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Insights into the source and partial melting conditions of tonalite–trondhjemite–granodiorite (TTG) intrusive suites provide essential constraints on the tectonic regimes prevailing before 2.5 Ga. As case studies on individual suites increase, the TTG group becomes more heterogeneous, offering detailed insights into the evolution of the Archean crust. This study focuses on the La Dauversière pluton, a TTG suite in the Chibougamau area, Abitibi greenstone belt, Canada, to unravel complex differentiation processes in a pluton with a relatively limited volume. According to whole-rock and zircon chemistry, the La Dauversière pluton is a TTG suite that contains less Na and light rare earth elements (LREE) than other TTG suites of the Abitibi greenstone belt. Whole-rock chemistry and melt inclusions in zircon also point to an atypical fractional crystallization process that favors K enrichment, contrasting with the Na enrichment trends observed in most TTG suites globally. Magma hybridization, with late magma pulses interacting with early phases partially crystallized at depth, likely explains the chemistry of the La Dauversière pluton. The source of these magmas differs from the basaltic source that gave rise to most TTG suites of the Abitibi greenstone belt, possibly because older basement occurs in the Chibougamau area and is lacking in the rest of the greenstone belt. The La Dauversière pluton underscores the importance of interpreting the petrogenesis of individual TTG suites before inferring global source processes and geodynamic settings. [ABSTRACT FROM AUTHOR]

Raman spectroscopy provides label‐free, specific analysis of biomolecular structure and interactions. It could have a greater impact with improved characterization of complex fingerprint vibrations. Many Raman peaks have been assigned to cholesterol, for example, but the molecular vibrations associated with those peaks are not known. In this report, time‐dependent density functional theory calculations of the Raman spectrum of cholesterol are compared to measurements on microcrystalline powder to identify 23 peaks in the Raman spectrum. Among them, a band of six peaks is found to be sensitive to the conformational structure of cholesterol's iso‐octyl chain. Calculations on 10 conformers in this spectral band are fit to experimental spectra to probe the cholesterol chain structure in purified powder and in phospholipid vesicles. In vesicles, the chain is found to bend perpendicular to the steroid rings, supporting the case that the chain is a dynamic structure that contributes to lipid condensation and other effects of cholesterol in biomembranes. Statement of Significance: Here we use density functional theory to identify a band of six peaks in cholesterol's Raman spectrum that is sensitive to the conformational structure of cholesterol's chain. Raman spectra were analyzed to show that in fluid‐phase lipid membranes, about half of the cholesterol chains point perpendicular to the steroid rings. This new method of label‐free structural analysis could make significant contributions to our understanding of cholesterol's critical role in biomembrane structure and function. More broadly, the results show that computational quantum chemistry Raman spectroscopy can make significant new contributions to molecular structure when spectra are interpreted with computational quantum chemistry. [ABSTRACT FROM AUTHOR]

Abstract Background Cervicitis, an infectious or noninfectious inflammation of the cervix, encompasses a wide range of clinical conditions, from asymptomatic infections to severe lesions, making its diagnosis difficult. Acute cervicitis may develop into pelvic inflammatory disease. In patients with cervicitis, current guidelines recommend testing for herpes simplex virus when external genital lesions are present. Here, we present the case of a patient with an atypical primary herpes simplex virus 2 infection manifesting as cervicitis without genital lesions. Case presentation A 29-year-old Caucasian woman was hospitalized for pelvic inflammatory disease. The patient complained of severe suprapubic pain, fever, and heavy vaginal discharge. The external genitalia were unremarkable, so empirical antibiotic treatment was initiated. Despite 48 hours of well-administered antibiotic therapy, her complaints persisted. Polymerase chain reaction for possible microbial causes was negative for Chlamydia trachomatis and Neisseria gonorrhoeae. There was no bacterial vaginosis. Repeat gynecological examinations with endovaginal ultrasound revealed an enlarged cervix, and pelvic magnetic resonance imaging supported a diagnosis of cervicitis. At this point, additional screening for other sexually transmitted infections and infectious disease-related etiologies of cervicitis was performed, and the polymerase chain reaction analysis of newly isolated samples was positive for herpes simplex virus 2. No antiviral treatment was initiated given the delay in diagnosing herpes simplex virus 2 infection and the slow but spontaneous abatement of symptoms. Conclusion Herpes simplex virus infection should be considered as a possible cause of cervicitis, even in the absence of typical genital lesions. Early detection of herpes simplex virus allows early treatment, helping to reduce the duration and severity of symptoms and therefore potentially reducing recurrences and improving disease control. These data and data from future cases might spur changes in the guidelines on cervicitis testing and treatment.

