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Abstract Usutu virus (USUV) and West Nile virus (WNV) are two closely related emerging mosquito-borne flaviviruses. Their natural hosts are wild birds, but they can also cause severe neurological disorders in humans. Both viruses are efficiently suppressed by type I interferon (IFN), which interferes with viral replication, dissemination, pathogenesis and transmission. Here, we show that the replication of USUV and WNV are inhibited through a common set of IFN–induced genes (ISGs), with the notable exception of ISG20, which USUV is resistant to. Strikingly, USUV was the only virus among all the other tested mosquito-borne flaviviruses that demonstrated resistance to the 3′–5′ exonuclease activity of ISG20. Our findings highlight that the intrinsic resistance of the USUV genome, irrespective of the presence of cellular or viral proteins or protective post-transcriptional modifications, relies on a unique sequence present in its 3′ untranslated region. Importantly, this genomic region alone can confer ISG20 resistance to a susceptible flavivirus, without compromising its infectivity, suggesting that it could be acquired by other flaviviruses. This study provides new insights into the strategy employed by emerging flaviviruses to overcome host defense mechanisms.

BackgroundArtemisia absinthium has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, represents a promising therapeutic approach. The bioactive compounds in A. absinthium could potentially inhibit NMT and serve as new treatment options for leishmaniasis.AimThis study aims to investigate the phytochemical composition, drug-likeness, and molecular dynamics of A. absinthium bioactive compounds targeting Leishmania NMT, identifying potent inhibitors that could serve as new drug candidates.MethodThe extract of A. absinthium was analyzed using High-Performance Liquid Chromatography (HPLC), identifying nine phenolic compounds, with kaempferol (10.72%) and chlorogenic acid (4.43%) being the most abundant. Drug-likeness and toxicity were evaluated using SwissADME and OSIRIS Property Explorer, focusing on adherence to Lipinski’s rule of five and Ghose’s filter. Molecular docking studies were conducted to evaluate the binding affinity of these compounds to NMT. Molecular dynamics (MD) simulations were performed to assess the stability and flexibility of the NMT-apigenin complex.ResultsMolecular docking identified apigenin as the most potent NMT inhibitor, with a binding energy of −9.6 kcal/mol, forming significant hydrogen bonds with threonine residues 203 and 189. Drug-likeness analysis revealed that most compounds adhered to Lipinski’s rule of five, indicating favorable pharmacokinetic properties. MD simulations confirmed the stability of the NMT-apigenin complex, with root mean square deviation (RMSD) values of 0.04 nm, root mean square fluctuation (RMSF) values between 0.05 and 0.35 nm, and radius of gyration (Rg) values ranging from 2.24 to 2.30 nm. Normal mode analysis further supported the complex’s stability and flexibility.ConclusionThe findings of this study underscore the potential of Artemisia absinthium compounds, particularly apigenin, as promising candidates for the development of new anti-leishmaniasis drugs. The potent inhibition of Leishmania NMT by apigenin, along with its favorable pharmacokinetic and stability profiles, supports its further exploration in antileishmanial drug development.

Objective: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer. Design: prospective, observational, multicenter cohort. Setting and participants: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score. Statistical methods: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni’ correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care). Results: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19–1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39–2.29] (p < 0.001). Conclusion: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer.

Urinary tract infections resulting from Escherichia coli, are prevalent and have become increasingly difficult to treat due to antibiotic resistance. This study aimed to explore the potential of propolis extract from beehives in Algeria’s Tiout region as a natural antibacterial agent against E. coli CECT_515. The phytochemical composition, antioxidant activity, and antibacterial action of the extract has been evaluated and compared to four synthetic antibiotics, both in vitro and in silico. The propolis extract had high levels of total polyphenol and total flavonoids, regarding its antioxidant properties, the extract showed an important ability of DPPH radicals scavenging, as determined by its IC50 value of 330.08±13.35 μg/mL. The excerpt showed important antibacterial efficacy against Escherichia coli, as demonstrated with important inhibition zones. The extract’s inhibitory effects were compared to four synthetic antibiotics, including gentamicin, pipemidic acid, cefazolin, and colistin, molecular docking analysis revealed that the propolis extract interacted with the active site of beta-lactamase, a protein responsible for antibiotic resistance, and showed binding affinities and conformational stability during molecular dynamics simulation for 250 ns. Overall, the results suggest that the propolis has significant antioxidant and antibacterial properties and could serve as a promising natural alternative to synthetic antibiotics for the treatment of E. coli infections.

