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José Angelo Lauletta Lindoso,1 Jackson Maurício Lopes Costa,2 Igor Thiago Queiroz,3 Hiro Goto41Instituto de Infectologia Emilio Ribas-SES- SP, São Paulo, São Paulo, Brazil; 2Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil; 3Departament of Infectious Diseases, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Sao Paulo, Brazil; 4Instituto de Medicina Tropical de São Paulo, and Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Sao Paulo, BrazilAbstract: Leishmaniases are vector-borne zoonotic diseases that are prevalent in tropical and subtropical areas in the world, with two million new cases occurring yearly. Visceral and tegumentary forms of leishmaniasis are known. The latter form may present as localized cutaneous or mucosal forms, disseminated, diffuse forms, or leishmaniasis recidiva cutis. Visceral leishmaniasis is caused by parasites of the species Leishmania (Leishmania) donovani and L. (L.) infantum, and tegumentary leishmaniasis is caused by 15 other species, with distinct distributions in the Old and New World. The varied clinical manifestations, the multitude of Leishmania species, and the increasing incidence of HIV coinfection make the diagnosis and treatment of leishmaniases complex. Since there are no solid data relating clinical manifestations, treatment outcomes and Leishmania species the decision regarding the best therapeutic option is almost entirely based on clinical manifestations. Because most of the literature is focused on leishmaniasis in the Old World, in this review we present data on the treatment of New World leishmaniasis in more detail. Ranked therapeutic options, clinical trials, and also observations, even with a restricted number of subjects, on treatment outcome of visceral and different forms of tegumentary leishmaniasis, are presented. Treatment for leishmaniasis in HIV-coinfected patients is addressed as well. Some of these data strongly suggest that the differences in the outcome of the treatment are related to the Leishmania species. Therefore, although it is not possible at most points of care to identify the species causing the infection – a process that requires a well equipped laboratory – the infecting species should be identified whenever possible. More recent approaches, such as the use of immunomodulators and immunotherapy, and the lines for development of new candidate drugs are mentioned.Keywords: tegumentary, visceral, therapy, HIV

Abemaciclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor used for hormone-receptor-positive and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer, can lead to elevated serum creatinine without implications on the true renal function. Although clinical trials have shown no increase in other kidney function biomarkers, this may still represent a challenge in cancer patients. We report a case of a 74-year-old female who presented with creatinine and cystatin-C elevation during treatment with abemaciclib without an equivalent decrease in measured glomerular filtration rate (GFR) with renal scintigraphy. The confirmation of adequate kidney function allowed for the maintenance of treatments that would otherwise be limited by renal impairment. Healthcare providers should be aware of abemaciclib's effect on serum creatinine but should not eliminate the possibility of actual kidney injury. Alternative biomarkers for GFR assessment are recommended, although the usefulness of cystatin-C in patients receiving abemaciclib should be investigated in greater depth., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ferreira et al.)

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats., Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1-PND5). The offspring were evaluated at PND45., Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status., Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life.

Species phenology - the timing of key life events - is being altered by ongoing climate changes with yet underappreciated consequences for ecosystem stability. While flowering is generally occurring earlier, we know much less about other key processes such as the time of fruit ripening, largely due to the lack of comprehensive long-term datasets. Here we provide information on the exact date and site where seeds of 4,462 taxa were collected for the Index Seminum (seed exchange catalogue) of the Botanic Garden of the University of Coimbra, between 1926 and 2013. Seeds were collected from spontaneous and cultivated individuals across Portugal, including both native and introduced taxa. The database consists of 127,747 curated records with information on the species, or infraspecific taxa (including authority), and the day and site where seeds were collected. All records are georeferenced and provided with a confidence interval for the collection site. Taxonomy was first curated manually by in-house botanists and then harmonized according to the GBIF backbone taxonomy., (© 2024. The Author(s).)

