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BackgroundPheochromocytomas (PCCs) and paragangliomas (PGLs) (PPGLs) are rare tumours arising from the chromaffin cells. There is evidence suggesting a link between hypoxemia and PPGLs. Chronic hypoxia can lead to gain of function somatic variants in the EPAS1 gene that encodes for hypoxia-inducible factor 2-alpha (HIF-2α), involved in PPGL tumorigenesis.ObjectiveTo describe a rare case of PCC in a pulmonary transplant patient and characterize the tumour’s genetic background.Clinical CaseA 47 year-old man underwent a lung transplant for chronic obstructive pulmonary disease associated with alpha-1 antitrypsin deficiency. He required home oxygen therapy for 3 years prior to transplant. Nineteen years after transplant, a CT-scan revealed a 5.8 cm x 3.9 cm heterogeneous right adrenal mass (HU of 7). Initial assessments indicated elevated 24-hour urinary catecholamines. Consequently, the patient underwent laparoscopic right adrenalectomy, confirming the PCC diagnosis.Genetic studies1) Germline PPGL multigene panel: After consent, the patient underwent a panel of 14 susceptibility genes for PPGLs that revealed no pathogenic variants. 2) Somatic genetic analysis for EPAS1 gene found no variants. However, tumoral RNA sequencing unveiled activation of the HIF pathway.ConclusionWe describe a rare case of PCC in a pulmonary transplant recipient, with genetic analyses showing no germline pathogenic variants and no somatic variants in the EPAS1 gene. RNA sequencing highlighted HIF pathway activation and angiogenic implications. Further research is necessary to elucidate the genetic and molecular mechanisms underlying PCCs in this specific case and determine its link with hypoxemia in the context of pulmonary disease.

Background: Inadequate and excessive gestational weight gain (GWG) are rising epidemiological health concerns, affecting a substantial proportion of pregnant women in high-income countries and contributing to a multitude of adverse maternal and infant health outcomes. The aim of this scoping review was to identify key structural vulnerability factors (SVFs) related to GWG, and to examine the extent, range, and nature of the existing literature to inform future research. Methods: Electronic searches were performed in October 2018 (updated in August 2019) in MEDLINE(R) ALL, EMBASE, PsycINFO, CINAHL, and Sociological Abstracts databases. Eligible studies had an observational design, had to be conducted before COVID-19, in a high-income country, have pregnant participants, and perform inferential statistics between an SVF and GWG. Results: Of the 157 included articles, the eight SVFs most commonly studied in association with GWG were race/ethnicity (n=91 articles), age (n=87), parity (n=48), education (n=44), income (n=39), marital status (n=28), immigration (n=19), and abuse (n=12). Substantial heterogeneity across study contexts, methodologies, populations, and findings was identified. Studies spanned 22 high-income countries, were predominantly conducted in the USA (77%), and most studies (60%) had a retrospective design. Race/ethnicity was the most extensively studied factor, covering the longest time period (since 1976) and having the largest sample size, and the second-highest proportion of studies reporting a significant relationship with GWG (79%), following immigration status (95%). Conclusions: Given the heterogeneity in findings across studies, adopting an intersectional approach may enhance our understanding of the complex interplay between SVFs and the social context in relation to GWG. This nuanced perspective is critical for informing future research and developing effective strategies to address the pervasive perinatal health challenges associated with inadequate and excessive GWG.

Mo2Ti2C3Tx MXene materials, bare or loaded with strongly anchored single Pt atoms, were investigated using various methods, including STEM, XPS, XAS and DFT calculations. Upon Pt impregnation, the delaminated Mo-rich MXene surface undergoes partial oxidation, which is reversed by an H2 thermal treatment at 400 °C. The optimized MXene shows high catalytic activity for CO2 hydrogenation to CO and smaller amounts of methane and methanol. Around and above the pretreatment temperature of 400 °C, the MXene is gradually defunctionalized from O- and F-containing groups and depleted in carbidic carbon, leading to deactivation. Single Pt atoms are cationic after impregnation, and reduce upon H2 treatment, filling surface Mo vacancies. Pt addition increases the MXene activity, in particular by facilitating H2 dissociation, but has little effect on the single-atom catalyst selectivity and on the rate dependence upon reactant partial pressures. The lowest Pt loading leads to the highest turnover frequency, indicating that the MXene surface sites are key to CO2 activation.

