Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis.

BACKGROUND: The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. OBJECTIVE: A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. METHODS: A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. RESULTS: A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. CONCLUSION: Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

ANTECEDENTES: O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. OBJETIVO: Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. MéTODOS: Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. RESULTADOS: Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. CONCLUSãO: Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

Preliminary Bioactivity Assessment of Myrothecium Species (Stachybotryaceae) Crude Extracts against Aedes aegypti (Diptera: Culicidae): A First Approach from This Phytopathogenic Fungi.

Mosquitoes, as insect vectors, play a crucial role in transmitting viruses and parasites, leading to millions of human deaths in tropical and subtropical regions worldwide. This study aimed to evaluate the effects of ethanolic extracts of three species within the genus Myrothecium (M. roridum, M. dimerum, and M. nivale) on Aedes aegypti mosquito larvae to assess the inhibitory effect on growth and development, as well as to determine mortality. We quantify the average lethal concentrations and provide a qualitative characterization of the chemical groups responsible for their potential. Phytochemical screening revealed the presence of alkaloids, flavonoids, and terpenoids in the ethanolic extracts of the three fungal species. Tannins were found only in the extracts of M. dimerum and M. roridum. We observed a clear dependence of the effects of the crude extracts on mosquito larvae on the concentrations used and the duration of exposure. The toxic effect was observed after 48 h at a concentration of 800 ppm for both M. dimerum and M. nivale, while M. roridum showed effectiveness after 72 h. All three species within the genus Myrothecium exhibited 100% biological activity after 72 h of exposure at 600 ppm. At lower concentrations, there was moderate growth and development inhibitory activity in the insect life cycle. The study highlights the effectiveness of crude Myrothecium extracts in combating mosquito larvae, with effects becoming apparent between 48 and 72 h of exposure. This initial approach underscores the potential of the fungus's secondary metabolites for further in-depth analysis of their individual effects or synergies between them.

Morpho-physiological and phytohormonal changes during the induction of adventitious root development stimulated by exogenous IBA application in Magnolia biondii Pamp / Alterações morfofisiológicas e fito-hormonais durante a indução do desenvolvimento radicular adventício estimulado pela aplicação exógena do AIB em Magnolia biondii Pamp

Magnolia biondii Pamp is an important ornamental tree species widely grown and used as a rootstock in the propagation of different Magnolia varieties. In the current studies, anatomical, physiological and endogenous hormones were studied to check the effect of IBA 750 mg/L on the adventitious rooting and to provide theoretical and technical support for the propagation of Magnolia biondii Pamp through stem cuttings. Two thousand stem cuttings were prepared and divided into two groups i.e., IBA treated cuttings and water control. For the evaluation of antioxidant enzyme activities, and endogenous hormones levels, samples were collected on the day of planting and each 5th day and further steps were carried out in the laboratory according to the protocols and proper precautions. For the anatomical observations, samples were collected on the 13th, 15th, and 17th day for IBA treated cuttings while 21st, 23rd, and 25th day for control. Collected samples were preserved in the FAA solution and further observations were carried out in the laboratory. Anatomical observations showed that it took 13 days for the differentiation of root primordia to the appearance of young adventitious roots in IBA treated cuttings, while it took 21 days to develop primordia in the control. Antioxidant enzyme activities involved in ROS were significantly higher in the IBA treated cuttings compared to control. POD showed a peak on the 13th day before the emergence of roots in IBA treated cuttings while it showed a peak on the 21st day in the control. PPO showed a peak on the 21st day in the IBA treated cuttings while it showed a peak on the 29th day in the control. SOD showed a peak on the 17th day in IBA treated cuttings, while it showed a peak on the 25th day in the control. Exogenous application of IBA enhanced the endogenous IAA and GA3 levels compared to CK, while it reduced the levels of ABA continuously at the time of rooting and then increased gradually. Inclusively, our study suggests that IBA 750 mg/L is efficient for the rooting of Magnolia biondii Pamp cuttings, as it enhanced the process of antioxidant enzyme activities, endogenous hormones levels and reduced the time of root formation which is evident from the anatomical observations.