Objectives: The primary objective of the present study was to evaluate and compare the ability of eight nutrition-related tools to predict 1-year mortality in older patients with cancer. Design, setting and participants: We studied older patients with cancer from the ELCAPA cohort and who had been referred for a geriatric assessment at one of 14 participating geriatric oncology clinics in the greater Paris area of France between 2007 and 2018. Measurements: The studied nutrition-related tools/markers were the body mass index (BMI), weight loss (WL) in the previous 6 months, the Mini Nutritional Assessment, the Geriatric Nutritional Risk Index (GNRI), the Prognostic Nutritional Index, the Glasgow Prognostic Score (GPS), the modified GPS, and the C-reactive protein/albumin ratio. Results: A total of 1361 patients (median age: 81; males: 51%; metastatic cancer: 49%) were included in the analysis. Most of the tools showed a progressively increase in the mortality risk as the nutrition-related risk category worsened (overall p-values

Abstract Background Anti-PD1/PDL1 immune checkpoint inhibitors (ICI) transformed the prognosis of patients with advanced non-small cell lung cancer (NSCLC). However, the response rate remains disappointing and toxicity may be life-threatening, making urgent identification of biomarkers predictive for efficacy. Immunologic Constant of Rejection signature (ICR) is a 20-gene expression signature of cytotoxic immune response with prognostic value in some solid cancers. Our objective was to assess its predictive value for benefit from anti-PD1/PDL1 in patients with advanced NSCLC. Methods We retrospectively profiled 44 primary tumors derived from NSCLC patients treated with ICI as single-agent in at least the second-line metastatic setting. Transcriptomic analysis was performed using the nCounter® analysis system and the PanCancer Immune Profiling Panel. We then pooled our data with clinico-biological data from four public gene expression data sets, leading to a total of 162 NSCLC patients treated with single-agent anti-PD1/PDL1. ICR was applied to all samples and correlation was searched between ICR classes and the Durable Clinical Benefit (DCB), defined as stable disease or objective response according to RECIST 1.1 for a minimum of 6 months after the start of ICI. Results The DCB rate was 29%; 22% of samples were classified as ICR1, 30% ICR2, 22% ICR3, and 26% ICR4. These classes were not associated with the clinico-pathological variables, but showed enrichment from ICR1 to ICR4 in quantitative/qualitative markers of immune response. ICR2-4 class was associated with a 5.65-fold DCB rate when compared with ICR1 class. In multivariate analysis, ICR classification remained associated with DCB, independently from PDL1 expression and other predictive immune signatures. By contrast, it was not associated with disease-free survival in 556 NSCLC TCGA patients untreated with ICI. Conclusion The 20-gene ICR signature was independently associated with benefit from anti-PD1/PDL1 ICI in patients with advanced NSCLC. Validation in larger retrospective and prospective series is warranted.

Abstract Background CIC‐rearranged sarcomas (CIC‐RS) represent the most frequent subset of “Ewing‐like” undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC‐RS included in the French NETSARC+ database. Methods Pediatric and adult patients from 13 French centers with a diagnosis of CIC‐RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC‐RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high‐grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan–Meier method and the log‐rank test was used to compare survival. Results Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2–87). With a median follow‐up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission. Conclusion FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen.

