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Abstract Background Bisphenol S (BPS) is the main substitute for bisphenol A (BPA), a well-known plasticiser and endocrine disruptor. BPS disrupts ovarian function in several species. Moreover, a few studies have reported that the effects of BPS might be modulated by the metabolic status, and none have characterised the granulosa cell (GC) proteome after chronic BPS exposure. Objectives This study aimed to decipher the mechanisms of action of chronic BPS exposure on the proteome of ewe GCs while considering the interaction between a deliberate contrasted metabolism and reproductive function. Methods Forty ewes were split into two groups with contrasted diets: restricted (R, n = 20) and well-fed (WF, n = 20). The R and WF ewes were subdivided according to the dose of BPS administered through the diet (0–50 µg/kg/day), forming four groups: R0, R50, WF0 and WF50. After 3-month BPS daily exposure, GCs were recovered during the pre-ovulatory stage and proteins were analysed by nano-liquid chromatography coupled with tandem mass spectrometry. Results Chronic exposure to BPS affected the GC proteome differently according to the ewe metabolic status. Fifty-nine out of 958 quantified proteins were differentially abundant between groups and are mainly involved in carbohydrate and lipid pathways. Unsupervised hierarchical clustering of differentially abundant proteins (DAPs) identified four clusters of 34, 6, 5 and 14 proteins according to the BPS exposure and diet interaction. Pairwise comparisons between groups also revealed a strong effect of BPS exposure and diet interaction. Functional analysis of DAPs highlighted that BPS upregulated β-glucuronidase (GUSB; p = 0.002), a protein especially able to deconjugate bisphenol glucuronides (BP-g). Moreover, among unexposed ewes, GUSB was detected only in well-fed ewes. Discussion Conjugation of glucuronides inhibits the oestrogenic activity of bisphenols. Upregulation of GUSB in ewes dosed with BPS would prolong the oestrogenic effects of BPS by deconjugating BPS-g into free BPS. In addition, literature has reported an up-regulation of GUSB in people suffering from obesity. Therefore, people suffering from obesity could be subjected to prolonged and aggravated exposure to BPS. These data highlighted the deleterious effects of BPS and its interaction with metabolic status.

Abstract Objective Patients with symptomatic lower extremity artery disease (LEAD) should have an optimal management in terms of lipid goal [i.e. controlled LDL-cholesterol (LDLc)] and medical treatment (triple therapy with an antiplatelet agent, a statin and an angiotensin-converting enzyme inhibitor or a angiotensin-receptor antagonist). Prevalence of LEAD patients with a LDLc

Abstract Background In vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8–16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%). Methods Bovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7–8. Expanded blastocysts on days 7–8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing. Results Under 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P

Abstract Sickle cell disease is a rare genetic disease resulting from an abnormality in hemoglobin. Hemostasis in the steady state, defined as ≥2 months without vaso‐occlusive crises, is poorly described in the literature. We report the routine hemostasis profile in steady state patients with sickle cell disease (SCD), including during pregnancy and according to phenotype. This retrospective study collected data over the period 2010 to 2021. Data on routine hemostasis parameters (prothrombin time [PT] activated partial thromboplastin time [aPTT], and platelets) were collected from medical records and were compared with laboratory norms including during pregnancy; the HbSS phenotype was compared with the HbSC, HbSB°thalassemia, and HbSB+thalassemia phenotypes. we included 119 adults (representing 190 day‐hospitals) with SCD who had attended at least one checkup in the steady state. Seven patients (15 day‐hospitals) on anticoagulants were excluded. Eleven (17 day‐hospitals) were pregnant. Mean routine hemostasis parameters were within normal values regardless of pregnancy. Mean PT was lower during pregnancy (12.3 ± 0.6 s vs. 13.2 ± 1.0 s; P = .01). PT and platelet counts were higher (P = .01) and aPTT was lower (P = .03) in men and nonpregnant women in the HbSS group compared with those in the HbSC group. routinely collected hemostasis parameters in steady state patients were within normal laboratory values, including in pregnant women. PT values differed significantly between pregnant women and nonpregnant women, and PT, aPTT, and platelet counts differed between HbSS, HbSC, and HbSB+thalassemia phenotypes.

