Guillaume Brachet

📃Scientific paper: Validation of a Disease-Free Survival Prediction Model Using UBE2C and Clinical Indicators in Breast Cancer Patients Abstract: OBJECTIVE: To explore the validation of a disease-free survival (DFS) model for predicting disease progression based on the combination of ubiquitin-conjugating enzyme E2 C (UBE2C) levels and clinical indicators in breast cancer patients. METHODS: We enrolled 121 patients with breast cancer, collected their baseline characteristics and follow-up data, and analyzed the UBE2C levels in tumor tissues. We studied the relationship between UBE2C expression in tumor tissues and disease progression events of patients. We used the Kaplan-Meier method for identifying the disease-free survival rate of patients, and the multivariate Cox regression analysis to study the risk factors affecting the prognosis of patients. We sought to develop and validate a model for predicting disease progression. RESULTS: We found that the level of expression of UBE2C could effectively distinguish the prognosis of patients. In the Receiver Operating Characteristic (ROC) curve analysis, the Area under the ROC Curve (AUC) = 0.826 (0.714–0.938) indicating that high levels of UBE2C was a high-risk factor for poor prognosis. After evaluating different models using the ROC curve, Concordance index (C-index), calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement Index (IDI), and other methods, we finally developed a model for the expression of Tumor-Node (TN) staging using Ki-67 and UBE2C, which had an AUC=0.870, 95% CI of 0.786–0.953. The traditional TN model had an... Continued on ES/IODE ➡️ https://etcse.fr/fbydQ ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: IL-7 as an adjuvant in mucosal vaccination against viral respiratory infections;Utilisation de l'IL-7 comme adjuvant de vaccination muqueuse contre les infections virales respiratoires Abstract: Mucosae are a prime site for infections, since they are the gateway to many pathogens. However, few vaccines have been developed to specifically target mucosal immunity. Recent data from our laboratory evidenced a local expression of IL-7 in intestinal mucosa during the acute phase of SIV infection in macaques. Acting as a danger signal, this overexpression of IL-7 led to chemokine production and immune cell infiltration to this mucosa. In addition, systemic injection of IL-7 to macaques rapidly stimulated both the production of chemokines and immune cells homing toward various mucosae (lung, intestine, skin). These results altogether suggest that IL-7 could be used as a mucosal vaccine adjuvant. At first, I confirmed that IL-7 was a danger signal, but this time for the lung mucosa. Indeed, during the acute phase of influenza virus (IAV) infection, an overproduction of IL-7 was observed in the lung mucosa. In line with data from our laboratory, this overexpression is followed by the production of different chemokines. Then, we wanted to understand in more detail the mechanisms of action of IL-7 on the pulmonary mucosa. To do this, mice received an intratracheal administration of IL-7, then they were sacrificed at different post administration time points. The results showed that IL-7 rapidly induced the production of various proinflammatory chemokines and cytokines in the lung mucosa. The local inflammation was transient, since at D10 post administration, the ex... Continued on ES/IODE ➡️ https://etcse.fr/JCw ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: IL-7 as an adjuvant in mucosal vaccination against viral respiratory infections;Utilisation de l'IL-7 comme adjuvant de vaccination muqueuse contre les infections virales respiratoires Abstract: Mucosae are a prime site for infections, since they are the gateway to many pathogens. However, few vaccines have been developed to specifically target mucosal immunity. Recent data from our laboratory evidenced a local expression of IL-7 in intestinal mucosa during the acute phase of SIV infection in macaques. Acting as a danger signal, this overexpression of IL-7 led to chemokine production and immune cell infiltration to this mucosa. In addition, systemic injection of IL-7 to macaques rapidly stimulated both the production of chemokines and immune cells homing toward various mucosae (lung, intestine, skin). These results altogether suggest that IL-7 could be used as a mucosal vaccine adjuvant. At first, I confirmed that IL-7 was a danger signal, but this time for the lung mucosa. Indeed, during the acute phase of influenza virus (IAV) infection, an overproduction of IL-7 was observed in the lung mucosa. In line with data from our laboratory, this overexpression is followed by the production of different chemokines. Then, we wanted to understand in more detail the mechanisms of action of IL-7 on the pulmonary mucosa. To do this, mice received an intratracheal administration of IL-7, then they were sacrificed at different post administration time points. The results showed that IL-7 rapidly induced the production of various