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Neurosurgeons receive extensive technical training, which equips them with the knowledge and skills to specialise in various fields and manage the massive amounts of information and decision-making required throughout the various stages of neurosurgery, including preoperative, intraoperative, and postoperative care and recovery. Over the past few years, artificial intelligence (AI) has become more useful in neurosurgery. AI has the potential to improve patient outcomes by augmenting the capabilities of neurosurgeons and ultimately improving diagnostic and prognostic outcomes as well as decision-making during surgical procedures. By incorporating AI into both interventional and non-interventional therapies, neurosurgeons may provide the best care for their patients. AI, machine learning (ML), and deep learning (DL) have made significant progress in the field of neurosurgery. These cutting-edge methods have enhanced patient outcomes, reduced complications, and improved surgical planning.

Introduction Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women’s sexual and reproductive health needs. We will gauge the DPP’s acceptability in two cross-over clinical trials.Methods and analysis PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16–40 years) and Harare, Zimbabwe (n=30, 16–24 years) will be randomised 1:1 to the order of regimens—DPP or two separate tablets—each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024.Ethics and dissemination PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand’s Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences.Trial registration numbers NCT04778514, NCT04778527.

Space travel exposes astronauts to several environmental challenges, including microgravity and radiation exposure. To overcome these stressors, the body undergoes various adaptations such as cardiovascular deconditioning, fluid shifts, metabolic changes, and alterations in the state of the bone marrow. Another area of concern is the potential impact of these adaptations on erythrocyte and haemoglobin concentrations, which can lead to what is commonly referred to as space anaemia or microgravity-induced anaemia. It is known that anaemia may result in impaired physical and cognitive performance, making early detection and management crucial for the health and wellbeing of astronauts during extended space missions. However, the effects and mechanisms of space anaemia are not fully understood, and research is underway to determine the extent to which it poses a challenge to astronauts. Further research is needed to clarify the long-term effects of microgravity on the circulatory system and to investigate possible solutions to address spaceflight-induced anaemia. This article reviews the potential link between spaceflight and anaemia, based on existing evidence from simulated studies (e.g., microgravity and radiation studies) and findings from spaceflight studies (e.g., International Space Station and space shuttle missions).

Background: Since the first year of the COVID-19 global pandemic, a hypothesis concerning the possible protection/immunity of beta-thalassemia carriers has remained in abeyance. Methods: Three databases (Pubmed Central, Scopus, and Google Scholar) were screened and checked in order to extract all studies about the incidence of confirmed COVID-19 cases, mortality rate, severity assessment, or ICU admission among patients with beta-thalassemia minor, were included in this analysis. The language was limited to English. Studies such as case reports, review studies, and studies that did not have complete data for calculating incidences were excluded. Results and discussion: a total of 3 studies out of 2265 were selected. According to our systematic-review meta-analysis, beta-thalassemia carriers could be less affected by COVID-19 than the general population [IRR = 0.9250 (0.5752; 1.4877)], affected by COVID-19 with a worst severity [OR = 1.5933 (0.4884; 5.1981)], less admissible into the ICU [IRR = 0.3620 (0.0025; 51.6821)], and more susceptible to die from COVID-19 or one of its consequences [IRR = 1.8542 (0.7819; 4.3970)]. However, all of those results remain insignificant with a bad p-value (respectively 0.7479, 0.4400, 0.6881, and 0.1610). Other large case-control or registry studies are needed to confirm these trends.