Global water demand and environmental concerns related to climate change require industries to develop high-efficiency wastewater treatment methods to remove pollutants. Likewise, toxic pollutants present in wastewater negatively affect the environment and human health, requiring effective treatment. Although conventional treatment processes remove carbon and nutrients, they are insufficient to remove pharmaceuticals, pesticides, and plasticizers. Electrochemical processes effectively remove pollutants from wastewater through the mineralization of non-biodegradable pollutants with consequent conversion into biodegradable compounds. Its advantages include easy operation, versatility, and short reaction time. In this way, this review initially provides a global water scenario with a view to the future. It comprises global demand, treatment methods, and pollution of water resources, addressing various contaminants such as heavy metals, nutrients, organic compounds, and emerging contaminants. Subsequently, the fundamentals of electrochemical treatments are presented as well as electrochemical treatments, highlighting the latest studies involving electrocoagulation, electroflocculation, electroflotation, capacitive deionization and its derivatives, eletrodeionization, and electrochemical advanced oxidation process. Finally, the challenges and perspectives were discussed. In this context, electrochemical processes have proven promising and effective for the treatment of water and wastewater, allowing safe reuse practices and purification with high contaminant removal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background: Acute kidney injury (AKI) is a common complication among cancer patients, often leading to longer hospital stays, discontinuation of cancer treatment, and a poor prognosis. This study aims to provide insight into the incidence of severe AKI in this population and identify the risk factors associated with renal replacement therapy (RRT) and in-hospital mortality., Methods: This retrospective cohort study included 3201 patients with cancer and severe AKI admitted to a Comprehensive Cancer Center between January 1995 and July 2023. Severe AKI was defined according to the KDIGO guidelines as grade ≥ 2 AKI with nephrological in-hospital follow-up. Data were analyzed in two timelines: Period A (1995-2010) and Period B (2011-2023)., Results: A total of 3201 patients (1% of all hospitalized cases) were included, with a mean age of 62.5 ± 17.2 years. Solid tumors represented 75% of all neoplasms, showing an increasing tendency, while hematological cancer decreased. Obstructive AKI declined, whereas the incidence of sepsis-associated, prerenal, and drug-induced AKI increased. Overall, 20% of patients required RRT, and 26.4% died during hospitalization. A predictive model for RRT (AUC 0.833 [95% CI 0.817-0.848]) identified sepsis and hematological cancer as risk factors and prerenal and obstructive AKI as protective factors. A similar model for overall in-hospital mortality (AUC 0.731 [95% CI 0.71-0.752]) revealed invasive mechanical ventilation (IMV), sepsis, and RRT as risk factors and obstructive AKI as a protective factor. The model for hemato-oncological patients' mortality (AUC 0.832 [95% CI 0.803-0.861]) included IMV, sepsis, hematopoietic stem cell transplantation, and drug-induced AKI. Mortality risk point score models were derived from these analyses., Conclusions: This study addresses the demographic and clinical features of cancer patients with severe AKI. The development of predictive models for RRT and in-hospital mortality, along with risk point scores, may play a role in the management of this population.

