Search

Abstract The underlying evolutionary mechanisms driving global expansions of pathogen strains are poorly understood. Vibrio parahaemolyticus is one of only two marine pathogens where variants have emerged in distinct climates globally. The success of a Vibrio parahaemolyticus clone (VpST3) in Latin America- the first spread identified outside its endemic region of tropical Asia- provided an invaluable opportunity to investigate mechanisms of VpST3 expansion into a distinct marine climate. A global collection of VpST3 isolates and novel Latin American isolates were used for evolutionary population genomics, pangenome analysis and combined with oceanic climate data. We found a VpST3 population (LatAm-VpST3) introduced in Latin America well before the emergence of this clone in India, previously considered the onset of the VpST3 epidemic. LatAm-VpST3 underwent successful adaptation to local conditions over its evolutionary divergence from Asian VpST3 isolates, to become dominant in Latin America. Selection signatures were found in genes providing resilience to the distinct marine climate. Core genome mutations and accessory gene presences that promoted survival over long dispersals or increased environmental fitness were associated with environmental conditions. These results provide novel insights into the global expansion of this successful V. parahaemolyticus clone into regions with different climate scenarios.

Abstract Incidental capture of non-target species poses a pervasive threat to many marine species, with sometimes devastating consequences for both fisheries and conservation efforts. Because of the well-known importance of vocalizations in cetaceans, acoustic deterrents have been extensively used for these species. In contrast, acoustic communication for sea turtles has been considered negligible, and this question has been largely unexplored. Addressing this challenge therefore requires a comprehensive understanding of sea turtles’ responses to sensory signals. In this study, we scrutinized the avenue of auditory cues, specifically the natural sounds produced by green turtles (Chelonia mydas) in Martinique, as a potential tool to reduce bycatch. We recorded 10 sounds produced by green turtles and identified those that appear to correspond to alerts, flight or social contact between individuals. Subsequently, these turtle sounds—as well synthetic and natural (earthquake) sounds—were presented to turtles in known foraging areas to assess the behavioral response of green turtles to these sounds. Our data highlighted that the playback of sounds produced by sea turtles was associated with alert or increased the vigilance of individuals. This therefore suggests novel opportunities for using sea turtle sounds to deter them from fishing gear or other potentially harmful areas, and highlights the potential of our research to improve sea turtles populations’ conservation.

Nowadays, ultra high molecular weight polyethylene (UHMWPE), allows the combination of lightweight, high strength and is praised for the design of severely loaded structures. It has become a good option for lightweight armour solutions. It is therefore important to characterise its mechanical behaviour. Up to now, strain rate effects on mechanical behaviour have been poorly explored. In this work, this issue is tackled by studying the strain rate influence on the in-plane deformation, in shear and tension of the Tensylon® HSBD30A, a UHMWPE dedicated to ballistic and blast protection. Two laminates of Tensylon® of respective orientation [0 °/90°]20 and [±45°]20 were subjected to static and split Hopkinson tensile bar (SHTB) tests. A new mounting system was designed, and new specimen shapes were used to match the experimental setup configurations. Digital image correlation (DIC) was used to measure the in-plane strain. A significant strain-rate dependence on the material behaviour.is evidenced. Besides, results exhibit a higher strength for the [0°/90°]20 specimen than for the [±45°]20 one. Despite some limitations, the proposed setup and measurement methods allowed visualisation of strain rate effects on the stress-strain relationship for strain rates ranging from the quasi-static regime to the dynamic one (1500 s–1).

Abstract Background Cancer cachexia is a life‐threatening, inflammation‐driven wasting syndrome that remains untreatable. Adiponectin, the most abundant adipokine, plays an important role in several metabolic processes as well as in inflammation modulation. Our aim was to test whether administration of AdipoRon (AR), a synthetic agonist of the adiponectin receptors, prevents the development of cancer cachexia and its related muscle atrophy. Methods The effect of AR on cancer cachexia was investigated in two distinct murine models of colorectal cancer. First, 7‐week‐old CD2F1 male mice were subcutaneously injected with colon‐26 carcinoma cells (C26) or vehicle (CT). Six days after injection, mice were treated for 5 days with AdipoRon (50 mg/kg/day; C26 + AR) or the corresponding vehicle (CT and C26). Additionally, a genetic model, the ApcMin/+ mouse, that develops spontaneously numerous intestinal polyps, was used. Eight‐week‐old male ApcMin/+ mice were treated with AdipoRon (50 mg/kg/day; Apc + AR) or the corresponding vehicle (Apc) over a period of 12 weeks, with C57BL/6J wild‐type mice used as controls. In both models, several parameters were assessed in vivo: body weight, grip strength and serum parameters, as well as ex vivo: molecular changes in muscle, fat and liver. Results The protective effect of AR on cachexia development was observed in both cachectic C26 and ApcMin/+ mice. In these mice, AR administration led to a significant alleviation of body weight loss and muscle wasting, together with rescued muscle strength (P

We revisit, and document new facts regarding, the financialization of U.S. energy markets in 2000–2010. We show that, after controlling for macroeconomic factors and physical energy market fundamentals, the strength of energy markets’ co-movements with the U.S. stock market is positively related to the energy paper market activity of hedge funds that trade both asset classes. This relation weakens when credit risk is elevated. We find, in contrast, no link with the aggregate positions of commodity index traders in energy futures markets. Our findings have implications for the ongoing debate regarding the financialization of commodities.

Abstract Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.