Abstract Background Nitric oxide (NO) is a strong vasodilator, selectively directed on pulmonary circulation through inhaled administration. In adult intensive care units (ICU), it is mainly used for refractory hypoxemia in mechanically ventilated patients. Several medical delivery devices have been developed to deliver inhaled nitric oxide (iNO). The main purpose of those devices is to guarantee an accurate inspiratory NO concentration, whatever the ventilator used, with NO2 concentrations lower than 0.3 ppm. We hypothesized that the performances of the different available iNO delivery systems could depend on their working principle and could be influenced by the ventilator settings. The objective of this study was to assess the accuracy of seven different iNO-devices combined with different ICU ventilators’ flow-by to reach inspiratory NO concentration targets and to evaluate their potential risk of toxicity. Methods We tested seven iNO-devices on a test-lung connected to distinct ICU ventilators offering four different levels of flow-by. We measured the flow in the inspiratory limb of the patient circuit and the airway pressure. The nitric oxide/nitrogen (NO/N2) flow was measured on the administration line of the iNO-devices. NO and NO2 concentrations were measured in the test-lung using an electrochemical analyzer. Results We identified three iNO-device generations based on the way they deliver NO flow: “Continuous”, “Sequential to inspiratory phase” (I-Sequential) and “Proportional to inspiratory and expiratory ventilator flow” (Proportional). Median accuracy of iNO concentration measured in the test lung was 2% (interquartile range, IQR -19; 36), -23% (IQR -29; -17) and 0% (IQR -2; 0) with Continuous, I-Sequential and Proportional devices, respectively. Increased ventilator flow-by resulted in decreased iNO concentration in the test-lung with Continuous and I-Sequential devices, but not with Proportional ones. NO2 formation measured to assess potential risks of toxicity never exceeded the predefined safety target of 0.5 ppm. However, NO2 concentrations higher than or equal to 0.3 ppm, a concentration that can cause bronchoconstriction, were observed in 19% of the different configurations. Conclusion We identified three different generations of iNO-devices, based on their gas administration modalities, that were associated with highly variable iNO concentrations’ accuracy. Ventilator’s flow by significantly impacted iNO concentration. Only the Proportional devices permitted to accurately deliver iNO whatever the conditions and the ventilators tested.

Abstract Biological neural networks do not only include long-term memory and weight multiplication capabilities, as commonly assumed in artificial neural networks, but also more complex functions such as short-term memory, short-term plasticity, and meta-plasticity - all collocated within each synapse. Here, we demonstrate memristive nano-devices based on SrTiO3 that inherently emulate all these synaptic functions. These memristors operate in a non-filamentary, low conductance regime, which enables stable and energy efficient operation. They can act as multi-functional hardware synapses in a class of bio-inspired deep neural networks (DNN) that make use of both long- and short-term synaptic dynamics and are capable of meta-learning or learning-to-learn. The resulting bio-inspired DNN is then trained to play the video game Atari Pong, a complex reinforcement learning task in a dynamic environment. Our analysis shows that the energy consumption of the DNN with multi-functional memristive synapses decreases by about two orders of magnitude as compared to a pure GPU implementation. Based on this finding, we infer that memristive devices with a better emulation of the synaptic functionalities do not only broaden the applicability of neuromorphic computing, but could also improve the performance and energy costs of certain artificial intelligence applications.

Abstract Although friction of liquids on solid surfaces is traditionally linked to wettability, recent works have unveiled the role of the solid’s internal excitations on interfacial dissipation. In order to directly evidence such couplings, we take advantage of the considerable variation of the molecular timescales of supercooled glycerol under mild change of temperature to explore how friction depends on the liquid’s molecular dynamics. Using a dedicated tuning-fork AFM, we measure the slippage of glycerol on mica. We report a 100 fold increase of slip length upon cooling, while liquid-solid friction exhibits a linear scaling with molecular relaxation rate at high temperature. This scaling can be explained by a contribution of mica’s phonons which resonate with density fluctuations in the liquid, allowing efficient momentum transfer to mica. These results suggest that engineering phononic spectra of materials could enhance flow performance in nanofluidic channels and industrially relevant membranes.

Abstract Background The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences. Methods We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015–2022. We performed interrupted time series analyses based on Poisson models for five age classes (12–18; 19–25; 26–50; 51–75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after. Results In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12–18 and 19–25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar. Conclusions The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.

Abstract Background Movement smoothness is a potential kinematic biomarker of upper extremity (UE) movement quality and recovery after stroke; however, the measurement properties of available smoothness metrics have been poorly assessed in this group. We aimed to measure the reliability, responsiveness and construct validity of several smoothness metrics. Methods This ancillary study of the REM-AVC trial included 31 participants with hemiparesis in the subacute phase of stroke (median time since stroke: 38 days). Assessments performed at inclusion (Day 0, D0) and at the end of a rehabilitation program (Day 30, D30) included the UE Fugl Meyer Assessment (UE-FMA), the Action Research Arm Test (ARAT), and 3D motion analysis of the UE during three reach-to-point movements at a self-selected speed to a target located in front at shoulder height and at 90% of arm length. Four smoothness metrics were computed: a frequency domain smoothness metric, spectral arc length metric (SPARC); and three temporal domain smoothness metrics (TDSM): log dimensionless jerk (LDLJ); number of submovements (nSUB); and normalized average rectified jerk (NARJ). Results At D30, large clinical and kinematic improvements were observed. Only SPARC and LDLJ had an excellent reliability (intra-class correlation > 0.9) and a low measurement error (coefficient of variation 0.8) and not to changes in movement straightness (non-significant correlations). Most construct validity hypotheses tested were verified except for TDSM with low correlations with clinical metrics at D0 (rSpearman

