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OBJECTIVE: The paper introduces a framework for the evaluation of the encoding of factual scientific knowledge, designed to streamline the manual evaluation process typically conducted by domain experts. Inferring over and extracting information from Large Language Models (LLMs) trained on a large corpus of scientific literature can potentially define a step change in biomedical discovery, reducing the barriers for accessing and integrating existing medical evidence. This work explores the potential of LLMs for dialoguing with biomedical background knowledge, using the context of antibiotic discovery. METHODS: The framework involves of three evaluation steps, each assessing different aspects sequentially: fluency, prompt alignment, semantic coherence, factual knowledge, and specificity of the generated responses. By splitting these tasks between non-experts and experts, the framework reduces the effort required from the latter. The work provides a systematic assessment on the ability of eleven state-of-the-art models LLMs, including ChatGPT, GPT-4 and Llama 2, in two prompting-based tasks: chemical compound definition generation and chemical compound-fungus relation determination. RESULTS: Although recent models have improved in fluency, factual accuracy is still low and models are biased towards over-represented entities. The ability of LLMs to serve as biomedical knowledge bases is questioned, and the need for additional systematic evaluation frameworks is highlighted. CONCLUSION: While LLMs are currently not fit for purpose to be used as biomedical factual knowledge bases in a zero-shot setting, there is a promising emerging property in the direction of factuality as the models become domain specialised, scale-up in size and level of human feedback.

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The recent geographic spread of Oropouche virus (OROV), coupled with an increase in cases and the emergence of previously unrecognized severe manifestations, has raised significant public health concerns. We report the case of a 40-year-old family farmer at 31 weeks of gestation who presented with fever, myalgia, and headache. OROV infection was confirmed by RT-qPCR, with other infections ruled out. Initially, maternal and fetal health assessments revealed no complications. However, within a week, the patient noted decreased fetal movements, and ultrasound confirmed fetal demise. Molecular diagnostics identified OROV RNA in multiple fetal tissues, confirming vertical transmission. This case highlights the urgent need to protect pregnant women against viral vectors and include OROV into the differential diagnosis of febrile illnesses. Furthermore, it is critical to further investigate the pathogenic mechanisms of this virus, which may lead to changes in public health policies and clinical guidelines.

La reciente propagación geográfica del virus Oropouche (OROV), junto con un aumento de casos y la aparición de manifestaciones graves no reconocidas previamente, ha suscitado importantes preocupaciones de salud pública. Informamos del caso de un agricultor familiar de 40 años de edad con 31 semanas de gestación que presentó fiebre, mialgia y dolor de cabeza. La infección por OROV se confirmó mediante RT-qPCR, y se descartaron otras infecciones. Inicialmente, las evaluaciones de salud materna y fetal no revelaron complicaciones. Sin embargo, en una semana, la paciente notó una disminución de los movimientos fetales y la ecografía confirmó la muerte fetal. Los diagnósticos moleculares identificaron ARN de OROV en múltiples tejidos fetales, lo que confirmó la transmisión vertical. Este caso destaca la necesidad urgente de proteger a las mujeres embarazadas contra los vectores virales e incluir OROV en el diagnóstico diferencial de enfermedades febriles. Además, es fundamental investigar más a fondo los mecanismos patogénicos de este virus, lo que puede conducir a cambios en las políticas de salud pública y las pautas clínicas.

A recente disseminação geográfica do vírus Oropouche (OROV), juntamente com um aumento de casos e o surgimento de manifestações graves não reconhecidas anteriormente, levantou preocupações significativas de saúde pública. Relatamos o caso de uma agricultora familiar de 40 anos com 31 semanas de gestação que apresentou febre, mialgia e dor de cabeça. A infecção por OROV foi confirmada por RT-qPCR, com outras infecções descartadas. Inicialmente, as avaliações de saúde materna e fetal não revelaram complicações. No entanto, dentro de uma semana, a paciente notou diminuição dos movimentos fetais, e o ultrassom confirmou a morte fetal. O diagnóstico molecular identificou o RNA do OROV em vários tecidos fetais, confirmando a transmissão vertical. Este caso destaca a necessidade urgente de proteger as mulheres grávidas contra vetores virais e incluir o OROV no diagnóstico diferencial de doenças febris. Além disso, é fundamental investigar mais profundamente os mecanismos patogênicos deste vírus, o que pode levar a mudanças nas políticas de saúde pública e diretrizes clínicas.

