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1.
Entropy (Basel) ; 26(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38392360

RESUMO

As a promising data analysis technique, sparse modeling has gained widespread traction in the field of image processing, particularly for image recovery. The matrix rank, served as a measure of data sparsity, quantifies the sparsity within the Kronecker basis representation of a given piece of data in the matrix format. Nevertheless, in practical scenarios, much of the data are intrinsically multi-dimensional, and thus, using a matrix format for data representation will inevitably yield sub-optimal outcomes. Tensor decomposition (TD), as a high-order generalization of matrix decomposition, has been widely used to analyze multi-dimensional data. In a direct generalization to the matrix rank, low-rank tensor modeling has been developed for multi-dimensional data analysis and achieved great success. Despite its efficacy, the connection between TD rank and the sparsity of the tensor data is not direct. In this work, we introduce a novel tensor ring sparsity measurement (TRSM) for measuring the sparsity of the tensor. This metric relies on the tensor ring (TR) Kronecker basis representation of the tensor, providing a unified interpretation akin to matrix sparsity measurements, wherein the Kronecker basis serves as the foundational representation component. Moreover, TRSM can be efficiently computed by the product of the ranks of the mode-2 unfolded TR-cores. To enhance the practical performance of TRSM, the folded-concave penalty of the minimax concave penalty is introduced as a nonconvex relaxation. Lastly, we extend the TRSM to the tensor completion problem and use the alternating direction method of the multipliers scheme to solve it. Experiments on image and video data completion demonstrate the effectiveness of the proposed method.

2.
Nutrients ; 15(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37960165

RESUMO

Colorectal cancer (CRC) is a significant health concern and is the third most commonly diagnosed and second deadliest cancer worldwide. CRC has been steadily increasing in developing countries owing to factors such as aging and epidemics. Despite extensive research, the exact pathogenesis of CRC remains unclear, and its causes are complex and variable. Numerous in vitro, animal, and clinical trials have demonstrated the efficacy of probiotics such as Lactobacillus plantarum in reversing the adverse outcomes of CRC. These findings suggest that probiotics play vital roles in the prevention, adjuvant treatment, and prognosis of CRC. In this study, we constructed a mouse model of CRC using an intraperitoneal injection of azomethane combined with dextran sodium sulfate, while administering 5-fluorouracil as well as high- and low-doses of L. plantarum Zhang-LL live or heat-killed strains. Weight changes and disease activity indices were recorded during feeding, and the number of polyps and colon length were measured after euthanasia. HE staining was used to observe the histopathological changes in the colons of mice, and ELISA was used to detect the expression levels of IL-1ß, TNF-α, and IFN-γ in serum. To investigate the specific mechanisms involved in alleviating CRC progression, gut microbial alterations were investigated using 16S rRNA amplicon sequencing and non-targeted metabolomics, and changes in genes related to CRC were assessed using eukaryotic transcriptomics. The results showed that both viable and heat-killed strains of L. plantarum Zhang-LL in high doses significantly inhibited tumorigenesis, colon shortening, adverse inflammatory reactions, intestinal tissue damage, and pro-inflammatory factor expression upregulation. Specifically, in the gut microbiota, the abundance of the dominant flora Acutalibacter muris and Lactobacillus johnsonii was regulated, PGE2 expression was significantly reduced, the arachidonic acid metabolism pathway was inhibited, and CD22-mediated B-cell receptor regulation-related gene expression was upregulated. This study showed that L. plantarum Zhang-LL live or heat-inactivated strains alleviated CRC progression by reducing the abundance of potentially pathogenic bacteria, increasing the abundance of beneficial commensal bacteria, mediating the arachidonic acid metabolism pathway, and improving host immunogenicity.


