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1.
Int J Ophthalmol ; 16(9): 1406-1416, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37724269

RESUMEN

With the rapid development of computer technology, the application of artificial intelligence (AI) to ophthalmology has gained prominence in modern medicine. As modern optometry is closely related to ophthalmology, AI research on optometry has also increased. This review summarizes current AI research and technologies used for diagnosis in optometry, related to myopia, strabismus, amblyopia, optical glasses, contact lenses, and other aspects. The aim is to identify mature AI models that are suitable for research on optometry and potential algorithms that may be used in future clinical practice.

2.
Neural Regen Res ; 18(10): 2307-2314, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37056152

RESUMEN

Slit-Robo GTPase-activating protein 2 (SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout (Srgap2+/-) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes (Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/- mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.

3.
Transl Oncol ; 27: 101597, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36502701

RESUMEN

PURPOSE: To establish and validate a nomogram model incorporating both liver imaging reporting and data system (LI-RADS) features and contrast enhanced magnetic resonance imaging (CEMRI)-based radiomics for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) falling the Milan criteria. METHODS: In total, 161 patients with 165 HCCs diagnosed with MVI (n = 99) or without MVI (n = 66) were assigned to a training and a test group. MRI LI-RADS characteristics and radiomics features selected by the LASSO algorithm were used to establish the MRI and Rad-score models, respectively, and the independent features were integrated to develop the nomogram model. The predictive ability of the nomogram was evaluated with receiver operating characteristic (ROC) curves. RESULTS: The risk factors associated with MVI (P<0.05) were related to larger tumor size, nonsmooth margin, mosaic architecture, corona enhancement and higher Rad-score. The areas under the ROC curve (AUCs) of the MRI feature model for predicting MVI were 0.85 (95% CI: 0.78-0.92) and 0.85 (95% CI: 0.74-0.95), and those for the Rad-score were 0.82 (95% CI: 0.73-0.90) and 0.80 (95% CI: 0.67-0.93) in the training and test groups, respectively. The nomogram presented improved AUC values of 0.87 (95% CI: 0.81-0.94) in the training group and 0.89 (95% CI: 0.81-0.98) in the test group (P<0.05) for predicting MVI. The calibration curve and decision curve analysis demonstrated that the nomogram model had high goodness-of-fit and clinical benefits. CONCLUSIONS: The nomogram model can effectively predict MVI in patients with HCC falling within the Milan criteria and serves as a valuable imaging biomarker for facilitating individualized decision-making.

4.
J Pharm Sci ; 112(1): 350-353, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36279955

RESUMEN

A thymol:4,4'-dipyridyl (2:1) cocrystal (Form I) is reported to suppress thymol sublimation. The cocrystal was prepared via solution-mediated phase transformation and its structure is sustained by O-H (phenol) ··· N (pyridyl) hydrogen bonds between two individual components. A cocrystal polymorph (Form II) was formed via solid state transformation or via vapor phase upon heating. Using gravimetry analysis, it was demonstrated that cocrystal Form I decreased the sublimation rate of thymol by 38-fold. This study demonstrates that cocrystallization is an effective approach to reduce vapor pressure and sublimation of solids, thus achieving odor-masking.


Asunto(s)
Timol , Cristalización , Enlace de Hidrógeno
5.
Inorg Chem ; 61(44): 17738-17745, 2022 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-36284508

RESUMEN

Metal-halide perovskites have been extensively investigated due to their fascinating structural diversity and outstanding optoelectronic properties. We report the photoluminescence and photoelectric response behavior of a nontypical Dion-Jacobson perovskite [(4AMTP)PbBr2]2PbBr4 (4AMTP = 4-aminomethyltetrahydropyran cation), featuring neutral PbBr2 layers incorporated into the cationic layers between the anionic [PbBr4]2- layers. A 4AMTP-coordinated PbBr2 unit constitutes the unique nontypical dication layer. The seven-coordinated PbBr6O unit forms a largely distorted decahedron with a short distance from the inorganic [PbBr4]2- layer. The photoluminescence behavior of [(4AMTP)PbBr2]2PbBr4 shows crystal size dependence. Larger crystals show purplish-blue emission with two peaks at 414 and 431 nm, whereas smaller grain size (<50 µm) crystals demonstrate a single emission peak at 425 nm. Meanwhile, it shows a blue-light photoelectric response under the illumination of 405 nm with an on/off ratio of 175 for single-crystal devices and 97 for thin-film devices. The photoresponse performance is proportional to the molar extinction coefficient of the absorption band edge.

