RESUMEN
Currently, clinically available coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) is time-consuming and complex. We propose a novel artificial intelligence-based fully-automated, on-site CT-FFR technology, which combines the automated coronary plaque segmentation and luminal extraction model with reduced order 3 dimentional (3D) computational fluid dynamics. A total of 463 consecutive patients with 600 vessels from the updated China CT-FFR study in Cohort 1 undergoing both CCTA and invasive fractional flow reserve (FFR) within 90 d were collected for diagnostic performance evaluation. For Cohort 2, a total of 901 chronic coronary syndromes patients with index CT-FFR and clinical outcomes at 3-year follow-up were retrospectively analyzed. In Cohort 3, the association between index CT-FFR from triple-rule-out CTA and major adverse cardiac events in patients with acute chest pain from the emergency department was further evaluated. The diagnostic accuracy of this CT-FFR in Cohort 1 was 0.82 with an area under the curve of 0.82 on a per-patient level. Compared with the manually dependent CT-FFR techniques, the operation time of this technique was substantially shortened by 3 times and the number of clicks from about 60 to 1. This CT-FFR technique has a highly successful (> 99%) calculation rate and also provides superior prediction value for major adverse cardiac events than CCTA alone both in patients with chronic coronary syndromes and acute chest pain. Thus, the novel artificial intelligence-based fully automated, on-site CT-FFR technique can function as an objective and convenient tool for coronary stenosis functional evaluation in the real-world clinical setting.
Asunto(s)
Inteligencia Artificial , Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Anciano , Pronóstico , Reserva del Flujo Fraccional Miocárdico/fisiología , Angiografía por Tomografía Computarizada/métodos , Estudios Retrospectivos , Angiografía Coronaria/métodosRESUMEN
Introduction: Introduction: symptom clusters (SCs) are highly prevalent among patients diagnosed with primary liver cancer. Malnutrition poses a heightened risk for a more pronounced total symptom cluster score. Objective: this study aimed to identify SCs and assess the nutritional status of patients undergoing transcatheter arterial chemoembolization (TACE). Furthermore, it aimed to investigate the association between nutritional status and symptom clusters. Methods: primary liver cancer patients who were scheduled to receive TACE were recruited. Symptoms data were collected using the MD Anderson Symptom Inventory (MDASI-C) and the Symptom Module specific to Primary Cancer (TSM-PLC). Nutritional assessment relied on the Nutritional Risk Screening-2002 (NRS-2002) and blood biochemistry. The SCs were extracted using exploratory factor analysis, while the relationship between SCs and nutritional status was evaluated using Spearman correlation analysis. Results: the study included 226 patients, four distinct symptom clusters emerged: emotional-psychological symptom cluster, upper gastrointestinal symptom cluster, post-embolization-related symptom cluster, and liver function impairment symptom cluster. 68.14 % of patients were found to be at high risk of malnutrition. Our study revealed significant differences in Scs scores between patients at risk of malnutrition and those without such risk (p < 0.050). Notably, we observed a positive correlation between NRS-2002 scores and the scores of all symptom clusters (r = 0.205 to 0.419, p < 0.001), while a negative correlation was observed between prealbumin levels and the scores of all symptom clusters (r = -0.183 to -0.454, p < 0.001). Conclusion: the study highlights the high risk of malnutrition among liver cancer patients receiving TACE and the positive correlation between high malnutrition risk and Scs scores.
Introducción: Introducción: los grupos de síntomas (SC, por sus siglas en inglés) son altamente prevalentes entre los pacientes diagnosticados de cáncer primario de hígado. La desnutrición aumenta el riesgo de que la puntuación total de los grupos de síntomas sea más pronunciada. Objetivo: este estudio estaba dirigido a identificar los SC y a evaluar el estado nutricional de los pacientes sometidos a quimioembolización arterial transcatéter (TACE, por sus siglas en inglés). Adicionalmente, estaba dirigido a investigar la asociación entre el estado nutricional y los grupos de síntomas. Métodos: se reclutaron pacientes con cáncer primario de hígado que tenían programado recibir TACE. Los datos de los síntomas se recolectaron mediante el Inventario de síntomas del MD Anderson (MDASI-C) y el Módulo de síntomas específicos del cáncer primario (TSM-PLC). La evaluación nutricional se basó en el cribado de riesgo nutricional 2002 (NRS-2002) y la bioquímica sanguínea. Los SC se extrajeron mediante un análisis factorial exploratorio, mientras que la relación entre los SC y el estado nutricional se evaluó mediante un análisis de correlación de Spearman. Resultados: el estudio incluyó 226 pacientes, de los cuales surgieron cuatro grupos de síntomas distintos: grupo de síntomas emocionales-psicológicos, grupo de síntomas gastrointestinales superiores, grupo de síntomas relacionados con la postembolización y grupo de síntomas de deterioro de la función hepática. El 68,14 % de los pacientes presentaban un alto riesgo de desnutrición. Nuestro estudio reveló diferencias significativas en las puntuaciones de los SC entre los pacientes con riesgo de desnutrición y aquellos sin dicho riesgo (p < 0,050). En particular, observamos una correlación positiva entre las puntuaciones del NRS-2002 y las puntuaciones de todos los grupos de síntomas (r = 0,205 a 0,419, p < 0,001), mientras que se observó una correlación negativa entre los niveles de prealbúmina y las puntuaciones de todos los grupos de síntomas (r = -0,183 a -0,454, p < 0,001). Conclusión: el estudio destaca el alto riesgo de desnutrición entre los pacientes con cáncer de hígado que reciben TACE y la correlación positiva entre el alto riesgo de desnutrición y las puntuaciones de los SC.
