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The South American species of the myrmecomorphic spider genus Mazax O. Pickard-Cambridge, 1898 (Castianeirinae, Corinnidae) are revised for the first time, increasing the number of known species from South America from two to six and the number of species in the genus from seven to 11. Here, we reevaluate the identity of Apochinomma acanthaspis Simon, 1896, propose its transfer to Mazax, and consider M. akephaloi Perger & Pett, 2022 as a junior synonym of M. acanthaspis comb. nov. Additional documentation of M. ramirezi Rubio & Danişman, 2014 is provided. The species M. pax Reiskind, 1969 and M. spinosa (Simon, 1898) are recorded from South America for the first time. Three new species are proposed, all based on both sexes: Mazax mokana sp. nov. and M. leonidas sp. nov. from Colombia, and M. tembe sp. nov. from Brazil. Emended diagnoses of the genus and of all six known South American species, as well as a key to males and females for all 11 species in the genus, are provided.

Dorvilleidae Chamberlin, 1919 is a family of Annelida containing some of the smallest ‘polychaetes’ species, being poorly studied worldwide, and with little knowledge regarding its diversity and occurrence. Samples obtained in oceanographic campaigns performed in the Southwest Atlantic Ocean (Brazilian coast) revealed a high number of specimens of dorvilleids, adding to our knowledge of the family’s biodiversity. A detailed morphological analysis of these organisms has revealed a new genus, Ceciamaralia gen. nov., with two new species. The new genus differs from other Dorvilleidae genera in (i) the robust and enlarged pharynx which are frequently everted, (ii) unique composition of maxillae, with an elongated pair of serrated basal plates and one pair of anterior free maxillary plates with a long and thin anterior spine and (iii) ventral cirri present only in few first chaetigers. Ceciamaralia lanai gen. et sp. nov. is characterized by the presence of a broad and large dorsal cirrus on a few anterior parapodia and by furcate chaeta in supra-acicular fascicles. While Ceciamaralia nonatoi gen. et sp. nov. presents one geniculate chaeta instead of one furcate, the absence of dorsal cirri and, in some specimens, the absence of palps. A cladistic analysis supported the monophyly of Ceciamaralia gen. nov. by four synapomorphies related to the unique morphology of its maxillae, pharynx and appendages. This study is part of several recent taxonomic studies aiming to elucidate and increase the knowledge of Dorvilleidae, since it is part of a Ph.D project focused on the family.

A hidroxiureia (HU) é usada para aumentar os níveis de hemoglobina fetal, reduzindo complicações como vasoclusão, hemólise e inflamação na anemia falciforme (AF). No entanto, a HU interfere na função das células-tronco e progenitoras hematopoéticas (CTPHs), o que pode limitar o sucesso de transplantes e terapias gênicas curativas. Considerando a falta de estudos na caracterização detalhada das CTPHs na AF, este estudo investigou a integridade imunofenotípica das CTPHs circulantes em pacientes com AF tratados (HU = 10) ou não tratados com HU (CT = 7), e analisou a diferenciação e proliferação das colônias de CTPHs em outros 5 pacientes com AF (HU = 3 e CT = 2). Para isso, as células mononucleares do sangue periférico (PBMC) de pacientes e doadores saudáveis (DS, n = 5) foram isoladas e analisadas por citometria de fluxo usando um painel de anticorpos específico para CTPHs, mais as moléculas CD49d e CD235a. Para cultura, 60 células foram selecionadas a partir da gate de CD34: sorting single cell, em uma placa de 96 poços e 1,7 x 103 por sorting convencional, em uma placa de 24 poços, numa densidade de 210 células por poço. A proliferação, perfil de diferenciação, e intensidade média de fluorescência foram avaliadas ao fim de 20 dias de incubação. A análise estatística foi realizada com o teste de Kruskal-Wallis e o teste de Dunn (p < 0.05). Observou-se que a contagem total de células viáveis CD34+ é maior nos pacientes com AF, com o grupo tratado com HU apresentando a maior mediana. As células CD34+CD49d+ são mais numerosas nos grupos HU e CT em comparação com os DS. No compartimento de células tronco multipotentes (CTM), diferenças significativas na contagem de células foram encontradas entre os pacientes tratados com HU e os DS (p < 0.01). As CTMs CD49d+ são mais frequentes no grupo CT, enquanto as CD235a+ são mais prevalentes no grupo HU. Em relação às células-tronco hematopoiéticas (CTH), os DS não apresentam essas populações no sangue periférico, indicando que a presença delas é característica da AF. A mediana de células CTHs positivas para CD49d e CD235a também é maior nos grupos HU e CT em comparação com os DS. No estudo de colônias, foi observado uma quantidade maior de colônias brancas do tipo granulócito-macrófago (CFU-GM) no grupo HU quando comparada ao grupo CT (ns), que apresenta uma prevalência de colônias vermelhas, como unidades formadoras de colônia-eritroide (CFU-E) e unidades formadoras de erupções (BFU-E) (ns). A presença do marcador de adesão celular e cinética hematopoiética CD49d, em CTHs circulantes sugere uma hematopoiese ineficaz, visto que a expressão normal dessa molécula se dá na medula óssea. A coexpressão de CD235a e CD34 indica uma diferenciação celular acelerada, já que esse receptor é presente em progenitores já comprometidos com a linhagem eritroide. A HU também deve influenciar na proliferação e diferenciação das colônias, dado que nesse grupo houve um aumento no número de colônias brancas, uma provável resposta celular para o caráter citotóxico da droga. Esses resultados revelam uma heterogeneidade imunofenotípica nas CTPHs dos pacientes com AF e uma contribuição significativa da HU para essas alterações. Parte das células envolvidas na hematopoiese desses pacientes demonstra comprometimento da sua função, o que pode afetar a eficácia das CTHs na terapia gênica. Financiamento: FUNDHERP, CTC/FAPESP (2013/08135-2), FAPESP (2022/09643-0), INCTC/CNPq (465539/2014-9).