6.
J Am Chem Soc ; 144(40): 18595-18606, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36190167

RESUMEN

2D hybrid lead halide perovskites exhibit versatile photoluminescent behaviors for narrowband to broadband emissions (BBEs) and have become attractive candidates for potential applications such as solid-state lighting. Establishing the relationship between the perovskite structural distortion and BBE is key but challenging in designing and optimizing the perovskite luminophores. Conventional attention is given to analyzing the intra-octahedron distortion of the [PbX6]4- (X = halide) unit that has not yet provided a clear structure-luminescence relationship. Herein, we introduce a descriptor, Pb displacement, to describe the inter-octahedron distortion to clarify the structure-emission relationship. The displacement of adjacent Pb centers represents the lattice distortion, which determines the broadband/narrowband emission instead of the octahedron distortion itself. We find a kite-type quadrilateral rule in (001) type 2D perovskites, that is, the degree to which the four octahedral central ions deviate from a square relates to the BBE. The kite-type arrangement of the Pb ions usually corresponds to the BBEs due to the large structure distortions. In contrast, the square-type arrangement of the Pb ions corresponds to the narrowband emissions because of the small distortions. The distortion descriptor magnifies the distortion scale, making it larger than the conventional one for the intra-octahedron distortion, which matches the general concept of excitons based on the scale of the crystal lattice. Therefore, the set of structural descriptors is better to correlate the perovskite structures and emission properties.

7.
Chem Biodivers ; 19(10): e202200767, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36098055

RESUMEN

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.


Asunto(s)
Selaginellaceae , Humanos , Selaginellaceae/química , Estructura Molecular , Glicósidos/farmacología , Glicósidos/química , Azúcares , Etanol , Extractos Vegetales
8.
Mol Pharm ; 19(11): 4191-4198, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-36049021

RESUMEN

An in vitro drug release test was developed to establish a level A in vitro-in vivo correlation (IVIVC) for predicting the in vivo performance of potassium chloride extended-release (ER) matrix tablets. Three ER formulations of potassium chloride with different in vitro release rates were designed using the USP dissolution test, and their urinary pharmacokinetic profiles were evaluated in healthy subjects. Due to the lack of IVIVC with the USP method, experiments were designed to investigate the effects of in vitro test conditions on drug release in order to match in vitro drug release with in vivo behaviors of different formulations. The evaluated in vitro variables included the type of USP apparatus, surfactant, and ionic strength of the dissolution medium. Based on the study findings and data analysis, a discriminatory drug release method was successfully developed that enabled the establishment and validation of a level A IVIVC model of the potassium chloride ER tablet using urinary pharmacokinetic data. This method uses USP apparatus I at 50 rpm in 900 mL of 150 mM NaCl solution containing 40 mM sodium dodecyl sulfate at 37 °C. The current study highlights the value of investigating test conditions in developing a predictive in vitro test method for establishing IVIVC.


Asunto(s)
Liberación de Fármacos , Humanos , Solubilidad , Cloruro de Potasio , Comprimidos , Preparaciones de Acción Retardada/farmacocinética , Técnicas In Vitro
9.
J Phys Chem Lett ; 13(18): 4119-4124, 2022 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-35503750

RESUMEN

Cationic components in the organic-inorganic hybrid perovskites (OIHPs) play an important role in the arrangement and tilting of the inorganic part that is responsible for semiconducting, luminescent, and photoelectronic properties. Herein, we report two 2D OIHP compounds, (cis-4ACHO)2(H3OBr)PbBr4 (1) and (trans-4ACHO)2(H3OCl)PbBr4 (2) (4ACHO = 4-aminocyclohexanol), showing both photoluminescence (PL) and photodetection (PD) that are tuned by the cis- and trans configurational isomerism of 4ACHO. Crystals of 1 and 2 exhibit similar packing structures but with different crystallographic symmetries. Compound 2 displays a broadband white-light emission with a higher PL efficiency (6.6%) than 1 (2.1%) that emits narrowband blue light while the PD property of 1 is better than 2 with a higher on/off ratio under the same conditions. The PL and PD of the two compounds show a seesaw relationship, which provides a new perspective for understanding the PL and PD properties in OIHPs.

