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1.
Rev Esp Enferm Dig ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501772

RESUMO

Vaccination in patients with advanced chronic liver disease (ACLD) is an essential part of their comprehensive healthcare. These individuals may have impaired phagocytic function and diminished production of opsonizing antibodies, resulting in increased susceptibility to bacterial infections, particularly pneumococcal pneumonia. Similarly, there is an increased risk of fulminant hepatitis due to hepatitis A and B viruses. The Ministry of Health updated specific vaccination recommendations for this group in 2018.

2.
Am J Biol Anthropol ; : e24921, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426243

RESUMO

OBJECTIVES: To investigate the association between the anthropometric status at birth and brain and bone growth during the first year of life. According to the brain-sparing hypothesis, we expect catch-up to be faster in head circumference (HC) than in body length. METHODS: This is a longitudinal design that included Argentinian infants under 12 months of age with at least three anthropometric records. We classified study participants into four growth status categories according to z-scores for HC (HCZ) and length (LAZ) at birth, with z-score = -2 as a threshold. We used the Count model to describe growth trajectories in HC and length in the first year of life according to the growth status at birth. Recovery indicator for HC and length was taken as the time until the predicted growth trajectory surpassed the threshold curve predicted by z-score = -2 for age. RESULTS: Growth models included 3399 infants. There were significant differences in the growth parameters between groups in all cases (p < 0.05). Within the group with a low HCZ and a low LAZ at birth, HC recovery was faster than length. In the case of a low z-score for only one of the variables, newborns with a low HCZ recovered faster than individuals born with a low LAZ. CONCLUSIONS: The postnatal growth pattern in HC and length is associated with the growth status of HC and length at birth. As we hypothesized, the fastest postnatal recovery occurs for HC in cases of intrauterine delayed growth.

3.
Nucleic Acids Res ; 52(6): 3358-3374, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38381063

RESUMO

A subset of circular RNAs (circRNAs) and linear RNAs have been proposed to 'sponge' or block microRNA activity. Additionally, certain RNAs induce microRNA destruction through the process of Target RNA-Directed MicroRNA Degradation (TDMD), but whether both linear and circular transcripts are equivalent in driving TDMD is unknown. Here, we studied whether circular/linear topology of endogenous and artificial RNA targets affects TDMD. Consistent with previous knowledge that Cdr1as (ciRS-7) circular RNA protects miR-7 from Cyrano-mediated TDMD, we demonstrate that depletion of Cdr1as reduces miR-7 abundance. In contrast, overexpression of an artificial linear version of Cdr1as drives miR-7 degradation. Using plasmids that express a circRNA with minimal co-expressed cognate linear RNA, we show differential effects on TDMD that cannot be attributed to the nucleotide sequence, as the TDMD properties of a sequence often differ when in a circular versus linear form. By analysing RNA sequencing data of a neuron differentiation system, we further detect potential effects of circRNAs on microRNA stability. Our results support the view that RNA circularity influences TDMD, either enhancing or inhibiting it on specific microRNAs.


Assuntos
MicroRNAs , Estabilidade de RNA , RNA Circular , MicroRNAs/genética , MicroRNAs/metabolismo , RNA/genética , RNA/metabolismo , RNA Circular/metabolismo , Humanos , Animais , Camundongos
4.
Children (Basel) ; 11(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38397251

RESUMO

BACKGROUND: Childhood myopia represents a global concern with increasing prevalence in recent decades. Lifestyle factors significantly impact myopia. AIM: To evaluate lifestyle factors in myopic children from a metropolitan area in Europe. METHODS: This was a descriptive study including myopic subjects aged 4-18 years. Patient demographic and clinical data were collected, including cycloplegic refraction in spherical equivalent refraction (SER) and axial length (AL). In addition, a questionnaire on lifestyle factors was conducted between September 2022 and April 2023. RESULTS: A total of 321 myopic children were included, aged 10.72 ± 3.05 years, of whom 51.4% were boys, with SER -2.25 ± 1.9 D and AL 24.54 ± 0.98 mm. The mean age of myopia onset was 7.69 ± 3.05 years. A total of 59.8% had family history of myopia. Those children who had <2 h/day of screen time (on weekdays) presented SER -2 ± 1.91 D, compared to those who had >2 h/day, SER: -2.50 ±1.88 D (p = 0.009). Children who spent <2 h/day doing near work after school were less myopic compared to those who spent >2 h/day (SER: -1.75 ± 1.83 vs. SER: -2.75 ± 1.82, respectively, p = 0.03). However, no significant association was observed between SER and AL and time spent outdoors nor between SER and AL and academic performance (p > 0.05). CONCLUSIONS: Screen time and near-work time appear to be lifestyle factors related to myopia.

