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Abstract Given the limited data on the real‐life therapeutic use of feline McDonough sarcoma (FMS)‐like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real‐life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3‐mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).

The COVID-19 pandemic has prompted a quest to understand why certain individuals remain uninfected or asymptomatic despite repetitive exposure to SARS-CoV-2. Here, we focused on six exposed females residing with their symptomatic and reinfected SARS-CoV-2 PCR-positive COVID-19 partners. Peripheral blood mononuclear cell samples from couples were analysed for poly (I:C)-induced mRNA expression of type I/III interferons and interferon-stimulated genes (ISGs). Remarkably, we found a significant upregulation of the ISG interferon-inducible protein with tetrapeptide repeats 3 (IFIT3) gene exclusively in exposed uninfected or asymptomatic females, suggesting a potential role in protective immunity against symptomatic COVID-19.

Abstract Background The genotype-by-environment interaction (GxE) in beef cattle can be investigated using reaction norm models to assess environmental sensitivity and, combined with genome-wide association studies (GWAS), to map genomic regions related to animal adaptation. Including genetic markers from whole-genome sequencing in reaction norm (RN) models allows us to identify high-resolution candidate genes across environmental gradients through GWAS. Hence, we performed a GWAS via the RN approach using whole-genome sequencing data, focusing on mapping candidate genes associated with the expression of reproductive and growth traits in Nellore cattle. For this purpose, we used phenotypic data for age at first calving (AFC), scrotal circumference (SC), post-weaning weight gain (PWG), and yearling weight (YW). A total of 20,000 males and 7,159 females genotyped with 770k were imputed to the whole sequence (29 M). After quality control and linkage disequilibrium (LD) pruning, there remained ∼ 2.41 M SNPs for SC, PWG, and YW and ∼ 5.06 M SNPs for AFC. Results Significant SNPs were identified on Bos taurus autosomes (BTA) 10, 11, 14, 18, 19, 20, 21, 24, 25 and 27 for AFC and on BTA 4, 5 and 8 for SC. For growth traits, significant SNP markers were identified on BTA 3, 5 and 20 for YW and PWG. A total of 56 positional candidate genes were identified for AFC, 9 for SC, 3 for PWG, and 24 for YW. The significant SNPs detected for the reaction norm coefficients in Nellore cattle were found to be associated with growth, adaptative, and reproductive traits. These candidate genes are involved in biological mechanisms related to lipid metabolism, immune response, mitogen-activated protein kinase (MAPK) signaling pathway, and energy and phosphate metabolism. Conclusions GWAS results highlighted differences in the physiological processes linked to lipid metabolism, immune response, MAPK signaling pathway, and energy and phosphate metabolism, providing insights into how different environmental conditions interact with specific genes affecting animal adaptation, productivity, and reproductive performance. The shared genomic regions between the intercept and slope are directly implicated in the regulation of growth and reproductive traits in Nellore cattle raised under different environmental conditions.

Abstract Microglia play diverse pathophysiological roles in Alzheimer’s disease (AD), with genetic susceptibility factors skewing microglial cell function to influence AD risk. CD33 is an immunomodulatory receptor associated with AD susceptibility through a single nucleotide polymorphism that modulates mRNA splicing, skewing protein expression from a long protein isoform (CD33M) to a short isoform (CD33m). Understanding how human CD33 isoforms differentially impact microglial cell function in vivo has been challenging due to functional divergence of CD33 between mice and humans. We address this challenge by studying transgenic mice expressing either of the human CD33 isoforms crossed with the 5XFAD mouse model of amyloidosis and find that human CD33 isoforms have opposing effects on the response of microglia to amyloid-β (Aβ) deposition. Mice expressing CD33M have increased Aβ levels, more diffuse plaques, fewer disease-associated microglia, and more dystrophic neurites compared to 5XFAD control mice. Conversely, CD33m promotes plaque compaction and microglia-plaque contacts, and minimizes neuritic plaque pathology, highlighting an AD protective role for this isoform. Protective phenotypes driven by CD33m are detected at an earlier timepoint compared to the more aggressive pathology in CD33M mice that appears at a later timepoint, suggesting that CD33m has a more prominent impact on microglia cell function at earlier stages of disease progression. In addition to divergent roles in modulating phagocytosis, scRNAseq and proteomics analyses demonstrate that CD33m+ microglia upregulate nestin, an intermediate filament involved in cell migration, at plaque contact sites. Overall, our work provides new functional insights into how CD33, as a top genetic susceptibility factor for AD, modulates microglial cell function. Graphical Abstract

In many Romance varieties the inverted order between subject clitic and verb characterizes interrogation contexts and, in Rhaeto-Romance languages, V2 contexts. This phenomenon gives rise to paradigms whereby in interrogative and V2 contexts the verb is followed by the enclitic form of the SCl, possibly also in combination with the proclitic subject. The enclisis on the verbal form has been dealt with as the result of the movement of the verb, typically in cartographic approaches, whereby the enclitic subject has been seen as the inverted proclitic form. Nevertheless, enclitics usually show a partially different form. Other authors deal with enclitics as inflections, whereby North Italy and Rhaeto-Romance varieties have an inflectional paradigm specialized for modal contexts such as interrogative clauses. V2 varieties with inversion contribute to suggesting a clearer and more complete explanation of this phenomenon. In this article we will motivate the inflectional nature of enclitics based on their distribution and in the light of the hypothesis that it is the result of syntactic Merge. As for inversion, we will propose a hypothesis based on the phasal organization of the clause and the domains of subject-verb agreement.

