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Summary Background and Aims Methods Results Conclusions While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, checkpoint inhibitor‐induced liver injury is a significant immune‐related side effect of this immunotherapy. This study focuses on the severity classifications and characteristics of patients with checkpoint inhibitor‐induced hepatitis.A retrospective analysis of patients with severe Checkpoint Inhibitor‐induced hepatitis grade 3 and 4 according to the recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data on clinicobiological characteristics, treatment and outcomes were collected from 3 university hospitals, and causality was assessed by using the updated Roussel Uclaf Causality Assessment Method. The severity of hepatitis was assessed using the Model for End‐stage Liver Disease score, the Drug‐Induced Liver Injury Network, and the Drug‐Induced Liver Injury International Expert Working Group classifications.We retrospectively included 100 patients presenting various hepatitis patterns with a median time to onset of 20 days after checkpoint inhibitors. Severity grading varied significantly among the classifications used. A lower incidence of severe cases was observed when using the Drug‐Induced Liver Injury classifications instead of the recommended CCTCAE classification, and this was correlated with outcomes.This retrospective study challenges the efficacy of the CTCAE classification in defining the severity of Checkpoint Inhibitor‐induced hepatitis and suggests that the traditional hepatology‐focused scores may be more relevant. The CTCAE classification is inconsistent and gives equal weight to jaundice and elevated transaminases, which leads to steroid overtreatment and limits the rechallenge of ICIs. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) remains the predominant opportunistic infection following solid organ transplantation (SOT). While valganciclovir is the drug of choice for CMV prophylaxis, its utility can be compromised due to the risk of cytopenia. Letermovir, a novel agent approved for CMV prophylaxis in allogeneic hematopoietic stem cell transplant recipients and high‐risk kidney transplant recipients, exhibits reduced toxicity. This study aims to present the practical application of letermovir as both primary and secondary prophylaxis against CMV in heart transplant recipients (HTR). Methods: In this observational, retrospective, single‐center study, we included all consecutive adult HTRs from June 2020 to January 2022 who were administered letermovir for CMV prophylaxis. We documented instances of CMV breakthrough infections, side effects related to letermovir, changes in neutropenia following the switch from valganciclovir to letermovir, and any drug interactions with the immunosuppressive regimen. Results: The study comprised 10 patients: two received primary prophylaxis with letermovir due to a high risk of CMV infection (donor‐positive, recipient‐negative serostatus), and eight received it as secondary prophylaxis following a CMV infection. The median duration of letermovir administration was 8 months (range 3–12 months). No CMV breakthrough infections were reported while on prophylaxis. However, three patients experienced CMV breakthrough infections after discontinuing letermovir prophylaxis (30%). No significant side effects were observed, although one patient reported digestive intolerance. Among the nine patients on tacrolimus, six needed reduced doses after switching to letermovir. Conclusion: This real‐life study appears to support the effectiveness of letermovir prophylaxis in HTR. Nonetheless, the risk of CMV infection post‐treatment cessation is notable. Further drug monitoring and research on the efficacy of letermovir for CMV prophylaxis in SOT patients is warranted. [ABSTRACT FROM AUTHOR]

Geodetically‐derived deformation rates are sometimes used to infer seismic hazard, implicitly assuming that short‐term (annual‐decadal) deformation is representative of longer‐term deformation. This is despite geological observations indicating that deformation/slip rates are variable over a range of timescales. Using geodetic data from 2016 to 2021, we observe an up to 7‐fold increase in vertical deformation rate in mid‐2019 across the Pisia‐Skinos normal fault in Greece. We hypothesize that this deformation is aseismic as there is no temporally correlated increase in the earthquake activity (M > 1). We explore four possible physical mechanisms, and our preferred hypothesis is that the transient deformation is caused by centimeter‐scale slip in the upper 5 km of the Pisia fault zone. This is the first observation of shallow tectonic (i.e., not related to human activities) aseismic deformation on a normal fault globally. Our results suggest that continental normal faults can exhibit variable deformation over shorter timescales than previously observed, and thus care should be taken when utilizing geodetic rates to quantify seismic hazard. Plain Language Summary: Slip rates of active faults are used in seismic hazard assessment to infer the frequency of damaging earthquakes. However slip rates are known to be variable when measured using different methodologies (e.g., geodesy, geomorphology) and timescales (years to millennia) for many types of faults in a range of tectonic settings. Hence we need to observe slip rates for different time scales and try to understand the mechanism(s) that cause slip rates to vary. In this paper, we present observations of vertical deformation around an active normal fault in the Gulf of Corinth, Greece. We see that the deformation is non‐uniform during 2016–2021 (the time period of data availability), and we analyze the data to find that the deformation rate increased in mid‐2019. To try and understand the physical mechanism that may have caused this increase in deformation rate, we use simple modeling to test four different hypotheses. We find that the best fit to the observations is for centimeters of slip occurring on shallowest few kilometers of the fault. Our results highlight the importance of understanding short‐term (annual‐decadal) processes happening on active faults, and the potential pitfalls of using slip rates measured over short‐timescales to infer seismic hazard. Key Points: Spatial variations in vertical ground motion (uplift/subsidence) correlate with the mapped trace of the Pisia‐Skinos fault in GreeceThe ground deformation is non‐uniform over the 6 years studied, and shows an up to 7× increase in rate, lasting at least 3 yearsThis transient interseismic deformation is hypothesized to be caused by shallow aseismic centimeter‐scale slip on the Pisia‐Skinos fault [ABSTRACT FROM AUTHOR]

If similar evolutionary forces maintain intra‐ and interspecific diversity, patterns of diversity at both levels of biological organization can be expected to covary across space. Although this prediction of a positive species‐genetic diversity correlation (SGDC) has been tested for several taxa in natural landscapes, no study has yet evaluated the influence of the community delineation on these SGDCs. In this study, we focused on tropical fishes of the Indo‐Pacific Ocean, using range‐wide single nucleotide polymorphism data for a deep‐sea fish (Etelis coruscans) and species presence data of 4878 Teleostei species. We investigated whether a diversity continuum occurred, for different community delineations (subfamily, family, order and class) and spatial extents, and which processes explained these diversity patterns. We found no association between genetic diversity and species richness (α‐SGDC), regardless of the community and spatial extent. In contrast, we evidenced a positive relationship between genetic and species dissimilarities (β‐SGDC) when the community was defined at the subfamily or family level of the species of interest, and when the Western Indian Ocean was excluded. This relationship was related to the imprint of dispersal processes across levels of biological organization in Lutjanidae. However, this positive β‐SGDC was lost when considering higher taxonomic communities and at the scale of the entire Indo‐Pacific, suggesting different responses of populations and communities to evolutionary processes at these scales. This study provides evidence that the taxonomic scale at which communities are defined and the spatial extent are pivotal to better understand the processes shaping diversity across levels of biological organization. [ABSTRACT FROM AUTHOR]

