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A foundational mechanism underlying human cooperation is reciprocity. In the context of repeated interactions with others, it is not always clear the degree to which in-kind responses reflect responsiveness to partners' prior behaviors ("reactive" responses), an interest unrelated to the partner ("nonreactive" responses), or any combination of the two. To disentangle these two types of responses, we presented children with sequential, one-shot, and costly interactions between themselves and either egalitarian or selfish peers. Study 1 tested direct, generalized, and normative reciprocal scenarios (N = 144 seven-year-old German children; 50% girls and 50% boys), finding that "nonreactive" responses were dominant for boys and manifested in the form of "selfish" resource distribution. Among girls, "reactive" responses were dominant and manifested in the form of in-kind resource distribution. Study 2 addressed even younger German children (N = 144; 4- to 8-year-old German children; 50% girls and 50% boys), exposing the same phenomenon among 4-year-olds, but not among 5.5-year-olds. Study 3 addressed 7-year-old Israeli children (N = 95; 49% girls and 51% boys), and replicated the basic phenomenon, with an additional cultural variation. The early emergence of gender differences in reciprocity and implications are discussed in cultural, socio-developmental, and evolutionary accounts.

The current study investigated whether age-related changes in the conceptualization of social groups influences interpretation of the pronoun we. Sixty-four 2- and 4-year-olds (N = 29 female, 50 White-identifying) viewed scenarios in which it was ambiguous how many puppets performed an activity together. When asked who performed the activity, a speaker puppet responded, "We did!" In one condition, the speaker was near one and distant from another puppet, implying a dyadic interpretation of we. In another condition, the speaker was distant from both, thus pulling for a group interpretation. In the former condition, 2- and 4-year-olds favored the dyadic interpretation. In the latter condition, only 4-year-olds favored the group interpretation. Age-related conceptual development "expands" the set of conceivable plural person referents.

Abstract Background Tobacco smoking is the leading cause of preventable death and disease worldwide, with over 8 million annual deaths attributed to cigarette smoking. This study investigates the impact of cigarette smoke and heated tobacco products (HTPs) on microglial function, focusing on toxicological profiles, inflammatory responses, and oxidative stress using ISO standard and clinically relevant conditions of exposure. Methods We assessed cell viability, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial function, unfolded protein response, and inflammation in human microglial cells (HMC3) exposed to cigarette smoke, HTP aerosol or nicotine. Results Our findings show that cigarette smoke significantly reduces microglial viability, increases ROS formation, induces lipid peroxidation, and reduces intracellular glutathione levels. Cigarette smoke also alters the expression of genes involved in mitochondrial dynamics and biogenesis, leading to mitochondrial dysfunction. Additionally, cigarette smoke impairs the unfolded protein response, activates the NF-κB pathway, and induces a pro-inflammatory state characterized by increased TNF and IL-18 expression. Furthermore, cigarette smoke causes DNA damage and decreases the expression of the aging marker Klotho β. In contrast, HTP, exhibited a lesser degree of microglial toxicity, with reduced ROS production, lipid peroxidation, and mitochondrial dysfunction compared to conventional cigarettes. Conclusion These results highlight the differential toxicological profile of cigarette smoke and HTP on microglial cells, suggesting a potential harm reduction strategy for neurodegenerative disease for smokers unwilling or unable to quit.

Anthemis L. 1753 is a species-rich genus of Asteraceae. It includes species of economic value as ornamental, edible and medicinal plants. We report here the complete chloroplast genome of Anthemis cretica subsp. calabrica (Arcang.) R. Fern. 1975, the first chloroplast genome of any Anthemis species. For the scope, we have used long reads obtained with Oxford Nanopore technology. The assembled plastome is 149,509 bp long and is subdivided in a large single-copy region (LSC, 82,317 bp), a small single-copy region (SSC, 18,212 bp) and two inverted repeat regions (IR: 24,490 bp). It comprehends 136 predicted genes, of which 92 protein-coding genes, 35 tRNAs, and 8 rRNAs. The overall GC content is 37.54%. The position of A. cretica subsp. calabrica in the phylogenetic tree is congruent with those of previous analyses based on a few chloroplast or nuclear regions.