Abstract Adherence to exercise is a crucial aspect of behavioral changes related to exercise. However, current models fail to predict behavioral change, and exercise programs struggle to foster adherence. In this Current Opinion article, we defined adherence as a process linking behavior and attitude. More specifically, exercise adherence is the process by which people’s behaviors conform to their attitudes and vice versa. Behavioral change theories should be able to predict changes, transformations, and modifications of behaviors; however, this is not currently the case. Prediction models of behavior are mainly focused on how to predict behavioral changes by affecting attitudes; however, these models have not considered the target behavior as a facilitator of adherence. Herein, a behavioral perspective is considered in three directions: first, exercise is a therapeutic modality that has the potential to improve motivation; second, chronic exercise helps sustain effort over time and increase executive functions and willpower; and third, exercise is an active behavior that has the potential to facilitate attitude change.

Abstract Background There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE). Methods The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical. Results A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility. Conclusions Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

Abstract The effective flow of electrons through bulk electrodes is crucial for achieving high-performance batteries, although the poor conductivity of homocyclic sulfur molecules results in high barriers against the passage of electrons through electrode structures. This phenomenon causes incomplete reactions and the formation of metastable products. To enhance the performance of the electrode, it is important to place substitutable electrification units to accelerate the cleavage of sulfur molecules and increase the selectivity of stable products during charging and discharging. Herein, we develop a single-atom-charging strategy to address the electron transport issues in bulk sulfur electrodes. The establishment of the synergistic interaction between the adsorption model and electronic transfer helps us achieve a high level of selectivity towards the desirable short-chain sodium polysulfides during the practical battery test. These finding indicates that the atomic manganese sites have an enhanced ability to capture and donate electrons. Additionally, the charge transfer process facilitates the rearrangement of sodium ions, thereby accelerating the kinetics of the sodium ions through the electrostatic force. These combined effects improve pathway selectivity and conversion to stable products during the redox process, leading to superior electrochemical performance for room temperature sodium-sulfur batteries.

Abstract Background The influence of socioeconomic deprivation on health inequalities is established, but its effect on critically ill patients remains unclear, due to inconsistent definitions in previous studies. Methods Prospective multicenter cohort study conducted from March to June 2018 in eight ICUs in the Greater Paris area. All admitted patients aged ≥ 18 years were enrolled. Socioeconomic phenotypes were identified using hierarchical clustering, based on education, health insurance, income, and housing. Association of phenotypes with 180-day mortality was assessed using Cox proportional hazards models. Results A total of 1,748 patients were included. Median age was 62.9 [47.4–74.5] years, 654 (37.4%) patients were female, and median SOFA score was 3 [1–6]. Study population was clustered in five phenotypes with increasing socioeconomic deprivation. Patients from phenotype A (n = 958/1,748, 54.8%) were without socioeconomic deprivation, patients from phenotype B (n = 273/1,748, 15.6%) had only lower education levels, phenotype C patients (n = 117/1,748, 6.7%) had a cumulative burden of 1[1–2] deprivations and all had housing deprivation, phenotype D patients had 2 [1–2] deprivations, all of them with income deprivation, and phenotype E patients (n = 93/1,748, 5.3%) included patients with 3 [2–4] deprivations and included all patients with health insurance deprivation. Patients from phenotypes D and E were younger, had fewer comorbidities, more alcohol and opiate use, and were more frequently admitted due to self-harm diagnoses. Patients from phenotype C (predominant housing deprivation), were more frequently admitted with diagnoses related to chronic respiratory diseases and received more non-invasive positive pressure ventilation. Following adjustment for age, sex, alcohol and opiate use, socioeconomic phenotypes were not associated with increased 180-day mortality: phenotype A (reference); phenotype B (hazard ratio [HR], 0.85; 95% confidence interval CI 0.65–1.12); phenotype C (HR, 0.56; 95% CI 0.34–0.93); phenotype D (HR, 1.09; 95% CI 0.78–1.51); phenotype E (HR, 1.20; 95% CI 0.73–1.96). Conclusions In a universal health care system, the most deprived socioeconomic phenotypes were not associated with increased 180-day mortality. The most disadvantaged populations exhibit distinct characteristics and medical conditions that may be addressed through targeted public health interventions.

Abstract Background Executive functions (EFs) and episodic memory are fundamental components of cognition that deteriorate with age and are crucial for independent living. While numerous reviews have explored the effect of exercise on these components in old age, these reviews screened and analyzed selected older adult populations, or specific exercise modes, thus providing only limited answers to the fundamental question on the effect of exercise on cognition in old age. This article describes the protocol for a systematic review and multilevel meta-analytic study aiming at evaluating the effectiveness of different types of chronic exercise in improving and/or maintaining EFs and long-term episodic memory in older adults. Methods and analysis The study protocol was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Several databases will be searched. Randomized controlled trials (RCTs) conducted in older adults aged ≥ 60 years providing any kind of planned, structured, and repetitive exercise interventions, and EFs and/or episodic memory measures as outcomes, published in English in peer-reviewed journals and doctoral dissertations will be included. Two independent reviewers will screen the selected articles, while a third reviewer will resolve possible conflicts. The Cochrane risk-of-bias tool will be used to assess the quality of the studies. Finally, data will be extracted from the selected articles, and the formal method of combining individual data from the selected studies will be applied using a random effect multilevel meta-analysis. The data analysis will be conducted with the metafor package in R. Discussion and conclusion This review will synthesize the existing evidence and pinpoint gaps existing in the literature on the effects of exercise on EFs and episodic memory in healthy and unhealthy older adults. Findings from this meta-analysis will help to design effective exercise interventions for older adults to improve and/or maintain EFs and episodic memory. Its results will be useful for many researchers and professionals working with older adults and their families. Systematic review registration PROSPERO CRD42022367111.

Abstract Objective This paper proposes a theoretical review that aims to understand the notion of adaptation according to the psychodynamic approach of Analytical Psychology, associated with the psychological construct of adaptive functioning, the latter being measurable through "conceptual, social, and practical" domains. Method Integrative literature review. Results Adaptive functioning domains may be analytically interpreted in terms of personality development, self-agency, adaptation to external and internal conditions, conscious skills, and unconscious aspects inferred from the clinical context. Conclusion The proposed theoretical construction is expected to be useful for clinical psychology and for mixed methods research, integrating results of psychological testing instruments based on adaptive functioning domains.

