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Background: The impact of geographical accessibility on cancer survival has been investigated in few studies, with most research focusing on access to reference care centers, using overall mortality and limited to specific cancer sites. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation. Methods: This study included a total of 151,984 cases diagnosed with the 10 most common cancer sites in 21 French cancer registries between 2013 and 2015. Access to primary care was estimated using two indexes: the Accessibilité Potentielle Localisée index (access to general practitioners) and the Scale index (access to a range of primary care clinicians). Mortality in excess was modelized using an additive framework based on expected mortality based on lifetables and observed mortality. Findings: Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. The maximum effect was found for breast cancer; the excess hazard ratio was estimated to be 1.69 (95% CI, 1.20–2.38) 1 year after diagnosis and 2.26 (95% CI, 1.07–4.80) 5 years after diagnosis. Interpretation: This study revealed that this differential access to primary care was associated with mortality in excess for patients with cancer and should become a priority for health policymakers to reduce these inequalities in health care accessibility. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation. Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. [ABSTRACT FROM AUTHOR]

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age‐standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5‐year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5‐year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five‐year cumulative rate of recurrence among resected patients with stage I–III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population‐based collection of cancer recurrence information is crucial to enhance efforts for evidence‐based management of colorectal cancer follow up. [ABSTRACT FROM AUTHOR]

We use a neural network model and Atacama Large Millimeter/submillimeter Array (ALMA) observations of HCN and HNC to constrain the physical conditions, most notably the cosmic-ray ionization rate (CRIR, ζ), in the Central Molecular Zone (CMZ) of the starburst galaxy NGC 253. Using output from the chemical code UCLCHEM, we train a neural network model to emulate UCLCHEM and derive HCN and HNC molecular abundances from a given set of physical conditions. We combine the neural network with radiative transfer modeling to generate modeled integrated intensities, which we compare to measurements of HCN and HNC from the ALMA Large Program ALCHEMI. Using a Bayesian nested sampling framework, we constrain the CRIR, molecular gas volume and column densities, kinetic temperature, and beam-filling factor across NGC 253's CMZ. The neural network model successfully recovers UCLCHEM molecular abundances with ∼3% error and, when used with our Bayesian inference algorithm, increases the parameter-inference speed tenfold. We create images of these physical parameters across NGC 253's CMZ at 50 pc resolution and find that the CRIR, in addition to the other gas parameters, is spatially variable with ζ ∼ a few ×10−14 s−1 at r ≳ 100 pc from the nucleus, increasing to ζ > 10−13 s−1 at its center. These inferred CRIRs are consistent within 1 dex with theoretical predictions based on nonthermal emission. Additionally, the high CRIRs estimated in NGC 253's CMZ can be explained by the large number of cosmic-ray-producing sources as well as a potential suppression of cosmic-ray diffusion near their injection sites. [ABSTRACT FROM AUTHOR]

Background: Few studies have assessed the participation of the spine in arm elevation. The primary aim of this exploratory study was to specify spinal movements during unilateral arm elevation. Methods: We used an EOS imaging system to assess 2D global posture (Sagittal Vertical Axis [SVA], T1 and T9 tilt and Central Sacral Line [CSL]) and segmental spine curves (C3-C7 in the sagittal plane only, and T1-T6, T7-T12 and L1-L5 in the sagittal and frontal planes) for four different left arm elevation levels: in the sagittal (Sa) plane (30°Sa: reference position, 140°Sa and 180°Sa), and in the scapular (Sc) plane (180°Sc), in ten right-handed asymptomatic participants (5 women; mean age 24.6 SD 3.0 years]. In addition, we estimated C1, head and pelvic orientation and head and pelvic linear displacement. We used Bayesian statistics (BF10 > 3 indicates a significant variation: moderate, strong, very strong or extreme evidence). Results: From 140°Sa to 180°Sa or Sc, the significant decrease in SVA and the T1-T9 tilt angles indicated a global backward spine bending (moderate to very strong evidence). The significant reversal of the C3-C7 lordosis at 30°Sa (-1.34 [2.53]°) to kyphosis at 180°Sa (13.88 [3.53]°, strong evidence) and 180°Sc (11.85 [2.75]°, extreme evidence) and the significant decrease in the T7-T12 kyphosis (26.58 [2.84]°at 30°Sa to 16.40 [2.65]° at 180°Sa and 17.60 [2.78]° at 180°Sc [all extreme evidence]) showed a global spine straightening. We found significant pelvic anteversion between 30°Sa and 140°Sa (moderate evidence) and persistent right spine bending and leftward head displacement (extreme evidence). The change in C1 orientation (extreme evidence) showed an atlanto-occipital extension. Conclusion: Simple unconstrained movements of unilateral arm elevation involve the whole spine, pelvis and head, including significant backward spinal bending, a reduction in the low cervical spine lordosis and the thoracic kyphosis, and atlanto-occipital extension. [ABSTRACT FROM AUTHOR]

Despite evidence in previous literature regarding vaccine safety, more data were needed as concerns about COVID-19 vaccines were raised, particularly regarding their effects on female fertility, exacerbated by the widespread dissemination of information without scientific evidence. This study aims to answer the question: does COVID-19 vaccination have any impact on female fertility at a population level. In this ecological study, vaccination rates against COVID-19 and birth rates in 100 different countries were correlated. In addition, the correlation between these two rates of interest and the Gini index were also analyzed. Data were retrieved from the World Population Prospects document produced by the Population Division of the United Nations Department of Economic and Social Affairs, from the World Health Organization (WHO) website, and from the World Bank website. Statistical analyses were conducted using the ANOVA test, and Pearson's correlation using the JASP software. For all analyses, results were considered significant if P < 0.05. In evaluating the trend of the birth rate in the countries included in the study, a persistent reduction of approximately 1.66% per year was observed between 2010 and 2022. From 2019 to 2022, the decline was close to 5%, resulting in an annual average reduction of 1.68%, which is similar to previous years. Among the selected countries, until December 2021, the average number of vaccine doses administered was 137 per 100 inhabitants. There was no observed correlation between the number of vaccine doses administered in different countries and the variation in the birth rate per thousand inhabitants between 2019 and 2022 (Pearson's r = 0.075; P = 0.455). A correlation was found between the Gini index and the birth rate, considering the base year of 2022, with a Pearson's r value of 0.376 (P < 0.01). This correlation remained consistent for all other years. A negative correlation was found between vaccine doses and the Gini index, with a Pearson's r value of -0.219 (P = 0.040). The findings of this article, as well as previous scientific evidence, do not identify any correlation between COVID-19 vaccines and female fertility issues. The associations analyzed in this study indicate the safety of vaccines for reproductive health and contribute to reducing vaccine hesitancy among the population of childbearing age. [ABSTRACT FROM AUTHOR]

