Ai based motion analysis software for sport and physical therapy assessment / Software de análisis de movimiento basado en ia para la evaluación del deporte y la fisioterapia / Software de análise de movimento baseado em ia para avaliação de esporte e fisioterapia

ABSTRACT Introduction: As the World Health Organization declared the novel coronavirus as a pandemic in March 2020, physical therapy is more difficult to execute, and social distancing is mandatory in the healthcare sector. Objective: In physical therapy, an online video analysis software that provides real-time graphic and numerical information about the patient's movement executions without direct personal contact would mean a significant improvement in eHealth treatment. Methods: We have developed a software layer on top of OpenPose human body position estimation software that can extract the time series of angles of arbitrary body parts using the output coordinates from OpenPose processing the data recorded by two cameras simultaneously. To validate the procedure of determining the joint angles using the Openpose software we have used the Kinovea software. Results: The comparison of the determined maximal knee angle in our and the Kinovea software, which is widely used in biomechanical measurements, was not significantly different (2.03±1.06°, p<0.05) Conclusion: This indicates, that the developed software can calculate the appropriate joint angles with the accuracy that physiotherapy treatments require. As, to our knowledge no such software yet exists, with the help of this software development, therapists could control and correct the exercises in real-time, and also from a distance, and physical therapy effectiveness could be increased. Level of Evidence II; Experimental, comparative.

RESUMEN Introducción: Como la Organización Mundial de la Salud declaró el nuevo coronavirus como una pandemia en marzo de 2020, la fisioterapia es más difícil de ejecutar, el distanciamiento social es obligatorio en el sector de la salud. Objetivo: En la práctica de fisioterapia un software de análisis de vídeo online que proporcione información gráfica y numérica en tiempo real sobre las ejecuciones de movimiento del paciente sin contacto personal directo supondría una mejora significativa en el tratamiento de la eSalud. Métodos: Fue desarrollado una capa de software sobre el software de estimación de posición del cuerpo humano OpenPose que puede extraer la serie temporal de ángulos de partes arbitrarias del cuerpo utilizando las coordenadas de salida de OpenPose procesando los datos registrados por dos cámaras simultáneamente. Para validar el procedimiento de determinación de los ángulos articulares mediante el software Openpose fue utilizado el software Kinovea. Resultados: La comparación del ángulo máximo de rodilla determinado en nuestro software y Kinovea, que es ampliamente utilizado en mediciones biomecánicas, no fue significativamente diferente (2,03±1,06°, p<0,05). Conclusión: Esto indica que el software desarrollado puede calcular los ángulos articulares adecuados con la precisión que requieren los tratamientos de fisioterapia. Dado que aún no existe dicho software, con la ayuda de este desarrollo de software, los terapeutas podrían controlar y corregir los ejercicios en tiempo real, y también a distancia, y se podría aumentar la eficacia de la fisioterapia. Nivel de Evidencia II; Experimental, comparativo.

RESUMO Introdução: Como a Organização Mundial da Saúde declarou o novo coronavírus como pandemia em março de 2020, a fisioterapia é mais difícil de executar, o distanciamento social é obrigatório no setor de saúde. Objetivo: Na prática da fisioterapia, um software de análise de vídeo online que fornece informações gráficas e numéricas em tempo real sobre as execuções de movimento do paciente sem contato pessoal direto significaria uma melhora significativa no tratamento eHealth. Métodos: Desenvolveu-se uma camada de software em cima do software de estimativa de posição do corpo humano OpenPose que pode extrair as séries temporais de ângulos de partes do corpo arbitrárias usando as coordenadas de saída do OpenPose processando os dados gravados por duas câmeras simultaneamente. Para validar o procedimento de determinação dos ângulos articulares utilizando o software Openpose utilizou-se o software Kinovea. Resultados: A comparação do ângulo máximo do joelho determinado em nosso e no software Kinovea, amplamente utilizado em medidas biomecânicas, não foi significativamente diferente (2,03±1,06°, p<0,05) Conclusão: Isso indica que o software desenvolvido pode calcular os ângulos articulares adequados com a precisão que os tratamentos de fisioterapia exigem. Como esse software ainda não existe, com a ajuda do desenvolvimento desse software, os terapeutas puderam controlar e corrigir os exercícios em tempo real, e também à distância, aumentando a eficácia da fisioterapia. Nível de Evidência II; Experimental, comparativo.