Information qualities such as usefulness, accuracy, and comprehensiveness are to some extent subjective. Information resources have different meanings to different people and at different moments. This apparent subjectivity hinders indexing based on qualities for retrieval and filtering purposes. We conceptualize this as the subjectivity problem and address it through two studies. Study One explores whether, on public fora, people consider qualities as claims they should agree upon. Study Two explores, through a vignettes study, which conditions foster this inter‐subjective validity of quality claims. We conclude that information qualities become agreeable given the right set of conditions. We discuss the need for transparency about information qualities and quality considerations in order to offer these conditions to end users. [ABSTRACT FROM AUTHOR]

Background: The clinical results following regenerative endodontic procedures (REPs) vary according to numerous parameters, including the presence of bacteria. This limitation reduces the indications for REPs and calls for the development of next generation antibacterial strategies (NGAS) providing alternatives to current antibacterial strategies (CAS) such as double or triple antibiotic paste (DAP/TAP) and (Ca(OH)2). Objectives: The present scoping review aims to describe the current trends regarding the use of such strategies and highlight future perspectives. Methods: Four databases (PUBMed, Cochrane, ClinicalTrials and Science Direct) were searched until 1st May 2023. Results: A total of 918 records were identified, 133 were screened and assessed for eligibility, and 87 articles were included. The findings show that (1) clinical studies are only available for CAS, (2) although next generation strategies are the most studied approach since 2017, they are all at the pre‐clinical stage, (3) most of the next generation strategies use galenic forms which offer cell support and colonization and which simultaneously contain antibacterial molecules as alternatives to CAS and to antibiotics in general, (4) standardization is required for future research, specifically regarding the bacterial strains studied, the use of biofilm studies and the cellular behaviour assessments. Conclusion: Although NGAS are promising strategies to improve REPs in the context of infection, the current evidence is mostly limited to pre‐clinical studies. Further methodological improvement is required to allow relevant comparisons between studies and to reduce the time from bench to bedside. [ABSTRACT FROM AUTHOR]

This article presents results of both 2D impedance sensing and biomimetic stimulation of cardiomyocyte cells cultured on a Thin‐Film‐Transistor platform. These results complete sensing results of electrophysiology previously obtained with similar device. [ABSTRACT FROM AUTHOR]

Background: Recurrence after Cytomegalovirus (CMV) infection in heart transplant recipients is difficult to predict, in spite of its high incidence. Secondary prophylaxis could reduce this burden; however, its duration remains unestablished. We evaluated the QuantiFERON®‐CMV test to see if it could predict CMV recurrence and help optimize the duration of secondary prophylaxis. Methods: This observational retrospective single center study included all heart transplant recipients who developed CMV infection between 2019 and 2021, with the CD8+ T‐cell‐mediated CMV immunity QuantiFERON®‐CMV test assessed at the time of (val)ganciclovir curative treatment completion. The main outcomes were CMV recurrence and duration of secondary prophylaxis. Secondary outcomes included immunosuppressive regimen, rejection, lymphocyte count, CMV viral load, infection type, and duration as possible confounding factors for recurrence. Results: Among the 15 patients included, five (33%) experienced recurrence, of whom three (60%) had a positive QuantiFERON®‐CMV test. The duration of secondary prophylaxis was similar regardless of QF‐CMV positivity. No confounding factor was significantly associated with CMV recurrence; however, it occurred in only 1/7 (14%) of the patients receiving an everolimus‐containing immunosuppressive regimen. Conclusion: In the population of heart transplant recipients, most of whom received ATG‐based induction, the QuantiFERON®‐CMV assay may not accurately predict CMV recurrence and would have not helped refining the duration of secondary prophylaxis in our patients. Other cell‐mediated immunity tests and strategies in this specific population, including everolimus‐containing regimens, may help predict and manage CMV recurrence. [ABSTRACT FROM AUTHOR]

A common separation approach for polar compounds involves coupling reversed‐phase liquid chromatography (RPLC) with hydrophilic interaction chromatography (HILIC) in two‐dimensional chromatography. The higher proportion of acetonitrile used in the HILIC mobile phase, which enhances mass spectrometry detection, encourages its use in the second dimension. Previous studies demonstrated that the HILIC column can be partially equilibrated within very short timeframes without compromising retention time stability, rendering it suitable in online comprehensive two‐dimensional liquid chromatography (LC×LC) setups. In addition, a specific number of conditioning cycles seems necessary to establish stable retention times. Here, the repeatability of HILIC when employed as second dimension in LC×LC was investigated, with a focus on determining the required number of conditioning cycles to achieve repeatable retention times. Various parameters influenced by the LC×LC online modulation system were studied, such as steep gradient slopes up to 8%, and very short equilibration times, less than or equal to dead time, as well as injection volume and solvent, which depend on the first dimension. Finally, the use of HILIC as a second dimension with tailored conditioning runs was applied to the analysis of hyaluronic acid hydrogel digests. The application of an RPLC×HILIC method using five conditioning runs yielded exceptional stability in second‐dimension retention times. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improving crop resistance to insect herbivores is a major research objective in breeding programs. Although genomic technologies have increased the speed at which large populations can be genotyped, breeding programs still suffer from phenotyping constraints. The pollen beetle (Brassicogethes aeneus) is a major pest of oilseed rape for which no resistant cultivar is available to date, but previous studies have highlighted the potential of white mustard as a source of resistance and introgression of this resistance appears to be a promising strategy. Here we present a phenotyping protocol allowing mid‐throughput (i.e., increased throughput compared to current methods) acquisition of resistance data, which could then be used for genetic mapping of QTLs. RESULTS: Contrasted white mustard genotypes were selected from an initial field screening and then evaluated for their resistance under controlled conditions using a standard phenotyping method on entire plants. We then upgraded this protocol for mid‐throughput phenotyping, by testing two alternative methods. We found that phenotyping on detached buds did not provide the same resistance contrasts as observed with the standard protocol, in contrast to the phenotyping protocol with miniaturized plants. This protocol was then tested on a large panel composed of hundreds of plants. A significant variation in resistance among genotypes was observed, which validates the large‐scale application of this new phenotyping protocol. CONCLUSION: The combination of this mid‐throughput phenotyping protocol and white mustard as a source of resistance against the pollen beetle offers a promising avenue for breeding programs aiming to improve oilseed rape resistance. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The behavioural revolution in law and economics led to the insight that command‐and‐control and market‐based instruments have limitations in bringing about behavioural change. Environmental behavioural instruments use persuasive strategies or techniques rather than direct incentives to encourage environmentally responsible decision‐making. This article investigates the potential and challenges of behavioural instruments in environmental policy based on a survey of theories and examples concerning environmental behavioural instruments. Behavioural instruments can reduce the information costs of environmental regulation while increasing self‐efficacy for environmental compliance. More importantly, behavioural instruments can be cheap and effective by activating various norms in specific contexts. However, the behavioural approach, because of its focus on individual compliance, may not be well suited to address (transboundary) externalities. Behavioural instruments are especially important in generating positive externalities by appealing to social norms. Such mechanisms are, however, less suited to internalising negative externalities. The effects of behavioural instruments may not be easily guaranteed (in the long run), especially when the environmental goal of the behavioural approach clashes with private interests or fails to consider individual differences and contextual factors. We therefore argue that behavioural instruments should be included alongside standard regulatory tools, thus reaching an optimal mix between both. [ABSTRACT FROM AUTHOR]