Abstract This paper presents a dataset of 3D sagittal left otolith meshes from 339 individual red mullet (Mullus barbatus). These immature specimens were collected from 17 geographical areas covering the entire Mediterranean Sea. Measured biological parameters were: fish total length (TL ± 1 mm, range from 125 to 238 mm), total weight (W ± 0.1 g, range from 14.9 to 168.0 g), sex (S), sexual maturity staging (Mat). The 3D otolith dataset comprises high-resolution meshes of otoliths obtained using microtomography (29.2 μm voxel size). The data offer valuable insights into the morphological variability and population structure of red mullet populations in the Mediterranean Sea. Potential applications of the dataset include age determination, stock identification, and population connectivity analysis. These applications aim to enhance the understanding of red mullet populations and contribute to the sustainable management of marine resources in the Mediterranean Sea.

Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Abstract Lower extremity peripheral artery disease (PAD) often results from atherosclerosis, and is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Individuals with T2DM exhibit a more severe manifestation and a more distal distribution of PAD compared to those without diabetes, adding complexity to the therapeutic management of PAD in this particular patient population. Indeed, the management of PAD in patients with T2DM requires a multidisciplinary and individualized approach that addresses both the systemic effects of diabetes and the specific vascular complications of PAD. Hence, cardiovascular prevention is of the utmost importance in patients with T2DM and PAD, and encompasses smoking cessation, a healthy diet, structured exercise, careful foot monitoring, and adherence to routine preventive treatments such as statins, antiplatelet agents, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. It is also recommended to incorporate glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) in the medical management of patients with T2DM and PAD, due to their demonstrated cardiovascular benefits. However, the specific impact of these novel glucose-lowering agents for individuals with PAD remains obscured within the background of cardiovascular outcome trials (CVOTs). In this review article, we distil evidence, through a comprehensive literature search of CVOTs and clinical guidelines, to offer key directions for the optimal medical management of individuals with T2DM and lower extremity PAD in the era of GLP-1RA and SGLT2i.

Abstract Background Bisphenol S (BPS) is a substitute for bisphenol A in plastic manufacturing and, as a potential endocrine disruptor, may alter the physiology of the oviduct, in which fertilization and early embryo development take place in mammals. The objective of this study was to assess the effect of a daily dietary exposure to BPS combined with a contrasted diet on the oviduct fluid proteome using an ovine model. Results Eighty adult cyclic ewes were allotted to four groups (20/group): overfed (OF) consuming 50 µg/kg/day of BPS in their diet, underfed (UF) consuming 50 µg/kg/day of BPS, and non-exposed controls in each diet group. After three months, the mean body condition score, plasma levels of glucose and non-esterified fatty acids were significantly higher in OF than in UF females. The proteins in collected OF samples (50 µg) were analyzed by nanoliquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS). Overall, 1563 proteins were identified, among which 848 were quantified. Principal component analysis of the data revealed a clear discrimination of samples according to the diet and a segregation between BPS-exposed and non-exposed females in overfed ewes. Hierarchical clustering of differentially abundant proteins (DAPs) identified two clusters of 101 and 78 DAPs according to the diet. Pairwise comparisons between groups revealed a stronger effect of BPS in OF than in UF females (70 vs. 24 DAPs) and a stronger effect of the diet in BPS-exposed than non-exposed females (56 vs. 36 DAPs). Functional analysis of DAPs showed an enrichment in metabolic processes, immune system, cell response to stress, and reproductive processes. Conclusions This work highlights for the first time the important impact of BPS on the oviduct proteome, with larger effects seen in OF than UF females. These results, together with previous ones, raise health concerns for everyone and call for a greater regulation of BPS in the food industry.

This study investigated drought and flooding changes in West Africa between 1983–2012 and projected near future (2025–2054) periods. The datasets used are the CHIRTS and CHIRPS-2 for observed reanalysis and five (05) models of ISIMIP2b for Shared Socio-economic Pathways (SSP1.2-6 and SSP5-8.5). Extremely and very wet days total precipitation (R95pTOT; R99pTOT) and Standardized Precipitation Evapotranspiration Index (SPEI) were employed to investigate floods and drought spatial distribution using Sen Slope trend analysis method. The results showed that there is a variability in the spatial distribution of extreme indices with an upward and downward trend of dry and wet rainfall periods in West Africa in both historical and projected periods. This observation suggests that the study area is faced with rainfall variability marked by extreme events. A further examination on the spatial and temporal distribution of flood occurrence showed that more flood events were observed in the Gulf of Guinea and Savannah countries, followed by an increase in uniform spatial distribution and moderate wet days both under SSP1.2.6, and SSP 5.8.5. In addition, result showed that an upward trend in wet periods can cause the occurrence of extreme events associated with floods in the context of global warming. However, with these scenarios negative changes are not excluded in the East, the Sahel and some western part of the Gulf of Guinea in the study area for the SSP5.8.5 scenario. Thus, the results revealed that the spatio- temporal variability of extreme rainfall can have repercussions on the hydrological functioning of watersheds, water availability and water-dependent activities.