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The mono- and divalent spacer cation investigation in sodium/indium-based 2D double perovskites revealed significant impacts on optoelectronic properties due to distortions in the inorganic layers. The strong electron-phonon coupling in a novel lead-free Dion-Jacobson phase highlights a promising class for broad-emission devices based on self-trapped excitons (STE), offering enhanced structural stability.

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OBJECTIVES: To evaluate the clinical performance of two flowable composites based on methacrylate and one based on ormocer in treating non-carious cervical lesions (NCCLs) after 48-month evaluation in a split-mouth double-blind clinical study design. METHODS: A total of 183 restorations were performed on NCCLs using a universal adhesive system (Futurabond U, Voco GmbH) with selective enamel etching on 27 participants: two participants received twelve restorations each, three received nine restorations each, and 22 participants received six restorations each. Three different flowable composites were employed (n = 61): a low-viscosity methacrylate-based composite (GrandioSO Flow, LVM), a high-viscosity methacrylate-based composite (GrandioSO Heavy Flow, HVM), and an ormocer-based flowable composite (Admira Fusion Flow, ORM). All restorations were evaluated using FDI and USPHS criteria after 48 months. Statistical analysis was conducted using Kaplan-Meier Survival analysis and Kruskal-Wallis analysis of variance rank (α = 0.05). RESULTS: After 48 months, 17 restorations were lost: LVM 6, HVM 9, ORM 2. The retention rates (95 % confidence interval) were 89.4 % for LVM, 80.4 % for HVM, and 95.6 % for ORM, with a significant difference between HVM vs. LVM and HVM vs. ORM (p < 0.05). Minor defects were observed in 30 restorations for marginal staining criteria (LVM 12, HVM 10, ORM 8) and in 71 restorations for marginal adaptation criteria (LVM 24, HVM 20, ORM 27) without significant difference between groups (p > 0.05). No restorations showed postoperative sensitivity or recurrence of caries. SIGNIFICANCE: The increased viscosity of flowable composites could reduce the clinical longevity in NCCLs after 48 months. Ormocer-based and low-viscosity methacrylate-based flowable composites showed a successful clinical performance in NCCLs after 48 months.

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The mountains in the Atlantic Forest domain are environments that harbor a high biodiversity, including species adapted to colder climates that were probably influenced by the climatic variations of the Pleistocene. To understand the phylogeographic pattern and assess the taxonomic boundaries between two sister montane species, a genomic study of the butterflies Actinote mantiqueira and A. alalia (Nymphalidae: Acraeini) was conducted. Analyses based on partial sequences of the mitochondrial gene COI (barcode region) failed to recover any phylogenetic or genetic structure discriminating the two species or sampling localities. However, single nucleotide polymorphisms gathered using Genotyping-by-Sequencing provided a strong isolation pattern in all analyses (genetic distance, phylogenetic hypothesis, clustering analyses, and F ST statistics) which is consistent with morphology, separating all individuals of A. alalia from all populations of A. mantiqueira. The three sampled mountain ranges where A. mantiqueira populations occur-Serra do Mar, Serra da Mantiqueira, and Poços de Caldas Plateau-were identified as three isolated clusters. Paleoclimate simulations indicate that both species' distributions changed according to climatic oscillations in the Pleistocene period, with the two species potentially occurring in areas of lower altitude during glacial periods when compared to the interglacial periods (as the present). Besides, a potential path between their distribution through the Serra do Mar Mountain range was inferred. Therefore, the Pleistocene climatic fluctuation had a significant impact on the speciation process between A. alalia and A. mantiqueira, which was brought on by isolation at different mountain summits during interglacial periods, as shown by the modeled historical distribution and the observed genetic structure.

