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1.
Genome Biol ; 25(1): 147, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844966

RESUMO

Current clustering analysis of spatial transcriptomics data primarily relies on molecular information and fails to fully exploit the morphological features present in histology images, leading to compromised accuracy and interpretability. To overcome these limitations, we have developed a multi-stage statistical method called iIMPACT. It identifies and defines histology-based spatial domains based on AI-reconstructed histology images and spatial context of gene expression measurements, and detects domain-specific differentially expressed genes. Through multiple case studies, we demonstrate iIMPACT outperforms existing methods in accuracy and interpretability and provides insights into the cellular spatial organization and landscape of functional genes within spatial transcriptomics data.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica/métodos , Humanos , Análise por Conglomerados , Processamento de Imagem Assistida por Computador/métodos
2.
J Safety Res ; 89: 116-134, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38858034

RESUMO

INTRODUCTION: Motor vehicle collisions are a leading source of mortality and injury on urban highways. From a temporal perspective, the determination of a road segment as being collision-prone over time can fluctuate dramatically, making it difficult for transportation agencies to propose traffic interventions. However, there has been limited research to identify and characterize collision-prone road segments with varying collision density patterns over time. METHOD: This study proposes an identification and characterization framework that profiles collision-prone roads with various collision density variations. We first employ the spatio-temporal network kernel density estimation (STNKDE) method and time-series clustering to identify road segments with different collision density patterns. Next, we characterize collision-prone road segments based on spatio-temporal information, consequences, vehicle types, and contributing factors to collisions. The proposed method is applied to two-year motor vehicle collision records for New York City. RESULTS: Seven clusters of road segments with different collision density patterns were identified. Road segments frequently determined as collision-prone were primarily found in Lower Manhattan and the center of the Bronx borough. Furthermore, collisions near road segments that exhibit greater collision densities over time result in more fatalities and injuries, many of which are caused by both human and vehicle factors. CONCLUSIONS: Collision-prone road segments with various collision density patterns over time have distinct differences in the spatio-temporal domain and the collisions that occur on them. PRACTICAL APPLICATIONS: The proposed method can help policymakers understand how collision-prone road segments change over time, and can serve as a reference for more targeted traffic treatment.


Assuntos
Acidentes de Trânsito , Veículos Automotores , Acidentes de Trânsito/estatística & dados numéricos , Humanos , Cidade de Nova Iorque/epidemiologia , Veículos Automotores/estatística & dados numéricos , Análise Espaço-Temporal , Análise por Conglomerados , Planejamento Ambiental
3.
J Transl Med ; 22(1): 548, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849800

RESUMO

BACKGROUND: Despite significant advancements in treatment strategies, multiple myeloma remains incurable. Additionally, there is a distinct lack of reliable biomarkers that can guide initial treatment decisions and help determine suitable replacement or adjuvant therapies when relapse ensues due to acquired drug resistance. METHODS: To define specific proteins and pathways involved in the progression of monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), we have applied super-SILAC quantitative proteomic analysis to CD138 + plasma cells from 9 individuals with MGUS and 37 with MM. RESULTS: Unsupervised hierarchical clustering defined three groups: MGUS, MM, and MM with an MGUS-like proteome profile (ML) that may represent a group that has recently transformed to MM. Statistical analysis identified 866 differentially expressed proteins between MM and MGUS, and 189 between MM and ML, 177 of which were common between MGUS and ML. Progression from MGUS to MM is accompanied by upregulated EIF2 signaling, DNA repair, and proteins involved in translational quality control, whereas integrin- and actin cytoskeletal signaling and cell surface markers are downregulated. CONCLUSION: Compared to the premalignant plasma cells in MGUS, malignant MM cells apparently have mobilized several pathways that collectively contribute to ensure translational fidelity and to avoid proteotoxic stress, especially in the ER. The overall reduced expression of immunoglobulins and surface antigens contribute to this and may additionally mediate evasion from recognition by the immune apparatus. Our analyses identified a range of novel biomarkers with potential prognostic and therapeutic value, which will undergo further evaluation to determine their clinical significance.