Objectives. To analyze the budget impact of upadacitinib (UPA) 15 mg + methotrexate (MTX) for the treatment of moderate-to-severe rheumatoid arthritis (RA) in patients with an inadequate response to conventional disease-modifying antirheumatic drugs (cDMARD-IR) from the perspective of social security and the private health sector in Argentina. Materials and methods. A budget impact analysis model was developed for a hypothetical cohort of 100,000 adults with health insurance coverage who were diagnosed with RA over a 5-year time horizon. The model parameters were obtained through literature review and validated by local experts. The costs are expressed in 2024 US dollars (USD). Results. The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR resulted in minimal increase, with a five-year total cumulative incremental cost of USD 1,855 for social security and USD 1,812 for the private health sector, representing 2% of the total budget. The acquisition cost of UPA was the most influential variable in the sensitivity analysis. Conclusions. The introduction of UPA 15 mg + MTX for the treatment of moderate-to-severe RA and cDMARD-IR can provide an effective treatment option with a minimal increase in costs for the healthcare system in Argentina, which is especially important in developing countries where health system budgets are more limited. Providing evidence-based estimates is a valuable tool for informing healthcare policies and can help policymakers make informed decisions about the allocation of healthcare resources to improve patient outcomes while also managing costs.

The synthesis of supported multielement transition metal phosphides (TMPs) to exploit the synergistic interplay between electronic and geometric effects resulting from the presence of different metals in the material and the arrangement of heterogeneous atoms is pivotal for reducing metal content while offering multiple active sites. However, the integration of Ni, Co, and P, for example, into a nanostructured carbon network to develop self‐supporting NixCoyP bimetallic phosphides is limited by several factors, including the synthesis and the discrepancy between the crystal structure of the respective monometallic phosphides. Moreover, conventional synthesis of supported TMPs often separates nanoparticles, support and phosphidation steps, which do not allow tailoring of physical and catalytic properties via particle support, electronic and geometric interactions. Herein, an innovative solid‐state, ex situ phosphidation‐free approach tailored to synthesize a library of self‐supporting NixCoyP TMPs in N,S,P‐modified nanostructured carbon networks generated together with NixCoyP particles is presented. Extensive multivariate characterization validates the unique properties of NixCoyP bimetallic materials with enhanced electrocatalytic performance for the hydrogen evolution reaction and the selective electroconversion of biomass‐derived 5‐hydroxymethylfurfural (5‐HMF) to value‐added 2,5‐furandicarboxylic acid (FDCA) with 90–100% Faradaic efficiency. Overall, the synthesis expands the possibilities for tailoring the microstructure of supported TMPs for improved physical/catalytic properties.

Abstract Background The α‐Gal syndrome (AGS) is characterized by the presence of specific IgE‐antibodies to the carbohydrate galactose‐α‐1,3‐galactose (α‐Gal). Sensitization to α‐Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α‐Gal in a high‐risk cohort of forestry employees (FE) in Luxembourg. Methods Questionnaires and serum samples of FE from Luxembourg (n = 219) were retrospectively analyzed. α‐Gal specific IgE was quantified by ImmunoCAP, α‐Gal specific IgG and subclasses IgG1–4 were determined by ELISA. Additionally, sera from population‐based controls (n = 150) and two groups of food‐allergic patients, patients with AGS (n = 45) and fish‐allergic patients (n = 22) were assessed for IgG antibody responses to α‐Gal and cod extract. Results Twenty‐one percent of FE was sensitized to α‐Gal (sIgE ≥ 0.1 kUA/L). Both sensitized and non‐sensitized FE exhibited high levels of α‐Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish‐allergic patients was similar to the profile of the controls for which anti‐α‐Gal responses were dominated by IgG2 antibodies. α‐Gal sIgG4 levels were either very low or undetectable in all groups. Conclusion Our study provides evidence for a continuous stimulation of α‐Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α‐Gal.