Effects of physical exercise on mood and sleep quality of college students under the covid-19 epidemic / Impacto del ejercicio físico en el estado de ánimo y la calidad del sueño de estudiantes universitarios en el contexto del covid-19 / Impacto do exercício físico no humor e na qualidade do sono de estudantes universitários no contexto do covid-19

ABSTRACT Introduction: The management of university campuses in the context of COVID-19 makes the mental health of college students draw much attention. Objective: To explore the effects of physical exercise under COVID-19 on sleep quality and mood of college students. Methods: 1983 college students from The Civil Aviation University of China were selected, and their physical exercise state, sleep quality, and emotional state were measured by a questionnaire. Results: Physical exercise has a significant positive effect on college students' mood and sleep quality, and sleep quality has a considerable impact on their mood. There is no gender difference in mood and sleep quality. The amount of physical exercise has a significant difference in sleep quality and mood. Compared with the students who do a lot of physical exercises, those who do a lot of physical exercises have higher sleep quality and more vital stronger emotional control ability. Conclusion: This study can provide a reference for universities to carry out mental health education during the particular period of epidemic prevention and control. Level of evidence II; Diagnostic Studies—Investigating a Diagnostic Test.

RESUMEN Introducción: la gestión del campus universitario en el contexto del COVID-19 hace que la salud mental de los estudiantes universitarios llame mucho la atención. Objetivo: explorar los efectos del ejercicio físico bajo COVID-19 sobre la calidad del sueño y el estado de ánimo de estudiantes universitarios. Métodos: se selecciona estudiantes universitarios 1983 de la universidad de aviación Civil de China, y se midió su estado de ejercicio físico, calidad del sueño y estado emocional mediante un cuestionario. Resultados: el ejercicio físico tiene un efecto positivo significativo en el estado de ánimo y la calidad del sueño de los estudiantes universitarios, y la calidad del sueño tiene un efecto significativo en su estado de ánimo. No hay diferencia de género en cuanto al estado de ánimo y la calidad del sueño. La cantidad de ejercicio físico tiene una diferencia significativa en la calidad del sueño y el estado de ánimo. En comparación con los estudiantes que hacen mucho ejercicio físico, los estudiantes que hacen mucho ejercicio físico tienen una mayor calidad de sueño y una mayor capacidad de control emocional. Conclusión: este estudio puede servir de referencia para que las universidades realicen educación en salud mental durante el período especial de prevención y control de epidemias. Nivel de Evidência II; Estudios diagnósticos: investigación de una prueba diagnóstica.

RESUMO Introdução: A gestão do campus universitário no contexto do COVID-19 faz com que a saúde mental dos universitários chame muita atenção. Objetivo: Explorar os efeitos do exercício físico sob o COVID-19 sobre a qualidade do sono e o humor dos estudantes universitários. Métodos: Foram selecionados 1983 estudantes universitários da Universidade de Aviação Civil da China, e seu estado de exercício físico, qualidade do sono e estado emocional foram medidos por um questionário. Resultados: O exercício físico tem um efeito positivo significativo no humor e na qualidade do sono dos estudantes universitários, e a qualidade do sono tem um efeito significativo em seu humor. Não há diferença de gênero no humor e na qualidade do sono. A quantidade de exercício físico tem diferença significativa na qualidade do sono e no humor. Em comparação com os alunos que fazem muito exercício físico, os alunos que fazem muito exercício físico têm maior qualidade de sono e maior capacidade de controle emocional. Conclusão: Este estudo pode fornecer referência para que as universidades realizem a educação em saúde mental durante o período especial de prevenção e controle de epidemias. Nível de evidência II; Estudos de Diagnóstico — Investigando um Teste de Diagnóstico.

