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1.
J Thorac Dis ; 16(6): 3764-3781, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38983163

RESUMEN

Background: Lung cancer is the most common primary malignant tumor of the lung, and as one of the malignant tumors that pose the greatest threat to the health of the population, the incidence rate has remained high in recent years. Previous studies have shown that KLRB1 is transcriptionally repressed in lung adenocarcinoma and correlates with lung adenocarcinoma prognosis. The objective of this study is to investigate the intrinsic mechanisms by which KLRB1 affects the malignant phenotypes of lung adenocarcinoma such as immune infiltration, proliferation, growth and metastasis. Methods: We assessed the expression levels of KLRB1 in publicly available databases and investigated its associations with clinical and pathological variables. Enrichment analysis was subsequently conducted to investigate possible signaling pathways and their associated biological functions. Statistical analysis, including Spearman correlation and the application of multigene prediction models, was utilized to assess the relationship between the expression of KLRB1 and the infiltration of immune cells. The diagnostic and prognostic value of KLRB1 was evaluated using Kaplan-Meier survival curves, diagnostic receptor operating characteristic (ROC) curves, histogram models, and Cox regression analysis. Specimens from lung adenocarcinoma (LUAD) patients were collected, the expression level of KLRB1 was detected by protein blotting analysis, and the expression level of KLRB1 was detected at the mRNA level by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Small interfering RNA (siRNA) was used to silence gene expression, and Transwell, Cell Counting Kit-8 (CCK-8) and colony formation assays were subsequently performed to analyze the effects of KLRB1 on LUAD cell migration, invasion and proliferation. Results: KLRB1 expression was lower in lung cancer tissue than in surrounding healthy tissue. Genes differentially expressed in the low and high KLRB1 expression groups were found to be significantly enriched in pathways related to immunity. KLRB1 exerted an impact on the MAPK/ERK signaling pathway, thereby modulating the growth and proliferation of LUAD cells. KLRB1 expression is linked to prognosis, immune infiltration, and cell migration and proliferation in LUAD. Conclusions: The evidence revealed a correlation between KLRB1 and both prognosis and immune infiltration in LUAD patients.

2.
Int J Med Sci ; 21(8): 1529-1540, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903926

RESUMEN

Introduction: Skin, being the body's largest organ, is susceptible to injuries. Despite the adoption of common treatments such as debridement, wound dressing, and infection control measures for skin injuries, the outcomes remain unsatisfactory, especially in diabetic patients or elderly patients. The use of adipose stem cell-derived apoptotic extracellular vesicles (apoEVs-ASCs) has been shown great therapeutic potential in wound repair. The effect of the donor age on the biological properties and functions of apoEVs-ASCs has not been reported. Methods: In this study, we isolated apoEVs-ASCs from young and aged rats. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were applied for the characteristics of apoEVs-ASCs. For aged and young apoEVs-ASCs groups, the proliferative and migration abilities in vitro, and wound healing function in vivo were contrastively evaluated and quantified for statistical analysis. Results: Our results showed that both young and aged apoEVs-ASCs induced skin healing and reduced scar formation. In addition, young apoEVs-ASCs had significantly higher proliferation, migration of fibroblasts and endothelial cells, and increased neo-angiogenesis ability, when compared with that of aged apoEVs-ASCs. Conclusion: Young apoEVs-ASCs should be employed for wound repair, which is associated with its superior promoting effect on wound healing.


Asunto(s)
Apoptosis , Proliferación Celular , Vesículas Extracelulares , Piel , Cicatrización de Heridas , Animales , Cicatrización de Heridas/fisiología , Vesículas Extracelulares/trasplante , Vesículas Extracelulares/metabolismo , Ratas , Piel/lesiones , Piel/patología , Tejido Adiposo/citología , Células Madre/citología , Células Madre/metabolismo , Humanos , Masculino , Movimiento Celular , Factores de Edad , Regeneración/fisiología , Ratas Sprague-Dawley
3.
Mol Psychiatry ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38879719

RESUMEN

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy.