Abstract Studies on MECP2 function and its implications in Rett Syndrome (RTT) have traditionally centered on neurons. Here, using human embryonic stem cell (hESC) lines, we modeled MECP2 loss-of-function to explore its effects on astrocyte (AST) development and dysfunction in the brain. Ultrastructural analysis of RTT hESC-derived cerebral organoids revealed significantly smaller mitochondria compared to controls (CTRs), particularly pronounced in glia versus neurons. Employing a multiomics approach, we observed increased gene expression and accessibility of a subset of nuclear-encoded mitochondrial genes upon mutation of MECP2 in ASTs compared to neurons. Analysis of hESC-derived ASTs showed reduced mitochondrial respiration and altered key proteins in the tricarboxylic acid cycle and electron transport chain in RTT versus CTRs. Additionally, RTT ASTs exhibited increased cytosolic amino acids under basal conditions, which were depleted upon increased energy demands. Notably, mitochondria isolated from RTT ASTs exhibited increased reactive oxygen species and influenced neuronal activity when transferred to cortical neurons. These findings underscore MECP2 mutation's differential impact on mitochondrial and metabolic pathways in ASTs versus neurons, suggesting that dysfunctional AST mitochondria may contribute to RTT pathophysiology by affecting neuronal health.

Abstract Although seagrasses are expected to thrive in future acidified oceans by overcoming low CO2 diffusion into plant tissues, the co‐occurrence of environmental stressors may affect their growth. Volcanic CO2 vents are often associated with toxic gases and metal‐rich fluids representing ideal sites to assess the effects of multiple stressors. We evaluated the response of Posidonia oceanica growing near shallow CO2 vents characterized by H2S spill‐out by comparing meadow structure and phenology to an area with no gas emissions. Seagrass descriptors at meadow, shoot and leaf level indicated that P. oceanica experienced stressful conditions at the vent area, in clear contrast to the flourishing features of P. oceanica previously described at CO2 vents with no evidence of toxic inputs. Furthermore, the reduction in both leaf δ34S and growth at the vent area indicates that sulfide intrusion occurs and affects seagrass growth performance, dampening the expected beneficial effects of high CO2 levels.

Abstract Abemaciclib demonstrated clinical benefit in women affected by HR+/HER2− advanced breast cancer (aBC). Drug-drug interactions (DDIs) can lead to reduced treatment efficacy or increased toxicity. This retro-prospective study aimed to evaluate outcomes, DDIs’ impact, and toxicities of abemaciclib combined with endocrine therapy in a real-world setting. Patients from 12 referral Italian hospitals with HR+/HER2− aBC who received abemaciclib were included. Clinical data about comorbidities, concurrent medications, outcomes, and adverse events (AE) were collected. Drug-PIN® (Personalized Interactions Network) is a tool recognizing the role of multiple interactions between active and/or pro-drug forms combined with biochemical and demographic patient data. The software was used to define the Drug-PIN score and Drug-PIN tier (green, yellow, dark yellow, and red) for each patient. Univariate and multivariate analyses were performed to identify predictors of patients’ PFS or toxicity. One hundred seventy-three patients were included. 13% of patients had >75years. The overall response rate (ORR) was 63%. The general population’s median PFS (mPFS) was 22 months (mo), while mOS were not reached. Patients treated with abemaciclib in combination with AI and fulvestrant had a mPFS of 36 and 19 mo, respectively. The most common toxicities were diarrhea, asthenia, and neutropenia detected in 63%,49%, and 49% of patients. The number of concomitant medications and comorbidities were not associated with survival outcomes (22 vs 17 mo, p = 0.068, p = 0.99). Drug-PIN tier from dark yellow to red and Drug-PIN score >12 were associated with shorter PFS compared to no/low-risk DDIs and score

Shared intentionality theory posits that at age 3, children expand their conception of plural agency to include 3- or more-person groups. We sought to determine whether this conceptual shift is detectable in children's pronoun use. We report the results of a series of Bayesian hierarchical generative models fitted to 479 English-speaking children's first-person plural, first-person singular, second-person, third-person plural, and third-person singular pronouns. As a proportion of pronouns, children used more first-person plural pronouns, only, after 3;0 compared to before. Additionally, children used more 1pp. pronouns when their mothers used more 1pp. pronouns. As a proportion of total utterances, all pronoun classes were used more often as children aged. These findings suggest that a shift in children's social conceptualizations at age 3 is reflected in their use of 1pp. pronouns.

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain’s physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain’s nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain’s dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou’s ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain’s response to injury and pathology, embracing Malabou’s concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice.