Assuntos
Colite , Lactobacillus plantarum , Probióticos , Animais , Camundongos , Lactobacillus plantarum/fisiologia , Ácido Araquidônico/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Colite/induzido quimicamente , Colite/terapia , Colite/microbiologia , Transformação Celular Neoplásica , Carcinogênese , Modelos Animais de Doenças , Sulfato de Dextrana
3.
Neuroimage ; 280: 120359, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37661079

RESUMO

The process of complex cognition, which includes language processing, is dynamic in nature and involves various network modes or cognitive modes. This dynamic process can be manifested by a set of brain states and transitions between them. Previous neuroimaging studies have shed light on how bilingual brains support native language (L1) and second language (L2) through a shared network. However, the mechanism through which this shared brain network enables L1 and L2 processing remains unknown. This study examined this issue by testing the hypothesis that L1 and L2 processing is associated with distinct brain state dynamics in terms of brain state integration and transition flexibility. A group of late Chinese-English bilinguals was scanned using functional magnetic resonance imaging (fMRI) while listening to eight short narratives in Chinese (L1) and English (L2). Brain state dynamics were modeled using the leading eigenvector dynamic analysis framework. The results show that L1 processing involves more integrated states and frequent transitions between integrated and segregated states, while L2 processing involves more segregated states and fewer transitions. Our work provides insight into the dynamic process of narrative listening comprehension in late bilinguals and sheds new light on the neural representation of language processing and related disorders.


Assuntos
Encéfalo , Cognição , Multilinguismo , Rede Nervosa , Humanos , Povo Asiático , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Cognição/fisiologia , Idioma , Narração , Compreensão/fisiologia , China , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia , Esforço de Escuta/fisiologia
4.
Front Immunol ; 13: 997287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36405706

RESUMO

The pathogeny of type 1 diabetes (T1D) is mainly provoked by the ß-cell loss due to the autoimmune attack. Critically, autoreactive T cells firsthand attack ß-cell in islet, that results in the deficiency of insulin in bloodstream and ultimately leads to hyperglycemia. Hence, modulating immunity to conserve residual ß-cell is a desirable way to treat new-onset T1D. However, systemic immunosuppression makes patients at risk of organ damage, infection, even cancers. Biomaterials can be leveraged to achieve targeted immunomodulation, which can reduce the toxic side effects of immunosuppressants. In this review, we discuss the recent advances in harness of biomaterials to immunomodulate immunity for T1D. We investigate nanotechnology in targeting delivery of immunosuppressant, biological macromolecule for ß-cell specific autoreactive T cell regulation. We also explore the biomaterials for developing vaccines and facilitate immunosuppressive cells to restore immune tolerance in pancreas.


Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Humanos , Materiais Biocompatíveis/uso terapêutico , Insulina/uso terapêutico , Pâncreas/patologia
5.
Int J Dent ; 2022: 4475394, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432543

RESUMO

Objective: To evaluate a newly developed self-adhesive resin cement on physical, mechanical, and adhesive properties and compare it with other commercial self-adhesive resin cements. Materials and Methods: Experimental self-adhesive resin cement (SARC) was formulated by our proprietary adhesive resin and filler technology. Maxcem Elite, RelyX Unicem 2, SpeedCem Plus, SmartCEM 2, and Calibra Universal 2 were selected for comparison. Working and setting times, film thickness, water sorption and solubility, flexural strength, and modulus were measured in accordance with ISO-4049. Consistency was tested according to modified ISO 4823. Shear bond strengths were conducted according to ISO 29022. The data were analyzed by one-way ANOVA and post hoc Tukey's tests (p ≤ 0.05). Results: All cements showed about 2-4 min working time and about 3-6 min setting time except that RelyX Unicem 2 has a longer working time (9'58") and setting time (10'18"). All cements meet ISO standards for film thickness (≤50 µm), water sorption (≤40 µg/mm3) except Maxcem Elite (46.19 µg/mm3), and water solubility (≤7.5 µg/mm3) except SmartCEM 2 (11.35 µg/mm3) and Calibra Universal (9.87 µg/mm3). Experimental SARC showed significantly higher flexural strength and modulus than other cements (p < 0.001). For self-curing, Experimental SARC has statistically higher bond strength than other cements (p < 0.001) except statistically the same as RelyX Unicem 2 (p > 0.05). For light-curing, Experimental SARC showed significantly higher bond strength than other cements (p < 0.001) except statistically the same as Maxcem Elite and RelyX Unicem 2 (p > 0.05). For dual-curing, the bond strength of Experimental SARC is significantly higher than that of other cements (p < 0.001). Conclusion: The newly developed self-adhesive resin cement exhibited favorable bonding capability and physical and mechanical properties compared to other commercial self-adhesive resin cements and is a good option for cementation of indirect restorations with potential long-term clinical success.