L'objectif de cette étude est d'analyser les liens entre les indices climatiques et la variabilité des séries de précipitations et de débits. Afin de mieux comprendre la non stationnarité des différentes stations, les données de débits et de pluviométries utilisées concernent la station de Tortiya (1960–1996). Les indices climatiques couplés à ces séries sont l'indice NAO (North Atlantic Oscillation) et l'ENSO (El Niño – Southern Oscillation) sur la même période d'étude. La méthodologie a consisté à appliquer l'analyse et la cohérence en ondelettes sur les séries temporelles. Ces méthodes ont mis en évidence les modes de variabilité dans les séries chronologiques : le mode infra annuel, le mode annuel et le mode interannuel (1–2 ans; 2–4 ans; 4–8 ans). D'une part, les résultats montrent que la variabilité du signal est expliquée dans les hautes fréquences (6 mois à 1 an) dans les différentes séries chronologiques. À cette fréquence, c'est le mode annuel (1 an) qui enregistre toute la variabilité du signal comprise entre 30 % et 70 %. D'autre part, ce travail présente aussi des signaux sur d'autres fréquences et périodes assez faibles. L'analyse en ondelette a révélé que le signal dominant est très largement significatif au niveau du cycle annuel. Par ailleurs, l'usage de la cohérence en ondelettes entre les indices climatiques (ENSO, NAO) et les précipitations, indiquent une forte influence du NAO sur les séries pluviométriques et de débits.

Due to pronounced hydroclimatic fluctuations and rapid urban growth, coastal lagoonal systems in the Southern Mediterranean semi-arid areas undergo pronounced shoreline retreats and increased coastal floodings. The socioeconomic impacts of these alarming coastal changes remain poorly uncharacterized. To address this deficiency, we calculate the Socioeconomic Vulnerability Index (SVI) based on the decadal changes in shoreline retreat and land use occupation considering the study case of the coastal lagoon of Ghar El Melh in Tunisia which is representative of several lagoonal systems in the southern Mediterranean basin. We first monitor the diachronic shoreline changes from 1882 to 2016 using aerial and orbital photogrammetric scenes combined with topographic and bathymetric maps. Using the Digital Shoreline Analysis System (DSAS) and historic bathymetric records, we then measure the changes in shoreline position from 1882 to 2016. Secondly, the above is correlated with the Land Use/Land Cover (LULC) assessment using a supervised classification algorithm from multiple Landsat 5-8 orbital photogrammetric scenes. We assess the SVI using five socioeconomic parameters: (1) population density, (2) land use change, (3) road network, and (4) settlements. Our results reveal the occurrence of severe coastal erosion with a maximum Net Shoreline Movement of −1580 m (±6 m) between 1882 and 2016. Moreover, the changes in land use from 1985 to 2021 reveal the extension in urban growth around the lagoon, rising from 5.4 % to 13.5 %. Whereas the vegetation coverage is decreasing by 9 % over the same period. The resulting SVI map reveals that 85 % of the lagoon area is characterized by high to very high vulnerability. This high coastal vulnerability is found to be primarily due to the extensive change in land occupation over the last few decades and is aggravated by the increase in hydroclimatic extremes.

The Republic of Djibouti is a small country in the Horn of Africa and as for most regions of Africa, ground rainfall stations are sparse. This study aims to compare at different time steps (annual, monthly, and daily) 15 rainfall estimation products (P-datasets) to 5 reference ground-based rainfall stations, over the period of 1980–1990. To classify the reliability of these products, several metrics were considered, the Kling Gupta Efficiency (KGE) and the Heidle Skills Scores (HSS at daily time step). For the study area, 5 P-datasets present high KGE values at annual and monthly time step: EWEMBI, GPCC, JRA-55 Adj, MSWEP and WFDEI-GPCC; the best 5 performing products at daily time step are CHIRPS, EWEMBI, JRA-55 Adj, MSWEP and WFDEI-GPCC. To complete this comparative analysis, it will be necessary to perform an analysis at the watershed scale and on a new temporal window.