Sedentary behavior among medical students: repercussions of the coronavirus pandemic / Conduta sedentária entre estudantes de medicina: repercussões da pandemia do coronavírus

ABSTRACT Introduction: In order to face COVID-19, social restriction measures were adopted that influenced the population's living habits, increasing sedentary lifestyle. Considering the high complexity and dedication required by the Medicine course, it becomes relevant to investigate the effect of the pandemic on the practice of physical exercise and sedentary behavior of these students. Objective: Identify changes in physical activity and sedentary behavior self-reported by medical students in the city of Salvador, Bahia, before and during the self-confinement imposed by the COVID-19 pandemic. Methods: Longitudinal, prospective, quantitative study carried out with regularly enrolled medical students over 18 years of age. A virtual, structured, anonymous, self-completed questionnaire was applied, containing sociodemographic and academic aspects. In addition, the International Physical Activity Questionnaire (IPAQ) was applied in its short version, considering the period before and during the pandemic. Through this, the level of physical activity, sedentary behavior and time spent walking and performing moderate and vigorous activities were measured. Results: 268 medical students were included, predominantly women (65.7%), white (50.0%) and mixed race (38.8%), aged 24.2 ± 5.5 years, single (90.7%), attending the clinical cycle (59.0%), in private institutions (78.4%). No statistically significant differences were identified in the level of physical activity and in the time spent with moderate and vigorous activities. However, there was a reduction in walking time (p<0.00001) and an increase in sedentary behavior (p=0.001) during the COVID-19 pandemic, with the greatest impact among women (p=0.0009). Conclusion: The repercussions of the COVID-19 pandemic have been shown to increase the sedentary behavior of medical students, especially among women, and to reduce activity time spent with walking. Longitudinal studies are needed to analyze the medium and long-term consequences of this change in the healthy lifestyle habits of medical students. Level of evidence II; Comparative prospective study.

Resumen Introducción: Frente al COVID-19 se adoptaron medidas de restricción social que influyeron en los hábitos de vida de la población, aumentando el sedentarismo. Considerando la alta complejidad y la dedicación exigida por la carrera de Medicina, se torna relevante investigar el efecto pandémico sobre la práctica de ejercicio físico y la conducta sedentaria de estos estudiantes. Objetivos: Identificar los cambios en la actividad física y en la conducta sedentaria auto-reportados por los estudiantes de Medicina de la ciudad de Salvador, Bahía, Brasil, antes y durante el auto-confinamiento impuesto por la pandemia de COVID-19. Métodos: Estudio longitudinal, prospectivo, cuantitativo, realizado con estudiantes de medicina regularmente matriculados, mayores de 18 años. Foi aplicado um questionário virtual, estruturado, anónimo, autocompletado, contendo aspectos sociodemográficos e académicos. Além disso, foi aplicado o International Physical Activity Questionnaire (IPAQ), em sua versão curta, considerando o período antes e durante a pandemia. A través de éste, se midió el nivel de actividad física, el comportamiento sedentario y el tiempo dedicado a caminar, así como las actividades moderadas y vigorosas. Resultados: Se incluyeron 268 estudiantes de medicina, predominantemente mujeres (65,7%), blancas (50,0%) y morenas (38,8%), de 24,2 ± 5,5 años de edad, solteras (90,7%), en el ciclo clínico (59,0%), en instituciones privadas (78,4%). No se identificaron diferencias estadísticamente significativas en el nivel de actividad física y el tiempo dedicado a actividades moderadas y vigorosas. Sin embargo, hubo una reducción en el tiempo de caminata (p<0,00001) y un aumento en la conducta sedentaria (p=0,001) durante la pandemia COVID-19, siendo mayor el impacto entre las mujeres (p=0,0009). Conclusión: Las repercusiones de la pandemia COVID-19 se manifestaron en el aumento de la conducta sedentaria entre los estudiantes de medicina, especialmente entre las mujeres, además de la reducción del tiempo de actividad dedicado a caminar. Son necesarios estudios longitudinales para analizar las consecuencias a medio y largo plazo de este cambio en los hábitos de vida saludables de los estudiantes de medicina. Nivel de evidencia II; Estudio Prospectivo Comparativo.