Human rhinovirus is the most frequently isolated virus during severe exacerbations of chronic respiratory diseases, like chronic obstructive pulmonary disease. In this disease, alveolar macrophages display significantly diminished phagocytic functions that could be associated with bacterial superinfections. However, how human rhinovirus affects the functions of macrophages is largely unknown. Macrophages treated with HRV16 demonstrate deficient bacteria-killing activity, impaired phagolysosome biogenesis, and altered intracellular compartments. Using RNA sequencing, we identify the small GTPase ARL5b to be upregulated by the virus in primary human macrophages. Importantly, depletion of ARL5b rescues bacterial clearance and localization of endosomal markers in macrophages upon HRV16 exposure. In permissive cells, depletion of ARL5b increases the secretion of HRV16 virions. Thus, we identify ARL5b as a novel regulator of intracellular trafficking dynamics and phagolysosomal biogenesis in macrophages and as a restriction factor of HRV16 in permissive cells. Synopsis: Human rhinovirus 16 impairs bacteria clearance and phagosome maturation in human macrophages in an ARL5b-dependent manner. In permissive cells, ARL5b is a restriction factor of human rhinovirus 16. Human rhinovirus 16 impairs bacterial clearance and phagosome maturation. ARL5b is upregulated by the human rhinovirus 16. ARL5b is responsible of defective phagolysosome biogenesis and bacterial clearance. ARL5b is a restriction factor of human rhinovirus 16 in permissive cells. Human rhinovirus 16 impairs bacteria clearance and phagosome maturation in human macrophages in an ARL5b-dependent manner. In permissive cells, ARL5b is a restriction factor of human rhinovirus 16. [ABSTRACT FROM AUTHOR]

Background: UV skin exposure is an important matter of public health, as the worldwide rising prevalence of skin cancers indicates. However, a wide majority of commercially available sunscreens are responsible for ocean ecosystem damages such as coral reef degradation and phytoplankton mortality. Aims: To answer the urge for new eco‐friendly UV filters, we studied the use of lecithin‐based multilamellar liposomes (MLLs) of controlled size and elasticity as a bio‐sourced and biodegradable alternative to classic sunscreens. These parameters control allows different skin layers targeting. Methods: The performance of two different MLLs compositions and a commercially available SPF50+ water‐resistant liposomal sunscreen was compared on skin explants. SC‐MLLs target the stratum corneum and Epi‐MLLs the whole epidermis. Preparations were applied prior to skin irradiation. Their efficiencies were evaluated histologically (hematoxylin and eosin staining plus cyclobutane pyrimidine dimer [CPD] immunostaining) and by skin barrier quality assessment (trans‐epithelial electrical resistance). Adhesiveness to the skin was also investigated. Results: Altogether, ex vivo results indicate MLLs offer a solar protection as effective as a SPF50+ water‐resistant liposomal sunscreen but with a better skin adhesiveness and an improved skin barrier function. Conclusion: Lecithin‐based MLLs of controlled physicochemical parameters can be used as a new eco‐friendly and water‐resistant agent for solar protection. The stratum corneum targeted action of SC‐MLLs appears to be more interesting, as SC‐MLLs exhibit an overall better performance than Epi‐MLLs at a lower cost. The skin barrier improvement showcased could be of interest to people suffering from dry skin or skin barrier impairment related disease. [ABSTRACT FROM AUTHOR]

The SimLife® model consists in a human cadaver dynamized by pulsatile vascularization. The objective was to evaluate the face, contents, and constructs validity of the SimLife® model in head and neck surgical oncology simulation. Head and neck surgical oncology simulation sessions on SimLife® models were organized with lateral neck dissection and total laryngectomy. Face and contents validity were addressed by questionnaires. Constructs validity was assessed by objective structured assessment of technical skills (OSATS) score. High realism was demonstrated for consistency of tissues (7.1 ± 1.4), color of arteries and veins (7.3 ± 1.9, 8.5 ± 1.1, respectively), and vein consistency (8.5 ± 1.2). The mean OSATS score was 19.7 ± 5.4 for residents and 32.7 ± 1.9 for senior surgeon (P =.0022). SimLife® is a hyperrealistic model for head and neck surgical oncology simulation and it might become a core component of the surgical resident curriculum. [ABSTRACT FROM AUTHOR]

Satisfying romantic relationships offer numerous social and health benefits, making it critical to understand the trajectory of relationship satisfaction. In recent years, research has begun to examine the role of automatic processes in relationship contexts. In particular, a growing number of studies have incorporated indirect (implicit) measures developed by socio-cognitive researchers to capture people's automatic partner attitudes—the spontaneous affective reactions toward their partner that people may at times be unable to access or unwilling to self-report in more direct (explicit) measures like questionnaires. In this paper, we review work illustrating how automatic partner attitudes can help explain, predict, and promote both the functioning and the well-being of romantic couples. That is, we integrate theoretical perspectives on interdependence, attachment, and attitudes to discuss empirical evidence relative to why automatic partner attitudes differ from self-reported judgments of relationship satisfaction, how such attitudes form in the context of real-world relationship experiences, and under which conditions they affect dyadic interactions in everyday life. Further, we identify important questions that remain unanswered and provide recommendations that may benefit future work on couples and beyond. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the postnatal outcome of children with antenatal colonic hyperechogenicity, currently considered as a sign of lysinuria‐cystinuria, but which may also be a sign of other disorders with a more severe prognosis. Method: We carried out a French multi‐centric retrospective study via 15 Multidisciplinary Center for Prenatal Diagnosis from January 2011 to January 2021. We included pregnancies for which fetal colonic hyperechogenicity had been demonstrated. We collected the investigations performed during pregnancy and at birth as well as the main clinical features of the mother and the child. We then established the prevalence of pathologies such as lysinuria‐cystinuria (LC), hypotonia‐cystinuria syndrome (HC), or lysinuric protein intolerance (LPI). Results: Among the 33 cases of colonic hyperechogenicity collected, and after exclusion of those lost to follow‐up, we identified 63% of children with lysinuria‐cystinuria, 8% with lysinuric rotein intolerance, and 4% with hypotonia‐cystinuria syndrome. Conclusion: Management of prenatal hyperechoic colon should include a specialized consultation with a clinical geneticist to discuss further investigations, which could include invasive amniotic fluid sampling for molecular diagnosis. A better understanding of diagnoses and prognosis should improve medical counseling and guide parental decision making. Key points: What's already known about this topic ? Currently, colonic hyperechogenicity is a sign of lysinuria‐cystinuria, but it can also be a sign of other disorders with a more severe prognosis. What does this study add? In this retrospective study, among fetuses with hyperechoic colon, we identified 63% of children with lysinuria‐cystinuria, 8% with lysinuric protein intolerance, and 4% with hypotonia‐cystinuria syndrome. These data are likely to modify the management of patients in whom a hyperechogenic fetal colon is identified. [ABSTRACT FROM AUTHOR]

