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Abstract Introduction Mental health is considered a major public health issue. Non-psychiatric physicians often engage in the treatment of mental disorders. The aim of this study was to describe psychiatric drug prescription knowledge and practices among non-psychiatric specialists and evaluate their training needs. Methods A descriptive cross-sectional study was conducted from September 1st to October 15th, 2021, in 3 Moroccan healthcare facilities and among private practitioners in Kenitra. We asked non-psychiatric specialists about their knowledge and current practices regarding psychotropic drugs, and their needs in psychiatric training. Results The study included a total of 150 participants. The majority of participants demonstrated insufficient knowledge regarding the selection of psychotropic drugs and the duration of pharmacotherapy. Specifically, 61.3% were unaware of the average duration of treatment for depression. 22.7% of participants did not feel comfortable when prescribing psychotropic drugs. Anxiolytics were the most commonly prescribed class of psychotropic drugs, accounting for 30.7% of prescriptions. The most common indications for psychotropic drugs prescription were anxiety (35.3%), followed by insomnia (34.7%) and depression (31.3%). The majority of participants (72%) reported receiving clinical training in psychiatry, with 74.7% expressing varying levels of satisfaction with their undergraduate psychiatry training, while 7.3% expressed dissatisfaction. Regarding CME, only 11.3% of participants engaged in at least one psychiatry-related CME session in the past two years. 54.7% of participants expressed interest in expanding their knowledge of prescribing psychotropic drugs. Around 40% of participants preferred trainings in psychotropic drugs prescription related to their specialty, while 34% were not interested in receiving further training. Conclusions Our study shows gaps in knowledge of non-psychiatric specialists, which raises concern regarding their ability to care for mental disorders. Educational efforts should be made to improve teaching of psychiatry from the undergraduate level. Continuing Medical Education should be tailored to the specific needs and preferred learning methods of non-psychiatric physicians.

Abstract Background Cancer has become a major health concern due to the increasing morbidity and mortality rates, and its negative social, economic consequences and the heavy financial burden incurred by cancer patients. About 40% of cancers are preventable. The aim of this study was to assess the knowledge, attitudes, and practices regarding cancer prevention, and associated characteristics to inform the development of targeted cancer prevention campaigns and policies. Methods We conducted a cross-sectional survey of adult patients at Mohamed Sekkat and Sidi Othmane Hospitals in Casablanca, Morocco. Data collection was conducted by two trained interviewers who administered the questionnaire in-person in the local language. An unsupervised clustering approach included 17 candidate variables for the cluster analysis. The variables covered a wide range of characteristics, including demographics, health perceptions and attitudes. Survey answers were calculated to compose qualitative ordinal categories, including a cancer attitude score and knowledge score. Results The cluster-based analysis showed that participants in cluster 1 had the highest mean attitude score (13.9 ± 2.15) and percentage of individuals with a high level of knowledge (50.8%) whereas the lowest mean attitude score (9.48 ± 2.02) and knowledge level (7.5%.) were found in cluster 3. The participants with the lowest cancer attitude scores and knowledge levels were aged 34 to 47 years old (middle age group), predominantly females, living in rural settings, and were least likely to report health professionals as a source of health information. Conclusions The findings showed that female individuals living in rural settings, belonging to an older age group, who were least likely to use health professionals as an information source had the lowest levels of knowledge and attitudes. These groups are amenable to targeted and tailored interventions aiming to modify their understanding of cancer in order to enhance the outcomes of Morocco’s on-going efforts in cancer prevention and control strategies.