proinflammatory chemokines and cytokines in the lung mucosa. The local inflammation was transient, since at D10 post administration, the ex... Continued on ES/IODE ➡️ https://etcse.fr/JCw ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: IL-7 as an adjuvant in mucosal vaccination against viral respiratory infections;Utilisation de l'IL-7 comme adjuvant de vaccination muqueuse contre les infections virales respiratoires Abstract: Mucosae are a prime site for infections, since they are the gateway to many pathogens. However, few vaccines have been developed to specifically target mucosal immunity. Recent data from our laboratory evidenced a local expression of IL-7 in intestinal mucosa during the acute phase of SIV infection in macaques. Acting as a danger signal, this overexpression of IL-7 led to chemokine production and immune cell infiltration to this mucosa. In addition, systemic injection of IL-7 to macaques rapidly stimulated both the production of chemokines and immune cells homing toward various mucosae (lung, intestine, skin). These results altogether suggest that IL-7 could be used as a mucosal vaccine adjuvant. At first, I confirmed that IL-7 was a danger signal, but this time for the lung mucosa. Indeed, during the acute phase of influenza virus (IAV) infection, an overproduction of IL-7 was observed in the lung mucosa. In line with data from our laboratory, this overexpression is followed by the production of different chemokines. Then, we wanted to understand in more detail the mechanisms of action of IL-7 on the pulmonary mucosa. To do this, mice received an intratracheal administration of IL-7, then they were sacrificed at different post administration time points. The results showed that IL-7 rapidly induced the production of various proinflammatory chemokines and cytokines in the lung mucosa. The local inflammation was transient, since at D10 post administration, the ex... Continued on ES/IODE ➡️ https://etcse.fr/JCw ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Editoriale da la Revue Prescrire International "A tale of risk Each drug has its own story. Some are fine tales of discovery: the discovery of a rare or not so rare disease, its serious or not so serious consequences, its natural course and causes, and then an effective treatment. In the best stories, the treatment benefits numerous patients for a very long time, its risks are considered acceptable, and the price society pays for it is fair. Often though, it’s an everyday story of markets, target populations, territories, influence, and so on, hard fought for and won. In short, a story that revolves around money… And for some drugs, the story ends. Perhaps the drug was withdrawn from the market, pulled discreetly and silently from the shelves, even though such decisions often indicate that the drug was more dangerous than beneficial, or that it was no longer sufficiently profitable. Or it might go out with more of a bang, with those who promoted the drug facing justice for the public health disaster it caused, and those responsible having to explain themselves in court. Sometimes the end was premeditated, to insidiously orchestrate the imminent arrival of a new drug, to fabricate a need or manufacture a shortage. What do these stories have in common? They all revolve around the same main characters: patients. It is patients who live with the disease and all of its consequences. It is patients who form groups to have their voices heard and to advance research. It is volunteers and patients who contribute to research by participating in preliminary studies, then in clinical trials, their bodies used to experiment with new substances, with no certainty whatsoever over the nature of the effects these substances will produce. It is patients who describe, or sometimes report, unexpected or serious adverse effects. Effects that may have severe sequelae, even when the drug responsible has been withdrawn, or even end in tragedy for some patients and the family and friends they leave behind. Whatever the drug, its story and how it is told, it is always patients who are exposed to the risks of diseases for which no acceptable treatment exists. But it is also patients who are exposed to the risks of inadequately evaluated drugs. Prescrire"

📃Scientific paper: Influenza viral infection consequences on endomembrane dynamics and stress signaling;Conséquences de l'infection des virus influenza sur l'appareillage membranaire et la signalisation de stress cellulaire Abstract: Influenza viruses are a major public health threat considering their high rates of fatality and morbidity. Upon virus entry, host cells experience modifications in endomembranes and organelles, including those used for virus trafficking and replication. Better understanding how viral infection could alter specifically organelles morphodynamics and contribute to cell adaptation to viral replication is essential to develop innovative anti-viral therapeutics strategies. The goal of my PhD project was to investigate endomembranes