Abstract Epithelial ovarian cancer is mostly discovered at the stage of peritoneal carcinosis. Complete cytoreductive surgery improves overall survival. The Fagotti score is a predictive score of resectability based on peritoneal laparoscopic exploratory. Our aim was to study the inter-observer concordance in an external validation of the Fagotti score. An observational, prospective, multicenter study was conducted using the Francogyn research network. The primary outcome was inter-observer concordance of the Fagotti score. 15 patients in which an ovarian mass was discovered were included. For each patient, the first exploratory laparoscopy before any treatment/chemotherapy was recorded. This bank of 15 videos was subject to blind review accompanied by a Fagotti score rating by 11 gynecological surgeons specializing in oncology. A total of 165 blind reviews were performed. Inter-observer concordance was very good for the Fagotti score with an intraclass correlation coefficient (ICC) of 0.83 [95% CI 0.71; 0.93]. Inter-observer concordance for the adjusted Fagotti score, which accounts for unexplorable areas with extensive carcinomatosis, resulted in an ICC of 0.64 [95% CI 0.46; 0.82]. According to the reviewers, the three least explorable parameters were mesentery involvement, stomach infiltration and liver damage. The ICC of the explorable Fagotti score, i.e. score with deletion of the parameters most often unexplored by laparoscopy, was 0.86 [0.75–0.94]. This study confirms the reproducibility of the Fagotti score during first assessment laparoscopies in cases of advanced ovarian cancer. The explorable Fagotti score has an equivalent or better inter-observer concordance than the Fagotti score.

Abstract In the realm of ophthalmology, precise measurement of tear film break-up time (TBUT) plays a crucial role in diagnosing dry eye disease (DED). This study aims to introduce an automated approach utilizing artificial intelligence (AI) to mitigate subjectivity and enhance the reliability of TBUT measurement. We employed a dataset of 47 slit lamp videos for development, while a test dataset of 20 slit lamp videos was used for evaluating the proposed approach. The multistep approach for TBUT estimation involves the utilization of a Dual-Task Siamese Network for classifying video frames into tear film breakup or non-breakup categories. Subsequently, a postprocessing step incorporates a Gaussian filter to smooth the instant breakup/non-breakup predictions effectively. Applying a threshold to the smoothed predictions identifies the initiation of tear film breakup. Our proposed method demonstrates on the evaluation dataset a precise breakup/non-breakup classification of video frames, achieving an Area Under the Curve of 0.870. At the video level, we observed a strong Pearson correlation coefficient (r) of 0.81 between TBUT assessments conducted using our approach and the ground truth. These findings underscore the potential of AI-based approaches in quantifying TBUT, presenting a promising avenue for advancing diagnostic methodologies in ophthalmology.

Interaction is a dynamic process that evolves in real time. Participants interpret and orient themselves towards turns of speech based on expectations of relevance and social/conversational norms (that have been extensively studied in the field of Conversation analysis). A true challenge to Human Robot Interaction (HRI) is to develop a system capable of understanding and adapting to the changing context, where the meaning of a turn is construed based on the turns that have come before. In this work, we identify issues arising from the inadequate handling of the sequential flow within a corpus of in-the-wild HRIs in an open-world university library setting. The insights gained from this analysis can be used to guide the design of better systems capable of handling complex situations. We finish by surveying efforts to mitigate the identified problems from a natural language processing/machine dialogue management perspective.

Abstract The Arctic polar nights bring extreme environmental conditions characterised by cold and darkness, which challenge the survival of organisms in the Arctic. Additionally, multiple anthropogenic stressors can amplify the pressure on the fragile Arctic ecosystems during this period. Determining how multiple anthropogenic stressors may affect the survival of Arctic life is crucial for ecological risk assessments and management, but this topic is understudied. For the first time, our study investigates the complex interactions of multiple stressors, exploring stressor temporal dynamics and exposure duration on a key Arctic copepod Calanus glacialis during the polar nights. We conducted experiments with pulse (intermittent) and press (continuous) exposure scenarios, involving microplastics, pyrene and warming in a fully factorial design. We observed significant effects on copepod survival, with pronounced impacts during later stressor phases. We also detected two‐way interactions between microplastics and pyrene, as well as pyrene and warming, further intensified with the presence of a third stressor. Continuous stressor exposure for 9 days (press‐temporal scenario) led to greater reductions in copepod survival compared to the pulse‐temporal scenario, characterised by two 3‐day stressor exposure phases. Notably, the inclusion of recovery phases, free from stressor exposure, positively influenced copepod survival, highlighting the importance of temporal exposure dynamics. We did not find behaviour to be affected by the different treatments. Our findings underscore the intricate interactions amongst multiple stressors and their temporal patterns in shaping the vulnerability of overwintering Arctic copepods with crucial implications for managing Arctic aquatic ecosystems under the fastest rate of ongoing climate change on earth.

Summary: Human CD8 tumor-infiltrating lymphocytes (TILs) with impaired effector functions and PD-1 expression are categorized as exhausted. However, the exhaustion-like features reported in TILs might stem from their activation rather than the consequence of T cell exhaustion itself. Using CRISPR-Cas9 and lentiviral overexpression in CD8 T cells from non-cancerous donors, we show that the T cell receptor (TCR)-induced transcription factor interferon regulatory factor 4 (IRF4) promotes cell proliferation and PD-1 expression and hampers effector functions and expression of nuclear factor κB (NF-κB)-regulated genes. While CD8 TILs with impaired interferon γ (IFNγ) production exhibit activation markers IRF4 and CD137 and exhaustion markers thymocyte selection associated high mobility group box (TOX) and PD-1, activated T cells in patients with COVID-19 do not demonstrate elevated levels of TOX and PD-1. These results confirm that IRF4+ TILs are exhausted rather than solely activated. Our study indicates, however, that PD-1 expression, low IFNγ production, and active cycling in TILs are all influenced by IRF4 upregulation after T cell activation.