The study aims to determine the relation between the micro-climate and the natural production of Amanita subviscosa, and Lactifluus gymnocarpoides, in the Guinea-Sudanian ecozone. Nine permanent plots of 50 ×50 m were installed in three different vegetations of the “Ouémé Supérieur” forest reserve in central Benin. The mycological surveys were carried out during three (3) mycological seasons, each from June to October at a frequency of two visits per week and per plot. The number of fruiting bodies and the fresh biomass were recorded. Microclimatic parameters (soil water content, air temperature, soil temperature, relative humidity and precipitation) were measured using a rain gauge and a HOBO micro station data logger installed at the middle of each plot. We tested several Generalized Linear Mixed Effects Models (GLMM) using the lme4 package to obtain the effect of recorded microclimate factor on the number of fruit bodies of each species and the Linear Mixed Effects Model (LMM) using the package nlme for fresh biomass. The study showed that soil water content is the main driver of fungal fruiting phenology and increased biomass production. The fruiting of A. subviscosa is positively affected by air temperature and soil water content (p = 0.0004) but negatively affected by relative air humidity. The fructification of L. gymnocarpoides is only positively affected by the air temperature and negatively affected by relative air humidity and soil water content. Soil water content significantly affects the fresh biomass of A. subviscosa (p≈0) while the fresh biomass of L. gymnocarpoides is significantly affected by soil water content and relative air humidity (p≈0). All species for their natural production have specific response at microclimate parameters variation.

The interplay between immune cells and malignant cells represents an essential chapter in the eradication of breast cancer. This widely distributed and diverse form of cancer represents a major threat to women worldwide. The incidence of breast cancer is related to several risk factors, notably genetic predisposition and family antecedents. Despite progress in treatment modalities varying from surgery and chemotherapy to radiotherapy and targeted therapies, persistently high rates of recurrence, metastasis, and treatment resistance underscore the urgent need for new therapeutic approaches. Immunotherapy has gained considerable ground in the treatment of breast cancer, as it takes advantage of the complex interactions within the tumor microenvironment. This dynamic interplay between immune and tumor cells has become a key point of focus in immunological research. This study investigates the role of various cancer markers, such as neoantigens and immune regulatory genes, in the diagnosis and treatment of breast tumors. Moreover, it explores the future potential of immune checkpoint inhibitors as therapeutically effective agents, as well as the challenges that prevent their efficacy, in particular tumor-induced immunosuppression and the difficulty of achieving tumor specificity.

Over the last decades, extracellular vesicles (EVs) have become increasingly popular for their roles in various pathologies, including cancer and neurological and immunological disorders. EVs have been considered for a long time as a means for normal cells to get rid of molecules it no longer needs. It is now well established that EVs play their biological roles also following uptake or by the interaction of EV surface proteins with cellular receptors and membranes. In this review, we summarize the current status of EV production and secretion in glioblastoma, the most aggressive type of glioma associated with high mortality. The main purpose is to shed light on the EVs as a universal mediator of interkingdom and intrakingdom communication in the context of tumor microenvironment heterogeneity. We focus on the immunomodulatory EV functions in glioblastoma-immune cross-talk to enhance immune escape and reprogram tumor-infiltrating immune cells. We critically examine the evidence that GBM-, immune cell-, and microbiome-derived EVs impact local tumor microenvironment and host immune responses, and can enter the circulatory system to disseminate and drive premetastatic niche formation in distant organs. Taking into account the current state of the art in intratumoral microbiome studies, we discuss the emerging role of bacterial EV in glioblastoma and its response to current and future therapies including immunotherapies.

The aim of this study is to assess the anti-inflammatory effects of volatile compounds derived from clove bud in vivo and in silico. Clove bud essential oil was obtained through hydrodistillation and subsequently analyzed using GC–MS. The analysis identified ten compounds, which were then subjected to molecular docking with Cyclooxygenase II (PDB ID: 3LN1). From these docking studies, two active compounds were selected for further investigation using a mouse ear edema model induced by DNFB. The results revealed that eugenol was the predominant compound in the essential oil constituting 68.51 %. The docking simulations demonstrated effective binding affinities for eugenol and acetyleugenol, with energies of -7.3 and -8.1 Kcal/mol, respectively, which were comparable to aspirin (-7.5 Kcal/mol). Additionally, both selected ligands exhibited non-toxic and non-carcinogenic properties based on ADMET predictions. In the in vivo experiments, significant anti-inflammatory activity was observed for both tested compounds. Notably, 48 h after the challenge, the presence of acetyleugenol resulted in a more pronounced reduction in ear swelling compared to eugenol. These findings hold promise for potential applications in future clinical studies aimed at harnessing the therapeutic benefits of clove bud derived compounds for anti-inflammatory purposes.

