found that there are arguments to support the role of ncRNAs in physiopathology, differential diagnosis from normal tissue, preinvasive and invasive tumors. In biofluids, despite small studies especially concerning miRNAs expression, promising data opens up new avenue to establish a non-invasive signature for lymph node status as well as a tool to predict response to neo- and adjuvant therapies, thus improving management algorithm of patients with CC.

Objective The objective of our study was to determine the main surgical factors associated with postoperative pains in patients undergoing adnexectomy. Material and Methods Patients that underwent adnexectomy in two French Gynecological centers between July, 2018 and March, 2020 were prospectively included and retrospectively analyzed. The main pre and per operative surgical factors were analyzed to assess their impact on immediate postoperative pain. Analgesic consumption was recorded for each patient and pain was evaluated using the validated numeric rating scale (ranging between 0 and 10). Results One hundred and seventeen patients underwent laparoscopic adnexectomy. Eighty-four patients (72%) experienced either no or minor postoperative pain (NRS ≤ 2). Seventeen patients (14.5%) required strong opioids (subcutaneous morphine injection) in the immediate postoperative period. The only two parameters that had a significant impact on immediate postoperative pain were the realization of a fascia closure and the duration of pneumoperitoneum longer than 60 minutes. Pneumoperitoneum pressure and size of ports were not significantly correlated with postoperative pain. Conclusion Fascia closure and increased surgical time were significantly associated with immediate postoperative pain and the need for strong opioids consumption. Surgical training to limit prolonged surgeries should be strongly emphasized to lower postoperative pain and limit opioids consumption.

Abstract Endometriosis, characterized by endometrial-like tissue outside the uterus, is thought to affect 2–10% of women of reproductive age: representing about 190 million women worldwide. Numerous studies have evaluated the diagnostic value of blood biomarkers but with disappointing results. Thus, the gold standard for diagnosing endometriosis remains laparoscopy. We performed a prospective trial, the ENDO-miRNA study, using both Artificial Intelligence (AI) and Machine Learning (ML), to analyze the current human miRNome to differentiate between patients with and without endometriosis, and to develop a blood-based microRNA (miRNA) diagnostic signature for endometriosis. Here, we present the first blood-based diagnostic signature obtained from a combination of two robust and disruptive technologies merging the intrinsic quality of miRNAs to condense the endometriosis phenotype (and its heterogeneity) with the modeling power of AI. The most accurate signature provides a sensitivity, specificity, and Area Under the Curve (AUC) of 96.8%, 100%, and 98.4%, respectively, and is sufficiently robust and reproducible to replace the gold standard of diagnostic surgery. Such a diagnostic approach for this debilitating disorder could impact recommendations from national and international learned societies.

Abstract Ultrasound-guided injections are an alternative to evaluate in the management of low back pain associated with osteoarthritis of the lumbar facet joints: it eliminates the risk of ionizing radiation for both the patient and the practitioner. This study aims to compare the short-term clinical efficacy of lumbar facet joints injections between ultrasound-guided injections and fluoroscopy-guided injections. Observational, retrospective, single-center study. Patients received one or two lumbar zygapophyseal joints injections under fluoroscopy or ultrasound and a follow-up consultation at one month. Data from 54 patients was collected. The median of the evolution of VAS at one month was − 30 mm [−50.0; −20.0] in the ultrasound group and – 29.5 mm [−47.0; −15.0] (p