PDA, the most frequent and aggressive subtype of pancreatic cancer, has a stroma-rich TME (̃80% of tumor mass). The characteristically hypoxic TME orchestrates an extensive metabolic reprogramming in immune, stromal and tumor cells, inducing epithelial-mesenchymal transition (EMT), promoting migration to regions better perfused and establishing physical and functional barriers that limit infiltration and affect the distribution and function of immune cells, resulting in a typically immuno-excluded profile associated with resistance to immunotherapies. Here, we sought to establish a 3D spheroid model of PDA's TME to dynamically evaluate spatial distribution of stromal and tumor cells, to phenotypically characterize the distribution of infiltrating immune cells and the contribution of hypoxia to these aspects. To this end, spheroids were generated with fluorescently-labeled cells from PDA (CAPAN-1) and stromal (HS-5) lines. The spatial distribution was evaluated at different times by automated quantitative microscopy (24h, 48h and 72h) or flow cytometry (72h). Fluorescently-labeled blood mononuclear cells (PBMCs) from healthy donors, activated or not with Ionomycin and PMA, were plated together with unlabeled tumor and stromal cells to incorporate into forming spheroids, or after their formation (24h post-plating) for infiltration evaluation. After 48h, the spheroids were enzymatically dissociated and T-cells were immunophenotyped by flow cytometry with CD4, CD8 and CD25 antibodies. The Image-iT Green Hypoxia reagent was used to fluorescently label the cells in the spheroid core hypoxic compartment. After 24h of plating, tumor and stromal cells were well distributed in the formed spheroid; however, after 48h and 72h, tumor cells migrated to spheroid periphery. In agreement, cytometry revealed higher proportion of tumor cells occupied the normoxic compartment, while the hypoxic compartment was enriched for stromal cells. Immunophenotyping showed a enrichment of CD4+ cells (̃70-90%) in relation to CD8+ cells (̃10-30%) in the hypoxic compartment in all experimental conditions. Of note, the CD8+ cells percentage in the hypoxic region was higher in conditions in which PBMCs were activated (̃20-30%), compared to non-activated (̃10%). In turn, normoxic regions had similar proportions of both populations (̃50% of each) in conditions with activated PBMCs, while with non-activated PBMCs a higher CD4+ cells (70%) proportion was observed. For activated PBMCs, in both conditions, we found higher CD25+ cells percentage among the CD4+ and CD8+ populations in the hypoxic compartment (̃90%), compared to normoxic compartment (̃60%). However, for PBMCs infiltrating spheroids already formed, there was a greater activation of lymphocytes, resulting in the presence of CD4+CD25High cells, with a supposedly regulatory profile (Tregs), enriched especially in the hypoxic compartment (̃9%). We successfully developed an experimental approach that allowed us to quantitatively and qualitatively characterize how the spatial distribution of tumor, stromal, and immune cells are affected by the hypoxia in the TME of a PDA model. Our in vitro approach may help to systematize the evaluation of new therapeutic approaches.

