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Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and aggressive liver cancer with limited therapeutic options. Precise classification and immunotherapy are perspectives to improve the treatments. We reported the role of septin 9 in apico‐basal polarity and epithelial‐to‐mesenchymal transition (EMT). Here, we aim to elucidate its role in iCCA. We analyzed single‐cell transcriptomes from human iCCA tumor cells based on phenotype and cell state. Knockdown of the septin 9 gene (SEPT9) was done using small interfering RNA (siRNA); interferon‐γ (IFN‐γ) stimulation was performed using different CCA cells; gene expressions were analyzed by reverse transcription and real‐time PCR analysis (RT‐qPCR); and immunofluorescence, immunoblotting, and flow cytometry were performed to assess the expression of proteins. The differential distributions of SEPT9 and vimentin (VIM) gene expressions allowed us to define specific cellular trajectories of malignant cells and thus identified distinct clusters of iCCA cells. One cluster was enriched in VIM and extracellular‐matrix (ECM) remodeling molecules, and another had high expression of SEPT9 and genes from the ‘don't eat me’ signal involved in immune escape. This antagonism between SEPT9 and VIM was confirmed by in vitro experiments. Notably, SEPT9 and ‘don't eat me’ gene expressions were inversely correlated to those of vimentin and the EMT markers. SEPT9 expression was upregulated by IFN‐γ and SEPT9 knockdown decreased expression of ‘don't eat me’ signal genes and increased expression of mesenchymal markers. Cancer Cell Line Encyclopedia (CCLE) transcriptome database analyses confirmed that iCCA cells enriched in septin 9 exhibit epithelial‐like features. This study revealed septin 9 as a cytoskeleton element of iCCA epithelial‐like cells and a regulator of the immune system response. It also brings new insights into the enigmatic relationship between EMT and immune response. Notably, we decoded a potential mechanism that could sensitize patients to immunotherapies.

Abstract Background Serological screening tests play a crucial role to diagnose gambiense human African trypanosomiasis (gHAT). Presently, they preselect individuals for microscopic confirmation, but in future “screen and treat” strategies they will identify individuals for treatment. Variability in reported specificities, the development of new rapid diagnostic tests (RDT) and the hypothesis that malaria infection may decrease RDT specificity led us to evaluate the specificity of 5 gHAT screening tests. Methods During active screening, venous blood samples from 1095 individuals from Côte d’Ivoire and Guinea were tested consecutively with commercial (CATT, HAT Sero-K-SeT, Abbott Bioline HAT 2.0) and prototype (DCN HAT RDT, HAT Sero-K-SeT 2.0) gHAT screening tests and with a malaria RDT. Individuals with ≥ 1 positive gHAT screening test underwent microscopy and further immunological (trypanolysis with T.b. gambiense LiTat 1.3, 1.5 and 1.6; indirect ELISA/T.b. gambiense; T.b. gambiense inhibition ELISA with T.b. gambiense LiTat 1.3 and 1.5 VSG) and molecular reference laboratory tests (PCR TBRN3, 18S and TgsGP; SHERLOCK 18S Tids, 7SL Zoon, and TgsGP; Trypanozoon S2-RT-qPCR 18S2, 177T, GPI-PLC and TgsGP in multiplex; RT-qPCR DT8, DT9 and TgsGP in multiplex). Microscopic trypanosome detection confirmed gHAT, while other individuals were considered gHAT free. Differences in fractions between groups were assessed by Chi square and differences in specificity between 2 tests on the same individuals by McNemar. Results One gHAT case was diagnosed. Overall test specificities (n = 1094) were: CATT 98.9% (95% CI: 98.1–99.4%); HAT Sero-K-SeT 86.7% (95% CI: 84.5–88.5%); Bioline HAT 2.0 82.1% (95% CI: 79.7–84.2%); DCN HAT RDT 78.2% (95% CI: 75.7–80.6%); and HAT Sero-K-SeT 2.0 78.4% (95% CI: 75.9–80.8%). In malaria positives, gHAT screening tests appeared less specific, but the difference was significant only in Guinea for Abbott Bioline HAT 2.0 (P = 0.03) and HAT Sero-K-Set 2.0 (P = 0.0006). The specificities of immunological and molecular laboratory tests in gHAT seropositives were 98.7–100% (n = 399) and 93.0–100% (n = 302), respectively. Among 44 reference laboratory test positives, only the confirmed gHAT patient and one screening test seropositive combined immunological and molecular reference laboratory test positivity. Conclusions Although a minor effect of malaria cannot be excluded, gHAT RDT specificities are far below the 95% minimal specificity stipulated by the WHO target product profile for a simple diagnostic tool to identify individuals eligible for treatment. Unless specificity is improved, an RDT-based “screen and treat” strategy would result in massive overtreatment. In view of their inconsistent results, additional comparative evaluations of the diagnostic performance of reference laboratory tests are indicated for better identifying, among screening test positives, those at increased suspicion for gHAT. Trial registration The trial was retrospectively registered under NCT05466630 in clinicaltrials.gov on July 15 2022. Graphical Abstract