Polysaccharide oxidative depolymerization is highly desirable to achieve recalcitrant biomass valorization. Inspired by recently discovered Lytic Polysaccharide Monooxygenases, mononuclear copper complexes have been prepared and studied in the literature. However, the activities were evaluated on different substrates and under various conditions. In this work we intended to establish a robust and reproducible activity assay, in aqueous solution at a pH close from neutrality and under mild conditions. We have evaluated several complexes on substrates of increasing complexity: the model substrate para‐nitrophenyl‐β‐D‐glucopyranoside (p‐NPG), cellobiose (glucose dimer), as well as on extended substrates (chitin, cellulose and bagasse from agave). The different assays were compared and proof‐of‐concept that bioinspired complexes can oxidatively promote polysaccharide depolymerization was obtained. Finally, we measured level of hydroxyl radicals released by the complexes under comparable experimental conditions and mechanistic pathways are discussed. [ABSTRACT FROM AUTHOR]

Urbanization is changing the conditions in which many species live, forcing them to adjust to these novel environments. Floral size and shape are critical traits for the reproduction of plants pollinated by animals as they are involved in the attraction of pollinators and in efficient pollination. Variation in size and shape could be affected by urbanization via its modification of the abiotic environment (habitat fragmentation, water availability, temperature, soil properties), or via its impact on the biotic environment of plants (pollination, herbivory). Although numerous studies have assessed the impact of urbanization on pollinator communities and many plant traits, few have investigated its impact on floral size and shape while quantifying the proportion of the total urbanization effect that is due to biotic interactions. In this study, we tested if urbanization and pollinator visitation rates affect the flower shape of the spotted jewelweed, Impatiens capensis. We quantified the size and shape of flowers in frontal and profile views using geometric morphometrics for 228 individuals from six populations from the region of Montreal, Canada. Pollinator visitation rates were estimated at each site and the main pollinators were found to be bumblebees, honeybees and hummingbirds. We found that floral size and shape are significantly correlated with urbanization as measured by the amount of vegetation in the surrounding environment of the plants (mean normalized vegetation index, NDVI) and by the visitation rates of bumblebees and honey bees. Partitioning of the total flower shape variation suggests that urbanization affects flower shape through abiotic factors and via its impact on pollinator visitation rates. While further studies from other cities are necessary to confirm the role of urbanization in shaping the floral shape of I. capensis, these results support the idea that urbanization could affect flower shapes. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab—a humanized monoclonal antibody—has been widely used to treat patients with hereditary hemorrhagic telangiectasia (HHT), but no randomized trial has yet been conducted. Methods: This study is a double‐blind multicenter randomized phase 2 trial with a 1:1 active‐treatment‐to‐placebo ratio. We included patients over the age of 18 with a confirmed diagnosis and the need for at least four red blood cell (RBC) units transfused in the 3 months before study enrollment. Bevacizumab was administered at a dose of 5 mg/kg every 14 days with a total of six injections. The primary efficacy criterion was a decrease of at least 50% in the cumulative number of RBC units transfused in a 3‐month period before and after treatment. Results: A total of 24 patients (12 in each group) were included and randomized at 4 different centers. In intention‐to‐treat analysis, 63.6% of patients (7/11) in the bevacizumab group versus 33.3% of patients (4/12) in the placebo group decreased the number of blood transfusions by at least 50% (p = 0.22). Hemoglobin levels significantly improved at 6 months in the bevacizumab versus placebo group (p = 0.02). The pharmacokinetics study revealed that patients with high exposure to bevacizumab had a significant decrease in RBC transfusions (p = 0.03). Fifty‐nine adverse events were observed, 34 in the placebo arm versus 25 in the bevacizumab arm. Conclusion: Though the present trial was underpowered, patients with HHT receiving bevacizumab required numerically fewer red blood cell transfusions than those receiving placebo, particularly those with high exposure. [ABSTRACT FROM AUTHOR]

Objective: Placental infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) can lead to placental insufficiency and in‐utero fetal death (IUFD). The objective of this study was to confirm and quantify the extent to which fetoplacental infection with SARS‐CoV‐2 is a cause of fetal death. Methods: This was a multicenter retrospective cohort study of fetal deaths that underwent postmortem examination between January 2020 and January 2022 in three fetal pathology units in Paris, France. All cases of IUFD and termination of pregnancy (TOP) occurring in 31 maternity hospitals in the Paris region undergo detailed placental pathological examination in these units. Databases were searched for cases of IUFD and TOP. Cases with fetal malformation or cytogenetic abnormality were excluded to avoid bias. We included cases of IUFD with a placental or undetermined cause and cases of TOP in the context of severe intrauterine growth restriction (IUGR). Placentas were sent to a single virology unit for reverse‐transcription polymerase chain reaction (RT‐PCR) testing by a single laboratory technician blinded to the initial postmortem examination report. Our primary endpoint was the proportion of positive placental SARS‐CoV‐2 RT‐PCR tests in the cohort. Results: Among 147 722 deliveries occurring over 2 years, 788 postmortem examinations for IUFD and TOP for severe IUGR were recorded, of which 462 (58.6%) were included. A total of 13/462 (2.8%) placentas tested positive for SARS‐CoV‐2 by RT‐PCR. Wild‐type virus and alpha and delta variants were identified. All positive cases had histological lesions consistent with placental dysfunction. There was a strong correlation between SARS‐CoV‐2 placentitis and the presence of chronic intervillositis and/or massive fibrin deposits in the placenta. When both lesion types were present, the specificity and negative predictive value for the diagnosis of placental SARS‐CoV‐2 infection were 0.99 (95% CI, 0.98–1.00) and 0.96 (95% CI, 0.94–0.98), respectively. Conclusions: At the height of the SARS‐CoV‐2 pandemic, the cause of more than half of fetal deaths in the Paris area was determined by postmortem analysis to be of placental or undetermined origin. Of these cases, 2.8% were due to placental SARS‐CoV‐2 infection with a specific pattern of histological involvement. This study highlights the need for SARS‐CoV‐2 screening in stillbirth assessment. The impact of vaccination coverage remains to be established. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