Asunto(s)
Quimioembolización Terapéutica , Neoplasias Hepáticas , Desnutrición , Estado Nutricional , Humanos , Masculino , Femenino , Quimioembolización Terapéutica/efectos adversos , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/complicaciones , Desnutrición/etiología , Desnutrición/terapia , Anciano , Adulto , Evaluación Nutricional , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: To evaluate the value of T1 mapping in predicting hepatic dysfunction and prognosis in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). MATERIAL AND METHODS: 100 consecutive patients with treatment-naive HCC treated with TACE were prospectively analyzed. Clinical, laboratory, and MRI parameters (liver and tumor T1 relaxation times (T1L, T1T)) before and/or following TACE were measured and calculated. Clinical parameters included the Child-Turcotte-Pugh (CTP) classification, Barcelona Clinic Liver Cancer Classification (BCLC) criteria, and albumin-bilirubin (ALBI) score. Laboratory parameters were the gold standard for hepatic dysfunction. T1L and T1T were combined by stepwise multivariate logistic regression to yield a T1-related probability index (T1com) for further analysis. Study endpoints included hepatic dysfunction and progression-free survival (PFS) rate. RESULTS: 38 patients (38%) were diagnosed with hepatic dysfunction following TACE. There was no significant difference in clinical parameters between the groups with and without hepatic dysfunction. Logistic regression analysis showed that T1L and T1T were independent risk factors for assessing hepatic dysfunction. T1com showed a better AUC than T1L and T1T (0.81 vs. 0.76 and 0.69, P = 0.007 and 0.006). Patients with low T1com (≤0.42) showed a better median PFS than patients with high T1com (>0.42) (167.0 vs. 215.9 days, P = 0.010). In comparison, CTP, BCLC, and ALBI scores were not statistically significant in predicting PFS in HCC patients treated with TACE (P > 0.05). CONCLUSION: Compared with widely used clinical parameters, T1 was more capable of predicting hepatic dysfunction after TACE. Stratification of patients with HCC undergoing TACE according to T1 may help clinicians to develop treatment strategies in preventing the occurrence of hepatic dysfunction and improving individual prognoses.
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Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Pronóstico , Bilirrubina , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the value of coronary computed tomographic angiography (CCTA)-based fractional flow reserve (CT-FFR) and plaque quantitative analysis in predicting adverse outcomes in patients with non-obstructive coronary heart disease (CAD). METHODS: Clinical data of patients with non-obstructive CAD who underwent CCTA at the Affiliated Hospital of Jiangnan University from March 2014 to March 2018 were retrospectively analyzed and followed up, and the occurrence of major adverse cardiovascular event (MACE) was recorded. The patients were divided into MACE and non-MACE groups according to the occurrence of MACE. The clinical data, CCTA plaque characteristics including plaque length, stenosis degree, minimum lumen area, total plaque volume, non-calcified plaque volume, calcified plaque volume, plaque burden (PB) and remodelling index (RI), and CT-FFR were compared between the two groups. Multivaritate Cox proportional risk model was used to evaluate the relationship between clinical factors, CCTA parameters and MACE. The receiver operator characteristic curve (ROC curve) was used to assess the predictive power of outcome prediction model based on different CCTA parameters. RESULTS: Finally 217 patients were included, of which 43 (19.8%) had MACE and 174 (80.2%) did not. The median follow-up interval was 24 (16, 30) months. The CCTA showed that patients in the MACE group had more severe stenosis than that in the non-MACE group [(44.3±3.8)% vs. (39.5±2.5)%], larger total plaque volume and non-calcified plaque volume [total plaque volume (mm3): 275.1 (197.1, 376.9), non-calcified plaque volume (mm3): 161.5 (114.5, 307.8) vs. 117.9 (77.7, 185.5)], PB and RI were larger [PB: 50.2% (42.1%, 54.8%) vs. 45.1% (38.2%, 51.7%), RI: 1.19 (0.93, 1.29) vs. 1.03 (0.90, 1.22)], CT-FFR value was lower [0.85 (0.80, 0.88) vs. 0.92 (0.87, 0.97)], and the differences were statistically significant (all P < 0.05). Cox regression analysis showed that non-calcified plaques volume [hazard ratio (HR) = 1.005. 