The influence of cobalt and cobalt–manganese oxide coating thickness on its ability to be a good diffusion barrier against Cr outward diffusion was investigated for stainless steel interconnects (AISI 441) of a solid oxide cell (SOC). The coatings were all synthesized using a DLI-MOCVD (Direct Liquid Injection-Metal Oxide Chemical Vapor Deposition) hot wall reactor. The study shows that a minimum cobalt oxide thickness of 300 nm was needed to be a good diffusion barrier against Cr for the 500-h exposure test. This observation was linked to the Mn concentration reached in the cobalt spinel during exposure. Indeed, during exposure at high temperature, Mn diffused from the substrate into the cobalt coating and transformed cobalt spinel into Co-Mn spinel. Whereas pure cobalt spinel was a good Cr diffusion barrier, cobalt-manganese spinel, Co3-xMnxO4, was not when x > 2. The thickness of the cobalt coatings must be chosen so that the Mn quantity coming into it from diffusion from the substrate does not degrade the protectiveness of the coating. [ABSTRACT FROM AUTHOR]

Durability is still a critical factor that limits solid oxide cell (SOC) technology industrialization. In order to maintain a good level of performance for the overall targeted lifetime of about 40 kh, the oxidation of the interconnects made of ferritic stainless steel and Cr volatilization from this material to the cell electrodes have to be restricted. CeCo-based coatings were applied by PVD HiPIMS on AISI441 alloy. Their ability to reduce the thickness of the poorly conductive formed oxide and improve Cr retention was studied at sample scale by measurements of weight gain and Cr content by ICP-OES after 5000 h of exposure in ambient air at 700 and 800 °C. In the testing conditions, post-test characterization by SEM/EDX showed that oxide scale thickness was reduced when coatings were applied compared to bare AISI441 steel. Moreover, the strong oxide scale spallation observed at 800 °C with bare AISI441 steel was avoided. Cr volatilization was also strongly decreased. Post-test SEM/EDX and ToF–SIMS characterization of a short stack integrating coatings on the air side in some repeat units (RU) confirmed the limited Cr diffusion in the strontium doped lanthanum manganite (LSM) contact layer when the coating is present after 5200 h of solid oxide electrolysis cell operation (SOEC). [ABSTRACT FROM AUTHOR]

The western Alpine belt is the focal point of moderate but constant seismic activity. Numerous geodynamic and seismological studies underline the many scientific questions linked to Alpine dynamic processes and the associated rate of deformation resulting from late continental collision phases, and the assessment of seismic hazard and its associated risks. Seismic monitoring in the northern French Alps was launched in 1987 with the installation of the first seismological network, hosted by the Earth Science Observatory at Grenoble Alpes University. Since then, the network has been updated over the years, keeping pace with technical developments in seismic instrumentation, monitoring and data management. The homogenization of information described in this scientific data paper is motivated by the need for a single instrumental seismic catalogue, consisting in arrival times picks and hypocenters using the same velocity model. The final catalogue SISMalp-1987–2023 (CC-BY-4.0) contains 50,822 weak-to-moderate earthquakes with local magnitude between −1.8 and 5.0; it can serve as a basis for all general seismotectonic and risk assessment studies in the region. [ABSTRACT FROM AUTHOR]

Background: Homo- and heteromerization of G protein-coupled receptors (GPCRs) plays an important role in the regulation of receptor functions. Recently, we demonstrated an interaction between the serotonin receptor 7 (5-HT7R), a class A GPCR, and the cell adhesion molecule CD44. However, the functional consequences of this interaction on 5-HT7R-mediated signaling remained enigmatic. Methods: Using a quantitative FRET (Förster resonance energy transfer) approach, we determined the affinities for the formation of homo- and heteromeric complexes of 5-HT7R and CD44. The impact of heteromerization on 5-HT7R-mediated cAMP signaling was assessed using a cAMP responsive luciferase assay and a FRET-based cAMP biosensor under basal conditions as well as upon pharmacological modulation of the 5-HT7R and/or CD44 with specific ligands. We also investigated receptor-mediated G protein activation using BRET (bioluminescence resonance energy transfer)-based biosensors in both, homo- and heteromeric conditions. Finally, we analyzed expression profiles for 5-HT7R and CD44 in the brain during development. Results: We found that homo- and heteromerization of the 5-HT7R and CD44 occur at similar extent. Functionally, heteromerization increased 5-HT7R-mediated cAMP production under basal conditions. In contrast, agonist-mediated cAMP production was decreased in the presence of CD44. Mechanistically, this might be explained by increased Gαs and decreased GαoB activation by 5-HT7R/CD44 heteromers. Unexpectedly, treatment of the heteromeric complex with the CD44 ligand hyaluronic acid boosted constitutive 5-HT7R-mediated cAMP signaling and receptor-mediated transcription, suggesting the existence of a transactivation mechanism. Conclusions: Interaction with the hyaluronan receptor CD44 modulates both the constitutive activity of 5-HT7R as well as its agonist-mediated signaling. Heteromerization also results in the transactivation of 5-HT7R-mediated signaling via CD44 ligand. [ABSTRACT FROM AUTHOR]

Pollen limitation has a considerable influence on forest masting, the highly variable and synchronised seed production, on which forest regeneration and ecosystem dynamics largely rely. Depending on the various mechanisms possibly involved in pollen limitation, the consequences of climate change on masting could be very different. These mechanisms were investigated in 10 oak populations along a climatic gradient using surveys of airborne pollen and fruiting rate as a proxy of pollen limitation. We found no support for the widely accepted hypothesis of the intra‐annual synchrony of flower phenology when considered in isolation. Instead, the fruiting rate was largely explained by a combination of intra‐annual flower phenology synchrony, annual investment in flowering and the effects of weather on pollen maturation and diffusion. These findings highlight the need for a cohesive theoretical framework for pollen limitation to accurately predict the impact of climate change on oak‐dominated ecosystems. [ABSTRACT FROM AUTHOR]

Phase change materials (PCMs) have gained a tremendous interest as a means to actively tune nanophotonic devices through the large optical modulation produced by their amorphous to crystalline reversible transition. Recently, materials such as Sb2S3 emerged as particularly promising low loss PCMs, with both large refractive index modulations and transparency in the visible and near‐infrared. Controlling the local and reversible phase transition in this material is of major importance for future applications, and an appealing method to do so is to exploit pulsed lasers. Yet, the physics and limits involved in the optical switching of Sb2S3 are not yet well understood. Here, the reversible laser‐induced phase transition of Sb2S3 is investigated, focusing specifically on the mechanisms that drive the optically induced amorphization, with multi‐physics considerations including the optical and thermal properties of the PCM and its environment. The laser energy threshold for reversibly changing the phase of the PCM is determined through both theoretical analysis and experimental investigation, not only between fully amorphous and crystalline states but also between partially recrystallized states. Then, the non‐negligible impact of the material's polycrystallinity and anisotropy on the power thresholds for optical switching is revealed. Finally, the challenges related to laser amorphization of thick Sb2S3 layers are addressed, as well as strategies to overcome them. These results enable a qualitative and quantitative understanding of the physics behind the optically‐induced reversible change of phase in Sb2S3 layers. [ABSTRACT FROM AUTHOR]