5.
Behav Sci (Basel) ; 14(2)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38392450

RESUMO

Over half of women with psychosis are mothers. Research suggests that mothers with psychosis face unique challenges affecting both their mental health prognosis and their relationship with their children. Moreover, those children have a higher risk of developing a mental disorder. Notwithstanding, interventions specifically tailored to these families remain largely uncovered. Metacognitive Training (MCT) has demonstrated its efficacy in improving cognitive insight, symptom management, and social cognition in people with psychosis. However, there is no evidence of the efficacy of MCT in a family setting (MCT-F). This study describes the first adaptation of MCT for mothers with psychosis and their adolescent children in an online group setting. The phases (assessment, decision, adaptation, production, topical experts' integration) of the ADAPT-ITT model were systematically applied through a participatory approach (n = 22), including a first-person perspective and involving qualitative (e.g., topical expert literature review and consensus groups, interviews, thematic analyses) and quantitative methods. While MCT's core components were retained, participants guided adaptations both in content and delivery. The findings suggest the importance of community engagement and sharing decision-making processes to demonstrate the acceptability and feasibility of the adapted intervention. Employing a structured approach such as the ADAPT-ITT model ensures readiness of the new training for efficacy trials.

6.
J Anat ; 244(5): 815-830, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38183319

RESUMO

Structural asymmetries of brain regions associated with lateralised functions have been extensively studied. However, there are fewer morphometric analyses of asymmetries of the gyri and sulci of the entire cortex. The current study assessed cortical asymmetries in a sample of healthy adults (N = 175) from an admixed population from South America. Grey matter volume and surface area of 66 gyri and sulci were quantified on T1 magnetic resonance images. The departure from zero of the differences between left and right hemispheres (L-R), a measure of directional asymmetry (DA), the variance of L-R, and an index of fluctuating asymmetry (FA) were evaluated for each region. Significant departures from perfect symmetry were found for most cortical gyri and sulci. Regions showed leftward asymmetry at the population level in the frontal lobe and superior lateral parts of the parietal lobe. Rightward asymmetry was found in the inferior parietal, occipital, frontopolar, and orbital regions, and the cingulate (anterior, middle, and posterior-ventral). Despite this general pattern, several sulci showed the opposite DA compared to the neighbouring gyri, which remarks the need to consider the neurobiological differences in gyral and sulcal development in the study of structural asymmetries. The results also confirm the absence of DA in most parts of the inferior frontal gyrus and the precentral region. This study contributes with data on populations underrepresented in the databases used in neurosciences. Among its findings, there is agreement with previous results obtained in populations of different ancestry and some discrepancies in the middle frontal and medial parietal regions. A significant DA not reported previously was found for the volume of long and short insular gyri and the central sulcus of the insula, frontomarginal, transverse frontopolar, paracentral, and middle and posterior parts of the cingulate gyrus and sulcus, gyrus rectus, occipital pole, and olfactory sulcus, as well as for the volume and area of the transverse collateral sulcus and suborbital sulcus. Also, several parcels displayed significant variability in the left-right differences, which can be partially attributable to developmental instability, a source of FA. Moreover, a few gyri and sulci displayed ideal FA with non-significant departures from perfect symmetry, such as subcentral and posterior cingulate gyri and sulci, inferior frontal and fusiform gyri, and the calcarine, transverse collateral, precentral, and orbital sulci. Overall, these results show that asymmetries are ubiquitous in the cerebral cortex.


