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Background: According to WHO, "noncommunicable diseases (NCDs) kill 41 million people" annually, as the primary cause of death globally. WHO's Global Action Plan for the prevention and control of NCDs 2013–2020 (extended) tackles this issue and its implications regarding inequalities between countries and populations. Based on combined behavioural, environmental and policy approaches, health promotion aims to reduce health inequities and address health determinants through 3 strategies: education, prevention and protection. It is a well-known fact that long-term efficiency in health promotion, that is to say the promotion of health and well-being, involves interventions and programmes which target / involve children [1]. As a focal point in communities and a key environment for children, school is an important setting to implement health promotion programmes, especially integrated approaches and interventions targeting Life Skills (LS). Indeed, LS contribute to health and well-being, particularly for pupils. This article presents the research protocol of a French integrated school-based health promotion interventional research programme which intends to support the health promoting schools (HPS) approach in France: Explo'Santé. It results from a partnership between the University of Lyon and the French League against Cancer. Methods: Explo'Santé is an observational study based on a mixed methods research design, which aims to evaluate the effects of a health promotion programme, to elicit its implementation process and identify contextual factors. This 3-year, complex programme targets primary school pupils aged 8 to 10. It incorporates health education sessions, to develop pupils' LS and health literacy (HL), and to promote healthy environments. Teachers and French League prevention officers are trained to support skill development and programme sustainability. Data collection includes quantitative data via questionnaires, to assess programme impact on approximately 700 pupils, as well as 36 teachers, and 6 prevention officers, as well as qualitative data collected via focus groups with pupils, and interviews with teachers, parents, prevention officers, and school heads, to understand the barriers and promoting factors to the implementation of the programme, the differences in process and effects in different contexts, and its potential for sustainability. Discussion: Explo'Santé was designed to contribute to school-based health promotion strategies, by including key players, promoting partnerships, targeting multiple levels of impact and effect, and to ensure every step is research-based and informed. Finally, this study aims to identify the elements which would enable Explo'Santé to become a model in France and internationally. [ABSTRACT FROM AUTHOR]

Fluorine magnetic resonance imaging ( 19 F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative 19 F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in 19 F-MRI. Importantly, the self-assembling 19 F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal 19 F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The 19 F-MRI and multimodal 19 F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising 19 F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of 19 F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry., Competing Interests: Competing interests statement:The authors declare no competing interest.

Lung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert CI ), is expressed from the p21 Cdkn1a locus. Expression of either TERT or TERT CI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERT CI . Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema., (© 2024. The Author(s).)

Background: Radiotherapy as a complement or an alternative to neurosurgery has a central role in the treatment of skull base grade I-II meningiomas. Radiotherapy techniques have improved considerably over the last two decades, becoming more effective and sparing more and more the healthy tissue surrounding the tumour. Currently, hypo-fractionated stereotactic radiotherapy (SRT) for small tumours and normo-fractionated intensity-modulated radiotherapy (IMRT) or proton-therapy (PT) for larger tumours are the most widely used techniques. It is expected a decrease of the risk of cognitive impairment with these modern techniques. However prospective data about cognitive long-term consequences of partial brain irradiation with SRT, PT, or IMRT remain very scarce to date. Methods: CANCER COG is one of the first multicentric study in the world to prospectively assess the cognitive performances of patients following different modalities of cerebral radiotherapy (stereotactic radiotherapy, proton therapy, intensity modulated radiotherapy) for the treatment of grade I-II skull base meningioma, up to at least 10 years after the end of radiotherapy. This longitudinal study includes the follow-up of 3 cohorts, including: patients treated with PRT, IMRT, and SRT. An additionally control group will be formed. The primary objective is to report long-term cognitive deterioration in each cohort until 10 years after the end of irradiation. The rate of clinical symptomatology improvement over time after irradiation, the evolution of health-related quality-of-life, anxiety/depression, fatigue, over time after irradiation, the tumoral local control after irradiation, the progression-free survival (PFS), the professional reintegration for working-age patients will also be assessed. CANCER COG aims to help clinicians to choose the best irradiation techniques with the best benefit/risk ratio. Inclusions started on september 2023. Trial registration: The study was registered on clinicaltrials.gov with the following number: NCT 06036706. [ABSTRACT FROM AUTHOR]