We model Coulomb stress transfer (CST) due to 30 strong earthquakes occurring on normal faults since 1509 CE in Calabria, Italy, including the influence of interseismic loading, and compare the results to existing studies of stress interaction from the Central and Southern Apennines, Italy. The three normal fault systems have different geometries and long‐term slip‐rates. We investigate the extent to which stress transfer can influence the occurrence of future earthquakes and what factors may govern the variability in earthquake recurrence in different fault systems. The Calabrian, Central Apennines, and Southern Apennines fault systems have 91%, 73%, and 70% of faults with mean positive cumulative CST in the time considered; this is due to fewer faults across strike, more across strike stress reductions, and greater along‐strike spacing in the three regions respectively. In regions with close along strike spacing or few faults across strike, such as Calabria and Southern Apennines, the stress loading history is mostly dominated by interseismic loading and most faults are positively stressed before an earthquake occur on them (96% of all faults that ruptured in Calabria; 94% of faults in Southern Apennines), and some of the strongest earthquakes occur on faults with the highest mean cumulative stress of all faults prior to the earthquake. In the Central Apennines, where across strike interactions are the predominant process, 79% of earthquakes occur on faults positively stressed. The results highlight that fault system geometry plays a central role in characterizing the stress evolution associated with earthquake recurrence. Plain Language Summary: Studies of fault interactions can improve our understanding of when and where the next earthquakes will occur. Here, we investigate how the orientation, length, location, and number of faults in a system influence the occurrence of future earthquakes, by modeling the stresses transferred during historical earthquakes and the regional stress in the Calabria region, southern Italy. We compare our results to similar models obtained for the Central Apennines and Southern Apennines in Italy. The Central Apennines hosts a complex fault system, with many overlapping faults, so that when an earthquake occurs, many of the surrounding faults experience a stress decrease. Whereas the Southern Apennines and Calabria have a simpler geometry, with fewer faults and less overlap, therefore the dominant process is stress increase. These characteristics influence the way faults build up stress, and we find that in regions with simpler geometry, a higher proportion of faults are positively stressed before an earthquake occurs on them, compared to regions with higher geometrical complexity. Our results show that fault system geometry plays a central role in characterizing the stress evolution associated with earthquake recurrence, and can possibly influence the occurrence of earthquake sequences that propagate between faults in a short time. Key Points: We compare Coulomb stress changes due to historical earthquakes and regional stress in three normal fault systems with different geometryFault system geometric complexity influences the number of faults that are positively stressed before they rupture in an earthquakeHigh slip rates and simple fault system geometry favor accumulation of high stress on faults and may promote triggered earthquake sequences [ABSTRACT FROM AUTHOR]

Assessing abundance and monitoring ecology and population trends are of critical importance for animal species of conservation concern. For sea turtles, annual nest counts represent the most common method of estimating population size. However, to develop a better understanding of population trends, these data need to be complemented by other reproductive parameters, which are lacking for many nesting populations across central Africa.To this end, an intensive capture–mark–recapture programme was conducted spanning 21 years (1997–2018) in the most important nesting sites on the Atlantic coast of central Africa (Gabon and Congo) for leatherback (Dermochelys coriacea) and olive ridley (Lepidochelys olivacea) sea turtles.A total of 18,105 encounters of 14,109 D. coriacea individuals and 2678 encounters of 2427 L. olivacea individuals were recorded. Biological and technical parameters such as clutch frequency, inter‐nesting interval, remigration interval, annual survival rate, somatic growth, size trends, tag loss and number of annual nesting females were estimated through a variety of methods and models.The study detected a decline in body size and low survival probability (not due to tag loss) in both species but no clear decline in estimated annual number of nesting females. High fidelity to nesting sites (<30 km for both species) implies that the current conservation strategy, protecting the main nesting areas, could be effective.We recommend that local conservation managers promote: (i) continued monitoring of the nesting activity of the two species through capture–mark–recapture programmes; (ii) continued nest counts at long‐term monitoring sites, which may also detect possible spatial shifts; and (iii) strengthening of cross‐border cooperation between Gabon and Republic of the Congo given the observed connectivity between nesting sites of the two countries. [ABSTRACT FROM AUTHOR]

The PIK3CA‐related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%–21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long‐term follow‐up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (ErbB2/HER2) is a tyrosine kinase receptor that is overexpressed in 25% of primary human breast cancers, as well as in multiple other cancers. HER2‐targeted therapies improved progression‐free and overall survival in patients with HER2+ breast cancers. However, associated resistance mechanisms and toxicity highlight the need for new therapeutic approaches for these cancers. We recently established that, in normal cells, HER2 is stabilized in a catalytically repressed state by direct interaction with members of the ezrin/radixin/moesin (ERM) family. In HER2‐overexpressing tumors, the low expression of moesin contributes to the aberrant activation of HER2. Through a screen designed to find moesin‐mimicking compounds, we identified ebselen oxide. We show that ebselen oxide, and some derivatives, conferred an efficient allosteric inhibition of overexpressed HER2, as well as mutated and truncated oncogenic forms of HER2, which are resistant to current therapies. Ebselen oxide selectively inhibited anchorage‐dependent and ‐independent proliferation of HER2+ cancer cells and showed a significant benefit in combination with current anti‐HER2 therapeutic agents. Finally, ebselen oxide significantly blocked HER2+ breast tumor progression in vivo. Collectively, these data provide evidence that ebselen oxide is a newly identified allosteric inhibitor of HER2 to be considered for therapeutic intervention on HER2+ cancers. [ABSTRACT FROM AUTHOR]

The three sympatric angel shark species occurring in the Mediterranean – Squatina squatina (the angelshark), Squatina aculeata (the sawback angelshark), and Squatina oculata (the smoothback angelshark) – are all classed as Critically Endangered on the International Union for Conservation of Nature (IUCN) Red List. There is a clear need to better quantify their current status, using appropriate non‐destructive methods, to help inform future conservation measures.This study introduces an environmental DNA (eDNA) assay able to detect and distinguish S. aculeata, S. oculata, and S. squatina in the Mediterranean Sea by combining probe‐based quantitative polymerase chain reaction (qPCR) technology and Sanger sequencing. The assay targets a 173‐bp barcode in the mitochondrial cytochrome c oxidase I (COI) gene. It was tested in silico, in vitro on tissue‐extracted DNA, and on eDNA extracted from filtration samples. This genus‐specific assay was applied to detect the presence of S. squatina in eDNA samples collected in Corsica, France.The target barcode was found in seven of 76 eDNA samples, revealing the presence of S. squatina in north‐western Corsica, where the shark has never been observed, and confirming its existence on the eastern coast. The study also demonstrates that using eDNA sampling, based on 30 L of seawater filtered close to the substrate with a waterproof peristaltic pump, it was possible to detect the eDNA of this rare benthic species.The results of detection can help identify critical areas for angel shark conservation and facilitate the development of local public awareness initiatives. This novel qPCR assay should be used for future applications in the Mediterranean and eastern Atlantic targeting angel sharks to better identify the remaining populations. In this study the qPCR assay was applied for S. squatina eDNA, but application to S. aculeata and S. oculata still needs to be validated in the field. [ABSTRACT FROM AUTHOR]

In France, high‐activity level wastes resulting from nuclear fission are conditioned in a homogeneous sodium‐aluminoborosilicate glass by high‐temperature vitrification. The tolerance of even a small fraction of crystals could enable an increase in the waste loadings, in addition to promoting process flexibility. If the waste loading were to be increased in French nuclear glass, cerianite (CeO2) crystals could precipitate. In this study, we investigated the cerianite crystallization in a simplified nuclear glass melt at different temperatures, Ce2O3 wt%, and shear conditions. Furthermore, the evolution of the viscosity along with cerianite precipitation was followed. It was found that Ce2O3 is highly soluble in the glass melt, as even for a Ce2O3 wt% as high as 10% wt, the cerianite fraction in dynamic conditions at 1100°C after 8 h of crystallization was less than 1% vol. In addition, shear strongly accelerates cerianite crystallization and a high Ce2O3 content can engender the precipitation of highly branched dendrites. The evolution of the cerianite fraction did not significantly affect the viscosity of the glass melt. Finally, unlike what has been observed in the well‐known platinum group metal (PGM)‐bearing melts, a glass melt containing.8 vol% of cerianite crystals remains Newtonian. [ABSTRACT FROM AUTHOR]