10.
Nat Prod Res ; 36(3): 772-779, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32762444

RESUMEN

Four new prenylflavonol glycosides (1-4) along with two known analogues (5-6) were isolated from the leaves of Cyclocarya paliurus for the first time. The structures of these compounds were characterized by comprehensive analysis of 1 D, 2 D NMR, HRESIMS, UV data and enzymatic hydrolysis. In bioassays, compounds 1-4 were evaluated for inhibitory effects on xanthine oxidase (XOD) and effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW264.7 cells. Moreover, compounds 1 and 2 showed outstanding XOD inhibitions with IC50 values of 18.16 ± 3.91 and 37.65 ± 5.67 µM, and exhibited inhibitions against LPS-induced NO production with IC50 values of 80.50 ± 3.09 and 82.28 ± 2.87 µM.


Asunto(s)
Juglandaceae , Triterpenos , Glicósidos/farmacología , Hojas de la Planta , Xantina Oxidasa
11.
Eur J Clin Pharmacol ; 78(3): 505-512, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34816285

RESUMEN

PURPOSES: The effects of preoperative statin treatment on acute kidney injury (AKI) remain controversial, and current clinical evidence regarding statin use in the elderly undergoing valve replacement surgery (VRS) is insufficient. The present study aimed to investigate the association between preoperative statin treatment and AKI after VRS in the elderly. METHODS: Three thousand seven hundred ninety-one elderly patients (≥ 60 years) undergoing VRS were included in this study and divided into 2 groups, according to the receipt of statin treatment before the operation: statin users (n = 894) and non-users (n = 2897). We determined the associations between statin use, AKI, and other adverse events using a multivariate model and propensity score-matched analysis. RESULTS: After propensity score-matched analysis, there was no difference between statin users and non-users in regard to postoperative AKI (72.5% vs. 72.4%, p = 0.954), in-hospital death (5.7% vs. 5.1%, p = 0.650) and 1-year mortality (log-rank = 0, p = 0.986). The multivariate analysis showed that statin use was not an independent risk factor for postoperative AKI (OR = 0.97, 95% CI: 0.90-1.17, p = 0.733), in-hospital mortality (OR = 1.12, 95% CI: 0.75-1.68, p = 0.568), or 1-year mortality (HR = 0.95, 95% CI: 0.70-1.28, p = 0.715). CONCLUSION: Preoperative statin treatment did not significantly affect the risk of AKI among elderly patients undergoing VRS.


Asunto(s)
Lesión Renal Aguda/epidemiología , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Complicaciones Posoperatorias/epidemiología , Anciano , Femenino , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Socioeconómicos
12.
AAPS J ; 23(4): 78, 2021 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-34076797

RESUMEN

Gene therapy has been experiencing a breakthrough in recent years, targeting various specific cell groups in numerous therapeutic areas. However, most recent clinical studies maintain the use of traditional viral vector systems, which are challenging to manufacture cost-effectively at a commercial scale. Non-viral vectors have been a fast-paced research topic in gene delivery, such as polymers, lipids, inorganic particles, and combinations of different types. Although non-viral vectors are low in their cytotoxicity, immunogenicity, and mutagenesis, attracting more and more researchers to explore the promising delivery system, they do not carry ideal characteristics and have faced critical challenges, including gene transfer efficiency, specificity, gene expression duration, and safety. This review covers the recent advancement in non-viral vectors research and formulation aspects, the challenges, and future perspectives.


Asunto(s)
Técnicas de Transferencia de Gen/tendencias , Terapia Genética/métodos , Vectores Genéticos , Terapia Genética/tendencias , Humanos
13.
Can Assoc Radiol J ; 72(2): 215-221, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32281391

RESUMEN

OBJECTIVES: To improve the infection control and prevention practices against coronavirus disease 2019 (COVID-19) in radiology department through loophole identification and providing rectifying measurements. METHODS: Retrospective analysis of 2 cases of health-care-associated COVID-19 transmission in 2 radiology departments and comparing the infection control and prevention practices against COVID-19 with the practices of our department, where no COVID-19 transmission has occurred. RESULTS: Several loopholes have been identified in the infection control and prevention practices against COVID-19 of the 2 radiology departments. Loopholes were in large part due to our limited understanding of the highly contagious coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is characterized by features not observed in other SARS viruses. We recommend to set up an isolation zone for handling patients who do not meet the diagnostic criteria of COVID-19 but are not completely cleared of the possibility of infection. CONCLUSIONS: Loopholes in the infection control and prevention practices against COVID-19 of the 2 radiology departments are due to poor understanding of the emerging disease which can be fixed by establishing an isolation zone for patients not completely cleared of SARS-CoV-2 infection.


