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This article presents the ENglish Reading Online (ENRO) project that offers data on English reading and listening comprehension from 7,338 university-level advanced learners and native speakers of English representing 19 countries. The database also includes estimates of reading rate and seven component skills of English, including vocabulary, spelling, and grammar, as well as rich demographic and language background data. We first demonstrate high reliability for ENRO tests and their convergent validity with existing meta-analyses. We then provide a bird's-eye view of first (L1) and second (L2) language comparisons and examine the relative role of various predictors of reading and listening comprehension and reading speed. Across analyses, we found substantially more overlap than differences between L1 and L2 speakers, suggesting that English reading proficiency is best considered across a continuum of skill, ability, and experiences spanning L1 and L2 speakers alike. We end by providing pointers for how researchers can mine ENRO data for future studies.

Abstract Background The identification and staging of Alzheimer’s Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. Methods One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. Results Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. Conclusions Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD.

Este artigo objetiva compreender de que modo as ferramentas de comunicação analógicas e digitais têm sido usadas na rádio comunitária Oeste FM para proporcionar a participação da comunidade, objetivando alcançar os princípios de uma rádio comunitária. O serviço de radiodifusão comunitária foi legalizado no Brasil em 1998 por meio da lei 9.612/98, que estabelece as diretrizes do referido serviço. Esta investigação foi realizada a partir de um Estudo de Caso, com apoio da pesquisa bibliográfica, documental, entrevista semiestruturada, estudo da usabilidade e design da homepage e estudo da programação da rádio. A principal hipótese deste trabalho, é que as ferramentas analógicas e digitais aproximam a comunidade nas ações da rádio e criam novas relações, intensificando a participação na gestão. Contudo, os resultados da pesquisa mostram que, apesar da disposição de ferramentas analógicas e digitais, a participação da comunidade é extremamente limitada e se resume em boa parte ao entretenimento, com ênfase no pedido musical. Portanto, não atende completamente aos objetivos de uma rádio comunitária.

Abstract This study aimed to characterize concepts of continuities and discontinuities in the intergenerational transmission of relational models, as well as marital and parental conflict resolution tactics. This was a qualitative study, in which 12 couples attended a semi-structured interview. Through thematic content analysis, the data was divided into two main themes: Intergenerational Continuities and Intergenerational Discontinuities. The continuities indicated both the repetition of positive and constructive aspects of family models, as well as the prevalence of destructive tactics, such as avoidance between spouses and the use of corporal punishment with the child. The discontinuities revealed a break from negative or destructive patterns and the adoption of positive parenting, in contrast to that of the family of origin.

BACKGROUND AND OBJECTIVES: The locus of control (LC) of pain is the perception of the individual about pain control. The investigation of the relationship between LC, dependence and depression in elderly patients is of great importance given the high prevalence of chronic diseases among this population. The objective of this study was to analyze the association between LC of pain in elderly patients and the level of dependence and prevalence of depression. METHODS: Ninety-one elderly individuals, aged over 60 years, were selected from the Association of Retirees, Pensioners, and Elderly of Lavras and Region (AAPIL) and all participants underwent a comprehensive anamnesis to effectively describe and characterize the sample. The Health Locus of Control Multidimensional Scale was used to assess perception of pain, the Yesavage Geriatric Depression Scale was used to determine the prevalence of depression, and Katz Index to evaluate functional capacity. Chi-square test was used to analyze nominal variables with a 95% level of significance. RESULTS: The majority of the elderly participants (83.5%) reported experiencing chronic pain, while 85.7% had no suspected depression. Internal control was the most prevalent type of LC among participants, and there was no significant relationship between LC of pain and depression. CONCLUSION: Findings suggest that the type of LC of pain reported by the elderly participants in this study does not significantly interfere with the likelihood of depression. These results contribute to the understanding of the relationship between LC, dependence, and depression among senior patients and may inform interventions to improve their quality of life.