We propose a new point-prediction model, the DEep Learning WAVe Emulating model (DELWAVE), which successfully emulates the behaviour of a numerical surface ocean wave model (Simulating WAves Nearshore, SWAN) at a sparse set of locations, thus enabling numerically cheap large-ensemble prediction over synoptic to climate timescales. DELWAVE was trained on COSMO-CLM (Climate Limited-area Model) and SWAN input data during the period of 1971–1998, tested during 1998–2000, and cross-evaluated over the far-future climate time window of 2071–2100. It is constructed from a convolutional atmospheric encoder block, followed by a temporal collapse block and, finally, a regression block. DELWAVE reproduces SWAN model significant wave heights with a mean absolute error (MAE) of between 5 and 10 cm, mean wave directions with a MAE of 10–25°, and a mean wave period with a MAE of 0.2 s. DELWAVE is able to accurately emulate multi-modal mean wave direction distributions related to dominant wind regimes in the basin. We use wave power analysis from linearised wave theory to explain prediction errors in the long-period limit during southeasterly conditions. We present a storm analysis of DELWAVE, employing threshold-based metrics of precision and recall to show that DELWAVE reaches a very high score (both metrics over 95 %) of storm detection. SWAN and DELWAVE time series are compared to each other in the end-of-century scenario (2071–2100) and compared to the control conditions in the 1971–2000 period. Good agreement between DELWAVE and SWAN is found when considering climatological statistics, with a small (≤ 5 %), though systematic, underestimate of 99th-percentile values. Compared to control climatology over all wind directions, the mismatch between DELWAVE and SWAN is generally small compared to the difference between scenario and control conditions, suggesting that the noise introduced by surrogate modelling is substantially weaker than the climate change signal.

A vegetação confere beleza à paisagem urbana e pode trazer benefícios para o conforto térmico e bem-estar das pessoas em regiões onde a temperatura é elevada. Este estudo se desenvolve no Centro Histórico de Cuiabá/MT, região de clima tropical continental, tombado em nível nacional e cuja configuração urbana se caracteriza por ruas e calçadas estreitas, o que limita a adoção de vegetação arbórea. Esta pesquisa objetiva avaliar os impactos no microclima e no conforto térmico dos pedestres decorrentes da simulação de implantação de vegetação arbórea na região do Centro Histórico de Cuiabá/MT. Empregou-se uma abordagem baseada em simulações computacionais utilizando o software ENVI-met, no qual a região foi modelada com a atual (9%) e com uma taxa de arborização projetada (20%), focando em analisar as variáveis ambientais de temperatura, umidade e velocidade do ar e temperatura radiante, nas calçadas e vias. No cenário projetado com maior quantidade de vegetação arbórea ocorreu elevação na temperatura do ar e redução da umidade relativa do ar no horário mais crítico do dia (14h). Por sua vez, devido ao efeito de reflexão e sombreamento proporcionado pelas folhas das copas, houve redução da temperatura média radiante e na velocidade do ar. Como consequência, o impacto na sensação térmica se deu mais sob as copas e com pouca extensividade ao redor dos espécimes arbóreos. Desta forma, um adequado posicionamento e espaçamento da arborização nas vias devem ser considerados ao se pensar a ambiência térmica dos pedestres dentro do centro histórico. Diante dos achados, aponta-se para debate sobre a perda da arborização existente nos espaços públicos e privados, a reflorestação e a conservação do patrimônio no perímetro de tombamento, cujas temáticas se caracterizam por serem inerentemente interligadas, devendo assim serem abordadas de forma coletiva.

In science, technology and assistance to smallholder farming or large crop acreages of Stevia rebaudiana is necessary to report data using information components to facilitate investors to understand the local field conditions to make assertive economic decisions for long periods. Stevia rebaudiana produces consistent natural sweeteners with safe performance as reported in a multitude of scientific publications. The leaf chemicals components are suitable to humans with healthy disorders affected by the consumption of sugarcane or many other industrial sweeteners. Otherwise, aspects related to the agriculture of sweeteners production still require additional discussion to improve qualitative and quantitative traits necessary for cultivating cost-effective crops. The current text highlighted some agriculture decisions necessary to make the crop more profitable to investors as researchers, agriculture influencers, farmer assistants and consultants of companies looking for alternatives within agro-ecological systems.

ABSTRACT: This trial was conducted to evaluate the effects of replacing soybean meal with microalgae meal (MM; Arthrospira spp.) during grower and finisher phases on productive performance, footpad dermatitis (FPD) occurrence, breast meat quality, amino acid digestibility and plasma metabolomics profile of broiler chickens. One thousand day-old Ross 308 male chicks were divided into 5 experimental groups (8 replicates, 25 birds/each): CON, fed a commercial soybean-based diet throughout the trial (0–41 d); F3 and F6, fed the CON diet up to 28 d of age and then a finisher diet (29–41 d) with either 30 or 60 g MM/kg, respectively; and GF3 and GF6, receiving CON diet until 14 d and then diets containing 30 or 60 g MM/kg from 15 to 41 d, respectively. All diets were iso-energetic and with a similar amino acid profile. Growth performances were recorded on a pen basis at the end of each feeding phase and apparent ileal amino acid digestibility was determined at 41 d. Footpad dermatitis occurrence was assessed on all processed birds, while breast and plasma samples were collected for meat quality and metabolomics analysis (proton nuclear magnetic resonance - 1H-NMR). At 41 d, CON group showed higher body weight than F6 and GF6 ones (2,541 vs. 2,412 vs. 2,384 g, respectively; P < 0.05). Overall, GF6 group exhibited the highest feed conversion ratio, while F3 did not present significant differences compared to CON (1.785 vs. 1.810 vs. 1.934 g feed/g gain, respectively for CON, F3 and GF6; P < 0.01). The occurrence and the risk of developing FPD were similar among groups. MM administration increased breast meat yellowness and reduced amino acid digestibility (P < 0.001). The 1H-NMR analysis revealed variations in the levels of some circulating metabolites, including histidine, arginine and creatine, which play important metabolic roles. Overall, these findings can contribute to expand the knowledge about the use of Arthrospira spp. as protein source in broiler diets.