Abstract Background Because of previously reported ethnic differences in determinants and markers of obesity and related metabolic disorders, we sought to investigate circulating levels of adiponectin and their correlates in a sub-Saharan African (sSA) population. Subjects and Methods We studied 70 non-diabetic volunteers (33M/37F) living in Yaoundé, Cameroon, aged 24–69 yr, with BMI 20–42 kg/m2. In all participants we measured waist circumference and total body fat by bioimpedance, and obtained a fasting venous blood sample for measurement of plasma glucose, serum insulin and adiponectin concentrations. We performed a euglycaemic hyperinsulinaemic clamp in 1/4 subjects, and HOMAIR was used as surrogate of fasting insulin sensitivity index since it best correlates to clamp measurements. Results Males had lower adiponectin levels than females (8.8 ± 4.3 vs. 11.8 ± 5.5 μg/L). There was no significant correlation between adiponectin and total body fat (rs = -0.03; NS), whereas adiponectin was inversely correlated with waist circumference (rs = -0.39; p = 0.001). Adiponectin correlated negatively with insulin resistance (rs = -0.35; p = 0.01). In a regression analysis using fasting adiponectin concentration as the dependent variable, and age, HOMAIR, waist circumference, and fat mass as predictors, waist circumference (β = -3.30; p = 0.002), fat mass (β = -2.68; p = 0.01), and insulin resistance (β = -2.38; p = 0.02) but not age (β = 1.11; p = 0.27) were independent predictors of adiponectin. When considering gender, these relations persisted with the exception of waist circumference in females. Conclusion Adiponectin correlates in this study population are comparable to those observed in Caucasians with the exception of waist circumference in women. The metabolic significance of waist circumference is therefore questioned in sSA women.

This study presents the synthesis, characterization, and antimicrobial efficacy of a novel pyrazoline carboxamide heterocyclic compound. Synthesized through a two-step process, involving the formation of an α,β-unsaturated ketone and subsequent conversion into a pyrazoline carboxamide derivative, the compound's structure and functional groups were confirmed using FT-IR, 1H NMR, and DEPT-135 techniques. The compound demonstrated high purity and yield, displaying significant inhibitory zones against micro-organisms, notably Listeria monocytogenes (14.2 ± 0.0 mm to 16.8 ± 1.3 mm) and Candida albicans (10.9 ± 0.6 mm to 17.8 ± 1.5 mm). Evaluation of drug-likeness and toxicity highlighted its potential for drug development. Molecular dock-ing studies indicated strong binding affinities to key antimicrobial target proteins, including DNA gyrase, penicillin-binding protein, and C. albicans sterol 14-α-demethylase. Molecular dynamics simulations revealed the com-pound's structural flexibility. These results make this new compound a candidate for further exploration in drug development, highlighting its potential therapeutic applications.

Notre objectif est de montrer comment des films de science-fiction ont traité l’augmentation des facultés corporelles et cognitives. Ces imaginaires cinématographiques permettent de nous interroger sur l’intérêt de telles innovations. Ils dressent le tableau d’un monde dans lequel l’artificialisation et la mécanisation de nombreuses activités mènent à une perte de contrôle sur celles-ci, ce qui nous ferait courir le risque, à terme, d’être privés de nos qualités d’humains. Cependant, nous montrerons que ces films ne s’interrogent pas pour autant sur la viabilité de ce type de société. En effet, ces fictions n’insistent pas sur les contraintes que ces transformations font pourtant peser sur l’environnement. Face à la crise écologique l’emprise des innovations technologiques sur l’ensemble des sociétés, loin d’apparaître comme une solution, risque au contraire d’être identifiée comme une partie du problème.

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes. Results: Among 952 patients (median [IQR] age 66 [57–73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67–6.79]; p

The mechanical properties of biological tissues are key to their integrity and function. Here, the authors engineer 3D microtissues from optogenetically modified fibroblasts and use light to quantify tissue elasticity and strain propagation using their own constituent cells as internal actuators.

The ever increasing field of application of nanodielectrics in electrical insulations calls for description of the mechanisms underlying the performance of these systems and for identification of the signs exposing their aging under high electric fields. Such approach is of particular interest to electrically insulating polymers because their chemical defects are of deleterious nature for their electrical properties and can largely degrade their performance at high electric fields. Although these defects usually leave spectroscopic signatures in terms of characteristic luminescence peaks, it is nontrivial to assign, in an unambiguous way, the identified peaks to specific chemical groups or defects because of the low intensity of the signal with the main reason being that the insulating polymers are weakly emitting materials under electric field. In this work, we go beyond the conventional electroluminescence technique to record spectroscopic features of insulating polymers. By introducing a single plane of silver nanoparticles (AgNPs) at the near-surface of thin polypropylene films, the electroluminescent signal is strongly enhanced by surface plasmons processes. The presence of AgNPs leads not only to a much higher electroluminescence intensity but also to a strong decrease of the electric field threshold for detection of light emission and to a phase-stabilization of the recorded spectra, thus improving the assignment of the characteristic luminescence peaks. Besides, the performed analyses bring evidence on the capability of AgNPs to trap and eject charges, and on the possibility to adjust the energetics of charge carriers in electrically insulating polymers at the electrode/dielectric contact via AgNPs.