Fused filament fabrication (FFF) is an extrusion-based additive manufacturing (AM) technology mostly used to produce thermoplastic parts. However, producing metallic or ceramic parts by FFF is also a sintered-based AM process. FFF for metallic parts can be divided into five steps: (1) raw material selection and feedstock mixture (including palletization), (2) filament production (extrusion), (3) production of AM components using the filament extrusion process, (4) debinding, and (5) sintering. These steps are interrelated, where the parameters interact with the others and have a key role in the integrity and quality of the final metallic parts. FFF can produce high-accuracy and complex metallic parts, potentially revolutionizing the manufacturing industry and taking AM components to a new level. In the FFF technology for metallic materials, material compatibility, production quality, and cost-effectiveness are the challenges to overcome to make it more competitive compared to other AM technologies, like the laser processes. This review provides a comprehensive overview of the recent developments in FFF for metallic materials, including the metals and binders used, the challenges faced, potential applications, and the impact of FFF on the manufacturing (prototyping and end parts), design freedom, customization, sustainability, supply chain, among others.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD) is associated with ACADM gene mutations, leading to an impaired function and/or structure of MCAD. Importantly, after import into the mitochondria, MCAD must incorporate a molecule of flavin adenine dinucleotide (FAD) per subunit and assemble into tetramers. However, the effect of MCAD amino acid substitutions on FAD incorporation has not been investigated. Herein, the commonest MCAD variant (p.K304E) and 11 additional rare variants (p.Y48C, p.R55G, p.A88P, p.Y133C, p.A140T, p.D143V, p.G224R, p.L238F, p.V264I, p.Y372N, and p.G377V) were functionally and structurally characterized. Half of the studied variants presented a FAD content <65 % compared to the wild-type. Most of them were recovered as tetramers, except the p.Y372N (mainly as dimers). No correlation was found between the levels of tetramers and FAD content. However, a correlation between FAD content and the cofactor's affinity, proteolytic stability, thermostability, and thermal inactivation was established. We showed that the studied amino acid changes in MCAD may alter the substrate chain-length dependence and the interaction with electron-transferring-flavoprotein (ETF) necessary for a proper functioning electron transfer thus adding additional layers of complexity to the pathological effect of ACADM missense mutations. Although the majority of the variant MCADs presented an impaired capacity to retain FAD during their synthesis, some of them were structurally rescued by cofactor supplementation, suggesting that in the mitochondrial environment the levels and activity of those variants may be dependent of FAD's availability thus contributing for the heterogeneity of the MCADD phenotype found in patients presenting the same genotype., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

(1) Background: Aspergillus flavus is a cosmopolitan mold with medical, veterinary, and agronomic concerns. Its morphological similarity to other cryptic species of the Flavi section requires molecular identification techniques that are not routinely performed. For clinical isolates of Aspergillus section Flavi , we present the molecular identification, susceptibility to six antifungal agents, and clinical context of source patients. (2) Methods: One hundred forty fungal clinical isolates were included in the study. These isolates, recovered over a 15-year period (2001-2015), were identified based on their morphological characteristics as belonging to section Flavi . After the subculture, sequencing of a part of the β-tubulin and calmodulin genes was performed, and resistance to azole antifungals was screened on agar plates containing itraconazole and voriconazole. Minimum inhibitory concentrations were determined for 120 isolates by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. (3) Results: Partial β-tubulin and calmodulin sequences analysis showed that 138/140 isolates were A. flavus sensu stricto , 1 isolate was A. parasiticus/sojae, and 1 was A. nomiae . Many of the isolates came from samples collected in the context of respiratory tract colonization. Among probable or proven aspergillosis, respiratory infections were the most frequent, followed by ENT infections. Antifungal susceptibility testing was available for isolates (n = 120, all A. flavus ss ) from one hospital. The MIC range (geometric mean MIC) in mg/L was 0.5-8 (0.77), 0.5-8 (1.03), 0.125-2 (0.25), 0.03-2 (0.22), 0.25-8 (1.91), and 0.03-0.125 (0.061) for voriconazole, isavuconazole, itraconazole, posaconazole, amphotericin B, and caspofungin, respectively. Two (1.67%) isolates showed resistance to isavuconazole according to current EUCAST breakpoints with MICs at 8 mg/L for isavuconazole and voriconazole. One of these two isolates was also resistant to itraconazole with MIC at 2 mg/L. (4) Conclusions: The present characterization of a large collection of Aspergillus belonging to the Flavi section confirmed that A. flavus ss is the predominant species. It is mainly implicated in respiratory and ENT infections. The emergence of resistance highlights the need to perform susceptibility tests on section Flavi isolates.