Abstract In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p

Abstract Background Quality traits are essential determinants of consumer preferences. Dioscorea alata (Greater Yam), is a starchy tuber crop in tropical regions. However, a comprehensive understanding of the genetic basis underlying yam tuber quality remains elusive. To address this knowledge gap, we employed population genomics and candidate gene association approaches to unravel the genetic factors influencing the quality attributes of boiled yam. Methods and Results Comparative genomics analysis of 45 plant species revealed numerous novel genes absent in the existing D. alata gene annotation. This approach, adding 48% more genes, significantly enhanced the functional annotation of three crucial metabolic pathways associated with boiled yam quality traits: pentose and glucuronate interconversions, starch and sucrose metabolism, and flavonoid biosynthesis. In addition, the whole-genome sequencing of 127 genotypes identified 27 genes under selection and 22 genes linked to texture, starch content, and color through a candidate gene association analysis. Notably, five genes involved in starch content and cell wall composition, including 1,3-beta Glucan synthase, β-amylase, and Pectin methyl esterase, were common to both approaches and their expression levels were assessed by transcriptomic data. Conclusions The analysis of the whole-genome of 127 genotypes of D. alata and the study of three specific pathways allowed the identification of important genes for tuber quality. Our findings provide insights into the genetic basis of yam quality traits and will help the enhancement of yam tuber quality through breeding programs.

Abstract A breakthrough technology, on-chip frequency comb sources offer broadband combs while being compact, energy-efficient, and cost-effective solutions for various applications from lidar to telecommunications. Yet, these sources encounter a fundamental trade-off between controllability and bandwidth: broadband combs, generated in microresonators, lack free-spectral range or spectral envelope control, while combs generated with electro-optic modulators can be carefully tailored but are limited in bandwidth. Here, we overcome this trade-off through agile spectral multiplication of narrowband combs. Exploiting the nonlinear dynamics of a multi-wavelength laser under modulated optical injection, we achieve spectral multiplication at frequency offsets from 26 GHz to 1.3 THz. Moreover, on-chip control allows for nano-second switching of the frequency offset. Compatible with generic platforms, our approach can be scaled up to cover several THz. When combined with THz photomixers, our system could enable low-cost, compact, and power-efficient THz comb sources, paving the way towards a new generation of THz applications.

Abstract An important challenge in active matter lies in harnessing useful global work from entities that produce work locally, e.g., via self-propulsion. We investigate here the active matter version of a classical capillary rise effect, by considering a non-phase separated sediment of self-propelled Janus colloids in contact with a vertical wall. We provide experimental evidence of an unexpected and dynamic adsorption layer at the wall. Additionally, we develop a complementary numerical model that recapitulates the experimental observations. We show that an adhesive and aligning wall enhances the pre-existing polarity heterogeneity within the bulk, enabling polar active particles to climb up a wall against gravity, effectively powering a global flux. Such steady-state flux has no equivalent in a passive wetting layer.

Abstract Semiconductor transistors operate by modulating the charge carrier concentration of a channel material through an electric field coupled by a capacitor. This mechanism is constrained by the fundamental transport physics and material properties of such devices—attenuation of the electric field, and limited mobility and charge carrier density in semiconductor channels. In this work, we demonstrate a new type of transistor that operates through a different mechanism. The channel material is a Weyl semimetal, NbP, whose resistivity is modulated via a magnetic field generated by an integrated superconductor. Due to the exceptionally large electron mobility of this material, which reaches over 1,000,000 cm2/Vs, and the strong magnetoresistive coupling, the transistor can generate significant transconductance amplification at nanowatt levels of power. This type of device can enable new low-power amplifiers, suitable for qubit readout operation in quantum computers.

We report on the development of low numerical aperture (NA) Nd-doped large mode area (LMA) fibers with optimized core/clad geometry to achieve high-power laser emission near 915 nm while maintaining near diffraction-limited output beam. The influence of clad-to-core ratio on the detrimental amplified spontaneous emission (ASE) at 1050 nm and on the beam quality was studied experimentally in different amplifier configurations. We also show that bending the Nd-doped LMA fiber to a precise radius of curvature significantly improves the overall laser performances of these fibers by limiting both higher-order modes and spurious ASE at 1050 nm. The possibility of all-fiber multi-stages amplifier configurations with diffraction-limited output beam is finally discussed.

The resistance of Arabidopsis thaliana to clubroot, a major disease of Brassicaceae caused by the obligate protist Plasmodiophora brassicae, is controlled in part by epigenetic factors. The detection of some of these epigenetic quantitative trait loci (QTLepi) has been shown to depend on experimental conditions. The aim of the present study was to assess whether and how temperature and/or soil water availability influenced both the detection and the extent of the effect of response QTLepi. The epigenetic recombinant inbred line (epiRIL) population, derived from the cross between ddm1-2 and Col-0 (partially resistant and susceptible to clubroot, respectively), was phenotyped for response to P. brassicae under four abiotic conditions including standard conditions, a 5°C temperature increase, drought, and flooding. The abiotic constraints tested had a significant impact on both the leaf growth of the epiRIL population and the outcome of the epiRIL–pathogen interaction. Linkage analysis led to the detection of a total of 31 QTLepi, 18 of which were specific to one abiotic condition and 13 common to at least two environments. EpiRIL showed significant plasticity under epigenetic control, which appeared to be specific to the traits evaluated and to the abiotic conditions. These results highlight that the environment can affect the epigenetic architecture of plant growth and immune responses and advance our understanding of the epigenetic factors underlying plasticity in response to climate change.