Magnolia biondii Pamp é uma importante espécie de árvore ornamental muito cultivada e utilizada como porta-enxerto na propagação de diferentes variedades de Magnolia. Nos estudos atuais, hormônios anatômicos, fisiológicos e endógenos foram estudados para verificar o efeito do AIB na dose de 750 mg / L no enraizamento adventício e fornecer suporte teórico e técnico para a propagação de M. biondii Pamp por meio de estacas. Duas mil estacas foram preparadas e divididas em dois grupos, ou seja, tratadas com AIB e controle de água. Para a avaliação das atividades das enzimas antioxidantes e dos níveis de hormônios endógenos, as amostras foram coletadas no dia do plantio e a cada 5 dias, enquanto as demais etapas foram realizadas em laboratório de acordo com os protocolos e os devidos cuidados. Para as observações anatômicas, as amostras foram coletadas no 13º, 15º e 17º dias para estacas tratadas com AIB e no 21º, 23º e 25º dias para o controle. As amostras coletadas foram preservadas em solução FAA, e outras observações foram realizadas em laboratório. Observações anatômicas mostraram a necessidade de 13 dias para a diferenciação dos primórdios radiculares até o aparecimento de raízes adventícias jovens em estacas tratadas com AIB e de 21 dias para o desenvolvimento dos primórdios no controle. As atividades das enzimas antioxidantes envolvidas nas ROS foram significativamente maiores nas estacas tratadas com AIB em comparação com o controle. A POD apresentou pico no 13º dia antes da emergência das raízes nas estacas tratadas com AIB, enquanto no 21º dia apresentou pico no controle. A PPO teve pico no 21º dia nas estacas tratadas com AIB e no 29º dia no controle. A SOD apresentou pico no 17º dia nas estacas tratadas com AIB e no 25º dia no controle. A aplicação exógena de AIB aumentou os níveis endógenos de IAA e GA3 em relação ao controle, enquanto reduziu os níveis de ABA continuamente no momento do enraizamento e, em seguida, aumentou gradativamente. Inclusive, nosso estudo sugere que o AIB na dose de 750 mg / L é eficiente para o enraizamento de estacas de M. biondii Pamp, visto que potencializou o processo de atividades de enzimas antioxidantes e os níveis de hormônios endógenos, além de reduzir o tempo de formação de raízes, o que fica evidente nas observações anatômicas.

Revolutionizing early Alzheimer's disease and mild cognitive impairment diagnosis: a deep learning MRI meta-analysis / Revolucionando a doença de Alzheimer precoce e o diagnóstico de comprometimento cognitivo leve: uma metanálise de aprendizagem profunda por ressonância magnética

Abstract Background The early diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains a significant challenge in neurology, with conventional methods often limited by subjectivity and variability in interpretation. Integrating deep learning with artificial intelligence (AI) in magnetic resonance imaging (MRI) analysis emerges as a transformative approach, offering the potential for unbiased, highly accurate diagnostic insights. Objective A meta-analysis was designed to analyze the diagnostic accuracy of deep learning of MRI images on AD and MCI models. Methods A meta-analysis was performed across PubMed, Embase, and Cochrane library databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on the diagnostic accuracy of deep learning. Subsequently, methodological quality was assessed using the QUADAS-2 checklist. Diagnostic measures, including sensitivity, specificity, likelihood ratios, diagnostic odds ratio, and area under the receiver operating characteristic curve (AUROC) were analyzed, alongside subgroup analyses for T1-weighted and non-T1-weighted MRI. Results A total of 18 eligible studies were identified. The Spearman correlation coefficient was -0.6506. Meta-analysis showed that the combined sensitivity and specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.84, 0.86, 6.0, 0.19, and 32, respectively. The AUROC was 0.92. The quiescent point of hierarchical summary of receiver operating characteristic (HSROC) was 3.463. Notably, the images of 12 studies were acquired by T1-weighted MRI alone, and those of the other 6 were gathered by non-T1-weighted MRI alone. Conclusion Overall, deep learning of MRI for the diagnosis of AD and MCI showed good sensitivity and specificity and contributed to improving diagnostic accuracy.