Molecular deuteration is a powerful diagnostic tool for probing the physical conditions and chemical processes in astrophysical environments. In this work, we focus on formaldehyde deuteration in the protobinary system NGC 1333 IRAS 4A, located in the Perseus molecular cloud. Using high-resolution (⁠|$\sim$| 100 au) ALMA (The Atacama Large Millimeter/submillimeter Array) observations, we investigate the [D |$_2$| CO]/[HDCO] ratio along the cavity walls of the outflows emanating from IRAS 4A1. Our analysis reveals a consistent decrease in the deuteration ratio (from |$\sim$| 60-20 per cent to |$\sim$| 10 per cent) with increasing distance from the protostar (from |$\sim$| 2000 to |$\sim$| 4000 au). Given the large measured [D |$_2$| CO]/[HDCO], both HDCO and D |$_2$| CO are likely injected by the shocks along the cavity walls into the gas-phase from the dust mantles, formed in the previous prestellar phase. We propose that the observed [D |$_2$| CO]/[HDCO] decrease is due to the density profile of the prestellar core from which NGC 1333 IRAS 4A was born. When considering the chemical processes at the base of formaldehyde deuteration, the IRAS 4A's prestellar precursor had a predominantly flat density profile within 3000 au and a decrease of density beyond this radius. [ABSTRACT FROM AUTHOR]

Pathogenic Shiga toxin–producing Escherichia coli (STEC) are an important cause of foodborne illness. The detection of STEC in finished products and during the manufacturing process has an important role as part of verification plans, to confirm that practices and procedures described in the food safety program are successfully applied to control STEC. The aim of this study is to evaluate the effect of temperature and pooling in detection and isolation of the major non-O157 STEC serogroups from meat samples with the use of alternative and standard methods. Bovine meat was experimentally inoculated with one of the "Top 6" non-O157 STEC strains (O26, O103, O111, O145, O45, and O121). Both ISO TS 13136:2012 and a novel alternative method were implemented to evaluate the impact of temperature and pooling. An increase of the enrichment temperature to 41.5 °C allowed the detection of the spiked strain in 10% more samples compared to enrichment at 37 °C. The use of 25- and 375-g sample tests demonstrated no statistically differences between both methods. And finally, this alternative method appears easy to use and time-saving for routine laboratory use. [ABSTRACT FROM AUTHOR]

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group. [ABSTRACT FROM AUTHOR]

Using Multimodal Critical Discourse Analysis, this paper examines a sample of X hashtags supporting or criticizing Johnny Depp or Amber Heard in their 2022 domestic abuse/defamation trial, where in both cases there were calls to cancel each. The analysis explores how the acts carried out by the targets for canceling, along with concrete details of their personal circumstances, become set aside as what we call "trigger-ready" interest groups become activated by a perceived transgression in relation to their own more narrow and heterogeneous concerns. Hashtags become an entanglement of vaguely articulated discourses relating to matters including fandom, gender, abuse and conspiracy. These discourses stack up against the target and coalesce into growing outrage. The analysis suggests that intensity of canceling bares little relationship to any actual transgression but to the extent to which these "trigger-ready" groups become involved. This may be a characteristic of wider patterns in online cancel campaigns. [ABSTRACT FROM AUTHOR]

This paper analyses spectropolarimetric observations of the classical T Tauri star (CTTS) GM Aurigae collected with SPIRou, the near-infrared spectropolarimeter at the Canada–France–Hawaii Telescope, as part of the SLS and SPICE Large Programs. We report for the first time results on the large-scale magnetic field at the surface of GM Aur using Zeeman Doppler imaging. Its large-scale magnetic field energy is almost entirely stored in an axisymmetric poloidal field, which places GM Aur close to other CTTSs with similar internal structures. A dipole of about 730 G dominates the large-scale field topology, while higher order harmonics account for less than 30 per cent of the total magnetic energy. Overall, we find that the main difference between our three reconstructed maps (corresponding to sequential epochs) comes from the evolving tilt of the magnetic dipole, likely generated by non-stationary dynamo processes operating in this largely convective star rotating with a period of about 6 d. Finally, we report a |$5.5\sigma$| detection of a signal in the activity-filtered radial velocity data of semi-amplitude |$110\pm 20$|  m s |$^{-1}$|  at a period of |$8.745\pm 0.009$|  d. If attributed to a close-in planet in the inner accretion disc of GM Aur, it would imply that this planet candidate has a minimum mass of |$1.10 \pm 0.30\, M_\mathrm{Jup}$| and orbits at a distance of |$0.082 \pm 0.002$|  au. [ABSTRACT FROM AUTHOR]

Context. The dust- and gas-rich protoplanetary disks around young stellar systems play a key role in star and planet formation. While considerable progress has recently been made in probing these disks on large scales of a few tens of astronomical units (au), the central au requires further investigation. Aims.We aim to unveil the physical processes at play in the innermost regions of the strongly accreting T Tauri Star S CrA N by means of near-infrared interferometric observations. As recent spectropolarimetric observations suggest that S CrA N might undergo intense ejection processes, we focus on the accretion–ejection phenomena and on the star–disk interaction region. Methods. We obtained interferometric observations with VLTI/GRAVITY in the K-band during two consecutive nights in August 2022. The analysis of the continuum emission, coupled with the differential analysis across the Brγ line, allows us to constrain the morphology of the dust and the gas distribution in the innermost regions of S CrA N and to investigate their temporal variability. These observations are compared to magnetospheric accretion–ejection models of T Tauri stars and to previous observations in order to elucidate the physical processes operating in these regions. Results. The K-band continuum emission is well reproduced with an azimuthally modulated dusty ring with a half-light radius of 0.24 au (∼20 R*), an inclination of ∼30°, and a position angle of ∼150°. As the star alone cannot explain such a large sublimation front, we propose that magnetospheric accretion is an important dust-heating mechanism leading to this continuum emission. The Brγ-emitting region (0.05–0.06 au; 5–7 R*) is found to be more compact than the continuum, to be similar in size or larger than the magnetospheric truncation radius. The on-sky displacements across the Brγ spectral channels are aligned along a position angle offset by 45° from the disk, and extend up to 2 R*. This is in agreement with radiative transfer models combining magnetospheric accretion and disk winds. These on-sky displacements remain unchanged from one night to another, while the line flux decreases by 13%, suggesting a dominant contribution of wind to the origin of the Brγ line. Conclusions. Our observations support the scenario where the Brγ line originates from a combination of (variable) accretion–ejection processes in the inner disk region. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) presents diverse symptoms and comorbidities, complicating its diagnosis and management. The primary objective of this cross-sectional, monocentric study was to assess digital gait sensor data's utility for monitoring and diagnosis of motor and gait impairment in PD. As a secondary objective, for the more challenging tasks of detecting comorbidities, non-motor outcomes, and disease progression subgroups, we evaluated for the first time the integration of digital markers with metabolomics and clinical data. Using shoe-attached digital sensors, we collected gait measurements from 162 patients and 129 controls in a single visit. Machine learning models showed significant diagnostic power, with AUC scores of 83–92% for PD vs. control and up to 75% for motor severity classification. Integrating gait data with metabolomics and clinical data improved predictions for challenging-to-detect comorbidities such as hallucinations. Overall, this approach using digital biomarkers and multimodal data integration can assist in objective disease monitoring, diagnosis, and comorbidity detection. [ABSTRACT FROM AUTHOR]