RESUMO Introdução: Foram adotadas medidas de restrição social para o enfrentamento da COVID-19 que influenciaram nos hábitos de vida da população, aumentando o sedentarismo. Considerando a alta complexidade e a dedicação exigida pelo curso de Medicina, torna-se relevante investigar o efeito da pandemia na prática de exercício físico e conduta sedentária desses estudantes. Objetivos: Identificar alterações na atividade física e na conduta sedentária autorrelatadas por acadêmicos de Medicina na cidade de Salvador, Bahia, antes e durante o autoconfinamento imposto pela pandemia de COVID-19. Métodos: Estudo longitudinal, prospectivo, quantitativo, realizado com estudantes de Medicina, maiores de 18 anos, regularmente matriculados. Foi aplicado um questionário virtual, estruturado, anônimo, de autopreenchimento, contendo aspectos sociodemográficos e acadêmicos. Além disso, foi aplicado o International Physical Activity Questionnaire (IPAQ), em sua versão curta, considerando o período antes e durante a pandemia. Através deste, foram mensurados nível de atividade física, conduta sedentária e tempo de realização de caminhada, além de atividades moderadas e vigorosas. Resultados: Foram incluídos 268 estudantes de Medicina, predominantemente mulheres (65,7%), da raça branca (50,0%) e parda (38,8%), com idade de 24,2 ± 5,5 anos, solteiros (90,7%), cursando o ciclo clínico (59,0%), em instituições privadas (78,4%). Não foram identificadas diferenças estatisticamente significantes no nível de atividade física e no tempo despendido com atividades moderadas e vigorosas. Entretanto, houve redução no tempo de caminhada (p<0,00001) e aumento da conduta sedentária (p=0,001) durante a pandemia de COVID-19, sendo o impacto maior entre as mulheres (p=0,0009). Conclusão: Foram demonstradas as repercussões da pandemia de COVID-19 no aumento da conduta sedentária dos estudantes de Medicina, principalmente entre as mulheres, além da redução do tempo de atividade despendido com caminhadas. Estudos longitudinais são necessários para analisar as consequências a médio e longo prazo dessa alteração nos hábitos de vida saudáveis de estudantes de Medicina. Nível de evidência II; Estudo Prospectivo Comparativo.

Global research trends related to coronavirus disease 2019 and the aged: a bibliometric analysis

ABSTRACT BACKGROUND: A bibliometric analysis covering only the production of original studies or considering world production until 2022 has yet to be conducted. The creation and advancement of vaccines have also influenced research priorities, demonstrating the need for a new approach to this subject. OBJECTIVES: To analyze worldwide scientific production related to coronavirus disease 2019 (COVID-19) and the aged and to describe what has already been produced. DESIGN AND SETTING: Bibliometric analysis with a quantitative approach. METHOD: The search terms "COVID-19," "SARS-CoV-2," "Aged," and "Elderly" were used to retrieve articles from the Web of Science database. A total of 684 articles were included in the analysis. Data were imported into RStudio Desktop Software and linked to R Software. The Bibliometrix R package and VOSviewer software were used for analysis. RESULTS: Most articles were published in 2020. These were produced by 4,937 authors and published in 379 journals. The keyword most used by the authors was "COVID-19." Publications from 77 countries were obtained. China had the highest article production ranking, and Spain collaborated the most. The articles addressed the implications of the pandemic on the aged, the relationship between vaccination in the aged, and the implications for the disease itself. CONCLUSION: Further research should be conducted, mainly concerning vaccines and vaccination of the aged, owing to the need for and importance of immunization in this risk group, including assessing the long-term effects of vaccines.

New records of Coronatella (Crustacea, Branchiopoda, Chydoridae) from Colombia with the first report of Coronatella undata and of the male of Coronatella monacantha

Abstract Biological samples obtained from a small temporary pond of northern Colombia yielded the first record Coronatella undata Sousa, Elmoor-Loureiro and Santos, 2015 and of the male of C. monacantha (Sars, 1901) for Colombia. In this study, the morphology of female of Coronatella undata and female and male of C. monacantha was described and compared to other species within the genus. C. undata was originally described from Brazil and, among the species of the Coronatella monacantha complex, seems to be closely related to C. acuticostata (Sars, 1903). C. undata shows some similarities with C. monacantha, but it can be identified by important diagnostic characters such as: 1) posterior-ventral corner of valve with two denticles, 2) seta on exopodite of trunk limb II rudimentary, 3) filter comb of trunk limb II with six setae, 4) ODL seta of trunk limb I shorter than longest seta of IDL. C. monacantha is the most reported species in the Neotropical region and the male most resemble C. paulinae Sousa, Elmoor-Loureiro & Santos, 2015 in relation to (i), length/wide of postabdomen ratio (ii) basal spine almost straight and (iii)) long basal spine reaching the mid-length of basal spine. However, they can be separated by (i) number of lateral seta on the antennule, (ii) postanal angle, (iii) position of gonopore (iv) presence of a denticle on posterior-ventral corner of valve