Persistent organic pollutants (POPs) are a group of organic chemical compounds. Contradictory results have emerged in epidemiological studies attempting to elucidate their relationship with breast cancer risk. This study explored the relationship between dietary exposures to multiple POPs and ER-positive breast cancer risk in the French E3N cohort study, using three different approaches to handle multicollinearity among exposures. Intakes of 81 POPs were estimated using food consumption data from a validated semi-quantitative food frequency questionnaire and food contamination data. In the first approach, hierarchical clustering was performed to identify clusters of correlated POPs. For each cluster, the levels of POPs belonging to it were averaged. These average levels were then included in a Cox model to estimate their associations with ER-positive breast cancer occurrence. The second and third approaches applied in the present study were Principal component Cox regression (PCR-Cox) and partial least squares Cox regression (PLS-Cox) respectively, both being dimension-reduction methods (respectively unsupervised and supervised) coupled to a Cox model, used to identify principal components of POPs and to estimate their associations with ER-positive breast occurrence. All models were adjusted for potential confounders previously identified using a directed acyclic graph. The study included 66,722 women with a median follow-up of 20.3 years, during which 3,739 developed an incident ER-positive breast cancer. The variable clustering method did not identify any association between the averaged variables and ER-positive breast cancer risk. Five components were retained using both the PCR-Cox and PLS-Cox methods explaining 82% and 77% of the variance in the initial exposure matrix respectively. Among these components, none was significantly associated with the occurrence of ER-positive breast cancer. This study provides an illustrative example of the application of three distinct statistical methods in the context of highly correlated environmental exposures, discussing their potential relevance and limitations within this specific framework. [ABSTRACT FROM AUTHOR]

Background: Proton therapy (PRT) is an innovative radiotherapeutic modality for the treatment of cancer with unique ballistic properties. The depth-dose distribution of a proton beam reduces exposure of healthy tissues to radiations, compared with photon-therapy (XRT). To date, only few indications for proton-therapy, like pediatric cancers, chordomas, or intra-ocular neoplasms, are reimbursed by Health systems. There is no published or recruiting prospective study evaluating the impact of proton-therapy or conventional irradiation on neurocognitive function for meningioma patients. Notably, long-term cognitive or ocular impact of these modern irradiation schemes remains poorly known. Yet, these patients had a long life-expectancy, and are at risk of developing long-term sequelae. Thus, according to its ballistic advantage, an improvement of patient functional outcomes and a reduction of neurocognitive long-term toxicity are expected if tissue sparing proton-therapy is used.Randomized trial seems crucial to further assess proton-therapy indication for patients with cavernous sinus meningioma. Methods: COG-PROTON-01 is the first worldwide randomized phase III prospective study evaluating long-term toxicity of these two irradiation modalities (PRT and XRT)for the treatment of cavernous sinus meningioma. Primary objective is to compare long-term cognitive and/or functional (visual, hearing, neurological and/or endocrinological) deterioration between patients treated by fractionated proton-therapy (PRT) or photon radiotherapy (XRT), 5 years after the end of irradiation. The primary endpoint is based on the individual neurocognitive test scores (grouped into five cognitive domains: attention, executive functioning, verbal memory, working memory, information processing speed) and on visual, hearing, endocrinological and neurological evaluations, five years after radiotherapy. Eligible patients with low-grade cavernous sinus meningioma will be 1:1 randomised, with stratification on age, sex, MoCA score. Overall, the inclusion of 160 patients is planned (80 in each arm). To be considered as positive, asumming that 47% of patients will not develop long-term cognitive disabilities deficits after XRT radiotherapy,, thus at least 70% of the patients treated with PRT should not develop functional impairment. First inclusions started on September 2023 (NCT05895344). Trial registration: The study was registered on clinicaltrials.gov on June 8, 2023 with the following number: NCT 05895344. [ABSTRACT FROM AUTHOR]