IntroductionGliomas represent the most prevalent and aggressive tumors within the central nervous system. Despite the current standard treatments, the median survival time for glioblastoma patients remains dismal, hovering around 14 months. While attempts have been made to inhibit the PD-1/PD-L1 and CTLA-4/CD80-CD86 axes through immunotherapy, the outcomes have yet to demonstrate significant efficacy. The immune checkpoint Butyrophilin 3A1 (BTN3A1) can either be involved in advantageous or detrimental function depending on the cancer type.MethodsIn our study, we utilized a Moroccan cohort to delve into the role of BTN3A1 in gliomas. A transcriptomic analysis was conducted on 34 patients, which was then corroborated through a protein analysis in 27 patients and validated using the TCGA database (n = 667).ResultsOur results revealed an elevated expression of BTN3A1 in glioblastoma (grade 4), as evidenced in both the TCGA database and our cohort of Moroccan glioma patients. Within the TCGA cohort, BTN3A1 expression was notably higher in patients with wild-type IDH. We observed a positive correlation between BTN3A1 expression and immune infiltration of B cells, CD8+ T cells, naive CD4+ T cells, and M2 macrophages. Patients exhibiting increased BTN3A1 expression also presented elevated levels of TGF‐β, IL‐10, and TIM‐3 compared to those with reduced BTN3A1 expression. Notably, patients with high BTN3A1 expression were associated with a poorer prognosis than their counterparts with lower expression.ConclussionOur findings suggest that BTN3A1 might promote the establishment of an immunosuppressive microenvironment. Consequently, targeting BTN3A1 could offer novel therapeutic avenues for the management of advanced gliomas.

Résumé : Depuis 2019, le Niger, est touché par des problèmes sociaux et surtout alimentaires à cause du contexte mondial et de leurs problèmes internes. Les prix des denrées alimentaires ne cessent de croitre au point de créer des mécontentements sociaux du fait de la cherté de la vie dans les ménages nigériens. Il est question dans cet article de montrer les facteurs susceptibles de créer des émeutes de la faim et les conséquences qui en résultent. L’objectif est de présenter la Covid 19, la Guerre Russo-Ukrainienne et le changement climatique comme des facteurs bouleversant la vie alimentaire de cet état africain. Mieux, il met l’accent sur les techniques de ce pays pour remédier à l’accès facile des produits alimentaires. La réalisation de ce travail, s’est appuyée sur la collecte de sources orales, écrites et les audio-visuelles. Ainsi, nous avons mené des enquêtes individuelles, la retranscription et la confrontation des données avec objectivité scientifique pour en tirer la vérité historique. Mots-clés : Covid19, Guerre Russie –Ukraine, Émeutes de la faim, Niger.

Plant-parasitic nematodes are a major threat to crop production in all agricultural systems. The scarcity of classical resistance genes highlights a pressing need to find new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality phased genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major parasitism stages. Analysis of the hologenome of the plant-nematode infection site identified metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that a highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is required for full pathogenicity. Knockout of either plant-encoded or now nematode-encoded steps in the pathway significantly reduces parasitic success. Our experiments establish a reference for cyst nematodes, further our understanding of the evolution of plant-parasitism by nematodes, and show that congruent differential expression of metabolic pathways in the infection hologenome represents a new way to find nematode susceptibility genes. The approach identifies genome-editing-amenable targets for future development of nematode-resistant crops.