Resumo Antecedentes O diagnóstico precoce da doença de Alzheimer (DA) e do comprometimento cognitivo leve (CCL) continua sendo um desafio significativo na neurologia, com métodos convencionais frequentemente limitados pela subjetividade e variabilidade na interpretação. A integração da aprendizagem profunda com a inteligência artificial (IA) na análise de imagens de ressonância magnética surge como uma abordagem transformadora, oferecendo o potencial para insights diagnósticos imparciais e altamente precisos. Objetivo Uma metanálise foi projetada para analisar a precisão diagnóstica do aprendizado profundo de imagens de ressonância magnética em modelos de DA e CCL. Métodos Uma metanálise foi realizada nos bancos de dados das bibliotecas PubMed, Embase e Cochrane seguindo as diretrizes Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), com foco na precisão diagnóstica do aprendizado profundo. Posteriormente, a qualidade metodológica foi avaliada por meio do checklist QUADAS-2. Medidas diagnósticas, incluindo sensibilidade, especificidade, razões de verossimilhança, razão de chances diagnósticas e área sob a curva característica de operação do receptor (area under the receiver operating characteristic curve [AUROC]) foram analisadas, juntamente com análises de subgrupo para ressonância magnética ponderada em T1 e não ponderada em T1. Resultados Um total de 18 estudos elegíveis foram identificados. O coeficiente de correlação de Spearman foi de -0,6506. A metanálise mostrou que a sensibilidade e a especificidade combinadas, a razão de verossimilhança positiva, a razão de verossimilhança negativa e a razão de chances de diagnóstico foram 0,84, 0,86, 6,0, 0,19 e 32, respectivamente. A AUROC foi de 0,92. O ponto quiescente do resumo hierárquico da característica de operação do receptor (hierarchical summary of receiver operating characteristic [HSROC]) foi 3,463. Notavelmente, as imagens de 12 estudos foram adquiridas apenas por ressonância magnética ponderada em T1, e as dos outros 6 foram obtidas apenas por ressonância magnética não ponderada em T1. Conclusão Em geral, a aprendizagem profunda da ressonância magnética para o diagnóstico de DA e CCL mostrou boa sensibilidade e especificidade e contribuiu para melhorar a precisão diagnóstica.

Comparative genomic analysis of Sanghuangporus sanghuang with other Hymenochaetaceae species.

Sanghuangporus sanghuang is a medicinal macrofungus with antioxidant and antitumor activities, and it is enriched with secondary metabolites such as polysaccharides, terpenes, polyphenols, and styrylpyrone compounds. To explore the putative core genes and gene clusters involved in sanghuang biosynthesis, we sequenced and assembled a 40.5-Mb genome of S. sanghuang (SH1 strain). Using antiSMASH, local BLAST, and NCBI comparison, 12 terpene synthases (TPSs), 1 non-ribosomal peptide synthase, and five polyketide synthases (PKSs) were identified in SH1. Combining the transcriptome analysis with liquid chromatography mass spectrometry-ion trap-time of flight analysis, we determined that ShPKS1, one phenylalanine aminolyase (ShPAL), and one P450 monooxygenase (ShC4H1) were associated with hispidin biosynthesis. Structural domain comparison indicated that ShPKS2 and ShPKS3 are involved in the biosynthesis of orsellinic acid and 2-hydroxy-6-methylbenzoic acid, respectively. Furthermore, comparative genomic analysis of SH1 with 14 other fungi from the Hymenochaetaceae family showed variation in the number of TPSs among different genomes, with Coniferiporia weirii exhibiting only 9 TPSs and Inonotus obliquus having 20. The number of TPSs also differed among the genomes of three strains of S. sanghuang, namely Kangneng (16), MS2 (9), and SH1 (12). The type and number of PKSs also varied among species and even strains, ranging from two PKSs in Pyrrhoderma noxium to five PKSs in S. sanghuang SH1. Among the three strains of S. sanghuang, both the structural domains and the number of PKSs in strains MS2 and SH1 were consistent, whereas strain Kangneng exhibited only four PKSs and lacked the PKS with the structural domain KS-AT-DH-KR-ACP. Additionally, Sanghuangporus species exhibited more similar PKSs to Inonotus, with higher gene similarity around five PKSs, while showing differences from those of other fungi in the same family, including Phellinus lamaoensis. This result supports the independent taxonomic significance of the genus Sanghuangporus to some extent.

