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  • Oxford University Press (OUP)  (8)
  • 1
    Online Resource
    Online Resource
    Molecular mechanisms underlying human spatial cognitive ability revealed with neurotransmitter and transcriptomic mapping
    Oxford University Press (OUP) ; 2023
    In:  Cerebral Cortex Vol. 33, No. 23 ( 2023-11-27), p. 11320-11328
    Details
    In: Cerebral Cortex, Oxford University Press (OUP), Vol. 33, No. 23 ( 2023-11-27), p. 11320-11328
    Abstract: Mental rotation, one of the cores of spatial cognitive abilities, is closely associated with spatial processing and general intelligence. Although the brain underpinnings of mental rotation have been reported, the cellular and molecular mechanisms remain unexplored. Here, we used magnetic resonance imaging, a whole-brain spatial distribution atlas of 19 neurotransmitter receptors, transcriptomic data from Allen Human Brain Atlas, and mental rotation performances of 356 healthy individuals to identify the genetic/molecular foundation of mental rotation. We found significant associations of mental rotation performance with gray matter volume and fractional amplitude of low-frequency fluctuations in primary visual cortex, fusiform gyrus, primary sensory-motor cortex, and default mode network. Gray matter volume and fractional amplitude of low-frequency fluctuations in these brain areas also exhibited significant sex differences. Importantly, spatial correlation analyses were conducted between the spatial patterns of gray matter volume or fractional amplitude of low-frequency fluctuations with mental rotation and the spatial distribution patterns of neurotransmitter receptors and transcriptomic data, and identified the related genes and neurotransmitter receptors associated with mental rotation. These identified genes are localized on the X chromosome and are mainly involved in trans-synaptic signaling, transmembrane transport, and hormone response. Our findings provide initial evidence for the neural and molecular mechanisms underlying spatial cognitive ability.
    Type of Medium: Online Resource
    ISSN: 1047-3211 , 1460-2199
    URL: Article
    DOI: 10.1093/cercor/bhad368
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1077450-6
    detail.hit.zdb_id: 1483485-6
    SSG: 12
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  • 2
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    Clinically Interpretable Machine Learning Models for Early Prediction of Mortality in Older Patients with Multiple Organ Dysfunction Syndrome: An International Multicenter Retrospective Study
    Oxford University Press (OUP) ; 2023
    In:  The Journals of Gerontology: Series A Vol. 78, No. 4 ( 2023-03-30), p. 718-726
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 78, No. 4 ( 2023-03-30), p. 718-726
    Abstract: Multiple organ dysfunction syndrome (MODS) is associated with a high risk of mortality among older patients. Current severity scores are limited in their ability to assist clinicians with triage and management decisions. We aim to develop mortality prediction models for older patients with MODS admitted to the ICU. Methods The study analyzed older patients from 197 hospitals in the United States and 1 hospital in the Netherlands. The cohort was divided into the young-old (65–80 years) and old-old (≥80 years), which were separately used to develop and evaluate models including internal, external, and temporal validation. Demographic characteristics, comorbidities, vital signs, laboratory measurements, and treatments were used as predictors. We used the XGBoost algorithm to train models, and the SHapley Additive exPlanations (SHAP) method to interpret predictions. Results Thirty-four thousand four hundred and ninety-seven young-old (11.3% mortality) and 21 330 old-old (15.7% mortality) patients were analyzed. Discrimination AUROC of internal validation models in 9 046 U.S. patients was as follows: 0.87 and 0.82, respectively; discrimination of external validation models in 1 905 EUR patients was as follows: 0.86 and 0.85, respectively; and discrimination of temporal validation models in 8 690 U.S. patients: 0.85 and 0.78, respectively. These models outperformed standard clinical scores like Sequential Organ Failure Assessment and Acute Physiology Score III. The Glasgow Coma Scale, Charlson Comorbidity Index, and Code Status emerged as top predictors of mortality. Conclusions Our models integrate data spanning physiologic and geriatric-relevant variables that outperform existing scores used in older adults with MODS, which represents a proof of concept of how machine learning can streamline data analysis for busy ICU clinicians to potentially optimize prognostication and decision making.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glac107
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2043927-1
    detail.hit.zdb_id: 1223643-3
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  • 3
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    A secreted protein (Canopy 2, CNPY2) enhances angiogenesis and promotes smooth muscle cell migration and proliferation
    Oxford University Press (OUP) ; 2015
    In:  Cardiovascular Research Vol. 105, No. 3 ( 2015-03-01), p. 383-393
    Details
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 105, No. 3 ( 2015-03-01), p. 383-393
    Type of Medium: Online Resource
    ISSN: 1755-3245 , 0008-6363
    URL: Article
    DOI: 10.1093/cvr/cvv010
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 1499917-1
    detail.hit.zdb_id: 80340-6
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  • 4
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    White Matter Structural and Network Topological Changes Underlying the Behavioral Phenotype of MECP2 Mutant Monkeys
    Oxford University Press (OUP) ; 2021
    In:  Cerebral Cortex Vol. 31, No. 12 ( 2021-10-22), p. 5396-5410
    Details
    In: Cerebral Cortex, Oxford University Press (OUP), Vol. 31, No. 12 ( 2021-10-22), p. 5396-5410
    Abstract: To explore the brain structural basis underlying the behavioral abnormalities associated with Rett syndrome (RTT), we carried out detailed longitudinal noninvasive magnetic resonance imaging analyses of RTT monkey models created by gene-editing, from weaning, through adolescence, till sexual maturation. Here, we report abnormal developmental dynamics of brain white matter (WM) microstructures and network topological organizations via diffusion tensor imaging. Specifically, disrupted WM microstructural integrity was observed at 9 months, but recovered thereafter, whereas WM network topological properties showed persistent abnormal dynamics from 9 to 37 months. Changes in the WM microstructure and WM network topology were correlated well with RTT-associated behavioral abnormalities including sleep latency, environmental exploration, and conflict encounters. Deleterious and protracted early WM myelination process likely lead to abnormal synaptic pruning, resulting in poor functional segregations. Together, this study provides initial evidence for changes in WM microstructure and network topological organization, which may underlie the neuro-patho-etilogy of RTT.