With climate change and intensification of the hydrological cycle, the stationarity of hydrological variables is becoming questionable, requiring appropriate flood assessment models. Frequency analysis is widely used for flood forecasting. This study aims to determine the most suitable models (stationary and non-stationary) for estimating the maximum flows observed at some stations spread across West Africa. A statistical analysis of the annual maximum flows in terms of homogeneity, stationarity, and independence was carried out through the Pettitt, modified Mann–Kendall, and Wald–Wolfowitz tests, respectively, to identify the stations whose flows are non-stationary. After that, the best-correlated climate covariates with the annual maximum flows of the non-stationary stations were determined. The covariates explored are the climatic indices of sea surface temperatures (SST). Finally, different non-stationary GEV models were derived by varying the scale and position parameters of the best-correlated index for each station. The results indicate that 56% of the annual maximum flow series are non-stationary. As per the Bayes information criterion (BIC) values, the performance of the non-stationary models (GEV, generalized extreme values) is largely greater than that of the stationary models. These good performances of non-stationary models using climatic indices open perspectives for the prediction of extreme flows in the study area.

BackgroundThe crosstalk between the immune system and cancer cells has aroused considerable interest over the past decades. To escape immune surveillance cancer cells evolve various strategies orchestrating tumor microenvironment. The discovery of the inhibitory immune checkpoints was a major breakthrough due to their crucial contribution to immune evasion. The A2AR receptor represents one of the most essential pathways within the TME. It is involved in several processes such as hypoxia, tumor progression, and chemoresistance. However, its clinical and immunological significance in human breast cancer remains elusive.MethodsThe mRNA expression and protein analysis were performed by RT-qPCR and immunohistochemistry. The log-rank (Mantel-Cox) test was used to estimate Kaplan-Meier analysis for overall survival. Using large-scale microarray data (METABRIC), digital cytometry was conducted to estimate cell abundance. Analysis was performed using RStudio software (7.8 + 2023.03.0) with EPIC, CIBERSORT, and ImmuneCellAI algorithms. Tumor purity, stromal and immune scores were calculated using the ESTIMATE computational method. Finally, analysis of gene set enrichment (GSEA) and the TISCH2 scRNA-seq database were carried out.ResultsGene and protein analysis showed that A2AR was overexpressed in breast tumors and was significantly associated with high grade, elevated Ki-67, aggressive molecular and histological subtypes, as well as poor survival. On tumor infiltrating immune cells, A2AR was found to correlate positively with PD-1 and negatively with CTLA-4. On the other hand, our findings disclosed more profuse infiltration of protumoral cells such as M0 and M2 macrophages, Tregs, endothelial and exhausted CD8+ T cells within A2ARhigh tumors. According to the Single-Cell database, A2AR is expressed in malignant, stromal and immune cells. Moreover, it is related to tumor purity, stromal and immune scores. Our results also revealed that CD8+T cells from A2ARhigh patients exhibited an exhausted functional profile. Finally, GSEA analysis highlighted the association of A2AR with biological mechanisms involved in tumor escape and progression.ConclusionThe present study is the first to elucidate the clinical and immunological relevance of A2AR in breast cancer patients. In light of these findings, A2AR could be deemed a promising therapeutic target to overcome immune evasion prevailing within the TME of breast cancer patients.

Plant-parasitic nematodes are a threat to crop production. Combining bioinformatics, genetic and biochemical approaches, the authors show that the plant pathogen beet cyst nematode possesses an incomplete vitamin B5 synthesis pathway, of potential prokaryotic origin, complemented by its plant host.

Abstract A field spray drift experiment using florpyrauxifen-benzyl was conducted to measure drift from commercial ground and aerial applications, evaluate soybean [Glycine max (L.) Merr.] impacts, and compare to United States Environmental Protection Agency (US EPA) drift models. Collected field data were consistent with US EPA model predictions. Generally, with both systems applying a Coarse spray in a 13-kph average wind speed, the aerial application had a 5.0- to 8.6-fold increase in drift compared to the ground application, and subsequently, a 1.7- to 3.6-fold increase in downwind soybean injury. Soybean reproductive structures were severely reduced following herbicide exposure, potentially negatively impacting pollinator foraging sources. Approximately a 25% reduction of reproductive structures up to 30.5-m downwind and nearly a 100% reduction at 61-m downwind were observed for ground and aerial applications, respectively. Aerial applications would require three to five swath width adjustments upwind to reduce drift potential similar to ground applications.

IntroductionUveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4.MethodsEvaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM.Results and discussionOur results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.

IntoroductionNuclear receptor subfamily 2 group F member 6 (NR2F6) is a promising checkpoint target for cancer immunotherapy. However, there has been no investigation of NR2F6 in glioma. Our study systematically explored the clinical characteristics and biological functions of NR2F6 in gliomas.MethodsWe extracted RNA sequencing (RNA-seq) data of 663 glioma samples from The Cancer Genome Atlas (TCGA) as the training cohort and 325 samples from the Chinese Glioma Genome Atlas (CGGA) as the validation cohort. We also confirmed the NR2F6 gene expression feature in our own cohort of 60 glioma patients. R language and GraphPad Prism softwares were mainly used for statistical analysis and graphical work.ResultsWe found that NR2F6 was significantly related to high tumor aggressiveness and poor outcomes for glioma patients. Functional enrichment analysis demonstrated that NR2F6 was associated with many biological processes that are related to glioma progression, such as angiogenesis, and with multiple immune-related functions. Moreover, NR2F6 was found to be significantly correlated with stromal and immune infiltration in gliomas. Subsequent analysis based on Gliomas single-cell sequencing datasets showed that NR2F6 was expressed in immune cells, tumor cells, and stromal cells. Mechanistically, results suggested that NR2F6 might act as a potential immunosuppression-mediated molecule in the glioma microenvironment through multiple ways, such as the recruitment of immunosuppressive cells, secretion of immunosuppressive cytokines, M2 polarization of macrophages, in addition to combining with other immune checkpoint inhibitors.ConclusionOur findings indicated that intracellular targeting of NR2F6 in both immune cells and tumor cells, as well as stromal cells, may represent a promising immunotherapeutic strategy for glioma. Stromal cells, may represent a promising immunotherapeutic strategy for glioma.

Gliomas are considered one of the most malignant cancers in the body. Despite current therapies, including surgery, chemotherapy, and radiotherapy, these tumors usually recur with more aggressive and resistant phenotypes. Indeed, the survival following these conventional therapies is very poor, which makes immunotherapy the subject of active research at present. The anti-tumor immune response could also be considered a prognostic factor since each stage of cancer development is regulated by immune cells. However, glioma microenvironment contains malignant cells that secrete numerous chemokines, cytokines and growth factors, promoting the infiltration of immunosuppressive cells into the tumor, which limit the functioning of the immune system against glioma cells. Recently, researchers have been able to reverse the immune resistance of cancer cells and thus activate the anti-tumor immune response through different immunotherapy strategies. Here, we review the general concept of glioma’s immune microenvironment and report the impact of its distinct components on the anti-tumor immune response. We also discuss the mechanisms of glioma cell evasion from the immune response and pinpoint some potential therapeutic pathways, which could alleviate such resistance.

IntroductionAmong all types of central nervous system cancers, glioma remains the most frequent primary brain tumor in adults. Despite significant advances in immunomodulatory therapies, notably immune checkpoint inhibitors, their effectiveness remains constrained due to glioma resistance. The discovery of TMIGD2 (Transmembrane and Immunoglobulin Domain Containing 2) as an immuno-stimulatory receptor, constitutively expressed on naive T cells and most natural killer (NK) cells, has emerged as an attractive immunotherapy target in a variety of cancers. The expression profile of TMIGD2 and its significance in the overall survival of glioma patients remains unknown.MethodsIn the present study, we first assessed TMIGD2 mRNA expression using the Cancer Genome Atlas (TCGA) glioma transcriptome dataset (667 patients), followed by validation with the Chinese Glioma Genome Atlas (CGGA) cohort (693 patients). Secondly, we examined TMIGD2 protein staining in a series of 25 paraffin-embedded blocks from Moroccan glioma patients. The statistical analysis was performed using GraphPad Prism 8 software.ResultsTMIGD2 expression was found to be significantly higher in astrocytoma, IDH-1 mutations, low-grade, and young glioma patients. TMIGD2 was expressed on immune cells and, surprisingly, on tumor cells of glioma patients. Interestingly, our study demonstrated that TMIGD2 expression was negatively correlated with angiogenesis, hypoxia, G2/M checkpoint, and epithelial to mesenchymal transition signaling pathways. We also demonstrated that dendritic cells, monocytes, NK cells, gd T cells, and naive CD8 T cell infiltration correlates positively with TMIGD2 expression. On the other hand, Mantel-Cox analysis demonstrated that increased expression of TMIGD2 in human gliomas is associated with good overall survival. Cox multivariable analysis revealed that TMIGD2 is an independent predictor of a good prognosis in glioma patients.DiscussionTaken together, our results highlight the tight implication of TMIGD2 in glioma progression and show its promising therapeutic potential as a stimulatory target for immunotherapy.