Chloroplast genomes (plastomes) represent a very important source of valuable information for phylogenetic and biogeographic reconstructions. The use of short reads (as those produced from Illumina sequencing), along with de novo read assembly, has been considered the “gold standard” for plastome reconstruction. However, short reads often cannot reconstruct long repetitive regions in chloroplast genomes. Long Nanopore (ONT) reads can help bridging long repetitive regions but are by far more error-prone than those produced by Illumina sequencing. Verbesina is the largest genus of tribe Heliantheae (Asteraceae) and includes species of economic importance as ornamental or as invasive weeds. However, no complete chloroplast genomes have been published yet for the genus. We utilized Illumina and Nanopore sequencing data and different assembly strategies to reconstruct the plastome of Verbesina alternifolia and evaluated the usefulness of the Nanopore assemblies. The two plastome sequence assemblages, one obtained with the Nanopore sequencing and the other inferred with Illumina reads, were identical, except for missing bases in homonucleotide regions. The best-assembled plastome of V. alternifolia was 152,050 bp in length and contained 80, 29, and four unique protein-coding genes, tRNAs, and rRNAs, respectively. When used as reference for mapping Illumina reads, all plastomes performed similarly. In a phylogenetic analysis including 28 other plastomes from closely related taxa (from the Heliantheae alliance), the two Verbesina chloroplast genomes grouped together and were nested among the other members of the tribe Heliantheae s.str. Our study highlights the usefulness of the Nanopore technology for assembling rapidly and cost-effectively chloroplast genomes, especially in taxonomic groups with paucity of publicly available plastomes.

Diabetic foot ulcer (DFU), one of the most significant complications of diabetes, is a condition that causes anatomical and functional alterations of the foot resulting in an important social and economic impact, related to disability and health care costs. Recently, three-dimensional bioprinting - which allows the fabrication of complex and biocompatible structures - has been identified as a promising approach in the field of regenerative medicine to promote the healing of chronic wounds, such as DFU. In this concise review we highlight the most relevant and recent attempts of using 3D bioprinted constructs in vivo - both on animals and people - in order to treat non-healing diabetic ulcers and prevent their worsening. Finally, we briefly focus on the future implications of bioprinting, suggesting its forthcoming importance not only for DFU treatment but also for other areas of clinical care.

Introduction: The molecular profile of colorectal cancer (CRC) plays a crucial role in understanding patient prognosis and treatment response. Within CRC, a distinct subgroup can be identified by the presence of the BRAF V600E mutation. This specific mutation, classified as Class I of BRAF mutations, is known to be associated with a poor prognosis and resistance to standard therapy. To determine the most effective treatment approach for this specific subgroup of CRC, we conducted a network meta-analysis (NMA) to compare various pharmacological interventions and evaluate their relative effectiveness in BRAF-mutated CRCs. Materials and methods: On July 31, 2023, we conducted a systematic search of PubMed, Cochrane Central Register of Controlled Trials, and Embase. The inclusion criteria were as follows: 1) reporting of outcomes in patients with BRAF-mutated CRC who underwent first-line chemotherapy; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. The data were combined using HRs for overall and progression-free survival (OS and PFS) using random-effects models. NMA was performed under the Bayesian framework, utilizing the GeMTC package. The relative rankings of the treatments were determined using SUCRA scores. Results: A total of 16 studies were included. When compared to standard chemotherapy (CT) doublets (such as FOLFOX or FOLFIRI), none of the comparison arms demonstrated a gain in OS. CT doublet + bevacizumab did not show significant superiority over either CT doublet alone or 5FU/capecitabine + bevacizumab. FOLFOXIRI and FOLFOXIRI + bevacizumab did not show superiority over any other treatment schedule that was compared. CT doublets + bevacizumab had the highest SUCRA score (0.87), followed by single-agent fluoropyrimidines + bevacizumab (0.61), and FOLFOXIRI (0.56). Regarding PFS, no regimen was found to be superior to the combination of CT doublet plus bevacizumab. However, FOLFOXIRI + bevacizumab + atezolizumab showed a tendency towards better results (HR = 0.26, 95 % CI 0.05–1.1). Conclusions: Our review suggests that a CT doublet with bevacizumab is the most favorable option for OS. However, a reasonable alternative could be a triplet CT without bevacizumab.