Background Fibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO2) compared with arterial blood gas (ABG) saturation (SaO2), the factors that influence the partial pressure of carbon dioxide (PaCO2) and the impact of PaCO2 on outcomes in patients with fibrotic ILD.Study design and methods Patients with fibrotic ILD enrolled in a large prospective registry with a room air ABG were included. Prespecified analyses included testing the correlation between SaO2 and SpO2, the difference between SaO2 and SpO2, the association of baseline characteristics with both the difference between SaO2 and SpO2 and the PaCO2, the association of baseline characteristics with acid-base category, and the association of PaCO2 and acid-base category with time to death or transplant.Results A total of 532 patients with fibrotic ILD were included. Mean resting SaO2 was 92±4% and SpO2 was 95±3%. Mean PaCO2 was 38±6 mmHg, with 135 patients having PaCO2 45 mmHg. Correlation between SaO2 and SpO2 was mild to moderate (r=0.39), with SpO2 on average 3.0% higher than SaO2. No baseline characteristics were associated with the difference in SaO2 and SpO2. Variables associated with either elevated or abnormal (elevated or low) PaCO2 included higher smoking pack-years and lower baseline forced vital capacity (FVC). Lower baseline lung function was associated with an increased risk of chronic respiratory acidosis. PaCO2 and acid-base status were not associated with time to death or transplant.Interpretation SaO2 and SpO2 are weakly-to-moderately correlated in fibrotic ILD, with limited ability to accurately predict this difference. Abnormal PaCO2 was associated with baseline FVC but was not associated with outcomes.

Background The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations. Methods and Results Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild‐type siblings underwent acute and chronic RPAO. They were subjected to full high‐fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild‐type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL‐6 (interleukin‐6) expression and decreased Gdf2 expression (corrected P value1). In this context, male rats expressed higher pulmonary levels of endothelin‐1 and IL‐6 than females. Conclusions Our novel 2‐hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex‐ and gene‐related effects.

Since 2003, the state-of-the-art Canadian Coast Guard Ship (CCGS) research icebreaker Amundsen has furrowed the Canadian Arctic waters to support novel research endeavors and collect oceanographic data. This paper presents the data acquisition, the processing methods and an overview of the data collected during the 2021 expedition as the ship traveled over 30 000 km during 122 d across the Canadian Arctic Ocean, collecting sea surface, atmospheric and seabed underway measurements. A total of 266 casts of a conductivity, temperature and depth profiler mounted on a Conductivity Temperature Depth rosette (CTD Rosette) were also conducted to monitor the main physical, chemical and biological parameters of the water column. More specifically, the data presented here were collected with the CTD Rosette across historical sampling transects in Davis Strait, the North Water Polynya (NOW) and Cape Bathurst. A 182 km dedicated survey using the Moving Vessel Profiler® (MVP), equipped with CTD, transmissometer, dissolved oxygen, fluorescence and sound velocity sensors, was conducted across Hudson Strait. We also present an overview of the data collected by the underway systems (seabed, thermosalinograph and atmospheric). Such data are essential in understanding the impacts of climate warming on the unique environments of the Canadian Arctic Ocean. Amundsen Science supports and promotes easy access and sharing of such valuable data to the scientific community.

Abstract Background t‐AML occurs after a primary malignancy treatment and retains a poor prognosis. Aims To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t‐AML. Results A total of 112 adult patients were included in this study. Fifty‐Five patients received intensive chemotherapy (IC), 33 non‐IC, and 24 best supportive care. At t‐AML diagnosis, 42% and 44% of patients presented an unfavorable karyotype and unfavorable 2010 ELN risk profile, respectively. Among treated patients (n = 88), 43 (49%) achieved complete remission: four out of 33 (12%) and 39 out of 55 (71%) in non‐IC and IC groups, respectively. With a median follow‐up of 5.5 months, the median overall survival (OS) and disease‐free survival (DFS) for the whole population were 9 months and 6.3 months, respectively, and for the 88 treated patients 13.5 months and 8.2 months, respectively. Univariate analysis on OS and DFS showed a significant impact of high white blood cells (WBC) and blast counts at diagnosis, unfavorable karyotype and ELN classification. Multivariate analysis showed a negative impact of WBC count at diagnosis and a positive impact of chemotherapy on OS and DFS in the whole population. It also showed a negative impact of previous auto‐HCT and high WBC count on OS and DFS and of IC on OS in treated patients which disappeared when we considered only confounding variables (age, previous cancers, marrow blasts, and 2010 ELN classification). In a pair‐matched analysis comparing IC treated t‐AML with de novo AML, there was no difference of OS and DFS between the two populations. Conclusion We showed, in this study that t‐AML patients with unfavorable features represented almost half of the population. Best outcomes obtained in patients receiving IC must be balanced by known confounding variables and should be improved by using new innovative agents and therapeutic strategies.