95% confidence interval (95%CI) was 1.025-4.866], PB ≥ 50% (HR = 3.146, 95%CI was 1.443-6.906), RI ≥ 1.10 (HR = 2.223, 95%CI was 1.002-1.009) and CT-FFR ≤ 0.87 (HR = 2.615, 95%CI was 1.016-6.732) were independent predictors of MACE (all P < 0.05). The model based on CCTA stenosis degree+CT-FFR+quantitative plaque characteristics (including non-calcified plaque volume, RI, PB) [area under the ROC curve (AUC) = 0.91, 95%CI was 0.87-0.95] had significantly better predictive efficacy for adverse outcomes than the model based on CCTA stenosis degree (AUC = 0.63, 95%CI was 0.54-0.71) and the model based on CCTA stenosis degree+CT-FFR (AUC = 0.71, 95%CI was 0.63-0.79; both P < 0.01). CONCLUSIONS: CT-FFR and plaque quantitative analysis based on CCTA are helpful in predicting adverse outcomes in patients with non-obstructive CAD. Non-calcified plaque volume, RI, PB and CT-FFR are important predictors of MACE. Compared with the prediction model based on stenosis degree and CT-FFR, the combined plaque quantitative index can significantly improve the prediction efficiency of adverse outcomes in patients with non-obstructive CAD.
Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Placa Aterosclerótica , Humanos , Angiografía Coronaria/métodos , Constricción Patológica , Estudios Retrospectivos , Curva ROC , Valor Predictivo de las Pruebas , Placa Aterosclerótica/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Enfermedad de la Arteria Coronaria/diagnóstico por imagenRESUMEN
Background A noninvasive coronary CT angiography (CCTA)-based radiomics technique may facilitate the identification of vulnerable plaques and patients at risk for future adverse events. Purpose To assess whether a CCTA-based radiomic signature (RS) of vulnerable plaques defined with intravascular US was associated with increased risk for future major adverse cardiac events (MACE). Materials and Methods In a retrospective study, an RS of vulnerable plaques was developed and validated using intravascular US as the reference standard. The RS development data set included patients first undergoing CCTA and then intravascular US within 3 months between June 2013 and December 2020 at one tertiary hospital. The development set was randomly assigned to training and validation sets at a 7:3 ratio. Diagnostic performance was assessed internally and externally from three tertiary hospitals using the area under the curve (AUC). The prognostic value of the RS for predicting MACE was evaluated in a prospective cohort with suspected coronary artery disease between April 2018 and March 2019. Multivariable Cox regression analysis was used to evaluate the RS and conventional anatomic plaque features (eg, segment involvement score) for predicting MACE. Results The RS development data set included 419 lesions from 225 patients (mean age, 64 years ± 10 [SD]; 68 men), while the prognostic cohort included 1020 lesions from 708 patients (mean age, 62 years ± 11; 498 men). Sixteen radiomic features, including two shape features and 14 textural features, were selected to build the RS. The RS yielded a moderate to good AUC in the training, validation, internal, and external test sets (AUC = 0.81, 0.75, 0.80, and 0.77, respectively). A high RS (≥1.07) was independently associated with MACE over a median 3-year follow-up (hazard ratio, 2.01; P = .005). Conclusion A coronary CT angiography-derived radiomic signature of coronary plaque enabled the detection of vulnerable plaques that were associated with increased risk for future adverse cardiac outcomes. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by De Cecco and van Assen in this issue.