6.
Nutrients ; 15(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36615827

RESUMO

Bifidobacterium, a common probiotic, is widely used in the food industry. Hyperglycemia in pregnancy has become a common disease that impairs the health of the mother and can lead to adverse pregnancy outcomes, such as preeclampsia, macrosomia, fetal hyperinsulinemia, and perinatal death. Currently, Bifidobacterium has been shown to have the potential to mitigate glycolipid derangements. Therefore, the use of Bifidobacterium-based probiotics to interfere with hyperglycemia in pregnancy may be a promising therapeutic option. We aimed to determine the potential effects of Bifidobacterium animalis subsp. lactis J-12 (J-12) in high-fat diet (HFD)/streptozotocin (STZ)-induced rats with hyperglycemia in pregnancy (HIP) and respective fetuses. We observed that J-12 or insulin alone failed to significantly improve the fasting blood glucose (FBG) level and oral glucose tolerance; however, combining J-12 and insulin significantly reduced the FBG level during late pregnancy. Moreover, J-12 significantly decreased triglycerides and total cholesterol, relieved insulin and leptin resistance, activated adiponectin, and restored the morphology of the maternal pancreas and hepatic tissue of HIP-induced rats. Notably, J-12 ingestion ameliorated fetal physiological parameters and skeletal abnormalities. HIP-induced cardiac, renal, and hepatic damage in fetuses was significantly alleviated in the J-12-alone intake group, and it downregulated hippocampal mRNA expression of insulin receptor (InsR) and insulin-like growth factor-1 receptor (IGF-1R) and upregulated AKT mRNA on postnatal day 0, indicating that J-12 improved fetal neurological health. Furthermore, placental tissue damage in rats with HIP appeared to be in remission in the J-12 group. Upon exploring specific placental microbiota, we observed that J-12 affected the abundance of nine genera, positively correlating with FBG and leptin in rats and hippocampal mRNA levels of InsR and IGF-1R mRNA in the fetus, while negatively correlating with adiponectin in rats and hippocampal levels of AKT in the fetus. These results suggest that J-12 may affect the development of the fetal central nervous system by mediating placental microbiota via the regulation of maternal-related indicators. J-12 is a promising strategy for improving HIP and pregnancy outcomes.


Assuntos
Bifidobacterium animalis , Hiperglicemia , Insulinas , Ratos , Gravidez , Feminino , Animais , Resultado da Gravidez , Bifidobacterium animalis/metabolismo , Dieta Hiperlipídica/efeitos adversos , Leptina/metabolismo , Estreptozocina , Placenta/metabolismo , Adiponectina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hiperglicemia/metabolismo , Bifidobacterium/metabolismo , RNA Mensageiro/metabolismo , Insulinas/metabolismo
7.
J Insect Sci ; 22(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34958664

RESUMO

Plant essential oils, with high bioactivity and biodegradability, provide promising alternatives to synthetic pesticides for pest control. Trans-anethole is the major component of essential oil from star anise, Illicium verum Hook. The compound has a strong contact toxicity against the green peach aphid, Myzus persicae (Sulzer) (Hemiptera: Aphididae), which is a major insect pest of many vegetables and crops. However, little information is known about how M. persicae responds to trans-anethole at the molecular level. We conducted a comparative transcriptome analysis of M. persicae in response to a LD50 dose of trans-anethole. A total of 559 differentially expressed genes were detected in the treated individuals, with 318 genes up-regulated, and 241 genes down-regulated. Gene ontology (GO) analysis revealed that these genes were classified into different biological processes and pathways. We also found that genes encoding ATP-binding cassette (ABC) transporters, DnaJ, and cuticle proteins were dramatically up-regulated in response to trans-anethole. To study the function of these genes, we performed RNA interference (RNAi) analysis. Knockdown of an ABC transporter gene (ABCG4) and a DnaJ gene (DnaJC1) resulted in a significantly increased mortality rate in M. persicae following trans-anethole exposure, indicating the involvement of these two genes in the toxicity response to trans-anethole. The findings provide new insights into the mechanisms of M. persicae in coping with plant essential oils.