Breast cancer is the most common type of tumor in women worldwide. Immune checkpoint inhibitors, particularly anti-PDL1, have shown promise as a therapeutic approach for managing this disease. However, this type of immunotherapy still fails to work for some patients, leading researchers to explore alternative immune checkpoint targets. The Ig suppressor of T cell activation domain V (VISTA) has emerged as a novel immune checkpoint that delivers inhibitory signals to T cells and has demonstrated encouraging results in various cancers. Our study investigated the association of VISTA expression with clinicopathological parameters in breast cancer patients, its involvement in the Epithelial-Mesenchymal-Transition (EMT) process, and its correlation with PD1 expression. Transcriptomic analysis revealed that VISTA was associated with lobular and metaplastic histological type, tumor size, lymph node status, ER and PR negative status, and the TNBC molecular subtype. Furthermore, VISTA expression was strongly associated with an immunosuppressive tumor microenvironment. Immunohistochemistry analysis corroborated the transcriptomic results, indicating that VISTA was expressed in most immune cells (94%) and was significantly expressed in breast cancer tumor cells compared to matched adjacent tissues. Our study also showed for the first time that VISTA overexpression in breast cancer cells could be associated with the EMT process. Additionally, we identified a positive correlation between VISTA and PD-1 expression. Together, these results highlight the immunosuppressive effect of VISTA in breast cancer patients and suggest that bi-specific targeting of VISTA and PD-1 in combination therapy could be beneficial for these patients.

The interplay between immune cells and malignant cells represents an essential chapter in the eradication of breast cancer. This widely distributed and diverse form of cancer represents a major threat to women worldwide. The incidence of breast cancer is related to several risk factors, notably genetic predisposition and family antecedents. Despite progress in treatment modalities varying from surgery and chemotherapy to radiotherapy and targeted therapies, persistently high rates of recurrence, metastasis, and treatment resistance underscore the urgent need for new therapeutic approaches. Immunotherapy has gained considerable ground in the treatment of breast cancer, as it takes advantage of the complex interactions within the tumor microenvironment. This dynamic interplay between immune and tumor cells has become a key point of focus in immunological research. This study investigates the role of various cancer markers, such as neoantigens and immune regulatory genes, in the diagnosis and treatment of breast tumors. Moreover, it explores the future potential of immune checkpoint inhibitors as therapeutically effective agents, as well as the challenges that prevent their efficacy, in particular tumor-induced immunosuppression and the difficulty of achieving tumor specificity. [ABSTRACT FROM AUTHOR]

Over the last decades, extracellular vesicles (EVs) have become increasingly popular for their roles in various pathologies, including cancer and neurological and immunological disorders. EVs have been considered for a long time as a means for normal cells to get rid of molecules it no longer needs. It is now well established that EVs play their biological roles also following uptake or by the interaction of EV surface proteins with cellular receptors and membranes. In this review, we summarize the current status of EV production and secretion in glioblastoma, the most aggressive type of glioma associated with high mortality. The main purpose is to shed light on the EVs as a universal mediator of interkingdom and intrakingdom communication in the context of tumor microenvironment heterogeneity. We focus on the immunomodulatory EV functions in glioblastoma-immune cross-talk to enhance immune escape and reprogram tumor-infiltrating immune cells. We critically examine the evidence that GBM-, immune cell-, and microbiome-derived EVs impact local tumor microenvironment and host immune responses, and can enter the circulatory system to disseminate and drive premetastatic niche formation in distant organs. Taking into account the current state of the art in intratumoral microbiome studies, we discuss the emerging role of bacterial EV in glioblastoma and its response to current and future therapies including immunotherapies. [ABSTRACT FROM AUTHOR]