Not available.

Imide-based ionic liquids (ILs) are intriguing candidates for constructing safer electrolytes and better rechargeable batteries. In this work, a sulfinyl-functionalized imide anion, (trifluoromethanesulfinyl) (trifluoromethanesulfonyl)imide anion ([(CF3SO) (CF3SO2)N]−, [qTFSI]−), is proposed as negative charge for building low-melting ILs and high-performing electrolytes. The physicochemical properties of [qTFSI]-based ILs and their electrolytes are extensively characterized, and the reference systems with the classic sulfonimide anion, bis(trifluoromethanesulfonyl)imide anion ([(CF3SO2)2N]−, [TFSI]−) are also comparatively investigated. It has been revealed that the [qTFSI]− anion shows lesser extent of negative charge delocalization as compared to the reference [TFSI]− anion, which is responsible for slightly stronger interactions between IL cations and the sulfinyl-functionalized anion. The asymmetric feature of the [qTFSI]− anion contributes to lower glass and melting transitions of the corresponding ILs vs. [TFSI]-based ones, which effectively expands the operational temperature of the rechargeable batteries. Furthermore, the co-utilization of [qTFSI]− with [TFSI]− is found to improve the electrochemical compatibility of Li metal anode with the IL-based electrolytes, sustaining better cycling stability of the Li symmetric cells. The current work offers an elegant approach for the design of new anions for interface-favorable ILs and their electrolytes.

IMPORTANCE:. Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated. OBJECTIVES:. To evaluate biomarkers’ impact in helping VAP diagnosis after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS:. This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included. MAIN OUTCOMES AND MEASURES:. The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group. RESULTS:. Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C–C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C. CONCLUSIONS AND RELEVANCE:. Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

RESUMO: Este artigo apresenta um estudo comparativo entre a obra literária A metamorfose, de Franz Kafka, e o filme homônimo produzido e dirigido por Jan Nemec, em 1975. Seguindo os preceitos teóricos para estudos de adaptações cinematográficas propostos por Robert Stam (2006) e Linda Hutcheon (2013), apresentamos uma análise das obras não em busca de uma suposta fidelidade do filme à obra literária, mas sim um estudo dos processos pelos quais o filme, baseando-se na obra literária, constrói significados através da linguagem cinematográfica. A análise mostrou que a obra fílmica não se limita a apenas retratar através de imagens o que na obra literária é narrado, mas que, através do uso de elementos da linguagem cinematográfica, há muitas possibilidades de construção de significados, como as que foram constatadas no presente estudo. Palavras-chaves: Adaptação fílmica. A Metamorfose. Jan Nemec. Franz Kafka. ABSTRACT: This article presents a comparative study between Franz Kafka's The Metamorphosis and the film of the same name produced and directed by Jan Nemec, in 1975. Based on the theories of film adaptation studies proposed by Robert Stam (2006) and Linda Huntcheon (2013), we present an analysis of these two works, not in search of an alleged fidelity of the film to the literary work, but rather a study of the processes by which the film, based on the literary work, constructs meanings through the cinematographic language. The analysis showed that the film adaptation is not limited to simply portraying through images what the literary work narrates, but, through the use of elements of the film language, there are many possibilities for constructing meanings, such as those found in this study. Key-words: Film adaptation. The Metamorphosis. Jan Nemec. Franz Kafka.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70–95%]) than MRA (20% [10–30%]), SGLT2i (30% [20–50%]) or (GLP1-RA (10% [5–15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15–40%) vs 18% [10%–25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5–5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers’ dosage reduction was the usual management.

Abstract Persistently high, worldwide mortality from cancer highlights the unresolved challenges of disease surveillance and detection that impact survival. Development of a non-invasive, blood-based biomarker would transform survival from cancer. We demonstrate the functionality of ultra-high content analyses of a newly identified population of tumor cells that are hybrids between neoplastic and immune cells in patient matched tumor and peripheral blood specimens. Using oligonucleotide conjugated antibodies (Ab-oligo) permitting cyclic immunofluorescence (cyCIF), we present analyses of phenotypes among tumor and peripheral blood hybrid cells. Interestingly, the majority of circulating hybrid cell (CHC) subpopulations were not identified in tumor-associated hybrids. These results highlight the efficacy of ultra-high content phenotypic analyses using Ab-oligo based cyCIF applied to both tumor and peripheral blood specimens. The combination of a multiplex phenotypic profiling platform that is gentle enough to analyze blood to detect and evaluate disseminated tumor cells represents a novel approach to exploring novel tumor biology and potential utility for developing the population as a blood-based biomarker in cancer.

Four measures of association, namely, Spearman’s ρ, Kendall’s τ, Blomqvist’s β and Hoeffding’s Φ2, are expressed in terms of copulas. Conveniently, this article also includes explicit expressions for their empirical counterparts. Moreover, copula representations of the four coefficients are provided for the multivariate case, and several specific applications are pointed out. Additionally, a numerical study is presented with a view to illustrating the types of relationships that each of the measures of association can detect.