    Type of Medium: Online Resource
    ISSN: 1047-3211 , 1460-2199
    URL: Article
    DOI: 10.1093/cercor/bhab166
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1077450-6
    detail.hit.zdb_id: 1483485-6
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  • 5
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    A Simple Nomogram for Predicting Hospital Mortality of Patients Over 80 Years in ICU: An International Multicenter Retrospective Study
    Oxford University Press (OUP) ; 2023
    In:  The Journals of Gerontology: Series A Vol. 78, No. 7 ( 2023-07-08), p. 1227-1233
    Details
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 78, No. 7 ( 2023-07-08), p. 1227-1233
    Abstract: This study aimed to develop and validate an easy-to-use intensive care unit (ICU) illness scoring system to evaluate the in-hospital mortality for very old patients (VOPs, over 80 years old). Methods We performed a multicenter retrospective study based on the electronic ICU (eICU) Collaborative Research Database (eICU-CRD), Medical Information Mart for Intensive Care Database (MIMIC-III CareVue and MIMIC-IV), and the Amsterdam University Medical Centers Database (AmsterdamUMCdb). Least Absolute Shrinkage and Selection Operator regression was applied to variables selection. The logistic regression algorithm was used to develop the risk score and a nomogram was further generated to explain the score. Results We analyzed 23 704 VOPs, including 3 726 deaths (10 183 [13.5% mortality] from eICU-CRD [development set] , 12 703 [17.2%] from the MIMIC, and 818 [20.8%] from the AmsterdamUMC [external validation sets]). Thirty-four variables were extracted on the first day of ICU admission, and 10 variables were finally chosen including Glasgow Coma Scale, shock index, respiratory rate, partial pressure of carbon dioxide, lactate, mechanical ventilation (yes vs no), oxygen saturation, Charlson Comorbidity Index, blood urea nitrogen, and urine output. The nomogram was developed based on the 10 variables (area under the receiver operating characteristic curve: training of 0.792, testing of 0.788, MIMIC of 0.764, and AmsterdamUMC of 0.808 [external validating] ), which consistently outperformed the Sequential Organ Failure Assessment, acute physiology score III, and simplified acute physiology score II. Conclusions We developed and externally validated a nomogram for predicting mortality in VOPs based on 10 commonly measured variables on the first day of ICU admission. It could be a useful tool for clinicians to identify potentially high risks of VOPs.
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    URL: Article
    DOI: 10.1093/gerona/glad124
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2043927-1
    detail.hit.zdb_id: 1223643-3
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  • 6
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    EyeDiseases: an integrated resource for dedicating to genetic variants, gene expression and epigenetic factors of human eye diseases
    Oxford University Press (OUP) ; 2021
    In:  NAR Genomics and Bioinformatics Vol. 3, No. 2 ( 2021-04-09)
    Details
    In: NAR Genomics and Bioinformatics, Oxford University Press (OUP), Vol. 3, No. 2 ( 2021-04-09)
    Abstract: Eye diseases are remarkably common and encompass a large and diverse range of morbidities that affect different components of the visual system and visual function. With advances in omics technology of eye disorders, genome-scale datasets have been rapidly accumulated in genetics and epigenetics field. However, the efficient collection and comprehensive analysis of different kinds of omics data are lacking. Herein, we developed EyeDiseases (https://eyediseases.bio-data.cn/), the first database for multi-omics data integration and interpretation of human eyes diseases. It contains 1344 disease-associated genes with genetic variation, 1774 transcription files of bulk cell expression and single-cell RNA-seq, 105 epigenomics data across 185 kinds of human eye diseases. Using EyeDiseases, we investigated SARS-CoV-2 potential tropism in eye infection and found that the SARS-CoV-2 entry factors, ACE2 and TMPRSS2 are highly correlated with cornea and keratoconus, suggest that ocular surface cells are susceptible to infection by SARS-CoV-2. Additionally, integrating analysis of Age-related macular degeneration (AMD) GWAS loci and co-expression data revealed 9 associated genes involved in HIF-1 signaling pathway and voltage-gate potassium channel complex. The EyeDiseases provides a valuable resource for accelerating the discovery and validation of candidate loci and genes contributed to the molecular diagnosis and therapeutic vulnerabilities with various eyes diseases.