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Enfermedad de la Arteria Coronaria , Placa Aterosclerótica , Masculino , Humanos , Persona de Mediana Edad , Angiografía por Tomografía Computarizada/métodos , Estudios Retrospectivos , Estudios Prospectivos , Enfermedad de la Arteria Coronaria/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/complicaciones , Angiografía Coronaria/métodos , Pronóstico , Valor Predictivo de las PruebasRESUMEN
OBJECTIVES: This study aimed to evaluate the synthetic MRI (syMRI), its combination with diffusion-weighted imaging (DWI), and morphological features for discriminating benign from metastatic retropharyngeal lymph nodes (RLNs). METHODS: Fifty-eight patients with a total of 63 RLNs (21 benign and 42 metastatic) were enrolled. The mean and standard deviation of syMRI-derived relaxometry parameters (T1, T2, PD; T1SD, T2SD, PDSD) were obtained from two different regions of interest (namely, partial-lesion and full-lesion ROI). The parameters derived from benign and metastatic RLNs were compared using Student's t or chi-square tests. Logistic regression analysis was used to construct a multi-parameter model of syMRI, syMRI + DWI, and syMRI + DWI + morphological features. Areas under the curve (AUC) were compared using the DeLong test to determine the best diagnostic approach. RESULTS: Benign RLNs had significantly higher T1, T2, PD, and T1SD values compared with metastatic RLNs in both partial-lesion and full-lesion ROI (all p < 0.05). The T1SD obtained from full-lesion ROI showed the best diagnostic performance among all syMRI-derived single parameters. The AUC of combined syMRI multiple parameters (T1, T2, PD, T1SD) were higher than those of any single parameter from syMRI. The combination of synthetic MRI and DWI can improve the AUC regardless of ROI delineation. Furthermore, the combination of synthetic MRI, DWI-derived quantitative parameters, and morphological features can significantly improve the overall diagnostic performance. CONCLUSIONS: The value of syMRI has been validated in differential diagnosis of benign and metastatic RLNs, and syMRI + DWI + morphological features can further improve the diagnostic efficiency for discriminating these two entities. KEY POINTS: ⢠Synthetic MRI was useful in differential diagnosis of benign and metastatic RLNs. ⢠The combination of syMRI, DWI, and morphological features can significantly improve the diagnostic efficiency.
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Imagen de Difusión por Resonancia Magnética , Ganglios Linfáticos , Humanos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Imagen de Difusión por Resonancia Magnética/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Imagen por Resonancia Magnética/métodos , Cuello , Diagnóstico Diferencial , Sensibilidad y EspecificidadRESUMEN
PURPOSE: To explore the value of morphology and diffusion features on CT and MRI in the characterization of external auditory canal and middle ear tumors (EAMETs). METHODS: Forty-seven patients with histologically proved EAMETs (23 benign and 24 malignant) who underwent CT and MRI were retrospectively analyzed in this study. CT and MRI characteristics (including size, shape, signal intensity, border, enhancement degree, and bone changes) and apparent diffusion coefficient (ADC) value were analyzed and compared between benign and malignant EAMETs. Logistic regression, receiver operating characteristic (ROC) curve, and Delong test were performed to assess the diagnostic performance. RESULTS: Compared with benign tumors, the malignant EAMETs are characterized by irregular shape, ill-defined border, invasive bone destruction, and intense enhancement (all p < 0.05). There were no significant differences on the size and signal intensity between benign and malignant tumors. The ADC value of malignant tumors were (879.96 ± 201.15) × 10-6 mm2/s, which was significantly lower than benign ones (p < 0.05). Logistic regression demonstrates the presence of ill-defined margin, invasive bone destruction, and low ADC value (≤ 920.33 × 10-6 mm2/s) have significant relationship with malignant EAMETs. The combination of characterization by morphology and diffusion features on CT and MRI can further improve the diagnostic efficiency when compared with morphology and diffusion features alone (both p < 0.05). CONCLUSION: Some CT and MRI characteristics are helpful in identifying malignant EAMETs from benign ones (especially ill-defined margin, invasive bone destruction, and low ADC value), and the combination of morphology and diffusion features on CT and MRI has best diagnostic efficiency for discriminating these two entities.
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Conducto Auditivo Externo , Neoplasias del Oído , Humanos , Estudios Retrospectivos , Conducto Auditivo Externo/diagnóstico por imagen , Sensibilidad y Especificidad , Imagen por Resonancia Magnética , Imagen de Difusión por Resonancia Magnética , Curva ROC , Neoplasias del Oído/diagnóstico por imagen , Diagnóstico Diferencial , Tomografía Computarizada por Rayos X , Oído Medio/diagnóstico por imagenRESUMEN
Large scale DNA oligo pools are emerging as a novel material in a variety of advanced applications. However, GC content and length cause significant bias in amplification of oligos. We systematically explored the amplification of one oligo pool comprising of over ten thousand distinct strands with moderate GC content in the range of 35-65%. Uniqual amplification of oligos result to the increased Gini index of the oligo distribution while a few oligos greatly increased their proportion after 60 cycles of PCR. However, the significantly enriched oligos all have relatively high GC content. Further thermodynamic analysis demonstrated that a high value of both GC content and Gibbs free energy could improve the replication of specific oligos during biased amplification. Therefore, this double-G (GC content and Gibbs free energy) driven replication advantage can be used as a guiding principle for the sequence design for a variety of applications, particularly for data storage.