4.
J Cardiothorac Surg ; 19(1): 366, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915108

RESUMEN

BACKGROUND: The prognostic value of cellular retinoic acid-binding protein 2 (CRABP2), in lung cancer patients remains to be uncertained. Therefore, our research attempted to assess the relationship between CRABP2 and survival analysis in lung cancer patients through meta-analysis. METHOD: Related literature retrieved from Cochrane Library, Ovid, Embase, PubMed, the CNKI, and the Web of Science. The latest update of the search was May 1, 2023. The outcome indicators included as effective measures in the study were hazard ratio (HR), and 95% confidence interval (CI). The Stata 12.0 software was used to analyze the data. RESULTS: A total of4 studies were finally enrolled in our meta-analysis. The increased plasma level of CRABP2 predicted poor OS in lung cancer patient with a combined HR of 1.14 (95% CI: 1.00-1.30), and were not associated with poor PFS with combined HR: 1.15% CI: 0.63-2.09) in lung cancer patients. CONCLUSIONS: Our meta-analysis found the increased plasma level of CRABP2 was associated with poor OS independently in NSCLC patients. The plasma CRABP2 level may be an indicator of biological aggressiveness of the tumor. Our research was promising regarding the feasibility and utility of plasma CRABP2 as a novel prognostic biomarker in NSCLC, and the findings warrant further investigation.


Asunto(s)
Biomarcadores de Tumor , Neoplasias Pulmonares , Receptores de Ácido Retinoico , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/mortalidad , Pronóstico , Biomarcadores de Tumor/sangre , Receptores de Ácido Retinoico/sangre , Receptores de Ácido Retinoico/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/mortalidad
5.
Science ; 384(6698): eadi5199, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38781369

RESUMEN

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multiomics datasets into a resource comprising >2.8 million nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550,000 cell type-specific regulatory elements and >1.4 million single-cell expression quantitative trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.


Asunto(s)
Encéfalo , Redes Reguladoras de Genes , Trastornos Mentales , Análisis de la Célula Individual , Humanos , Envejecimiento/genética , Encéfalo/metabolismo , Comunicación Celular/genética , Cromatina/metabolismo , Cromatina/genética , Genómica , Trastornos Mentales/genética , Corteza Prefrontal/metabolismo , Corteza Prefrontal/fisiología , Sitios de Carácter Cuantitativo
6.
bioRxiv ; 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38562822

RESUMEN

Single-cell genomics is a powerful tool for studying heterogeneous tissues such as the brain. Yet, little is understood about how genetic variants influence cell-level gene expression. Addressing this, we uniformly processed single-nuclei, multi-omics datasets into a resource comprising >2.8M nuclei from the prefrontal cortex across 388 individuals. For 28 cell types, we assessed population-level variation in expression and chromatin across gene families and drug targets. We identified >550K cell-type-specific regulatory elements and >1.4M single-cell expression-quantitative-trait loci, which we used to build cell-type regulatory and cell-to-cell communication networks. These networks manifest cellular changes in aging and neuropsychiatric disorders. We further constructed an integrative model accurately imputing single-cell expression and simulating perturbations; the model prioritized ~250 disease-risk genes and drug targets with associated cell types.

7.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38493342

RESUMEN

Dynamic compartmentalization of eukaryotic DNA into active and repressed states enables diverse transcriptional programs to arise from a single genetic blueprint, whereas its dysregulation can be strongly linked to a broad spectrum of diseases. While single-cell Hi-C experiments allow for chromosome conformation profiling across many cells, they are still expensive and not widely available for most labs. Here, we propose an alternate approach, scENCORE, to computationally reconstruct chromatin compartments from the more affordable and widely accessible single-cell epigenetic data. First, scENCORE constructs a long-range epigenetic correlation graph to mimic chromatin interaction frequencies, where nodes and edges represent genome bins and their correlations. Then, it learns the node embeddings to cluster genome regions into A/B compartments and aligns different graphs to quantify chromatin conformation changes across conditions. Benchmarking using cell-type-matched Hi-C experiments demonstrates that scENCORE can robustly reconstruct A/B compartments in a cell-type-specific manner. Furthermore, our chromatin confirmation switching studies highlight substantial compartment-switching events that may introduce substantial regulatory and transcriptional changes in psychiatric disease. In summary, scENCORE allows accurate and cost-effective A/B compartment reconstruction to delineate higher-order chromatin structure heterogeneity in complex tissues.