Abstract Background This study explores the impact of disrupting the circadian clock through a Cycle gene knockout (KO) on the transcriptome of Aedes aegypti mosquitoes. The investigation aims to uncover the resulting alterations in gene expression patterns and physiological processes. Results Transcriptome analysis was conducted on Cyc knockout (AeCyc -/-) and wild-type mosquitoes at four time points in a light-dark cycle. The study identified system-driven genes that exhibit rhythmic expression independently of the core clock machinery. Cyc disruption led to altered expression of essential clock genes, affecting metabolic processes, signaling pathways, stimulus responses and immune responses. Notably, gene ontology enrichment of odorant binding proteins, indicating the clock's role in sensory perception. The absence of Cyc also impacted various regulation of metabolic and cell cycle processes was observed in all time points. Conclusions The intricate circadian regulation in Ae. aegypti encompasses both core clock-driven and system-driven genes. The KO of Cyc gene instigated extensive gene expression changes, impacting various processes, thereby potentially affecting cellular and metabolic functions, immune responses, and sensory perception. The circadian clock's multifaceted involvement in diverse biological processes, along with its role in the mosquito's daily rhythms, forms a nexus that influences the vector's capacity to transmit diseases. These insights shed light on the circadian clock's role in shaping mosquito biology and behavior, opening new avenues for innovative disease control strategies.

Abstract Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical responses in cancer patients. In this phase III clinical trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant treatment with nDCs (n = 99) or placebo (n = 49). Active treatment consisted of intranodally injected autologous CD1c+ conventional and plasmacytoid DCs loaded with tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas the secondary endpoints included median RFS, 2-year and median overall survival, adverse event profile, and immunological response The 2-year RFS rate was 36.8% in the nDC treatment group and 46.9% in the control group (p = 0.31). Median RFS was 12.7 months vs 19.9 months, respectively (hazard ratio 1.25; 90% CI: 0.88−1.79; p = 0.29). Median overall survival was not reached in both treatment groups (hazard ratio 1.32; 90% CI: 0.73−2.38; p = 0.44). Grade 3−4 study-related adverse events occurred in 5% and 6% of patients. Functional antigen-specific T cell responses could be detected in 67.1% of patients tested in the nDC treatment group vs 3.8% of patients tested in the control group (p

RESUMO Considerando as dramáticas mudanças no mercado monetário internacional durante a década de 1980, este artigo discute a necessidade de restabelecer a coordenação monetária interna.

Abstract Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient cells, Rheb knockdown or Rapamycin treatment paradoxically increases TFEB phosphorylation at the mTORC1-sites and relocalizes TFEB from nucleus to cytoplasm. In mice, Rapamycin treatment normalizes lysosomal gene expression, similar to TFEB knockout, suggesting that Rapamycin’s benefit in TSC is TFEB-dependent. These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.

Composite materials are of increasing interest in aircraft and spacecraft structures, and carbon fiber reinforced polymers (CFRP) have emerged as materials meeting quality standards for structural applications in the aircraft industry. Despite their high mechanical properties, CFRPs are associated with high production costs. Building on recent research by the authors, this paper investigates the use of ply-level hybridization to reduce manufacturing costs while maintaining the mechanical performance of the manufactured material. Focusing on the causes of nonlinear response under off-axis tensile loading, the paper involves cyclic load-unload (LU) tensile tests conducted at off-axis angles of 15°, 30°, and 45° to predict mechanical characteristics and damage evolution. Residual strains are directly extracted from load-unload stress-strain responses. Three distinct methods for estimating cycle modulus are employed and compared for damage variable formulation. The research findings reveal dependencies of both the damage variable and residual strains on the off-axis angle. Furthermore, the method used to assess the modulus during cycling loading significantly influences the damage variable estimation. Encouragingly, the hybrid laminates exhibit reduced internal damage and matrix plasticity compared to reference counterparts, indicating a positive effect on the mechanical performances of hybridized CFRPs in addition to the cost reduction.

Introduction: Titanium-based implants can be used to fill voids in bone reconstruction surgery. Through additive manufacturing (AM), it is possible to produce titanium implants with osteoconductive properties such as high porosity and low stiffness. AM facilitates a level of design flexibility and personalization that is not feasible with traditional techniques.Methods: In this study, osseointegration into titanium alloy (Ti-6Al-4V) lattices was investigated for 12 weeks post-implantation using a novel bicortical load-bearing ovine model. The objective was to assess the safety and efficacy of AM-fabricated implants using two lattice structures of contrasting stiffness spanning the full width of the femoral condyle.Results: This was achieved by evaluating implant osseointegration and bone–implant contact properties by histomorphometry, scoring local implant tissue responses via histopathology, and micro-computed tomography reconstruction.Discussion: We found that Ti-6Al-4V implants facilitated widespread and extensive osseointegration, with bone maturation ongoing at the conclusion of the trial period. Following the implantation period, no adverse clinical indications that could be directly ascribed to the presence of the implanted device were identified, as determined by macroscopic and microscopic observation.

—This paper presents a new control methodology for achieving smooth gait transitions for a hexapod robot using Central Pattern Generators (CPGs). The approach involves modifying the Phase Oscillator within the CPG network to enable smooth transitions between different gaits in order to improve the adaptability to changing environmental conditions. The foot trajectory generator is designed based on the CPG output, allowing the possibility of online adjustment of foot trajectory parameters, such as step height and size, as well as the robot's speed and direction. Our simulation demonstrates the effectiveness of the modified oscillator in achieving smoother gait transitions with a transition time falls close to the output period of the CPG oscillators, and experiments on a real hexapod robot validate the feasibility and efficiency of our approach in considering online adjustability of trajectory parameters, confirming the potential of this methodology to enhance the locomotion capabilities of legged robots for navigating complex terrains.