Background: Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk. Methods: We used data from a nested case–control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects). Results: The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00–5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13–4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93–4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05–1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75–1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol. Conclusion: Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations. [ABSTRACT FROM AUTHOR]

This article examines the legal response to a controversy on dietary information in the context of commercial court and appellate court rulings. Against a backdrop of health and environmental crises, the construction of information on such risks has become a sensitive issue for market actors, as a result of which courts are asked to arbitrate conflicts. This is particularly important at a time when informational mediations carried out by new actors increasingly take the form of digital ratings and augmented information. The dispute involving the firm Yuca and the French agro-industrial processed meat sector is a case in point. This paper analyses the structural arguments put forward in this legal dispute at the first instance and appeal stages. In the light of law and socio-economics, it untangles questions pertaining to the link between denigration and freedom of expression and the definition of the role of scientific research and consensus in the decisions. This leads us to shed light on the contents of the changing missions of two central types of actors: the mediators who monitor and regulate market practices and the judges that arbitrate these mediations and settle controversies. [ABSTRACT FROM AUTHOR]

Study Question: Are body size across the life course and adult height associated with endometriosis?Summary Answer: Endometriosis is associated with lean body size during childhood, adolescence and adulthood; tall total adult height; and tall sitting height.What Is Known Already: The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis.Study Design, Size, Duration: We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2-3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors.Participants/materials, Setting, Methods: A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women.Main Results and the Role Of Chance: The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20-25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162-164 cm: OR = 1.28, 95% CI = 1.12-1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18-1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05-1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis.Limitations Reasons For Caution: Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias.Wider Implications Of the Findings: The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further.Study Funding/competing Interest(s): The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011-302078). The authors have no conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Many pathogens including viruses enter cells by endocytosis. We identified and evaluated novel endocytosis inhibitors capable of blocking the entry of the HIV-1 Transactivation of Transcription protein (Tat) protein into neuronal cells and investigated their potential protective properties against Tat-induced neurotoxicity. In this study, the compounds Les-6631 and Les-6633 were synthesized and assessed. The effects of these compounds on the internalization of dextran and the cell-penetrating peptide (CPP) Tat-Cy5 complex in nerve cells were examined. In addition, the ability of these compounds to protect against oxidative stress and DNA damage induced by the full-length Tat protein was investigated. Les-6631 and Les-6633 were found to inhibit endocytosis better than the classical endocytosis inhibitor chlorpromazine, thereby effectively preventing the entry of the Tat protein into nerve cells. Moreover, compounds demonstrated the capacity to reduce oxidative stress and protect DNA from Tat-induced damage. In a neuro-AIDS model, both compounds proved effective in preventing neurotoxicity associated with HIV-1 infection, indicating its potential for therapeutic applications. Les-6631 and Les-6633 thus can protect cells from the harmful effects of pathogens. Their use in a neuro-AIDS model suggests a potential application in protective therapies for the nervous system in patients with HIV. NEW & NOTEWORTHY This study identifies novel rhodadyn-based inhibitors, Les-6631 and Les-6633, which selectively block dynamin's GTPase activity while sparing clathrin-mediated pathways. They effectively inhibit cellular uptake, protect neural cells from HIV-1 Tat-induced oxidative stress, and reduce mitochondrial and DNA damage. Their selective dynamin inhibition and antioxidant properties highlight their therapeutic potential for neurodegeneration and viral infections, offering cell protection without disrupting essential endocytic functions.

Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and colorectal cancer risk overall and by sex, cancer subsite, and age at diagnosis., Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for colorectal cancer risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied., Results: We found no evidence for an association of genetically predicted plasma total ghrelin levels and colorectal cancer risk (0.95, 95% confidence interval, 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset colorectal cancer., Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified colorectal cancer risk., Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with colorectal cancer risk., (©2024 The Authors; Published by the American Association for Cancer Research.)