Resumo Amostras biológicas obtidas de uma pequena lagoa temporária do norte da Colômbia proporcionaram o primeiro registro de Coronatella undata Sousa, Elmoor-Loureiro e Santos, 2015 e do macho de Coronatella monacantha (Sars, 1901) na Colômbia. Neste estudo, foi descrita a morfologia de fêmeas de C. undata e de fêmeas e machos de C. monacantha, comparando-a com outras espécies do gênero. Coronatella undata foi descrita originalmente no Brasil e, entre as espécies do complexo C. monacantha, parece estar intimamente relacionada com Coronatella acuticostata (Sars, 1903). Coronatella undata apresenta algumas semelhanças com C. monacantha, mas pode ser identificada por seus principais caracteres, tais como: 1) ângulo posterior ventral da valva com dois dentículos; 2) cerda rudimentar no exopodito do ramo do tronco II; 3) filtro da gnatobase do apêndice torácico II com seis cerdas; 4) cerda ODL do membro do tronco I mais curta que a cerda mais longa do IDL. Coronatella monacantha é a espécie mais relatada na região neotropical, e o macho se assemelha mais a Coronatella paulinae Sousa, Elmoor-Loureiro & Santos em relação à/ao: (i) razão comprimento / largura do pós-abdômen, (ii) espinho basal quase reto e (iii) espinho basal longo com a metade do comprimento do espinho basal. No entanto, eles podem ser separados pelo/pela: (i) número de cerdas laterais na antênula, (ii) ângulo postanal, (iii) posição do gonóporo e (iv) presença de dentículo no canto ventral posterior da valva.

Assessment of Endothelial Barrier Functions in Extra Embryonic Vasculature of Chick Embryo as an Alternative Model.

Vascular permeability, a tightly regulated process, is a direct measure of angiogenic and immune responses in the endothelium altered in several acute and chronic diseases such as sepsis, high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE), ischemia, and coronavirus disease 2019 (COVID-19) endotheliitis. Both endogenous and exogenous factors such as cytokines, chemokines, and hormones may affect vascular permeability. The conventional tools available for the measurement of vascular permeability in vitro and in vivo based on collagen-coated Transwell and dye-based spectrophotometric methods are indirect measures of permeability. In this chapter, we present our live in ovo protocols based on dextran-Texas red and avian chorioallantoic membrane assay developed using custom-made equipment to assess leakiness of endothelial cell barrier both in vitro and in vivo. Further, we validate this assay using different stressors such as ischemia and hypoxia known to affect endothelial barrier properties by potentiating actin stress fiber disorganization and disrupting the cell-cell junctions.

Relation between Apolipoprotein E in Alzheimer's Disease and SARS-CoV-2 and their Treatment Strategy: A Review.

COVID-19, which primarily affects the pulmonary system, turned out to be a global pandemic, whereas the effects on other systems are still unknown. SARS-CoV-2, binds to angiotensinconverting enzyme 2 (ACE2) receptors in the lungs, causing pneumonia-like symptoms. The same ACE receptors are also present in organs other than the lungs. Therefore, there is a need to study the impact of coronavirus on other human body organs. Recently, UK Biobank reports on the genetic risk factor of the virus attack. A double mutation in the apolipoprotein E (APOE4) allele has shown a significant role in COVID-19. The same APOE4 mutation has already been proven to hold a key role in developing early-onset Alzheimer's disease (EOAD). Despite this data, Alzheimer's disease is believed to be a comorbidity of COVID-19. Previous virus attacks on the same viral family, Coronaviridae, produced neurological effects like neurodegeneration, neuronal inflammation, and other central nervous system-related dysfunctions. Since the long-term implications of COVID-19 are unknown, more research into the impact of the virus on the central nervous system is needed. Both COVID-19 and AD share a common genetic factor, so that AD patients may have a greater risk of SARS-CoV-2. Here, in this review, we have briefly discussed the role of APOE4 in the pathogenesis of AD and SARS-CoV-2, along with their treatment strategy, current scenario, and possible future directions.

