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Methionine adenosyltransferase 2 A (MAT2A) mediates the synthesis of methyl donor S-Adenosylmethionine (SAM), providing raw materials for methylation reactions in cells. MAT2A inhibitors are currently used for the treatment of tumors with methylthioadenosine phosphorylase (MTAP) deficiency in clinical research. Methyltransferase like 3 (METTL3) catalyzes N6-methyladenosine (m6A) modification of mRNA in mammalian cells using SAM as the substrate which has been shown to affect the tumorigenesis of non-small cell lung cancer (NSCLC) from multiple perspectives. MAT2A-induced SAM depletion may have the potential to inhibit the methyl transfer function of METTL3. Therefore, in order to expand the applicability of inhibitors, improve anti-tumor effects and reduce toxicity, the combinational effect of MAT2A inhibitor AG-270 and METTL3 inhibitor STM2457 was evaluated in NSCLC. The results showed that this combination induced cell apoptosis rather than cell cycle arrest, which was non-tissue-specific and was independent of MTAP expression status, resulting in a significant synergistic anti-tumor effect. We further elucidated that the combination-induced enhanced apoptosis was associated with the decreased m6A level, leading to downregulation of PI3K/AKT protein, ultimately activating the apoptosis-related proteins. Unexpectedly, although combination therapy resulted in metabolic recombination, no significant change in methionine metabolic metabolites was found. More importantly, the combination also exerted synergistic effects in vivo. In summary, the combination of MAT2A inhibitor and METTL3 inhibitor showed synergistic effects both in vivo and in vitro, which laid a theoretical foundation for expanding the clinical application research of the two types of drugs.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Sinergismo Farmacológico , Neoplasias Pulmonares , Metionina Adenosiltransferasa , Metiltransferasas , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Inhibidores Enzimáticos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Metionina Adenosiltransferasa/metabolismo , Metionina Adenosiltransferasa/antagonistas & inhibidores , Metionina Adenosiltransferasa/genética , Metiltransferasas/metabolismo , Metiltransferasas/antagonistas & inhibidores , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Terrestrial silicon (Si) from biogeochemically weathered rocks and soils into oceans must pass through several water bodies, resulting in some Si immobilized. Hence, the knowledge on Si distribution characteristics in different water bodies at a basin scale is helpful to understand Si immobilization. A total of 65 surface sediments and corresponding overlying water samples were sampled from six water bodies (Dianchi Lake, DL; Dadu River, DR; Tuojiang River, TR; Honghu Lake, HL; Donghu Lake, DhL; Taihu Lake, TL) in the Yangtze River Basin of China, total dissolved Si (TDSi) in overlying water and exchangeable Si (Ex-Si), active non-biogenic Si (NBSi), and total acid dissolved Si (TADSi) in sediments were analyzed. Water chemical parameters (pH, EC, and TDP) and sediment components (LOI, TN, TP, and TADFe) showed that the water environment characteristics of six water bodies differed. TDSi differed among regions and between lakes and rivers, significantly higher in water bodies in the upper reaches and rivers than the middle or lower reaches and lakes (p < 0.05), respectively. Ex-Si in sediments in the upper reaches was significantly higher than in the middle or lower reaches (p < 0.05), except for DhL, whose Ex-Si was the highest. Mean TADSi and active NBSi were significantly higher in lakes than rivers (p < 0.05). Oxidation of sediments significantly increased TDSi in overlying water and active NBSi in sediments (p < 0.01). Si forms in six water bodies significantly depended on components of the sediments (e.g. active Ca2+, Mg2+, Fe, and Al3+) and water chemical parameters (p < 0.05). Our results suggest that immobilization of Si in water bodies in the Yangtze River Basin depends on the types of water bodies and sediments, lakes and Fe-Al dominated sediments have a high potential to immobilize Si, but anthropogenic interference should not be ignored.
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Monitoreo del Ambiente , Sedimentos Geológicos , Ríos , Silicio , China , Silicio/análisis , Ríos/química , Sedimentos Geológicos/química , Sedimentos Geológicos/análisis , Contaminantes Químicos del Agua/análisis , Lagos/químicaRESUMEN
PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.