Abstract Background The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. Results Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (p

Cell-generated forces play a major role in coordinating the large-scale behavior of cell assemblies, in particular during development, wound healing, and cancer. Mechanical signals propagate faster than biochemical signals, but can have similar effects, especially in epithelial tissues with strong cell–cell adhesion. However, a quantitative description of the transmission chain from force generation in a sender cell, force propagation across cell–cell boundaries, and the concomitant response of receiver cells is missing. For a quantitative analysis of this important situation, here we propose a minimal model system of two epithelial cells on an H-pattern (‘cell doublet’). After optogenetically activating RhoA, a major regulator of cell contractility, in the sender cell, we measure the mechanical response of the receiver cell by traction force and monolayer stress microscopies. In general, we find that the receiver cells show an active response so that the cell doublet forms a coherent unit. However, force propagation and response of the receiver cell also strongly depend on the mechano-structural polarization in the cell assembly, which is controlled by cell–matrix adhesion to the adhesive micropattern. We find that the response of the receiver cell is stronger when the mechano-structural polarization axis is oriented perpendicular to the direction of force propagation, reminiscent of the Poisson effect in passive materials. We finally show that the same effects are at work in small tissues. Our work demonstrates that cellular organization and active mechanical response of a tissue are key to maintain signal strength and lead to the emergence of elasticity, which means that signals are not dissipated like in a viscous system, but can propagate over large distances.

Influenza A viruses (IAVs) possess a segmented genome consisting of eight viral RNAs (vRNAs) associated with multiple copies of viral nucleoprotein (NP) and a viral polymerase complex. Despite the crucial role of RNA structure in IAV replication, the impact of NP binding on vRNA structure is not well understood. In this study, we employed SHAPE chemical probing to compare the structure of NS and M vRNAs of WSN IAV in various states: before the addition of NP, in complex with NP, and after the removal of NP. Comparison of the RNA structures before the addition of NP and after its removal reveals that NP, while introducing limited changes, remodels local structures in both vRNAs and long-range interactions in the NS vRNA, suggesting a potentially biologically relevant RNA chaperone activity. In contrast, NP significantly alters the structure of vRNAs in vRNA/NP complexes, though incorporating experimental data into RNA secondary structure prediction proved challenging. Finally, our results suggest that NP not only binds single-stranded RNA but also helices with interruptions, such as bulges or small internal loops, with a preference for G-poor and C/U-rich regions.

In this paper, nanocomposites (TiO _2 in SiO _2 ) are produced by an advanced hybrid aerosol-PECVD method based on direct liquid injection of a non-commercial colloidal solution in an O _2 / hexamethyldisiloxane (HMDSO) low-pressure plasma. Dielectric properties are investigated at nanoscale using techniques derived from Atomic Force Microcopy in terms of relative dielectric permittivity, charge injection and transport. Results show that a concentration in TiO _2 up to 14% by volume makes it possible to increase the relative dielectric permittivity up to 4.8 while maintaining the insulating properties of the silica matrix. For a TiO _2 concentration in the range 15%–37% by volume, the relative dielectric permittivity increases (up to 11 for 37% TiO _2 by volume) and only few agglomerated nanoparticles lowering the insulating properties are observed. For TiO _2 concentration above 40% by volume, the relative dielectric permittivity still increases but the quantity of agglomerated nanoparticles is very high, which greatly increases the charge transport dynamic and degrades the insulating properties. Finally, 37% of TiO _2 by volume in the SiO _2 matrix appears to be the best compromise, between high dielectric permittivity and low leakage current for the MIM applications aimed.