This paper introduces a novel control strategy for multifunctional grid-tied inverters in industrial/commercial power systems, aiming to address the compensation of instantaneous power oscillations. The proposed strategy is derived from the Conservative Power Theory, which offers the ability to extract and analyze oscillating power terms directly in the abc frame. To demonstrate the efficacy of the proposed strategy, simulation results are presented, considering a scenario with a three-phase multi-functional grid-tied inverter with an LCL filter operating in a laboratory scale prototype. The power system includes various types of loads, such as linear, non-linear, unbalanced loads and a three-phase induction motor with capacitive compensation. Simulation results show the effectiveness of the proposed strategy in coping with the active power dispatch provided by the inverter, concomitantly ensuring that the induction motor operates with constant torque, as well as that the industrial/commercial electric system operates with improved power quality. Furthermore, the proposed strategy is also validated by means of experimental results obtained from a 3.6 kVA inverter prototype. The experimental findings affirm that the compensation of the targeted oscillating power terms is successfully achieved. Such a validation underscores the practical viability of applying the proposed strategy to real-world scenarios.

The recent fast development of the microalgae-related biotechnologies has enabled the availability of sustainable and nutrients-rich raw materials to be used as substitution of conventional sources in aquafeed formulation. However the cost of energy of the photobioreactors used to produce these microorganisms still constrained their wider inclusion into aquafeed compounds. By exploiting industrial waste outputs, Nannochloropsis sp. and Spirulina sp. were produced and utilised to formulate two experimental enrichments (LM1 and LM2). During a 60 days trial, their efficacy have been tested as Artemia metanauplii enrichments in the diet of European seabass (Dicentrarchus labrax) larvae, in comparison to a commercial control. Larvae were fed with isonitrogenous and isolipidic dietary treatments. Each dietary treatment presented a specific profile for the long chain polyunsaturated fatty acids ARA, DHA and EPA. Ratio of DHA/EPA in enriched Artemia of 4:1 as in the case of LM1 and LM2 in the presence of 1.4% of ARA (as a % on total fatty acid) guaranteed equal results to the control which displayed a ratio of DHA/EPA of 2:1 with 2.2% of ARA. No significant effects of the dietary treatments were detected in final survival, growth performance and incidence of skeletal anomalies. Regarding oxidative status, larvae fed with LM2 enrichment presented lower catalase activity than control larvae with no signs of oxidative damage, suggesting a potential antioxidant effect of LM2. The present study contributes to expanding the existing literature on successful utilisation of microalgae and cyanobacteria, used to produce valuable nutrients, in a perspective of circular nutrients economy.

The ability to encode different operations into a single miniaturized optical device is required to reduce the complexity and size of optical paths for light manipulation, which usually employs dynamic optical components, interferometric setups, and/or multiple bulky elements in cascade. A very efficient solution is provided by metalenses, which are flat optical elements able to generate and manipulate structured light beams in a compact and efficient way, offering a powerful and attractive tool in many fields, such as life science and telecommunications. In this work, we present the design and test of transmission dielectric bi-functional metalenses that exploit both the dynamic and the geometric phases, to enable the spin-controlled manipulation of different focused orbital angular momentum (OAM) beams, depending on the circularly polarized state in input. In detail, we provide numerical algorithms for the design and simulation of the meta-optics in the telecom infrared, the fabrication processes, and the optical characterization under different impinging polarized optical vortices. This solution provides new integrated flat optics for applications in imaging, optical tweezing and trapping, optical computation, and high-capacity telecommunication and encryption.