Morpho-physiological and phytohormonal changes during the induction of adventitious root development stimulated by exogenous IBA application in Magnolia biondii Pamp

Abstract Magnolia biondii Pamp is an important ornamental tree species widely grown and used as a rootstock in the propagation of different Magnolia varieties. In the current studies, anatomical, physiological and endogenous hormones were studied to check the effect of IBA 750 mg/L on the adventitious rooting and to provide theoretical and technical support for the propagation of Magnolia biondii Pamp through stem cuttings. Two thousand stem cuttings were prepared and divided into two groups i.e., IBA treated cuttings and water control. For the evaluation of antioxidant enzyme activities, and endogenous hormones levels, samples were collected on the day of planting and each 5th day and further steps were carried out in the laboratory according to the protocols and proper precautions. For the anatomical observations, samples were collected on the 13th, 15th, and 17th day for IBA treated cuttings while 21st, 23rd, and 25th day for control. Collected samples were preserved in the FAA solution and further observations were carried out in the laboratory. Anatomical observations showed that it took 13 days for the differentiation of root primordia to the appearance of young adventitious roots in IBA treated cuttings, while it took 21 days to develop primordia in the control. Antioxidant enzyme activities involved in ROS were significantly higher in the IBA treated cuttings compared to control. POD showed a peak on the 13th day before the emergence of roots in IBA treated cuttings while it showed a peak on the 21st day in the control. PPO showed a peak on the 21st day in the IBA treated cuttings while it showed a peak on the 29th day in the control. SOD showed a peak on the 17th day in IBA treated cuttings, while it showed a peak on the 25th day in the control. Exogenous application of IBA enhanced the endogenous IAA and GA3 levels compared to CK, while it reduced the levels of ABA continuously at the time of rooting and then increased gradually. Inclusively, our study suggests that IBA 750 mg/L is efficient for the rooting of Magnolia biondii Pamp cuttings, as it enhanced the process of antioxidant enzyme activities, endogenous hormones levels and reduced the time of root formation which is evident from the anatomical observations.

Resumo Magnolia biondii Pamp é uma importante espécie de árvore ornamental muito cultivada e utilizada como porta-enxerto na propagação de diferentes variedades de Magnolia. Nos estudos atuais, hormônios anatômicos, fisiológicos e endógenos foram estudados para verificar o efeito do AIB na dose de 750 mg / L no enraizamento adventício e fornecer suporte teórico e técnico para a propagação de M. biondii Pamp por meio de estacas. Duas mil estacas foram preparadas e divididas em dois grupos, ou seja, tratadas com AIB e controle de água. Para a avaliação das atividades das enzimas antioxidantes e dos níveis de hormônios endógenos, as amostras foram coletadas no dia do plantio e a cada 5 dias, enquanto as demais etapas foram realizadas em laboratório de acordo com os protocolos e os devidos cuidados. Para as observações anatômicas, as amostras foram coletadas no 13º, 15º e 17º dias para estacas tratadas com AIB e no 21º, 23º e 25º dias para o controle. As amostras coletadas foram preservadas em solução FAA, e outras observações foram realizadas em laboratório. Observações anatômicas mostraram a necessidade de 13 dias para a diferenciação dos primórdios radiculares até o aparecimento de raízes adventícias jovens em estacas tratadas com AIB e de 21 dias para o desenvolvimento dos primórdios no controle. As atividades das enzimas antioxidantes envolvidas nas ROS foram significativamente maiores nas estacas tratadas com AIB em comparação com o controle. A POD apresentou pico no 13º dia antes da emergência das raízes nas estacas tratadas com AIB, enquanto no 21º dia apresentou pico no controle. A PPO teve pico no 21º dia nas estacas tratadas com AIB e no 29º dia no controle. A SOD apresentou pico no 17º dia nas estacas tratadas com AIB e no 25º dia no controle. A aplicação exógena de AIB aumentou os níveis endógenos de IAA e GA3 em relação ao controle, enquanto reduziu os níveis de ABA continuamente no momento do enraizamento e, em seguida, aumentou gradativamente. Inclusive, nosso estudo sugere que o AIB na dose de 750 mg / L é eficiente para o enraizamento de estacas de M. biondii Pamp, visto que potencializou o processo de atividades de enzimas antioxidantes e os níveis de hormônios endógenos, além de reduzir o tempo de formação de raízes, o que fica evidente nas observações anatômicas.

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.

PURPOSE: Bone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells. In humans, BMP2 variants result in a multiple congenital anomaly syndrome through a haploinsufficiency mechanism. We sought to expand the phenotypic spectrum and highlight phenotypes of patients harboring monoallelic missense variants in BMP2. METHODS: We used retrospective chart review to examine phenotypes from an international cohort of 18 individuals and compared these with published cases. Patient-derived missense variants were modeled in zebrafish to examine their effect on the ability of bmp2b to promote embryonic ventralization. RESULTS: The presented cases recapitulated existing descriptions of BMP2-related disorders, including craniofacial, cardiac, and skeletal anomalies and exhibit a wide phenotypic spectrum. We also identified patients with neural tube defects, structural brain anomalies, and endocrinopathies. Missense variants modeled in zebrafish resulted in loss of protein function. CONCLUSION: We use this expansion of reported phenotypes to suggest multidisciplinary medical monitoring and management of patients with BMP2-related skeletal dysplasia spectrum.