The CTO-ARC (Chronic Total Occlusion Academic Research Consortium) recognized that a nonstandardized definition of chronic total occlusion (CTO) percutaneous coronary intervention approaches can bias the complications' attribution to each crossing strategy. The study sought to describe the numbers, efficacy, and safety of each final CTO crossing strategy according to CTO-ARC recommendations. In this cross-sectional study, data were retrieved from the European Registry of Chronic Total Occlusions between 2021 and 2022. Out of 8,673 patients, antegrade and retrograde approach were performed in 79.2% and 20.8% of cases, respectively. The antegrade approach included antegrade wiring and antegrade dissection and re-entry, both performed with or without retrograde contribution (antegrade wiring without retrograde contribution: n = 5,929 [68.4%]; antegrade wiring with retrograde contribution: n = 446 [5.1%]; antegrade dissection and re-entry without retrograde contribution: n = 353 [4.1%]; antegrade dissection and re-entry with retrograde contribution: n = 137 [1.6%]). The retrograde approach included retrograde wiring (n = 735 [8.4%]) and retrograde dissection and re-entry (n = 1,073 [12.4%]). Alternative antegrade crossing was associated with lower technical success (70% vs 86% vs 93.1%, respectively; P < 0.001) and higher complication rates (4.6% vs 2.9% vs 1%, respectively; P < 0.001) as compared with retrograde and true antegrade crossing. However, alternative antegrade crossing was applied mostly as a rescue strategy (96.1%). The application of CTO-ARC definitions allowed the reclassification of 6.7% of procedures as alternative antegrade crossing with retrograde or antegrade contribution which showed higher MACCE and lower technical success rates, as compared with true antegrade and retrograde crossing. [Display omitted] [ABSTRACT FROM AUTHOR]

In 2021, Campylobacteriosis was the main gastrointestinal disease in the European Union since 2007 according to the European Centre for Disease Prevention and Control. In the Republic of Ireland, the incidence of the disease is particularly high with approximately 3,000 cases per annum, raising significant concerns for national health authorities with an expected increase in the number of cases in the light of climate change. The current study sought to assess the spatio-temporal patterns of campylobacteriosis in the Republic of Ireland using 20,391 cases from January 2011 to December 2018. An ensemble of spatial statistics techniques including seasonal decomposition, spatial clustering and space-time scanning, were used to elucidate the main individual and spatio-temporal characteristics of the disease in the country. Findings revealed that cases from the paediatric age group (i.e., under 5 years old) were more likely to occur in rural areas (aOR: 1.1.27, CI 95% 1.14-1.41) while cases from the intermediate age group (i.e., >5 &

Abstract Background Nutritional impairment is common in cancer patients and is associated with poor outcomes. Only few studies focused on cachexia. We assessed the prevalence of cachexia in older cancer patients, identified associated risk factors, and evaluated its impact on 6 month overall mortality. Methods A French nationwide cross‐sectional survey (performed in 55 geriatric oncology clinics) of older cancer patients aged ≥70 referred for geriatric assessment prior to treatment choice and initiation. Demographic, clinical, and nutritional data were collected. The first outcome was cachexia, defined as loss of more than 5% of bodyweight over the previous 6 months, or a body mass index below 20 kg/m2 with weight loss of more than 2%, or sarcopenia (an impaired Strength, Assistance with walking, Rise from chair, Climb stairs and Falls score) with weight loss of more than 2%. The second outcome was 6 month overall mortality. Results Of the 1030 patients included in the analysis [median age (interquartile range): 83 (79–87); males: 48%; metastatic cancer: 42%; main cancer sites: digestive tract (29%) and breast (16%)], 534 [52% (95% confidence interval: 49–55%)] had cachexia. In the multivariate analysis, patients with breast (P

Les arts visuels sont parvenus à faire du zombie une figure incontournable de la culture populaire. Le médium cinématographique a contribué à construire avec lui un imaginaire du désastre sur fond de pandémie. Nous montrerons l’adéquation du zombie avec un imaginaire collectif pour lequel le monde à venir s’inscrit sous le signe de l’effondrement.

The Wnt-pathway has a critical role in development and tissue homeostasis and has attracted increased attention to develop anticancer drugs due to its aberrant activation in many cancers. In this study, we identified a novel small molecule series with a thienopyrimidine scaffold acting as a downstream inhibitor of the β-catenin-dependent Wnt-pathway. This novel chemotype was investigated using Wnt-dependent triple-negative breast cancer (TNBC) cell lines. Structure activity relationship (SAR) exploration led to identification of low micromolar compounds such as 5a, 5d, 5e and a novel series with quinazoline scaffold such as 9d. Further investigation showed translation of activity to inhibit cancer survival of HCC1395 and MDA-MB-468 TNBC cell lines without affecting a non-cancerous breast epithelial cell line MCF10a. This anti-proliferative effect was synergistic to docetaxel treatment. Collectively, we identified novel chemotypes acting as a downstream inhibitor of β-catenin-dependent Wnt-pathway that could expand therapeutic options to manage TNBC.