Asunto(s)
Cromatina , Cromosomas , Cromatina/genética , ADN , Conformación Molecular , Epigénesis Genética
8.
bioRxiv ; 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38464236

RESUMEN

Multimodal measurements have become widespread in genomics, however measuring open chromatin accessibility and splicing simultaneously in frozen brain tissues remains unconquered. Hence, we devised Single-Cell-ISOform-RNA sequencing coupled with the Assay-for-Transposase-Accessible-Chromatin (ScISOr-ATAC). We utilized ScISOr-ATAC to assess whether chromatin and splicing alterations in the brain convergently affect the same cell types or divergently different ones. We applied ScISOr-ATAC to three major conditions: comparing (i) the Rhesus macaque (Macaca mulatta) prefrontal cortex (PFC) and visual cortex (VIS), (ii) cross species divergence of Rhesus macaque versus human PFC, as well as (iii) dysregulation in Alzheimer's disease in human PFC. We found that among cortical-layer biased excitatory neuron subtypes, splicing is highly brain-region specific for L3-5/L6 IT_RORB neurons, moderately specific in L2-3 IT_CUX2.RORB neurons and unspecific in L2-3 IT_CUX2 neurons. In contrast, at the chromatin level, L2-3 IT_CUX2.RORB neurons show the highest brain-region specificity compared to other subtypes. Likewise, when comparing human and macaque PFC, strong evolutionary divergence on one molecular modality does not necessarily imply strong such divergence on another molecular level in the same cell type. Finally, in Alzheimer's disease, oligodendrocytes show convergently high dysregulation in both chromatin and splicing. However, chromatin and splicing dysregulation most strongly affect distinct oligodendrocyte subtypes. Overall, these results indicate that chromatin and splicing can show convergent or divergent results depending on the performed comparison, justifying the need for their concurrent measurement to investigate complex systems. Taken together, ScISOr-ATAC allows for the characterization of single-cell splicing and chromatin patterns and the comparison of sample groups in frozen brain samples.

9.
Comb Chem High Throughput Screen ; 27(11): 1602-1610, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38204250

RESUMEN

BACKGROUND: Lung cancer is a life-threatening disease that is still prevalent worldwide. This study aims to evaluate the effects of matricin, a sesquiterpene, on the carcinogenic agent benzo(a)pyrene [B(a)P]-induced lung cancer in Swiss albino mice. METHODS: Lung cancer was induced by oral administration of B(a)P at 50 mg/kg b. wt. in model Swiss-albino mice (group II) as well in experimental group III, and treated with matricin (100 mg/kg b. wt.) in group III. Upon completion of treatment for 18 weeks, the changes in body weight, tumor formation, enzymatic and non-enzymatic antioxidant levels (GSH, SOD, GPx, GR, QR, CAT), lipid peroxidation (LPO) level, pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß), immunoglobulin levels (IgG, IgM), apoptosis markers (Bax, Bcl-xL), tumor markers (carcinoembryogenic antigen (CEA), neuron-specific enolase (NSE)), and histopathological (H&E) alterations were determined. RESULTS: The results indicate that B(a)P caused a significant increase of tumor formation in the lungs, increased tumor markers and inflammatory cytokines in serum, and depletion of enzymatic/ non-enzymatic antioxidants and immunoglobulins, compared to the untreated control group. Matricin treatment significantly reversed the changes caused by B(a)P as evidenced by the biochemical and histopathological assays. CONCLUSION: The changes caused by matricin clearly indicate the cancer-preventive effects of matricin against B(a)P-induced lung cancer in animal models, which can be attributed to the antioxidant activity, immunomodulation, and mitigation of the NF-kß pathway.