Assuntos
Córtex Cerebral , Substância Cinzenta , Adulto , Humanos , Substância Cinzenta/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Lobo Frontal , Giro do Cíngulo , Imageamento por Ressonância Magnética/métodos , América do Sul
7.
Psicol. educ. (Madr.) ; 30(1): 57-66, Ene. 2024. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-228962

RESUMO

The present study seeks to ascertain whether the academic procrastination of university pre-service teachers varied during the COVID-19 pandemic when compared to data collected from another sample (n = 794) taken before the pandemic, and the reasons that might explain this. 910 pre-service teachers responded to the PASS scale, Academic Procrastination Scale, Unintentional Procrastination Scale, Active Procrastination Scale, and the New General Self-Efficacy Scale during the pandemic. The results reflect greater procrastination than for the pre-pandemic sample; 37.8% felt that their procrastination had increased due to the pandemic, which was more evident amongst women, whereas 8.7% reported having procrastinated less, displaying the highest level of self-efficacy. In both instances, the most commonly alleged reasons were greater time management, together with changes they were forced to make in their study habits. We discuss the implications that might need to be considered when planning and organizing teaching, should a similar situation occur again. (AU)


El objetivo de este trabajo es conocer si la procrastinación académica de los estudiantes universitarios de formación del profesorado varió durante la pandemia de COVID-19 en comparación con datos recogidos de otra muestra (n = 794) antes de la pandemia y los motivos que lo justifican. Han participado 910 estudiantes, que respondieron a la escala PASS, la Escala de Procrastinación Académica, la Escala de Procrastinación Involuntaria, la Escala de Procrastinación Activa y la Nueva Escala de Autoeficacia General durante la pandemia. Los resultados indican una mayor procrastinación que la muestra prepandemia. Un 37.8% cree haber aumentado su procrastinación por la pandemia, sobre todo las mujeres, mientras el 8.7% afirman procrastinar menos, siendo los que mayor autoeficacia tienen. En ambos casos, los motivos más frecuentes han sido el disponer de más tiempo, junto a cambios en sus hábitos de estudio. Se comentan las implicaciones para la organización docente en caso de repetirse una situación similar. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Procrastinação , Universidades , Estudantes , Espanha , Pandemias , Motivação
8.
Clin Child Psychol Psychiatry ; 29(1): 232-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37541309

RESUMO

Low- and middle-income countries face heterogeneity in the way clinicians' approach Autism Spectrum Disorder (ASD) diagnosis and treatment. The current study analyzes the diagnostic tools, laboratory tests, pharmacological and psychosocial interventions received by patients during the steps to diagnosis and treatment of two specialized care centers. Researchers interviewed families with a child with ASD receiving services at either a child psychiatric or a pediatric hospital. Of the total sample, 47% reported clinicians not using a diagnostic tool, 20% reported not receiving any psychosocial intervention, and 88% reported receiving a pharmacological prescription. Patients at the pediatric hospital were more likely to receive interventions with some components of Applied Behavioral Analysis, Early Start Denver Model, Treatment and Education of Autistic and Related Communication Handicapped Children, and Sensory integration therapy; while patients at the psychiatric hospital were more likely to undergo learning, daily living skills, and socialization therapies. Patients at the psychiatric hospital received significantly more requests to obtain auditory and vision tests whilst genetic testing and imaging were more common in the pediatric hospital. The range and variability in terms of diagnostic tools, laboratory tests, and treatment options observed for both sites reflect a lack of consensus. Recommendations to improve ASD diagnostic and treatment in Mexico are given.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Crianças com Deficiência , Humanos , Criança , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/psicologia , México , Comunicação
9.
Rev. esp. enferm. dig ; 116(4): 228-229, 2024.
Artigo em Inglês | IBECS | ID: ibc-232473

RESUMO

We present the case of a patient with liver cirrhosis and several previous episodes of ascitic decompensation, who was admitted for bacterial peritonitis secondary to Capnocytophaga canimorsus infection. The initial clinical presentation, diagnosis, treatment and resolution are described. This is the first case described of peritonitis caused by this agent in a patient with similar characteristics. (AU)


Assuntos
Humanos , Masculino , Idoso , Infecções Bacterianas , Peritonite , Capnocytophaga
10.
J Environ Sci (China) ; 139: 114-122, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105039

RESUMO

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this century. In this paper we pursue two objectives. First, we analyze the evolution of GHG emissions in Spain in 2008-2018, at both the global and sectoral levels, with the variation in emissions decomposed into a set of determining factors. Second, we propose several actions specifically oriented to more tightly controlling the level of emissions. Our results showed a remarkable reduction (18.44%) in GHG emissions, mainly due to the intensity effect, but also to the production-per-capita effect. We detected somewhat different patterns among the various sectors analyzed. While the intensity effect was the most influential one in the agricultural, transport, and others sectors, the production-per-capita effect was predominant in the case of industry. The carbonization effect was revealed as crucial in the commerce sector. The above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy, also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in emissions. Additional efforts in areas like innovation, R&D, diffusion of more eco-friendly technologies, and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Efeito Estufa , Agricultura , Indústrias
11.
J Tradit Complement Med ; 13(6): 575-587, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38020546