Introduction: Triple-negative (TN) breast cancer represents one third of pregnancy-associated breast cancers (PABC). The aims of the current study were to describe oncological and obstetrical outcomes of patients with TN-PABC and to compare their prognosis with TN-non-PABC patients using a propensity score. Materials and methods: Between January 2005 and December 2020, data of patients with histologically proven TN-PABC were collected and compared with data of TN-non-PABC patients under the age of 46 years diagnosed during the same period using a propensity score (PS). Results: After PS matching (tumor size and lymph node involvement),there were 59 patients in each group. The median follow-up was 14 months (IQR 4.8–40.1) for the TN-PABC group and 60 months (IQR 30.7–101.4) for the TN-non-PABC group. Eight recurrences occurred in the TN-PABC group and 10 in the TN-non-PABC group (adjusted OR (AOR) = 0.60 (0.21–1.60), HR (Cox adjusted model- AHR) = 1.25 (0.53–2.94)). Two patients died in the TN-PABC group, and six in the TN-non-PABC group with an AOR = 0.23 (0.03–1.01) and an AHR = 0.58 (0.12–2.69). All the patients diagnosed during the second (n = 17) and third trimesters (n = 28) continued their pregnancies, with a median term at delivery of 38 WG (IQR 36–39). All patients gave birth to healthy newborns. Conclusion: Although the TN subtype is associated with poor prognosis in pregnant patients due to advanced stage at diagnosis and high lymph node involvement, our PS-matched case-control study showed that pregnancy per se does not worsen the prognosis in terms of recurrence-free and overall survival.

Abstract Endometriosis—a systemic and chronic condition occurring in women of childbearing age—is a highly enigmatic disease with unresolved questions. While multiple biomarkers, genomic analysis, questionnaires, and imaging techniques have been advocated as screening and triage tests for endometriosis to replace diagnostic laparoscopy, none have been implemented routinely in clinical practice. We investigated the use of machine learning algorithms (MLA) in the diagnosis and screening of endometriosis based on 16 key clinical and patient-based symptom features. The sensitivity, specificity, F1-score and AUCs of the MLA to diagnose endometriosis in the training and validation sets varied from 0.82 to 1, 0–0.8, 0–0.88, 0.5–0.89, and from 0.91 to 0.95, 0.66–0.92, 0.77–0.92, respectively. Our data suggest that MLA could be a promising screening test for general practitioners, gynecologists, and other front-line health care providers. Introducing MLA in this setting represents a paradigm change in clinical practice as it could replace diagnostic laparoscopy. Furthermore, this patient-based screening tool empowers patients with endometriosis to self-identify potential symptoms and initiate dialogue with physicians about diagnosis and treatment, and hence contribute to shared decision making.

Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of Theileria parva, and their immunogenicity in cattle. p67C is a truncation of p67, the major surface protein of the sporozoite stage of T. parva, an apicomplexan parasite that causes an often-fatal bovine disease called East Coast fever (ECF) in sub-Saharan Africa. Compared to I32-19 and I32-28, we found that I53-50 nanoparticle scaffolds displaying p67C had the best biophysical characteristics. p67C-I53-50 also outperformed the other two nanoparticles in stimulating p67C-specific IgG1 and IgG2 antibodies and CD4+ T-cell responses, as well as sporozoite neutralizing capacity. In experimental cattle vaccine trials, p67C-I53-50 induced significant immunity to ECF, suggesting that the I53-50 scaffold is a promising candidate for developing novel nanoparticle vaccines. To our knowledge this is the first application of computationally designed nanoparticles to the development of livestock vaccines.

BackgroundTakotsubo cardiomyopathy (TTC) is a rare entity after cardiac surgery.AimsTo describe patients’ profile who developed postoperative TTC after cardiac surgery, management, and outcomes.MethodsWe performed a systematic literature search to extract cases of TTC after adult cardiac surgery (from 1990 to 2021). Additionally, we extracted all cases of TTC in a prospective single-center cohort database of 10,000+ patients (from 2007 to 2019). We then combined all cases in a single cohort to describe its clinical features.ResultsFrom 694 screened articles, we retained 71 individual cases published in 20 distinct articles (19 cases reports and 1 case-series). We combined these to 10 cases extracted from our cohort [among 10,682 patients (0.09%)]. Overall, we included 81 cases. Patients were aged 68 ± 10 years-old and 64/81 (79%) were women. Surgery procedures included mitral valve and/or tricuspid valve surgery in 70/81, 86%. TTC was diagnosed in the first days after surgery [median 4 (1–4) days]. Incidence of cardiogenic shock, defined as requirement of vasopressor and/or inotropic support was 24/29, 83% (data available on 29/81 patients). Refractory cardiogenic appeared in 5/81, 6% who required implantation of arterio-venous extra-corporeal membrane oxygenation, and 6/81, 7%, intra-aortic balloon pump. In-hospital mortality was 5/81, 6%.ConclusionThis systematic review, based on case reports and case series, showed that postoperative TTC appears as a rare complication after cardiac surgery and mainly occurred after mitral and/or tricuspid valve repair procedures. In this population, TTC is associated with high rate of cardiogenic shock.