Herbal Substances with Antiviral Effects: Features and Prospects for the Treatment of Viral Diseases with Emphasis on Pro-Inflammatory Cytokines.

Viral diseases have a significant impact on human health, and three novel coronaviruses (CoV) have emerged during the 21st century. In this review, we have emphasized the potential of herbal substances with antiviral effects. Our investigation focused on the features and prospects of viral disease treatment, with a particular emphasis on proinflammatory cytokines. We conducted comprehensive searches of various databases, including Science Direct, CABI Direct, Web of Science, PubMed, and Scopus. Cytokine storm mechanisms play a crucial role in inducing a pro-inflammatory response by triggering the expression of cytokines and chemokines. This response leads to the recruitment of leukocytes and promotes antiviral effects, forming the first line of defense against viruses. Numerous studies have investigated the use of herbal medicine candidates as immunomodulators or antivirals. However, cytokine-storm-targeted therapy is recommended for patients with acute respiratory distress syndrome caused by SARS-CoV to survive severe pulmonary failure. Our reviews have demonstrated that herbal formulations could serve as alternative medicines and significantly reduce complicated viral infections. Furthermore, they hold promising potential as specific antiviral agents in experimental animal models.

Impact of COVID-19 on Anxiety and Depression - Biopsychosocial Factors.

Anxiety and depression are prevalent mental disorders around the world. The etiology of both diseases is multifactorial, involving biological and psychological issues. The COVID-19 pandemic settled in 2020 and culminated in several changes in the routine of individuals around the world, affecting mental health. People infected with COVID-19 are at greater risk of developing anxiety and depression, and individuals previously affected by these disorders have worsened the condition. In addition, individuals diagnosed with anxiety or depression before being affected by COVID-19 developed the severe illness at higher rates than individuals without mental disorders. This harmful cycle involves several mechanisms, including systemic hyper-inflammation and neuroinflammation. Furthermore, the context of the pandemic and some previous psychosocial factors can aggravate or trigger anxiety and depression. Disorders are also risks for a more severe picture of COVID-19. This review discusses research on a scientific basis, which brings evidence on biopsychosocial factors from COVID-19 and the context of the pandemic involved in anxiety and depression disorders.

Computer-aided Drug Discovery Approaches in the Identification of Natural Products against SARS-CoV-2: A Review.

The COVID-19 pandemic is raising a worldwide search for compounds that could act against the disease, mainly due to its mortality. With this objective, many researchers invested in the discovery and development of drugs of natural origin. To assist in this search, the potential of computational tools to reduce the time and cost of the entire process is known. Thus, this review aimed to identify how these tools have helped in the identification of natural products against SARS-CoV-2. For this purpose, a literature review was carried out with scientific articles with this proposal where it was possible to observe that different classes of primary and, mainly, secondary metabolites were evaluated against different molecular targets, mostly being enzymes and spike, using computational techniques, with emphasis on the use of molecular docking. However, it is noted that in silico evaluations still have much to contribute to the identification of an anti- SARS-CoV-2 substance, due to the vast chemical diversity of natural products, identification and use of different molecular targets and computational advancement.

Graph Convolutional Capsule Regression (GCCR): A Model for Accelerated Filtering of Novel Potential Candidates for SARS-CoV-2 based on Binding Affinity.

BACKGROUND: There has been a growing interest in discovering a viable drug for the new coronavirus (SARS-CoV-2) since the beginning of the pandemic. Protein-ligand interaction studies are a crucial step in the drug discovery process, as it helps us narrow the search space for potential ligands with high drug-likeness. Derivatives of popular drugs like Remdesivir generated through tools employing evolutionary algorithms are usually considered potential candidates. However, screening promising molecules from such a large search space is difficult. In a conventional screening process, for each ligand-target pair, there are time-consuming interaction studies that use docking simulations before downstream tasks like thermodynamic, kinetic, and electrostatic-potential evaluation. OBJECTIVE: This work aims to build a model based on deep learning applied over the graph structure of the molecules to accelerate the screening process for novel potential candidates for SARS-CoV-2 by predicting the binding energy of the protein-ligand complex. METHODS: In this work, 'Graph Convolutional Capsule Regression' (GCCR), a model which uses Capsule Neural Networks (CapsNet) and Graph Convolutional Networks (GCN) to predict the binding energy of a protein-ligand complex is being proposed. The model's predictions were further validated with kinetic and free energy studies like Molecular Dynamics (MD) for kinetic stability and MM/GBSA analysis for free energy calculations. RESULTS: The GCCR showed an RMSE value of 0.0978 for 81.3% of the concordance index. The RMSE of GCCR converged around the iteration of just 50 epochs scoring a lower RMSE than GCN and GAT. When training with Davis Dataset, GCCR gave an RMSE score of 0.3806 with a CI score of 87.5%. CONCLUSION: The proposed GCCR model shows great potential in improving the screening process based on binding affinity and outperforms baseline machine learning models like DeepDTA, KronRLS, Sim- Boost, and other Graph Neural Networks (GNN) based models like Graph Convolutional Networks (GCN) and Graph Attention Networks (GAT).