Asunto(s)
Benzo(a)pireno , Neoplasias Pulmonares , Animales , Ratones , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevención & control , Modelos Animales de Enfermedad , Sesquiterpenos/farmacología , Sesquiterpenos/química , Antioxidantes/farmacología , Masculino , Citocinas/metabolismo , Carcinogénesis/efectos de los fármacos , Carcinogénesis/inducido químicamente , Apoptosis/efectos de los fármacos
10.
Top Stroke Rehabil ; 31(3): 301-310, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37651207

RESUMEN

OBJECTIVES: This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient's lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis. RESULTS: The dice similarity coefficient between each patient's lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =-0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02). CONCLUSION: The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.


Asunto(s)
Afasia , Accidente Cerebrovascular , Humanos , Semántica , Imagen por Resonancia Magnética , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/patología , Afasia/diagnóstico por imagen , Afasia/etiología , Afasia/terapia , Encéfalo/patología
11.
Sci Rep ; 13(1): 22825, 2023 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-38129509

RESUMEN

During the COVID19 pandemic, there is a pronounced collective mental health issue among college students. Forecasting the trend of emotional changes in on-campus students is crucial to effectively address this issue. This study proposes an Attention-LSTM neural network model that performs deep learning on key input sequence information, so as to predict the distribution of emotional states in college students. By testing 60 consecutive days of emotional data, the model successfully predicts students' emotional distribution, triggers and resolution strategies, with an accuracy rate of no less than 99%. Compared with models such as ARIMA, SARIMA and VAR, this model shows significant advantages in accuracy, operational efficiency, and data collection requirements. The integration of deep learning technology with student management in this study offers a novel approach to address emotional issues among students under exceptional circumstances.


Asunto(s)
COVID-19 , Disfunción Cognitiva , Humanos , COVID-19/epidemiología , Pandemias , Estudiantes , Emociones
12.
Angew Chem Int Ed Engl ; 62(39): e202308410, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37578640

RESUMEN

Electroluminescent (EL) clusters emerged rapidly, owing to their organic-inorganic hybrid character useful for comprehensive performance integration and the potential for large-scale display and lighting applications. However, despite their good photoluminescent (PL) properties, until present, no efficient EL monodentate ligand-based clusters were reported due to structural variation during processing and excitation and exciton confinement on cluster-centered quenching states. Here we demonstrate an effective bulky passivation strategy for efficient cluster light-emitting diodes with a monophosphine Cu4 I4 cube named [TMeOPP]4 Cu4 I4 . With terminal pyridine groups, an active matrix named TmPyPB supports an effective host-cluster interplay for configuration fixation, structural stabilization, and exciton-confinement optimization. Compared to common inactive hosts, the passivation effects of TmPyPB markedly reduce trap-state densities by 24-40 % to suppress nonradiative decay, resulting in state-of-the-art PL and EL quantum yields reaching 99 % and 15.6 %, respectively, which are significantly improved by about 7-fold. TmPyPB simultaneously increases EL luminance to 104 nits, which is ≈100-fold that of the non-doped analogue.

13.
J Inflamm Res ; 15: 3719-3731, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35789664

RESUMEN

Background: The routine clinical nutritional and inflammatory indicators such as serum albumin, total cholesterol and lymphocytes have been widely investigated in the prognosis of small cell lung cancer (SCLC). The Naples prognostic score (NPS), based on nutritional and inflammatory status, has been identified as a prognostic impactor in several malignancies. However, the prognostic role of NPS in SCLC has not been elucidated. This study aims to evaluate the prognostic effect of NPS in SCLC patients. Patients and Methods: Patients with SCLC were recruited at Hebei General Hospital between April 2015 and August 2021. Pretreatment clinical and laboratory data were obtained. Participants were assigned into three groups according to NPS (group 0: NPS=0, group 1: NPS=1 or 2, group 2: NPS=3 or 4). Kaplan-Meier and Cox regression analysis were performed to assess the prognostic significance of NPS. The RMS package in R software was used to draw the nomogram predictive model. Results: A total of 128 patients were enrolled. The median progression-free survival (PFS) and overall survival (OS) was 7.2 and 12.3 months, respectively. The median PFS and OS was 12.3 vs 19.8 months, 7.6 vs 14.1 months and 6.0 vs 8.45 months for the three groups respectively. There were significant differences in both OS and FPS among the three groups. Survival analysis showed that NPS was significantly correlated with both OS and PFS (P<0.05). Lower NPS is associated with longer OS and PFS. Multivariate analysis showed that NPS has an independent prognostic impact on OS (P<0.05). The nomogram predictive model showed that NPS has good predictive power for survival rates. Conclusion: NPS is an independent prognostic factor for OS in SCLC patients. Low NPS may predict longer OS. Therefore NPS plays a vital role in the nomogram predictive model of survival rates in SCLC patients.

