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Scar tissue size following myocardial infarction is an independent predictor of cardiovascular outcomes, yet little is known about factors regulating scar size. We demonstrate that collagen V, a minor constituent of heart scars, regulates the size of heart scars after ischemic injury. Depletion of collagen V led to a paradoxical increase in post-infarction scar size with worsening of heart function. A systems genetics approach across 100 in-bred strains of mice demonstrated that collagen V is a critical driver of postinjury heart function. We show that collagen V deficiency alters the mechanical properties of scar tissue, and altered reciprocal feedback between matrix and cells induces expression of mechanosensitive integrins that drive fibroblast activation and increase scar size. Cilengitide, an inhibitor of specific integrins, rescues the phenotype of increased post-injury scarring in collagen-V-deficient mice. These observations demonstrate that collagen V regulates scar size in an integrin-dependent manner.
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Cicatriz/metabolismo , Colágeno Tipo V/deficiencia , Colágeno Tipo V/metabolismo , Lesiones Cardíacas/metabolismo , Contracción Miocárdica/genética , Miofibroblastos/metabolismo , Animales , Cicatriz/genética , Cicatriz/fisiopatología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Colágeno Tipo V/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Femenino , Fibrosis/genética , Fibrosis/metabolismo , Regulación de la Expresión Génica/genética , Integrinas/antagonistas & inhibidores , Integrinas/genética , Integrinas/metabolismo , Isoproterenol/farmacología , Masculino , Mecanotransducción Celular/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microscopía de Fuerza Atómica/instrumentación , Microscopía Electrónica de Transmisión , Contracción Miocárdica/efectos de los fármacos , Miofibroblastos/citología , Miofibroblastos/patología , Miofibroblastos/ultraestructura , Análisis de Componente Principal , Proteómica , RNA-Seq , Análisis de la Célula IndividualRESUMEN
Post-replication repair (PRR) allows tolerance of chemical- and UV-induced DNA base lesions in both an error-free and an error-prone manner. In classical PRR, PCNA monoubiquitination recruits translesion synthesis (TLS) DNA polymerases that can replicate through lesions. We find that PRR responds to DNA replication stress that does not cause base lesions. Rad5 forms nuclear foci during normal S phase and after exposure to types of replication stress where DNA base lesions are likely absent. Rad5 binds to the sites of stressed DNA replication forks, where it recruits TLS polymerases to repair single-stranded DNA (ssDNA) gaps, preventing mitotic defects and chromosome breaks. In contrast to the prevailing view of PRR, our data indicate that Rad5 promotes both mutagenic and error-free repair of undamaged ssDNA that arises during physiological and exogenous replication stress.
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Roturas del ADN de Cadena Simple , ADN Helicasas/metabolismo , Reparación del ADN , Replicación del ADN , ADN de Hongos/metabolismo , ADN de Cadena Simple/metabolismo , Mutación , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , Sitios de Unión , Cromosomas Fúngicos , ADN Helicasas/genética , ADN de Hongos/genética , ADN de Cadena Simple/genética , ADN Polimerasa Dirigida por ADN/genética , ADN Polimerasa Dirigida por ADN/metabolismo , Mitosis , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , Antígeno Nuclear de Célula en Proliferación/metabolismo , Unión Proteica , Reparación del ADN por Recombinación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Proteínas de Saccharomyces cerevisiae/genética , UbiquitinaciónRESUMEN
The visualization of accurate colour information using quantum dots has been explored for decades, and commercial products employing environmentally friendly materials are currently available as backlights1. However, next-generation electroluminescent displays based on quantum dots require the development of an efficient and stable cadmium-free blue-light-emitting device, which has remained a challenge because of the inferior photophysical properties of blue-light-emitting materials2,3. Here we present the synthesis of ZnSe-based blue-light-emitting quantum dots with a quantum yield of unity. We found that hydrofluoric acid and zinc chloride additives are effective at enhancing luminescence efficiency by eliminating stacking faults in the ZnSe crystalline structure. In addition, chloride passivation through liquid or solid ligand exchange leads to slow radiative recombination, high thermal stability and efficient charge-transport properties. We constructed double quantum dot emitting layers with gradient chloride content in a light-emitting diode to facilitate hole transport, and the resulting device showed an efficiency at the theoretical limit, high brightness and long operational lifetime. We anticipate that our efficient and stable blue quantum dot light-emitting devices can facilitate the development of electroluminescent full-colour displays using quantum dots.