A re-analysis of the morphological phylogeny of the Nopinae is made, based on an update in the description of Aamunops Galán-Sánchez & Álvarez-Padilla, 2022 and the addition of the recently described genera Nopsma Sánchez-Ruiz, Brescovit & Bonaldo, 2020 and Roddemberryus Sánchez-Ruiz & Bonaldo, 2023. Two new species, Aamunops hoof sp. nov. (male) and Aamunops yiselae sp. nov. (male and female), are also described, which allows a better understanding of the genus morphology and resulted in an emended diagnosis. The description of Aamunops has been updated to include several characteristics of the ultrastructural morphology, legs, chelicerae, palps and female genitalia. The inclusion of these new characters of Aamunops along with those of Nopsma and Roddemberryus in the previous data matrix resulted in a new, completely different hypothesis of the relationships of the nopine genera: Nopsma is part of a group formed by Cubanops and Nyetnops, while Aamunops and Roddemberryus are grouped with representatives of Tarsonops. The four-eyed Nopsides ceralbonus Chamberlin, 1924 was recovered as the most basal species of Nopinae. The relationships among genera of Nopinae and the phylogenetic position of three species, whose taxonomic position is doubtful (Cubanops luquillo Sánchez-Ruiz, Brescovit & Alayón, 2015, Orthonops confuso Galán-Sánchez & Álvarez-Padilla, 2022 and Tarsonops irataylori Bond & Taylor, 2013), is also discussed.

Abstract Background The clam Chamelea gallina is an ecologically and economically important marine species in the Northwestern Adriatic Sea, which currently suffers from occasional, and still unexplained, widespread mortality events. In order to provide some glimpses in this direction, this study explores the connections between microbiome variations at the clam-sediment interface and the nutritional status of clams collected at four Italian production sites along the Emilia Romagna coast, with different mortality incidence, higher in the Northern sites and lower in the Southern sites. Results According to our findings, each production site showed a peculiar microbiome arrangement at the clam-sediment interface, with features that clearly differentiate the Northern and Southern sites, with the latter also being associated with a better nutritional status of the animal. Interestingly, the C. gallina digestive gland microbiome from the Southern sites was enriched in some health-promoting microbiome components, capable of supplying the host with essential nutrients and defensive molecules. Furthermore, in experiments conducted under controlled conditions in aquaria, we provided preliminary evidence of the prebiotic action of sediments from the Southern sites, allowing to boost the acquisition of previously identified health-promoting components of the digestive gland microbiome by clams from the Northern sites. Conclusions Taken together, our findings may help define innovative microbiome-based management strategies for the preservation of the productivity of C. gallina clams in the Adriatic Sea, through the identification and maintenance of a probiotic niche at the animal-sediment interface.

Perfect vortices, whose ring profile is independent of the topological charge, play a key role in telecommunications and particle micro-manipulation. In this work, we report the compact generation of a new kind of double-ring perfect vortices, called double-ring perfect vector beams, by exploiting dual-functional silicon metaoptics. In particular, we develop and test a new paradigm to generate those beams with the possibility of selecting different topological charges between the two rings. The generated beams are characterized through a filtering method, proving that the two rings have a vectorial nature with the same magnitude and either the same or different topological charges. Their unique properties suggest promising applications for optical tweezing and manipulation of low refractive-index particles, trapping of cold atoms, and high-capacity communications.

Six scorpion species were recorded using pitfalltraps with drift-fences in the Amazonian terrafirme forest of Estação Científica Ferreira Penna,Floresta Nacional de Caxiuanã, Melgaço, Pará,Brazil, during four expeditions in 2003: Brotheassp. (relative abundance 0.6); Broteochactasparvulus Pocock, 1897 (0.22), Tityus paraensisKraepelin, 1896 (0.06); Tityus silvestris Pocock,1897 (0.04); Ananteris balzanii Thorell, 1891(0.04) and Tityus strandi Werner, 1939 (0.02).Abundance in the non-flooded forest is higherthan the flooded forest probably due to theavailability of dry shelters. Five new records arepresented for the Juruti Plateau, Pará: buthidsTityus metuendus Pocock, 1897, T. silvestrisPocock, 1897, T. strandi Werner, 1939; chactidsBrotheas overali Lourenço, 1988, andBroteochactas parvulus Pocock, 1897.

Increasing sea levels and water temperatures have been detected at several coastal locations worldwide with severe consequences on the communities and ecosystems. Coastal lagoons are particularly vulnerable to such changes due to their low land elevation and limited connections with the open sea. Here the recent and future climatic changes in the Lagoon of Venice (Italy) are investigated using in-situ observations and high-resolution hydrodynamic modeling. Trend analysis was applied to observed time series of meteorological and oceanographic climate essential variables to identify significant long-term changes in mean and extreme values. The mean relative sea level rose at a rate of 4.9 mm per year in Venice due to the combined action of eustacy and subsidence while air and sea temperatures increased on average by 1.8 and 1.1°C in 30 years, respectively. These rates, as well as climate projections, were used following a pseudo-global-warming approach to investigate the near future (up to 2050) evolution of the lagoon's dynamics focusing on sea level and temperature extremes. The lagoon will amplify the temperature changes expected for the Adriatic Sea, especially in the shallow tidal flats where the intensity of the marine heat waves will be more than four times larger than that in the open sea. Moreover, the model allowed us to perform “what-if” scenarios to explore to which extent the flood protection MoSE barriers will modify the lagoon's dynamics. According to the simulations, the number of floods and therefore of the MoSE closure strongly increases with sea level rise. In the most severe scenario, MoSE will have to close for more than 20% of the time in October, November, and December resulting in the reduction of water exchange with the open sea and exacerbation of marine cold spells. Some considerations on the implications of the expected changes on the lagoon's ecology are proposed.