Purpose: Anorexia Nervosa (AN) is a serious and potentially lethal mental disorder characterised by a deliberate quest to reduce one's weight. It can have multiple physical and psychological consequences. The clinical presentation of AN can include gastrointestinal symptoms, however, the pathophysiology of these symptoms in the context of AN remains uncertain. It is hypothesised that patients with AN may have an increase in intestinal permeability, which could lead to an increase in faecal calprotectin (fCP), a marker of intestinal inflammation. No relation between AN and elevation of fCP has been previously described in literature. Methods: Eight patients hospitalised for AN have a dosage of fCP. Results: Calprotectine was found to be elevated in 50% of cases, with or without any underlying comorbid gastrointestinal disease. Only the duration of illness tended to be associated with the increase in fCP suggesting a greater alteration as a function related to the time of denutrition. Conclusion: Although these findings provide insights in the potential pathophysiology of gastrointestinal symptoms in AN, further studies that evaluate the factors associated with elevated fCP in patients with AN are needed. Key points: What is already known on this subject? To our knowledge, our study is the first to describe faecal calprotectin (fCP) levels in patients who are malnourished due to anorexia nervosa (AN) and describe the patients' clinical characteristics in order to better explain the gastrointestinal tract implication in AN symptoms. What this study adds? This study's finding of a possible elevation of fCP in patients with AN raises interesting questions on the pathophysiology of AN, and the possibility of an underlying inflammatory process in these patients. Although this is a preliminary study, as the sample size is small, it is therefore important for clinicians to acknowledge that fCP can be elevated in patients with AN without any other disease. The literature remains scarce regarding the relationship between the gastrointestinal tract and AN, although it is a predominant aspect of the symptomatology of the disease. This offers opportunities and strengthen the need for further research on the effects of restriction, renutrition and weight gain on the gastrointestinal tract in patients with AN, and the possible role and use of fCP in this disease. [ABSTRACT FROM AUTHOR]

Aim: Coastal fishes have a fundamental role in marine ecosystem functioning and contributions to people, but face increasing threats due to climate change, habitat degradation and overexploitation. The extent to which human pressures are impacting coastal fish biodiversity in comparison with geographic and environmental factors at large spatial scale is still under scrutiny. Here, we took advantage of environmental DNA (eDNA) metabarcoding to investigate the relationship between fish biodiversity, including taxonomic and genetic components, and environmental but also socio‐economic factors. Location: Tropical, temperate and polar coastal areas. Time period: Present day. Major taxa studied: Marine fishes. Methods: We analysed fish eDNA in 263 stations (samples) in 68 sites distributed across polar, temperate and tropical regions. We modelled the effect of environmental, geographic and socio‐economic factors on α‐ and β‐diversity. We then computed the partial effect of each factor on several fish biodiversity components using taxonomic molecular units (MOTU) and genetic sequences. We also investigated the relationship between fish genetic α‐ and β‐diversity measured from our barcodes, and phylogenetic but also functional diversity. Results: We show that fish eDNA MOTU and sequence α‐ and β‐diversity have the strongest correlation with environmental factors on coastal ecosystems worldwide. However, our models also reveal a negative correlation between biodiversity and human dependence on marine ecosystems. In areas with high dependence, diversity of all fish, cryptobenthic fish and large fish MOTUs declined steeply. Finally, we show that a sequence diversity index, accounting for genetic distance between pairs of MOTUs, within and between communities, is a reliable proxy of phylogenetic and functional diversity. Main conclusions: Together, our results demonstrate that short eDNA sequences can be used to assess climate and direct human impacts on marine biodiversity at large scale in the Anthropocene and can further be extended to investigate biodiversity in its phylogenetic and functional dimensions. [ABSTRACT FROM AUTHOR]

Protist plankton are major members of open‐water marine food webs. Traditionally divided between phototrophic phytoplankton and phagotrophic zooplankton, recent research shows many actually combine phototrophy and phagotrophy in the one cell; these protists are the "mixoplankton." Under the mixoplankton paradigm, "phytoplankton" are incapable of phagotrophy (diatoms being exemplars), while "zooplankton" are incapable of phototrophy. This revision restructures marine food webs, from regional to global levels. Here, we present the first comprehensive database of marine mixoplankton, bringing together extant knowledge of the identity, allometry, physiology, and trophic interactivity of these organisms. This mixoplankton database (MDB) will aid researchers that confront difficulties in characterizing life traits of protist plankton, and it will benefit modelers needing to better appreciate ecology of these organisms with their complex functional and allometric predator–prey interactions. The MDB also identifies knowledge gaps, including the need to better understand, for different mixoplankton functional types, sources of nutrition (use of nitrate, prey types, and nutritional states), and to obtain vital rates (e.g. growth, photosynthesis, ingestion, factors affecting photo' vs. phago' ‐trophy). It is now possible to revisit and re‐classify protistan "phytoplankton" and "zooplankton" in extant databases of plankton life forms so as to clarify their roles in marine ecosystems. [ABSTRACT FROM AUTHOR]

An understanding of the midterm sequelae in COVID‐19 and their association with corticosteroids use are needed. Between March and July 2020, we evaluated 1227 survivors of COVID‐19, 3 months posthospitalization, of whom 213 had received corticosteroids within 7 days of admission. Main outcome was any midterm sequelae (oxygen therapy, shortness of breath, one major clinical sign, two minor clinical signs or three minor symptoms). Association between corticosteroids use and midterm sequelae was assessed using inverse propensity‐score weighting models. Our sample included 753 (61%) male patients, and 512 (42%) were older than 65 years. We found a higher rate of sequelae among users than nonusers of corticosteroids (42% vs. 35%, odds ratio [OR] 1.40 [1.16–1.69]). Midterm sequelae were more frequent in users of low‐dose corticosteroids than nonusers (64% vs. 51%, OR 1.60 [1.10–2.32]), whereas no association between higher doses (≥20 mg/day equivalent of dexamethasone) and sequelae was evidenced (OR 0.95 [0.56–1.61]). Higher risk of sequelae with corticosteroids use was observed among subjects with propensity score below the 90th percentile. Our study suggest that corticosteroids use during hospitalization for COVID‐19 is associated with higher risk of midterm sequelae. [ABSTRACT FROM AUTHOR]

This study investigates the site‐directed immobilization of a hybrid catalyst bearing a biquinoline‐based‐Pd(II) complex (1) and a robust laccase within cavities of a silica foam to favor veratryl alcohol oxidation. We performed the grafting of 1 at a unique surface located lysine of two laccase variants, either at closed (1⊂UNIK157) or opposite position (1⊂UNIK71) of the enzyme oxidation site. After immobilization into the cavities of silica monoliths bearing hierarchical porosity, we show that catalytic activity is dependent on the orientation and loading of each hybrid, 1⊂UNIK157 being twice as active than 1⊂UNIK71 (203 TON vs 100 TON) when operating under continuous flow. These systems can be reused 5 times, with an operational activity remaining as high as 40 %. We show that the synergy between 1 and laccase can be tuned within the foam. This work is a proof of concept for controlling the organization of a heterogeneous hybrid catalyst using a Pd/laccase/silica foam. [ABSTRACT FROM AUTHOR]