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As graphene-related technology advances, the benefits of graphene metamaterials become more apparent. In this study, a surface-isolated exciton-based absorber is built by running relevant simulations on graphene, which can achieve more than 98% perfect absorption at multiple frequencies in the MWIR (MediumWavelength Infra-Red (MWIR) band as compared to the typical absorber. The absorber consists of three layers: the bottom layer is gold, the middle layer is dielectric, and the top layer is patterned with graphene. Tunability was achieved by electrically altering graphene's Fermi energy, hence the position of the absorption peak. The influence of graphene's relaxation time on the sensor is discussed. Due to the symmetry of its structure, different angles of light source incidence have little effect on the absorption rate, leading to polarization insensitivity, especially for TE waves, and this absorber has polarization insensitivity at ultra-wide-angle degrees. The sensor is characterized by its tunability, polarisation insensitivity, and high sensitivity, with a sensitivity of up to 21.60 THz/refractive index unit (RIU). This paper demonstrates the feasibility of the multi-frequency sensor and provides a theoretical basis for the realization of the multi-frequency sensor. This makes it possible to apply it to high-sensitivity sensors.
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Na4 MnV(PO4 )3 /C (NMVP) has been considered an attractive cathode for sodium-ion batteries with higher working voltage and lower cost than Na3 V2 (PO4 )3 /C. However, the poor intrinsic electronic conductivity and Jahn-Teller distortion caused by Mn3+ inhibit its practical application. In this work, the remarkable effects of Zr-substitution on prompting electronic and Na-ion conductivity and also structural stabilization are reported. The optimized Na3.9 Mn0.95 Zr0.05 V(PO4 )3 /C sample shows ultrafast charge-discharge capability with discharge capacities of 108.8, 103.1, 99.1, and 88.0 mAh g-1 at 0.2, 1, 20, and 50 C, respectively, which is the best result for cation substituted NMVP samples reported so far. This sample also shows excellent cycling stability with a capacity retention of 81.2% at 1 C after 500 cycles. XRD analyses confirm the introduction of Zr into the lattice structure which expands the lattice volume and facilitates the Na+ diffusion. First-principle calculation indicates that Zr modification reduces the band gap energy and leads to increased electronic conductivity. In situ XRD analyses confirm the same structure evolution mechanism of the Zr-modified sample as pristine NMVP, however the strong ZrO bond obviously stabilizes the structure framework that ensures long-term cycling stability.
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Visible light communication(VLC) is a new method of indoor communication. It can provide an effective solution for indoor positioning. Fingerprint-based visible light positioning(VLP) has been widely studied for its feasibility and high accuracy. The acquisition of 'fingerprint database' is crucial for accurate VLP. However, sparse sensors such as photodiode(PD) can only be arranged because of the space-limited scenario and high costs. Correspondingly, it results in the loss of the fingerprint database. Therefore, it is indispensable to solve the problem of how to effectively and accurately recover the fingerprint database from measurements of sparsely arranged sensors. In this paper, we propose a spatio-temporal constraint tensor completion (SCTC) algorithm based on CANDECOMP/PARAFAC (CP) decomposition to recover the fingerprint database from measurements of sparsely arranged sensors. Specifically, we model the measurements from the spatial and temporal dimensions as a tensor, and formulate the optimization problem based on the low-rank feature of the tensor. To improve the recovery accuracy, spatial and temporal constraint matrices are introduced to effectively constrain the optimization direction when completing the tensor. Spatial constraint matrices are constructed by utilizing the mode-n expansion matrix of the tensor based on the undirected graph theory. Accordingly, the Toeplitz matrix is used as the temporal constraint matrix to excavate the temporal correlation of the tensor. Since the optimization problem is non-convex and difficult to solve, we introduce CP decomposition to decompose the tensor into several factor matrices. By solving the factor matrices, the original tensor is reconstructed. The performance of the proposed SCTC algorithm is confirmed via experimental measured data.
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Integrated cross-scale milli/microlenses offer irreplaceable functions in modern integrated optics with the advantage of reducing the size of the optical system to millimeters or microns. However, the technologies for fabricating millimeter-scale lenses and microlenses are always incompatible, which makes the successful fabrication of cross-scale milli/microlenses with a controlled morphology challenging. Here, ion beam etching is proposed as a means to fabricate smooth millimeter-scale lenses on various hard materials. In addition, by combining femtosecond laser modification and ion beam etching, an integrated cross-scale concave milli/microlens (27,000 microlenses on a lens with a diameter of 2.5 mm) is demonstrated on fused silica, and can be used as the template for a compound eye. The results provide a new, to the best of our knowledge, route for the flexible fabrication of cross-scale optical components for modern integrated optical systems.