Designing a Multi-epitope Vaccine against the SARS-CoV-2 Variant based on an Immunoinformatics Approach.

BACKGROUND: SARS-CoV-2 is a life-threatening virus in the world. Scientific evidence indicates that this pathogen will emerge again in the future. Although the current vaccines have a pivotal role in the control of this pathogen, the emergence of new variants has a negative impact on their effectiveness. OBJECTIVES: Therefore, it is urgent to consider the protective and safe vaccine against all subcoronavirus species and variants based on the conserved region of the virus. Multi-epitope peptide vaccine (MEV), comprised of immune-dominant epitopes, is designed by immunoinformatic tools and it is a promising strategy against infectious diseases. METHODS: Spike glycoprotein and nucleocapsid proteins from all coronavirus species and variants were aligned and the conserved region was selected. Antigenicity, toxicity, and allergenicity of epitopes were checked by a proper server. To robust the immunity of the multi-epitope vaccine, cholera toxin b (CTB) and three HTL epitopes of tetanus toxin fragment C (TTFrC) were linked at the N-terminal and C-terminal of the construct, respectively. Selected epitopes with MHC molecules and the designed vaccines with Toll-like receptors (TLR-2 and TLR-4) were docked and analyzed. The immunological and physicochemical properties of the designed vaccine were evaluated. The immune responses to the designed vaccine were simulated. Furthermore, molecular dynamic simulations were performed to study the stability and interaction of the MEV-TLRs complexes during simulation time by NAMD (Nanoscale molecular dynamic) software. Finally, the codon of the designed vaccine was optimized according to Saccharomyces boulardii. RESULTS: The conserved regions of spike glycoprotein and nucleocapsid protein were gathered. Then, safe and antigenic epitopes were selected. The population coverage of the designed vaccine was 74.83%. The instability index indicated that the designed multi-epitope was stable (38.61). The binding affinity of the designed vaccine to TLR2 and TLR4 was -11.4 and -11.1, respectively. The designed vaccine could induce humoral and cellular immunity. CONCLUSION: In silico analysis showed that the designed vaccine is a protective multi-epitope vaccine against SARS-CoV-2 variants.

Enhancing the optical properties of [P(MMA-co-AN)/ZrO2]TF by doping fluorescein dye, TD-DFT/DMOl3 simulations and COVID-19 main protease docking.

Poly methyl methacrylate-co-acrylonitrile [P(MMA-co-AN)]HB hybrid blend was first synthesized by precipitation polymerization and characterized by static light scattering. With a thickness of 200 ± 5 nm, the hybrid nanocomposite of [P(MMA-co-AN)/ZrO2]HNC thin films were fabricated by spin coating method. X-Ray diffraction studies showed a monoclinic cell structure with an average crystalline size of 180 nm for the fabricated films. An improvement in the optical properties were figured out when fluorescein dye was doped in the hybrid nanocomposite. Where the optical energy gap was decreased from 4.31 to 4.025 eV for fluorescein doped hybrid nanocomposite. While a possible energy transfer between ZrO2 and fluorescein was investigated in the laser photoluminescence spectra. DFT-CASTEP simulations were deployed to calculate the theoretical optical properties for the molecules under consideration. The structural and optical simulations of [P(MMA-co-AN)/ZrO2]HNC were found to match the experimental data. Molecular docking studies of [P(MMA-co-AN)/ZrO2]Iso against the main protease of novel corona virus COVID 19 (PDB code 6LU7 Hormone) showed an interesting interaction.