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ADN , Composición de Base , ADN/genética , Reacción en Cadena de la Polimerasa , TermodinámicaRESUMEN
RNA-guided CRISPR (RNA-targeting clustered regularly interspaced short palindromic repeats) effector Cas13d is the smallest Class II subtype VI proteins identified so far. Here, two recently identified Cas13d effectors from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) were characterized and applied for sensitive nucleic acid detection. We demonstrated that the special target triggered collateral cleavage of these two Cas13d orthologs could provide rapid target RNA detection in picomolar range and then the tolerance for mismatch between crRNA and target RNA was characterized as well. Finally, an additional single mismatch was introduced into crRNA to enhance the two Cas13d orthologs mediated detection of low variant allele fraction, 0.1% T790M. Overall, this study demonstrated that both EsCas13d and RspCas13d could robustly detect target RNA carrying special single-nucleotide variation with high specificity and sensitivity, thereby providing newly qualified machinery in toolbox for efficient molecular diagnostics.
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Proteínas Asociadas a CRISPR/química , Sistemas CRISPR-Cas , Eubacterium/química , Polimorfismo de Nucleótido Simple , ARN/química , ARN/genética , Ruminococcus/químicaRESUMEN
Fragmented DNA from blood plasma, i.e., cell-free DNA, has received great interest as a noninvasive diagnostic biomarker for "point-of-care" testing or liquid biopsy. Here, we present a new approach for accurate genotyping of highly fragmented DNA. Based on toehold-mediated strand displacement, a toehold-assisted padlock probe and toehold blocker were designed and demonstrated with new controllability in significantly suppressing undesired cross-reaction, promoting target recycling and point mutation detection by tuning the thermodynamic properties. Furthermore, toehold-assisted padlock probe systems were elaborately designed for 14 different single-nucleotide variants (SNVs) and were demonstrated to be able to detect low concentration of variant alleles (0.1%). In addition, a target, spanning a narrow sequence window of 29 nucleotides on average is sufficient for the toehold-assisted padlock probe system, which is valuable for the analysis of highly fragmented DNA molecules from clinical samples. We further demonstrated that the toehold-assisted padlock probe, in combination with a unique asymmetric PCR technique, could detect more target SNVs at low allele fractions (1%) in highly fragmented cfDNA. This allows accurate genotyping and provides a new commercial approach for high-resolution analysis of genetic variation.
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Técnicas Biosensibles , ADN/genética , Genotipo , Límite de Detección , NucleótidosRESUMEN
BACKGROUND: Paravalvular regurgitation (PVR) following transcatheter aortic valve replacement (TAVR) is associated with increased morbidity and mortality. PVR continues to plague TAVR jeopardizing long-term results. New device iterations, such as the self-expandable Evolut PRO valve, aim to decrease PVR while maintaining optimal hemodynamics. This study sought to evaluate clinical and hemodynamic performance of the Evolut PRO system at 3 years. METHODS: The Evolut PRO US Clinical Study included 60 patients at high or extreme surgical risk undergoing TAVR with the Evolut PRO valve at 8 centers in the United States. Clinical outcomes were evaluated using Valve Academic Research Consortium (VARC)-2 criteria and included all-cause mortality, cardiovascular mortality, disabling stroke and valve complications. An independent core laboratory centrally assessed all echocardiographic measures. RESULTS: At 3 years, all-cause mortality was 25.8% (cardiovascular mortality 16.5%) and the disabling stroke rate was 10.7%. There were no cases of repeat valve intervention, endocarditis or coronary obstruction. Valve thrombosis was identified in 1 patient 2 years post-procedure and was treated medically. Hemodynamics at 3 years included a mean gradient of 7.2 ± 4.5 mm Hg, an effective orifice area of 2.0 ± 0.5 cm2, and 88.2% of patients had no or trace PVR. The remaining patients had mild PVR. Most of the surviving patients (80.6%) had New York Heart Association class I symptoms at 3 years. CONCLUSION: Outcomes at 3-years following TAVR with a contemporary self-expanding prosthesis are favorable, with no signal of valve deterioration, excellent hemodynamics including very low prevalence of PVR.