A case of an adult with borderline AADC deficiency symptoms is presented here. Genetic analysis revealed that the patient carries two AADC variants (NM_000790.3: c.1040G > A and c.679G > C) in compound heterozygosis, resulting in p.Arg347Gln and p.Glu227Gln amino acid alterations. While p.Arg347Gln is a known pathogenic variant, p.Glu227Gln is unknown. Combining clinical features to bioinformatic and molecular characterization of the AADC protein population of the patient (p.Arg347Gln/p.Arg347Gln homodimer, p.Glu227Gln/p.Glu227Gln homodimer, and p.Glu227Gln/p.Arg347Gln heterodimer), we determined that: i) the p.Arg347Gln/p.Arg347Gln homodimer is inactive since the alteration affects a catalytically essential structural element at the active site, ii) the p.Glu227Gln/p.Glu227Gln homodimer is as active as the wild-type AADC since the alteration occurs at the surface and does not change the chemical nature of the amino acid, and iii) the p.Glu227Gln/p.Arg347Gln heterodimer has a catalytic efficiency 75% that of the wild-type since only one of the two active sites is compromised, thus demonstrating a positive complementation. By this approach, the molecular basis for the mild presentation of the disease is provided, and the experience made can also be useful for personalized therapeutic decisions in other mild AADC deficiency patients. Interestingly, in the last few years, many previously undiagnosed or misdiagnosed patients have been identified as mild cases of AADC deficiency, expanding the phenotype of this neurotransmitter disease.

Estrogens are discharged consistently from wastewater treatment plants and other sources into surface waters, impacting reproduction and development in humans and wildlife populations at trace concentrations (nanogram per liter). Rabbit food (RF) was previously found to abiotically transform estrogens, but the specific functional components remain unknown. This study aimed to identify vitamins and vegetable materials capable of transforming the model estrogen 17α-ethynylestradiol (EE2). Individual vitamins and vegetable mixtures were incubated with EE2 solutions and analyzed via LC-MS/MS. Transformation capacity was evaluated along with process optimization. Highest transformation was observed with vitamin B complex, whereby 23% of initial EE2 was transformed into unknown products. In the presence of a solid phase, the fraction of EE2 extractable after exposure to vitamins D3 and C were 21.3 and 18.6%, respectively. As for vegetable materials, the lowest observed transformation capacity, mt, was for mint. On the other hand, carrot leaves, and corn had comparable mt values to those of RF, while the mt value for radish leaves exceeded the value for RF by 16%. Vegetables used in this study are considered inexpensive materials, which were found to promote the removal of EE2 via enhanced adsorption and/or catalytic reaction, these insights can facilitate development of green water treatment technologies to remove unmetabolized estrogens. Further optimization studies found dose to impact treatment, whereas temperature from 25 to 45 °C showed negligible effects, while extreme acidic/alkaline conditions reduced efficacy significantly, indicating a pH dependence.

BackgroundLarge language models (LLMs) have raised both interest and concern in the academic community. They offer the potential for automating literature search and synthesis for systematic reviews but raise concerns regarding their reliability, as the tendency to generate unsupported (hallucinated) content persist. ObjectiveThe aim of the study is to assess the performance of LLMs such as ChatGPT and Bard (subsequently rebranded Gemini) to produce references in the context of scientific writing. MethodsThe performance of ChatGPT and Bard in replicating the results of human-conducted systematic reviews was assessed. Using systematic reviews pertaining to shoulder rotator cuff pathology, these LLMs were tested by providing the same inclusion criteria and comparing the results with original systematic review references, serving as gold standards. The study used 3 key performance metrics: recall, precision, and F1-score, alongside the hallucination rate. Papers were considered “hallucinated” if any 2 of the following information were wrong: title, first author, or year of publication. ResultsIn total, 11 systematic reviews across 4 fields yielded 33 prompts to LLMs (3 LLMs×11 reviews), with 471 references analyzed. Precision rates for GPT-3.5, GPT-4, and Bard were 9.4% (13/139), 13.4% (16/119), and 0% (0/104) respectively (P

BackgroundEnvironmental and behavioral factors are responsible for 12.6 million deaths annually and contribute to 25% of deaths and chronic diseases worldwide. Through the One Health initiative, the World Health Organization and other international health organizations plan to improve these indicators to create healthier environments by 2030. To meet this challenge, training primary care professionals should be the priority of national policies. General practitioners (GPs) are ready to become involved but need in-depth training to gain and apply environmental health (EH) knowledge to their practice. In response, we designed the Primary Care Environment and Health (PCEH) online course in partnership with the Occitanie Regional Health Agency in France. This course was used to train GP residents from the Montpelier-Nimes Faculty of Medicine in EH knowledge. The course was organized in 2 successive parts: (1) an asynchronous e-learning modular course focusing on EH knowledge and tools and (2) 1 day of face-to-face sessions. ObjectiveThis study assessed the impact of the e-learning component of the PCEH course on participants’ satisfaction, knowledge, and behavior changes toward EH. MethodsThis was a pilot before-and-after study. Four modules were available in the 6-hour e-learning course: introduction to EH, population-based approach (mapping tools and resources), clinical cases, and communication tools. From August to September 2021, we recruited first-year GP residents from the University of Montpellier (N=130). Participants’ satisfaction, knowledge improvements for 19 EH risks, procedure to report EH risks to health authorities online, and behavior change (to consider the possible effects of the environment on their own and their patients’ health) were assessed using self-reported questionnaires on a Likert scale (1-5). Paired Student t tests and the McNemar χ2 test were used to compare quantitative and qualitative variables, respectively, before and after the course. ResultsA total of 74 GP residents completed the e-learning and answered the pre- and posttest questionnaires. The mean satisfaction score was 4.0 (SD 0.9) out of 5. Knowledge scores of EH risks increased significantly after the e-learning course, with a mean difference of 30% (P