Assuntos
Derivados de Alilbenzenos , Anisóis , Afídeos , Proteínas de Insetos/genética , Óleos Voláteis , Derivados de Alilbenzenos/farmacologia , Animais , Anisóis/farmacologia , Afídeos/efeitos dos fármacos , Afídeos/genética , Expressão Gênica , Óleos Voláteis/farmacologia
8.
Angew Chem Int Ed Engl ; 60(34): 18742-18749, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34115447

RESUMO

Mitochondria are the subcellular bioenergetic organelles. The analysis of their morphology and topology is essential to provide useful information on their activity and metabolism. Herein, we report a label-free shadow electrochemiluminescence (ECL) microscopy based on the spatial confinement of the ECL-emitting reactive layer to image single living mitochondria deposited on the electrode surface. The ECL mechanism of the freely-diffusing [Ru(bpy)3 ]2+ dye with the sacrificial tri-n-propylamine coreactant restrains the light-emitting region to a micrometric thickness allowing to visualize individual mitochondria with a remarkable sharp negative optical contrast. The imaging approach named "shadow ECL" (SECL) reflects the negative imprint of the local diffusional hindrance of the ECL reagents by each mitochondrion. The statistical analysis of the colocalization of the shadow ECL spots with the functional mitochondria revealed by classical fluorescent biomarkers, MitoTracker Deep Red and the endogenous intramitochondrial NADH, validates the reported methodology. The versatility and extreme sensitivity of the approach are further demonstrated by visualizing single mitochondria, which remain hardly detectable with the usual biomarkers. Finally, by alleviating problems of photobleaching and phototoxicity associated with conventional microscopy methods, SECL microscopy should find promising applications in the imaging of subcellular structures.


Assuntos
Técnicas Eletroquímicas , Medições Luminescentes , Mitocôndrias/química , Biomarcadores/análise , Corantes Fluorescentes/química , Compostos Organometálicos/química , Propilaminas/química
9.
Dent Mater ; 37(7): 1150-1155, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33849756

RESUMO

OBJECTIVE: To determine the mechanical properties of a newly-developed CAD/CAM resin composite block and compare with other resin composite blocks and a polymer-infiltrated ceramic block. METHODS: Experimental composite block was formulated by our proprietary resin and filler technologies and cured via Hot Isostatic Pressing (HIP). Bar-shaped specimens (1 × 4×12 - 13 mm, n = 10) for flexural strength, flexural modulus and modulus of resilience were sectioned from block materials and measured in accordance to modified ISO-6872. Cylinder specimens for compressive strength (2 × 4 mm, n = 8) and for diametral tensile strength (6 × 3 mm, n = 8) were milled from the block materials and tested according to ASTM-D695 and ANSI/ADA-Specification #27, respectively. Block specimens (5 mm, n = 3) for Vickers hardness were polished and measured for five indentations on each specimen. The data was analyzed by one-way ANOVA and post-hoc Tukey tests (p ≤ 0.05). RESULTS: Experimental composite block showed higher or significantly higher flexural strength, flexural modulus, modulus of resilience, compressive strength, diametral tensile strength and Vickers hardness than the other commercially available block materials except Vita Enamic for flexural modulus and hardness and Cerasmart for modulus of resilience. Some positive correlations were observed among the different mechanical properties. SIGNIFICANCE: New composite block exhibited higher mechanical properties as compared to commercially available composite block materials. Superior mechanical properties for resin composite block materials were obtained by composite and curing processing technologies. Resin composite blocks with higher mechanical properties are good options for the fabrication of CAD/CAM indirect restorations.