The individual results of SARS-CoV-2 serological tests measured after the first pandemic wave of 2020 cannot be directly interpreted as a probability of having been infected. Plus, these results are usually returned as a binary or ternary variable, relying on predefined cut-offs. We propose a Bayesian mixture model to estimate individual infection probabilities, based on 81,797 continuous anti-spike IgG tests from Euroimmun collected in France after the first wave. This approach used serological results as a continuous variable, and was therefore not based on diagnostic cut-offs. Cumulative incidence, which is necessary to compute infection probabilities, was estimated according to age and administrative region. In France, we found that a "negative" or a "positive" test, as classified by the manufacturer, could correspond to a probability of infection as high as 61.8% or as low as 67.7%, respectively. "Indeterminate" tests encompassed probabilities of infection ranging from 10.8 to 96.6%. Our model estimated tailored individual probabilities of SARS-CoV-2 infection based on age, region, and serological result. It can be applied in other contexts, if estimates of cumulative incidence are available. [ABSTRACT FROM AUTHOR]

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Introduction: DNA damage repair genes are altered in 20–35% of metastatic castration-resistant prostate cancer (mCRPC). Poly-ADP (Adénosine Diphosphate)-ribose polymerase inhibitors (PARPi) showed significant activity for these selected tumors, especially with homologous recombination repair (HRR) deficiency. These alterations could also predict platinum sensitivity. Although carboplatin was inconclusive in unselected mCRPC, the literature suggests an anti-tumoral activity in mCRPC with HHR gene alterations. We aimed to assess the efficacy of carboplatin monotherapy in mCRPC patients with HRR deficiency. Methods: This prospective multicenter single-arm two-stage phase II addressed mCRPC men with HRR somatic and/or germline alterations, pretreated with ⩾2 taxane chemotherapy regimens and one androgen receptor pathway inhibitor. Prior PARPi treatment was allowed. Enrolled patients received intravenous carboplatin (AUC5) every 21 days for 6–9 cycles. The primary endpoint was the best response rate according to adapted PCWG3 guidelines: radiological response (RECIST 1.1 criteria) and/or biological response [⩾50% prostate-specific antigen (PSA) decline]. Results: A total of 15 out of 16 enrolled patients started carboplatin treatment. Genomic alterations were identified for BRCA2 (n = 5), CDK12 (n = 3), ATM (n = 3) CHEK2 (n = 2), CHEK1 (n = 1), and BRCA1 (n = 1) genes. Objective response (partial biological response + stable radiological response) was achieved in one patient (6.7%), carrying a BRCA2 mutation and not pre-treated with PARPi; stable disease was observed for five patients (33.5%). Among seven patients (46.7%) with previous PARPi treatment, four patients (57.1%) had a stable disease. The median progression-free and overall survivals were 1.9 [95% confidence interval (95% CI), 1.8–9.5] and 8.6 months (95% CI, 4.3–19.5), respectively. The most common severe (grade 3–4) treatment-related toxicities were thrombocytopenia (66.7%), anemia (66.7%), and nausea (60%). Overall, 8 (53.3%) patients experienced a severe hematological event. Conclusion: The study was prematurely stopped as pre-planned considering the limited activity of carboplatin monotherapy in heavily pre-treated, HHR-deficient mCRPC patients. Larger experience is needed in mCRPC with BRCA alterations. Trial registration: NCT03652493, EudraCT ID number 2017-004764-35. [ABSTRACT FROM AUTHOR]