Abstract The identification of large vessel occlusion with underlying intracranial atherosclerotic disease (ICAS-LVO) before endovascular treatment (EVT) continues to be a challenge. We aimed to analyze baseline clinical-radiological features associated with ICAS-LVO that could lead to a prompt identification. We performed a retrospective cross-sectional study of consecutive patients with stroke treated with EVT from January 2020 to April 2022. We included anterior LVO involving intracranial internal carotid artery and middle cerebral artery. We analyzed baseline clinical and radiological variables associated with ICAS-LVO and evaluated the diagnostic value of a multivariate logistic regression model to identify ICAS-LVO before EVT. ICAS-LVO was defined as presence of angiographic residual stenosis or a trend to re-occlusion during EVT procedure. A total of 338 patients were included in the study. Of them, 28 patients (8.3%) presented with ICAS-LVO. After adjusting for confounders, absence of atrial fibrillation (OR 9.33, 95% CI 1.11–78.42; p = 0.040), lower hypoperfusion intensity ratio (HIR [Tmax > 10 s/Tmax > 6 s ratio], (OR 0.69, 95% CI 0.50–0.95; p = 0.025), symptomatic intracranial artery calcification (IAC, OR .15, 95% CI 1.64–26.42, p = 0.006), a more proximal occlusion (ICA, MCA-M1: OR 4.00, 95% CI 1.23–13.03; p = 0.021), and smoking (OR 2.91, 95% CI 1.08–7.90; p = 0.035) were associated with ICAS-LVO. The clinico-radiological model showed an overall well capability to identify ICAS-LVO (AUC = 0.88, 95% CI 0.83–0.94; p

Magnetic solitons hold great promise for token-based computing applications due to their intrinsic properties, including small size, topological stability, ultra-low power manipulation, and potentially ultra-fast operation. In particular, they have been proposed as reliable memory units that enable the execution of various logic tasks with in-situ memory. A critical challenge remains the identification of optimal soliton and efficient manipulation techniques. Previous research has primarily focused on the manipulation of two-dimensional solitons, such as skyrmions, domain walls, and vortices, by applied currents. The discovery of novel methods to control magnetic parameters, such as the interfacial Dzyaloshinskii-Moriya interaction, through strain, temperature gradients, and applied voltages offers new avenues for energetically efficient manipulation of magnetic structures. In this work, we present a comprehensive study using numerical and analytical methods to investigate the stability and motion of various magnetic textures under the influence of DMI gradients. Our results show that Néel and Bloch-type skyrmions, as well as radial vortices, exhibit motion characterized by finite skyrmion Hall angles, while circular vortices undergo expulsion dynamics. This study provides a deeper and crucial understanding of the stability and gradient-driven dynamics of magnetic solitons, paving the way for the design of scalable spintronics token-based computing devices.

Abstract Synthetic antiferromagnetic structures can exhibit the advantages of high velocity similarly to antiferromagnets with the additional benefit of being imaged and read-out through techniques applied to ferromagnets. Here, we explore the potential and limits of synthetic antiferromagnets to uncover ways to harness their valuable properties for applications. Two synthetic antiferromagnetic systems have been engineered and systematically investigated to provide an informed basis for creating devices with maximum potential for data storage, logic devices, and skyrmion racetrack memories. The two systems considered are (system 1) CoB/Ir/Pt of N repetitions with Ir inducing the negative coupling between the ferromagnetic layers and (system 2) two ferromagnetically coupled multilayers of CoB/Ir/Pt, coupled together antiferromagnetically with an Ir layer. From the hysteresis, it is found that system 1 shows stable antiferromagnetic interlayer exchange coupling between each magnetic layer up to N = 7. Using Kerr imaging, the two ferromagnetic multilayers in system 2 are shown to undergo separate maze-like switches during hysteresis. Both systems are also studied as a function of temperature and show different behaviors. Micromagnetic simulations predict that in both systems the skyrmion Hall angle is suppressed with the skyrmion velocity five times higher in system 1 than system 2.

Background: Mastocytosis (MS) is a rare disease that can involve various organs, including the bone. Given the incidence of the disease in the global population, MS poses a challenge for physicians, and early therapeutic intervention in the initial stages could significantly impact the quality of life of affected patients. Objective: The aim of this scoping review was to provide an overview of secondary osteoporosis in systemic mastocytosis (SM), focusing on the heterogeneity of its manifestations, the benefits of early diagnosis, and appropriate pharmacological treatment. Design: A technical expert panel (TEP) consisting of 8 physicians with expertise in metabolic bone diseases conducted the review following the PRISMA-ScR model. A strength of this study is that it provides various therapeutic approaches for patients with bone involvement in SM, although the limited available literature on the topic constituted a limitation. The TEP sought evidence regarding the following diagnostic and therapeutic modalities in the management of SM: “bisphosphonate therapy”, “zoledronic acid therapy”, “denosumab therapy”, “IFN-alpha therapy”, and “IFN-alpha therapy in combination with pamidronate”. Results: Clinical data showed a correlation between densitometric outcomes, serum tryptase levels, and mast cell infiltration in the bone marrow, between increased bone mineral density and the presence of osteosclerosis in cases of advanced SM, between the severity of osteoporosis and hypertryptasemia, and also provided results on the long-term effects of bisphosphonate therapy, the therapeutic efficacy of zoledronic acid administration, the positive effect of denosumab on the reduction of serum tryptase levels (even if is proved in a limited numbers of cases) and the prevention of new fractures, and the effect of IFN-alpha in more severe cases of SM, either alone or in combination with pamidronate. Conclusions: Studies have demonstrated the effectiveness of various treatments depending on the form of mastocytosis, whether indolent systemic or advanced systemic, in the prognosis of the disease. However, this role should be further investigated in additional clinical studies, considering the limited data on the use of these interventions.