Numerical weather prediction centers increasingly make use of cloudy and rainy microwave radiances. Currently, the high microwave frequencies are simulated using simplified assumptions regarding the radiative properties of frozen hydrometeors. In particular, one single particle shape is often used for all precipitating frozen particles, all over the globe, and for all cloud types. In this paper, a multi‐SSP (single scattering properties) approach for 1D Bayesian inversions is examined. Two experiments were set up: (1) one with three SSPs and (2) one with the previous SSPs plus one which leads to very cold brightness temperature distributions. For that purpose, we used observations from the GPM Microwave Imager radiometer over 2 months period and forecasts from the Météo‐France convective scale AROME model. The results showed that mixtures of SSP are chosen by the inversion method for meteorological conditions with low scattering and that a single particle is chosen for those with high scattering to perform the inversions. Despite the fact that no specific weather scenes were found to be associated with a particular SSP the most efficient scattering particles can be favored for some of them. [ABSTRACT FROM AUTHOR]

On June 12, 2004, a meteorite passed through Earth's atmosphere and landed under the television in the living room of a house in Auckland, New Zealand. Textural characteristics, the chemistry of olivine (Fa23–24) and orthopyroxene (Fs20.7), and the bulk rock triple oxygen isotopes (δ17O + 3.1; δ18O + 4.2‰) from the interior of the completely unweathered (W0) 1.3 kg meteorite, hereafter referred to as Auckland, suggest it to be a strongly metamorphosed fragment from the interior of a low iron ordinary chondrite (L6) parent asteroid. The occurrence of maskelynite but shock fracturing of olivine and pyroxene indicates Auckland experienced extreme shock metamorphism (S5), likely during Ordovician fragmentation of the asteroid parent. The fusion crust consists of three zones: (1) an innermost zone containing narrow Fe‐Ni‐S‐bearing veins that migrated along pre‐existing shock fractures in olivine and pyroxene; (2) a middle zone in which the meteorite partially melted to form a silicate glass and immiscible blebs of metal and troilite, and is accompanied by unmelted silicate minerals; and (3) an approximately 0.1 mm wide vesicular‐rich outermost layer that largely melted, volatilizing sulfides, before quenching to form glass and olivine. Oxygen isotope values of the bulk rock and/or maskelynite of melted rim and modified substrate are 2–3‰ greater than the meteorite interior and indicate that up to 19% of terrestrial atmospheric O2 was incorporated into the fusion crust during the formation. The fusion crust migrated inwards as ablation occurred, enabling melting, migration, and re‐precipitation ± loss of sulfide and metal components, with the prominent glassy rim therefore forming from an already chemically modified zone. [ABSTRACT FROM AUTHOR]

The cause of magmatic tempo in an active plate margin remains controversial, partly due to lack of structural analysis. During 130–105 Ma, the magmatism in the South China Block (SCB) was significantly reduced (lull) and restricted around the Changle‐Nan'ao Belt (CNB) while the magmatism was highly active (flare‐up) in North China. For unveiling the tectonic role on magmatism, a multidisciplinary study including field and microscopic structural observations, magnetic fabric measurement (AMS), and zircon/monazite dating was conducted on the plutons with oriented minerals in the CNB. Structural analysis and AMS results show a highly clustered NE‐striking vertical foliation developed during the emplacement indicating a syn‐emplacement NW‐SE shortening regime. The geochronology results confirm that the emplacement occurred during 130–105 Ma. Regional geologic correlation indicates that the collision between the Dangerous Grounds‐West Philippines Block and SCB was responsible for this shortening regime. The collected depleted zircon εHf(t) data suggest that a possible collision‐triggered slab break‐off caused the syn‐collisional magmatic activity around the CNB. This study shows that the magmatic lull in the SCB was coeval with a crustal shortening regime due to the arrival of a microcontinent carried by the subduction slab, while the magmatic flare‐up was coeval with an extensional regime due to the subduction roll‐back and retreat as evidenced by the Cretaceous evolution of the SCB before and after the collision and that of North China which is unaffected by the collision. The cause of magmatic tempo in the continental margin is largely due to the tectonic evolution of underlain subduction slabs. Plain Language Summary: Magmatic activity is closely connected to human life as it provides us with useful metals, releases greenhouse gases, triggers natural hazards. It is necessary to explore what controls a magmatic activity. Several previous studies considered that a shortening regime with thickened crust causes strong magmatism (flare‐up). The South China Block (SCB) featured by alternating magmatic flare‐up and lulls, provides an appropriate research target to test this hypothesis. During the Cretaceous, the SCB was dominated by an extensional regime caused by the Paleo‐Pacific oceanic slab subduction. However, our structural analyses on the SCB document a shortening regime caused by the collision between the SCB and a microcontinent carried by the Paleo‐Pacific oceanic slab in the period of the Cretaceous. During the collision, the SCB was generally featured by a magmatic lull, although magmatic activity was only observed around the Changle‐Nan'ao Belt, probably caused by the break‐off of the subducted Paleo‐Pacific oceanic slab. Before and after the collision, the extensional regime caused by Paleo‐Pacific oceanic slab subduction was coeval with magmatic flare‐up. This study questions the previous claims and proposes that the tectonic evolution of the subducting slab may control the magmatic flare‐up and lull in the overlain active continental margin. Key Points: The 130–105 Ma syn‐tectonic plutons intruded the Changle‐Nan'ao Belt in a NW‐SE shortening regime caused by a microcontinent collisionThe shortening/extension regimes were coeval with magmatic lull/flare‐up in the East Asia Continental Margin during the CretaceousThe collision causing break‐off can account for the plutonism in the Changle‐Nan'ao Belt during the magmatic lull of the South China Block [ABSTRACT FROM AUTHOR]

The ongoing outbreak of monkeypox virus (MPXV) is the largest one in historically non‐endemic countries. Early reports described atypical epidemiological and clinical presentations. We investigated MPXV DNA detection in oropharyngeal samples (OPS), and compared the viral load to that in lesion samples at diagnosis in patients infected with MPXV. We retrospectively included patients suspected to have monkeypox in Northern France, who underwent a MPXV PCR in the Virology Laboratory, University Hospital of Lille, from May 23 to August 18, 2022. Overall, a total of 228 patients (376 samples) were included. A positive result in at least one sample was found in 138 patients (60.5%). We compared PCR results between OPS and lesion samples (i.e., cutaneous or anal/rectal samples) in patients with both samples. A positive result in OPS was observed in 54 out of 60 patients (90%). The viral load in OPS (median Ct value = 29.5; interquartile range [IQR] = 24.7−34) was significantly lower than that in lesion samples (median Ct value = 17.8; IQR = 16.3 and 19.7) (p < 0.0001). This report shows that pharyngeal sampling does not bring additional information for the initial diagnosis in patients presenting with typical lesions. [ABSTRACT FROM AUTHOR]