Oxazolidinones (linezolid and tedizolid) adverse reactions include thrombocytopenia, the mechanism of which is still largely unknown. In cultured cells, oxazolidinones impair mitochondrial protein synthesis and oxidative metabolism. As mitochondrial activity is essential for megakaryocyte differentiation and maturation into platelets, we examined whether oxazolidinones impair these processes ex vivo and alter, in parallel, the activity of mitochondrial cytochrome c -oxidase (CYTOX; enzyme partly encoded by the mitochondrial genome) and cell morphology. Human CD34+ cells were isolated, incubated with cytokines (up to 14 days) and clinically relevant oxazolidinone concentrations or in control conditions, and used for (i) clonogenic assays [counting of megakaryocyte (CFU-Mk), granulocyte-monocyte (CFU-GM), burst-forming unit-erythroid (BFU-E) colonies]; (ii) the measure of the expression of megakaryocyte surface antigens (CD34 to CD41 and CD42); (iii) counting of proplatelets; (iv) the measurement of CYTOX activity; and (v) cell morphology (optic and electron microscopy). Oxazolidinones caused a significant decrease in BFU-E but not CFU-Mk or CFU-GM colonies. Yet, the megakaryocytic lineage was markedly affected, with a decreased differentiation of CD34+ into CD41+/CD42+ cells, an abolition of proplatelet formation and striking decrease in the numbers of large polylobulated nucleus megakaryocytes, with a complete loss of intracellular demarcation membrane system, disappearance of mitochondria, and suppression of CYTOX activity. These alterations were more marked in cells incubated with tedizolid than linezolid. These data suggest that oxazolidinones may induce thrombocytopenia by impairing megakaryocytic differentiation through mitochondrial dysfunction. Pharmacological interventions to prevent this toxicity might therefore be difficult as mitochondrial toxicity is most probably inherently linked to their antibacterial activity., Competing Interests: P.M.T. and F.V.B. have received speaker's and advisory boards' honoraria from Bayer and Merck (holders of marketing rights of tedizolid) and research grants from Trius Pharmaceuticals (now part of Merck) for preclinical studies of tedizolid. These companies were not involved in the design and performance of the studies presented here and did not take any part in their interpretation and/or decision to submit them to publication. The other authors have no conflict of interest to disclose in relation to the present work.

Cancers only develop if they escape immunosurveillance, and the success of cancer immunotherapies relies in most cases on their ability to restore effector T-cell functions, particularly IFNγ production. Revolutionizing the treatment of many cancers, immunotherapies targeting immune checkpoints such as PD1 can increase survival and cure patients. Unfortunately, although immunotherapy has greatly improved the prognosis of patients, not all respond to anti-PD1 immunotherapy, making it crucial to identify alternative treatments that could be combined with current immunotherapies to improve their effectiveness. Here, we show that iron supplementation significantly boosts T-cell responses in vivo and in vitro. The boost was associated with a metabolic reprogramming of T cells in favor of lipid oxidation. We also found that the "adjuvant" effect of iron led to a marked slowdown of tumor cell growth after tumor cell line transplantation in mice. Specifically, our results suggest that iron supplementation promotes antitumor responses by increasing IFNγ production by T cells. In addition, iron supplementation improved the efficacy of anti-PD1 cancer immunotherapy in mice. Finally, our study suggests that, in patients with cancer, the quality and efficacy of the antitumor response following anti-PD1 immunotherapy may be modulated by plasma ferritin levels. In summary, our results suggest the benefits of iron supplementation on the reactivation of antitumor responses and support the relevance of a fruitful association between immunotherapy and iron supplementation., (©2024 American Association for Cancer Research.)

Background and Aims: The liver is an innervated organ that develops a variety of chronic liver disease (CLD). Axon guidance cues (AGCs), of which ephrins, netrins, semaphorins and slits are the main representative, are secreted or membrane‐bound proteins that can attract or repel axons through interactions with their growth cones that contain receptors recognizing these messengers. While fundamentally implicated in the physiological development of the nervous system, the expression of AGCs can also be reinduced under acute or chronic conditions, such as CLD, that necessitate redeployment of neural networks. Methods: This review considers the ad hoc literature through the neglected canonical neural function of these proteins that is also applicable to the diseased liver (and not solely their observed parenchymal impact). Results: AGCs impact fibrosis regulation, immune functions, viral/host interactions, angiogenesis, and cell growth, both at the CLD and HCC levels. Special attention has been paid to distinguishing correlative and causal data in such datasets in order to streamline data interpretation. While hepatic mechanistic insights are to date limited, bioinformatic evidence for the identification of AGCs mRNAs positive cells, protein expression, quantitative regulation, and prognostic data have been provided. Liver‐pertinent clinical studies based on the US Clinical Trials database are listed. Future research directions derived from AGC targeting are proposed. Conclusion: This review highlights frequent implication of AGCs in CLD, linking traits of liver disorders and the local autonomic nervous system. Such data should contribute to diversifying current parameters of patient stratification and our understanding of CLD. [ABSTRACT FROM AUTHOR]

Purpose: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. Methods: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. Results: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). Conclusion: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A. [ABSTRACT FROM AUTHOR]