Background: To address the increasing global demand for Total Knee Arthroplasty and reduce the need for revisions, several technologies combining 3D planning and artificial intelligence have emerged. These innovations aim to enhance customization, improve component positioning accuracy and precision. The integration of these advancements paves the way for the development of personalized and connected knee implant. Questions/purposes: These groundbreaking advancements may necessitate changes in surgical practices. Hence, it is important to comprehend surgeons' intentions in integrating these technologies into their routine procedures. Our study aims to assess how surgeons' preferences will affect the acceptability of using this new implant and associated technologies within the entire care chain. Methods: We employed a Discrete Choice Experiment, a predictive technique mirroring real-world healthcare decisions, to assess surgeons' trade-off evaluations and preferences. Results: A total of 90 experienced surgeons, performing a significant number of procedures annually (mostly over 51) answered. Analysis indicates an affinity for technology but limited interest in integrating digital advancements like preoperative software and robotics. However, they are receptive to practice improvements and considering the adoption of future sensors. Conclusions: In conclusion, surgeons prefer customized prostheses via augmented reality, accepting extra cost. Embedded sensor technology is deemed premature by them.

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83–0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders.

Summary: The viral vector-based COVID-19 vaccine Ad26.COV2.S has been recommended by the WHO since 2021 and has been administered to over 200 million people. Prior studies have shown that Ad26.COV2.S induces durable neutralizing antibodies (NAbs) that increase in coverage of variants over time, even in the absence of boosting or infection. Here, we studied humoral responses following Ad26.COV2.S vaccination in individuals enrolled in the initial Phase 1/2a trial of Ad26.COV2.S in 2020. Through 8 months post vaccination, serum NAb responses increased to variants, including B.1.351 (Beta) and B.1.617.2 (Delta), without additional boosting or infection. The level of somatic hypermutation, measured by nucleotide changes in the VDJ region of the heavy and light antibody chains, increased in Spike-specific B cells. Highly mutated mAbs from these sequences neutralized more SARS-CoV-2 variants than less mutated comparators. These findings suggest that the increase in NAb breadth over time following Ad26.COV2.S vaccination is mediated by affinity maturation.

Abstract The northeastern part of the North Atlantic subpolar gyre is a key passage for the Atlantic Meridional Overturning Circulation upper cell. To this day, the precise pathway and intensity of bottom currents in this area is not clear. In this study, we make use of regional high resolution numerical modeling to suggest that the main bottom current flowing south of Iceland originates from both the Faroe‐Banks Channel and the Iceland‐Faroe Ridge and then flows along the topographic slope. When flowing over the rough topography, this bottom current generates a 200 m large bottom mixed layer. We further demonstrate that many submesoscale structures are generated at the southernmost tip of the Icelandic shelf, which subsequently spread water masses in the Iceland Basin. These findings have major implication for the understanding of the water masses transport in the North Atlantic, and also for the distribution of benthic species along the Icelandic shelf.

Polyphosphates (polyP) are chains of inorganic phosphates that can reach over 1,000 residues in length. In Escherichia coli, polyP is produced by the polyP kinase (PPK) and is thought to play a protective role during the response to cellular stress. However, the molecular pathways impacted by PPK activity and polyP accumulation remain poorly characterized. In this work, we used label-free mass spectrometry to study the response of bacteria that cannot produce polyP (Δppk) during starvation to identify novel pathways regulated by PPK. In response to starvation, we found 92 proteins significantly differentially expressed between wild-type and Δppk mutant cells. Wild-type cells were enriched for proteins related to amino acid biosynthesis and transport, while Δppk mutants were enriched for proteins related to translation and ribosome biogenesis, suggesting that without PPK, cells remain inappropriately primed for growth even in the absence of the required building blocks. From our data set, we were particularly interested in Arn and EptA proteins, which were down-regulated in Δppk mutants compared to wild-type controls, because they play a role in lipid A modifications linked to polymyxin resistance. Using western blotting, we confirm differential expression of these and related proteins in K-12 strains and a uropathogenic isolate, and provide evidence that this mis-regulation in Δppk cells stems from a failure to induce the BasRS two-component system during starvation. We also show that Δppk mutants unable to up-regulate Arn and EptA expression lack the respective L-Ara4N and pEtN modifications on lipid A. In line with this observation, loss of ppk restores polymyxin sensitivity in resistant strains carrying a constitutively active basR allele. Overall, we show a new role for PPK in lipid A modification during starvation and provide a rationale for targeting PPK to sensitize bacteria towards polymyxin treatment. We further anticipate that our proteomics work will provide an important resource for researchers interested in the diverse pathways impacted by PPK.

Abstract The opportunistic fungal infection cryptococcal meningoencephalitis is a major cause of death among people living with HIV in sub‐Saharan Africa. We report pharmacokinetic (PK) and safety data from a randomized, four‐period crossover phase I trial of three sustained‐release (SR) oral pellet formulations of 5‐flucytosine conducted in South Africa. These formulations were developed to require less frequent administration, to provide a convenient alternative to the current immediate release (IR) formulation, A. Formulations B, C, and D were designed to release 5‐flucytosine as a percentage of the nominal dose in vitro. We assessed their safety and PK profiles in a single dose (1 × 3000 mg at 0 h), relative to commercial IR tablets (Ancotil 500 mg tablets; 3 × 500 mg at 0 h and 3 × 500 mg at 6 h) in healthy, fasted participants. Forty‐two healthy participants were included. All treatments were well‐tolerated. The primary PK parameters, maximum observed plasma concentration (Cmax) and area under the concentration‐time profiles, were significantly lower for the SR formulations than for the IR tablets, and the geometric mean ratios fell outside the conventional bioequivalence limits. The median maximum time to Cmax was delayed for the SR pellets. Physiologically‐based PK modeling indicated a twice‐daily 6400 mg dose of SR formulation D in fasted condition would be optimal for further clinical development. This regimen is predicted to result in a rapid steady‐state plasma exposure with effective and safe trough plasma concentration and Cmax values, within the therapeutic boundaries relative to plasma exposure after four times per day administration of IR tablets (PACTR202201760181404).