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Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/cirugía , Hemodinámica , Humanos , Diseño de Prótesis , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
In DNA data storage, the massive sequence complexity creates challenges in repeatable and efficient information readout. Here, our study clearly demonstrated that PCR created significant DNA amplification biases due to its inherent mechanism of inefficient priming, product-as-template, and error-spreading prone, which greatly hinder subsequent applications such as data retrieval in DNA-based storage. To mitigate the amplification bias, we recruited an isothermal DNA amplification by combining strand displacement amplification (SDA) with magnetic beads (MB) DNA immobilization for robust, repeated, and low-bias amplification of DNA oligo pool, comprising over 100 thousand oligos, in a primer-free and low-error-spreading fashion. Furthermore, we introduced oligo pool normalization (OPN), a cost-effective and scalable method for normalizing an oligo pool, by which oligo pools comprising from 256 to 1024 distinct oligos were simply modified with improved Gini-index. Therefore, we believe that the combination of SDA and OPN can provide an ideal amplification mechanism for a low-bias copy of a large oligo pool, which is of vital importance for successful data retrieval in DNA information storage.
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Oligonucleótidos/metabolismo , Secuencia de Bases , Cartilla de ADN/metabolismo , Biblioteca de Genes , Ácidos Nucleicos Inmovilizados/química , Ácidos Nucleicos Inmovilizados/metabolismo , Magnetismo , Técnicas de Amplificación de Ácido Nucleico , Oligonucleótidos/genéticaRESUMEN
DNA emerged as a novel potential material for mass data storage, offering the possibility to cheaply solve a great data storage problem. Large oligonucleotide pools demonstrated high potential of large-scale data storage in test tube, meanwhile, living cell with high fidelity in information replication. Here we show a mixed culture of bacterial cells carrying a large oligo pool that was assembled in a high-copy-number plasmid was presented as a stable material for large-scale data storage. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias, the large oligonucleotide pools in the mixed culture were constant over multiple successive passages. Finally, over ten thousand distinct oligos encompassing 2304 Kbps encoding 445 KB digital data, were stored in cells, the largest storage in living cells reported so far and present a previously unreported approach for bridging the gap between in vitro and in vivo systems.
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Bacterias/genética , Computadores Moleculares/tendencias , ADN Bacteriano/genética , Almacenamiento y Recuperación de la Información/tendencias , Bacterias/crecimiento & desarrollo , Humanos , Plásmidos/genética , Análisis de Secuencia de ADNRESUMEN
As a key element of genome editing, donor DNA introduces the desired exogenous sequence while working with other crucial machinery such as CRISPR-Cas or recombinases. However, current methods for the delivery of donor DNA into cells are both inefficient and complicated. Here, we developed a new methodology that utilizes rolling circle replication and Cas9 mediated (RC-Cas-mediated) in vivo single strand DNA (ssDNA) synthesis. A single-gene rolling circle DNA replication system from Gram-negative bacteria was engineered to produce circular ssDNA from a Gram-positive parent plasmid at a designed sequence in Escherichia coli. Furthermore, it was demonstrated that the desired linear ssDNA fragment could be cut out using CRISPR-associated protein 9 (CRISPR-Cas9) nuclease and combined with lambda Red recombinase as donor for precise genome engineering. Various donor ssDNA fragments from hundreds to thousands of nucleotides in length were synthesized in E. coli cells, allowing successive genome editing in growing cells. We hope that this RC-Cas-mediated in vivo ssDNA on-site synthesis system will be widely adopted as a useful new tool for dynamic genome editing.
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Replicación del ADN/genética , ADN de Cadena Simple/biosíntesis , ADN de Cadena Simple/genética , Escherichia coli/genética , Edición Génica/métodos , Proteína 9 Asociada a CRISPR/metabolismo , Sistemas CRISPR-Cas , ADN Circular/biosíntesis , ADN Circular/genética , Nucleótidos/metabolismo , Plásmidos/genética , ARN Guía de Kinetoplastida/metabolismoRESUMEN
BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis who are at increased risk for death from surgery; less is known about TAVR in low-risk patients. METHODS: We performed a randomized noninferiority trial in which TAVR with a self-expanding supraannular bioprosthesis was compared with surgical aortic-valve replacement in patients who had severe aortic stenosis and were at low surgical risk. When 850 patients had reached 12-month follow-up, we analyzed data regarding the primary end point, a composite of death or disabling stroke at 24 months, using Bayesian methods. RESULTS: Of the 1468 patients who underwent randomization, an attempted TAVR or surgical procedure was performed in 1403. The patients' mean age was 74 years. The 24-month estimated incidence of the primary end point was 5.3% in the TAVR group and 6.7% in the surgery group (difference, -1.4 percentage points; 95% Bayesian credible interval for difference, -4.9 to 2.1; posterior probability of noninferiority >0.999). At 30 days, patients who had undergone TAVR, as compared with surgery, had a lower incidence of disabling stroke (0.5% vs. 1.7%), bleeding complications (2.4% vs. 7.5%), acute kidney injury (0.9% vs. 2.8%), and atrial fibrillation (7.7% vs. 35.4%) and a higher incidence of moderate or severe aortic regurgitation (3.5% vs. 0.5%) and pacemaker implantation (17.4% vs. 6.1%). At 12 months, patients in the TAVR group had lower aortic-valve gradients than those in the surgery group (8.6 mm Hg vs. 11.2 mm Hg) and larger effective orifice areas (2.3 cm2 vs. 2.0 cm2). CONCLUSIONS: In patients with severe aortic stenosis who were at low surgical risk, TAVR with a self-expanding supraannular bioprosthesis was noninferior to surgery with respect to the composite end point of death or disabling stroke at 24 months. (Funded by Medtronic; ClinicalTrials.gov number, NCT02701283.).