Abstract The availability of static tiny optical devices is mandatory to reduce the complexity of optical paths that typically use dynamic optical components and/or many standard elements for the generation of complex states of light, leading to unprecedented levels of miniaturization and compactness of optical systems. In particular, the design of flat and integrated optical elements capable of multiple vector beams generation with high resolution in the visible and infrared range is very attractive in many fields, from life science to information and communication technology. In this regard, we propose dual-functional transmission dielectric metalenses that act simultaneously on the dynamic and geometric phases in order to manipulate independently right-handed and left-handed circularly polarized states of light and generate focused vector beams in a compact and versatile way. In the specific, starting from the mathematical fundamentals for the compact generation of vector beams using dual-functional optical elements, we provide the numerical algorithms for the computation of metaoptics and apply those techniques to the design and fabrication of silicon metalenses which are able to generate and focus different vector beams in the telecom infrared, depending on the linear polarization state in input. This approach provides new integrated optics for applications in the fields of high-resolution microscopy, optical manipulation, and optical communications, both in the classical and single-photon regimes.

Abstract COVID-19 vaccines have dramatically reduced rates of severe infection requiring hospitalization. However, SARS-CoV-2 variants have reduced vaccine effectiveness at preventing any symptomatic infection. This real-world study analyzed binding and neutralizing antibodies generated after complete vaccination and boosting across three vaccine platforms. Binding antibodies decayed most slowly in people under 60 with hybrid immunity. Neutralizing antibodies against Omicron BA.1 were reduced compared to other variants. The anamnestic anti-spike IgG response to the first boost was more pronounced than after the second boost. Monitoring of the effects of SARS-CoV-2 mutations on disease severity and the effectiveness of therapeutics is warranted.

Abstract Background AMBRA1 is an intrinsically disordered protein, working as a scaffold molecule to coordinate, by protein-protein interaction, many cellular processes, including autophagy, mitophagy, apoptosis and cell cycle progression. The zebrafish genome contains two ambra1 paralogous genes (a and b), both involved in development and expressed at high levels in the gonads. Characterization of the zebrafish paralogous genes mutant lines generated by CRISPR/Cas9 approach showed that ambra1b knockout leads to an all-male population. Results We demonstrated that the silencing of the ambra1b gene determines a reduction of primordial germ cells (PGCs), a condition that, in the zebrafish, leads to the development of all-male progeny. PGC reduction was confirmed by knockdown experiments and rescued by injection of ambra1b and human AMBRA1 mRNAs, but not ambra1a mRNA. Moreover, PGC loss was not rescued by injection with human AMBRA1 mRNA mutated in the CUL4-DDB1 binding region, thus suggesting that interaction with this complex is involved in PGC protection from loss. Results from zebrafish embryos injected with murine Stat3 mRNA and stat3 morpholino suggest that Ambra1b could indirectly regulate this protein through CUL4-DDB1 interaction. According to this, Ambra1 +/− mice showed a reduced Stat3 expression in the ovary together with a low number of antral follicles and an increase of atretic follicles, indicating a function of Ambra1 in the ovary of mammals as well. Moreover, in agreement with the high expression of these genes in the testis and ovary, we found significant impairment of the reproductive process and pathological alterations, including tumors, mainly limited to the gonads. Conclusions By exploiting ambra1a and ambra1b knockout zebrafish lines, we prove the sub-functionalization between the two paralogous zebrafish genes and uncover a novel function of Ambra1 in the protection from excessive PGC loss, which seems to require binding with the CUL4-DDB1 complex. Both genes seem to play a role in the regulation of reproductive physiology.

Resumo Este artigo analisa sistemas de inteligência artificial como agentes temporalizadores em uma história mais do que humana. Engaja-se em uma discussão interdisciplinar abrangendo a sociologia dos algoritmos, a ética informacional e a filosofia da mente para, com base na teoria da história, avaliar como a onipresença da automação adiciona novas dimensões ao estudo da condição histórica contemporânea. O argumento diz que a temporalização artificial se origina da simulação da linguagem natural por meio de algoritmos de aprendizado. O artigo esclarece isso através de uma descrição em código e uma demonstração em imagem técnica, ilustrando a 'renderização' ou 'digitalização' de experiências humanas em padrões de dados, posteriormente replicados ou atualizados por agentes artificiais. Esse processo destaca a vetorização e manipulação estatística da experiência e representa o que denomino "computação necessária". Em contraste, o texto sugere que uma "computação contingente", capaz de produzir algo novo, transcende o mero discurso técnico. Assim, enfatiza-se o papel da ética e transparência na gestão de dados e no treinamento de sistemas de IA, cruciais para compreender a Inteligência Artificial como um campo histórico aberto a formas cognitivas potencialmente não-humanas.