Objectives Recurring cystitis (RC) is a common complaint among women. It has a significant impact on patients’ quality of life. The physical discomfort and psychological distress related to RC are rarely addressed and women’s needs in terms of information and advice have not been sufficiently explored, particularly in France in spite of their frequent episodes of RC. This study aimed to assess women’s needs and expectations in view of developing a patient information leaflet to help them understand and better cope with their condition, thus offering them more autonomy and empowering them to self-manage whenever possible.Method Qualitative study using recorded semistructured interviews with patients suffering from RC.Setting Interviews conducted with women suffering from RC in Corsica, France.Participants 26 patients interviewed between January 2018 and April 2018.Results Knowledge of the condition was heterogeneous, but most women reported a major impact on daily life, a high level of anxiety, various management strategies and wished to avoid taking antibiotics, preferring alternative approaches. Patients reported a lack of understanding and sympathy on the part of physicians and society and wished for more autonomy with delayed/back-up prescriptions, a multidisciplinary follow-up and, most of all, appropriate information.Conclusion The information leaflet should improve patients’ knowledge and capacity for self-care, contribute to standardise practice and limit inappropriate antibiotic use.

Breast cancer in women is the second most common cancer and the fifth leading cause of cancer death worldwide. Although earlier diagnosis and detection of breast cancer has resulted in lower mortality rates, further advances in prevention, detection, and treatment are needed to improve outcomes and survival for women with breast cancer as well as to offer a personalized therapeutic approach. It is now well-established that non-coding RNAs (ncRNAs) represent 98% of the transcriptome but in-depth knowledge about their involvement in the regulation of gene expression is lacking. A growing body of research indicates that ncRNAs are essential for tumorigenesis by regulating the expression of tumour-related genes. In this review, we focus on their implication in breast cancer genesis but also report the latest knowledge of their theragnostic and therapeutic role. We highlight the need for accurate quantification of circulating ncRNAs which is determinant to develop reliable biomarkers. Further studies are mandatory to finally enter the era of personalized medicine for women with breast cancer.

Cutibacterium acnes is one of the most abundant bacteria on the skin. Being exposed to oxygen and oxic stress, the secretion of the bacterial antioxidant protein RoxP ensures an endogenous antioxidant system for the preservation of skin health. To investigate the impact of the antioxidant RoxP on oxidation of the bacteria, wildtype and an isogenic roxp mutant were cultured in anaerobic and oxic conditions. The carbonylated status of proteins were recorded, as were the most significant modifications in a relative intensity of free fatty acids (FFA) and lipids containing fatty acids (FA), such as di- (DG) and triglycerides (TG), di- (DGDG) and sulfoquinozyldiacylglycerol (SQDG) and ceramides. Concerning the fatty acid types, it was observed that the free fatty acids contained mainly C12:0–C26:0 in hydroxy and acylated forms, the DG contained mainly C29:0–C37:0, the TG contained mainly C19:0–C33:0, and the DGDG/SQDGs contained very long fatty acids (C29:0–C37:0) demonstrating the interdependence of de novo synthesis of lipids and RoxP. The area of DGDG peaks (924.52, 929.56 and 930.58) were affected by bacterial growth conditions, with the exception of m/z 910.61. Moreover, the FFA unsaturation is wider in the SQDG species (C30:0 to C36:6) than in DG, TG or free FFA species. It could be concluded that both environmental oxidative statuses, as well as the prevalence of bacterial antioxidant systems, significantly shape the lipidome of C. acnes.