14.
BMC Med Inform Decis Mak ; 22(Suppl 2): 147, 2022 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-35655307

RESUMEN

BACKGROUND: Knowledges graphs (KGs) serve as a convenient framework for structuring knowledge. A number of computational methods have been developed to generate KGs from biomedical literature and use them for downstream tasks such as link prediction and question answering. However, there is a lack of computational tools or web frameworks to support the exploration and visualization of the KG themselves, which would facilitate interactive knowledge discovery and formulation of novel biological hypotheses. METHOD: We developed a web framework for Knowledge Graph Exploration and Visualization (KGEV), to construct and visualize KGs in five stages: triple extraction, triple filtration, metadata preparation, knowledge integration, and graph database preparation. The application has convenient user interface tools, such as node and edge search and filtering, data source filtering, neighborhood retrieval, and shortest path calculation, that work by querying a backend graph database. Unlike other KGs, our framework allows fast retrieval of relevant texts supporting the relationships in the KG, thus allowing human reviewers to judge the reliability of the knowledge extracted. RESULTS: We demonstrated a case study of using the KGEV framework to perform research on COVID-19. The COVID-19 pandemic resulted in an explosion of relevant literature, making it challenging to make full use of the vast and heterogenous sources of information. We generated a COVID-19 KG with heterogenous information, including literature information from the CORD-19 dataset, as well as other existing knowledge from eight data sources. We showed the utility of KGEV in three intuitive case studies to explore and query knowledge on COVID-19. A demo of this web application can be accessed at http://covid19nlp.wglab.org . Finally, we also demonstrated a turn-key adaption of the KGEV framework to study clinical phenotypic presentation of human diseases by Human Phenotype Ontology (HPO), illustrating the versatility of the framework. CONCLUSION: In an era of literature explosion, the KGEV framework can be applied to many emerging diseases to support structured navigation of the vast amount of newly published biomedical literature and other existing biological knowledge in various databases. It can be also used as a general-purpose tool to explore and query gene-phenotype-disease-drug relationships interactively.


Asunto(s)
COVID-19 , Humanos , Pandemias , Reconocimiento de Normas Patrones Automatizadas , Fenotipo , Reproducibilidad de los Resultados
15.
J Comput Biol ; 29(7): 619-633, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35584295

RESUMEN

Recent advances in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) have allowed simultaneous epigenetic profiling over thousands of individual cells to dissect the cellular heterogeneity and elucidate regulatory mechanisms at the finest possible resolution. However, scATAC-seq is challenging to model computationally due to the ultra-high dimensionality, low signal-to-noise ratio, complex feature interactions, and high vulnerability to various confounding factors. In this study, we present Translator, an efficient transfer learning approach to capture generalizable chromatin interactions from high-quality (HQ) reference scATAC-seq data to obtain robust cell representations in low-to-moderate quality target scATAC-seq data. We applied Translator on various simulated and real scATAC-seq datasets and demonstrated that Translator could learn more biologically meaningful cell representations than other methods by incorporating information learned from the reference data, thus facilitating various downstream analyses such as clustering and motif enrichment measurements. Moreover, Translator's block-wise deep learning framework can handle nonlinear relationships with restricted connections using fewer parameters to boost computational efficiency through Graphics Processing Unit (GPU) parallelism. Finally, we have implemented Translator as a free software package available for the community to leverage large-scale, HQ reference data to study target scATAC-seq data.