Long Noncoding RNA Expression Independently Predicts Outcome in Pediatric Acute Myeloid Leukemia.

PURPOSE: Optimized strategies for risk classification are essential to tailor therapy for patients with biologically distinctive disease. Risk classification in pediatric acute myeloid leukemia (pAML) relies on detection of translocations and gene mutations. Long noncoding RNA (lncRNA) transcripts have been shown to associate with and mediate malignant phenotypes in acute myeloid leukemia (AML) but have not been comprehensively evaluated in pAML. METHODS: To identify lncRNA transcripts associated with outcomes, we evaluated the annotated lncRNA landscape by transcript sequencing of 1,298 pediatric and 96 adult AML specimens. Upregulated lncRNAs identified in the pAML training set were used to establish a regularized Cox regression model of event-free survival (EFS), yielding a 37 lncRNA signature (lncScore). Discretized lncScores were correlated with initial and postinduction treatment outcomes using Cox proportional hazards models in validation sets. Predictive model performance was compared with standard stratification methods by concordance analysis. RESULTS: Training set cases with positive lncScores had 5-year EFS and overall survival rates of 26.7% and 42.7%, respectively, compared with 56.9% and 76.3% with negative lncScores (hazard ratio, 2.48 and 3.16; P < .001). Pediatric validation cohorts and an adult AML group yielded comparable results in magnitude and significance. lncScore remained independently prognostic in multivariable models, including key factors used in preinduction and postinduction risk stratification. Subgroup analysis suggested that lncScores provide additional outcome information in heterogeneous subgroups currently classified as indeterminate risk. Concordance analysis showed that lncScore adds to overall classification accuracy with at least comparable predictive performance to current stratification methods that rely on multiple assays. CONCLUSION: Inclusion of the lncScore enhances predictive power of traditional cytogenetic and mutation-defined stratification in pAML with potential, as a single assay, to replace these complex stratification schemes with comparable predictive accuracy.

Role and mechanism of miR-548-3p/ DAG1 in the occurrence and malignant transformation of laryngeal carcinoma / Papel y mecanismo de miR-548-3p/DAG1 en la aparición y transformación maligna del carcinoma de laringe

Abstract The AMC-HN-8 cell line and the primary human laryngeal epithelial cell lines were utilized in this work to explore the molecular mechanism of miR-548-3p regulating the gene DAG1 to induce the occurrence and malignant transformation of laryngeal carcinoma. Non-coding RNA miR-548- 3p overexpression plasmid, interference plasmid and blank plasmid were constructed, and the plasmids were transfected into AMC-HN-8 cells, respectively. Meanwhile, a non-transfected plasmid group and a human laryngeal epithelial primary cell group were set up. Five groups of cells were named as NC (Normal control), Model, Ov-miR-548-3p, Sh-miR-548-3p and Blank-plasmid group. The luciferase reporter experiment was used to analyze the regulation characteristics of hsa-miR-548-3p on dystrophin-associated glycoprotein 1 (DAG1). Immunofluorescence was used to analyze the relative expression characteristics of the protein DAG1. The cell cloning experiment was used to analyze the proliferation characteristics of AMC-HN-8. The scratch healing test was used to analyze the migration ability of AMC-HN-8. The transwell test was used to analyze the invasion ability of AMC-HN-8. The RT-PCR was used to analyze the expression level of miR-548-3p. Western blot experiments were used to analyze the expression of protein DAG1, laminin α2 (LAMA2) and utrophin (UTRN). The luciferase report experiment and immunofluorescence test found that the expression of DAG1 and miR-548-3p are positively correlated. Cell cloning, scratching and migration experiments identified that the activity of laryngeal cancer cells was positively correlated with the expression of DAG1. The results of Western blot analysis further strengthened the above conclusions. Through carrying out research on the cellular levels, our work has demonstrated that miR-548-3p regulated the content of protein DAG1, and then further induced malignant transformation of laryngeal carcinoma.