Background: Inflammation is implicated in breast cancer development, and diet is one of the modifiable risk factors involved in the regulation of chronic inflammation. Previous studies on the association between breast cancer risk and Dietary Inflammatory Indexes (DII) derived from food frequency questionnaires and data on inflammatory potential of dietary components have reported inconsistent results. Objective: To investigate the association between the DII and the risk of breast cancer using data from a large population-based cohort study. Design: A total of 67,879 women from the E3N cohort were followed from 1993 to 2014. A total of 5686 breast cancer cases were diagnosed during the follow-up. The food frequency questionnaire administered at baseline in 1993 was used to calculate an adapted DII. Cox proportional hazard models using age as the time scale were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Spline regression was used to determine any dose–response relationship. We also evaluated effect modification by menopausal status, body mass index, smoking status and alcohol consumption. Results: The median DII score of the study population was slightly pro-inflammatory (DII = + 0.39); ranged from – 4.68 in the lowest quintile to + 4.29 in the highest quintile. The HR increased linearly with the DII (HR per 1SD = 1.04 [95% CI: 1.01, 1.07]), and reached 1.13 [95% CI: 1.04, 1.23] in the 5th quintile group as compared to the first. A positive linear dose–response relationship was also observed when modeling DII with spline functions. Slightly higher HRs were observed in non-smokers (HR for 1-SD increase 1.06 [95% CI: 1.02, 1.10]; p trend = 0.001) and in low-alcohol consumers (≤ 1 glass/day) (HR for 1-SD increase 1.05 [95% CI: 1.01, 1.08]; p trend = 0.002). Conclusion: Our results suggest a positive association between DII and breast cancer risk. Consequently, the promotion of anti-inflammatory diet may contribute to breast cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. Methods: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. Results: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05–1.58] for women), smoking (OR = 1.54 [95% CI 1.13–2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06–1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26–1.36], OR = 1.37 [95% CI 1.33–1.42] and OR = 1.34 [95% CI 1.29–1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. Conclusions: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms. [ABSTRACT FROM AUTHOR]