Abstract An inverse social gradient in early childhood overweight has been consistently described in high-income countries; however, less is known about the role of migration status. We studied the social patterning of overweight in preschool children according to the mother’s socio-economic and migration background. For 9250 children of the French ELFE birth cohort with body mass index collected at age 3.5 years, we used nested logistic regression to investigate the association of overweight status in children with maternal educational level, occupation, household income and migration status. Overall, 8.3% (95%CI [7.7–9.0]) of children were classified as overweight. The odds of overweight was increased for children from immigrant mothers (OR 2.22 [95% CI 1.75–2.78]) and descendants of immigrant mothers (OR 1.35 [1.04–2.78]) versus non-immigrant mothers. The highest odds of overweight was also observed in children whose mothers had low education, were unemployed or students, or were from households in the lowest income quintile. Our findings confirm that socio-economic disadvantage and migration status are risk factors for childhood overweight. However, the social patterning of overweight did not apply uniformly to all variables. These new and comprehensive insights should inform future public health interventions aimed at tackling social inequalities in childhood overweight.

In this study, a series of N-arylamino-7-chloroquinolines were synthesized via an alkylation reaction involving aniline derivatives (2) and 4,7-dichloroquinoline (1). Additionally, the synthesis of a library of N-aryl-N-benzylamino-7-chloroquinoline analogues, modified on the aniline nitrogen, has also reported. A structure-activity relationship (SAR) study was conducted to evaluate the biological efficacy and safety of these derivatives against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfW2) Plasmodium falciparum strains. Compounds 5i and 5c showed promising efficacy against the Pf3D7 strain with IC50 values of 0.25 μM and 0.54 μM, respectively, while compound 5l demonstrated significant activity against the PfW2 strain with an IC50 of 5.82 μM. The cytotoxicity of these compounds was also evaluated on HUVEC cell lines. Additionally, their pharmacological and pharmacokinetic (ADME) properties were studied to predict their fate and identify promising candidates for further clinical studies.

The technological advancement occurring in the world today has a potency to create positive and negative side effects especially on children. The positive side may entail increased empathy and acceptance of diversity through modelling the prosocial behaviours, while the negative can be manifest in aggressive behaviour, risky sexual behaviour, and substance abuse. These challenges pose a need to draw a particular attention to children's rights of protection and care in relation to the use of technology. This paper sought to critically explore the way in which children adapt technology skills and the way they respond towards media influences. The findings revealed that the adaptive technology skills are needed in providing a considerable guidance for child protection and careful engagement towards digital information as part of their rights to natural growth and development.

Summary: Background: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children. Methods: We conducted a retrospective, descriptive study examining clinical data for children aged 1–59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016–June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration. Findings: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted

Introduction: Inflammatory odontogenic cysts are lesions that develop from the cellular remains of odontogenesis. They are lesions that may recur after incomplete surgical enucleation with a variable clinical appearance depending on the clinical form. These clinical variations could be explained by the biological behaviour of the lesion cells which can be explored by the study of the cell proliferation index (Ki67). This justifies the initiation of this work whose objective was to study the level of expression of Ki67 and to measure the index of proliferation in odontogenic inflammatory cysts. Material and method: This was a cross-sectional study with an analytical aim on surgical parts of odontogenic inflammatory cysts over a period of 31 months in the odontostomatology department of the Hôpital Général Idrissa Pouye. The Ki67 immunohistochemistry study was performed on 3μ thick histological sections of paraffin-fixed tissue. The inclusion criteria were any surgical specimen of odontogenic inflammatory cyst that we could collect. The variables studied were sociodemographic, clinical and histopathological. Results: Radiculo-dental cysts represented 80.5% of the surgical specimens collected and residual cysts 12.2%. The percentage of Ki67-labelled cells was greater than 15% in 80.5% of the odontogenic inflammatory cysts and less than 7% in 19.5% of the cases. In addition, intense labelling was noted in radiculo-dental cysts and weak labelling in the other clinical forms of inflammatory odontogenic cysts obtained. An association was noted between the percentage of Ki67 labelled cells and histological types (p-value