Asunto(s)
Secuenciación de Inmunoprecipitación de Cromatina , Análisis de Datos , Cromatina/genética , Aprendizaje Automático , Análisis de la Célula Individual/métodos , Transposasas
16.
Genes (Basel) ; 13(4)2022 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-35456427

RESUMEN

Mapping chromatin insulator loops is crucial to investigating genome evolution, elucidating critical biological functions, and ultimately quantifying variant impact in diseases. However, chromatin conformation profiling assays are usually expensive, time-consuming, and may report fuzzy insulator annotations with low resolution. Therefore, we propose a weakly supervised deep learning method, InsuLock, to address these challenges. Specifically, InsuLock first utilizes a Siamese neural network to predict the existence of insulators within a given region (up to 2000 bp). Then, it uses an object detection module for precise insulator boundary localization via gradient-weighted class activation mapping (~40 bp resolution). Finally, it quantifies variant impacts by comparing the insulator score differences between the wild-type and mutant alleles. We applied InsuLock on various bulk and single-cell datasets for performance testing and benchmarking. We showed that it outperformed existing methods with an AUROC of ~0.96 and condensed insulator annotations to ~2.5% of their original size while still demonstrating higher conservation scores and better motif enrichments. Finally, we utilized InsuLock to make cell-type-specific variant impacts from brain scATAC-seq data and identified a schizophrenia GWAS variant disrupting an insulator loop proximal to a known risk gene, indicating a possible new mechanism of action for the disease.


Asunto(s)
Cromatina , Redes Neurales de la Computación , Factor de Unión a CCCTC/genética , Genoma , Aprendizaje Automático Supervisado
17.
J Biomed Inform ; 128: 104031, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35183765

RESUMEN

Preterm birth affects more than 10% of all births worldwide. Such infants are much more prone to Growth Faltering (GF), an issue that has been unsolved despite the implementation of numerous interventions aimed at optimizing preterm infant nutrition. To improve the ability for early prediction of GF risk for preterm infants we collected a comprehensive, large, and unique clinical and microbiome dataset from 3 different sites in the US and the UK. We use and extend machine learning methods for GF prediction from clinical data. We next extend graphical models to integrate time series clinical and microbiome data. A model that integrates clinical and microbiome data improves on the ability to predict GF when compared to models using clinical data only. Information on a small subset of the taxa is enough to help improve model accuracy and to predict interventions that can improve outcome. We show that a hierarchical classifier that only uses a subset of the taxa for a subset of the infants is both the most accurate and cost-effective method for GF prediction. Further analysis of the best classifiers enables the prediction of interventions that can improve outcome.


Asunto(s)
Microbiota , Nacimiento Prematuro , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Aprendizaje Automático
18.
Thorac Cancer ; 13(5): 742-749, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35040271

RESUMEN

OBJECTIVE: To clarify the effect of miR-181b on the biological function of small-cell lung cancer (SCLC) and explore the effect of clinical resistance on SCLC. METHODS: Blood samples were collected from 30 SCLC patients and 30 non-SCLC patients in our department from 2017 to 2019 to detect the expression level of miR-181b.The expression level of miR-181b was detected in SCLC cells by RT-PCR, and screening of downstream target genes by gene chip, verification with luciferase, and Western blotting. In addition, collect the general data of 30 SCLC patients and 30 non-SCLC patients (control group), the patients were diagnosed by pathology and undergoing EC protocol in the Department of Thoracic Surgery and Oncology of our hospital to detect the expression level of mir-181b in different periods. Furthermore, in the SCLC cell line, EC chemotherapy was administered to detect the sensitivity of drug resistance and nondrug resistance. RESULTS: miR-181b in SCLC patients was lower than in normal people as well as the drug-sensitive cell line. ACE2 was verified as a downstream target of miR-181b by gene chip screening. First-line chemotherapy can promote the recovery of miR-181b, but cannot repair to normal levels. miR-181b can enhance the drug sensitivity of SCLC drug-resistant cells. CONCLUSION: miR-181b directly targets ACE2 to affect the biological characteristics of SCLC. The expression level of miR-181b is highly related to the drug resistance of SCLC, which suggests that miR-181b could be a potential biomarker candidate for treatment efficacy of SCLC.