Autism spectrum disorder (ASD) represents a set of heterogeneous neurodevelopmental conditions defined by impaired social interactions and repetitive behaviors. The number of reported cases has increased over the past decades, and ASD is now a major public health burden. So far, only treatments to alleviate symptoms are available, with still unmet need for an effective disease treatment to reduce ASD core symptoms. Genetic predisposition alone can only explain a small fraction of the ASD cases. It has been reported that environmental factors interacting with specific inter-individual genetic background may induce immune dysfunctions and contribute to the incidence of ASD. Such dysfunctions can be observed at the central level, with increased microglial cells and activation in ASD brains or in the peripheral blood, as reflected by high circulating levels of pro-inflammatory cytokines, abnormal activation of T-cell subsets, presence of auto-antibodies and of dysregulated microbiota profiles. Altogether, the dysfunction of immune processes may result from immunogenetically-determined inefficient immune responses against a given challenge followed by chronic inflammation and autoimmunity. In this context, immunomodulatory therapies might offer a valid therapeutic option. Mesenchymal stromal cells (MSC) immunoregulatory and immunosuppressive properties constitute a strong rationale for their use to improve ASD clinical symptoms. In vitro studies and pre-clinical models have shown that MSC can induce synapse formation and enhance synaptic function with consequent improvement of ASD-like symptoms in mice. In addition, two preliminary human trials based on the infusion of cord blood-derived MSC showed the safety and tolerability of the procedure in children with ASD and reported promising clinical improvement of core symptoms. We review herein the immune dysfunctions associated with ASD provided, the rationale for using MSC to treat patients with ASD and summarize the current available studies addressing this subject.

Context: The third generation of cryptocurrencies gathers cryptocurrencies that are as diverse as the market is big (e.g., Dogecoin or Litecoin). While Dogecoin is seen as a memecoin, the other gathers a very different category of investors. To our knowledge, no study has independently assessed the crypto community’s economical impact on these cryptocurrencies. Furthermore, various methodological possibilities exist to forecast cryptocurrency price—mainly coming from online communities.Method: Our study has retrospectively studied (from 01/01/2015 to 03/11/2021)—using open access data—the association strength (using normalized mutual information) and the linear correlation (using Pearson’s correlation) between Twitter activity and cryptocurrency economical attributes. In addition, we have computed different models (ADF, ARIMA, and Interpretable MultiVvariable Long Short-Term Memory recurrent neural network) that forecast past price values and assessed their precision.Findings and conclusions: While the average Dogecoin transaction value is impacted by tweets, tweets are impacted by Litecoin transactions number and average Litecoin transaction value. Tweet number is impacted by Dogecoin whale behavior, but no significant relationship was found between Litecoin whales and tweets. The forecasting error resulting from our ARIMA (0,0,0) models was 0.08% (with Litecoin) and 0.22% (with Dogecoin). Therefore, those are just the beginning of scientific findings that may lead to building a trading robot based on these results. However, in itself, this study is only for academic discussion, and conclusions need to be drawn by further research. The authors cannot be liable if any financial investment is made based on its conclusions.

Systemic Sclerosis (SSc) is a chronic autoimmune disease with high morbidity and mortality. Autologous Hematopoietic Stem Cell Transplantation (AHSCT) is the best therapeutic option for rapidly progressive SSc, allowing increased survival with regression of skin and lung fibrosis. The immune determinants of the clinical response after AHSCT have yet to be well characterized. In particular, the pivotal role of the Human Leukocyte Antigen (HLA) system is not well understood, including the role of non-classical immuno-modulatory HLA-E and HLA-G molecules in developing tolerance and the role of Natural Killer cells (NK) in the immunomodulation processes. We retrospectively tested whether the genetic and/or circulating expression of the non-classical HLA-E and HLA-G loci, as well as the imputed classical HLA determinants of HLA-E expression, influence the observed clinical response to AHSCT at 12- and 24-month follow-up. In a phenotypically well-defined sample of 46 SSc patients classified as clinical responders or non-responders, we performed HLA genotyping using next-generation sequencing and circulating levels of HLA-G and quantified HLA-E soluble isoforms by ELISA. The -21HLA-B leader peptide dimorphism and the differential expression level of HLA-A and HLA-C alleles were imputed. We observed a strong trend towards better clinical response in HLA-E*01:03 or HLA-G 14bp Del allele carriers, which are known to be associated with high expression of the corresponding molecules. At 12-month post-AHSCT follow-up, higher circulating levels of soluble HLA-E were associated with higher values of modified Rodnan Skin Score (mRSS) (p = 0.0275), a proxy of disease severity. In the non-responder group, the majority of patients carried a double dose of the HLA-B Threonine leader peptide, suggesting a non-efficient inhibitory effect of the HLA-E molecules. We did not find any correlation between the soluble HLA-G levels and the observed clinical response after AHSCT. High imputed expression levels of HLA-C alleles, reflecting more efficient NK cell inhibition, correlated with low values of the mRSS 3 months after AHSCT (p = 0.0087). This first pilot analysis of HLA-E and HLA-G immuno-modulatory molecules suggests that efficient inhibition of NK cells contributes to clinical response after AHSCT for SSc. Further studies are warranted in larger patient cohorts to confirm our results.