Abstract Background Excessive screen time in infancy and childhood has been associated with consequences on children’s development and health. International guidelines call for no screen time before age 2 years, whereas in France, the most prominent guidelines recommend no screen before age 3 years. However, data are lacking on parental adherence to the no-screen guideline for toddlers and factors of adherence in France. Using data from the French nationwide Elfe birth cohort, we estimated adherence to the no-screen guideline at age 2 years and examined related factors, including sociodemographic characteristics, parental leisure activities and screen time. Methods In 2011, 18,329 newborns and their parents were enrolled in 349 randomly selected maternity units across mainland France. At age 2 years, screen exposure of 13,117 toddlers was reported by parents in phone interviews. Data on sociodemographic characteristics, parental leisure activities and screen time were collected from both parents. Three patterns of parental leisure activities were derived by principal component analysis: literate (e.g.,reading), screen-based, and physical/artistic activities. Multivariable logistic regression models were used to examine the associations of sociodemographic characteristics, parental leisure activities and parental screen time with adherence to the no-screen guideline for toddlers. Results Overall, 1809/13,117 (13.5%) families adhered to the no-screen guideline for toddlers. Adherence was reduced with maternal age

Overexpression of isoform δ of phosphoinositide 3-kinase (PI3Kδ) promotes stemness in hepatocellular carcinoma cell lines and mouse liver, whereas its inhibition promotes EMT, suggesting a key role for PI3Kδ in epithelial plasticity.

IntroductionHigh prevalence of overweight and obesity already observed in preschool children suggests the involvement of early-life risk factors. Preconception period and pregnancy are crucial windows for the implementation of child obesity prevention interventions with parental lifestyle factors as relevant targets. So far, most studies have evaluated their role separately, with only a few having investigated their potential synergistic effect on childhood obesity. Our objective was to investigate parental lifestyle patterns in the preconception and pregnancy periods and their association with the risk of child overweight after 5 years.Materials and methodsWe harmonized and interpreted results from four European mother-offspring cohorts participating in the EndObesity Consortium [EDEN, France; Elfe, France; Lifeways, Ireland; and Generation R, Netherlands] with data available for 1,900, 18,000, 1,100, and 9,500 families, respectively. Lifestyle factors were collected using questionnaires and included parental smoking, body mass index (BMI), gestational weight gain, diet, physical activity, and sedentary behavior. We applied principal component analyses to identify parental lifestyle patterns in preconception and pregnancy. Their association with risk of overweight (including obesity; OW-OB) and BMI z-scores between 5 and 12 years were assessed using cohort-specific multivariable logistic and linear and regression models (adjusted for potential confounders including parental age, education level, employment status, geographic origin, parity, and household income).ResultsAmong the various lifestyle patterns derived in all cohorts, the two explaining the most variance were characterized by (1) “high parental smoking, low maternal diet quality (and high maternal sedentary behavior in some cohorts)” and, (2) “high parental BMI and low gestational weight gain.” Patterns characterized by high parental BMI, smoking, low diet quality or high sedentary lifestyle before or during pregnancy were associated with higher risk of OW-OB in children, and BMI z-score at any age, with consistent strengths of associations in the main cohorts, except for lifeways.ConclusionThis project provides insight into how combined parental lifestyle factors in the preconception and pregnancy periods are associated with the future risk of child obesity. These findings are valuable to inform family-based and multi-behavioural child obesity prevention strategies in early life.