GPR56, an adhesion G-protein coupled receptor (aGPCRs) with constitutive and ligand-promoted activity, is involved in many physiological and pathological processes. Whether the receptor's constitutive or ligand-promoted activation occur through the same molecular mechanism, and whether different activation modes lead to functional selectivity between G proteins is unknown. Here we show that GPR56 constitutively activates both G12 and G13. Unlike constitutive activation and activation with 3-α-acetoxydihydrodeoxygedunin (3αDOG), stimulation with an antibody, 10C7, directed against GPR56's extracellular domain (ECD) led to an activation that favors G13 over G12. An autoproteolytically deficient mutant, GPR56-T383A, was also activated by 10C7 indicating that the tethered agonist (TA) exposed through autocatalytic cleavage, is not required for this activation modality. In contrast, this proteolysis-resistant mutant could not be activated by 3αDOG indicating different modes of activation by the two ligands. We show that an N-terminal truncated GPR56 construct (GPR56-Δ1-385) is devoid of constitutive activity but was activated by 3αDOG. Similarly to 3αDOG, 10C7 promoted the recruitment of β-arrestin-2 but GPR56 internalization was β-arrestin independent. Despite the slow activation mode of 10C7 that favors G13 over G12, it efficiently activated the downstream Rho pathway in BT-20 breast cancer cells. These data show that different GPR56 ligands have different modes of activation yielding differential G protein selectivity but converging on the activation of the Rho pathway both in heterologous expressions system and in cancer cells endogenously expressing the receptor. 10C7 is therefore an interesting tool to study both the processes underlying GPR56 activity and its role in cancer cells. [ABSTRACT FROM AUTHOR]

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use. [ABSTRACT FROM AUTHOR]

Introduction: While there is an interest in defining longitudinal change in people with chronic illness like Parkinson's disease (PD), statistical analysis of longitudinal data is not straightforward for clinical researchers. Here, we aim to demonstrate how the choice of statistical method may influence research outcomes, (e.g., progression in apathy), specifically the size of longitudinal effect estimates, in a cohort. Methods: In this retrospective longitudinal analysis of 802 people with typical Parkinson's disease in the Luxembourg Parkinson's study, we compared the mean apathy scores at visit 1 and visit 8 by means of the paired two-sided t-test. Additionally, we analysed the relationship between the visit numbers and the apathy score using linear regression and longitudinal two-level mixed effects models. Results: Mixed effects models were the only method able to detect progression of apathy over time. While the effects estimated for the group comparison and the linear regression were smaller with high p-values (+ 1.016/ 7 years, p = 0.107, -0.056/ 7 years, p = 0.897, respectively), effect estimates for the mixed effects models were positive with a very small p-value, indicating a significant increase in apathy symptoms by + 2.345/ 7 years (p < 0.001). Conclusion: The inappropriate use of paired t-tests and linear regression to analyse longitudinal data can lead to underpowered analyses and an underestimation of longitudinal change. While mixed effects models are not without limitations and need to be altered to model the time sequence between the exposure and the outcome, they are worth considering for longitudinal data analyses. In case this is not possible, limitations of the analytical approach need to be discussed and taken into account in the interpretation. [ABSTRACT FROM AUTHOR]

Introduction: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. Study design: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE Objectives: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. Methods: Settings and participants: It is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. Variables: Full details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methods: The data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. Results: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual. [ABSTRACT FROM AUTHOR]

Kisspeptin, a key neuropeptide derived from the KISS1R gene, is renowned for its critical role in regulating the hypothalamic–pituitary–gonadal axis and reproductive hormone secretion. Beyond its primary function in reproductive biology, emerging research has illuminated its influence in various cancers, mediating significant effects through its interaction with the G protein-coupled receptor, kisspeptin receptor. This interaction has been implicated in modulating cellular processes such as proliferation and metastasis, making it a potential target for therapeutic intervention. Our study initially screened ten kisspeptin-10 analogs through cytotoxic effects of kisspeptin-10 (KP10) and its analogs in several cancer types, including cervical, prostate, breast, and gastric cancers, with a particular focus on cervical cancer, where the most profound effects were observed. Further exploration using kinase array assays revealed that these analogs specifically alter key kinases involved in cancer progression. Migration assays demonstrated a substantial decrease in cell motility, and Bioluminescence Resonance Energy Transfer assays confirmed these analogs' strong interactions with the kisspeptin receptor. Overall, our results indicate that these KP10 analogs not only hinder cervical cancer cell proliferation but also curtail migration through targeted modulation of kinase signaling, suggesting their potential as therapeutic agents in managing cervical cancer progression. This comprehensive approach underscores the therapeutic promise of exploiting kisspeptin signaling in cancer treatment strategies. [ABSTRACT FROM AUTHOR]

Social interactions among individuals within a species profoundly influence behavioural and life history traits, impacting fitness. While extensively studied in cooperative and eusocial species, the effects of social environment on fitness in non-social species, particularly insects, remain less explored. Our study investigates the impact of social environment, specifically male density, on fitness-related traits in the hymenopteran parasitoid Venturia canescens. The research focuses on longevity, reproductive behaviours (latency before mating, mating probability and duration), and offspring production capacity. Through a lifespan study, males were exposed to either isolation or regular encounters with conspecific males, alternating with periods of female presence or absence. Results show a trend of reduced longevity in socially exposed males and a significant decline in mating success with age in the social context. However, reproductive behaviours and offspring produced by males remain unaffected. This study sheds light on the intricate interplay between social environment, ageing, and reproductive strategies in non-social insect species, emphasizing the need for further exploration of social effects on male behaviour and notably potential influences of interactions between male and females but also between females. Significance Statement: Impacts of social interactions on individuals were largely explored in social species, but remain little studied in non-social ones. This study aims at testing the impact of male-male interactions before the encounter of a female (past social interactions) on male reproductive behaviours and longevity in a non-social parasitoid wasp. We show that longevity is negatively affected by the past social interactions in this wasp. Those interactions also impose a decline in male mating probability with age (senescence pattern) or mating experience (number of matings). Latency before mating, mating duration and offspring production are not influenced by social environment. On the other hand, offspring production increases with mating experience. [ABSTRACT FROM AUTHOR]