Resumen En este trabajo se utilizaron la línea celular AMC-HN-8 y la línea celular epitelial laríngea humana primaria, para explorar el mecanismo molecular regulador del miR-548-3p sobre el gen DAG1 para inducir la aparición y la transformación maligna del carcinoma laríngeo. Se construyeron el plásmido de sobreexpresión de miR-548-3p de ARN no codificante, el plásmido de interferencia y el plásmido en blanco, y los plásmidos se transfectaron en células AMCHN-8 respectivamente. Mientras tanto, se establecieron un grupo de plásmidos no transfectados y un grupo de células primarias epiteliales laríngeas humanas. Se nombraron cinco grupos de células como NC (control normal), modelo, OvmiR-548-3p, Sh-miR-548-3p y grupo de plásmido en blanco. El experimento indicador de luciferasa se utilizó para analizar las características de regulación de hsa-miR-548-3p en la glicoproteína 1 asociada a distrofina (DAG1). Se utilizó inmunofluorescencia para analizar las características de expresión relativa de la proteína DAG1. El experimento de clonación celular se utilizó para analizar las características de proliferación de AMC-HN-8. Se utilizó la prueba de cicatrización por rascado para analizar la capacidad de migración de AMC-HN-8. La prueba de transwell se utilizó para analizar la capacidad de invasión de AMCHN-8. Se utilizó RT-PCR para analizar el nivel de expresión de miR-548-3p. Se usó un experimento de transferencia Western (Western blot) para analizar las expresiones de la proteína DAG1, laminina α2 (LAMA2) y utrofina (UTRN). El experimento de reporte de luciferasa y la prueba de inmunofluorescencia encontraron que la expresión de DAG1 y miR-548-3p están positivamente correlacionadas. Los experimentos de clonación celular, rascado y migración, identificaron que la actividad de las células cancerosas de laringe se correlacionó positivamente con la expresión de DAG1. Los resultados del análisis de transferencia Western fortalecieron aún más las conclusiones anteriores. A través de la investigación a nivel celular, nuestro proyecto ha demostrado que miR-548-3p regula el contenido de la proteína DAG1 y luego induce la transformación maligna del carcinoma de laringe.

Involuntary Administration of Long-Acting Injectable Antipsychotics for Competency Restoration.

In implementing the decisions in the landmark case Sell v. United States, jurisdictions have adopted mechanisms for the involuntary medication of defendants to restore competency to stand trial. These procedures attempt to balance the liberty and privacy rights of the accused against the government's responsibility to ensure timely prosecution and fair trial. The question of which medications are most appropriate for this goal, however, remains open. This article reviews the legal status of the administration of long-acting injectable (LAI) antipsychotics for sustained competency restoration. We explore case law and discuss the theoretical and empirical benefits and drawbacks to this practice, considering recent technological advancements in LAI development. Some courts have regarded LAI use pursuant to Sell as equivalent or superior to immediate-acting medications, whereas others have regarded LAIs as either more intrusive or medically riskier. We conclude that the use of LAIs may be carefully integrated into treatment plans to restore and maintain trial competency amid competing interests.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes.

OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Influence of small-group experiential learning of integrated traditional Chinese and Western medicine on the oral health knowledge, beliefs, and behaviors of elderly patients with diabetes

SUMMARY OBJECTIVE: This study aimed at the oral health problems of elderly patients with diabetes. A training course of integrated traditional Chinese and Western medicine was constructed, helping patients improve their oral health quality of life. METHODS: A randomized controlled prospective experimental study was conducted. A total of 190 elderly patients were divided randomly into an observation group and a control group with 95 cases in each. The control group received regular health education, while the observation group was based on the control group to implement the integrated experiential learning of traditional Chinese and Western medicine in small groups. The oral health knowledge, attitude, behavior, and blood glucose control status along with the oral health quality of life of the two groups were compared before the intervention and at 3-month postintervention. RESULTS: Three months after the intervention, the fasting blood glucose control and the 2-h postprandial blood glucose/glycosylated hemoglobin levels in the observation group were significantly better than in the control group, and the difference was statistically significant (p<0.05). The oral health quality of life in the observation group was significantly better than in the control group, and the difference was statistically significant (p<0.05). CONCLUSION: The small-group experiential learning model of integrated Chinese and Western medicine can promote the transformation of knowledge-beliefs-behaviors in elderly patients with diabetes, which is conducive to controlling blood sugar levels and improving the quality of oral health.