Abstract Heterozygosity-rich regions (HRR) are genomic regions of high heterozygosity, which may harbor loci related to key functional traits such as immune response, survival rate, fertility, and other fitness traits. This study considered 30 Italian and 19 worldwide goat breeds genotyped with the Illumina GoatSNP50k BeadChip. The aim of the work was to study inter-breed relationships and HRR patterns using Sliding Window (SW) and Consecutive Runs (CR) detection methods. Genetic relationships highlighted a clear separation between non-European and European breeds, as well as the north–south geographic cline within the latter. The Pearson correlation coefficients between the descriptive HRR parameters obtained with the SW and CR methods were higher than 0.9. A total of 166 HRR islands were detected. CHI1, CHI11, CHI12 and CHI18 were the chromosomes harboring the highest number of HRR islands. The genes annotated in the islands were linked to various factors such as productive, reproductive, immune, and environmental adaptation mechanisms. Notably, the Montecristo feral goat showed the highest number of HRR islands despite the high level of inbreeding, underlining potential balancing selection events characterizing its evolutionary history. Identifying a species-specific HRR pattern could provide a clearer view of the mechanisms regulating the genome modelling following anthropogenic selection combined with environmental interaction.

The demand for Artificial Intelligence (AI) based solutions is exponentially increasing in all application fields, including low-power devices on the edge. However, due to their limited computational capabilities, these devices, which run Central Processing Units (CPUs) tailored to embedded applications, are typically not optimized to run complex neural networks. Providing ad-hoc extensions to the instruction set architecture of a RISC-V processor can be a viable solution to address this issue. In this work, we propose the use of the PyTorch Graph Lowering (Glow)–LLVM toolchain to understand the impact of compiled code of AI models on a RISC-V machine and extend its instruction set to improve runtime performance. This approach allows code profiling, detection of computational bottlenecks, and provisioning of the necessary CPU enhancements to be implemented in the LLVM backend before hardware implementation. After profiling known Artificial Neural Networks (ANNs) quantized to int8 (particularly, a single perceptron, RESNET18, VGG11, and LENET5), we have identified and devised three additional instructions, we named LWM, LWA and LWS respectively indicating Load Word-and-Multiply, -Add, and -Subtract. As a result, we obtained an edge AI-oriented, significantly improved processor description in terms of inference time and program density, ready to be hardware-designed. For $128\times 128$ RGB images, the custom extensions enabled up to $13\times $ speed up compared to RV32I and $5\times $ compared to RV32IM, with a maximum of 11.7% lower code. Together with these findings the paper systematically highlights the main methodological steps to include new instructions in an LLVM backend.

Abstract Robertsonian translocation 1;29 (rob(1;29)), a widespread chromosomal anomaly affecting cattle fertility, appears to have originated from a common ancestor. This study utilizes routine SNP data to investigate the chromosomal region associated with rob(1;29) and confirm the presence of a shared haplotype among carriers in diverse Italian breeds. Three datasets were employed: Dataset 1 included 151 subjects from 5 beef cattle breeds genotyped with the GGP Bovine 33 k SNP chip; Dataset 2 encompassed 800 subjects from 32 Italian breeds genotyped with the Illumina 50 k SNP chip, sourced from the BOVITA dataset; Dataset 3 combined Dataset 2 with 21 karyologically tested subjects from breeds with a high carrier frequency, genotyped using the Affymetrix 65 K SNP chip. FST analysis pinpointed a distinctive genomic region on the first six Mb of BTA29, the centromeric region involved in the translocation. Haplotype comparisons within this non-recombining region revealed a common haplotype shared among all carriers, supporting the theory of a common ancestor. Principal component and haplotype analysis allowed clear differentiation of rob(1;29) homozygous and heterozygous carriers. Expanding to Dataset 2 revealed rob(1;29) carriers in unexpected breeds, all sharing the same ancestral haplotype. Notably, previously untested breeds, including Cinisara, exhibited a high carrier prevalence (nearly 50%), confirmed by karyological analysis. This study validates the presence of a shared haplotype among all identified rob(1;29) carriers, reinforcing the common ancestor theory as the origin of this translocation's spread throughout the cattle population. Furthermore, it underscores the potential of SNP data analysis as a rapid, accurate, and cost-effective tool for broad rob(1;29) screening, given the translocation's consistent nature across all analyzed breeds.