Assuntos
Progressão da Doença , Gamopatia Monoclonal de Significância Indeterminada , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Proteômica , Masculino , Feminino , Biossíntese de Proteínas , Pessoa de Meia-Idade , Idoso , Análise por Conglomerados , Plasmócitos/imunologia , Plasmócitos/patologia , Plasmócitos/metabolismo , Transdução de Sinais , Proteoma/metabolismo , Controle de Qualidade
4.
Health Place ; 88: 103262, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38833849

RESUMO

Life course theories suggest that the relationship between residential (dis)advantage and health is best understood by examining the ordering and duration of cumulative exposures across the life course. This study employs sequence and cluster analysis on two decades of residential histories linked to the Survey of the Health of Wisconsin to define typologies of exposure to residential (dis)advantage and use these typologies to predict self-rated fair/poor health. Exposure to residential (dis)advantage is mostly stable across the adult life course and greater disadvantage predicts fair/poor health. Longitudinal exposures to residential (dis)advantage shape health independently of and in tandem with individual-level resources.


Assuntos
Classe Social , Humanos , Wisconsin , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Nível de Saúde , Características de Residência , Idoso , Inquéritos Epidemiológicos , Análise por Conglomerados , Disparidades nos Níveis de Saúde
5.
Sci Rep ; 14(1): 13127, 2024 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849404

RESUMO

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.


Assuntos
Neoplasias Gástricas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , Resistencia a Medicamentos Antineoplásicos , Modelos Biológicos , Terapia de Alvo Molecular/métodos , Análise por Conglomerados , Análise de Componente Principal , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
6.
J Transl Med ; 22(1): 551, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851695

RESUMO

BACKGROUND: Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. METHODS: We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. RESULTS: We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. CONCLUSIONS: These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.


Assuntos
Biomarcadores Tumorais , Glioblastoma , Análise de Célula Única , Microambiente Tumoral , Humanos , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Análise por Conglomerados , Mapas de Interação de Proteínas , Variações do Número de Cópias de DNA/genética , Agregação Celular , Perfilação da Expressão Gênica
7.
Sci Data ; 11(1): 568, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824125

RESUMO

Technological advances in massively parallel sequencing have led to an exponential growth in the number of known protein sequences. Much of this growth originates from metagenomic projects producing new sequences from environmental and clinical samples. The Unified Human Gastrointestinal Proteome (UHGP) catalogue is one of the most relevant metagenomic datasets with applications ranging from medicine to biology. However, the low levels of sequence annotation may impair its usability. This work aims to produce a family classification of UHGP sequences to facilitate downstream structural and functional annotation. This is achieved through the release of the DPCfam-UHGP50 dataset containing 10,778 putative protein families generated using DPCfam clustering, an unsupervised pipeline grouping sequences into single or multi-domain architectures. DPCfam-UHGP50 considerably improves family coverage at protein and residue levels compared to the manually curated repository Pfam. In the hope that DPCfam-UHGP50 will foster future discoveries in the field of metagenomics of the human gut, we release a FAIR-compliant database of our results that is easily accessible via a searchable web server and Zenodo repository.


Assuntos
Proteoma , Humanos , Trato Gastrointestinal/metabolismo , Análise por Conglomerados , Anotação de Sequência Molecular , Metagenômica , Bases de Dados de Proteínas
8.
BMC Cancer ; 24(1): 669, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824496

RESUMO

BACKGROUND: Cancer has become a major health concern due to the increasing morbidity and mortality rates, and its negative social, economic consequences and the heavy financial burden incurred by cancer patients. About 40% of cancers are preventable. The aim of this study was to assess the knowledge, attitudes, and practices regarding cancer prevention, and associated characteristics to inform the development of targeted cancer prevention campaigns and policies. METHODS: We conducted a cross-sectional survey of adult patients at Mohamed Sekkat and Sidi Othmane Hospitals in Casablanca, Morocco. Data collection was conducted by two trained interviewers who administered the questionnaire in-person in the local language. An unsupervised clustering approach included 17 candidate variables for the cluster analysis. The variables covered a wide range of characteristics, including demographics, health perceptions and attitudes. Survey answers were calculated to compose qualitative ordinal categories, including a cancer attitude score and knowledge score. RESULTS: The cluster-based analysis showed that participants in cluster 1 had the highest mean attitude score (13.9 ± 2.15) and percentage of individuals with a high level of knowledge (50.8%) whereas the lowest mean attitude score (9.48 ± 2.02) and knowledge level (7.5%.) were found in cluster 3. The participants with the lowest cancer attitude scores and knowledge levels were aged 34 to 47 years old (middle age group), predominantly females, living in rural settings, and were least likely to report health professionals as a source of health information. CONCLUSIONS: The findings showed that female individuals living in rural settings, belonging to an older age group, who were least likely to use health professionals as an information source had the lowest levels of knowledge and attitudes. These groups are amenable to targeted and tailored interventions aiming to modify their understanding of cancer in order to enhance the outcomes of Morocco's on-going efforts in cancer prevention and control strategies.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Neoplasias , Humanos , Marrocos/epidemiologia , Feminino , Masculino , Adulto , Neoplasias/psicologia , Neoplasias/epidemiologia , Pessoa de Meia-Idade , Análise por Conglomerados , Estudos Transversais , Inquéritos e Questionários , Adulto Jovem , Idoso , Adolescente
9.
Front Public Health ; 12: 1105518, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827622