Assuntos
Resinas Compostas , Desenho Assistido por Computador , Cerâmica , Resistência à Flexão , Dureza , Teste de Materiais , Estresse Mecânico , Propriedades de Superfície
10.
J Nanosci Nanotechnol ; 21(10): 5319-5328, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875125

RESUMO

Transition metal and nitrogen co-doped carbon-based catalysts (TM-N-C) have become the most promising catalysts for Pt/C due to their wide range of sources, low cost, high catalytic activity, excellent stability and strong resistance to poisoning, especially Fe-N-C metal-organic frameworks (MOFs), which are some of the most promising precursors for the preparation of Fe-N-C catalysts due to their inherent properties, such as their highly ordered three-dimensional framework structure, controlled porosity, and tuneable chemistry. Based on these, in this paper, different iron sources were added to synthesis a sort of zeolitic imidazole frameworks (ZIF-8). Then the imidazole salt in ZIF-8 was rearranged into high N-doped carbon by high-temperature pyrolysis to prepare the Fe-N-C catalyst. We studied the physical characteristics of the catalysts by different iron sources and their effects on the catalytic properties of the oxygen reduction reaction (ORR). From the point of morphology, various iron sources have a positive influence on maintaining the morphology of ZIF-8 polyhedron. Fe-N/C-Fe(NO3)3 has the same anion as zinc nitrate, and can maintain a polyhedral morphology after high-temperature calcination. It had the highest ORR catalytic activity compared to the other four catalyst materials, which proved that there is a certain relationship between morphology and performance. This paper will provide a useful reference and new models for the development of high-performance ORR catalysts without precious metals.

11.
Naunyn Schmiedebergs Arch Pharmacol ; 394(1): 205-216, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32500187

RESUMO

Tamoxifen is an estrogen modulator widely used in the treatment of patients with ESR/ER-positive breast cancer; however, resistance limits its clinical application. Autophagy alterations have recently been suggested as a new mechanism for tamoxifen resistance. Glucose transporter 1 (GLUT1) has been reported to be associated with the development and metastasis of breast cancer, but the relationship among GLUT1, autophagy, and endocrine resistance remains unclear. Our present study found that GLUT1 expression and autophagy flux were upregulated in the tamoxifen-resistant breast cancer cell line MCF-7/TAMR-1 and that knockdown of GLUT1 promoted sensitization to tamoxifen. Moreover, knockdown of GLUT1 significantly decreased the enhancement of autophagy flux in tamoxifen-resistant cell lines. Furthermore, inhibiting autophagy in tamoxifen-resistant cells resulted in sensitization to tamoxifen. We conclude that GLUT1 contributes to tamoxifen resistance in breast cancer and that tamoxifen-resistant cells become resensitized to tamoxifen after GLUT1 silencing. These findings suggest GLUT1 as a new factor clinically associated with resistance to tamoxifen.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Transportador de Glucose Tipo 1/metabolismo , Tamoxifeno/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Antagonistas de Estrogênios/uso terapêutico , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Transcriptoma/efeitos dos fármacos
12.
Int J Nanomedicine ; 15: 6749-6760, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982231

RESUMO

BACKGROUND: The combination of radiotherapy (RT) and chemotherapy, as a standard treatment for breast cancer in the clinic, is unsatisfactory due to chemoradioresistance and severe side effects. METHODS AND RESULTS: To address these issues, a cancer cell-erythrocyte hybrid membrane-coated doxorubicin (DOX)-loaded gold nanocage (CM-EM-GNCs@DOX) was constructed for near-infrared light (NIR)-activated photothermal/radio/chemotherapy of breast cancer. CM-EM-GNCs@DOX inherited an excellent homologous target ability from the cancer cell membrane and an immune evasion capability from the erythrocyte membrane, together resulting in highly efficient accumulation in the tumor site with decreased clearance. Following the highly efficient uptake of CM-EM-GNCs@DOX in cancer cells, the RT efficacy was remarkably amplified due to the radiosensitization effect of CM-EM-GNCs@DOX, which reduced the needed radiotherapeutic dose. Importantly, with NIR irradiation, CM-EM-GNCs@DOX exerted a high photothermal effect, which not only ruptured CM-EM-GNCs@DOX to release DOX for precise and controllable chemotherapy, but also potentiated chemo/radiotherapy by photothermal therapy. CONCLUSION: Therefore, a highly efficient and safe combined photothermal/radio/chemotherapy approach was achieved in vitro and in vivo by CM-EM-GNCs@DOX, which provided a promising strategy for treating breast cancer.