Background: Antiphospholipid antibody syndrome (APS) is an acquired autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy complications. Recently, thrombotic APS was linked to increased neutrophil extracellular traps (NET) formation, suggesting an association between NETs and the severity of APS-related thrombosis. Methods: We performed a retrospective study on patients tested for presence of antiphospholipid antibodies (990 negative and 374 positive) to evaluate the association between the neutrophil activation state, estimated by the neutrophil reactive index (NEU-RI), a parameter routinely available from some haematology analysers, and antiphospholipid antibodies. Results: We do not observe a difference in NEU-RI values between positive and negative patients globally. However, interestingly, we highlight an association between high titers of IgM and low NEU-RI values indicating a lower neutrophil activation. Conclusion: Our data are in line with the recent questioning about the putative clinical consistency of positive solid-phase aPL IgM. Bullet points: NEUT-RI is described as an accurate biomarker of neutrophil activation. High-titers of anti-phospholipid IgM is associated with lower NEUT-RI values. Lower NEUT-RI values suggest lower neutrophil activation in these patients. High titers of anticardiolipin IgG are associated with higher NEUT-RI values. IgM aPL positivity may constitute a distinct entity obeying a different mechanism. [ABSTRACT FROM AUTHOR]

Oxygen 3‐isotope ratios of magnetite and carbonates in aqueously altered carbonaceous chondrites provide important clues to understanding the evolution of the fluid in the asteroidal parent bodies. We conducted oxygen 3‐isotope analyses of magnetite, dolomite, and breunnerite in two sections of asteroid Ryugu returned samples, A0058 and C0002, using a secondary ion mass spectrometer (SIMS). Magnetite was analyzed by using a lower primary ion energy that reduced instrumental biases due to the crystal orientation effect. We found two groups of magnetite data identified from the SIMS pit morphologies: (1) higher δ18O (from 3‰ to 7‰) and ∆17O (~2‰) with porous SIMS pits mostly from spherulitic magnetite, and (2) lower δ18O (~ −3‰) and variable ∆17O (0‰–2‰) mostly from euhedral magnetite. Dolomite and breunnerite analyses were conducted using multi‐collection Faraday cup detectors with precisions ≤0.3‰. The instrumental bias correction was applied based on carbonate compositions in two ways, using Fe and (Fe + Mn) contents, respectively, because Ryugu dolomite contains higher amounts of Mn than the terrestrial standard. Results of dolomite and breunnerite analyses show a narrow range of ∆17O; 0.0‰–0.3‰ for dolomite in A0058 and 0.2‰–0.8‰ for dolomite and breunnerite in C0002. The majority of breunnerite, including large ≥100 μm grains, show systematically lower δ18O (~21‰) than dolomite (25‰–30‰ and 23‰–27‰ depending on the instrumental bias corrections). The equilibrium temperatures between magnetite and dolomite from the coarse‐grained lithology in A0058 are calculated to be 51 ± 11°C and 78 ± 14°C, depending on the instrumental bias correction scheme for dolomite; a reliable temperature estimate would require a Mn‐bearing dolomite standard to evaluate the instrumental bias corrections, which is not currently available. These results indicate that the oxygen isotope ratios of aqueous fluids in the Ryugu parent asteroid were isotopically heterogeneous, either spatially, or temporary. Initial water ice accreted to the Ryugu parent body might have ∆17O > 2‰ that was melted and interacted with anhydrous solids with the initial ∆17O < 0‰. In the early stage of aqueous alteration, spherulitic magnetite and calcite formed from aqueous fluid with ∆17O ~ 2‰ that was produced by isotope exchange between water (∆17O > 2‰) and anhydrous solids (∆17O < 0‰). Dolomite and breunnerite, along with some magnetite, formed at the later stage of aqueous alteration under higher water‐to‐rock ratios where the oxygen isotope ratios were nearly at equilibrium between fluid and solid phases. Including literature data, δ18O of carbonates decreased in the order calcite, dolomite, and breunnerite, suggesting that the temperature of alteration might have increased with the degree of aqueous alteration. [ABSTRACT FROM AUTHOR]

In order to gain insights on the conditions of aqueous alteration on asteroid Ryugu and the origin of water in the outer solar system, we developed the measurement of water content in magnetite at the micrometer scale by secondary ion mass spectrometry (NanoSIMS) and determined the H and Si content of coarse‐grained euhedral magnetite grains (polyhedral magnetite) and coarse‐grained fibrous (spherulitic) magnetite from the Ryugu polished section A0058‐C1001. The hydrogen content in magnetite ranges between ~900 and ~3300 wt ppm equivalent water and is correlated with the Si content. Polyhedral magnetite has low and homogenous silicon and water content, whereas fibrous magnetite shows correlated Si and water excesses. These excesses can be explained by the presence of hydrous Si‐rich amorphous nanoinclusions trapped during the precipitation of fibrous magnetite away from equilibrium and testify that fibrous magnetite formed from a hydrous gel with possibly more than 20 wt% water. An attempt to determine the water content in sub‐μm framboids indicates that additional calibration and contamination issues must be addressed before a safe conclusion can be drawn, but hints at elevated water content as well. The high water content in fibrous magnetite, expected to be among the first minerals to crystallize at low water–rock ratio, points to the control of water content by local conditions of magnetite precipitation rather than large‐scale alteration conditions. Systematic lithological variations associated with water‐rich and water‐poor magnetite suggest that the global context of alteration may be better understood if local water concentrations are compared with millimeter‐scale distribution of the various morphologies of magnetite. Finally, the high water content in the magnetite precursor gel indicates that the initial O isotopic composition in alteration water must not have been very different from that of the earliest magnetite crystals. [ABSTRACT FROM AUTHOR]

We report Nd and Sm isotopic compositions of four samples of Ryugu returned by the Hayabusa2 mission, including "A" (first touchdown) and "C" (second touchdown) samples, and several carbonaceous chondrites to evaluate potential genetic relationships between Ryugu and known chondrite groups and track the cosmic ray exposure history of Ryugu. We resolved Nd and Sm isotopic anomalies in small (<20 ng Nd and Sm) sample sizes via thermal ionization mass spectrometer using 1013 Ω amplifiers. Ryugu samples exhibit resolvable negative μ142Nd values consistent with carbonaceous chondrite values, suggesting that Ryugu is related to the parent bodies of carbonaceous chondrites. Ryugu's negative μ149Sm values are the result of exposure to galactic cosmic rays, as demonstrated by the correlation between 150Sm/152Sm and 149Sm/152Sm ratios that fall along the expected neutron capture correlation line. The neutron fluence calculated in the "A" samples (2.75 ± 1.94 × 1015 n cm−2) is slightly higher compared to the "C" samples (0.95 ± 2.04 × 1015 n cm−2), though overlapping within measurement uncertainty. The Sm results for Ryugu, at this level of precision, thus are consistent with a well‐mixed surface layer at least to the depths from which the "A" and "C" samples derive. [ABSTRACT FROM AUTHOR]

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed wholeexome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCTlike features and FN1::TEK fusions. [ABSTRACT FROM AUTHOR]