RESUMO

The COVID-19 pandemic had a strong territorial dimension, with a highly asymmetric impact among Romanian counties, depending on pre-existing vulnerabilities, regions' economic structure, exposure to global value chains, specialization, and overall ability to shift a large share of employees to remote working. The aim of this paper is to assess the role of Romanian local authorities during this unprecedented global medical emergency by capturing the changes of public spending at the local level between 2010 and 2021 and amid the COVID-19 pandemic, and to identify clusters of Romanian counties that shared similar characteristics in this period, using a panel data quantitative model and hierarchical cluster analysis. Our empirical analysis shows that between 2010-2021, the impact of social assistance expenditures was higher than public investment (capital spending and EU funds) on the GDP per capita at county level. Additionally, based on various macroeconomic and structural indicators (health, labour market performance, economic development, entrepreneurship, and both local public revenues and several types of expenditures), we determined seven clusters of counties. The research contributes to the discussion regarding the increase of economic resilience but also to the evidence-based public policies implementation at local level.


Assuntos
COVID-19 , Romênia/epidemiologia , COVID-19/epidemiologia , COVID-19/economia , Humanos , SARS-CoV-2 , Pandemias/economia , Política Pública , Análise por Conglomerados , Governo Local
10.
Hum Brain Mapp ; 45(8): e26682, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825977

RESUMO

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.


Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Obesidade , Análise de Componente Principal , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Adulto , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Análise por Conglomerados , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia
11.
Front Public Health ; 12: 1378426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832230

RESUMO

Background: Tuberculosis remains a global health threat, and the World Health Organization reports a limited reduction in disease incidence rates, including both new and relapse cases. Therefore, studies targeting tuberculosis transmission chains and recurrent episodes are crucial for developing the most effective control measures. Herein, multiple tuberculosis clusters were retrospectively investigated by integrating patients' epidemiological and clinical information with median-joining networks recreated based on whole genome sequencing (WGS) data of Mycobacterium tuberculosis isolates. Methods: Epidemiologically linked tuberculosis patient clusters were identified during the source case investigation for pediatric tuberculosis patients. Only M. tuberculosis isolate DNA samples with previously determined spoligotypes identical within clusters were subjected to WGS and further median-joining network recreation. Relevant clinical and epidemiological data were obtained from patient medical records. Results: We investigated 18 clusters comprising 100 active tuberculosis patients 29 of whom were children at the time of diagnosis; nine patients experienced recurrent episodes. M. tuberculosis isolates of studied clusters belonged to Lineages 2 (sub-lineage 2.2.1) and 4 (sub-lineages 4.3.3, 4.1.2.1, 4.8, and 4.2.1), while sub-lineage 4.3.3 (LAM) was the most abundant. Isolates of six clusters were drug-resistant. Within clusters, the maximum genetic distance between closely related isolates was only 5-11 single nucleotide variants (SNVs). Recreated median-joining networks, integrated with patients' diagnoses, specimen collection dates, sputum smear microscopy, and epidemiological investigation results indicated transmission directions within clusters and long periods of latent infection. It also facilitated the identification of potential infection sources for pediatric patients and recurrent active tuberculosis episodes refuting the reactivation possibility despite the small genetic distance of ≤5 SNVs between isolates. However, unidentified active tuberculosis cases within the cluster, the variable mycobacterial mutation rate in dormant and active states, and low M. tuberculosis genetic variability inferred precise transmission chain delineation. In some cases, heterozygous SNVs with an allelic frequency of 10-73% proved valuable in identifying direct transmission events. Conclusion: The complex approach of integrating tuberculosis cluster WGS-data-based median-joining networks with relevant epidemiological and clinical data proved valuable in delineating epidemiologically linked patient transmission chains and deciphering causes of recurrent tuberculosis episodes within clusters.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Sequenciamento Completo do Genoma , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Masculino , Tuberculose/transmissão , Tuberculose/epidemiologia , Feminino , Estudos Retrospectivos , Criança , Pré-Escolar , Adolescente , Análise por Conglomerados , Adulto , Lactente
12.
BMC Genomics ; 25(1): 566, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840049