IntroductionCoronavirus disease 2019 (COVID-19) poses an important risk of morbidity and of mortality, in patients after solid organ transplantation. Recommendations have been issued by various transplantation societies at the national and European level to manage the immunosuppressive (IS) regimen upon admission to intensive care unit (ICU).MethodThe aim of this study was to evaluate the adequacy of IS regimen minimization strategy in kidney transplant recipients hospitalized in an ICU for severe COVID-19, in relation to the issued recommendations.ResultsThe immunosuppressive therapy was minimized in all patients, with respectively 63% and 59% of the patients meeting the local and european recommendations upon admission. During ICU stay, IS was further tapered leading to 85% (local) and 78% (european) adequacy, relative to the guidelines. The most frequent deviation was the lack of complete withdrawal of mycophenolic acid (22%). Nevertheless, the adequacy/inadequacy status was not associated to the ICU- or one-year-mortality.DiscussionIn this single-center cohort, the only variable associated with a reduction in mortality was vaccination, emphasizing that the key issue is immunization prior to infection, not restoration of immunity during ICU stay.

IntroductionApproximately one-quarter of Canadians experience chronic pain, a debilitating condition often necessitating opioid use, which raises concerns regarding dependency and overdose risks. As an alternative, we developed the HYlaDO program (Hypnose de la Douleur, hypnosis of Pain in French), a novel self-hypnosis approach for chronic pain management. The development of this program followed the ORBIT model, a comprehensive framework for designing interventions encompassing several phases ranging from design to efficacy assessment.MethodsIn the present work, we conducted a preliminary evaluation of the HYlaDO program with 21 participants (18 of the 21 patients were included in the analysis). The primary objective was to determine one session of the program’s effectiveness in altering pain, anxiety and relaxation via pre-post analysis. The secondary goal was to examine the long-term effects across the same measures, in addition to the overall quality of life.ResultsThe results highlight the benefits of our approach, while participants reported short-term significant pain reduction, decreased anxiety, and increased relaxation. Additionally, preliminary trends suggest improvements in physical activity and quality of life metrics.DiscussionThese positive outcomes highlight HYlaDO’s potential as an alternative to opioid therapy for chronic pain. Encouraged by these results, we aim to extend our research to a broader and more diverse cohort, paving the way for comprehensive randomized controlled trials. This expansion will further validate HYlaDO’s efficacy and its role in transforming chronic pain management.

Real walking is the most natural locomotion method for exploring Virtual Environments (VE), enhancing the immersion of Virtual Reality (VR). Redirected Walking (RDW) is employed to enable real walking within limited tracking spaces in large VEs by subtly manipulating the mapping between the virtual and real environments. However, the effectiveness of RDW is greatly influenced by the convex shape and size of the manually defined physical tracking space, subsequently impacting the user’s immersive experience. To improve performance, one strategy is to integrate exploration methods from mobile robotics with RDW. This will expand the usable tracking space, facilitating dynamic environments and rapid exploration. For this, we adapted a Unity framework for an RDW algorithm to facilitate simulations for such an exploration. We conducted a simulation with artificially created non-convex explorable tracking spaces and pre-recorded path elements, simulating two adapted RDW artificial potential field (APF) concepts. Three conceptualized modes were applied: repulsive APF, exploration APF, and exploration APF with a distance threshold. Additionally, one APF was extended with a frontier-based exploration approach that utilized the path between the user’s position and a targeted frontier. The analysis revealed a significant trade-off between exploration and immersion. APF combined with frontier-based the exploration technique showed the fastest exploration speed, but - however - resulted in the lowest distance between resets.

Pneumocystis pneumonia (PcP) remains life-threatening in kidney transplant recipients (KTR). Our study investigated risk factors one-year before PcP. We conducted a monocentric, case-control study including all KTR at the Dijon University Hospital (France) with a diagnosis of PcP between 2005 and 2022 (cases), and matched control KTR with no history of PcP (3 controls/case). Among all 1,135 KTR, 57 cases (5%) and 169 matched-controls were included. PcP was associated with 18% mortality. Compared to controls, cases were older, with a higher immunological risk, and CMV infection was more frequent in the year preceding the occurrence of PcP (23% vs. 4%; p < 0.001). As early as 1 year before PcP, lymphocyte counts were lower and serum creatinine levels were higher in cases, but immunosuppressive regimens were not significantly different. Multivariable analysis identified lymphocyte count, serum creatinine level, being treated by immunosuppressive therapy other than anti-rejection drugs, and CMV infection in the year preceding the time PcP as independently associated with the occurrence of PcP. PcP was associated with an increased risk of subsequent chronic rejection (27% vs. 3%; p = 0.001) and return to dialysis (20% vs. 3%; p = 0.002). The occurrence of CMV infection and a low lymphocyte count could redefine the indications for continuation or reinitiation of anti-Pneumocystis prophylaxis.