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Quantum dot (QD) light-emitting diodes (LEDs) are ideal for large-panel displays because of their excellent efficiency, colour purity, reliability and cost-effective fabrication1-4. Intensive efforts have produced red-, green- and blue-emitting QD-LEDs with efficiencies of 20.5 per cent4, 21.0 per cent5 and 19.8 per cent6, respectively, but it is still desirable to improve the operating stability of the devices and to replace their toxic cadmium composition with a more environmentally benign alternative. The performance of indium phosphide (InP)-based materials and devices has remained far behind those of their Cd-containing counterparts. Here we present a synthetic method of preparing a uniform InP core and a highly symmetrical core/shell QD with a quantum yield of approximately 100 per cent. In particular, we add hydrofluoric acid to etch out the oxidative InP core surface during the growth of the initial ZnSe shell and then we enable high-temperature ZnSe growth at 340 degrees Celsius. The engineered shell thickness suppresses energy transfer and Auger recombination in order to maintain high luminescence efficiency, and the initial surface ligand is replaced with a shorter one for better charge injection. The optimized InP/ZnSe/ZnS QD-LEDs showed a theoretical maximum external quantum efficiency of 21.4 per cent, a maximum brightness of 100,000 candelas per square metre and an extremely long lifetime of a million hours at 100 candelas per square metre, representing a performance comparable to that of state-of-the-art Cd-containing QD-LEDs. These as-prepared InP-based QD-LEDs could soon be usable in commercial displays.
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OBJECTIVE: Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer. BACKGROUND: Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate. METHODS: A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation. RESULTS: At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN-). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN- and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis. CONCLUSIONS: LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.
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PURPOSE: To develop a novel deep learning approach for 4D-MRI reconstruction, named Movienet, which exploits space-time-coil correlations and motion preservation instead of k-space data consistency, to accelerate the acquisition of golden-angle radial data and enable subsecond reconstruction times in dynamic MRI. METHODS: Movienet uses a U-net architecture with modified residual learning blocks that operate entirely in the image domain to remove aliasing artifacts and reconstruct an unaliased motion-resolved 4D image. Motion preservation is enforced by sorting the input image and reference for training in a linear motion order from expiration to inspiration. The input image was collected with a lower scan time than the reference XD-GRASP image used for training. Movienet is demonstrated for motion-resolved 4D MRI and motion-resistant 3D MRI of abdominal tumors on a therapeutic 1.5T MR-Linac (1.5-fold acquisition acceleration) and diagnostic 3T MRI scanners (2-fold and 2.25-fold acquisition acceleration for 4D and 3D, respectively). Image quality was evaluated quantitatively and qualitatively by expert clinical readers. RESULTS: The reconstruction time of Movienet was 0.69 s (4 motion states) and 0.75 s (10 motion states), which is substantially lower than iterative XD-GRASP and unrolled reconstruction networks. Movienet enables faster acquisition than XD-GRASP with similar overall image quality and improved suppression of streaking artifacts. CONCLUSION: Movienet accelerates data acquisition with respect to compressed sensing and reconstructs 4D images in less than 1 s, which would enable an efficient implementation of 4D MRI in a clinical setting for fast motion-resistant 3D anatomical imaging or motion-resolved 4D imaging.