The Ouémé River basin extends over almost half of Benin's territory, entirely located in a humid tropical climate. This river system includes a deltaic zone (delta of the Ouémé) known for its high agricultural potential and thus subject to a socio-economic development agenda. The Ouémé delta is facing recurrent floods that maintain rural agricultural population into a retrograding crisis with significant damages such as losses of properties. The objective of this study is to improve decision-making in the Ouémé basin through the simulation of exceptional floods using the HEC-RAS model. The HEC RAS model is a conceptual model, which works through mathematical and physical formulas to implement environmental phenomena for forecasting, understanding and analysis purposes. The model inputs used are basin GIS data, hydro-meteorological data, characteristics of existing hydraulic structures, etc. The targeted outputs include 1D/2D/3D view plans with support of satellite images, tables, graphs and curves. It is worth mentioning that the model provides outputs compatible with other tools, such as civil engineering (Civil 3D, Revit, Infraworks, etc.) and GIS, that help to expand the valorization fields. The implementation of the model in the Ouémé basin has made it possible to note: (i) that the recurring effect of losses and damages is justified by the settlement of the population on the river banks; (ii) that there is an important agricultural production in areas of high flood risk; (iii) that depending on the occurrence of the phenomenon, the flooded extent and the height of submersion remains variable, and more important for extreme flooding; (iv) about 12.07 % occurrence of river flood against 13.24 % for flash flood at a return period of 30 years. Moreover, it is very relevant to note that most of flood waters converge to the western part of the basin (an area with a low risk of flooding, stretched over 63.68 km2) and to the eastern part around the Damè-Wogon depression (an area at high risk of flooding, stretched over 10.49 km2).

A numerical model of packing applied to rigid objects is presented. It aims at describing a random stack of polymer composite chips in order to model the packing step of an existing recycling technique. The geometric properties of the stack play a major role in the mechanical properties of the recycled products. Short, simple and effective geometric descriptors of the stack are proposed. Their ability to differentiate random stacks is illustrated with an example. Then, a validation is proposed based on experimental data obtained from a bench specially designed for this work. The tests consist in the free fall of square chips. Finally, the developed model is compared to other models (free fall and packing of fibers) in order to enforce its relevance in the simulation of packing of rigid objects.

Summary: Background: The clinical relevance of recurrent venous thromboembolism (VTE) after discontinuing anticoagulation in patients with COVID-19-associated VTE remains uncertain. We estimated the incidence rates and mortality of VTE recurrences developing after discontinuing anticoagulation in patients with COVID-19-associated VTE. Methods: A prospective, multicenter, non-interventional study was conducted between March 25, 2020, and July 26, 2023, including patients who had discontinued anticoagulation after at least 3 months of therapy. All patients from the registry were analyzed during the study period to verify inclusion criteria. Patients with superficial vein thrombosis, those who did not receive at least 3 months of anticoagulant therapy, and those who were followed for less than 15 days after discontinuing anticoagulation were excluded. Outcomes were: 1) Incidence rates of symptomatic VTE recurrences, and 2) fatal PE. The rate of VTE recurrences was defined as the number of patients with recurrent VTE divided by the patient-years at risk of recurrent VTE during the period when anticoagulation was discontinued. Findings: Among 1106 patients with COVID-19-associated VTE (age 62.3 ± 14.4 years; 62.9% male) followed-up for 12.5 months (p25-75, 6.3–20.1) after discontinuing anticoagulation, there were 38 VTE recurrences (3.5%, 95% confidence interval [CI]: 2.5–4.7%), with a rate of 3.1 per 100 patient-years (95% CI: 2.2–4.2). No patient died of recurrent PE (0%, 95% CI: 0–7.6%). Subgroup analyses showed that patients with diagnosis in 2021–2022 (vs. 2020) (Hazard ratio [HR] 2.86; 95% CI 1.45–5.68) or those with isolated deep vein thrombosis (vs. pulmonary embolism) (HR 2.31; 95% CI 1.19–4.49) had significantly higher rates of VTE recurrences. Interpretation: In patients with COVID-19-associated VTE who discontinued anticoagulation after at least 3 months of treatment, the incidence rate of recurrent VTE and the case-fatality rate was low. Therefore, it conceivable that long-term anticoagulation may not be required for many patients with COVID-19-associated VTE, although further research is needed to confirm these findings. Funding: Sanofi and Rovi, Sanofi Spain.