A playwright, philosopher, and president, Václav Havel was well known at home and abroad for all his "careers" and contributions. This article compares and contrasts the recognition accorded to Havel at home and abroad, examining differing assessments and aspects of his legacy—his key contributions to politics, history, and the history of ideas. Within the Czech Republic, we refer to processes and types of memorialization such as local media, exhibitions, how Havel is and was referenced in protest, and more "official" memorials. This national process of reclaiming Havel increasingly brings his domestic profile into accord with his long-standing international stature—which was decidedly not the case while he was in political office. By following avenues of evidence and example from institutional and official levels to more decentralized, local, and unofficial initiatives, we explore which aspects of Havel's own usable past are referenced, which in turn illuminates how collective memory is shaped. The process of memorializing Havel and paying tribute to his ideas and legacy is necessarily unfinished. Although he died in 2011, how Havel is remembered will continue to evolve, along with larger national and international discussions of dissidence and the impact of Charter 77, as both he and the Velvet Revolution continue to resonate in movements for political change in authoritarian regimes. [ABSTRACT FROM AUTHOR]

Background: Inference of Gene Regulatory Networks (GRNs) is a difficult and long-standing question in Systems Biology. Numerous approaches have been proposed with the latest methods exploring the richness of single-cell data. One of the current difficulties lies in the fact that many methods of GRN inference do not result in one proposed GRN but in a collection of plausible networks that need to be further refined. In this work, we present a Design of Experiment strategy to use as a second stage after the inference process. It is specifically fitted for identifying the next most informative experiment to perform for deciding between multiple network topologies, in the case where proposed GRNs are executable models. This strategy first performs a topological analysis to reduce the number of perturbations that need to be tested, then predicts the outcome of the retained perturbations by simulation of the GRNs and finally compares predictions with novel experimental data. Results: We apply this method to the results of our divide-and-conquer algorithm called WASABI, adapt its gene expression model to produce perturbations and compare our predictions with experimental results. We show that our networks were able to produce in silico predictions on the outcome of a gene knock-out, which were qualitatively validated for 48 out of 49 genes. Finally, we eliminate as many as two thirds of the candidate networks for which we could identify an incorrect topology, thus greatly improving the accuracy of our predictions. Conclusion: These results both confirm the inference accuracy of WASABI and show how executable gene expression models can be leveraged to further refine the topology of inferred GRNs. We hope this strategy will help systems biologists further explore their data and encourage the development of more executable GRN models. [ABSTRACT FROM AUTHOR]

Aims. The physical properties of galactic molecular outflows are important as they could constrain outflow formation mechanisms. In this work, we study the properties of the southwest (SW) outflow streamer including gas kinematics, optical depth, dense gas fraction, and shock strength through molecular emission in the central molecular zone of the starburst galaxy NGC 253. Methods. We imaged the molecular emission in NGC 253 at a spatial resolution of 1.6″(∼27 pc at D ∼ 3.5 Mpc) based on data from the ALMA Comprehensive High-resolution Extragalactic Molecular Inventory (ALCHEMI) large program. We traced the velocity and velocity dispersion of molecular gas with the CO(1–0) line and studied the molecular spectra in the region of the SW streamer, the brightest CO streamer in NGC 253. We constrained the optical depth of the CO emission with the CO/13CO(1–0) ratio, the dense gas fraction with the HCN/CO(1–0), H13CN/13CO(1–0) and N2H+/13CO(1–0) ratios, as well as the shock strength with the SiO(2–1)/13CO(1–0) and CH3OH(2k–1k)/13CO(1–0) ratios. Results. The CO/13CO(1–0) integrated intensity ratio is ∼21 in the SW streamer region, which approximates the C/13C isotopic abundance ratio. The higher integrated intensity ratio compared to the disk can be attributed to the optically thinner environment of CO(1–0) emission inside the SW streamer. The HCN/CO(1–0) and SiO(2–1)/13CO(1–0) integrated intensity ratios both approach ∼0.2 in three giant molecular clouds (GMCs) at the base of the outflow streamers, which implies a higher dense gas fraction and strength of fast shocks in those GMCs than in the disk, while the HCN/CO(1–0) integrated intensity ratio is moderate in the SW streamer region. The contours of those two integrated intensity ratios are extended in the directions of outflow streamers, which connect the enhanced dense gas fraction and shock strength with molecular outflow. Moreover, the molecular gas with an enhanced dense gas fraction and shock strength located at the base of the SW streamer shares the same velocity as the outflow. Conclusions. The enhanced dense gas fraction and shock strength at the base of the outflow streamers suggest that star formation inside the GMCs can trigger shocks and further drive the molecular outflow. The increased CO/13CO(1–0) integrated intensity ratio coupled with the moderate HCN/CO(1–0) integrated intensity ratio in the SW streamer region are consistent with the picture that the gas velocity gradient inside the streamer may decrease the optical depth of CO(1–0) emission, as well as the dense gas fraction in the extended streamer region. [ABSTRACT FROM AUTHOR]

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαβγ proteins, followed by the recruitment of GPCR kinases and βarrestin (βarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both βarr and Gβγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V2 receptor (V2R)–βarr complex scaffolds Gβγ at the plasma membrane through a direct interaction with βarr, enabling its transport to endosomes. Gβγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of βarr in mediating sustained G protein signaling. A V2R–βarrestin–Gβγ complex forms at the plasma membrane and translocates to endosomes. This sheds light on G protein subunit translocation and βarr's role in sustained signaling. [ABSTRACT FROM AUTHOR]

Background: Several tools are used to assess postoperative weight loss after bariatric surgery, including the percentage of excess body weight loss (%EWL), percentage of total weight loss (%TWL), and percentage of excess body mass index (BMI) loss (%EBMIL). A repeated series of measurements should be considered to assess weight loss as accurately as possible. This study aimed to test weight loss metrics. Methods: Data were obtained from a prospective database of patients with obesity who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) between 2016 and 2017 in a French tertiary referral bariatric center. A multilevel mixed-effects linear regression model with repeated measures was used to analyze repeated weight measurements over time. Results: A total of 435 patients underwent LRYGB (n = 266) or LSG (n = 169). At 2 years, the average %EWL, %EBMIL, and %TWL were 56.8%, 61.3%, and 26.6%, respectively. Patients who underwent LSG experienced lower weight loss (β: − 4233 in %TWL model, β: − 6437 in %EWL model, and β: − 6989 in %EBMIL model) than those who underwent LRYGB. In multivariate mixed analysis, preoperative BMI was not significantly associated with %TWL at 2 years (β, − 0.09 [− 0.22–0.03] p = 0.1). Preoperative BMI was negatively associated with both %EWL (β, − 1.61 [− 1.84–− 1.38] p < 0.0001) and %EBMIL (β, − 1.91 [− 2.16–− 1.66] p < 0.0001). Conclusion: This is the first study to assess %TWL use for postoperative weight measurement, using a multilevel mixed-effects linear regression model %TWL is the measure of choice to assess weight loss following bariatric surgery. [ABSTRACT FROM AUTHOR]