Introduction: Intradetrusor BotulinumtoxinA (BTA) injections are recommended for patients with overactive bladder (OAB) refractory to lifestyle changes and medical intervention. It is preferable to perform injections using a flexible cystoscope under local anesthetic (LA) rather than under spinal or general anesthetic owing to the associated anesthetic risks, increased costs, and need for repeated inpatient admission. Injections under LA can be difficult to tolerate for some patients. This review aims to assess interventions that may improve the tolerability of intradetrusor BTA injections under LA. Methods: A systematic review was performed using Ovid of Embase + Embase classic and MEDLINE® ALL in November 2021. Articles were included if they reported objectively measured pain scores during LA intradetrusor BTA injections for refractory OAB. The risk of bias was assessed using Cochrane risk of bias tools. Meta‐analysis was not performed owing to the heterogeneity of outcome measures. Results: Ten studies were included in this review with a total of 429 participants. The review identified alkalinized lidocaine, electromotive drug administration (EMDA), opiate suppositories, lidocaine bladder instillations, number of injections, and dose of BTA as interventions aimed at improving tolerability. Conclusion: EMDA of intravesical alkalinized lidocaine, intravesical, alkalinized lidocaine without EMDA, and a reduction in the number of injection site were all associated with improvements in patient tolerability during LA BTA injections. Further research should address which subgroups of patients find the procedure most painful and would benefit most from these interventions. [ABSTRACT FROM AUTHOR]

Oxygen isotopes are useful for tracing interactions between magmas, crustal rocks and surface-derived waters. We use them here to consider links between voluminous silicic magmatism and large-scale hydrothermal circulation in New Zealand's central Taupō Volcanic Zone (TVZ). We present >350 measurements of plagioclase, quartz, hornblende and groundmass glass δ18O values from 40 eruptions from three discrete magmatic systems: Ōkataina and Taupō calderas, and the smaller Northeast Dome system. For each mineral, mean δ18O values vary by ~1% (δ18Oplag = +6.7-7.8%, δ18Oqtz = +7.7-+8.7%, δ18Ohbl = +5.4-+6.4%, δ18Oglass = +7.1-+8.0%), and inter-mineral fractionations mostly reflect high-temperature equilibria. Outliers (e.g., ~+6% or >+10% plagioclase) represent contaminants incorporated on short-enough timescales to preserve disequilibrium (~102 yrs for plagioclase). Melt δ18O values calculated from phenocrysts are ~+7.3-+8.0%. Where multiple magmas were involved in the same eruption their δ18Omelt values are indistinguishable, implying that their parental mushes were isotopically well-mixed. However, small (≤0.5%) but consistent δ18Omelt value gradients occur over millennial timescales at Ōkataina and Taupō, with short-term ~0.4-0.5% decreases in δ18Omelt values over successive post-caldera eruptions correlating with increases in 87Sr/86Sr. These changes reflect tens of percent assimilation of a mixture of hydrothermally altered silicic plutonic material and higher-87Sr/86Sr greywacke. These examples represent the first evidence for assimilation of altered crust into TVZ magmas. The subtle and short-lived isotopic signals of these interactions are only recognized through the high temporal resolution of the TVZ eruptive record and complementary radiogenic isotope data. Similar interactions may have been obscured in other nominally highor normal-δ18O magmatic systems. [ABSTRACT FROM AUTHOR]

Densification of ceramic electrolytes is a key enabler in producing electrolyte pellets for solid‐state batteries. This requires understanding the correlation between the starting grain size of electrolytes, chemical phase evolution and degree of compaction which determine ion conductivity and chemical stability of solid electrolytes. In our work we were able to optimize the densification process of LATP at 700 °C with a high total ionic conductivity of 3.45×10−4 S cm−1 after hot pressing, balancing pristine LATP crystallite size and AlPO4 impurity formation. By combining several techniques such as in situ heating X‐ray diffraction (XRD), scanning electron microscopy (SEM) and nuclear magnetic resonance (NMR), we explored the formation mechanism of AlPO4 during the synthesis process of NASICON‐type Li1.5Al0.5Ti1.5(PO4)3 (LATP) electrolyte and we showed the effects of the annealing temperature on the crystal size of the material. Density functional theory (DFT) calculations on the chemical stability of the electrolyte imply a metastable behaviour of LATP furtherly enhanced by particle nano‐structuring at high temperature. Our results point to facile manufacturing of ceramic electrolytes towards energy dense and safe solid‐state battery technology. [ABSTRACT FROM AUTHOR]

CD4+ T lymphocytes play a major role in the establishment and maintenance of immunity. They are activated by antigenic peptides derived from extracellular or newly synthesized (endogenous) proteins presented by the MHC‐II molecules. The pathways leading to endogenous MHC‐II presentation remain poorly characterized. We demonstrate here that the autophagy receptor, T6BP, influences both autophagy‐dependent and ‐independent endogenous presentation of HIV‐ and HCMV‐derived peptides. By studying the immunopeptidome of MHC‐II molecules, we show that T6BP affects both the quantity and quality of peptides presented. T6BP silencing induces the mislocalization of the MHC‐II‐loading compartments and rapid degradation of the invariant chain (CD74) without altering the expression and internalization kinetics of MHC‐II molecules. Defining the interactome of T6BP, we identify calnexin as a T6BP partner. We show that the calnexin cytosolic tail is required for this interaction. Remarkably, calnexin silencing replicates the functional consequences of T6BP silencing: decreased CD4+ T cell activation and exacerbated CD74 degradation. Altogether, we unravel T6BP as a key player of the MHC‐II‐restricted endogenous presentation pathway, and we propose one potential mechanism of action. Synopsis: The autophagy receptor T6BP (TAX1BP1) stabilizes the invariant chain (CD74) and regulates MHC‐II trafficking, thereby favoring the presentation of high‐affinity peptides to virus‐specific CD4+ T cells. T6BP loss prevents the activation of HIV‐ and HCMV‐specific CD4+ T cell clones.T6BP expression affects the quality and the diversity of peptides presented by MHC‐II molecules.T6BP interacts with the cytoplasmic tail of calnexin to favor MHC‐II molecule chaperoning by the invariant chain (CD74).Calnexin loss replicates T6BP silencing: decreased CD4+ T cell activation and exacerbated CD74 degradation. [ABSTRACT FROM AUTHOR]

This article explores the problem of information structure in ancient Greek direct constituent questions from the perspective of wh‐placement. It begins with the observation that wh‐items are intrinsically focused and that typologically, wh‐placement is predictable based on the focusing properties in some languages, such as Indonesian (in situ strategy) and Basque or Hungarian (focus position strategy), but not in others, such as English (specific wh‐position strategy). Ancient Greek has multiple ways to express narrow focusing, e.g., in situ or in a preverbal devoted position. Puzzlingly, with respect to whPs, the former way is only marginally attested and there is no good evidence for the latter way. Instead, based on syntactic and prosodic tests, we show that ancient Greek offers a third strategy, in which a high position in the structure is available. Nevertheless, when this result is recast in the framework of Phase Theory, the tests of wh‐duplication and stranding indicate that whPs must go through all three positions, receiving their argument function in situ, checking their focus feature preverbally and verifying their wh‐feature in the high position. The specificity of 'why' questions is addressed along the way. [ABSTRACT FROM AUTHOR]