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The lack of synthesized information regarding biodiversity is a major problem among researchers, leading to a pervasive cycle where ecologists make field campaigns to collect information that already exists and yet has not been made available for a broader audience. This problem leads to long-lasting effects in public policies such as spending money multiple times to conduct similar studies in the same area. We aim to identify this knowledge gap by synthesizing information available regarding two Brazilian long-term biodiversity programs and the metadata generated by them. Using a unique dataset containing 1904 metadata, we identified patterns of metadata distribution and intensity of research conducted in Brazil, as well as where we should concentrate research efforts in the next decades. We found that the majority of metadata were about vertebrates, followed by plants, invertebrates, and fungi. Caatinga was the biome with least metadata, and that there's still a lack of information regarding all biomes in Brazil, with none of them being sufficiently sampled. We hope that these results will have implications for broader conservation and management guiding, as well as to funding allocation programs.

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An often-overlooked question of the biodiversity crisis is how natural hazards contribute to species extinction risk. To address this issue, we explored how four natural hazards, earthquakes, hurricanes, tsunamis, and volcanoes, overlapped with the distribution ranges of amphibians, birds, mammals, and reptiles that have either narrow distributions or populations with few mature individuals. To assess which species are at risk from these natural hazards, we combined the frequency and magnitude of each natural hazard to estimate their impact. We considered species at risk if they overlapped with regions where any of the four natural hazards historically occurred (n = 3,722). Those species with at least a quarter of their range subjected to a high relative impact were considered at high risk (n = 2,001) of extinction due to natural hazards. In total, 834 reptiles, 617 amphibians, 302 birds, and 248 mammals were at high risk and they were mainly distributed on islands and in the tropics. Hurricanes (n = 983) and earthquakes (n = 868) affected most species, while tsunamis (n = 272), and volcanoes (n = 171) affected considerably fewer. The region with the highest number of species at high risk was the Pacific Ring of Fire, especially due to volcanoes, earthquakes, and tsunamis, while hurricane-related high-risk species were concentrated in the Caribbean Sea, Gulf of Mexico, and northwestern Pacific Ocean. Our study provides important information regarding the species at risk due to natural hazards and can help guide conservation attention and efforts to safeguard their survival.

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Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide's low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

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Hybridization allows adaptations to be shared among lineages and may trigger the evolution of new species1,2. However, convincing examples of homoploid hybrid speciation remain rare because it is challenging to demonstrate that hybridization was crucial in generating reproductive isolation3. Here we combine population genomic analysis with quantitative trait locus mapping of species-specific traits to examine a case of hybrid speciation in Heliconius butterflies. We show that Heliconius elevatus is a hybrid species that is sympatric with both parents and has persisted as an independently evolving lineage for at least 180,000 years. This is despite pervasive and ongoing gene flow with one parent, Heliconius pardalinus, which homogenizes 99% of their genomes. The remaining 1% introgressed from the other parent, Heliconius melpomene, and is scattered widely across the H. elevatus genome in islands of divergence from H. pardalinus. These islands contain multiple traits that are under disruptive selection, including colour pattern, wing shape, host plant preference, sex pheromones and mate choice. Collectively, these traits place H. elevatus on its own adaptive peak and permit coexistence with both parents. Our results show that speciation was driven by introgression of ecological traits, and that speciation with gene flow is possible with a multilocus genetic architecture.

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Butterfly eyespots are wing patterns reminiscent of vertebrate eyes, formed by concentric rings of contrastingly coloured scales. Eyespots are usually located close to the wing margin and often regarded as the single most conspicuous pattern element of butterfly wing colour displays. Recent efforts to understand the processes involved in the formation of eyespots have been driven mainly by evo-devo approaches focused on model species. However, patterns of change implied by phylogenetic relationships can also inform hypotheses about the underlying developmental mechanisms associated with the formation or disappearance of eyespots, and the limits of phenotypic diversity occurring in nature. Here we present a combined evidence phylogenetic hypothesis for the genus Eunica, a prominent member of diverse Neotropical butterfly communities, that features notable variation among species in eyespot patterns on the ventral hind wing surface. The data matrix consists of one mitochondrial gene region (COI), four nuclear gene regions (GAPDH, RPS5, EF1a and Wingless) and 68 morphological characters. A combined cladistic analysis with all the characters concatenated produced a single most parsimonious tree that, although fully resolved, includes many nodes with modest branch support. The phylogenetic hypothesis presented corroborates a previously proposed morphological trend leading to the loss of eyespots, together with an increase in the size of the conserved eyespots, relative to outgroup taxa. Furthermore, wing colour pattern dimorphism and the presence of androconia suggest that the most remarkable instances of sexual dimorphism are present in the species of Eunica with the most derived eyespot patterns, and are in most cases accompanied by autapomorphic combinations of scent scales and "hair pencils". We discuss natural and sexual selection as potential adaptive explanations for dorsal and ventral wing patterns.