Assuntos
Neoplasias da Mama/terapia , Membrana Celular/química , Doxorrubicina/administração & dosagem , Nanoestruturas/química , Fototerapia/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Membrana Eritrocítica/química , Feminino , Ouro/química , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Células MCF-7 , Fusão de Membrana , Camundongos , Camundongos Nus , Nanoestruturas/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacologia , Células RAW 264.7 , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Nanosci Nanotechnol ; 19(12): 7777-7784, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196289

RESUMO

Activated carbon support Pd nanoparticles (NPs) modified by various WO3-shaped catalysts were prepared and applied as an efficient anode catalyst for direct formic acid fuel cells. Three forms of WO3 (nanosheets, nanoparticles, nanobars) modified activated carbon hybrids were first prepared via different syntheses, and then used as supports to synthesize three types of Pd-WO3/C catalysts by a NaBH4 reduction method. The morphology, structure, and electrochemical performances of the as-prepared Pd-WO3/C catalysts were characterized and analyzed. We can see that the noble metal particles loaded with activated carbon modified by WO3 exhibit small particle size and uniform dispersion from the transmission electron microscope image. The synthesized composite catalysts was used for the formic acid electrooxidation and showed excellent catalytic performance. The oxidation peak current density of the Pd/WO3-Nanosheets/C (40.04 mA·cm-2 was the highest, approximately 1.2 times that of Pd/C (33.00 mA·cm-2. Additionally, the long-term stability (i-t) test results show that the Pd/WO3-Nanosheets/C catalyst exhibits superior stability during formic acid electrooxidation. The reason for the increase in performance can be attributed to the following: the large specific surface area of WO3 decreases the adsorption strength of intermediates such as COad on Pd and prevents the accumulation of poisonous intermediates, thereby promoting the oxidation reaction of formic acid in the direct pathway; the catalyst-support interaction between precious metal Pd and WO3, substantially improving the catalytic performance of Pd-WO3/C catalysts.

14.
J Am Med Inform Assoc ; 25(1): 54-60, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29126253

RESUMO

Objective: Electronic health record (EHR)-based phenotyping infers whether a patient has a disease based on the information in his or her EHR. A human-annotated training set with gold-standard disease status labels is usually required to build an algorithm for phenotyping based on a set of predictive features. The time intensiveness of annotation and feature curation severely limits the ability to achieve high-throughput phenotyping. While previous studies have successfully automated feature curation, annotation remains a major bottleneck. In this paper, we present PheNorm, a phenotyping algorithm that does not require expert-labeled samples for training. Methods: The most predictive features, such as the number of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes or mentions of the target phenotype, are normalized to resemble a normal mixture distribution with high area under the receiver operating curve (AUC) for prediction. The transformed features are then denoised and combined into a score for accurate disease classification. Results: We validated the accuracy of PheNorm with 4 phenotypes: coronary artery disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. The AUCs of the PheNorm score reached 0.90, 0.94, 0.95, and 0.94 for the 4 phenotypes, respectively, which were comparable to the accuracy of supervised algorithms trained with sample sizes of 100-300, with no statistically significant difference. Conclusion: The accuracy of the PheNorm algorithms is on par with algorithms trained with annotated samples. PheNorm fully automates the generation of accurate phenotyping algorithms and demonstrates the capacity for EHR-driven annotations to scale to the next level - phenotypic big data.


Assuntos
Algoritmos , Big Data , Registros Eletrônicos de Saúde , Fenótipo , Área Sob a Curva , Conjuntos de Dados como Assunto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Classificação Internacional de Doenças , Peptídeos , Medicina de Precisão
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