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Imagen por Resonancia Magnética , Técnicas de Imagen Sincronizada Respiratorias , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Movimiento (Física) , Aceleración , Técnicas de Imagen Sincronizada Respiratorias/métodos , Procesamiento de Imagen Asistido por Computador/métodos , RespiraciónRESUMEN
PURPOSE: To identify significant MRI features associated with macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), and to assess the distribution of Liver Imaging Radiology and Data System (LI-RADS, LR) category assignments. METHODS: PubMed and EMBASE were searched up to March 28, 2023. Random-effects model was constructed to calculate pooled diagnostic odds ratios (DORs) and 95% confidence intervals (CIs) for each MRI feature for differentiating MTM-HCC from NMTM-HCC. The pooled proportions of LI-RADS category assignments in MTM-HCC and NMTM-HCC were compared using z-test. RESULTS: Ten studies included 1978 patients with 2031 HCCs (426 (20.9%) MTM-HCC and 1605 (79.1%) NMTM-HCC). Six MRI features showed significant association with MTM-HCC: tumor in vein (TIV) (DOR = 2.4 [95% CI, 1.6-3.5]), rim arterial phase hyperenhancement (DOR =2.6 [95% CI, 1.4-5.0]), corona enhancement (DOR = 2.6 [95% CI, 1.4-4.5]), intratumoral arteries (DOR = 2.6 [95% CI, 1.1-6.3]), peritumoral hypointensity on hepatobiliary phase (DOR = 2.2 [95% CI, 1.5-3.3]), and necrosis (DOR = 4.2 [95% CI, 2.0-8.5]). The pooled proportions of LI-RADS categories in MTM-HCC were LR-3, 0% [95% CI, 0-2%]; LR-4, 11% [95% CI, 6-16%]; LR-5, 63% [95% CI, 55-71%]; LR-M, 12% [95% CI, 6-19%]; and LR-TIV, 13% [95% CI, 6-22%]. In NMTM-HCC, the pooled proportions of LI-RADS categories were LR-3, 1% [95% CI, 0-2%]; LR-4, 8% [95% CI, 3-15%]; LR-5, 77% [95% CI, 71-82%]; LR-M, 5% [95% CI, 3-7%]; and LR-TIV, 6% [95% CI, 2-11%]. MTM-HCC had significantly lower proportion of LR-5 and higher proportion of LR-M and LR-TIV categories. CONCLUSIONS: Six MRI features showed significant association with MTM-HCC. Additionally, compared to NMTM-HCC, MTM-HCC are more likely to be categorized LR-M and LR-TIV and less likely to be categorized LR-5. CLINICAL RELEVANCE STATEMENT: Several MR imaging features can suggest macrotrabecular-massive hepatocellular carcinoma subtype, which can assist in guiding treatment plans and identifying potential candidates for clinical trials of new treatment strategies. KEY POINTS: ⢠Macrotrabecular-massive hepatocellular carcinoma is a subtype of HCC characterized by its aggressive nature and unfavorable prognosis. ⢠Tumor in vein, rim arterial phase hyperenhancement, corona enhancement, intratumoral arteries, peritumoral hypointensity on hepatobiliary phase, and necrosis on MRI are indicative of macrotrabecular-massive hepatocellular carcinoma. ⢠Various MRI characteristics can be utilized for the diagnosis of the macrotrabecular-massive hepatocellular carcinoma subtype. This can prove beneficial in guiding treatment decisions and identifying potential candidates for clinical trials involving novel treatment approaches.
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Systematic reviews offer radiologists a comprehensive synthesis of all relevant evidence pertaining to a specific question, aiding them in shaping their clinical practices. It is crucial for radiologists to familiarize themselves with the methods used in systematic reviews and meta-analyses and to understand the limitations. By doing so, they can effectively appraise and interpret results, enabling them to make informed decisions based on the evidence provided in systematic reviews and meta-analyses.