Archaeological systematics, together with spatial and chronological information, are commonly used to infer cultural evolutionary dynamics in the past. For the study of the Palaeolithic, and particularly the European Final Palaeolithic and earliest Mesolithic, proposed changes in material culture are often interpreted as reflecting historical processes, migration, or cultural adaptation to climate change and resource availability. Yet, cultural taxonomic practice is known to be variable across research history and academic traditions, and few large-scale replicable analyses across such traditions have been undertaken. Drawing on recent developments in computational archaeology, we here present a data-driven assessment of the existing Final Palaeolithic/earliest Mesolithic cultural taxonomy in Europe. Our dataset consists of a large expert-sourced compendium of key sites, lithic toolkit composition, blade and bladelet production technology, as well as lithic armatures. The dataset comprises 16 regions and 86 individually named archaeological taxa ('cultures'), covering the period between ca. 15,000 and 11,000 years ago (cal BP). Using these data, we use geometric morphometric and multivariate statistical techniques to explore to what extent the dynamics observed in different lithic data domains (toolkits, technologies, armature shapes) correspond to each other and to the culture-historical relations of taxonomic units implied by traditional naming practice. Our analyses support the widespread conception that some dimensions of material culture became more diverse towards the end of the Pleistocene and the very beginning of the Holocene. At the same time, cultural taxonomic unit coherence and efficacy appear variable, leading us to explore potential biases introduced by regional research traditions, inter-analyst variation, and the role of disjunct macroevolutionary processes. In discussing the implications of these findings for narratives of cultural change and diversification across the Pleistocene-Holocene transition, we emphasize the increasing need for cooperative research and systematic archaeological analyses that reach across research traditions.

Qatar's rapid industrialization, notably in its capital city Doha, has spurred a surge in land reclamation projects, leading to a constriction of the entrance to Doha Bay. By reducing and deflecting the ocean circulation, land reclamation projects have reduced the effective dispersion of wastewater introduced into the bay and hence degraded the water quality. Here, we assess fluctuations in water residence time across three distinct eras (1980, 2000, and 2020) to gauge the impact of successive land reclamation developments. To do this, we couple the multi-scale ocean model SLIM with a Lagrangian model for water residence time within Doha's coastal area. We consider three different topographies of Doha's shoreline to identify which artificial structures contributed the most to increase water residence time. Our findings reveal that the residual ocean circulation in Doha Bay was predominantly impacted by northern developments post-2000. Between 1980 and 2000, the bay's residence time saw a modest rise, of about one day on average. However, this was followed by a substantial surge, of three to six days on average, between 2000 and 2020, which is mostly attributable to The Pearl mega artificial island development. Certain regions of the bay witnessed a tripling of water residence time. Given the ongoing population expansion along the coast, it is anticipated that the growth of artificial structures and coastal reclamation will persist, thereby exacerbating the accumulation of pollutants in the bay. Our findings suggest that artificial offshore structures can exert far-reaching, non-local impacts on water quality, which need to be properly assessed during the planning stages of such developments.

This study examined the impact of training load periodization on neuromuscular readiness in elite football players using the Locomotor Efficiency Index (LEI) as a measure of performance optimization. Throughout the 2021/22 and 2022/23 seasons, 106 elite male players (age: 19.5 ± 3.9 years) from an Italian professional football club were monitored using Global Positioning Systems (GPS) external load data. The LEI was derived from a machine learning model, specifically random forest regression, which compared predicted and actual PlayerLoad™ values to evaluate neuromuscular efficiency. Players were categorized by weekly LEI into three readiness states: bad, normal, and good. Analysis focused on the variation in weekly LEI relative to weekly load percentage variation (large decrease, moderate decrease, no variation, moderate increase, large increase), which included total distance, high-speed distance (above 25.2 km/h), and mechanical load, defined as the sum of accelerations and decelerations. Statistical analysis showed significant differences only with variations in total distance and mechanical load. Specifically, reducing weekly loads improved LEI in players in lower readiness states, while maintaining or slightly increasing loads promoted optimal readiness. This approach enables coaches to tailor training prescriptions more effectively, optimizing workload and recovery to sustain player performance throughout a demanding season.

In the past decade, the therapeutic arsenal for metastatic bladder cancer has expanded considerably, with the development of immune checkpoint inhibitors (ICIs), antibody–drug conjugates such as enfortumab vedotin, and anti-fibroblast growth factor receptor agents. Clinical trials evaluating ICIs as neoadjuvants, adjuvants, or first- or second-line treatments have produced conflicting results. However, first-line therapeutic strategies have been redefined by the recent publication of results from two clinical trials: CheckMate-901, which demonstrated the superiority of combined treatment with nivolumab and chemotherapy in extending overall survival, and EV-302, which demonstrated that combined treatment with pembrolizumab and enfortumab vedotin reduced the risk of death by 53%. In this review, we discuss the role of ICIs, alone or in combination, in bladder cancer management in the metastatic and adjuvant settings in 2024, considering the latest published trials. The potential role of ICIs as neoadjuvants is also discussed.

Teaching point: Chondrosarcoma of the lower rib may present with only minimal calcified chondroid matrix and may be misinterpreted as a liver lesion.

Introduction: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. Materials and methods: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. Results: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. Conclusion: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

Large gastric hernias are common and usually cause minor symptoms. Rarely, complete intrathoracic herniation of the stomach is complicated by strangulation. The underlying mechanism can be gastric volvulus or the less recognized phenomenon of gastric fundus redescent. We describe a case where this rare but potentially lethal complication of gastric herniation is present. Additionally, we show that gastric pneumatosis, a sign associated with ischemia, can be initially visualized on a plain chest radiograph in this setting. Teaching point: Redescent of the fundus is a possible, but unrecognized cause of gastric strangulation in intrathoracic stomachs.