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The present study describes the immature stages of Opoptera syme (Hübner, [1821]) using SEM and Micro-CT to generate 2D and 3D models to study the morphology and chaetotaxy, and present information on the natural history, behavior, and population biology. In laboratory, eggs were laid singly, and the isolated larvae passed through six to seven instars. Host plant in the study site is unknown, but larvae are known to feed on bamboos; in laboratory, larvae accepted the ornamental bamboo Bambusa textilis McClure, 1940. Adults are diurnal and univoltine, flying from December to April (the austral summer). The present study adds information to the biology and natural history of Brassolini, an iconic and still poorly known tribe of Neotropical butterflies.

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OBJECTIVE: To evaluate the effect of prolonged (P) polymerization time of a universal adhesive system applied in etch-and-rinse (ER) or self-etch (SE) strategies on the clinical performance of restorations in non-carious cervical lesions (NCCLs), after 36 months of clinical service. METHODS: A total of 140 restorations were randomly placed in 35 subjects according to the polymerization time groups: ER (10 s); ER-P (40 s); SE (10 s); and SE-P (40 s) at 1,200 mW/cm2. Composite resin was placed incrementally. The restorations were evaluated immediately and after 6, 12, 18, and 36 months using the FDI criteria. Data were analyzed using the Kaplan-Meier survival test for retention loss, and the Kruskal-Wallis' test for secondary outcomes (α = 0.05). RESULTS: After 36 months, 19 restorations were lost: ER 6, ER-P 2, SE 9, SE-P 2. The retention rates were 82.3% for ER; 94.1 % for ER-P; 73.5 % for SE; and 94.1 % for SE-P, with a significant difference between ER vs. ER-P and SE vs. SE-P, as well as ER vs. SE-P and ER-P vs. SE (p < 0.0001). Minor defects were observed in 18 restorations for the marginal staining criteria: ER 5, ER-P 2, SE 8, SE-P 3; and in 33 restorations for the marginal adaptation criteria: ER 11, ER-P 4, SE 12, and SE-P 6 (p > 0.05). No restorations showed recurrence of caries or postoperative sensitivity. CONCLUSIONS: A prolonged polymerization time of 40 s improves the clinical performance of the universal adhesive for both adhesive strategies evaluated, even after 36 months. CLINICAL SIGNIFICANCE: Prolonging the polymerization time of a universal adhesive from 10 to 40 s has been shown to improve its clinical performance when used in NCCLs.

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Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

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X-ray micro-computed tomography imaging (micro-CT) is valuable for systematic research since it permits the non-destructive scanning and imaging of internal structures of very rare species and/or type specimens. Additionally, micro-CT allows to view the morphology and the functional anatomy of structures in their natural anatomical position, without deformations that typically occur using classical dissection protocols. In this study we provide the description of two new species of lichen moths (Lepidoptera: Erebidae, Lithosiini) from the Atlantic Forest in eastern Brazil: Nodozana heliae Moraes sp. nov. from Rio de Janeiro state and Epeiromulona pataxo Moraes & Aguiar sp. nov. from Bahia state. The male and female genitalia as well as the wing morphology were examined by means of non-destructive micro-CT, subsequent 3D model reconstruction, 360 degree spinning animations, 2D images from different angles, and those were compared against classical genitalia dissections from the same specimens. We conclude that techniques complement each other, micro-CT being particularly useful to study wing venation, sclerotized internal structures and muscles, while classical dissection is useful to study membranous structures, particularly in the female genitalia, abdominal skin and specialised scales on the male 8th sternite.