In this paper, we report near-infrared observations of the classical T Tauri star TW Hya with the SPIRou high-resolution spectropolarimeter and velocimeter at the 3.6-m Canada–France–Hawaii Telescope in 2019, 2020, 2021, and 2022. By applying Least-Squares Deconvolution (LSD) to our circularly polarized spectra, we derived longitudinal fields that vary from year to year from –200 to +100 G, and exhibit low-level modulation on the 3.6 d rotation period of TW Hya, despite the star being viewed almost pole-on. We then used Zeeman–Doppler Imaging to invert our sets of unpolarized and circularly polarized LSD profiles into brightness and magnetic maps of TW Hya in all four seasons, and obtain that the large-scale field of this T Tauri star mainly consists of a 1.0–1.2 kG dipole tilted at about 20° to the rotation axis, whereas the small-scale field reaches strengths of up to 3–4 kG. We find that the large-scale field is strong enough to allow TW Hya to accrete material from the disc on the polar regions at the stellar surface in a more or less geometrically stable accretion pattern, but not to succeed in spinning down the star. We also report the discovery of a radial velocity signal of semi-amplitude |$11.1^{+3.3}_{-2.6}$| m s−1 (detected at 4.3σ) at a period of 8.3 d in the spectrum of TW Hya, whose origin may be attributed to either a non-axisymmetric density structure in the inner accretion disc, or to a |$0.55^{+0.17}_{-0.13}$| MꝜ candidate close-in planet (if orbiting in the disc plane), at an orbital distance of 0.075 ± 0.001 au. [ABSTRACT FROM AUTHOR]

This article proposes a practical guide including good laboratory practices followed by a critical review about the application of isotope dilution mass spectrometry (ID-MS) measurement to radionuclide analyses. Several national and international scientific institutions (French Alternative Energies and Atomic Energy Commission, French Radioprotection and Nuclear Safety Institute, European Commission, International Atomic Energy Agency, and Belgian Nuclear Research Centre) participated in this review by sharing their good laboratory practices. ID-MS is one of the primary ratio methods of measurement in the International System of Units. It can produce highly accurate results, as potential sources of bias can be controlled. Many hints are given to obtain the best performance. In addition, a script written with the open source software Octave is provided to calculate the optimal parameters of the {sample–spike} mixture easily. Radionuclide analysis by ID-MS applies to many different fields (environmental, biological, reference materials, irradiated samples, process control, nuclear safeguards and nuclear forensics). [ABSTRACT FROM AUTHOR]

The formation of planets in our solar system encompassed various stages of accretion of planetesimals that formed in the protoplanetary disk within the first few million years at different distances to the sun. Their chemical diversity is reflected by compositionally variable meteorite groups from different parent bodies. There is general consensus that their formation location is roughly constrained by a dichotomy of nucleosynthetic isotope anomalies, relating carbonaceous (C) meteorite parent bodies to the outer protoplanetary disk and the non-carbonaceous (NC) parent bodies to an origin closer to the sun. It is a common idea, that in these inner parts of the protoplanetary disks, planetesimal accretion processes were faster. Testing such scenarios requires constraining formation ages of meteorite parent bodies. Although isotopic age dating can yield precise formation ages of individual mineral constituents of meteorites, such ages frequently represent mineral cooling ages that can postdate planetesimal formation by millions or tens of millions of years, depending on the cooling history of individual planetesimals at different depths. Nevertheless, such cooling ages provide a detailed thermal history which can be fitted by thermal evolution models that constrain the formation age of individual parent bodies. Here we apply state-of-the-art thermal evolution models to constrain planetesimal formation times particular in the outer solar system formation region of C meteorites. We infer a temporally distributed accretion of various parent bodies from < 0.6 Ma to ≈ 4 Ma after solar system formation, with 3.7 Ma and 2.5 - 2.75 Ma for the parent bodies of CR1-3 chondrites and the Flensburg carbonaceous chondrite, and < 0.6 and < 0.7 Ma for the parent bodies of differentiated achondrites NWA 6704 and NWA 011, respectively. This implies that accretion processes in the C reservoir started as early as in the NC reservoir and were operating throughout typical protoplanetary disk lifetimes, thereby producing differentiated parent bodies with carbonaceous compositions in addition to undifferentiated C chondrite parent bodies. The accretion times correlate inversely with the degree of the meteorites' alteration, metamorphism, or differentiation. The accretion times for the CM, CI, Ryugu, and Tafassite parent bodies of 3.8 Ma, 3.8 Ma, 1 - 3 Ma, and 1.1 Ma, respectively, fit well into this correlation in agreement with the thermal and alteration conditions suggested by these meteorites. Our results indicate that individual planetesimals formed rapidly (i.e., within < 1 Ma), however, distinct planetesimals formed recurrently throughout the total lifetime of the protoplanetary disk. Rapid individual formation is consistent with streaming instabilities assisted by gravitational collapse. However, obviously not the total dust inventory was consumed at early disk evolution stages, so there must have been some delay mechanisms, e.g. collisional destruction of precursor aggregates due to high impact velocities induced by radial drift phenomena. This counterbalance enabled late ( > 2 - 3 Ma) accretion of C planetesimals beyond the snow line which escaped severe planetesimal heating and volatile loss, hence, preserving their volatiles, especially water. Only this delayed formation of water-rich planetesimals allowed Earth to accrete sufficient water to become a habitable planet, preventing it from being a bone dry planet. [ABSTRACT FROM AUTHOR]

Background and Aims: To measure the impact of socio-economic environment on the incidence of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Method: The study used data from the French Network of Cancer Registries (FRANCIM) between 2006 and 2016. Classification of patients into HCC and iCCA was performed according to the topographical and morphological codes of the 3rd edition of the International Classification of Diseases for Oncology. Patient addresses were geolocalized and assigned to an IRIS, the smallest French geographic unit. Socio-economic environment was assessed by the European Deprivation Index (EDI). Sex- and age-standardized incidence rates with 95% confidence intervals (CI) were estimated per 100 000 inhabitants, by national quintiles, for each IRIS, sex and age group. Quintile 1 (Q1) characterized the most affluent areas. A Poisson regression was performed to model the impact of deprivation. Results: We included 22 249 cases (79.64% HCC, 16.97% iCCA). Incidence rates were 11.46 and 2.39 per 100 000 person-years for HCC and iCCA, respectively. There was an over-incidence of HCC in quintiles 2, 3, 4 and 5 compared to quintile 1: Q1 10.28 [9.9--10.66] per 100 000 person-years, Q2 11.43 [10.48--12.47] (p < .0001), Q3 11.81 [10.82--12.89] (p < .0001), Q4 12.26 [11.25--13.37] (p < .001) and Q5 11.53 [10.57-- 12.57] (p < .0001). By contrast, there was no difference for iCCa. Deprivation was significantly associated with HCC in men (p = .0018) and women (p = .0009), but not with iCCA (p = .7407). Conclusion: The incidence of HCC is related to socio-economic environment, unlike iCCA. HCC and iCCA should be studied separately in epidemiological studies. [ABSTRACT FROM AUTHOR]