Asunto(s)
Neoplasias Pulmonares , MicroARNs , Enzima Convertidora de Angiotensina 2 , Línea Celular Tumoral , Resistencia a Medicamentos , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/biosíntesis , MicroARNs/genética , MicroARNs/metabolismo
19.
PM R ; 14(8): 913-921, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34310072

RESUMEN

BACKGROUND: Nonverbal cognitive training for aphasia has gained popularity. Prior research has found that cognitive status correlates with language function. OBJECTIVE: To determine whether nonverbal computer-assisted executive control training (CAET) to improve cognitive status affects language performance in patients with aphasia (PWA) and executive dysfunction. DESIGN: A single blind randomized trial. SETTING: Department of Rehabilitation, Affiliated Hospital of Xuzhou Medical University. PARTICIPANTS: A total of 68 individuals were randomized, underwent treatment and were included in the analysis (CAET group, n = 33; control group, n = 35). INTERVENTIONS: The experimental group was treated with 4 weeks of traditional speech and language therapy (SLT) combined with CAET. The control group underwent SLT only. MAIN OUTCOME MEASURES: Western Aphasia Battery [WAB]) with executive dysfunction (as assessed by the verbal fluency test [VFT], the Proverbs Test, the Tower of London Test [TLT], the Stroop Color and Word Test [SCWT], and the Trail Making Test [TMT]). RESULTS: Differences between pre- and posttreatment language outcomes except oral naming (group × time, p = .236) were significantly greater in the experimental group compared with the control group: spontaneous speech (group × time, p = .026), auditory comprehension (group × time, p < .001), speech repetition (group × time, p = .001), and aphasia quotient (AQ; group × time, p < .001). A similar effect was observed for cognitive function such as Trial Making Test (TMT)-A (group × time, p = .006), TMT-B (group × time, p = .005), and verbal fluency test (VFT-V; group × time, p = .018). CONCLUSION: The study demonstrates that CAET combined with SLT can yield favorable language outcomes for PWA, especially improvements in auditory comprehension and AQ. CAET combined with SLT generates benefits in both cognitive function and language performance.


Asunto(s)
Afasia , Accidente Cerebrovascular , Afasia/etiología , Afasia/terapia , Computadores , Función Ejecutiva , Humanos , Método Simple Ciego , Resultado del Tratamiento
20.
Artículo en Inglés | MEDLINE | ID: mdl-34721629

RESUMEN

To evaluate the efficacy of acupuncture combined with rehabilitation training in patients with intensive care unit (ICU)-acquired muscle weakness (ICUAW), a single-blinded, randomized, sham-controlled clinical trial is designed for execution. In total, 56 participants with ICUAW will be randomly assigned to the treatment and control groups with 28 participants in each group. The participants will be treated with acupunctures or sham procedures at LI15, LI11, ST36, GB34, and ST31, 5 times per week for a total of 20 sessions in 4 weeks while they will receive rehabilitation training. Patients will be followed up every month for 3 months after treatment. The primary outcomes include changes in quadriceps femoris muscle area, thickness, vastus intermediate muscle thickness, subcutaneous tissue thickness, and ultrasonic intensities of the rectus femoris. The secondary outcomes consist of the modified Barthel index score and the Medical Research Council total score. Participants' mechanical ventilation, the rate of detachment at the second week, the 28-day survival rate, and the occurrence of adverse reactions will be measured, and any side effects will be reported and recorded. Patient outcomes between the treatment and control groups will be compared and statistically tested. We anticipate that the therapeutic regimen of acupuncture combined with rehabilitation training would be more effective than the rehabilitation training alone for the treatment of the ICUAW. The findings of this study could help develop a better strategy for the treatment of the ICUAW disease and explore a clinical application of an acupuncture technique. Trial registration: Chinese Clinical Trial Register ChiCTR2000038779. Registered 30 September, 2020, https://www.chictr.org.cn/showproj.aspx?proj=62284.

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