Collective modes are responsible for the emergence of novel quantum phases in topological materials. In the quasi-one dimensional (1D) Weyl semimetal (TaSe4)2I, a charge density wave (CDW) opens band gaps at the Weyl points, thus turning the system into an axionic insulator. Melting the CDW would restore the Weyl phase, but 1D fluctuations extend the gapped regime far above the 3D transition temperature (T CDW = 263 K), thus preventing the investigation of this topological phase transition with conventional spectroscopic methods. Here we use a non-equilibrium approach: we perturb the CDW phase by photoexcitation, and we monitor the dynamical evolution of the band structure by time- and angle-resolved photoelectron spectroscopy. We find that, upon optical excitation, electrons populate the linearly dispersing states at the Fermi level (E F ), and fill the CDW gap. The dynamics of both the charge carrier population and the band gap renormalization (BGR) show a fast component with a characteristic time scale of a few hundreds femtoseconds. However, the BGR also exhibits a second slow component on the μs time scale. The combination of an ultrafast response and of persistent changes in the spectral weight at E F, and the resulting sensitivity of the linearly dispersing states to optical excitations, may explain the high performances of (TaSe4)2I as a material for broadband infrared photodetectors.

The majority of the new words that we learn every day as adults are morphologically complex; yet, we do not know much about the role of morphology in novel word learning. In this study, we tackle this issue by comparing the learning of: (i) suffixed novel words (e.g. flibness); (ii) novel words that end in non-morphological, but frequent letter chunks (e.g. fliban); and (iii) novel words with non-morphological, low-frequency endings (e.g. flibov). Words are learned incidentally through sentence reading, while the participants’ eye movements are monitored. We show that morphology has a facilitatory role compared with the other two types of novel words, both during learning and in a post-learning recognition memory task. We also showed that participants attributed meaning to word parts (if flibness is a state of happiness, then flib must mean happy), but this process was not specifically triggered by the presence of a suffix (flib must also mean happy in fliban and flibov), thus suggesting that the brain tends to assume similar meanings for similar words and word parts.

Climate change and heat stress pose significant challenges to livestock. Local breeds, particularly small ruminants, are gaining importance due to their adaptability to harsh climates. However, the extensive system they are commonly reared in leaves them exposed to the effects of climate change. This study aims to describe the distribution and climate-related challenges faced by registered Italian sheep and goat breeds over the past seven decades. Geolocalized data from all registered small ruminant farms were combined with climatic information retrieved from the “ERA-5-Land hourly data from 1950 to present” dataset. These data were used to calculate average daily temperature, temperature humidity index (THI), and total precipitation during summer. Additionally, THI-based heat waves (HWs) were examined, including the yearly number of HW days and mean THI during HW days. These data were analysed through linear regression models including region or breed, year, and their interaction as fixed factors. The climate data indicate a concerning trend of rising summer temperatures, THI, and HW frequency and intensity, particularly over the past three decades. Central-northern Italy, including the Po Valley and the Alpine Arch, is the most affected region, impacting breeds like Rosset and Brogne sheep, and Lariana and Frisa Valtellinese goats. This is of particular concern because these populations have not been selected for hot climates, and their already small population size exacerbates the problem. Conversely, southern Italy, characterized by hotter and drier temperatures, remained relatively stable. Breeds from this region, such as Girgentana and Nicastrese goats and Nera di Arbus sheep, might represent excellent case studies for climatic adaptation and potential resources for selection for resilience in the face of ongoing climate changes. The findings presented here are essential for the development of monitoring and intervention strategies for breeds facing future vulnerabilities, as well as for designing experiments to explore environmental adaptability in small ruminants.

Colloid-based computing devices offer remarkable fault tolerance and adaptability to varying environmental conditions due to their amorphous structure. An intriguing observation is that a colloidal suspension of ZnO nanoparticles in dimethylsulfoxide (DMSO) exhibits reconfiguration when exposed to electrical stimulation and produces spikes of electrical potential in response. This study presents a novel laboratory prototype of a ZnO colloidal computer, showcasing its capability to implement various Boolean functions featuring two, four and eight inputs. During our experiments, we input binary strings into the colloid mixture, where a logical ‘True’ state is represented by an impulse of an electrical potential. In contrast, the absence of the electrical impulse denotes a logical ‘False’ state. The electrical responses of the colloid mixture are recorded, allowing us to extract truth tables from the recordings. Through this methodological approach, we demonstrate the successful implementation of a wide range of logical functions using colloidal mixtures. We provide detailed distributions of the logical functions discovered and offer speculation on the potential impacts of our findings on future and emerging unconventional computing technologies. This research highlights the exciting possibilities of colloid-based computing and paves the way for further advancements.