Morphological index of fetal cerebral ventricular development: a diagnostic ultrasound study / Índice morfológico del desarrollo ventricular cerebral fetal: un estudio ecográfico diagnóstico

SUMMARY: To establish an unprovable diagnostic indicative index reference for ultrasound examination of the fetal cerebral ventricles, based on the morphological characteristics throughout fetal nervous system development. Key ultrasonic morphological indicators of fetal ventricular development, which includes frontal horn width (FHW), occipital horn width (OHW), width of 3rd ventricle, cavity of septum pellucidum (CSP), width and length of 4th ventricle and thalamo-occipital distance (TOD) had been measured and analyzed collectively. All data of the indicators was collected on singleton pregnant woman between 16-39 weeks of gestational age (GA), between November 2017 and June 2021 at the Second Hospital of Dalian Medical University. A total of 235 pregnant women were enrolled in the cross section study; another 36 pregnant women voluntarily joined a timeline-tracking follow-up study (cohort study) under the same examining criteria. A decrease of FHW and OHW of the lateral ventricles was observed as GA increased; while dimensional values of TOD, 3rd ventricle, CSP, as well as 4th ventricle increased with GA. Most of these indicators showed an enhanced variation tendency within a certain period of GA. Moreover, values of FHW and TOD showed asymmetry of the two hemispheres within the whole GA. Our findings revealed the morphological regularity of fetal ventricular development, which would instructively enhance the relative clinical ultrasound diagnosis; moreover, TOD also showed regularly changes as GA increased, suggesting that TOD should be considered as an additional routine ultrasonic indicator for fetal ventricular development.

RESUMEN: El objetivo del estudio fue establecer un índice de referencia indicativo diagnóstico no demostrable para el examen ecográfico de los ventrículos cerebrales fetales, basado en las características morfológicas a lo largo del desarrollo del sistema nervioso fetal. Indicadores morfológicos ultrasónicos clave del desarrollo ventricular fetal, que incluyen el ancho del cuerno frontal (FHW), el ancho del cuerno occipital (OHW), el ancho del tercer ventrículo, la cavidad del septo pelúcido (CSP), el ancho y el largo del cuarto ventrículo y la distancia tálamo-occipital (TOD) fueron medidos y analizados conjuntamente. Todos los datos de los indicadores se recopilaron en mujeres embarazadas de un solo feto entre 16 y 39 semanas de edad gestacional (EG), entre noviembre de 2017 y junio de 2021 en el Segundo Hospital de la Universidad Médica de Dalian. Un total de 235 mujeres embarazadas se inscribieron en el estudio transversal; otras 36 mujeres embarazadas se unieron voluntariamente a un estudio de seguimiento de línea de tiempo (estudio de cohorte) bajo los mismos criterios de examen. Se observó una disminución de FHW y OHW de los ventrículos laterales a medida que aumentaba la GA; mientras que los valores dimensionales de TOD, tercer ventrículo, CSP y cuarto ventrículo aumentaron con GA. La mayoría de estos indicadores mostraron una tendencia de variación mejorada dentro de un cierto período de GA. Además, los valores de FHW y TOD mostraron asimetría de los dos hemisferios dentro de toda la AG. Nuestros hallazgos revelaron la regularidad morfológica del desarrollo ventricular fetal, lo que mejoraría de manera instructiva el diagnóstico clínico de ultrasonido relativo; además, TOD también mostró cambios regulares a medida que aumentaba la GA, lo que sugiere que TOD debe considerarse como un indicador ultrasónico de rutina adicional para el desarrollo ventricular fetal.

Urban road greenbelt configuration: The perspective of PM2.5 removal and air quality regulation.