Background: Colitis for so many years had been considered a disease exclusive only to developed countries; surprisingly, its incidence is now increasing worldwide. This study investigated Mimosa pudica leaf water extract anti-colitis potential on acetic acid-induced colitis in rats. Methods: Following 24 h fasting, 36 rats (both sexes) intrarectally received acetic acid (4%, 1 mL) to induce colitis. Afterward, they were separated into groups and treated twice a day (for 9 days) with distilled water; Mimosa pudica (25, 50, or 100 mg/kg); and Prednisolone (5 mg/kg). Body weight and quantity of feces were recorded. On day 9, animals were sacrificed, colon ulcerations number and weight/length ratio; GSH and MDA levels; MPO activity, and IL-1β were determined. Results: Colitis caused a significant drop in animals’ body weight - 30% decrease in colitis control against + 27% increase in the neutral control rats. Mimosa pudica at 25 mg/kg on day 9 brought a + 7% increase. Colitis led to an increase in the weight of feces in colitis rats with 14.28 ± 0.98 g (day 8). On this same day, the extract reduced feces weight (4.42 ± 0.31 g at 100 mg/kg), the number of colon ulcerations, and the mean colon weight/length ratio (P < 0.001). Colitis conditions increased MDA and decreased GSH. Mimosa pudica reversed these biomarkers. Colitis caused a marked increase in MPO activity and IL-1β concentration in colitis rats. This was reversed by the extract. Conclusions: Overall, our results proved the beneficial effects of Mimosa pudica leaf extract in protecting animals against colitis.

To mitigate the adverse effects of excessive consumption of animal proteins on both the environment and human well-being, a transition is needed toward plant-based proteins. Such a shift requires a change in eating behaviours, both at home and elsewhere. Focusing on hospitality and leisure settings, the aim of this study is threefold: firstly, to evaluate the alignment between the organisational policies and support mechanisms on one side and employees’ beliefs and daily experiences towards healthy and sustainable food on the other; secondly, to explore the staff’s readiness to embrace the protein transition using the stages of change model; and thirdly, to outline the prerequisites needed to ensure that employees show healthy and sustainable food behaviour drawing upon the COM-B model (motivation, opportunity, and capability for behavioural interventions) and the behaviour change wheel. Findings from a multi-case-study approach, which utilises a combination of research methods, suggest that employees across all cases exhibit a limited degree of readiness. Moreover, while the motivation to shift toward more healthy and sustainable food is high, capability and opportunity are rated low. To address this, various intervention strategies tailored to the context of hospitality and leisure are proposed that are pertinent to the cases under investigation.

A study with 36 German participants (divided in 3 age groups: 1 gr. 7-11 years; 2 gr. 12-18 years and 3 gr. 19-50 years) was conducted to test the Polyvagal Theory. Our data analysis evaluated a therapeutic intervention using the so-called SSP (Safe and Sound Protocol) developed by Stephen Porges. Frequency modulated music stimulates the parasympathetic vagus nerve with an (musical) input process evaluated by the brain as socially-communicatively salient (musical signals with enhanced prosodic characteristics of human voices). Thus, acoustical processes of (musical) perception become available to the brain's assessment of social signals via the neurophysiology of the ANS. This, in turn, allows for internally processed signals of social safety, resulting in a reduced sense of stress from external sensory inputs. The SSP aims to generally reduce sensory hypersensitivity by stimulating the vagus nerve via the middle ear – and thus, to contribute to a better capacity of (down)-regulating sensory hypersensitivity. In the current study, we demonstrated that participants with ASD showed reduced hyper-sensitivity (visual, auditory, tactile and digestive) after using the SSP. In a second data analysis, we tested the overall impact of language ability and the influence on hyper sensory sensitivity in the autism spectrum. It seems that language ability in general already leads to better regulation and integration of sensory inputs via cognitive-linguistic processing in cortex areas: if a strong sensory stimulus can be assigned and evaluated linguistically, the strength of the stimulus is adjusted thereby. Conversely, different language abilities did not result in a more effective response to the SSP. Since the SSP amplifies prosodic elements of human speech in a characteristic way, the effect of reduced sensitivity to stimuli seems to be due to the autonomic response to paraverbal signals. The results are statistically analyzed using ANOVA. Disclosure Statement No potential conflict of interest was reported by the authors. * Corresponding author: Hristo Kyuchukov, 0000-0002-1965-8908 hristo.kyuchukov@us.edu.pl

Abstract In the last decade, clinical studies have investigated the clinical relevance of circulating cell-free-DNA (ccfDNA) as a diagnostic and prognosis tool in various diseases including cancers. However, limited knowledge on ccfDNA biology restrains its full development in the clinical practice. To improve our understanding, we evaluated the impact of the circadian rhythm on ccfDNA release in healthy subjects over a 24-h period. 10 healthy female subjects underwent blood sampling at 8am and 20 healthy male subjects underwent serial blood sampling (8:00 AM, 9:00 AM, 12:00 PM, 4:00 PM, 8:00 PM, 12:00 AM, 4 AM (+ 1 Day) and 8 AM (+ 1 Day)). We performed digital droplet-based PCR (ddPCR) assays to target 2 DNA fragments (69 & 243 bp) located in the KRAS gene to determine the ccfDNA concentration and fragmentation profile. As control, half of the samples were re-analyzed by capillary miniaturized electrophoresis (BIAbooster system). Overall, we did not detect any influence of the circadian rhythm on ccfDNA release. Instead, we observed a decrease in the ccfDNA concentration after meal ingestion, suggesting either a post-prandial effect or a technical detection bias due to a higher plasma load in lipids and triglycerides. We also noticed a potential effect of gender, weight and creatinine levels on ccfDNA concentration.