A broadband 77/79 GHz transmitter (TX) front-end for automotive long range radar (LRR) and short range radar (SRR) applications is presented in this paper. To achieve the best system performance one new TX architecture with two specifically designed voltage controlled oscillators (VCOs) is implemented in a 28 nm CMOS technology. Furthermore, the degradation of the VCO phase noise due to the TX integration is analyzed in detail and solutions to minimize the impacts are proposed and verified. Experimental results of a 20 GHz push-push VCO1 measured at the 77 GHz TX output show a continuous tuning range of 4.75 GHz, a coarse tuning range of 3.2 GHz and an average phase noise of −100 dBc/Hz @ 1 MHz, while a 26 GHz VCO2 with third harmonic signal extraction achieves a continuous and coarse tuning range of 7.5 GHz and 4.2 GHz with an average phase noise of −96 dBc/Hz @ 1 MHz at 79 GHz TX output. Moreover, a record pushing performance of $\rm { 100 MHz/V at 77/79 GHz TX output has been achieved according to the authors’ best knowledge. The whole TX chip consumes about 860 mW from a single 2.1 V supply while providing more than 16 dBm output power over the whole frequency band.

Cotonou, the economic capital of Benin, is suffering from the impacts of climate change, particularly evident through recurrent floods. To effectively manage these floods and address this issue, it is crucial to have a deep understanding of return periods and hydroclimatic parameters (such as intensity-duration-frequency (IDF) curves and related coefficients), which are essential for designing stormwater drainage structures. Determining return periods and these parameters requires statistical analysis of extreme events, and this analysis needs to be regularly updated in response to climate change. The objective of this study was to determine the necessary return periods and hydroclimatic parameters to improve stormwater drainage systems in the city and its surroundings areas. This required annual maximum precipitation series of 1, 2, 3, 6, 12, and 24 h for 20 years length (1999–2018) as well as flood record data. The intensity series, derived by dividing the amount of rainfall by its duration, was adjusted using Gumbel’s law. IDF curves were constructed based on Montana and Talbot models, and their coefficients were determined according to the corresponding return periods. In 2010, which witnessed devastating floods in the country, the return period for the most intense rainfall events was 40 years, followed by 2013 with a return period of 13.4 years. Consequently, the commonly used 10-year return period for the design of stormwater drainage structures in Cotonou is insufficient. The Talbot model produced the lowest mean square errors for each quantile series and coefficients of determination closest to one, indicating that the parameters obtained from this model are well suited for designing hydraulic structures in Cotonou. The hydroclimatic parameters presented in this study will contribute to the improved design of hydraulic structures in the city of Cotonou.

When nematodes invade and subsequently migrate within plant roots, they generate cell wall fragments (in the form of oligogalacturonides; OGs) that can act as damage-associated molecular patterns and activate host defence responses. However, the molecular mechanisms mediating damage responses in plant-nematode interactions remain unexplored. Here, we characterized the role of a group of cell wall receptor proteins in Arabidopsis, designated as polygalacturonase-inhibiting proteins (PGIPs), during infection with the cyst nematode Heterodera schachtii and the root-knot nematode Meloidogyne incognita. PGIPs are encoded by a family of two genes in Arabidopsis, and are involved in the formation of active OG elicitors. Our results show that PGIP gene expression is strongly induced in response to cyst nematode invasion of roots. Analyses of loss-of-function mutants and overexpression lines revealed that PGIP1 expression attenuates infection of host roots by cyst nematodes, but not root-knot nematodes. The PGIP1-mediated attenuation of cyst nematode infection involves the activation of plant camalexin and indole-glucosinolate pathways. These combined results provide new insights into the molecular mechanisms underlying plant damage perception and response pathways during infection by cyst and root-knot nematodes, and establishes the function of PGIP in plant resistance to cyst nematodes.