No Brasil, o estado de Mato Grosso é o principal produtor de soja, sua produção colabora com cerca de 29% da produção nacional. A produtividade das plantas de soja está relacionada, dentre outras atividades, com o manejo correto de doenças, essa eficiência no manejo fúngico ocorre principalmente quando se tem conhecimento das características do microrganismo alvo. Portanto, o objetivo deste trabalho foi avaliar a sensibilidade de Colletotrichum plurivorum e Colletotrichum truncatum a fungicidas disponíveis no mercado. Foram realizados ensaios em placas de Petri, com os fungicidas homogeneizados em meio de cultura batata-dextrose-ágar (BDA) e posterior incubação em incubadora com Demanda Bioquímica de Oxigênio (BOD). Avaliou-se o crescimento micelial diariamente, esporulação e germinação de esporos. Os ensaios comprovaram que C. plurivorum e C. truncatum possuem sensibilidade diferente aos ingredientes ativos estudados, sendo que C. plurivorum apresenta maior sensibilidade aos produtos. O fungicida Mancozebe e a associação Azoxistrobina + Mancozebe + Protioconazol proporcionaram eficiente controle no desenvolvimento de C. truncatum. Os fungicidas Picoxistrobina + Benzovindiflupir e Azoxistrobina + Mancozebe + Protioconazol, promoveram maior eficiência no controle de C. plurivorum.

Introdução: Sabe-se que o programa de Stewardship é uma importante ferramenta para manejar a resistência bacteriana e sua principal estratégia é tratar o paciente com o antimicrobiano (ATM) certo, na dose certa e no tempo certo. Entre os profissionais atuantes no Stewardship, cabe ao farmacêutico clínico avaliar a prescrição médica, acompanhar os exames laboratoriais e protocolos institucionais e realizar intervenções relacionadas ao uso de medicamentos. Objetivo: Identificar as intervenções realizadas pelo farmacêutico relacionadas ao uso de ATM em prescrições de pacientes adultos de um hospital de nível terciário de Londrina no ano de 2022, categorizando as intervenções e demonstrar o papel do farmacêutico no programa de Stewardship. Métodos: Estudo realizado em um hospital de nível terciário, as intervenções farmacêuticas relacionadas a ATM realizadas no período de 2022, foram classificadas conforme a ferramenta PRAT (identificação do problema relacionado a terapia antimicrobiana) baseada na classificação de problemas relacionados a medicamentos, sendo categorizadas como intervenções relacionadas a indicação, efetividade ou segurança. Resultados: Foram avaliadas 22069 prescrições e realizadas 1843 intervenções farmacêuticas relacionadas aos ATM, sendo 45% relacionadas à segurança (potencial de reação adversa ou toxicidade), 38% à efetividade (questionamento do efeito terapêutico antiinfecioso), 10% à indicação (necessidade ou não do antimicrobiano ou à indicação ou não do uso de acordo com parâmetros clínicos e laboratoriais) e 7% que não se enquadram nas categorias anteriores. As principais intervenções realizadas foram referentes às interações medicamento-medicamento (31%), sendo realizado o reaprazamento dos medicamentos para resolução do problema. A dose prescrita está relacionada a 24% dos problemas encontrados, sendo realizado o ajuste da dose como intervenção, seguido por prescrição de medicamento desnecessário (11%), sendo sugerido então a suspensão do ATM. Problemas relacionados a frequência, intervalo de administração, são de 8% e problemas relacionados a administração do medicamento são 7%. Conclusão: Evidenciou-se que a análise criteriosa da prescrição pelo farmacêutico clínico e suas intervenções são fundamentais para garantir a segurança do paciente e para a efetividade do seu tratamento, contribuindo então para o uso racional de ATM que, redução da resistência bacteriana, o principal objetivo de um programa de Stewardship.