Mesenchymal Stem Cells Therapy for COVID-19: From Basic Research to Clinical Trial.

The novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a serious challenge for human health. In severe cases, patients suffer from acute respiratory distress syndrome even organ failure, usually owing to the dysregulated immune response and widespread inflammation. Considering that there is no known cure for COVID-19 despite the increased morbidity and mortality rate of COVID-19, modalities targeting immunity and inflammation may be promising therapeutics against COVID-19. Mesenchymal stem cells (MSCs) possessing immunomodulatory, anti-inflammatory, anti-apoptotic, and antiviral properties, can be of potential benefit to a subset of severe and critically ill patients with COVID-19. In the present study, we described the underlying mechanisms of MSCs therapy and provided a thorough research study on the recent clinical trials of MSCs for SARS-CoV-2 infection.

Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery.

Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon´s isolated compounds from 2017-2020. We found that only α-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 M^pro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 M^pro with docking scores of -11.2 and -11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the M^pro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.

Screening of Inhibitors against Idiopathic Pulmonary Fibrosis: Few-shot Machine Learning and Molecule Docking based Drug Repurposing.

INTRODUCTION: Idiopathic pulmonary fibrosis is a chronic progressive disorder and is diagnosed as post-COVID fibrosis. Idiopathic pulmonary fibrosis has no effective treatment because of the low therapeutic effects and side effects of currently available drugs. AIM: The aim is to screen new inhibitors against idiopathic pulmonary fibrosis from traditional Chinese medicines. METHODS: Few-shot-based machine learning and molecule docking were used to predict the potential activities of candidates and calculate the ligand-receptor interactions. In vitro A549 cell model was taken to verify the effects of the selected leads on idiopathic pulmonary fibrosis. RESULTS: A logistic regression classifier model with an accuracy of 0.82 was built and, combined with molecule docking, used to predict the activities of candidates. 6 leads were finally screened out and 5 of them were in vitro experimentally verified as effective inhibitors against idiopathic pulmonary fibrosis. CONCLUSION: Herbacetin, morusin, swertiamarin, vicenin-2, and vitexin were active inhibitors against idiopathic pulmonary fibrosis. Swertiamarin exhibited the highest anti-idiopathic pulmonary fibrosis effect and should be further in vivo investigated for its activity.

Association Between Low Anti-spike Antibody Levels After the Third Dose of SARS-CoV-2 Vaccination and Hospitalization due to Symptomatic Breakthrough Infection in Kidney Transplant Recipients.

Background: Whether anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels post-third coronavirus disease (COVID-19) vaccination correlate with worse outcomes due to breakthrough infection is unclear. We evaluated the association between anti-SARS-CoV-2 antibody levels and symptomatic breakthrough infection or hospitalization during the Omicron surge in kidney transplant recipients. Methods: In total, 287 kidney transplant recipients expected to receive a third vaccination were enrolled between November 2021 and February 2022. The Abbott SARS-CoV-2 IgG II Quant test (Abbott, Chicago, IL, USA) was performed within three weeks before and four weeks after the third vaccination. The incidence of symptomatic breakthrough infection and hospitalization from two weeks to four months post-third vaccination was recorded. Results: After the third vaccination, the seropositive rate and median antibody titer of the 287 patients increased from 57.1% to 82.2% and from 71.7 (interquartile range [IQR] 7.2-402.8) to 1,612.1 (IQR 153.9-5,489.1) AU/mL, respectively. Sixty-four (22.3%) patients had symptomatic breakthrough infections, of whom 12 required hospitalization. Lower anti-receptor-binding domain (RBD) IgG levels (<400 AU/mL) post-third vaccination were a risk factor for symptomatic breakthrough infection (hazard ratio [HR]=3.46, P<0.001). Anti-RBD IgG levels <200 AU/mL were a critical risk factor for hospitalization (HR=36.4, P=0.007). Conclusions: Low anti-spike IgG levels after third vaccination in kidney transplant recipients were associated with symptomatic breakthrough infection and, particularly, with hospitalization during the Omicron surge. These data can be used to identify patients requiring additional protective measures, such as passive immunization using monoclonal antibodies.