Many dietary guidelines recommend restricting the consumption of processed red meat (PRM) in favour of healthier foods such as fish, to reduce the risk of chronic conditions such as hypertension and diabetes. The objective of this study was to estimate the potential effect of replacing PRM for fatty fish, lean fish, red meat, eggs, pulses, or vegetables, on the risk of incident hypertension and diabetes. This was a prospective study of women in the E3N cohort study. Cases of diabetes and hypertension were based on self-report, specific questionnaires, and drug reimbursements. In the main analysis, information on regular dietary intake was assessed with a single food history questionaire, and food substitutions were modelled using cox proportional hazard models. 95 % confidence intervals were generated via bootstrapping. 71 081 women free of diabetes and 45 771 women free of hypertension were followed for an average of 18·7 and 18·3 years, respectively. 2681 incident cases of diabetes and 12 327 incident cases of hypertension were identified. Relative to PRM, fatty fish was associated with a 15 % lower risk of diabetes (HR = 0·85, 95 CI (0·73, 0·97)) and hypertension (HR = 0 85 (0·79, 0·91)). Between 3 and 10 % lower risk of hypertension or diabetes was also observed when comparing PRM with vegetables, unprocessed red meat or pulses. Relative to PRM, alternative protein sources such as fatty fish, unprocessed red meat, vegetables or pulses was associated with a lower risk of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Despite experimental studies suggesting a disease-modifying role of oestrogens, results from epidemiological studies on the relation of reproductive characteristics and hormonal exposures with Parkinson disease in women are conflicting. We used the data from the E3N cohort study including 98,068 women aged 40-65y in 1990 followed until 2018. Parkinson disease was ascertained using a validation process based on drug claim databases and medical records. Reproductive characteristics and hormonal exposures were self-reported (11 questionnaires). Associations of exposures with Parkinson disease incidence were investigated using time-varying Cox proportional hazards regression with a 5-year exposure lag and age as the time scale adjusted for confounders. We identified 1165 incident Parkinson disease cases during a mean follow-up of 22.0 years (incidence rate = 54.7 per 100 000 person-years). Parkinson disease incidence was higher in women with early (<12y, hazard ratio [HR] = 1.21, 95% confidence interval [CI] = 1.04-1.40) or late age at menarche (≥14y, HR = 1.18, 95% CI = 1.03-1.35) than in women with menarche at 12-13y. Nulliparity was not associated with Parkinson disease, but Parkinson disease incidence increased with the number of children in parous women (P-trend = 0.009). Women with artificial (surgical, iatrogenic) menopause were at greater risk than women with natural menopause (HR = 1.28, 95% CI = 1.09-1.47), especially when artificial menopause occurred at an early age (≤45.0 years). Postmenopausal hormone therapy tended to mitigate greater risk associated with artificial or early menopause (≤45.0 years). While fertility treatments were not associated with Parkinson disease overall, ever users of clomiphene were at greater Parkinson disease risk than never users (HR = 1.81, 95% CI = 1.14-2.88). Other exposures (breastfeeding, oral contraceptives) were not associated with Parkinson disease. Our findings suggest that early and late age at menarche, higher parity, and artificial menopause, in particular at an early age, are associated with increased Parkinson disease incidence in women. In addition, there was some evidence that use of exogenous hormones may increase (fertility treatments) or decrease (postmenopausal hormone therapy) Parkinson disease incidence. These findings support the hypothesis that hormonal exposures play a role in the susceptibility to neurodegenerative diseases. If confirmed, they could help to identify subgroups at high risk for Parkinson disease. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies have found that menopausal hormone therapy (MHT) use is associated with an increased ovarian cancer risk. However, whether different MHT types confer the same level of risk is unclear. We estimated the associations between different MHT types and the risk of ovarian cancer in a prospective cohort. Methods The study population included 75 606 postmenopausal women from the E3N cohort. Exposure to MHT was identified from self-reports in biennial questionnaires between 1992 and 2004 and from drug claim data matched to the cohort between 2004 and 2014. Hazard ratios and 95% confidence intervals (CIs) of ovarian cancer were estimated using multivariable Cox proportional hazards models with MHT as a time-varying exposure. Tests of statistical significance were 2-sided. Results Over an average 15.3 years follow-up, 416 ovarian cancers were diagnosed. Hazard ratios of ovarian cancer associated with ever use of estrogens combined with progesterone or dydrogesterone and ever use of estrogens combined with other progestagen were equal to 1.28 (95% CI = 1.04 to 1.57) and 0.81 (95% CI = 0.65 to 1.00), respectively (P homogeneity = .003), compared with never use. The hazard ratio for unopposed estrogen use was 1.09 (95% CI = 0.82 to 1.46). We found no trend according to duration of use or time since last use except for estrogens combined with progesterone or dydrogesterone, which showed decreasing risk with increasing time since last use. Conclusion Different MHT types may impact ovarian cancer risk differentially. The possibility that MHT containing progestagens other than progesterone or dydrogesterone may confer some protection should be evaluated in other epidemiological studies. [ABSTRACT FROM AUTHOR]

This paper analyses the role played by members of the Curie family in the visual diplomacy of cancer treatments. This relationship started in 1921, when Marie Curie travelled to the US, accompanied by her two daughters, Ève and Irène, to receive a gram of radium at the White House from President Warren Harding. In the years that followed, Ève Curie, as the biographer and natural heir of radium discoverers Marie and Pierre Curie, continued to contribute to the visual diplomacy of cancer campaigning. Two events will be analysed through an interdisciplinary lens, merging history of science and visual-diplomacy studies, to show how the legacy of the Curies played out in the international consolidation of pre-war transnational alliances in the fight against cancer. One involves the picture of the chargé d'affaires of the France Republic, Jules Henry, receiving the biography authored by Ève, Madame Curie , at the French embassy in Washington. The other concerns the photograph of Ève visiting the Portuguese Oncology Institute (IPO) in 1940, which was immediately reproduced in the Institute's bulletin in order to raise awareness of cancer prevention strategies, and also captured in film as a propaganda tool for the Estado Novo regime (1933–74). [ABSTRACT FROM AUTHOR]