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Medicina Basada en la Evidencia , Radiología , Humanos , Medicina Basada en la Evidencia/métodos , Revisiones Sistemáticas como Asunto , Radiografía , RadiólogosRESUMEN
Background: A Society of Abdominal Radiology (SAR) Pancreatic Ductal Adenocarcinoma (PDAC) Disease-Focused Panel (DFP) consensus statement described findings suspicious for local recurrence (LR) on surveillance imaging after PDAC resection. Objective: To evaluate the interreader agreement and predictive utility of potential imaging findings of LR on serial surveillance CT examinations after Whipple procedure for PDAC, using the SAR PDAC DFP consensus statement. Methods: This retrospective study included 126 patients (mean age, 68.5±10.3 years; 72 men, 54 women) who underwent Whipple surgery for PDAC between January 2009 and December 2014. Three radiologists independently reviewed baseline and subsequent postoperative contrast-enhanced abdominopelvic CT examinations performed within 2 years postoperatively, evaluating features in the SAR PDAC DFP consensus statement relating to surgical bed stranding, surgical bed soft tissue, vessel encasement, main pancreatic duct dilatation, and ascites. Interreader agreement was calculated. The reference standard for LR development within 2 years postoperatively incorporated all available information. Imaging features' frequencies were calculated for recurrence examinations (i.e., first surveillance examinations indicating LR). For baseline postoperative examinations, features associations' with eventual LR development were assessed by multivariable logistic regression analysis. Results: LR developed within 2 years postoperatively in 81/126 patients. For both baseline and subsequent examinations, agreement for stranding and soft tissue morphology were poor, for vessel encasement was fair, for soft tissue and ascites were moderate, and for main pancreatic duct dilatation was substantial. On recurrence examinations, across readers, new or increased stranding was present in 27-77%; new or increased soft tissue, 80-86%; soft tissue with vessel encasement and luminal narrowing, 36-59%; new or increased main pancreatic duct dilatation, 25-26%; and new or increased ascites, 20-23%. On baseline postoperative examinations, independent predictors of eventual LR were soft tissue for all three readers (OR=2.78-6.85) and stranding for reader 1 (OR=3.59); main pancreatic duct dilatation and ascites were not independent predictors of LR for any reader. Conclusion: This study highlights the role of soft tissue, particularly when associated with vessel encasement and luminal narrowing, in raising suspicion for LR after PDAC resection. Clinical Impact: This study supports the SAR PDAC DFP consensus statement, while highlighting opportunities for continued optimization.
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BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients. METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score. RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported. CONCLUSION: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.
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Acetilcisteína , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Acetilcisteína/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Volumen Espiratorio Forzado/efectos de los fármacos , Administración por Inhalación , Capacidad Vital/efectos de los fármacos , Expectorantes/administración & dosificación , Expectorantes/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.
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Enfermedad Pulmonar Obstructiva Crónica , Tuberculosis , Humanos , Estudios de Cohortes , Factores de Riesgo , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Incidencia , HospitalizaciónRESUMEN
Background Diffusion-weighted (DW) imaging is useful in detecting tumor in the primary tumor bed in locally advanced rectal cancer (LARC) after neoadjuvant therapy, but its value in detecting extramural venous invasion (EMVI) and tumor deposit is not well validated. Purpose To evaluate diagnostic accuracy and association with patient prognosis of viable EMVI and tumor deposit on DW images in patients with LARC after neoadjuvant therapy using whole-mount pathology specimens. Materials and Methods This retrospective study included patients who underwent neoadjuvant therapy and surgery from 2018 to 2021. Innovative five-point Likert scale was used by two radiologists to independently evaluate the likelihood of viable EMVI and tumor deposit on restaging DW MRI scans in four axial quadrants (12 to 3 o'clock, 3 to 6 o'clock, 6 to 9 o'clock, and 9 to 12 o'clock). Diagnostic accuracy was assessed at both the per-quadrant and per-patient level, with whole-mount pathology as the reference standard. Weighted κ values for interreader agreement and Cox regression models for disease-free survival and overall survival analyses were used. Results A total of 117 patients (mean age, 56 years ± 12 [SD]; 70 male, 47 female) were included. Pathologically proven viable EMVI and tumor deposit was detected in 29 of 117 patients (25%) and in 44 of 468 quadrants (9.4%). Per-quadrant analyses showed an area under the receiver operating characteristics curve of 0.75 (95% CI: 0.68, 0.83), with sensitivity and specificity of 55% and 96%, respectively. Good interreader agreement was observed between the radiologists (κ = 0.62). Per-patient analysis showed sensitivity and specificity of 62% and 93%, respectively. The presence of EMVI and tumor deposit on restaging DW MRI scans was associated with worse disease-free survival (hazard ratio [HR], 5.6; 95% CI: 2.4, 13.3) and overall survival (HR, 8.9; 95% CI: 1.6, 48.5). Conclusion DW imaging using the five-point Likert scale showed high specificity and moderate sensitivity in the detection of viable extramural venous invasion and tumor deposits in LARC after neoadjuvant therapy, and its presence on restaging DW MRI scans is associated with worse prognosis. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Méndez and Ayuso in this issue.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Extensión Extranodal , Estudios Retrospectivos , Invasividad Neoplásica/diagnóstico por imagen , Invasividad Neoplásica/patología , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Stretchable energy storage devices receive a considerable attention at present due to their growing demand for powering wearable electronics. A vital component in stretchable energy storage devices is its electrode which should endure a large and repeated number of mechanical deformations during its prolonged use. It is crucial to develop a technology to fabricate highly deformable electrode in an easy and an economic manner. Here, the fabrication of stretchable electrode substrates using 3D-printing technology is reported. The ink for fabricating it contains a mixture of sacrificial sugar particles and polydimethylsiloxane resin which solidifies upon thermal curing. The printed stretchable substrate attains a porous structure after leaching the sugar particles in water. The resulting printed porous stretchable substrates are then utilized as electrodes for Li-ion batteries (LIBs) after loading them with electrode materials. The batteries with stretchable electrodes exhibit a decent electrochemical performance comparable to that of the conventional electrodes. The stretchable electrodes also exhibit a stable electrochemical performance under various mechanical deformations and even after several hundreds of stretch/release cycles. This work provides a feasible route for constructing LIBs with high stretchability and enhanced electrochemical performance thereby providing a platform for realizing stretchable batteries for next generation wearable electronics.