The exploration of outflows in protobinary systems presents a challenging yet crucial endeavour, offering valuable insights into the dynamic interplay between protostars and their evolution. In this study, we examine the morphology and dynamics of jets and outflows within the IRAS 4A protobinary system. This analysis is based on ALMA observations of SiO(5–4), H2CO(30, 3–20, 3), and HDCO(41, 4–31, 3) with a spatial resolution of ∼150 au. Leveraging an astrochemical approach involving the use of diverse tracers beyond traditional ones has enabled the identification of novel features and a comprehensive understanding of the broader outflow dynamics. Our analysis reveals the presence of two jets in the redshifted emission, emanating from IRAS 4A1 and IRAS 4A2, respectively. Furthermore, we identify four distinct outflows in the region for the first time, with each protostar, 4A1 and 4A2, contributing to two of them. We characterize the morphology and orientation of each outflow, challenging previous suggestions of bends in their trajectories. The outflow cavities of IRAS 4A1 exhibit extensions of 10 and 13 arcsec with position angles (PA) of 0° and -12°, respectively, while those of IRAS 4A2 are more extended, spanning 18 and 25 arcsec with PAs of 29° and 26°. We propose that the misalignment of the cavities is due to a jet precession in each protostar, a notion supported by the observation that the more extended cavities of the same source exhibit lower velocities, indicating they may stem from older ejection events. [ABSTRACT FROM AUTHOR]

G protein–coupled receptors (GPCRs) regulate cellular signaling processes by coupling to diverse combinations of heterotrimeric G proteins composed of Gα, Gβ, and Gγ subunits. Biosensors based on bioluminescence resonance energy transfer (BRET) have advanced our understanding of GPCR functional selectivity. Some BRET biosensors monitor ligand-induced conformational changes in the receptor or G proteins, whereas others monitor the recruitment of downstream effectors to sites of G protein activation. Here, we compared the ability of conformation-and activation-based BRET biosensors to assess the coupling of various class A and B GPCRs to specific Gα proteins in cultured cells. These GPCRs included serotonin 5-HT2A and 5-HT7 receptors, the GLP-1 receptor (GLP-1R), and the M3 muscarinic receptor. We observed different signaling profiles between the two types of sensors, highlighting how data interpretation could be affected by the nature of the biosensor. We also found that the identity of the Gβγ subunits used in the assay could differentially influence the selectivity of a receptor toward Gα subtypes, emphasizing the importance of the receptor-Gβγ pairing in determining Gα coupling specificity. Last, the addition of epitope tags to the receptor could affect stoichiometry and coupling selectivity and yield artifactual findings. These results highlight the need for careful sensor selection and experimental design when probing GPCR–G protein coupling. Editor's summary: Bioluminescence resonance energy transfer (BRET)–based biosensors are commonly used to determine the specific G proteins that are activated by a particular G protein–coupled receptor (GPCR). Wright et al. found that the type of biosensor and other aspects of the experimental design, such as whether the receptor was tagged and the specific Gβ and Gγ subunits expressed in the cells, influenced whether the assay detected GPCR coupling to a particular Gα subunit. These findings have the potential to improve the design of BRET-based assays to accurately determine GPCR functional selectivity. —Annalisa M. VanHook [ABSTRACT FROM AUTHOR]

In situ iron isotope ratios (δ56Fe) in sulfide measured by secondary ion mass spectrometry (SIMS) can provide valuable information on several of Earth's surface processes. SIMS relies on the use of a matrix‐matched reference material to correct for instrumental mass fractionation. To date Balmat pyrite has been widely used as a reference material, on the assumption of its homogeneous δ56Fe composition. However, several studies have reported divergent bulk δ56Fe values, which may jeopardise its use. Here, we combined bulk solution MC‐ICP‐MS and in situ SIMS δ56Fe measurements on two Balmat batches: the Balmat‐Original published in Whitehouse and Fedo (2007) and Balmat‐UNIL. Despite similar compositions, this study demonstrates the existence of two isotopically distinct Balmat populations. With respect to Balmat‐Original (δ56Fe = ‐0.39 ± 0.05‰, 2s), Balmat‐UNIL is isotopically 'lighter' with a bulk solution MC‐ICP‐MS composition of ‐1.46 ± 0.024‰. Additionally, Balmat‐UNIL has two subpopulations: the first is characterised by δ56Fe values of ‐1.46 ± 0.25‰, whereas the second agrees with the original Balmat batch. In each Balmat‐UNIL subpopulation, the intra‐grain and inter‐grain variabilities are sufficient to use Balmat as a reference material for δ56Fe isotope measurements by SIMS. This study revealed at least two end‐member compositions of Balmat pyrite and calls for a careful batch‐specific determination of bulk δ56Fe. [ABSTRACT FROM AUTHOR]

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is increasingly used to analyze cultural heritage materials because it can simultaneously detect organic and inorganic materials while mapping them on a surface. The precise identification of a pigment in a specific layer of a painting or of remaining color on a statue can inform about the technique used or the time of manufacture as well as expose possible forgeries when anachronistic ingredients are identified. Reference spectra are required to confidently identify a given pigment using ToF-SIMS. This database focuses on six white pigments made from calcium-rich natural or synthetized materials, prepared following traditional processes. Such pigments are frequently found in the preparation layers, namely, "ground," separating the support from the observable paint layers, and providing a smooth surface to hold the paint on while preventing its absorption by the substrate. Differentiating between these pigments is helpful to better describe the painting practice. Here, ToF-SIMS reference spectra using a Bi3+ primary ion species are presented for both polarities. [ABSTRACT FROM AUTHOR]

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is increasingly used to analyze cultural heritage materials because it can simultaneously detect organic and inorganic materials while mapping them on a surface. The precise identification of a pigment in a specific layer of a painting or of remaining color on a statue can inform about the technique used or the time of manufacture as well as expose possible forgeries when anachronistic ingredients are identified. Reference spectra are required to confidently identify a given pigment using ToF-SIMS. This paper focuses on four blue pigments manufactured following historical recipes: two natural ground and processed lapis lazuli pigments, one synthetic ultramarine pigment, and the blue-colored ground cobalt glass pigment smalt. The positive and negative polarity ToF-SIMS reference spectra using a Bi3+ primary ion species are presented. Differentiating these family of pigments is of interest as they have similar compositions but are used in very different contexts. It is particularly noteworthy that the two natural lapis lazuli pigments can be distinguished from the synthetic counterpart ultramarine using ToF-SIMS. [ABSTRACT FROM AUTHOR]

ToF-SIMS is increasingly used to analyze cultural heritage materials because it can simultaneously detect organic and inorganic materials while mapping them on a surface. The precise identification of a pigment in a specific layer of a painting or of remaining color on a statue can inform about the technique used or the time of manufacture as well as expose possible forgeries when anachronistic ingredients are identified. Reference spectra are required to confidently identify a given pigment using ToF-SIMS. This database focuses on eight lead-based historical inorganic pigments, manufactured following traditional recipes. Lead pigments have been widely used in painting until the late 19th century. Here, the positive polarity ToF-SIMS reference spectra using a Bi3+ primary ion species are presented. [ABSTRACT FROM AUTHOR]