ObjectivesThe study aims to describe the output of routine health screening performed in French nursery schools by the maternal and child health services among children aged 3–4 years and to quantify the level of early socioeconomic health disparities.MethodsIn 30 participating départements, data on screening for vision and hearing impairments, overweight and thinness, dental health, language, psychomotor development, and immunizations were collected for children born on specific dates in 2011 and enrolled in nursery school in 2014–2016. Information was collected on the children, their socioeconomic characteristics and on the school attended. Odds of abnormal screening results were compared for each socioeconomic factor by logistic regressions adjusted for age, sex, prematurity and bilingualism.ResultsAmong the 9,939 children screened, prevalence of disorders was 12.3% for vision, 10.9% for hearing, 10.4% for overweight, 7.3% for untreated caries, 14.2% for language and 6.6% for psychomotricity. Newly detected visual disorders were more frequent in disadvantaged areas. Children with unemployed parents were three time more likely to have untreated caries and twice as likely to present language or psychomotor impairments; 52% were referred to a health professional following screening compared to 39% of children with employed parents. Except for children in disadvantaged areas, vaccine coverage was lower among disadvantaged groups.ConclusionThe prevalences of impairments, which are higher among disadvantaged children, highlight the potential preventive impact of systematic screening under the comprehensive maternal and child healthcare program. These results are important to quantify early socioeconomic inequalities in a Western country known for its generous social welfare system. A more holistic approach to child health is needed with a coherent system involving families and aligning primary care, local child health professionals, general practitioners, and specialists. Further results are needed to evaluate its impact on later child development and health.

Abstract Background Screen media use in early childhood has largely increased in recent years, even more so during the COVID-19 epidemic, and there is much discussion regarding its influence on neurodevelopment, including Autism Spectrum Disorder (ASD). Methods We examined the relationship between use of TV, computer, tablet and smartphone at age 2 years and risk of ASD assessed in telephone-based questionnaires among 12,950 children participating in the nationally representative ELFE (‘Etude Longitudinale Française sur les Enfants’) birth cohort study in France. Results In inverse-probability weighted (IPW) multinomial regression analyses, children’s weekly or daily screen media use was associated with an increased likelihood of an intermediate risk of ASD (IPW-controlled OR for weekly use:1.07, 95% CI 1.02—1.12; IPW-controlled OR for daily use:1.05, 95% CI 1.02—1.08) but inversely associated with a high risk (IPW-controlled OR for weekly use: 0.60, 95% CI 0.50—0.73; IPW-controlled OR for daily use: 0.75, 95% CI 0.62—0.91), as ascertained by the M-CHAT. This was confirmed when studying TV as well as computer/tablet exposure separately. Conclusions Overall, our nationally-representative study conducted among a large sample of 2-year-old children, indicates a complex relationship between screen exposure and ASD risk.

Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous and aggressive liver cancer with limited therapeutic options. Precise classification and immunotherapy are perspectives to improve the treatments. We reported the role of septin 9 in apico‐basal polarity and epithelial‐to‐mesenchymal transition (EMT). Here, we aim to elucidate its role in iCCA. We analyzed single‐cell transcriptomes from human iCCA tumor cells based on phenotype and cell state. Knockdown of the septin 9 gene (SEPT9) was done using small interfering RNA (siRNA); interferon‐γ (IFN‐γ) stimulation was performed using different CCA cells; gene expressions were analyzed by reverse transcription and real‐time PCR analysis (RT‐qPCR); and immunofluorescence, immunoblotting, and flow cytometry were performed to assess the expression of proteins. The differential distributions of SEPT9 and vimentin (VIM) gene expressions allowed us to define specific cellular trajectories of malignant cells and thus identified distinct clusters of iCCA cells. One cluster was enriched in VIM and extracellular‐matrix (ECM) remodeling molecules, and another had high expression of SEPT9 and genes from the 'don't eat me' signal involved in immune escape. This antagonism between SEPT9 and VIM was confirmed by in vitro experiments. Notably, SEPT9 and 'don't eat me' gene expressions were inversely correlated to those of vimentin and the EMT markers. SEPT9 expression was upregulated by IFN‐γ and SEPT9 knockdown decreased expression of 'don't eat me' signal genes and increased expression of mesenchymal markers. Cancer Cell Line Encyclopedia (CCLE) transcriptome database analyses confirmed that iCCA cells enriched in septin 9 exhibit epithelial‐like features. This study revealed septin 9 as a cytoskeleton element of iCCA epithelial‐like cells and a regulator of the immune system response. It also brings new insights into the enigmatic relationship between EMT and immune response. Notably, we decoded a potential mechanism that could sensitize patients to immunotherapies. [ABSTRACT FROM AUTHOR]