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Suministros de Energía Eléctrica , Siliconas , Iones , Electrodos , Litio/química , Azúcares , Impresión TridimensionalRESUMEN
Stem-cell-based therapeutics have shown immense potential in treating various diseases that are currently incurable. In particular, partial recovery of Parkinson's disease, which occurs due to massive loss or abnormal functionality of dopaminergic (DAnergic) neurons, through the engraftment of stem-cell-derived neurons ex vivo is reported. However, precise assessment of the functionality and maturity of DAnergic neurons is still challenging for their enhanced clinical efficacy. Here, a novel conductive cell cultivation platform, a graphene oxide (GO)-incorporated metallic polymer nanopillar array (GOMPON), that can electrochemically detect dopamine (DA) exocytosis from living DAnergic neurons, is reported. In the cell-free configuration, the linear range is 0.5-100 µm, with a limit of detection of 33.4 nm. Owing to its excellent biocompatibility, a model DAnergic neuron (SH-SY5Y cell) can be cultivated and differentiated on the platform while their DA release can be quantitatively measured in a real-time and nondestructive manner. Finally, it is showed that the functionality of the DAnergic neurons derived from stem cells can be precisely assessed via electrochemical detection of their DA exocytosis. The developed GOMPON is highly promising for a wide range of applications, including real-time monitoring of stem cell differentiation into neuronal lineages, evaluating differentiation protocols, and finding practical stem cell therapies.
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Grafito , Neuroblastoma , Humanos , Polímeros , Dopamina , Pirroles , Oro , Neuronas , Técnicas ElectroquímicasRESUMEN
Deoxyribonuclease-I (DNase-I), a representative endonuclease, is an important biomarker for the diagnosis of infectious diseases and cancer progression. However, enzymatic activity decreases rapidly ex vivo, which highlights the need for precise on-site detection of DNase-I. Here, a localized surface plasmon resonance (LSPR) biosensor that enables the simple and rapid detection of DNase-I is reported. Moreover, a novel technique named electrochemical deposition and mild thermal annealing (EDMIT) is applied to overcome signal variations. By taking advantage of the low adhesion of gold clusters on indium tin oxide substrates, both the uniformity and sphericity of gold nanoparticles are increased under mild thermal annealing conditions via coalescence and Ostwald ripening. This ultimately results in an approximately 15-fold decrease in LSPR signal variations. The linear range of the fabricated sensor is 20-1000 ng mL-1 with a limit of detection (LOD) of 127.25 pg mL-1 , as demonstrated by spectral absorbance analyses. The fabricated LSPR sensor stably measured DNase-I concentrations from samples collected from both an inflammatory bowel disease (IBD) mouse model, as well as human patients with severe COVID-19 symptoms. Therefore, the proposed LSPR sensor fabricated via the EDMIT method can be used for early diagnosis of other infectious diseases.