RESUMO

BACKGROUND: Advances of spatial transcriptomics technologies enabled simultaneously profiling gene expression and spatial locations of cells from the same tissue. Computational tools and approaches for integration of transcriptomics data and spatial context information are urgently needed to comprehensively explore the underlying structure patterns. In this manuscript, we propose HyperGCN for the integrative analysis of gene expression and spatial information profiled from the same tissue. HyperGCN enables data visualization and clustering, and facilitates downstream analysis, including domain segmentation, the characterization of marker genes for the specific domain structure and GO enrichment analysis. RESULTS: Extensive experiments are implemented on four real datasets from different tissues (including human dorsolateral prefrontal cortex, human positive breast tumors, mouse brain, mouse olfactory bulb tissue and Zabrafish melanoma) and technologies (including 10X visium, osmFISH, seqFISH+, 10X Xenium and Stereo-seq) with different spatial resolutions. The results show that HyperGCN achieves superior clustering performance and produces good domain segmentation effects while identifies biologically meaningful spatial expression patterns. This study provides a flexible framework to analyze spatial transcriptomics data with high geometric complexity. CONCLUSIONS: HyperGCN is an unsupervised method based on hypergraph induced graph convolutional network, where it assumes that there existed disjoint tissues with high geometric complexity, and models the semantic relationship of cells through hypergraph, which better tackles the high-order interactions of cells and levels of noise in spatial transcriptomics data.


Assuntos
Perfilação da Expressão Gênica , Humanos , Animais , Camundongos , Perfilação da Expressão Gênica/métodos , Transcriptoma , Aprendizado Profundo , Análise por Conglomerados , Biologia Computacional/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Bulbo Olfatório/metabolismo
13.
PLoS One ; 19(6): e0302025, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38843173

RESUMO

In dengue-endemic areas, transmission control is limited by the difficulty of achieving sufficient coverage and sustainability of interventions. To maximize the effectiveness of interventions, areas with higher transmission could be identified and prioritized. The aim was to identify burden clusters of Dengue virus (DENV) infection and evaluate their association with microclimatic factors in two endemic towns from southern Mexico. Information from a prospective population cohort study (2·5 years of follow-up) was used, microclimatic variables were calculated from satellite information, and a cross-sectional design was conducted to evaluate the relationship between the outcome and microclimatic variables in the five surveys. Spatial clustering was observed in specific geographic areas at different periods. Both, land surface temperature (aPR 0·945; IC95% 0·895-0·996) and soil humidity (aPR 3·018; IC95% 1·013-8·994), were independently associated with DENV burden clusters. These findings can help health authorities design focused dengue surveillance and control activities in dengue endemic areas.


Assuntos
Vírus da Dengue , Dengue , Microclima , Humanos , Dengue/epidemiologia , Dengue/transmissão , México/epidemiologia , Feminino , Masculino , Estudos Transversais , Adulto , Adolescente , Estudos Prospectivos , Criança , Doenças Endêmicas , Adulto Jovem , Pessoa de Meia-Idade , Pré-Escolar , Umidade , Análise por Conglomerados , Temperatura
14.
PLoS Negl Trop Dis ; 18(6): e0012186, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38843214