IntroductionPhenotypic complexity in species complexes and recently radiated lineages has resulted in a diversity of forms that have historically been classified into separate taxa. Increasingly, with the proliferation of high-throughput sequencing methods, additional layers of complexity have been recognized, such as frequent hybridization and reticulation, which may call into question the previous morphological groupings of closely related organisms.MethodsWe investigated Northern European, Asian, and Beringian populations of Ranunculus auricomus agg. with phylogenomic analysis of 736 genes and 27,586 SNPs in order to deduce the interrelatedness and hybrid origin of this phenotypically and taxonomically complicated group from Europe characterized by a history of hybridization, polyploidy, apomixis, and recent radiation. The ploidy levels and the reproductive mode of the Northern European populations were assessed via flow cytometric seed screening. In addition, in order to examine the phenotypic plasticity of the dwarf forms previously described as species and summarized as the Ranunculus monophyllus group, we conducted climate chamber experiments under cold (northern) and warm (temperate) conditions.ResultsThe Northern European populations are tetra- to hexaploid and propagate primarily through apomixis. The complex is characterized by highly reticulate relationships. Genetic differentiation of the main clusters has occurred between the above-mentioned geographical regions. We find evidence for the hybrid origin of the taxa in these areas with differing genomic contributions from the geographically nearest European sexual progenitor species. Furthermore, polyphyly in the taxa of the R. monophyllus group is supported. Experiments show low lability in the traits associated with the R. monophyllus group.DiscussionWe conclude that multiple adaptations of hybrids to colder climates and shorter vegetation periods have shaped the phenotypes of the R. monophyllus group, and we suggest a formal classification as nothotaxa within the R. auricomus group.

This article is devoted to the provocative proposal of a plausible relationship between Grotowski’s last season (above all his idea of the Performer) and a certain tradition of the Italian actor’s theatre. We understand this relationship and this provocation essentially in terms of micro-theatricality and intra-theatricality. By intra-theatricality we mean that method of composition which is inscribed in the tranches de vie of layered, multi-generational actors, in their ability to reuse existential sequences and to reproduce on stage the complex relational routine that the company represents as a community. Apart from the fact that the distance between the twentieth-century Performer and the traditional Italian actor has often been emphasized, there is something in the traditional profile of the Italian actor that, in the mid-twentieth century, paradoxically coincides with the mission that Grotowski assigns to the Performer. The purpose of this article is to explore these analogies.

Numerous scientific papers have compared different treatment options in the management of myofascial pain syndrome. This study evaluated the efficacy of Extracorporeal ShockWave Treatment (ESWT) and mesotherapy in patients with Myofascial Pain Syndrome (MPS) in terms of improvement in pain, functional capacity, and quality of life. A case–control study was conducted on 54 patients, who were randomized into 2 groups: group A, consisting of 27 patients, who were treated with 5 sessions of focal ESWT on a weekly basis; and group B, consisting of 27 patients, who underwent 5 sessions of mesotherapy with Thiocolchicoside fl 4 mg/2 mL and Mepivacaine fl 10 mg/1 mL on a weekly basis. Patients were evaluated at enrollment (T0), after 5 weeks, at the end of rehabilitation treatment (T1), and at a follow- up 30 days after the end of treatment (T2), by administering rating scales (Numeric Rating Scale (NRS) - Pressure Pain Threshold (PPT) – Short Form-36 (SF-36)). The results showed that focal ESWT and Mesoterapy are two valid and effective treatment options in reducing algic symptoms and improving short- and long-term quality of life. However, the use of ESWTs, despite being mildly painful but tolerated, has been shown to be superior to mesotherapy in terms of pain reduction and increased functional capacity.