RESUMO

Scientific evidence exists about the association between neurological diseases (i.e., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, depression, and memory loss) and oxidative damage. The increasing worldwide incidence of such diseases is attracting the attention of researchers to find palliative medications to reduce the symptoms and promote quality of life, in particular, in developing countries, e.g., South America and Africa. Among potential alternatives, extracts of Cannabis Sativa L. are suitable for people who have neurological disorders, spasticity, and pain, nausea, resulting from diseases such as cancer and arthritis. In this review, we discuss the latest developments in the use of Cannabis, its subtypes and constituents, extraction methods, and relevant pharmacological effects. Biomedical applications, marketed products, and prospects for the worldwide use of Cannabis Sativa L. extracts are also discussed, providing the bibliometric maps of scientific literature published in representative countries from South America (i.e., Brazil) and Africa (i.e., South Africa). A lack of evidence on the effectiveness and safety of Cannabis, besides the concerns about addiction and other adverse events, has led many countries to act with caution before changing Cannabis-related regulations. Recent findings are expected to increase the social acceptance of Cannabis, while new technologies seem to boost the global cannabis market because the benefits of (-)-trans-delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) use have been proven in several studies in addition to the potential to general new employment.

12.
Children (Basel) ; 10(11)2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38002917

RESUMO

In the early years of schooling, peer groups are key to fostering students' overall learning and development. Yet it has been found that around 10% of children suffer from peer rejection in the classroom, with this problem entailing negative consequences both in the short and long term. The problem proves difficult for adults to detect, which usually leads to a delay in measures being taken to intervene and prevent it. This study applies an experimental design with pre-test and post-test measurements in two groups-experimental and control-in order to address the problem of rejection in the early years of schooling. It explores aspects such as sociometric type, degree of victimisation, social and antisocial behaviour, as well as problematic situations among 637 students at six schools. We then implement an intervention programme for socioemotional competence throughout a school year in an effort to improve students' social skills and relationships, focusing specifically on preventing and reducing the rejection experienced by some of these children. The programme comprises 35 teaching activities and strategies that promote the development of competences for student inclusion (curbing aggression, encouraging teamwork, fostering self-esteem, etc.) and that seek to involve all students, teachers, and relatives by offering an array of complementary resources that enrich the initiatives applied (a programme calendar, assessment notebook, questionnaires, related website, material resources). After the intervention programme, it was found that the experimental group had reduced the percentage of students who suffered rejection from 9.9% to 7.3%, although the same was not true of the control group, which went from 9.5% of rejected students to 10.2%. The reduction in the percentage of rejected students in the experimental group after the application of the programme is an encouraging result that invites us to continue working on more comprehensive interventions to prevent and reduce this phenomenon.

13.
Front Microbiol ; 14: 1244319, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876785

RESUMO

Introduction: Around 10% of the coding potential of Mycobacterium tuberculosisis constituted by two poorly understood gene families, the pe and ppe loci, thought to be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. Understanding the genetic diversity of pe/ppe families is essential to facilitate their potential translation into tools for tuberculosis prevention and treatment. Methods: To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis and M. bovis BCG. Individual pe/ppe gene alignments were extracted and diversity and conservation across the different lineages studied. Results: The pe/ppe genes were classified into three groups based on the level of protein sequence conservation relative to H37Rv, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements, such as duplications and gene fusions, were observed between pe and pe_pgrs genes. Inter-lineage diversity revealed lineage-specific SNPs and indels. Discussion: The high level of pe/ppe genes conservation, together with the lineage-specific findings, suggest their phylogenetic informativeness. However, structural variants and gene rearrangements differing from the reference were also identified, with potential implications for pathogenicity. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control.