RESUMO

The combined region of eastern Tennessee and western North Carolina has a persistently high risk of pediatric La Crosse virus neuroinvasive disease (LACV-ND). To guide public health intervention in this region, the objectives of this retrospective ecological study were to investigate the geographic clustering and predictors of pediatric LACV-ND risk at the ZIP code tabulation area (ZCTA) level. Data on pediatric cases of LACV-ND reported between 2003 and 2020 were obtained from Tennessee Department of Health and North Carolina Department of Health and Human Services. Purely spatial and space-time scan statistics were used to identify ZCTA-level clusters of confirmed and probable pediatric LACV-ND cases from 2003-2020, and a combination of global and local (i.e., geographically weighted) negative binomial regression models were used to investigate potential predictors of disease risk from 2015-2020. The cluster investigation revealed spatially persistent high-risk and low-risk clusters of LACV-ND, with most cases consistently reported from a few high-risk clusters throughout the entire study period. Temperature and precipitation had positive but antagonistic associations with disease risk from 2015-2020, but the strength of those relationships varied substantially across the study area. Because LACV-ND risk clustering in this region is focally persistent, retroactive case surveillance can be used to guide the implementation of targeted public health intervention to reduce the disease burden in high-risk areas. Additional research on the role of climate in LACV transmission is warranted to support the development of predictive transmission models to guide proactive public health interventions.


Assuntos
Encefalite da Califórnia , Vírus La Crosse , Humanos , North Carolina/epidemiologia , Tennessee/epidemiologia , Criança , Estudos Retrospectivos , Encefalite da Califórnia/epidemiologia , Encefalite da Califórnia/virologia , Pré-Escolar , Análise por Conglomerados , Masculino , Feminino , Lactente , Adolescente , Fatores de Risco
15.
Lipids Health Dis ; 23(1): 166, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835073

RESUMO

INTRODUCTION: ST-segment elevation myocardial infarction (STEMI) represents the most harmful clinical manifestation of coronary artery disease. Risk assessment plays a beneficial role in determining both the treatment approach and the appropriate time for discharge. Hierarchical agglomerative clustering (HAC), a machine learning algorithm, is an innovative approach employed for the categorization of patients with comparable clinical and laboratory features. The aim of the present study was to investigate the role of HAC in categorizing STEMI patients and to compare the results of these patients. METHODS: A total of 3205 patients who were diagnosed with STEMI at the university hospital emergency clinic between 2015 and 2023 were included in the study. The patients were divided into 2 different phenotypic disease clusters using the HAC method, and their outcomes were compared. RESULTS: In the present study, a total of 3205 STEMI patients were included; 2731 patients were in cluster 1, and 474 patients were in cluster 2. Mortality was observed in 147 (5.4%) patients in cluster 1 and 108 (23%) patients in cluster 2 (chi-square P value < 0.01). Survival analysis revealed that patients in cluster 2 had a significantly greater risk of death than patients in cluster 1 did (log-rank P < 0.001). After adjustment for age and sex in the Cox proportional hazards model, cluster 2 exhibited a notably greater risk of death than did cluster 1 (HR = 3.51, 95% CI = 2.71-4.54; P < 0.001). CONCLUSION: Our study showed that the HAC method may be a potential tool for predicting one-month mortality in STEMI patients.


Assuntos
Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Análise por Conglomerados , Angiografia Coronária , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Aprendizado de Máquina
16.
J Transl Med ; 22(1): 556, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858765

RESUMO

BACKGROUND: The poor chemo-response and high DNA methylation of ovarian clear cell carcinoma (OCCC) have attracted extensive attentions. Recently, we revealed the mutational landscape of the human kinome and additional cancer-related genes and found deleterious mutations in ARID1A, a component of the SWI/SNF chromatin-remodeling complex, in 46% of OCCC patients. The present study aims to comprehensively investigate whether ARID1A loss and genome-wide DNA methylation are co-regulated in OCCC and identify putative therapeutic targets epigenetically regulated by ARID1A. METHODS: DNA methylation of ARID1Amt/ko and ARID1Awt OCCC tumors and cell lines were analyzed by Infinium MethylationEPIC BeadChip. The clustering of OCCC tumors in relation to clinical and mutational status of tumors were analyzed by hierarchical clustering analysis of genome-wide methylation. GEO expression profiles were used to identify differentially methylated (DM) genes and their expression level in ARID1Amt/ko vs ARID1Awt OCCCs. Combining three pre-ranked GSEAs, pathways and leading-edge genes epigenetically regulated by ARID1A were revealed. The leading-edge genes that passed the in-silico validation and showed consistent ARID1A-related methylation change in tumors and cell lines were regarded as candidate genes and finally verified by bisulfite sequencing and RT-qPCR. RESULTS: Hierarchical clustering analysis of genome-wide methylation showed two clusters of OCCC tumors. Tumor stage, ARID1A/PIK3CA mutations and TP53 mutations were significantly different between the two clusters. ARID1A mutations in OCCC did not cause global DNA methylation changes but were related to DM promoter or gene-body CpG islands of 2004 genes. Three pre-ranked GSEAs collectively revealed the significant enrichment of EZH2- and H3K27me3-related gene-sets by the ARID1A-related DM genes. 13 Leading-edge DM genes extracted from the enriched gene-sets passed the expression-based in-silico validation and showed consistent ARID1A-related methylation change in tumors and cell lines. Bisulfite sequencing and RT-qPCR analysis showed promoter hypermethylation and lower expression of IRX1, TMEM101 and TRIP6 in ARID1Amt compared to ARID1Awt OCCC cells, which was reversed by 5-aza-2'-deoxycytidine treatment. CONCLUSIONS: Our study shows that ARID1A loss is related to the differential methylation of a number of genes in OCCC. ARID1A-dependent DM genes have been identified as key genes of many cancer-related pathways that may provide new candidates for OCCC targeted treatment.