BackgroundHealthy eating during pregnancy has favorable effects on glycemic control and is associated with a lower risk of gestational diabetes mellitus (GDM). According to Diabetes Canada, there is a need for an effective and acceptable intervention that could improve glucose homeostasis and support pregnant individuals at risk for GDM.AimsThis unicentric randomized controlled trial (RCT) aims to evaluate the effects of a nutritional intervention initiated early in pregnancy, on glucose homeostasis in 150 pregnant individuals at risk for GDM, compared to usual care.MethodsPopulation: 150 pregnant individuals ≥18 years old, at ≤14 weeks of pregnancy, and presenting ≥1 risk factor for GDM according to Diabetes Canada guidelines. Intervention: The nutritional intervention initiated in the first trimester is based on the health behavior change theory during pregnancy and on Canada’s Food Guide recommendations. It includes (1) four individual counseling sessions with a registered dietitian using motivational interviewing (12, 18, 24, and 30 weeks), with post-interview phone call follow-ups, aiming to develop and achieve S.M.A.R.T. nutritional objectives (specific, measurable, attainable, relevant, and time-bound); (2) 10 informative video clips on healthy eating during pregnancy developed by our team and based on national guidelines, and (3) a virtual support community via a Facebook group. Control: Usual prenatal care. Protocol: This RCT includes three on-site visits (10–14, 24–26, and 34–36 weeks) during which a 2-h oral glucose tolerance test is done and blood samples are taken. At each trimester and 3 months postpartum, participants complete web-based questionnaires, including three validated 24-h dietary recalls to assess their diet quality using the Healthy Eating Food Index 2019. Primary outcome: Difference in the change in fasting blood glucose (from the first to the third trimester) between groups. This study has been approved by the Ethics Committee of the Centre de recherche du CHU de Québec-Université Laval.DiscussionThis RCT will determine whether a nutritional intervention initiated early in pregnancy can improve glucose homeostasis in individuals at risk for GDM and inform Canadian stakeholders on improving care trajectories and policies for pregnant individuals at risk for GDM.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT05299502, NCT05299502

This article acknowledges a lack of academic works on beauty in the field of game studies and aims to remedy it by showing how beauty is an important concept to understand video games for, at least, two reasons. Firstly, thinking about video games through the lens of beauty allows us to reflect upon the cultural relevance of video games, not as artwork carrying meaning, but as devices improving and expanding our sensibility. Then, we can propose a more general model of the ludic experience, rooted in these analyses, that is ingrained with the heterogeneity and diversity of ludic pleasures and attitudes.

Abstract Background Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low‐dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real‐life conditions. Method This retrospective, real‐life study collected data on venetoclax use and management in a French cohort with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Result Of 118 patients, 81 were in second line/beyond (71.6% also hypomethylating agent [HMA]; 23.5% lowdose cytarabine [LDAC]) and 37 in first line. For venetoclax initiation, 57.3% underwent ramp up and 74.6% were hospitalized. Median venetoclax duration was 2.5 months (range 0.03‐16.2). With all treatment lines and regimens, most common grade 3/4 adverse events were hematologic (overall 96.4% of patients) and infections (57.1%). Dosage adjustments for drug interactions and safety varied between centers. In second‐line/beyond, median progression‐free survival was 4.0 months (95% confidence interval [CI] 2.7‐12.8) with venetoclax‐HMA and 3.4 months (1.3‐8.9) with venetoclax‐LDAC; overall response rate was 51.9% and 41.2%, respectively. Thus, we showed that venetoclax‐based treatment yields promising findings in patients with AML, but to address treatment complexity, practice harmonization is needed.