(1) Aim: The aim of this study was to determine the relationship between lower limb bone deformities and body functions, activity, and participation in ambulant children with CP and whether changing bone morphology affects outcomes in these domains. (2) Methods: A systematic literature search (PROSPERO CRD42020208416) of studies reporting correlations between measures of lower limb bone deformities and measures of body function, activity or participation, or post-surgical outcomes in these domains was conducted from 1990 to 2023 in Medline, Scopus, and Cochrane Library. We assessed study quality with the Checklist for Case Series (CCS) and a quality assessment developed by Quebec University Hospital. Meta-analysis was not possible; therefore, descriptive synthesis was performed. (3) Results: A total of 12 of 3373 screened articles were included. No studies evaluated the relationships between bone deformities and activity or participation, or the effect of isolated bone surgery on these domains. Correlations between bone deformities and body functions were poor-to-moderate. Internal hip rotation during gait improved after femoral derotation osteotomy. (4) Conclusions: A shift in paradigm is urgently required for the research and management of bone deformities in children with CP to include the activity and participation domains of the ICF, as well as consider more psychological aspects such as self-image.

The design of new generation fast nuclear reactors requires highly accurate cross-section measurements in the MeV energy region. The 242Pu fission cross section is of particular interest for Pu incineration and nuclear waste production. There are discrepancies around 1 MeV incident neutron energy between libraries and among experimental data. Some data suggest the presence of a strong structure between 1 and 1.2 MeV whereas it is barely visible on some other data and its shape is very different among evaluations. The large majority of the 242Pu(n,f) measurements have been carried out with respect to the 235U(n,f) secondary-standard cross section. This introduces a strong correlation between measurements from different research teams. Moreover, this reference cross section exhibits structures, in particular a steep increase of +10% at 1 MeV. Therefore, we aim to re-measure the 242Pu(n,f) cross section relative to the primary-standard 1H(n,n)p cross section, by using a proton recoil detector. This standard has a very high accuracy (0.4%), is not used for other 242Pu measurements, and is structureless. An experiment has been carried out in October 2022 at the MONNET facility in JRC Geel, with incident neutron energies from 0.9 MeV to 2.0 MeV. The experimental setup will be presented, and the analysis procedure will be detailed.

Artificial intelligence (AI) is gaining increasing interest in the field of medicine because of its capacity to process big data and pattern recognition. Cardiotocography (CTG) is widely used for the assessment of foetal well-being and uterine contractions during pregnancy and labour. It is characterised by inter- and intraobserver variability in interpretation, which depends on the observers’ experience. Artificial intelligence (AI)-assisted interpretation could improve its quality and, thus, intrapartal care. Cardiotocography (CTG) raw signals from labouring women were extracted from the database at the University Hospital of Bern between 2006 and 2019. Later, they were matched with the corresponding foetal outcomes, namely arterial umbilical cord pH and 5-min APGAR score. Excluded were deliveries where data were incomplete, as well as multiple births. Clinical data were grouped regarding foetal pH and APGAR score at 5 min after delivery. Physiological foetal pH was defined as 7.15 and above, and a 5-min APGAR score was considered physiologic when reaching ≥7. With these groups, the algorithm was trained to predict foetal hypoxia. Raw data from 19,399 CTG recordings could be exported. This was accomplished by manually searching the patient’s identification numbers (PIDs) and extracting the corresponding raw data from each episode. For some patients, only one episode per pregnancy could be found, whereas for others, up to ten episodes were available. Initially, 3400 corresponding clinical outcomes were found for the 19,399 CTGs (17.52%). Due to the small size, this dataset was rejected, and a new search strategy was elaborated. After further matching and curation, 6141 (31.65%) paired data samples could be extracted (cardiotocography raw data and corresponding maternal and foetal outcomes). Of these, half will be used to train artificial intelligence (AI) algorithms, whereas the other half will be used for analysis of efficacy. Complete data could only be found for one-third of the available population. Yet, to our knowledge, this is the most exhaustive and second-largest cardiotocography database worldwide, which can be used for computer analysis and programming. A further enrichment of the database is planned.

Recently, a staging system using 4 grades has been proposed to quantify the extent of cardiac damage associated with aortic stenosis (AS), namely AS-related cardiac damage staging (ASCDS). ASCDS is independently associated with all-cause mortality and important clinical outcomes. To evaluate whether it might be associated with the occurrence of conduction system disorders after TAVI, a total of 119 symptomatic patients with severe AS who underwent a TAVI were categorized according to ASCDS: group 1 (13.5%): no or LV damage; group 2 (58.8%): left atrial/mitral valve damage, atrial fibrillation (AF); group 3 (27.7%): low-flow state, pulmonary vasculature/tricuspid valve/RV damage. After TAVI, 34% of patients exhibited LBBB and 10% high-degree atrioventricular block (HD-AVB). No patient in group 1 developed HD-AVB whereas new LBBB was frequent in groups 2 and 3. Twenty-one patients presented with paroxysmal AF with a higher rate for each group increment (group 1: n = 0, 0%; group 2: n = 11, 15.7%; group 3: n = 10, 30.3%) (p = 0.012). Patients in group 3 had the higher rate of permanent pacemaker implantation (PPMI) (group 1: n = 1, 6.3%; group 2: n = 7, 10%; group 3: n = 9, 27.3%) (p = 0.012). In conclusion, ASCDS might help identify patients at higher risk of conduction disorders and PPMI requirement after TAVI.