Assuntos
Adenocarcinoma de Células Claras , Metilação de DNA , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares , Neoplasias Ovarianas , Fatores de Transcrição , Humanos , Metilação de DNA/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Linhagem Celular Tumoral , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Genoma Humano , Mutação/genética , Epigênese Genética , Análise por Conglomerados
17.
Arch Cardiovasc Dis ; 117(6-7): 392-401, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38834393

RESUMO

BACKGROUND: Intensive cardiac care units (ICCUs) were created to manage ventricular arrhythmias after acute coronary syndromes, but have diversified to include a more heterogeneous population, the characteristics of which are not well depicted by conventional methods. AIMS: To identify ICCU patient subgroups by phenotypic unsupervised clustering integrating clinical, biological, and echocardiographic data to reveal pathophysiological differences. METHODS: During 7-22 April 2021, we recruited all consecutive patients admitted to ICCUs in 39 centers. The primary outcome was in-hospital major adverse events (MAEs; death, resuscitated cardiac arrest or cardiogenic shock). A cluster analysis was performed using a Kamila algorithm. RESULTS: Of 1499 patients admitted to the ICCU (69.6% male, mean age 63.3±14.9 years), 67 (4.5%) experienced MAEs. Four phenogroups were identified: PG1 (n=535), typically patients with non-ST-segment elevation myocardial infarction; PG2 (n=444), younger smokers with ST-segment elevation myocardial infarction; PG3 (n=273), elderly patients with heart failure with preserved ejection fraction and conduction disturbances; PG4 (n=247), patients with acute heart failure with reduced ejection fraction. Compared to PG1, multivariable analysis revealed a higher risk of MAEs in PG2 (odds ratio [OR] 3.13, 95% confidence interval [CI] 1.16-10.0) and PG3 (OR 3.16, 95% CI 1.02-10.8), with the highest risk in PG4 (OR 20.5, 95% CI 8.7-60.8) (all P<0.05). CONCLUSIONS: Cluster analysis of clinical, biological, and echocardiographic variables identified four phenogroups of patients admitted to the ICCU that were associated with distinct prognostic profiles. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05063097.


Assuntos
Unidades de Cuidados Coronarianos , Fenótipo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Análise por Conglomerados , Medição de Risco , Mortalidade Hospitalar , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Infarto do Miocárdio sem Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Prognóstico , Fatores de Tempo , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/terapia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/diagnóstico , Estudos Prospectivos , Parada Cardíaca/terapia , Parada Cardíaca/fisiopatologia , Parada Cardíaca/diagnóstico , Parada Cardíaca/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Idoso de 80 Anos ou mais , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade
18.
Sensors (Basel) ; 24(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38894336