alteration during influenza viral infection. Using stress-adapted experimental framework, I show that influenza virus infection modifies mitochondria morphodynamics by promoting mitochondrial elongation and by altering endoplasmic reticulum (ER)-mitochondria tethering in host cells. My results suggest that virus induced mitochondria hyper-elongation is promoted by fission associated protein DRP1 relocalization to the cytosol, thus enhancing a pro-fusion status. Moreover, we identify a small organic molecule, we named Mito-C, which is addressed to mitochondria and rapidly provokes mitochondrial network fragmentation. Biochemical analyses reveal that Mito-C target the NEET protein family, previously reported to regulate mitochondrial iron and ROS homeostasis. One of the NEET proteins, NAF-1, is proposed in this study for the first time to play a role in regulation of mitochondria morphodynamics. Finally, I show that altering mitochondrial hyper-... Continued on ES/IODE ➡️ https://etcse.fr/T5 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Multiple independent introductions of highly pathogenic avian influenza H5 viruses during the 2020–2021 epizootic in France Abstract: International audience; During winter 2020-2021, France and other European countries were severely affected by highly pathogenic avian influenza H5 viruses of the Gs/GD/96 lineage, clade 2.3.4.4b. In total, 519 cases occurred, mainly in domestic waterfowl farms in Southwestern France. Analysis of viral genomic sequences indicated that 3 subtypes of HPAI H5 viruses were detected (H5N1, H5N3, H5N8), but most French viruses belonged to the H5N8 subtype genotype A, as Europe. Phylogenetic analyses of HPAI H5N8 viruses revealed that the French sequences were distributed in 9 genogroups, suggesting 9 independent introductions of H5N8 from wild birds, in addition to the 2 introductions of H5N1 and H5N3. Continued on ES/IODE ➡️ https://etcse.fr/IzJ5m ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Evaluation of the anti-infective potential of the seed endophytic fungi of Corchorus olitorius through metabolomics and molecular docking approach Abstract: Background Endophytic fungi are very rich sources of natural antibacterial and antifungal compounds. The main aim of this study is to isolate the fungal endophytes from the medicinal plant Corchorus olitorius seeds (F. Malvaceae ), followed by antimicrobial screening against various bacterial and fungal strains. Results Seven endophytic fungal strains belonging to different three genera were isolated, including Penicillium , Fusarium , and Aspergillus . The seven isolated endophytic strains revealed selective noticeable activity against Escherichia coli (ATCC25922) with varied IC_50s ranging from 1.19 to 10 µg /mL, in which Aspergillus sp. (Ar 6) exhibited the strongest potency against E. coli (ATCC 25,922) and candida albicans (ATCC 10,231) with IC_50s 1.19 and 15 µg /mL, respectively. Therefore, the chemical profiling of Aspergillus sp. (Ar 6) crude extract was performed using LC-HR-ESI-MS and led to the dereplication of sixteen compounds of various classes (1–16). In-silico analysis of the dereplicated metabolites led to highlighting the compounds responsible for the antimicrobial activity of Aspergillus sp. extract. Moreover, molecular docking showed the potential targets of the metabolites; Astellatol (5), Aspergillipeptide A (10), and Emericellamide C (14) against E. coli and C. albicans . Conclusion These results will expand the knowledge of endophytes and provide us with new approaches to face the global antibiotic resistance problem and the future production... Continued on ES/IODE ➡️ https://etcse.fr/354UF ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: An anti-influenza combined therapy assessed by single cell RNA-sequencing Abstract: Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA-sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types. We showed that each cell type comprises multiple sub-types, whose proportions are altered by H1N1 infection, and assessed the ability of the treatments to restore them. To the best of our knowledge this is the first study investigating the effectiveness of an antiviral therapy against influenza virus by single cell transcriptomic studies. When combined with interferon lambda, virucidal sialylated cyclodextrins inhibit the replication of a clinical H1N1 influenza strain in ex vivo human airway epithelia more efficiently than when delivered alone. Continued on ES/IODE ➡️ https://etcse.fr/d1s ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: An anti-influenza combined therapy assessed by single cell RNA-sequencing Abstract: Influenza makes millions of people ill every year, placing a large burden on the healthcare system and the economy. To develop a treatment against influenza, we combined virucidal sialylated cyclodextrins with interferon lambda and demonstrated, in human airway epithelia, that the two compounds inhibit the replication of a clinical H1N1 strain more efficiently when administered