The Republic of Ireland regularly reports the highest annual crude incidence rates of Shiga toxin–producing Escherichia coli (STEC) enteritis in the European Union, ≈10 times the average. We investigated spatiotemporal patterns of STEC enteritis in Ireland using multiple statistical tools. Overall, we georeferenced 2,755 cases of infection during January 2013–December 2017; we found >1 case notified in 2,340 (12.6%) of 18,641 Census Small Areas. We encountered the highest case numbers in children 0–5 years of age (n = 1,101, 39.6%) and associated with serogroups O26 (n = 800, 29%) and O157 (n = 638, 23.2%). Overall, we identified 17 space-time clusters, ranging from 2 (2014) to 5 (2017) clusters of sporadic infection per year; we detected recurrent clustering in 3 distinct geographic regions in the west and mid-west, all of which are primarily rural. Our findings can be used to enable targeted epidemiologic intervention and surveillance.

Abstract Understanding patient progression from symptomatic COVID-19 infection to a severe outcome represents an important tool for improved diagnoses, surveillance, and triage. A series of models have been developed and validated to elucidate hospitalization, admission to an intensive care unit (ICU) and mortality in patients from the Republic of Ireland. This retrospective cohort study of patients with laboratory-confirmed symptomatic COVID-19 infection included data extracted from national COVID-19 surveillance forms (i.e., age, gender, underlying health conditions, occupation) and geographically-referenced potential predictors (i.e., urban/rural classification, socio-economic profile). Generalised linear models and recursive partitioning and regression trees were used to elucidate COVID-19 progression. The incidence of symptomatic infection over the study-period was 0.96% (n = 47,265), of whom 3781 (8%) required hospitalisation, 615 (1.3%) were admitted to ICU and 1326 (2.8%) died. Models demonstrated an increasingly efficacious fit for predicting hospitalization [AUC 0.816 (95% CI 0.809, 0.822)], admission to ICU [AUC 0.885 (95% CI 0.88 0.89)] and death [AUC of 0.955 (95% CI 0.951 0.959)]. Severe obesity (BMI ≥ 40) was identified as a risk factor across all prognostic models; severely obese patients were substantially more likely to receive ICU treatment [OR 19.630] or die [OR 10.802]. Rural living was associated with an increased risk of hospitalization (OR 1.200 (95% CI 1.143–1.261)]. Urban living was associated with ICU admission [OR 1.533 (95% CI 1.606–1.682)]. Models provide approaches for predicting COVID-19 prognoses, allowing for evidence-based decision-making pertaining to targeted non-pharmaceutical interventions, risk-based vaccination priorities and improved patient triage.

Abstract Background Ireland frequently reports the highest annual Crude Incidence Rates (CIRs) of cryptosporidiosis in the EU, with national CIRs up to ten times the EU average. Accordingly, the current study sought to examine the spatiotemporal trends associated with this potentially severe protozoan infection. Methods Overall, 4509 cases of infection from January 2008 to December 2017 were geo-referenced to a Census Small Area (SA), with an ensemble of geo-statistical approaches including seasonal decomposition, Local Moran’s I, and space–time scanning used to elucidate spatiotemporal patterns of infection. Results One or more confirmed cases were notified in 3413 of 18,641 Census SAs (18.3%), with highest case numbers occurring in the 0–5-year range (n = 2672, 59.3%). Sporadic cases were more likely male (OR 1.4) and rural (OR 2.4), with outbreak-related cases more likely female (OR 1.4) and urban (OR 1.5). Altogether, 55 space–time clusters (≥ 10 confirmed cases) of sporadic infection were detected, with three “high recurrence” regions identified; no large urban conurbations were present within recurrent clusters. Conclusions Spatiotemporal analysis represents an important indicator of infection patterns, enabling targeted epidemiological intervention and surveillance. Presented results may also be used to further understand the sources, pathways, receptors, and thus mechanisms of cryptosporidiosis in Ireland.