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Técnicas Biosensibles , COVID-19 , Nanopartículas del Metal , Animales , Ratones , Humanos , Resonancia por Plasmón de Superficie/métodos , Oro/química , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , DesoxirribonucleasasRESUMEN
Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other acute myeloid leukemia-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (P=0.969), relapse incidence (P=0.600) or non-relapse mortality (P=0.570). Donor CHIP did not impair neutrophil (P=0.460) or platelet (P=0.250) engraftment, the rates of acute (P=0.490), or chronic graft-versus-host disease (P=0.220). No significant difference was noted for secondary malignancy following HSCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HSCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pretransplant evaluation of donors prior to stem cell donation.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Hematopoyesis Clonal , Estudios de Seguimiento , Trasplante Homólogo/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodosRESUMEN
OBJECTIVES: Percutaneous radiofrequency ablation (RFA) is one of the curative treatments for hepatocellular carcinoma (HCC), but local tumor progression (LTP) has been a main limitation of RFA. This study aims to evaluate the LTP of percutaneous no-touch RFA (NtRFA) for HCC ≤ 5 cm and compare with conventional RFA (intratumoral puncture) through a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane Library were searched for studies on percutaneous NtRFA for HCC ≤ 5 cm. The pooled proportions of the overall and cumulative incidence rates at 1, 2, and 3 years for LTP after NtRFA were assessed using a random-effects model. For studies comparing NtRFA with conventional RFA, relative risks (RR) and hazard ratios (HR) were meta-analytically pooled with LTP as the outcome. RESULTS: Twelve studies with 900 patients were included. The pooled overall rate of LTP after NtRFA was 6% (95% CI, 4-8%). The pooled 1-, 2-, and 3-year cumulative incidence rates of LTP were 3% (95% CI, 2-5%), 5% (95% CI, 3- 9%), and 8% (95% CI, 6-11%), respectively. Compared to conventional RFA, the pooled RR and HR of LTP were 0.26 (95% CI, 0.16-0.41) and 0.28 (95% CI, 0.11-0.70), respectively (both p < 0.01). Subgroup analysis including only randomized controlled studies also showed better local tumor control of NtRFA with HR of 0.13 (95% CI, 0.14-0.42). CONCLUSIONS: Percutaneous NtRFA is an effective treatment for HCC ≤ 5 cm with an overall LTP rate of 6% and provides lower LTP compared with conventional RFA. KEY POINTS: ⢠The pooled 1-, 2-, and 3-year cumulative incidence rates of local tumor progression after no-touch radiofrequency ablation for HCC ≤ 5 cm were 3% (95% CI, 2-5%), 5% (95% CI, 3-9%), and 8% (95% CI, 6-11%). ⢠No-touch radiofrequency ablation had significantly lower rates of local tumor progression compared to conventional radiofrequency ablation (hazard ratio, 0.28; 95% CI, 0.11-0.70; relative risk, 0.26; 95% CI, 0.16-0.41; p < 0.01, respectively).
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Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patología , Ablación por Catéter/efectos adversos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND. Accumulating evidence indicates that hepatocellular adenoma (HCA) may have a higher frequency of hepatobiliary phase (HBP) iso- or hyperintensity than previously reported. OBJECTIVE. The purpose of this study was to evaluate the proportion of HCA that shows iso- or hyperintensity in the HBP of gadoxetic acid-enhanced MRI, stratified by HCA subtype (HNF1a-inactivated [H-HCA], inflammatory [I-HCA], ß-catenin-activated [B-HCA], and unclassified [U-HCA] HCA), and to assess the diagnostic performance of HBP iso- or hyperintensity for differentiating focal nodular hyperplasia (FNH) from HCA. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched through February 14, 2022, for articles reporting HBP signal intensity on gadoxetic acid-enhanced MRI among pathologically proven HCAs, stratified by subtype. The pooled proportion of HBP iso- or hyperintensity was determined for each subtype and compared using metaregression. Diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from all HCA subtypes combined and from B-HCA and U-HCA combined was assessed using bivariate modeling. EVIDENCE SYNTHESIS. Twenty-eight studies (12 original investigations, 16 case reports or case series) were included, yielding 364 patients with 410 HCAs (112 H-HCAs, 203 I-HCAs, 33 B-HCAs, 62 U-HCAs). Pooled proportion of HBP iso- or hyperintensity was 14% (95% CI, 4-26%) among all HCAs, 0% (95% CI, 0-2%) among H-HCAs, 11% (95% CI, 0-29%) among U-HCAs, 14% (95% CI, 2-31%) among I-HCAs, and 59% (95% CI, 26-88%) among B-HCAs; metaregression showed significant difference among subtypes (p < .001). In four studies reporting diagnostic performance information, HBP iso- or hyperintensity had sensitivity of 99% (95% CI, 57-100%) and specificity of 89% (95% CI, 82-94%) for differentiating FNH from all HCA subtypes and sensitivity of 99% (95% CI, 53-100%) and specificity of 65% (95% CI, 44-80%) for differentiating FNH from B-HCA or U-HCA. CONCLUSION. HCA subtypes other than H-HCA show proportions of HBP iso- or hyperintensity ranging from 11% (U-HCA) to 59% (B-HCA). Low prevalence of B-HCA has contributed to prior reports of high diagnostic performance of HBP iso- or hyperintensity for differentiating FNH from HCA. CLINICAL IMPACT. Radiologists should recognize the low specificity of HBP iso- or hyperintensity on gadoxetic acid-enhanced MRI for differentiating FNH from certain HCA subtypes.