Objective: The molecular diagnosis of extreme forms of obesity, in which accurate detection of both copy number variations (CNVs) and point mutations, is crucial for an optimal care of the patients and genetic counseling for their families. Whole-exome sequencing (WES) has benefited considerably this molecular diagnosis, but its poor ability to detect CNVs remains a major limitation. We aimed to develop a method (CoDE-seq) enabling the accurate detection of both CNVs and point mutations in one step. Methods: CoDE-seq is based on an augmented WES method, using probes distributed uniformly throughout the genome. CoDE-seq was validated in 40 patients for whom chromosomal DNA microarray was available. CNVs and mutations were assessed in 82 children/young adults with suspected Mendelian obesity and/or intellectual disability and in their parents when available (ntotal = 145). Results: CoDE-seq not only detected all of the 97 CNVs identified by chromosomal DNA microarrays but also found 84 additional CNVs, due to a better resolution. When compared to CoDE-seq and chromosomal DNA microarrays, WES failed to detect 37% and 14% of CNVs, respectively. In the 82 patients, a likely molecular diagnosis was achieved in >30% of the patients. Half of the genetic diagnoses were explained by CNVs while the other half by mutations. Conclusions: CoDE-seq has proven cost-efficient and highly effective as it avoids the sequential genetic screening approaches currently used in clinical practice for the accurate detection of CNVs and point mutations. Keywords: Augmented whole-exome sequencing, Copy number variation, Intellectual disability, Molecular diagnosis, Next-generation sequencing, Obesity

Abstract: To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements. At the 1-year post-AHSCT evaluation of the total set of transplanted SSc patients, thymic rebound led to renewal of the immune system, with higher T-cell receptor (TCR) diversity, positive correlation between recent thymic emigrant and Treg counts, and higher expression of CTLA-4 and GITR on Tregs, when compared with pretransplant levels. In parallel, increased bone marrow output of newly generated naive B-cells, starting at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At 6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10 levels than before transplant. When the nonresponder patients were evaluated separately, Treg and Breg counts did not increase after AHSCT, and high TCR repertoire overlap between pre- and posttransplant periods indicated maintenance of underlying disease mechanisms. These data suggest that clinical improvement of SSc patients is related to increased counts of newly generated Tregs and Bregs after AHSCT as a result of coordinated thymic and bone marrow rebound.

Multiscale characterization of the textile preform made of natural fibers is an indispensable way to understand and assess the mechanical properties and behavior of composite. In this study, a multiscale experimental characterization is performed on three-dimensional (3D) warp interlock woven fabrics made of flax fiber on the fiber (micro), roving (meso), and fabric (macro) scales. The mechanical tensile properties of the flax fiber were determined by using the impregnated fiber bundle test. The effect of the twist was considered in the back-calculation of the fiber stiffness to reveal the calculation limits of the rule of mixture. Tensile tests on dry rovings were carried out while considering different twist levels to determine the optimal amount of twist required to weave the flax roving into a 3D warp interlock. Finally, at fabric-scale, six different 3D warp interlock architectures were woven to understand the role of the architecture of binding rovings on the mechanical properties of the dry 3D fabric. The results reveal the importance of considering the properties of the fiber and roving at these scales to determine the more adequate raw material for weaving. Further, the characterization of the 3D woven structures shows the preponderant role of the binding roving on their structural and mechanical properties.

Primary cultures of cardiomyocytes represent a useful model for analyzing cardiac cell biology as well as pathogenesis of several cardiovascular disorders. Our aim was to standardize protocols for determining the damage of cardiac cells cultured in vitro by measuring the creatine kinase and its cardiac isotype and lactate dehydrogenase activities in the supernatants of mice cardiomyocytes submitted to different protocols of cell lysis. Our data showed that due to its higher specificity, the cardiac isotype creatine kinase was the most sensitive as compared to the others studied enzymatic markers, and can be used to monitor and evaluate cardiac damage in in vitro assays.