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas/métodos , Prótesis Valvulares Cardíacas , Diseño de Prótesis , Accidente Cerebrovascular/etiología , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Anciano , Insuficiencia de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/mortalidad , Fibrilación Atrial/etiología , Teorema de Bayes , Ecocardiografía , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversosRESUMEN
The development of designing and searching inexpensive electrocatalysts with high activity for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is significant to enable water splitting as a future renewable energy source. Herein, we synthesize a new CoP(MoP)-CoMoO3 heterostructure coated by a N-doped carbon shell [CoP(MoP)-CoMoO3@CN] via thermal decomposition and phosphatizing of the CoMoO4·0.9H2O nanowires encapsulated in N-doped carbon. At 10 mA·cm-2, this CoP(MoP)-CoMoO3@CN nanocomposite exhibits superior electrocatalytic activity at low overpotentials of 296 mV for OER and 198 mV for HER in alkaline media. More importantly, we achieve a current density of 10 mA·cm-2 at 1.55 V by using this CoP(MoP)-CoMoO3@CN as both cathode and anode for overall water splitting. This promising performance could be due to the high activity of CoP(MoP)-CoMoO3 and the good conductivity of the external mesoporous N-carbon shell, which makes the CoP(MoP)-CoMoO3@CN nanowires a competitive alternative to noble-metal-based catalysts for water splitting.
RESUMEN
Electrochemical water splitting is a promising way for the sustainable production of hydrogen, but the efficiency of the overall water-splitting reaction largely depends on the oxygen evolution reaction (OER) because of its sluggish kinetics. Herein, a series of hierarchical ZnCo2 O4 /Co3 O4 /NC-CNT (NC-CNT=nitrogen-rich carbon nanotube) mesoporous dodecahedrons grafted to carbon nanotubes have been synthesized from ZnCo bimetallic zeolitic imidazolate frameworks (ZnCo-ZIFs) through sequential pyrolysis in nitrogen and mild oxidation in air. The simultaneous modulation of oxygen vacancies, composition, and hierarchical mesoporous architecture remarkably enhanced their electronic conduction and the amount and reactivity of accessible actives; thus boosting their intrinsic activity in the OER. The optimal ZnCo2 O4 /Co3 O4 /NC-CNT-700 sample exhibited a large current density of 50â mA cm-2 at a potential of 1.65â V, a small Tafel slope of 88.5â mV dec-1 , and superior stability in alkaline media. This work should provide a facile strategy for the rational design of advanced OER catalysts by simultaneous engineering of oxygen vacancies and composition.
RESUMEN
To engineer low-cost, high-efficiency, and stable oxygen evolution reaction (OER) catalysts, structure effects should be primarily understood. Focusing on this, we systematically investigated the relationship between structures of materials and their OER performances by taking four 2D α-Ni(OH)2 as model materials, including layer-stacked bud-like Ni(OH)2-NB, flower-like Ni(OH)2-NF, and petal-like Ni(OH)2-NP as well as the ultralarge sheet-like Ni(OH)2-NS. For the first three (layer-stacking) catalysts, with the decrease of stacked layers, their accessible surface areas, abilities to adsorb OH-, diffusion properties, and the intrinsic activities of active sites increase, which accounts for their steadily enhanced activity. As expected, Ni(OH)2-NP shows the lowest overpotential (260 mV at 10 mA cm-2) and Tafel slope (78.6 mV dec-1) with a robust stability over 10 h among the samples, which also outperforms the benchmark IrO2 (360 mV and 115.8 mV dec-1) catalyst. Interestingly, Ni(OH)2-NS relative to Ni(OH)2-NP exhibits even faster substance diffusion due to the sheet-like structure, but shows inferior OER activity, which is mainly because the Ni(OH)2-NP with a smaller size possesses more active boundary sites (higher reactivity of active sites) than Ni(OH)2-NS, considering the adsorption properties and accessible surface areas of the two samples are quite similar. By comparing the different structures and their OER behaviors of four α-Ni(OH)2 samples, our work may shed some light on the structure effect of 2D materials and accelerate the development of efficient OER catalysts.