Asunto(s)
Adenoma de Células Hepáticas , Hiperplasia Nodular Focal , Neoplasias Hepáticas , Humanos , Adenoma de Células Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/diagnóstico por imagen , Medios de Contraste , Sensibilidad y Especificidad , Gadolinio DTPA , Imagen por Resonancia Magnética , Aminas , Estudios Retrospectivos , Diagnóstico DiferencialRESUMEN
This study aimed to verify the relationship between the level of understanding of health information and health behaviors among Korean adults. In total, 228 984 adults who participated in the 2021 Korea Community Health Survey were included. Participants were divided into three groups according to age (19-44, 45-64 and 65+). The ability to understand verbal and written health information was included, and its association with health behaviors, including smoking, alcohol consumption and preventive health service uptake, was assessed. Associations between the ability to understand health information and health behaviors were analyzed using chi-squared tests and multiple logistic regression analyses. Approximately 22.7% and 20% of the participants responded that verbal and written health information were easy to understand, respectively, with significant differences by age group. Compared to those with easy-to-understand verbal health information, those with difficulty in understanding had a higher risk of current cigarette smoking and monthly drinking and were less likely to engage in more than moderate physical activity, walking, influenza vaccination in 1 year, cancer examination in 2 years and medical examination in 2 years. Difficulty in understanding or no interest in written health information was also associated with unhealthy behaviors. A strong ability to understand health information is related to positive health behaviors. However, there are differences in the associations by age group, which should be considered when establishing a health literacy improvement strategy. These findings could promote health literacy and ultimately contribute to helping individuals make better choices for positive health behaviors.
Asunto(s)
Promoción de la Salud , Neoplasias , Humanos , Adulto , Conductas Relacionadas con la Salud , Encuestas y Cuestionarios , Neoplasias/prevención & control , República de CoreaRESUMEN
BACKGROUND: Chronic lung diseases, such as chronic obstructive pulmonary disease or asthma, are associated with an increased risk of dementia. However, few data are available regarding the risk of dementia in individuals with bronchiectasis. OBJECTIVES: To explore the association between bronchiectasis and the risk of incident dementia using a longitudinal population-based cohort. METHODS: A total of 4,068,560 adults older than 50 years without previous dementia were enrolled from the Korean National Health Insurance Service database in 2009. They were followed up until the date of the diagnosis of dementia or December 31, 2020. The study exposure was the diagnosis of bronchiectasis, and the primary outcome was incident dementia comprising Alzheimer's disease and vascular dementia. RESULTS: During the median follow-up duration of 9.3 years, the incidence of all-cause dementia was 1.6-fold higher in individuals with bronchiectasis than in those without bronchiectasis (15.0 vs. 9.3/1000 person-years, p < .001). In the multivariable Cox regression analysis, the risk of all dementia was significantly higher in individuals with bronchiectasis than in those without bronchiectasis (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 1.04-1.14). In a subgroup analysis by dementia type, individuals with bronchiectasis had an increased risk of Alzheimer's disease compared to those without bronchiectasis (aHR 1.07, 95% CI 1.01-1.12); the risk of vascular dementia did not significantly differ between the two groups (aHR 1.05, 95% CI 0.90-1.21). CONCLUSION: Bronchiectasis was associated with an increased risk of dementia, especially Alzheimer's disease.