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Digital tomosynthesis (DTS) technology has attracted much attention in the field of nondestructive testing of printed circuit boards (PCB) due to its high resolution and suitability to thin slab objects. However, the traditional DTS iterative algorithm is computationally demanding, and its real-time processing of high-resolution and large volume reconstruction is infeasible. To address this issue, we in this study propose a multiple multi-resolution algorithm, including two multi-resolution strategies: volume domain multi-resolution and projection domain multi-resolution. The first multi-resolution scheme employs a LeNet-based classification network to divide the roughly reconstructed low-resolution volume into two sub-volumes namely, (1) the region of interest (ROI) with welding layers that necessitates high-resolution reconstruction, and (2) the remaining volume with unimportant information which can be reconstructed in low-resolution. When X-rays in adjacent projection angles pass through many identical voxels, information redundancy is prevalent between the adjacent image projections. Therefore, the second multi-resolution scheme divides the projections into non-overlapping subsets, using only one subset for each iteration. The proposed algorithm is evaluated using both the simulated and real image data. The results demonstrate that the proposed algorithm is approximately 6.5 times faster than the full-resolution DTS iterative reconstruction algorithm without compromising image reconstruction quality.
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Algoritmos , Procesamiento de Imagen Asistido por Computador , Procesamiento de Imagen Asistido por Computador/métodos , Fantasmas de Imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Cushing's disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. CASE PRESENTATION: A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. CONCLUSIONS: We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.
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Adenoma Hipofisario Secretor de ACTH , Adenoma , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Neoplasias Hipofisarias , Adenoma Hipofisario Secretor de ACTH/diagnóstico , Adenoma Hipofisario Secretor de ACTH/genética , Adenoma Hipofisario Secretor de ACTH/cirugía , Adenoma/diagnóstico , Adenoma/genética , Adenoma/cirugía , Hormona Adrenocorticotrópica , Endopeptidasas/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Femenino , Células Germinativas/patología , Humanos , Mutación , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Neoplasias Hipofisarias/genética , Neoplasias Hipofisarias/cirugía , Receptores Acoplados a Proteínas G , Ubiquitina Tiolesterasa/genéticaRESUMEN
Trans-ferulic acid-4-ß-glucoside (FAG) is a monomer extracted from Radix Aconiti Lateralis Preparata, which is a potential candidate for the prevention and treatment of cold injury. To determine the concentration of FAG in rats, it is essential to develop an ultra-performance liquid chromatography coupled with MS/MS method. Chromatographic separation was achieved by an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm). A Xevo triple quadrupole tandem mass spectrometer was used to quantitatively determine FAG in the negative-ion mode. The standard calibration curve was linear over the concentration range of 0.1-100 µg/mL and 0.0626-31.28 µg/g for rat plasma and liver tissue homogenate samples, respectively. The inter- and intra-batch precision (% relative standard deviation) of the assay was ≤8.29%, and accuracy (% relative error) ranged from -7.41 to 10.99%. The matrix effect was between 92.99 and 102.39%. The oral absolute bioavailability of FAG was obtained as 1.80%. The results of tissue distribution suggested that FAG spread rarely in the liver and brown adipose, which was not propitious to exert its ability to treat cold injury. In general, these studies were significant to provide necessary information for further study.
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Glucósidos , Espectrometría de Masas en Tándem , Animales , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Ácidos Cumáricos , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodos , Distribución TisularRESUMEN
G-quadruplexes (G4s) are DNA or RNA structures formed by guanine-rich repeating sequences. Recently, G4s have become a highly attractive therapeutic target for BRCA-deficient cancers. Here, we show that a substituted quinolone amide compound, MTR-106, stabilizes DNA G-quadruplexes in vitro. MTR-106 displayed significant antiproliferative activity in homologous recombination repair (HR)-deficient and PARP inhibitor (PARPi)-resistant cancer cells. Moreover, MTR-106 increased DNA damage and promoted cell cycle arrest and apoptosis to inhibit cell growth. Importantly, its oral and i.v. administration significantly impaired tumor growth in BRCA-deficient xenograft mouse models. However, MTR-106 showed modest activity against talazoparib-resistant xenograft models. In rats, the drug rapidly distributes to tissues within 5 min, and its average concentrations were 12-fold higher in the tissues than in the plasma. Overall, we identified MTR-106 as a novel G-quadruplex stabilizer with high tissue distribution, and it may serve as a potential anticancer agent.
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Antineoplásicos/farmacología , Proteína BRCA1/biosíntesis , Proteína BRCA2/biosíntesis , G-Cuádruplex/efectos de los fármacos , Animales , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/fisiología , Humanos , Masculino , Ratones , Ratones Desnudos , Neoplasias/patología , Ftalazinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Ratas , Ratas Sprague-Dawley , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
A new hypervalent-iodine(III)-mediated tandem reaction involving oxidative dearomatization and inâ situ aziridination of phenolic amines is described, providing a mild and effective method for the assembly of structurally interesting and synthetically useful aziridines. Importantly, the densely functionalized aziridines resulting from this unprecedented tandem reaction offer a platform for expeditious access to architecturally diverse aza-heterocycles through transformations initiated by selective ring-opening of aziridines.