Background All the cellular partners of the vascular system and especially endothelial cells are involved in the pathophysiology of the vasoocclusive crises associated with sickle cell disease. In sickle cell disease, circulating cells adhere abnormally to endothelial cells in a chronic pro-inflammatory context. Hydroxycarbamide is the only drug with demonstrated efficacy to reduce the frequency of vasoocclusive crises. Here, we investigated the effects of hydroxycarbamide and/or cytokines on the expression of genes related to adhesion events in endothelial cells from three different vascular sites.Design and Methods Endothelial cells representative of the macro- (HUVEC) or microcirculation (TrHBMEC and HPMEC) were grown in the presence or absence of hydroxycarbamide and/or cytokines (TNFα and IFNγ). Expression of genes encoding adhesion proteins was analyzed by RQ-PCR, ELISA, flow cytometry, in situ ELISA for extracellular matrix proteins, and Western blot.Results In cells from the microcirculation, expression of TSP-1, vWF, and PECAM-1 genes was decreased by hydroxycarbamide and/or cytokine treatment at the mRNA level. In the macro-circulation their expression was unaffected or increased. Hydroxycarbamide significantly decreased vWF incorporated in the TrHBMEC extracellular matrix. CD36 mRNA was strongly down-regulated by cytokines in HPMEC, the only cell type in which it is expressed. Hydroxycarbamide decreased soluble PECAM-1 in HUVEC supernatants.Conclusions Our results highlight the heterogeneity of vascular endothelial cell responses to hydroxycarbamide and/or cytokines depending upon their origin. They also suggest that hydroxycarbamide has an anti-adhesogenic effect on endothelial cells, but by mechanisms which could vary according to their macro- or microcirculation and organ origin.

Objective The molecular diagnosis of extreme forms of obesity, in which accurate detection of both copy number variations (CNVs) and point mutations, is crucial for an optimal care of the patients and genetic counseling for their families. Whole-exome sequencing (WES) has benefited considerably this molecular diagnosis, but its poor ability to detect CNVs remains a major limitation. We aimed to develop a method (CoDE-seq) enabling the accurate detection of both CNVs and point mutations in one step. Methods CoDE-seq is based on an augmented WES method, using probes distributed uniformly throughout the genome. CoDE-seq was validated in 40 patients for whom chromosomal DNA microarray was available. CNVs and mutations were assessed in 82 children/young adults with suspected Mendelian obesity and/or intellectual disability and in their parents when available ( n total = 145). Results CoDE-seq not only detected all of the 97 CNVs identified by chromosomal DNA microarrays but also found 84 additional CNVs, due to a better resolution. When compared to CoDE-seq and chromosomal DNA microarrays, WES failed to detect 37% and 14% of CNVs, respectively. In the 82 patients, a likely molecular diagnosis was achieved in >30% of the patients. Half of the genetic diagnoses were explained by CNVs while the other half by mutations. Conclusions CoDE-seq has proven cost-efficient and highly effective as it avoids the sequential genetic screening approaches currently used in clinical practice for the accurate detection of CNVs and point mutations. [ABSTRACT FROM AUTHOR]

Context A better understanding of “patient pathway” thanks to data analysis can lead to better treatments for patients. The ClinMine project, supported by the French National Research Agency (ANR), aims at proposing, from various case studies, algorithmic and statistical models able to handle this type of pathway data, focusing primarily on hospital data. Methods This article presents two of these case studies, focusing on the integration of temporal data within analysis. First, the hypothesis that some aspects of the patient pathway can be described, even predicted, from the management process of the hospital medical mail is studied. Therefore a specific functional data analysis is driven, and several types of patients have been detected. The second case study deals with the detection of profiles through a biclustering of the patients. The difficulty to simultaneously deal with heterogeneous data, including temporal data is exposed and a method is proposed. Results Experiments are driven on real data coming from a hospital. Results on these data show the effectiveness of the two proposed methods. Conclusion The project ClinMine aimed at dealing with hospital data in order to provide a better understanding of “patient pathway”. The two methods proposed here show their ability to simultaneously deal with heterogeneous data, including temporal aspects, and manages to give information for the understanding of “patient pathway” (identification of interesting clusters of patients). [ABSTRACT FROM AUTHOR]