This study aims to understand airline passengers' satisfaction trends by analyzing the most influential factors on satisfaction before and during the COVID-19 pandemic. The sample consists of a dataset with 9745 passenger reviews published on airlinequality.com. The reviews were analyzed with a sentiment analysis tool calibrated for the aviation industry for accuracy. Machine learning algorithms were then implemented to predict review sentiment based on airline company, travelers' type and class, and country of origin. Findings show passengers were unhappy before the pandemic, aggravated after the COVID-19 outbreak. The staff's behavior is the main factor influencing passengers' satisfaction. Predictive modeling showed that it is possible to predict negative review sentiments with satisfactory performance rather than positive reviews. The main takeaway is that passengers, after the pandemic, are most worried about refunds and aircraft cabin cleanliness. From a managerial standpoint, airline companies can benefit from the created knowledge to adjust their strategies in agreement and meet their customers' expectations., (© 2023 The Authors.)

Lignocellulosic biomasses have a complex and compact structure, requiring physical and/or chemical pretreatments to produce glucose before hydrolysis. Mathematical modeling of enzymatic hydrolysis highlights the interactions between cellulases and cellulose, evaluating the factors contributing to reactor scale-up and conversion rates. Furthermore, this study evaluated the influence of two pretreatments (hydrothermal and organosolv) on the kinetics of enzymatic hydrolysis of sugarcane bagasse. The kinetic parameters of the model were estimated using the Pikaia genetic algorithm with data from the experimental profiles of cellulose, cellobiose, glucose, and xylose. The model considered the phenomenon of non-productive adsorption of cellulase on lignin and inhibition of cellulase by xylose. Moreover, it included the behavior of cellulase adsorption on the substrate throughout hydrolysis and kinetic equations for obtaining xylose from xylanase-catalyzed hydrolysis of xylan. The model for both pretreatments was experimentally validated with bagasse concentration at 10% w / v . The Plackett-Burman design identified 17 kinetic parameters as significant in the behavior of process variables. In this way, the modeling and parameter estimation methodology obtained a good fit from the experimental data and a more comprehensive model.

Background: Seed dispersal is a critical process in plant colonisation and demography. Fruits and seeds can be transported by several vectors (typically animals, wind and water), which may have exerted strong selective pressures on plant's morphological traits. The set of traits that favour dispersal by a specific vector have been historically considered as seed dispersal syndromes. As seed dispersal syndromes have a great potential to predict how seeds move (i.e. the relative importance of the standard mechanisms of seed dispersal), they have attracted the attention of naturalists and researchers for centuries. However, given that observations of actual dispersal events and colonisation are seldom reported, there is still much confusion in current studies failing to properly discriminate between seed dispersal syndromes (i.e. sets of traits that favour a particular mechanism) and actual seed dispersal (i.e. the vector that moves a given seed in one dispersal event). This distinction is important because the presence of any seed dispersal syndrome does not preclude the seed being occasionally dispersed by other non-standard mechanisms (i.e. different from the one predicted). Similarly, the absence of seed dispersal syndromes does not prevent seeds from being dispersed. The correct coding of seed dispersal syndromes thus requires a systematic and evolutive, rather than a phenomenological approach. Unfortunately, such approach has rarely been implemented at a community-level and no comprehensive datasets of seed dispersal syndromes are yet available for any entire flora., New Information: This database contains categorisation of the native European flora into eight seed dispersal syndromes. Information for a total of 9,874 species retrieved from the volumes of Flora Europaea were analysed. Earlier versions of this database, which only coded for the presence of four long-distance dispersal syndromes (endozoochorous, epizoochorous, thalassochorous and anemochorous diaspores), were used in four previous studies. Here, we present a fully revised and expanded database, including the presence of four additional short-distance dispersal syndromes (myrmecochorous, vertebrate hoarding, freshwater hydrochorous and ballochorous diaspores), a nomenclatural update for all species and the codification of 416 additional species.Roughly half (51.3%) of the native European flora produce diaspores without traits clearly associated with facilitating seed dispersal. The other half (48.7%) of the European plant species produces diaspores with some specialised traits associated with seed dispersal, most of which (79.9%) with a potential to facilitate long-distance dispersal events. The most common diaspores are those with anemochorous (23.5%), epizoochorous (8.0%), endozoochorous (7.8%), myrmecochorous (7.2%), thalassochorous (2.3%), freshwater dispersal (2.1%), ballochorous (4.6%) and vertebrate hoarding associated traits (0.2%). Two-thirds (66.3%) of the European shrub and tree species have diaspores with some specialisation for biotic seed dispersal., (Pablo Vargas, Ruben Heleno, José M. Costa.)