14.
Nat Commun ; 14(1): 6756, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875466

RESUMO

High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Terapia Neoadjuvante/métodos , Biomarcadores Tumorais/genética
15.
Pediatr. aten. prim ; 25(99)3 oct. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-226236

RESUMO

Introducción: la falta de actividad física y el sedentarismo en niños se asocia con una mayor adiposidad, bajo nivel de aptitud cardiovascular y riesgo de enfermedades cardiovasculares. Sin embargo, cumplir con las recomendaciones de actividad física se relaciona con mejoras en la salud mental, disminución de la ansiedad y depresión, así como adopción de hábitos saludables. Objetivos: evaluar la relación entre los diferentes dominios de la actividad física y del sedentarismo, medidos de forma objetiva, y los componentes de la condición física en niños españoles de 4 y 5 años. Población y métodos: estudio transversal dentro del proyecto “Observatorio y programa de intervención de ejercicio físico y estilos de vida en familia para niños y niñas de 4 a 5 años en Atención Primaria” (https://observatorioactividadfisica.es). La condición física se evaluó con la batería PREFIT y la cantidad e intensidad de actividad física mediante un acelerómetro tri-axial GENEActiv durante 7 días consecutivos las 24 horas del día. Resultados: la muestra evaluada fue de 70 niños (38 niños y 32 niñas) con una media (intervalo de confianza [IC] del 95%) de 4,83 años. No se observaron diferencias significativas en la condición física entre niños y niñas. Los niños realizaron una actividad física de mayor intensidad y tiempo que las niñas. Además, se encontró una fuerte relación significativa entre los componentes de la condición física y los dominios de la actividad física. Conclusiones: estos hallazgos resaltan la importancia de promover estilos de vida activos desde temprana edad y la necesidad de programas de entrenamiento estructurado para reducir el sedentarismo y mejorar la condición física en esta población (AU)


Introduction: lack of physical activity and sedentary lifestyles in children are associated with increased adiposity, low cardiovascular fitness, and risk of cardiovascular disease. On the other hand, adherence to physical activity recommendations is associated with improvements in mental health, decreased anxiety and depression, and healthier habits.Objectives: to assess the relationship between different domains of physical activity and sedentary behaviour, measured objectively, and components of physical fitness in Spanish children aged 4 and 5 years.Population and methods: cross-sectional study within the project “Observatory and intervention programme on physical exercise and lifestyles in families for children aged 4 to 5 years in primary care” (https://observatorioactividadfisica.es). Physical fitness was assessed with the PREFIT battery. To measure the amount and intensity of physical activity, participants wore a GENEActiv triaxial accelerometer on the non-dominant hand for 7 consecutive days, 24 hours a day.Results: the study sample included 70 children (38 boys and 32 girls) with a mean age of 4.83 years (95% confidence interval [CI]). There were no significant differences in physical fitness between boys and girls, but we found differences in physical activity. Boys were physically active for longer durations and with higher intensity than girls. We also found a significant and strong association between the components of physical fitness and physical activity domains in children aged 4 and 5 years.Conclusions: these findings highlight the importance of promoting active lifestyles from an early age and the need for structured training programs to reduce sedentary behaviour and improve physical fitness in this population. (AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Atividade Motora , Comportamento Sedentário , Comportamento Infantil , Saúde da Criança , Estudos Transversais
16.
ACG Case Rep J ; 10(8): e01114, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37601303

RESUMO

Budd-Chiari syndrome (BCS) is a rare condition characterized by the obstruction of hepatic venous outflow. It is estimated to affect 1 in 100,000 people worldwide. In cases of new BCS, inherited and acquired hypercoagulability states must be evaluated. Coronavirus disease 2019 (COVID-19) can induce a hypercoagulable state because of its extensive inflammatory response, and while it has been reported to cause portal vein thrombosis, it rarely causes BCS. This article presents a case of a 22-year-old man who developed fulminant symptoms and was subsequently diagnosed with BCS and portal vein thrombosis secondary to COVID-19 infection, after ruling out other inherited and acquired causes of BCS. In addition, a literature review is provided to understand the presentation and management of such patients. Although most patients improve with medical management, this article emphasizes the consideration of liver transplant for patients who do not improve.