Abstract Somatostatin receptors are clinically validated GPCR biomarkers for diagnosis and treatment of various neuroendocrine tumors (NET). Among the five somatostatin receptors, SST2 and SST3 are associated with apoptosis and cell cycle arrest, making these receptor subtypes better differentiated targets in precision oncology. In this study we performed immunohistochemistry of paired tissue microarrays containing 1125 cores, representing 43 tumor types, each stained for SST2 and SST3. A 12-point immunoreactive scoring (IRS) range was used for interpretation of the staining results. We analyzed the results twice, using the conventional positivity IRS cutoffs ≥ 3 and more stringent ≥ 6. Evaluation of receptors expression dynamics was performed for tumor-nodes-metastases (TNM) defined subgroups (ovarian and hepatocellular adenocarcinomas) as a function of their tumor stage. Our results indicate that two-thirds of tested cores exhibit clinically significant expression of at least SST2 or SST3 (IRS ≥ 6). The expression prevalence of both receptors tends to decline with tumor progression. However, an unexpected upregulation of both SST2 and SST3 reemerged in metastases suggesting conserved receptors genetic potential during tumor life cycle. We suggest that SST2 and SST3 should be further explored as potential biomarkers and therapeutic tools for maximizing the efficiency of somatostatin-based precision oncology of solid tumors beyond NET.

Objective: Systematically review evidence on using GLP-1RAs for reducing BEB in BED and BN. Methods: Comprehensive literature search (PubMed and Google Scholar) conducted for studies evaluating GLP-1Ras for BEB. Extracted data on study characteristics, efficacy, and safety. Results: Studies show that GLP-1RAs (liraglutide and dulaglutide) reduce BE frequency and comorbidities in addition to favorable psychiatric side effect profile compared to current options. However, large-scale, blinded placebo-controlled trials are lacking. Conclusion: Early findings suggest promising effects of GLP-1RAs on BEB. However, rigorous clinical trials are needed to firmly establish efficacy, dosing, safety, and comparative effectiveness before considering GLP-1RAs a viable novel approach.

[This corrects the article DOI: 10.1371/journal.pone.0228677.].

IntroductionThere is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics.MethodsThis protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis.ConclusionThe results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs.Protocol registration numberThis protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418).

Antecedentes: La sospecha de disfunción endotelial (DE) permitirá prevenir la aterosclerosis acelerada y la muerte prematura. Objetivo: Establecer la utilidad de la termografía en el cribado de la función endotelial en adultos con factores de riesgo cardiovascular. Material y métodos: Estudio transversal analítico de prueba diagnóstica. El incremento del diámetro de la arteria braquial < 11 % a un minuto posisquemia significó probable DE, confirmada si el diámetro fue ≥ 11 % posnitroglicerina sublingual. Se obtuvieron fotografías termográficas al minuto de la región palmar. Se aplicó estadística descriptiva, curva ROC, pruebas U de Mann-Whitney, chi cuadrada o exacta de Fisher. Resultados: Se incluyeron 38 sujetos, mediana de edad de 50 años, con 624 mediciones termográficas; nueve presentaron DE (vasodilatación mediada por flujo de 2.5 %). El mejor punto de corte para la función endotelial normal en sujetos con factores de riesgo cardiovascular fue ≥ 36 °C al minuto de isquemia, con sensibilidad de 85%, especificidad de 70%, valores predictivos positivo y negativo de 78 y 77%, área bajo la curva de 0.796, razón de verisimilitud positiva de 2.82 y razón de verisimilitud negativa de 0.22. Conclusión: La medición de la temperatura en la región palmar mediante termografía infrarroja ≥ 36 °C tras un minuto de isquemia es práctica, no invasiva y económica para el cribado de la función endotelial normal en adultos con factores de riesgo cardiovascular.

ContextHereditary alpha-tryptasemia (HαT) is associated with elevated basal serum tryptase (bST) and is associated with a higher risk of severe anaphylactic reactions in patients with clonal mast cell disorders or IgE-mediated Hymenoptera venom-induced anaphylaxis. The consequence of this genetic trait remains to be determined in other allergic diseases and food allergy in particular.ObjectivesHere, we describe three cases of peanut allergy among siblings from a single family of four: two of them were associated with HαT, and the third one was associated with the tryptase wild-type genotype.MethodsTPSAB1/TPSB2 genotypes were determined by digital PCR. After the case description, we provided a review of the literature regarding bST levels and tryptase genotypes in anaphylaxis, with a particular focus on food allergy.ResultsCompared to the sibling with the conventional tryptase genotype, the two siblings with HαT presented a lower peanut threshold at the initial oral food challenge, higher peanut skin prick test reactivity, higher levels of specific IgE to peanut, Ara h 2, and Ara h 6, and a lower IgG4/IgE ratio after 10 years of oral immunotherapy.ConclusionThe tryptase genotype and HαT status might modify the clinical presentation and biological features of food allergy.

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the outer loop of the channel and substitution at position 428 from serine to proline (S428P), respectively. Heterologous expression of P632L and S428P into HEK cells produced no hERG current compared to the wild type (WT). Moreover, the co-transfection of WT and P632L yielded no hERG current; however, the co-transfection of WT and S428P yielded partial hERG current. Action potentials were prolonged in a complete or partial blockade of hERG current from computer simulations which was more severe in Purkinje than ventricular myocytes. Three dimensional simulations revealed a higher susceptibility to reentry in the presence of hERG current blockade. Our experimental findings suggest that both P632L and S428P mutations may impair the KCNH2 gene. The Purkinje cells exhibit a more severe phenotype than ventricular myocytes, and the hERG current blockade renders the ventricles an arrhythmogenic substrate from computer modeling.