About 0.3% of all variants are due to de novo mobile element insertions (MEIs). The massive development of next-generation sequencing has made it possible to identify MEIs on a large scale. We analyzed exome sequencing (ES) data from 3232 individuals (2410 probands) with developmental and/or neurological abnormalities, with MELT, a tool designed to identify MEIs. The results were filtered by frequency, impacted region and gene function. Following phenotype comparison, two candidates were identified in two unrelated probands. The first mobile element (ME) was found in a patient referred for poikilodermia. A homozygous insertion was identified in the FERMT1 gene involved in Kindler syndrome. RNA study confirmed its pathological impact on splicing. The second ME was a de novo Alu insertion in the GRIN2B gene involved in intellectual disability, and detected in a patient with a developmental disorder. The frequency of de novo exonic MEIs in our study is concordant with previous studies on ES data. This project, which aimed to identify pathological MEIs in the coding sequence of genes, confirms that including detection of MEs in the ES pipeline can increase the diagnostic rate. This work provides additional evidence that ES could be used alone as a diagnostic exam., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

Muscular dystrophies are a heterogeneous group of highly debilitating diseases that result in muscle atrophy and weakness. The lack of suitable cellular and animal models that reproduce specific aspects of their pathophysiology is one of the reasons why there are no curative treatments for these disorders. This highlights a considerable gap between current laboratory models and clinical practice. We strongly believe that organs-on-chip could help to fill this gap. Organs-on-chip, and in particular muscles-on-chip, are microfluidic devices that integrate functional skeletal muscle tissues. Biosensors in these systems allow monitoring of muscle homeostasis or drug responses in situ. This Perspective outlines the potential of organs-on-chip as advanced models for muscular dystrophies, as well as the current challenges and future opportunities for this technology., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

The wine sector faces important challenges related to sustainability issues and the impact of climate change. More frequent extreme climate conditions (high temperatures coupled with severe drought periods) have become a matter of concern for the wine sector of typically dry and warm regions, such as the Mediterranean European countries. Soil is a natural resource crucial to sustaining the equilibrium of ecosystems, economic growth and people's prosperity worldwide. In viticulture, soils have a great influence on crop performance (growth, yield and berry composition) and wine quality, as the soil is a central component of the terroir . Soil temperature (ST) affects multiple physical, chemical and biological processes occurring in the soil as well as in plants growing on it. Moreover, the impact of ST is stronger in row crops such as grapevine, since it favors soil exposition to radiation and favors evapotranspiration. The role of ST on crop performance remains poorly described, especially under more extreme climatic conditions. Therefore, a better understanding of the impact of ST in vineyards (vine plants, weeds, microbiota) can help to better manage and predict vineyards' performance, plant-soil relations and soil microbiome under more extreme climate conditions. In addition, soil and plant thermal data can be integrated into Decision Support Systems (DSS) to support vineyard management. In this paper, the role of ST in Mediterranean vineyards is reviewed namely in terms of its effect on vines' ecophysiological and agronomical performance and its relation with soil properties and soil management strategies. The potential use of imaging approaches, e.g. thermography, is discussed as an alternative or complementary tool to assess ST and vertical canopy temperature profiles/gradients in vineyards. Soil management strategies to mitigate the negative impact of climate change, optimize ST variation and crop thermal microclimate (leaf and berry) are proposed and discussed, with emphasis on Mediterranean systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Costa, Egipto, Aguiar, Marques, Nogales and Madeira.)