    Type of Medium: Online Resource
    ISSN: 2631-9268
    URL: Article
    DOI: 10.1093/nargab/lqab050
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 3009998-5
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  • 7
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    Proteomic analysis of aged and OPTN E50K retina in the development of normal tension glaucoma
    Oxford University Press (OUP) ; 2021
    In:  Human Molecular Genetics Vol. 30, No. 11 ( 2021-05-31), p. 1030-1044
    Details
    In: Human Molecular Genetics, Oxford University Press (OUP), Vol. 30, No. 11 ( 2021-05-31), p. 1030-1044
    Abstract: Progressive degeneration of retinal ganglion cells (RGCs) is a major characteristic of glaucoma, whose underlying mechanisms are still largely unknown. An E50K mutation in the Optineurin (OPTN) gene is a leading cause of normal tension glaucoma (NTG), directly affecting RGCs without high intraocular pressure and causing severe glaucomatous symptoms in clinical settings. A systematic analysis of the NTG mouse model is crucial for better understanding of the underlying pathological mechanisms for glaucoma. To elucidate proteomic and biochemical pathway alterations during NTG development, we established an OPTN E50K mutant mouse model through CRISPR/Cas9. Retinal proteins from resulting mice exhibiting glaucomatous phenotypes were subject to tandem mass tag-labeled quantitative proteomics and then analyzed through bioinformatics methods to characterize the molecular and functional signatures of NTG. We identified 6364 quantitative proteins in our proteomic analysis. Bioinformatics analysis revealed that OPTN E50K mice experienced protein synthesis dysregulation, age-dependent energy defects and autophagy-lysosome pathway dysfunction. Certain biological features, including amyloid deposition, RNA splicing, microglia activation and reduction of crystallin production, were similar to Alzheimer’s disease. Our study is the first to describe proteomic and biochemical pathway alterations in NTG pathogenesis during disease advancement. Several proteomic signatures overlapped with retinal changes found in the ad mice model, suggesting the presence of common mechanisms between age-related degenerative disorders, as well as prospective new targets for diagnostic and therapeutic strategies.
    Type of Medium: Online Resource
    ISSN: 0964-6906 , 1460-2083
    URL: Article
    DOI: 10.1093/hmg/ddab099
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1474816-2
    detail.hit.zdb_id: 1108742-0
    SSG: 12
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  • 8
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    Apatinib plus Chemotherapy as a Second-Line Treatment in Unresectable Non-Small Cell Lung Carcinoma: A Randomized, Controlled, Multicenter Clinical Trial
    Oxford University Press (OUP) ; 2020
    In:  The Oncologist Vol. 25, No. 11 ( 2020-11-01), p. e1640-e1649
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 25, No. 11 ( 2020-11-01), p. e1640-e1649
    Abstract: Click here to access other published clinical trials. Lessons Learned The efficacy of second-line treatment for advanced non-small cell lung carcinoma (NSCLC) without a sensitizing driver gene mutation is still unsatisfactory. The combination of apatinib and chemotherapy improved progression-free survival in the second-line therapy of advanced NSCLC without a sensitizing mutation. This study offers a new treatment strategy for second-line treatment of such patients but requires confirmation in a larger multi-institutional trial. Background This study explored the efficacy and safety of apatinib combined with single-agent chemotherapy versus single-agent chemotherapy in the second-line treatment of advanced non-small-cell lung carcinoma (NSCLC) without driver mutations. Methods In this double-arm, open label, exploratory clinical study, we enrolled patients with unresectable locally advanced or advanced NSCLC without driver mutations that had progressed following first-line chemotherapy. The subjects were allocated into an experimental group and a control group by 2:1. The experimental group received apatinib combined with four cycles of docetaxel or pemetrexed until disease progression, intolerable toxicity, or discontinuation at the patient' request. The control group only received four cycles of docetaxel or pemetrexed. The primary endpoints were progression-free survival (PFS), and the secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. Results Thirty-seven patients were enrolled. The efficacy of 33 patients was evaluated. The median PFS was 5.47 versus 2.97 months, the DCR was 95% versus 73%, and the objective response rate (ORR) was 27% versus 9% in the experimental versus control group. The OS was still under follow-up. The most common adverse effects included hypertension, hand-foot skin reaction (HFSR), and fatigue. Conclusion Apatinib combined with single-agent chemotherapy may be a novel option for second-line treatment of advanced NSCLC
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1634/theoncologist.2020-0519
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1409038-7
    detail.hit.zdb_id: 2023829-0
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