La certificación en el turismo puede servir tanto de estímulo para mejorar la gestión de los recursos turísticos como de incentivo para los visitantes, puesto que a menudo ofrecen garantía de buenas experiencias turísticas. En tal sentido, es necesario realizar investigaciones que muestren las características de los sistemas de certificación turística en los destinos. El objetivo de este artículo es describir los sistemas de certificación turísticas en las Américas. Para el estudio se consideró un total de 59 sistemas de certificación turística en el continente, con niveles operativos globales, subglobales, nacionales, regionales y locales. La metodología se sustentó en una investigación de tipo documental, caracterización cualitativa y cuantitativa de los sistemas de certificación, utilizando la estadística descriptiva y el programa SPSS para el procesamiento de los datos. Entre los resultados se obtuvo que la mayor categoría certificada en el continente es “Proveedores de alojamiento”; “Estados Unidos” posee el mayor número de programas de certificación; el nivel operativo predominante entre los sistemas de certificación es el “Regional”. Se concluye que, muchos países de América utilizan los mismos criterios de sistemas globales para construir sus programas de certificación turística nacionales, en línea con las políticas ambientales y turísticas propias de cada país.

Vates phoenix Rivera et al., 2020 (Mantodea: Mantidae) is endemic to the Atlantic Rainforest of Brazil, known to the states of Rio de Janeiro and São Paulo. Integrating field collection and records from iNaturalist, the species’ distribution is extended further south, west and north, with confirmed new occurrences to the states of Paraná, Santa Catarina, Minas Gerais, Espírito Santo, and Bahia. The observations provide insights into the species’ natural history and the importance of combining multiple data sources, including citizen science, to provide greater information on elusive species.

The history of the discovery, use, and development of dyes is closely linked to the history of humanity itself. Among the first records of human civilization are cave paintings made from, e.g., fruits, plants, minerals, and insects. Over the centuries, using different techniques, colors have been given to all types of materials and products, from clothing to food. The chemicals responsible for colors are dyes - a vast collection of molecules of the most varied compositions, but which have in common the absorption of light within the visible window of the electromagnetic spectrum. This article aims not only to review the properties of some classes of natural dyes, their origins, and their applications but also to describe the various computational chemistry methods involved in designing new bio-inspired molecules.

Across the world’s oceans, our knowledge of the habitats on the seabed is limited. Increasingly, video/imagery data from remotely operated underwater vehicles (ROVs) and towed and drop cameras, deployed from vessels, are providing critical new information to map unexplored benthic (seabed) habitats. However, these vessel-based surveys involve considerable time and personnel, are costly, require favorable weather conditions, and are difficult to conduct in remote, offshore, and deep marine habitats, which makes mapping and surveying large areas of the benthos challenging. In this study, we present a novel and efficient method for mapping diverse benthic habitats on the continental shelf, using animal-borne video and movement data from a benthic predator, the Australian sea lion (Neophoca cinerea). Six benthic habitats (between 5-110m depth) were identified from data collected by eight Australian sea lions from two colonies in South Australia. These habitats were macroalgae reef, macroalgae meadow, bare sand, sponge/sand, invertebrate reef and invertebrate boulder habitats. Percent cover of benthic habitats differed on the foraging paths of sea lions from both colonies. The distributions of these benthic habitats were combined with oceanographic data to build Random Forest models for predicting benthic habitats on the continental shelf. Random forest models performed well (validated models had a >98% accuracy), predicting large areas of macroalgae reef, bare sand, sponge/sand and invertebrate reef habitats on the continental shelf in southern Australia. Modelling of benthic habitats from animal-borne video data provides an effective approach for mapping extensive areas of the continental shelf. These data provide valuable new information on the seabed and complement traditional methods of mapping and surveying benthic habitats. Better understanding and preserving these habitats is crucial, amid increasing human impacts on benthic environments around the world.

ObjectivesPreterm birth occurs in more than 10% of U.S. births and is the leading cause of U.S. neonatal deaths, with estimated annual costs exceeding $25 billion USD. Using real-world data, we modeled the potential clinical and economic utility of a prematurity-reduction program comprising screening in a racially and ethnically diverse population with a validated proteomic biomarker risk predictor, followed by case management with or without pharmacological treatment.MethodsThe ACCORDANT microsimulation model used individual patient data from a prespecified, randomly selected sub-cohort (N = 847) of a multicenter, observational study of U.S. subjects receiving standard obstetric care with masked risk predictor assessment (TREETOP; NCT02787213). All subjects were included in three arms across 500 simulated trials: standard of care (SoC, control); risk predictor/case management comprising increased outreach, education and specialist care (RP-CM, active); and multimodal management (risk predictor/case management with pharmacological treatment) (RP-MM, active). In the active arms, only subjects stratified as higher risk by the predictor were modeled as receiving the intervention, whereas lower-risk subjects received standard care. Higher-risk subjects' gestational ages at birth were shifted based on published efficacies, and dependent outcomes, calibrated using national datasets, were changed accordingly. Subjects otherwise retained their original TREETOP outcomes. Arms were compared using survival analysis for neonatal and maternal hospital length of stay, bootstrap intervals for neonatal cost, and Fisher's exact test for neonatal morbidity/mortality (significance, p