17.
bioRxiv ; 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37398168

RESUMO

Classification is a fundamental task in biology used to assign members to a class. While linear discriminant functions have long been effective, advances in phenotypic data collection are yielding increasingly high-dimensional datasets with more classes, unequal class covariances, and non-linear distributions. Numerous studies have deployed machine learning techniques to classify such distributions, but they are often restricted to a particular organism, a limited set of algorithms, and/or a specific classification task. In addition, the utility of ensemble learning or the strategic combination of models has not been fully explored.We performed a meta-analysis of 33 algorithms across 20 datasets containing over 20,000 high-dimensional shape phenotypes using an ensemble learning framework. Both binary (e.g., sex, environment) and multi-class (e.g., species, genotype, population) classification tasks were considered. The ensemble workflow contains functions for preprocessing, training individual learners and ensembles, and model evaluation. We evaluated algorithm performance within and among datasets. Furthermore, we quantified the extent to which various dataset and phenotypic properties impact performance.We found that discriminant analysis variants and neural networks were the most accurate base learners on average. However, their performance varied substantially between datasets. Ensemble models achieved the highest performance on average, both within and among datasets, increasing average accuracy by up to 3% over the top base learner. Higher class R2 values, mean class shape distances, and between- vs. within-class variances were positively associated with performance, whereas higher class covariance distances were negatively associated. Class balance and total sample size were not predictive.Learning-based classification is a complex task driven by many hyperparameters. We demonstrate that selecting and optimizing an algorithm based on the results of another study is a flawed strategy. Ensemble models instead offer a flexible approach that is data agnostic and exceptionally accurate. By assessing the impact of various dataset and phenotypic properties on classification performance, we also offer potential explanations for variation in performance. Researchers interested in maximizing performance stand to benefit from the simplicity and effectiveness of our approach made accessible via the R package pheble.

19.
J Vis Exp ; (195)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37318260

RESUMO

Neuroimages are a valuable tool for studying brain morphology in experiments using animal models. Magnetic resonance imaging (MRI) has become the standard method for soft tissues, although its low spatial resolution poses some limits for small animals. Here, we describe a protocol for obtaining high-resolution three-dimensional (3D) information on mouse neonate brains and skulls using micro-computed tomography (micro-CT). The protocol includes those steps needed to dissect the samples, stain and scan the brain, and obtain morphometric measurements of the whole organ and regions of interest (ROIs). Image analysis includes the segmentation of structures and the digitization of point coordinates. In sum, this work shows that the combination of micro-CT and Lugol's solution as a contrast agent is a suitable alternative for imaging the perinatal brains of small animals. This imaging workflow has applications in developmental biology, biomedicine, and other sciences interested in assessing the effect of diverse genetic and environmental factors on brain development.


Assuntos
Meios de Contraste , Processamento de Imagem Assistida por Computador , Animais , Camundongos , Microtomografia por Raio-X/métodos , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Imageamento Tridimensional/métodos
20.
Biomed Pharmacother ; 164: 114997, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37311279

RESUMO

The SARS-CoV-2 pandemic made evident that there are only a few drugs against coronavirus. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety profile. Starting from a list of 116 drug candidates, we used molecular modelling tools to rank the 44 most promising inhibitors. Next, we tested their efficacy as antivirals against α and ß coronaviruses, such as the HCoV-229E and SARS-CoV-2 variants. Four drugs, OSW-1, U18666A, hydroxypropyl-ß-cyclodextrin (HßCD) and phytol, showed in vitro antiviral activity against HCoV-229E and SARS-CoV-2. The mechanism of action of these compounds was studied by transmission electron microscopy and by fusion assays measuring SARS-CoV-2 pseudoviral entry into target cells. Entry was inhibited by HßCD and U18666A, yet only HßCD inhibited SARS-CoV-2 replication in the pulmonary Calu-3 cells. Compared to the other cyclodextrins, ß-cyclodextrins were the most potent inhibitors, which interfered with viral fusion via cholesterol depletion. ß-cyclodextrins also prevented infection in a human nasal epithelium model ex vivo and had a prophylactic effect in the nasal epithelium of hamsters in vivo. All accumulated data point to ß-cyclodextrins as promising broad-spectrum antivirals against different SARS-CoV-2 variants and distant alphacoronaviruses. Given the wide use of ß-cyclodextrins for drug encapsulation and their high safety profile in humans, our results support their clinical testing as prophylactic antivirals.


Assuntos
COVID-19 , Fármacos Dermatológicos , beta-Ciclodextrinas , Humanos , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/uso terapêutico , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
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