Asunto(s)
COVID-19/prevención & control , Arquitectura y Construcción de Hospitales/métodos , Control de Infecciones/métodos , Mejoramiento de la Calidad , Servicio de Radiología en Hospital , SARS-CoV-2 , Humanos , Estudios Retrospectivos
14.
Nat Prod Res ; 35(21): 4018-4024, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32316785

RESUMEN

Three previously undescribed dammarane triterpenoid glycosides (1-3) along with five known analogues (4-8) were isolated from the leaves of Cyclocarya paliurus. Their structures and configurations were determined on the basis of comprehensive spectroscopic analyses, chemical hydrolysis and DFT GIAO 13C NMR calculation. All the isolates were evaluated cytotoxic activities against seven human cancer cell lines (MCF-7, PC-3, Du145, NCI-H1975, PC-9, SKVO3 and HepG2). Moreover, compound 4 showed a wide spectrum of cytotoxicity against human cancer cells with IC50 values ranging from 11.31 to 29.51 µM.


Asunto(s)
Juglandaceae , Triterpenos , Glicósidos/farmacología , Humanos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Hojas de la Planta , Triterpenos/farmacología
15.
Chin J Acad Radiol ; 3(4): 175-180, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33225216

RESUMEN

The COVID-19 epidemic has swept across China and spread to other countries. The rapid spreading of COVID-19 and panic combined with the lack of a hierarchical medical system in China have resulted in a huge number of hospital visiting which are overwhelming local medical system and increasing the incidence of cross infection. To meliorate this situation, we adopted the management concept of the system of Tiered Diagnosis and Treatment and developed an online tool for self-triage based on the mostly used multi-purpose smartphone app Wechat in China. This online tool helps people perform self-triage so that they can decide whether to quarantine at home or visit hospital. This tool further provides instructions for home quarantine and help patients make an appointment online if hospital visiting suggested. This smartphone application can reduce the burden on hospitals without losing the truly COVID-19 patients and protect people from the danger of cross infection.

16.
Bioorg Chem ; 101: 104018, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32629277

RESUMEN

Eight new prenylflavonol glycosides (1-8), along with five known analogues (9-13) were isolated from the n-butanol extract of the dried leaves of Cyclocarya paliurus (family Juglandaceae) for the first time. The structures of these compounds were characterized by comprehensive analysis of 1D, 2D NMR, HRESIMS, UV data and acid hydrolysis. In bioassay, all these thirteen prenylflavonol glycosides exhibited inhibitory effects on xanthine oxidase (XOD) activity. Especially compounds 2 and 7, showed outstanding IC50 values of 31.81 ± 2.20 and 29.71 ± 3.69 µM, respectively.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Flavonoles/farmacología , Glicósidos/farmacología , Juglandaceae/química , Hojas de la Planta/química , Xantina Oxidasa/antagonistas & inhibidores , Extractos Vegetales/química , Análisis Espectral/métodos , Relación Estructura-Actividad
17.
Magn Reson Imaging ; 70: 57-63, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32325235