together rather than alone. We investigated the mechanism of action of the combined treatment by single cell RNA-sequencing analysis and found that both the single and combined treatments impair viral replication to different extents across distinct epithelial cell types. We showed that each cell type comprises multiple sub-types, whose proportions are altered by H1N1 infection, and assessed the ability of the treatments to restore them. To the best of our knowledge this is the first study investigating the effectiveness of an antiviral therapy against influenza virus by single cell transcriptomic studies. When combined with interferon lambda, virucidal sialylated cyclodextrins inhibit the replication of a clinical H1N1 influenza strain in ex vivo human airway epithelia more efficiently than when delivered alone. Continued on ES/IODE ➡️ https://etcse.fr/d1s ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: The impact of vascular access type on survival in haemodialysis: time for a paradigm shift? A prospective cohort study Abstract: Introduction Although arteriovenous autologous fistula is the vascular access of choice due to better long-term outcome than central venous catheters, the use of central venous catheters is increasing. Our study aims to describe the survival and epidemiological features of a cohort of dialysis patients with a focus on the role of vascular access. Methods Our study comprises a follow-up period from 2001 to 2020 in a single center. Descriptive analysis was performed on baseline data. Moreover, we analysed predictive variables of death with univariable and multivariable logistic regressions. Predictors of survival were analysed by univariable and multivariable Cox regression. Results Our analysis includes 754 patients undergoing chronic haemodialysis. In the multivariable logistic regression, the use of tunnelled catheters resulted protective against death from any cause (Odds Ratio 0.43; p  = 0.017). In the multivariable Cox analysis, being “late referral” was associated with decreased survival in the first 6 months since haemodialysis start (Hazard Ratio 3.79; p  = 0.001). In the subgroup of elderly (age ≥ 75 years) patients ( n  = 201/472) with a follow up of 7–60 months, multivariable logistic regression showed that tunnelled catheters at the start of haemodialysis were associated with lower mortality (Odds Ratio, 0.25; p  = 0.021), whereas vascular disease was found to be the main risk factor for death (Odds Ratio, 5.11; p  = 0.000). Moreover, vascular disease w... Continued on ES/IODE ➡️ https://etcse.fr/eYs1T ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Thyroid-related adverse events induced by immune checkpoint inhibitors Abstract: Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the “thyroid storm”. Early prediction of occurrence and detection of the thyroid irAEs should be a priority for the clinician, in order to avoid critical situations. Moreover, they are recently considered both a prognostic marker and a means of overseeing treatment response, since they indicate an efficient activation of the immune system. Therefore, a multidisciplinary approach including both oncologists and endocrinologists is recommended when immune checkpoint inhibitors are used in the clinic. Continued on ES/IODE ➡️ https://etcse.fr/ObXo ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: Evolutionary and temporal dynamics of emerging influenza D virus in Europe (2009-22) Abstract: International audience; Influenza D virus (IDV) is an emerging influenza virus that was isolated for the first time in 2011 in the USA from swine with respiratory illness. Since then, IDV has been detected worldwide in different animal species, and it was also reported in humans. Molecular epidemiological studies revealed the circulation of two major clades, named D/OK and D/660. Additional divergent clades have been described but have been limited to specific geographic areas (i.e. Japan and California). In Europe, IDV was detected for the first time in France in 2012 and subsequently also in Italy, Luxembourg, Ireland, the UK, Switzerland, and Denmark. To understand the time of introduction and the evolutionary dynamics of IDV on the continent, molecular screening of bovine and swine clinical samples was carried out in different European countries, and phylogenetic analyses were performed on all available and newly generated sequences. Until recently, D/OK was the only clade detected in this area. Starting from 2019, an increase in D/660 clade detections was observed, accompanied by an increase in the overall viral genetic diversity and genetic reassortments. The time to the most recent common ancestor (tMRCA) of all existing IDV sequences was estimated as 1995-16 years before its discovery, indicating that the virus could have started its global spread in this time frame. Despite the D/OK and D/660 clades having a similar mean tMRCA (2007), the mea... Continued on ES/IODE ➡️ https://etcse.fr/dxj ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.