A hidroxiureia (HU) é um medicamento que aumenta os níveis de hemoglobina fetal nos eritrócitos, diminuindo complicações clínicas como vasoclusão, hemólise e inflamação sistêmica associadas à anemia falciforme (AF). Contudo, a HU interfere em aspectos essenciais do nicho hematopoiético, como a proliferação, a renovação e a diferenciação das células-tronco e progenitoras hematopoéticas (CTPHs). Isso limita as perspectivas de sucesso em procedimentos como o transplante de células-tronco e a terapia gênica, que são as únicas abordagens terapêuticas curativas. Considerando a falta de estudos na caracterização detalhada das CTPHs na AF, este estudo avaliou a integridade imunofenotípica das populações de CTPHs circulantes em pacientes com AF, tratados (HU, n = 10) ou não (CT, n = 7) com HU. Para tanto, as células mononucleares do sangue periférico (PBMC) de pacientes e doadores saudáveis (HD, n = 5) foram isoladas por gradiente de densidade e avaliadas por citometria de fluxo, utilizando um painel de anticorpos específico para CTPHs, além das moléculas CD49d e CD235a. A análise estatística foi conduzida por meio do teste de Kruskal-Wallis e do teste de comparações múltiplas de Dunn (p < 0.05). A contagem total de células viáveis CD34 é maior nos grupos com AF, sendo que o grupo HU apresentou a maior mediana. Os níveis de células CD34CD49d são maiores entre os pacientes dos grupos CT e HU. No que diz respeito ao compartimento de progenitores hematopoiéticos multipotentes (HMC), também foram observadas diferenças significativas na contagem total entre pacientes tratados com HU e controles (p < 0.01). As HMCs positivas para CD49d são mais frequentes no grupo CT, enquanto CD235a é mais presente no grupo HU. Ao analisar especificamente as células-tronco hematopoiéticas (HSC), observou-se que, diferentemente dos pacientes, os indivíduos controle não apresentam essas populações no sangue periférico, indicando que a presença dessas células na circulação é uma característica inerente à AF. Além disso, a mediana da quantidade de células HSCs positivas para CD49d e CD235a também é maior nos grupos CT e HU do que no grupo HD. Tendo em vista que o CD49d é um marcador de adesão e cinética hematopoiética, sua presença em maior quantidade nas células-tronco indica uma hematopoiese possivelmente ineficaz. Já a presença do CD235a junto ao marcador CD34 está relacionada com uma diferenciação celular acelerada. Esses achados evidenciam uma heterogeneidade imunofenotípica nas CTPHs nos indivíduos com AF e, principalmente, uma contribuição da HU para essas alterações. Além disso, mostram que parte das células envolvidas na hematopoiese desses indivíduos pode estar comprometida e, portanto, inadequada para terapias que envolvam edição gênica. Nas próximas etapas, ensaios para avaliação da capacidade de proliferação e diferenciação in vitro dessas populações e grupos de pacientes deverão ser executados para testar a funcionalidade das células sob a influência da HU. Financiamento: FUNDHERP, CTC/FAPESP (2013/08135-2), FAPESP (2022/09643-0), INCTC/CNPq (465539/2014-9).

Introduction: Hydroxyurea, the 1st line treatment for SCD, induces HbF, inhibiting polymerization of mutant HbS and cell sickling. However, laboratory tests that assess HbF induction do not quantify the % of effectively protected RBCs (%pRBC), i.e. those with HbF content (cHbF)>10 pg/RBC. While chromatography (HPLC) determines the HbF% among blood Hb (HbF%), classical flow cytometry (cFC) provides the % HbF+ RBCs (Fcell%), including RBCs with very little HbF. We have developed an unprecedented method of quantitative CF (qFC) that uses an internal cellular control, composed of samples of umbilical cord blood (UCB) and adult blood with known mean HbF contents (MCHbF), allowing the distribution of cHbF/RBC in the population is determined, including the %pRBC. Aim: Validate the method and demonstrate its potential clinical application in SCD. Methods: The MCHbF of 9 UCB samples were pre-calculated, multiplying the HbF% by the respective MCH obtained with a hematological analyzer, and compared with the MCHbF derived by qFC, in order to evaluate the correlation and linearity of the method. A total of 40 samples from 29 SCD (SS) patients had their hematimetric indices and %pRBC determined. From these, %Fcell (n = 27) and HbF% (n = 15) were obtained, totaling 12 samples characterized by all methods, which were evaluated for correlation between themselves and with hematimetric data. Hb10% had %Fcell>99%. In contrast, %pRBC correlated strongly and linearly across all HbF% (r = 0.89, p < 0.0001). In line, both HbF% and %pRBC showed significant positive correlations with RBC counts, Hb, and hematocrit (Hct); and negative correlations with the % reticulocytes (%Ret) and Red Cell Distribution Width (RDW). However, %Fcell correlated only with Hct. Considering all 27 samples evaluated, %Fcell correlated further only with Hb and RDW; however, %pRBC was further correlated positively with MCHC, and negatively with WB cells, Ret No, and % immature Ret. Correlations improved for all 40 samples. The potential of %pRBC to predict high-risk patients was much higher (AUC=0.969, p < 0.0001) than that of %Fcell (AUC=0.873, p = 0.0019), with a sensitivity of 94.4% and a specificity of 88.9%, for %pRBC