The establishment of the road green belt (RGB) is an effective means to reduce particle matter (PM2.5) emissions from road traffic. This study tested the ability of 23 common tree species in Shenzhen to reduce PM2.5 concentrations using field investigations and wind tunnel tests. The association between leaf microstructure and individual reduction ability was also analyzed. Finally, the impact of three RGB configurations (i.e., arbor, shrub, arbor + shrub) on road PM2.5 dispersion and deposition was simulated using the ENVI-met three-dimensional aerodynamic model, based on which an optimal RGB configuration was proposed. There were three key findings of the tests. First, the wind speed was the main factor affecting the PM2.5 concentration (54.2%), followed by vehicle flow (27.7%), temperature (14.2%), and time factor (7.6%). Second, the range of dry deposition velocity (Vd) was 0.04-6.4 m/s, and the dominant dust-retaining plant species were the evergreen trees, Ficus microcarpa and Ficus altissima, and the evergreen shrubs, Codiaeum variegatum and Fagraea ceilanica. A higher proportion of grooves or larger stomata would increase the probability that the blade would capture PM2.5. Third, the shrub RGB demonstrated the best performance in terms of pollutant dispersion; its PM2.5 concentration at the respiratory height (RH, 1.5 m) on the pedestrian crossing was 15-20% lower than the other RGB configurations. In terms of pollutant deposition, the arbor + shrub composite RGB was two-fold better than the other RGB configurations. Moreover, it was more advantageous to plant shrub RGBs in street canyons to achieve a balance between the lowest concentration and the largest deposition of PM2.5 pollutants. The findings of this study will facilitate the RGB configurations with good dust retention ability.

Prognostic implications of immune-related eight-gene signature in pediatric brain tumors.

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

Prognostic implications of immune-related eight-gene signature in pediatric brain tumors

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

Comparative transcriptome analysis reveals candidate genes related to cadmium accumulation and tolerance in two almond mushroom (Agaricus brasiliensis) strains with contrasting cadmium tolerance.

Cadmium (Cd) is a toxic metal occurring in the environment naturally. Almond mushroom (Agaricus brasiliensis) is a well-known cultivated edible and medicinal mushroom. In the past few decades, Cd accumulation in A.brasiliensis has received increasing attention. However, the molecular mechanisms of Cd-accumulation in A. brasiliensis are still unclear. In this paper, a comparative transcriptome of two A.brasiliensis strains with contrasting Cd accumulation and tolerance was performed to identify Cd-responsive genes possibly responsible for low Cd-accumulation and high Cd-tolerance. Using low Cd-accumulating and Cd-tolerant (J77) and high Cd-accumulating and Cd-sensitive (J1) A.brasiliensis strains, we investigated 0, 2 and 5 mg L-1 Cd-effects on mycelium growth, Cd-accumulation and transcriptome revealed by RNA-Seq. A total of 57,884 unigenes were obtained. Far less Cd-responsive genes were identified in J77 mycelia than those in J1 mycelia (e.g., ABC transporters, ZIP Zn transporter, Glutathione S-transferase and Cation efflux (CE) family). The higher Cd-accumulation in J1 mycelia might be due to Cd-induced upregulation of ZIP Zn transporter. Cd impaired cell wall, cell cycle, DNA replication and repair, thus decreasing J1 mycelium growth. Cd-stimulated production of sulfur-containing compounds, polysaccharides, organic acids, trehalose, ATP and NADPH, and sequestration of Cd might be adaptive responses of J1 mycelia to the increased Cd-accumulation. DNA replication and repair had better stability under 2 mg L-1 Cd, but greater positive modifications under 5 mg L-1 Cd. Better stability of DNA replication and repair, better cell wall and cell cycle stability might account for the higher Cd-tolerance of J77 mycelia. Our findings provide a comprehensive set of DEGs influenced by Cd stress; and shed light on molecular mechanism of A.brasiliensis Cd accumulation and Cd tolerance.

Enhancing the tolerance of Clostridium saccharoperbutylacetonicum to lignocellulosic-biomass-derived inhibitors for efficient biobutanol production by overexpressing efflux pumps genes from Pseudomonas putida.

Furan aldehydes and phenolic compounds generated during biomass pretreatment can inhibit fermentation for biofuel production. Efflux pumps actively transport small molecules out of cells, thus sustaining normal microbial metabolism. Pseudomonas putida has outstanding tolerance to butanol and other small molecules, and we hypothesize that its efflux pump could play essential roles for such robustness. Here, we overexpressed efflux pump genes from P. putida to enhance tolerance of hyper-butanol producing Clostridium saccharoperbutylacetonicum to fermentation inhibitors. Interestingly, overexpression of the whole unit resulted in decreased tolerance, while overexpression of the subunit (srpB) alone exerted significant enhanced robustness of the strain. Compared to the control, the engineered strain had enhanced capability to grow in media containing 17% more furfural or 50% more ferulic acid, and produced ~14 g/L butanol (comparable to fermentation under regular conditions without inhibitors). This study provided valuable reference for boosting microbial robustness towards efficient biofuel production from lignocellulosic materials.