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Immersive technology, such as extended reality, holds promise as a tool for educating ophthalmologists about the effects of low vision and for enhancing visual rehabilitation protocols. However, immersive simulators have not been evaluated for their ability to induce changes in the oculomotor system, which is crucial for understanding the visual experiences of visually impaired individuals. This study aimed to assess the REALTER (Wearable Egocentric Altered Reality Simulator) system’s capacity to induce specific alterations in healthy individuals’ oculomotor systems under simulated low-vision conditions. We examined task performance, eye movements, and head movements in healthy participants across various simulated scenarios. Our findings suggest that REALTER can effectively elicit behaviors in healthy individuals resembling those observed in individuals with low vision. Participants with simulated binocular maculopathy demonstrated unstable fixations and a high frequency of wide saccades. Individuals with simulated homonymous hemianopsia showed a tendency to maintain a fixed head position while executing wide saccades to survey their surroundings. Simulation of tubular vision resulted in a significant reduction in saccade amplitudes. REALTER holds promise as both a training tool for ophthalmologists and a research instrument for studying low vision conditions. The simulator has the potential to enhance ophthalmologists’ comprehension of the limitations imposed by visual disabilities, thereby facilitating the development of new rehabilitation protocols.

Nowadays, several countries are developing or adopting genomic selection in the dairy goat sector. The most used method to estimate breeding values is Single-Step Genomic Best Linear Unbiased Prediction (ssGBLUP) which offers several advantages in terms of computational process and accuracy of the estimated breeding values (EBVs). Saanen and Alpine are the predominant dairy goat breeds in Italy, and both have similar breeding programs where EBVs for productive traits are currently calculated using BLUP. This work describes the implementation of genomic selection for these two breeds in Italy, aligning with the selection practices already carried out in the international landscape. The available dataset included 3 611 genotyped animals, 11 470 lactation records, five traits (milk, protein and fat yields, and fat and protein percentages), and three-generation pedigrees. EBVs were estimated using BLUP, GBLUP, and ssGBLUP both with single and multiple trait approaches. The methods were compared in terms of correlation between EBVs and genetic trends. Results were also validated with the linear regression method excluding part of the phenotypic data. In both breeds, EBVs and GEBVs were strongly correlated and the trend of each trait was similar comparing the three methods. The average increase in accuracy across traits and methods amounted to +13 and +10% from BLUP to ssGBLUP for Alpine and Saanen breeds, respectively. Results indicated higher prediction accuracy and correlation for GBLUP and ssGBLUP compared to BLUP, implying that the use of genotypes increases the accuracy of EBVs, particularly in the absence of phenotypic data. Therefore, ssGBLUP is likely to be the most effective method to enhance genetic gain in Italian Saanen and Alpine goats.

Properties of the broad line region (BLR) in active galactic nuclei (AGNs) are commonly used to estimate the mass of the supermassive black hole (SMBH) that powers an AGN. However, the understanding of the physics behind the BLR remains incomplete. The AGNs exhibit strong optical variability, observed in the change of the profiles and fluxes of broad emission lines. Utilizing this variability provides an opportunity to constrain the physics of the BLR, and understand the interplay of the BLR with SMBH and surrounding regions. Here, we present the long-term monitoring campaign of a sample of the known broad-line AGNs (identified as LoTerm AGN). The aim of this study is to show the importance of sustained and dedicated campaigns that continually collect spectroscopic data of the known AGNs over extended timescales, providing unique insight into the origin and structure of the BLR. LoTerm AGN is a collaborative network of seven moderate-size telescopes equipped for spectroscopy. We focus on the recent spectral data of the known changing-look AGN, NGC 3516. Specifically, we examine the broad hydrogen Balmer Hα line observed in the period 2020–2023, demonstrating that this AGN remains active with the BLR signatures observed in the spectra. No significant change in the broad line profile of Hα line is observed during this recent period.