The rechargeable alkaline aqueous zinc-air batteries (ZABs) are prospective candidates to supply the energy demand for their high theoretical energy density, inherent safety, and environmental friendliness. However, their practical application is mainly restricted by the unsatisfactory efficiency of the air electrode, leading to an intense search for high-efficient oxygen electrocatalysts. In recent years, the composites of carbon materials and transition metal chalcogenides (TMC/C) have emerged as promising alternatives because of the unique properties of these single compounds and the synergistic effect between them. In this sense, this review presented the electrochemical properties of these composites and their effects on the ZAB performance. The operational fundamentals of the ZABs were described. After elucidating the role of the carbon matrix in the hybrid material, the latest developments in the ZAB performance of the monometallic structure and spinel of TMC/C were detailed. In addition, we report topics on doping and heterostructure due to the large number of studies involving these specific defects. Finally, a critical conclusion and a brief overview sought to contribute to the advancement of TMC/C in the ZABs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To assess the ABC 2 -SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score)., Materials and Methods: Consecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC 2 -SPH was used as the reference score, and comparisons between ABC 2 -SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality., Results: ABC 2 -SPH had an area under the curve of 0.716 (95% CI 0.693-0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC 2 -SPH and SAPS-3, 4C Mortality Score, and the novel severity score., Conclusion: ABC 2 -SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nogueira, Nobre, Pires, Ramos, Ribeiro, Aguiar, Vigil, Gomes, Santos, Miranda, Durães, Costa, Schwarzbold, Gomes, Pessoa, Matos, Cimini, Carvalho, Ponce, Manenti, Cenci, Anschau, Costa, Nascimento, Bartolazzi, Grizende, Vianna, Nepomuceno, Ruschel, Zandoná, Castro, Souza, Carneiro, Bicalho, Vilaça, Bonardi, Oliveira, Lutkmeier, Francisco, Araújo, Delfino-Pereira and Marcolino.)

Genotype analysis has revealed a high genetic diversity in strains of Toxoplasma gondii , isolated from a wide range of intermediate hosts and different geographic origins. Diversity is notably striking for parasites from wild hosts in South America, generally referred as non-archetypal genotypes. Those genotypes are implicated in the etiology of severe clinical disease, multivisceral toxoplasmosis, associated with high rate of mortality in immunocompetent individuals. Can we accept specific antibodies produced during T. gondii infection as biomarkers to identify infecting genotypes? Scientific evidence supports a positive response to this question; however, the genetic diversity of T. gondii genotypes organized into 16 haplogroups and collectively defined in 6 major clades, provides a reminder of the complexity and difficulty for the purpose. This review discusses serological approaches to genotyping T. gondii ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sousa, Fernandes and Correia da Costa.)

The symptoms of Myotonic Dystrophy Type 1 (DM1) are multi-systemic and life-threatening. The neuromuscular disorder is rooted in a non-coding CTG microsatellite expansion in the DM1 protein kinase ( DMPK ) gene that, upon transcription, physically sequesters the Muscleblind-like (MBNL) family of splicing regulator proteins. The high-affinity binding occurring between the proteins and the repetitions disallow MBNL proteins from performing their post-transcriptional splicing regulation leading to downstream molecular effects directly related to disease symptoms such as myotonia and muscle weakness. In this study, we build on previously demonstrated evidence showing that the silencing of miRNA-23b and miRNA-218 can increase MBNL1 protein in DM1 cells and mice. Here, we use blockmiR antisense technology in DM1 muscle cells, 3D mouse-derived muscle tissue, and in vivo mice to block the binding sites of these microRNAs in order to increase MBNL translation into protein without binding to microRNAs. The blockmiRs show therapeutic effects with the rescue of mis-splicing, MBNL subcellular localization, and highly specific transcriptomic expression. The blockmiRs are well tolerated in 3D mouse skeletal tissue inducing no immune response. In vivo, a candidate blockmiR also increases Mbnl1/2 protein and rescues grip strength, splicing, and histological phenotypes.