Background: The increase in prescriptions of antiretrovirals (ARVs) implies the increasing occurrence of side effects, including skin manifestations. The objective of this work was to identify the epidemiological and therapeutic aspects of drug eruptions during ARV treatment in the support and counseling units (SCU) of commune IV of the district of Bamako. Material and methods: In a documentary study, the data of patients living with HIV (PLHIV) followed in the SCUs between January 2008 and December 2010, i.e. 3 years, in strict respect of their confidentiality were collected. Parameters of interest included epidemiological, clinical and therapeutic characteristics. Results: The frequency of drug eruptions was 2.85% of cases, ie 50 patients out of 1748 PLWHA. Women accounted for 76% of cases with a sex ratio of 0.32. The mean age was 30.8 ± 11.46 years with extremes ranging from 5 to 60 years. PLHIV were in WHO clinical stage III, or 48% of cases. The mean time to onset of drug eruption was 23.5 ± 17.7 days. Common clinical manifestations were pruritus (24%), rash (22%) and Lyell’s syndrome (12%). 96% of patients (48 cases) were on ARVs, of which 78% were on nevirapine and 14% on efavirenz. The treatment was symptomatic. Conclusion: Antiretrovirals are sources of drug eruption despite their benefits in the treatment of HIV/AIDS. Rigorous monitoring is essential to prevent these harmful effects.

Cette contribution interroge les différentes formes d’instrumentalisation de la randonnée pédestre par des organisations professionnelles. Il a été question d’identifier les modes de justifications exposés dans le discours de responsables de clubs d’entreprise de randonnée pédestre pour rendre compte des modalités d’usage de cette activité sportive en milieu professionnel au Sénégal. Grace à l’observation participante et à une trentaine d’entretiens individuels semi directifs menés auprès des acteurs de la randonnée pédestre au Sénégal (employés participants, responsables d’entreprise, organisateurs), les différentes catégories d’organismes professionnels (entreprises commerciales, administrations publiques, organisations internationales, représentations diplomatiques…) qui ont recouru à cette activité physique et sportive ont été identifiés. Aussi, divers enjeux (sanitaire, managériale, communicationnel…) ont motivé l’usage de la randonnée pédestre par ces organisations dont certaines espèrent améliorer la productivité leurs travailleurs. This contribution questions the different forms of instrumentalization of hiking by professional organizations. It was a question of identifying the modes of justifications exposed in the speeches of managers of corporate hiking clubs to account for the modalities of use of this sporting activity in a professional environment in Senegal. Thanks to the participant observation and about thirty semi-structured individual interviews conducted with the actors of hiking in Senegal (participating employees, company managers, organizers), the different categories of professional organizations (commercial companies, administrations organizations, international organizations, diplomatic representations, etc.) who have used this physical and sporting activity have been identified. Also, various issues (health, managerial, communicational...) have motivated the use of hiking by these organizations, some of which hope to improve the productivity of their workers.

Nous rapportons l’observation d’une patiente de 60 ans qui avait consulté pour une polyarthrite chronique acromélique bilatérale, symétrique, déformante associant une acroparesthésie en gants et en chaussettes révélant une lèpre lépromateuse. La maladie de Hansen a un tropisme surtout cutané et neurologique. Les manifestations rhumatologiques viennent en troisième position. Exceptionnellement inaugurales, elles constituent une cause d’errance diagnostique.

The study deals with the use of attapulgite as a corrosion inhibitor of two metals, namely aluminum and zinc, and their alloy (aluzinc), in a 0.5 M hydrochloric acid medium. The study was carried out by monitoring the free-corrosion potential and performing dynamic polarization measurements (Tafel curves) at different concentrations of inhibitor in solution. The measurements suggested that in a 0.5 M acidic medium, the surface of each of the three materials was attacked. The decrease in current density was very noticeable in aluminum and zinc at a level of 2 g×L-1. A weak tendency to passivity was noticed for zinc and aluzinc. The experimental results obtained showed a decrease in the current intensity in the presence of the corrosion inhibitor in the acidic medium. The maximum inhibitory efficiency rate reached for the metals and their alloy was higher than 99 %. This percentage was obtained for aluminum and zinc in the presence of 4 g×L-1 of attapulgite and 3 g×L-1 for aluzinc.