RESUMEN

PURPOSE: To explore quantitative parameters obtained by dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) with Gd-EOB-DTPA in discriminating early-stage liver fibrosis (LF) in a rabbit model. MATERIALS AND METHODS: LF was established in 60 rabbits by the injection of 50% CCl4 oil solution, whereas 30 rabbits served as the control group. All rabbits underwent pathological examination to determine the LF stage using the METAVIR classification system. DCE MRI was performed, and quantitative parameters, including Ktrans, Kep, Ve, Vp and Re were measured and evaluated among the different LF stages using spearman correlation coefficients and receiver operating characteristic curve. RESULTS: In all, 24, 25, and 22 rabbits had stage F0, stage F1, and stage F2 LF, respectively. Ktrans (r = 0.803) increased, and Kep (r = -0.495) and Re (r = -0.701) decreased with LF stage progression (P < 0.001), while no significant correlation was found for Ve or Vp. Ktrans and Re were significantly different between all LF stage pairs compared (F0 vs. F1, F0 vs. F2, F1 vs. F2, F0 vs. F1-F2, P < 0.05). With the exception of F0 vs. F1, Kep differed significantly between stages (P < 0.05). The AUC of Ktrans was higher than that of other quantitative parameters, with an AUC of 0.92, 0.99, 0.94 and 0.92 for staging F0 vs. F1, F0 vs. F2, F1 vs. F2, and F0 vs. F1-F2, respectively. CONCLUSION: Among quantitative parameters of Gd-EOB-DTPA DCE MRI, Ktrans was the best predictor for quantitatively differentiating early-stage LF.


Asunto(s)
Tetracloruro de Carbono/toxicidad , Medios de Contraste , Gadolinio DTPA , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/diagnóstico por imagen , Imagen por Resonancia Magnética , Animales , Cirrosis Hepática/patología , Masculino , Curva ROC , Conejos
18.
Acad Radiol ; 27(5): 614-617, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32276755

RESUMEN

The COVID-19 epidemic, which is caused by the novel coronavirus SARS-CoV-2, has spread rapidly to become a world-wide pandemic. Chest radiography and chest CT are frequently used to support the diagnosis of COVID-19 infection. However, multiple cases of COVID-19 transmission in radiology department have been reported. Here we summarize the lessons we learned and provide suggestions to improve the infection control and prevention practices of healthcare workers in departments of radiology.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Transmisión de Enfermedad Infecciosa/prevención & control , Control de Infecciones/normas , Pandemias/prevención & control , Neumonía Viral/prevención & control , Servicio de Radiología en Hospital/normas , Radiología/normas , COVID-19 , Infecciones por Coronavirus/clasificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Desinfección/normas , Humanos , Control de Infecciones/métodos , Pandemias/clasificación , Aislamiento de Pacientes , Neumonía Viral/clasificación , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Salud Pública/educación , Radiología/educación
20.
Nutr Metab Cardiovasc Dis ; 30(3): 393-399, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-31791635

RESUMEN

BACKGROUND AND AIMS: The prognostic nutritional index (PNI) had been associated with adverse outcomes in numerous clinical conditions. However, its influence on idiopathic dilated cardiomyopathy (DCM) was not determined. This aim of this study was to determine the predictive ability of PNI in patients with idiopathic DCM. METHODS AND RESULTS: A total of 1021 consecutive patients with idiopathic DCM were retrospectively included and divided into three groups based on admission PNI tertiles: <41.7 (n = 339), 41.7-47.3 (n = 342), >47.3 (n = 340). The association of PNI with in-hospital major adverse clinical events (MACEs) and death during follow-up was evaluated. In-hospital mortality (2.9% vs. 1.5% vs. 0.0%, respectively; p = 0.006) and MACEs (13.6% vs. 6.7% vs. 3.5%, respectively; p < 0.001) decreased from the lowest to the highest PNI tertile. The optimal cut-off value of PNI to predict in-hospital MACEs was 44.0 (area under the curve: 0.689; 95% confidence interval [CI]: 0.626-0.753; p < 0.001). Multivariate analysis showed that a PNI≤44.0 was an independent risk factor of in-hospital MACEs (odd ratio: 2.86; 95% CI: 1.64-4.98; p < 0.001) and all-cause mortality at a median follow-up of 27 months (hazard ratio: 1.67; 95% CI: 1.11-2.49; p = 0.013). In addition, patients with a PNI≤44.0 had a lower cumulative survival rate during follow-up (log-rank: 35.62; p < 0.001). CONCLUSION: The PNI was an independent risk factor for in-hospital MACEs and all-cause mortality at a median follow-up of 27 months in patients with idiopathic DCM; hence, it may be considered a tool for risk assessment.


Asunto(s)
Cardiomiopatía Dilatada/fisiopatología , Dieta , Estado Nutricional , Valor Nutritivo , Adulto , Anciano , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/mortalidad , Cardiomiopatía Dilatada/terapia , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
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