O objetivo desta pesquisa quantitativa foi caracterizar a demanda de violência familiar, no atendimento psicológico on-line, durante a Pandemia por Covid-19, na perspectiva de psicólogas(os) clínicas(os), do estado de Santa Catarina. Participaram 50 psicólogas(os) clínicas(os), que responderam um questionário on-line, através do Google Forms. Para análise dos dados, foram utilizadas análises de estatística descritiva e inferencial. Em termos de resultados, observou-se que dentre as(os) clientes que sofreram violência, houve predomínio de mulheres e adolescentes do gênero feminino. As principais violências relatadas foram a psicológica, auto infligida e física, praticadas, sobretudo, pelo marido, companheiro, pai, mãe ou pela(o) própria(o) cliente. Setores da rede de proteção e garantia de direitos foram pouco procurados pelas(os) profissionais (n = 6). Em relação às dificuldades ou facilidades no manejo clínico a casos de violência, 21 participantes consideraram mais difícil atender situações de violência na modalidade on-line do que presencial e mais da metade respondeu se sentir sensibilizada(o) ao atender essas situações. Este estudo possibilitou conhecer características do atendimento psicológico on-line a demandas de violência familiar, na prática clínica privada, frente ao cenário de pandemia, tema ainda pouco visibilizado em estudos nacionais empíricos.

We aimed to examine the drug retention rate (DRR) of the interleukin-17 inhibitor ixekizumab in a real-world monocentric cohort of psoriatic arthritis (PsA) patients and to assess the predictors of drug discontinuation. Consecutive PsA patients who underwent treatment with ixekizumab from October 2019 to February 2023 were enrolled in this observational, retrospective, monocentric study. Clinical records were assessed at baseline and throughout the follow-up period. We collected sociodemographic data, smoking habits, body mass index, the presence of Human Leukocyte Antigen B27, comorbidities, disease involvement and duration, previous therapy, discontinuation of ixekizumab, reasons for discontinuation, and adverse events (AEs). DRR was evaluated as time to drug discontinuation and assessed through Kaplan–Meier curves. Baseline factors predicting drug discontinuation were investigated through logistic regression models. Eighty PsA patients were included in this study. Ixekizumab was administered at a dose of 160 mg by subcutaneous injection at baseline, followed by 80 mg every four weeks thereafter. Ixekizumab had a 38-month-cumulative DRR of 43.8%, accounting for both inefficacy and AEs. When considering only inefficacy, the DRR was 62.6%. Comorbidities (p = 0.665), obesity (p = 0.665), smoking (p = 0.884), disease duration ≤ 2 years (p = 0.071), axial (p = 0.131) and skin involvement (p = 0.460), and previous therapies, including conventional synthetic (p = 0.504) and biological (p = 0.474) Disease-Modifying Antirheumatic Drugs (bDMARDs), as well as the number of previous bDMARDs or targeted synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs), did not significantly affect the DRR (p = 0.349). Multivariate analysis found no independent predictors of drug discontinuation. The most frequent AEs leading to discontinuation were skin reactions; no severe infections were observed. In our real-world study, comorbidities, disease duration, and previous therapies did not affect the DRR of ixekizumab. Ixekizumab had a favorable safety profile, with no severe AEs observed.

Background: After ischemic stroke, there is no general consensus on the optimal position for the head of patients in the acute phase. This observational study aimed to measure the variations in cortical oxygenation using noninvasive functional near-infrared spectroscopy (fNIRS) at different degrees of head positioning on a bed. Methods: Consecutive ischemic stroke patients aged 18 years or older with anterior circulation ischemic stroke within 48 h of symptom onset who could safely assume different positions on a bed were included. A 48-channel fNIRS system was placed in the bilateral sensorimotor cortex. Then, the bed of each patient was moved into four consecutive positions: (1) seated (90° angle between the head and bed surface); (2) lying at 30°; (3) seated again (90°); and (4) lying flat (0°). Each position was maintained for 90 s; the test was conducted 48 h after stroke onset and after 5 ± 1 days. The variations in oxygenated hemoglobin in the global brain surface and for each hemisphere were recorded and compared. Results: Twenty-one patients were included (males, n = 11; age, 79 ± 9 years; ASPECTS, 8 ± 2). When evaluating the affected side, the median oxygenation was significantly greater in the lying-flat (0°) and 30° positions than in the 90° position (p < 0.001 for both comparisons). No significant differences between the supine position and the 30° position were found, although oxygenation was slightly lower in the 30° position than in the supine position (p = 0.063). No differences were observed when comparing recanalized and nonrecanalized patients separately or according to stroke severity. The evaluation conducted 5 days after the stroke confirmed the previous data, with a significant difference in oxygenation at 0° and 30° compared to 90°. Conclusions: This preliminary study suggested that there are no substantial differences in brain oxygenation between the lying-flat head position and the 30° laying position.