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Chikungunya (CHIK) is a re-emerging viral infection endemic in tropical and subtropical areas. While the typical clinical presentation is an acute febrile syndrome, long-term articular complications and even death can occur. This review characterizes the global epidemiological and economic burden of chikungunya. The search included studies published from 2007 to 2022 in MEDLINE, Embase, LILACS, and SciELO for a thorough evaluation of the literature. Rayyan software was used for data analysis, and data were summarized descriptively and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventy-six publications were included. Chikungunya is widely distributed in the tropics, including Africa, Asia, South America, and Oceania/the Pacific Islands, and co-circulates with other simultaneous arboviruses such as DENV, ZIKV, and YFV. Chikungunya infection can lead to chronic articular manifestations with a significant impact on the quality of life in the long term. In addition, it generates absenteeism and economic and social losses and can cause fatal infections in vulnerable populations, mainly in high-risk patients with co-morbidities and at the extremes of age. Reported costs associated with CHIKV diseases are substantial and vary by region, age group, and public/private delivery of healthcare services. The chikungunya disease burden includes chronicity, severe infections, increased hospitalization risks, and associated mortality. The disease can impact the economy in several spheres, significantly affecting the health system and national economies. Understanding and measuring the full impact of this re-emerging disease is essential.

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A brief historical review regarding the type locality of Euptychiastigmatica Godman, 1905 was conducted, which suggests that its type locality is actually Rio de Janeiro, Brazil, rather than northeastern Argentina, as previously purported. Consequently, E.stigmatica and its senior synonym E.cyanites Butler, 1871, are regarded to be two species-group names representing a taxon in the euptychiine genus Caeruleuptychia Forster, 1964 known from the Brazilian Atlantic Forest. A lectotype is designated for E.cyanites. Additionally, two closely related species are named and described using an integrative approach with morphological and molecular evidence. Caeruleuptychiaharrisi Nakahara & Freitas, sp. nov. and C.aemulatio Nakahara & Willmott, sp. nov. both occur in Amazonia and COI barcode data recovered these taxa as part of the caerulea clade of Caeruleuptychia.

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BACKGROUND: There is an increasing interest in the use of Deep Learning (DL) based methods as a supporting analytical framework in oncology. However, most direct applications of DL will deliver models with limited transparency and explainability, which constrain their deployment in biomedical settings. METHODS: This systematic review discusses DL models used to support inference in cancer biology with a particular emphasis on multi-omics analysis. It focuses on how existing models address the need for better dialogue with prior knowledge, biological plausibility and interpretability, fundamental properties in the biomedical domain. For this, we retrieved and analyzed 42 studies focusing on emerging architectural and methodological advances, the encoding of biological domain knowledge and the integration of explainability methods. RESULTS: We discuss the recent evolutionary arch of DL models in the direction of integrating prior biological relational and network knowledge to support better generalisation (e.g. pathways or Protein-Protein-Interaction networks) and interpretability. This represents a fundamental functional shift towards models which can integrate mechanistic and statistical inference aspects. We introduce a concept of bio-centric interpretability and according to its taxonomy, we discuss representational methodologies for the integration of domain prior knowledge in such models. CONCLUSIONS: The paper provides a critical outlook into contemporary methods for explainability and interpretability used in DL for cancer. The analysis points in the direction of a convergence between encoding prior knowledge and improved interpretability. We introduce bio-centric interpretability which is an important step towards formalisation of biological interpretability of DL models and developing methods that are less problem- or application-specific.

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Stability and maintenance of the crystal structure are the main drawbacks of the application of organic-inorganic perovskites in photovoltaic devices. The ΔT = 62 K robust shift of the structural phase transition observed here allows us to conduct a comprehensive study at room temperature of the tetragonal versus cubic phase on MAPbI3. The absence of the shift in the cubic transition for all-inorganic CsPbI3 samples confirms the importance of both orientation and dynamics of the organic cations. Our results provide a unique opportunity to evaluate the physical properties of both cubic and tetragonal phases of MAPbI3 at the same temperature, eliminating different phonon effects as possible causes for different properties. Besides higher electrical resistivity, the perovskite cubic phase presents a faster charge carrier lifetime than the tetragonal phase and partial PL quenching, pointing toward increased trap-assisted nonradiative recombination. The light absorption coefficient in the cubic phase is larger than the absorption in the tetragonal phase in the green region.