RESUMO

The paranasal sinuses, a bilaterally symmetrical system of eight air-filled cavities, represent one of the most complex parts of the equine body. This study aimed to extract morphometric measures from computed tomography (CT) images of the equine head and to implement a clustering analysis for the computer-aided identification of age-related variations. Heads of 18 cadaver horses, aged 2-25 years, were CT-imaged and segmented to extract their volume, surface area, and relative density from the frontal sinus (FS), dorsal conchal sinus (DCS), ventral conchal sinus (VCS), rostral maxillary sinus (RMS), caudal maxillary sinus (CMS), sphenoid sinus (SS), palatine sinus (PS), and middle conchal sinus (MCS). Data were grouped into young, middle-aged, and old horse groups and clustered using the K-means clustering algorithm. Morphometric measurements varied according to the sinus position and age of the horses but not the body side. The volume and surface area of the VCS, RMS, and CMS increased with the age of the horses. With accuracy values of 0.72 for RMS, 0.67 for CMS, and 0.31 for VCS, the possibility of the age-related clustering of CT-based 3D images of equine paranasal sinuses was confirmed for RMS and CMS but disproved for VCS.


Assuntos
Imageamento Tridimensional , Seios Paranasais , Cavalos , Animais , Análise por Conglomerados , Seios Paranasais/diagnóstico por imagem , Imageamento Tridimensional/métodos , Tomografia Computadorizada Multidetectores/métodos , Algoritmos
19.
Math Biosci Eng ; 21(4): 5604-5633, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38872550

RESUMO

The epidemiology of pandemics is classically viewed using geographical and political borders; however, these artificial divisions can result in a misunderstanding of the current epidemiological state within a given region. To improve upon current methods, we propose a clustering algorithm which is capable of recasting regions into well-mixed clusters such that they have a high level of interconnection while minimizing the external flow of the population towards other clusters. Moreover, we analyze and identify so-called core clusters, clusters that retain their features over time (temporally stable) and independent of the presence or absence of policy measures. In order to demonstrate the capabilities of this algorithm, we use USA county-level cellular mobility data to divide the country into such clusters. Herein, we show a more granular spread of SARS-CoV-2 throughout the first weeks of the pandemic. Moreover, we are able to identify areas (groups of counties) that were experiencing above average levels of transmission within a state, as well as pan-state areas (clusters overlapping more than one state) with very similar disease spread. Therefore, our method enables policymakers to make more informed decisions on the use of public health interventions within their jurisdiction, as well as guide collaboration with surrounding regions to benefit the general population in controlling the spread of communicable diseases.


Assuntos
Algoritmos , COVID-19 , Pandemias , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/transmissão , COVID-19/prevenção & controle , Humanos , Estados Unidos/epidemiologia , Pandemias/prevenção & controle , Análise por Conglomerados , Dinâmica Populacional , Política de Saúde
20.
Mol Biol Rep ; 51(1): 738, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874633

RESUMO

BACKGROUND: Interspecific hybrids of rohu (Labeo rohita) and catla (Labeo catla) are common, especially in India due to constrained breeding. These hybrids must segregate from their wild parents as part of conservational strategies. This study intended to screen the hybrids from wild rohu and catla parents using both morphometric and molecular approaches. METHODS & RESULTS: The carp samples were collected from Jharkhand and West Bengal, India. The correlation and regression analysis of morphometric features are considered superficial but could be protracted statistically by clustering analysis and further consolidated by nucleotide variations of one mitochondrial and one nuclear gene to differentiate hybrids from their parents. Out of 21 morphometric features, 6 were used for clustering analysis that exhibited discrete separation among rohu, catla, and their hybrids when the data points were plotted in a low-dimensional 2-D plane using the first 2 principal components. Out of 40 selected single nucleotide polymorphism (SNP) positions of the COX1 gene, hybrid showed 100% similarity with catla. Concerning SNP similarity of the 18S rRNA nuclear gene, the hybrid showed 100% similarity with rohu but not with catla; exhibiting its probable parental inheritance. CONCLUSIONS: Along with morphometric analysis, the SNP comparison study together points towards strong evidence of interspecific hybridization between rohu and catla, as these hybrids share both morphological and molecular differences with either parent. However, this study will help screen the hybrids from their wild parents, as a strategy for conservational management.


Assuntos
Carpas , Hibridização Genética , Polimorfismo de Nucleotídeo Único , Animais , Carpas/genética , Carpas/anatomia & histologia , Hibridização Genética/genética , Polimorfismo de Nucleotídeo Único/genética , Índia , RNA Ribossômico 18S/genética , Filogenia , Cyprinidae/genética , Cyprinidae/anatomia & histologia , Quimera/genética , Análise por Conglomerados
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