RESUMEN
OBJECTIVES: This study sought to evaluate the Medtronic Evolut PRO Transcatheter Aortic Valve System in patients with severe symptomatic aortic stenosis. BACKGROUND: A next-generation self-expanding transcatheter aortic valve was designed with an external pericardial wrap with the intent to reduce paravalvular leak while maintaining the benefits of a low-profile, self-expanding, and repositionable supra-annular valve. METHODS: The Medtronic Evolut PRO Clinical Study included 60 patients undergoing transcatheter aortic valve replacement with the Evolut PRO valve at 8 investigational sites in the United States. Clinical outcomes at 30 days were evaluated using Valve Academic Research Consortium-2 criteria. The 2 primary safety endpoints were the incidence of all-cause mortality at 30 days and the incidence of disabling stroke at 30 days. The primary efficacy endpoint was the proportion of patients with no or trace prosthetic valve regurgitation at 30 days. An independent echocardiographic core laboratory (Mayo Clinic, Rochester, Minnesota) was used to adjudicate all echocardiographic assessments. RESULTS: All 60 patients received the Evolut PRO valve. At 30 days, 1 patient (1.7%) died and 1 patient (1.7%) experienced a nonfatal disabling stroke. Paravalvular regurgitation at 30 days was absent or trace in 72.4% of patients and was mild in the remainder of patients, with no patients having worse than mild paravavlular leak. The mean atrioventricular gradient was 6.4 ± 2.1 mm Hg and effective orifice area was 2.0 ± 0.5 cm2 at 30 days. CONCLUSIONS: The safety and efficacy results of this study support the use of the Evolut PRO System for the treatment of severe symptomatic aortic stenosis in patients who are at increased surgical risk, resulting in excellent hemodynamics and minimal paravalvular leak (The Medtronic TAVR 2.0 US Clinical Study; NCT02738853).
Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Mitral/prevención & control , Pericardio/cirugía , Reemplazo de la Válvula Aórtica Transcatéter/instrumentación , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Causas de Muerte , Ecocardiografía , Femenino , Hemodinámica , Humanos , Masculino , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/mortalidad , Insuficiencia de la Válvula Mitral/fisiopatología , Estudios Prospectivos , Diseño de Prótesis , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/mortalidad , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: Clinical outcomes in large patient populations from real-world clinical practice with a next-generation self-expanding transcatheter aortic valve are lacking. OBJECTIVES: This study sought to document the clinical and device performance outcomes of transcatheter aortic valve replacement (TAVR) with a next-generation, self-expanding transcatheter heart valve (THV) system in patients with severe symptomatic aortic stenosis (AS) in routine clinical practice. METHODS: The FORWARD (CoreValve Evolut R FORWARD) study is a prospective, single-arm, multinational, multicenter, observational study. An independent clinical events committee adjudicated safety endpoints based on Valve Academic Research Consortium-2 definitions. An independent echocardiographic core laboratory evaluated all echocardiograms. From January 2016 to December 2016, TAVR with the next-generation self-expanding THV was attempted in 1,038 patients with symptomatic, severe AS at 53 centers on 4 continents. RESULTS: Mean age was 81.8 ± 6.2 years, 64.9% were women, the mean Society of Thoracic Surgeons Predicted Risk of Mortality was 5.5 ± 4.5%, and 33.9% of patients were deemed frail. The repositioning feature of the THV was applied in 25.8% of patients. A single valve was implanted in the proper anatomic location in 98.9% of patients. The mean aortic valve gradient was 8.5 ± 5.6 mm Hg, and moderate or severe aortic regurgitation was 1.9% at discharge. All-cause mortality was 1.9%, and disabling stroke occurred in 1.8% at 30 days. The expected-to-observed early surgical mortality ratio was 0.35. A pacemaker was implanted in 17.5% of patients. CONCLUSIONS: TAVR using the next-generation THV is clinically safe and effective for treating older patients with severe AS at increased operative risk. (CoreValve Evolut R FORWARD Study [FORWARD]; NCT02592369).