Abstract A systematic review was conducted on studies reporting steroid injections with ultrasound for de Quervain. From 10 studies included and 379 wrists, 73.9% reported complete resolution of symptoms, 18.2% with partial and 7.9% without resolution. When compared to the landmark‐guided technique, ultrasound guidance showed significantly higher rates of symptom resolution (P = 0.0132) and lower pain scores (P

Composite materials, among them Carbon Fiber Reinforced Polymers (CFRP), have become a key material in structural applications for lightweight structures such as spacecraft and aircraft. CFRP can be found under various quality grades and their mechanical performances increase with their cost and quality grade. In order to limit the costs of the material without degrading technical performances, hybridization could be of interest. However, assessing the conservation of quality standards of hybridized CFRP is crucial. This paper investigates the off-axis mechanical response of ply-level hybrid carbon composites, with varying thickness and material quality. Two types of carbon fiber prepregs were combined in the same laminate using symmetric and asymmetric stacking sequences. Monotonic quasi-static off-axis tests were performed to evaluate the non-linear stress-strain behavior of the laminates, with Digital Image Correlation used to measure strain. The apparent elastic modulus and the in-plane shear modulus were evaluated from the tensile tests at three off-axis angles. The results indicate that the hybrid laminates exhibit higher failure stress levels compared to simple laminates, with an intermediate failure strain. Overall, this study provides insights into the off-axis mechanical behavior of ply-level hybrid carbon fiber composites, with potential applications in the design of composite structures.

To support climate change adaptation in the communities of Nunavik, an innovative multitechnique approach to map permafrost conditions and assess risks of geohazards at the community-scale level was applied. Four maps were produced for each community: (1) a surficial geology map, (2) a map of permafrost conditions based on ground-ice content and depth to bedrock, (3) a map of potential for construction, and (4) a geohazard risk assessment map. Local ground temperature data from thermistor cables were used to calibrate 1D numerical models to estimate future permafrost temperature changes and probable rates of degradation in different environmental settings within the communities and under different climate change scenarios for the 2019–2100 period. Throughout this project, abundant consultations were held in communities and with stakeholders to better understand their concerns and to provide pragmatic recommendations for improving construction methods and land-use planning to face the challenges of permafrost thaw. Specific recommendations were made to the higher levels of government for improving construction practices. Inuit aspirations, culture, and leadership remain essential in integrating permafrost geotechnical knowledge in planning a safe future for the communities.

The whole practice of an anthropology of the contemporary – and the questions that arise from this practice – are remarkably "condensed," so to speak, in this article by Gustavo Lins Ribeiro (GLR). The contemporary world that any anthropologist may set out to study is defined not through a monographic and myopic gaze (typical to the ethnological tradition that still forms part of our legacy, after all), but through an exploration of the connections between ethnographic observation and diverse levels of constraints and forces – connections that are too quickly summarized by the local/global formula. It seems to me more precise to say that this contemporary world may be understood through a relationship between situation and context. The situation is what I can observe and experience directly; the context is what I cannot see immediately, but can grasp through different procedures, more or less concrete or abstract, more or less empirical or theoretical. What mediates between the two? This is my understanding of the question that occupies GLR in his article. It is rich in the domain of the self-reflexivity and epistemology of anthropology – indeed, of any field-based social science. All the article’s proposals and observations are fascinating and inspirational. They inspire me to think with them, to question, compare and develop the author’s ideas. In this commentary, I shall mention just a few of the avenues for further study suggested by the article, in light of my own practice.

Abstract The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model‐informed drug development can be used to assess prognostic and predictive clinical factors or biomarkers associated with treatment response. Most pharmacometric models have thus far been developed using data from randomized clinical trials, and further studies are needed to translate their findings into the real‐world setting. We developed a tumor growth inhibition model based on real‐world clinical and imaging data in a population of 91 advanced melanoma patients receiving ICIs (i.e., ipilimumab, nivolumab, and pembrolizumab). Drug effect was modeled as an ON/OFF treatment effect, with a tumor killing rate constant identical for the three drugs. Significant and clinically relevant covariate effects of albumin, neutrophil to lymphocyte ratio, and Eastern Cooperative Oncology Group (ECOG) performance status were identified on the baseline tumor volume parameter, as well as NRAS mutation on tumor growth rate constant using standard pharmacometric approaches. In a population subgroup (n = 38), we had the opportunity to conduct an exploratory analysis of image‐based covariates (i.e., radiomics features), by combining machine learning and conventional pharmacometric covariate selection approaches. Overall, we demonstrated an innovative pipeline for longitudinal analyses of clinical and imaging RWD with a high‐dimensional covariate selection method that enabled the identification of factors associated with tumor dynamics. This study also provides a proof of concept for using radiomics features as model covariates.

Abstract Before the debut of lithium-ion batteries (LIBs) in the commodity market, solid-state lithium metal batteries (SSLMBs) were considered promising high-energy electrochemical energy storage systems before being almost abandoned in the late 1980s because of safety concerns. However, after three decades of development, LIB technologies are now approaching their energy content and safety limits imposed by the rocking chair chemistry. These aspects are prompting the revival of research activities in SSLMB technologies at both academic and industrial levels. In this perspective article, we present a personal reflection on solid polymer electrolytes (SPEs), spanning from early development to their implementation in SSLMBs, highlighting key milestones. In particular, we discuss the SPEs’ characteristics taking into account the concept of coupled and decoupled SPEs proposed by C. Austen Angell in the early 1990s. Possible remedies to improve the physicochemical and electrochemical properties of SPEs are also examined. With this article, we also aim to highlight the missing blocks in building ideal SSLMBs and stimulate research towards innovative electrolyte materials for future rechargeable high-energy batteries.

Abstract Quadruped robots require robust and general locomotion skills to exploit their mobility potential in complex and challenging environments. In this work, we present an implementation of a robust end-to-end learning-based controller on the Solo12 quadruped. Our method is based on deep reinforcement learning of joint impedance references. The resulting control policies follow a commanded velocity reference while being efficient in its energy consumption and easy to deploy. We detail the learning procedure and method for transfer on the real robot. We show elaborate experiments. Finally, we present experimental results of the learned locomotion on various grounds indoors and outdoors. These results show that the Solo12 robot is a suitable open-source platform for research combining learning and control because of the easiness in transferring and deploying learned controllers.