Genomic surveillance is key to elucidate coronavirus disease (COVID-19) transmission chains and to monitor emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants associated with partial or complete immune escape [...]

Intense transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Africa might promote emergence of variants. We describe 10 SARS-CoV-2 lineages in Benin during early 2021 that harbored mutations associated with variants of concern. Benin-derived SARS-CoV-2 strains were more efficiently neutralized by antibodies derived from vaccinees than patients, warranting accelerated vaccination in Africa.

Abstract In human gliomas, anti-tumor T cell responses are inhibited through induction of local and systemic immunosuppression. Immune checkpoint blockade is proving to be a success in several types of cancers. However, many studies reported that the treatment of glioblastoma patients with anti-CTLA-4 or anti-PD-1 has no survival benefit compared to standard chemotherapy. This study aimed to investigate the expression and role of VISTA, a newly described immune checkpoint regulator, in human gliomas. mRNA expression was assessed in a total of 87 samples from glioma patients. 57 glioma tissues were taken at different grades. 20 peripheral blood mononuclear cells (PBMC) samples were taken before surgery and ten after surgery, all from the same set of patients. As for the control, ten specimens of PBMC were taken from healthy donors. Protein expression using immunohistochemistry was performed for 30 patients. The Cancer Genome Atlas (TCGA) data set, was also used to investigate VISTA expression through analysis of RNA-seq data of 667 glioma patients. In the Moroccan cohort, VISTA gene expression was significantly upregulated in glioma tissues related to PBMC of healthy donors. This high expression was specific to patient tissues since VISTA expression in PBMC was low when assessed either before or after surgery. Besides, VISTA exhibited higher expression levels in grade III/IV relative to grade I/II glioma patients. Interestingly, VISTA correlated positively with PD-1 expression. PD-1 also showed elevated expressions in higher glioma grades. The TCGA cohort corroborated these observations. Indeed, VISTA was also found to be strongly expressed in high grades. It was positively correlated with other critical immune checkpoints. Finally, increased VISTA transcript levels were associated with weak overall survival of glioma patients. Our study highlighted a correlation between high levels of VISTA expression and poor prognosis in glioma patients. VISTA might be involved in glioma progression and could be considered as a possible new therapeutic target, especially in advanced gliomas.

West African populations are increasingly exposed to heavy rainfall events which cause devastating floods. For the design of rainwater drainage facilities (to protect populations), practitioners systematically use the Gumbel distribution regardless of rainfall statistical behaviour. The objective of this study is twofold. The first is to update existing knowledge on heavy rainfall frequency analysis in West Africa to check whether the systematic preference for Gumbel's distribution is not misleading, and subsequently to quantify biases induced by the use of the Gumbel distribution on stations fitting other distributions. Annual maximum daily rainfall of 12 stations located in the Benin sections of the Niger and Volta Rivers' basins covering a period of 96 years (1921–2016) were used. Five statistical distributions (Gumbel, GEV, Lognormal, Pearson type III, and Log-Pearson type III) were used for the frequency analysis and the most appropriate distribution was selected based on the Akaike (AIC) and Bayesian (BIC) criteria. The study shows that the Gumbel's distribution best represents the data of 2/3 of the stations studied, while the remaining 1/3 of the stations fit better GEV, Lognormal, and Pearson type III distributions. The systematic application of Gumbel's distribution for the frequency analysis of extreme rainfall is therefore misleading. For stations whose data best fit the other distributions, annual daily rainfall maxima were estimated both using these distributions and the Gumbel's distribution for different return periods. Depending on the return period, results demonstrate that the use of the Gumbel distribution instead of these distributions leads to an overestimation (of up to +6.1 %) and an underestimation (of up to −45.9 %) of the annual daily rainfall maxima and therefore to an uncertain design of flood protection facilities. For better validity, the findings presented here should be tested on larger datasets.