Leishmaniases, a group of diseases caused by the species of the protozoan parasite Leishmania, remains a significant public health concern worldwide. Host immune responses play a crucial role in the outcome of Leishmania infections, and several mediators that regulate inflammatory responses are potential targets for therapeutic approaches. Annexin A1 (AnxA1), an endogenous protein endowed with anti-inflammatory and pro-resolving properties, has emerged as a potential player. We have shown that during L. braziliensis infection, deficiency of AnxA1 exacerbates inflammatory responses but does not affect parasite burden. Here, we have investigated the role of AnxA1 in L. amazonensis infection, given the non-healing and progressive lesions characteristic of this infectious model. Infection of AnxA1 KO BALB/c mice resulted in increased lesion size and tissue damage associated with higher parasite burdens and enhanced inflammatory response. Notably, therapeutic application of the AnxA1 peptidomimetic Ac2–26 improves control of parasite replication and increases IL-10 production in vivo and in vitro, in both WT and AnxA1 KO mice. Conversely, administration of WRW4, an inhibitor of FPR2/3, resulted in larger lesions and decreased production of IL-10, suggesting that the effects of AnxA1 during L. amazonensis infection are associated with the engagement of these receptors. Our study illuminates the role of AnxA1 in L. amazonensis infection, demonstrating its impact on the susceptibility phenotype of BALB/c mice. Furthermore, our results indicate that targeting the AnxA1 pathway by using the Ac2–26 peptide could represent a promising alternative for new treatments for leishmaniasis.

Schistosomiasis is an intravascular infectious disease that impacts over 200 million people globally. In its chronic stage, it leads to mesenteric inflammation with significant involvement of monocytes/macrophages. Endothelial cells lining the vessel lumens play a crucial role, and mount of evidence links this disease to a downregulation of endoprotective cell signaling favoring a primed and proinflammatory endothelial cell phenotype and therefore the loss of immunovascular homeostasis. One hallmark of infectious and inflammatory conditions is the release of nucleotides into the extracellular milieu, which, in turn, act as innate messengers, activating purinergic receptors and triggering cell-to-cell communication. ATP influences the progression of various diseases through P2X and P2Y purinergic receptor subtypes. Among these receptors, P2Y2 (P2Y2R) and P2X7 (P2X7R) receptors stand out, known for their roles in inflammation. However, their specific role in schistosomiasis has remained largely unexplored. Therefore, we hypothesized that endothelial P2Y2R and P2X7R could contribute to monocyte adhesion to mesenteric endothelial cells in schistosomiasis. Using a preclinical murine model of schistosomiasis associated with endothelial dysfunction and age-matched control mice, we showed that endothelial P2Y2R and P2X7R activation increased monocyte adhesion to cultured primary endothelial cells in both groups. However, a distinct upregulation of endothelial P2Y2R-driven canonical Ca2+ signaling was observed in the infected group, amplifying adhesion. In the control group, the coactivation of endothelial P2Y2R and P2X7R did not alter the maximal monocyte adhesion induced by each receptor individually. However, in the infected group, this coactivation induced a distinct upregulation of P2Y2R-P2X7R-driven canonical signaling, IL-1β release, and VCAM-1 expression, with underlying mechanisms involving inflammasome and NF-κB signaling. Therefore, current data suggest that schistosomiasis alters endothelial cell P2Y2R/P2X7R signaling during inflammation. These discoveries advance our understanding of schistosomiasis. This intricate interplay, driven by PAMP-triggered endothelial P2Y2R/P2X7R cross-talk, emerges as a potential key player in the mesenteric inflammation during schistosomiasis.

Skilled readers are typically most accurate at identifying words when fixating them slightly left of the central character, the so-called optimal viewing position. There are two main explanations for this effect, which are not mutually exclusive. The first claims that the optimal viewing position lies left-of-center due to the particular constraints of the human perceptual system. The second explains the effect in terms of the beginnings of words generally being more informative about word identity. The complexities of natural languages make it difficult to tease apart the relative contribution of each explanation. We explore this issue through the lens of a Bayesian cognitive model and two experiments using artificial lexicons in which we can carefully control how information is distributed across wordforms. Our results replicate previous findings and further suggest that readers may use implicit knowledge about information distribution to minimize uncertainty when targeting words.