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OBJECTIVE: The role of perioperative protein-enriched enteral nutrition for patients with primary liver cancer is unclear. We investigated the efficacy of perioperative protein-enriched enteral nutrition for patients with primary liver cancer followed hepatectomy. METHODS: Patients with primary liver cancer that underwent hepatectomy between January 2016 and 2018 were enrolled. Patients in the treatment group was given enteral nutrition (TP-MCT) in addition to the regular diet. The primary outcome measures were duration of hospital stay and length of postoperative hospital stay. Secondary outcome measures included time to first flatus and time to first defecation. RESULTS: There was a significant reduction of time to first flatus and time to first defecation in the treatment group, when compared with the control group (time to first flatus: P = 0.001, time to first defecation: P < 0.001). CONCLUSIONS: It is found that addition of protein-enriched enteral nutrition (TP-MCT) improved postoperative recovery for patients with primary liver cancer following hepatectomy, with a significant reduction in time to first flatus and time to first defecation.
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Nutrición Enteral , Neoplasias Hepáticas , Hepatectomía , Humanos , Tiempo de Internación , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias , Periodo PosoperatorioRESUMEN
PURPOSE: Robotic-assisted surgery and robotic-assisted ventral mesh rectopexy are gaining attention in the treatment of rectal prolapse and increased positive findings are proposed. The objective of this meta-analysis was to investigate whether robotic-assisted ventral mesh rectopexy is comparable with the conventional laparoscopic approach surgery. METHODS: Five major databases (PubMed, Sciencedirect, Web of Science, Embase, and Cochrane Library) were searched for eligible studies. Observational studies of the effect and safety of robotic-assisted and laparoscopic approaches on ventral mesh rectopexy were included. Odd ratios (OR) and weight mean difference (WMD) were used for dichotomous data and continuous data analysis. Clinical outcomes, functional outcomes, and cost-effectiveness data were extracted for meta-analysis. RESULTS: Compared to the laparoscopic approach, a significant shorter length of hospital stay (LOS), lesser intraoperative blood loss, and lower post-operative complication rate of RVMR group were observed. However, operation time of RVMR was significant increased. The expense of RVMR was higher than LVMR; mean Wexner scores and fecal incontinence were lower in RVMR group while there were no statistical differences. CONCLUSION: The result of the current analysis revealed that the robotic-assisted ventral mesh rectopexy is effective and feasible in the treatment of rectal prolapse. However, long-term follow-up and results are needed for the promotion of this approach. There is a long way for robotic-assisted surgery to become a gold standard in rectal surgery.
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Laparoscopía , Prolapso Rectal , Procedimientos Quirúrgicos Robotizados , Humanos , Laparoscopía/efectos adversos , Prolapso Rectal/cirugía , Recto/cirugía , Recurrencia , Procedimientos Quirúrgicos Robotizados/efectos adversos , Mallas Quirúrgicas/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: We aimed to determine whether heart rate variability (HRV) was correlated to long-term outcome in patients who received mechanical thrombectomy (MT) under general anesthesia for emergent large vessel occlusion (ELVO). METHODS: Data from 106 patients receiving MT under general anesthesia to treat ELVO between January 1, 2017 and December 31, 2019 were collected in a multicenter chart review. Univariate analysis, Chi-square test, and bivariate logistic regression were performed to assess the correlations between preoperative risk factors such as HRV and long-term outcome (as indicated by the modified Rankin score [mRS] at 90 days after MT). RESULTS: Bivariate logistic regression revealed that decreased LF/HF (low frequency/high frequency in HRV) ratio was correlated with unfavorable functional outcome as indicated by mRS ≥ 2 (odds ratio [OR], 0.650; 95% confidence interval [CI], 0.157-0.839; p = 0.018), and functionally dependent outcome as indicated by mRS ≥ 3 (OR, 0.704; 95% CI, 0.360-0.914; p = 0.021). It was also found that ELVO in the right anterior circulation was correlated with lower LF/HF ratio, as compared with ELVO in the contralateral side (p < 0.05). CONCLUSION: Our retrospective study demonstrated that worse outcome in patients with ELVO who received MT under general anesthesia induced autonomic changes and that decreased LF/HF ratio.
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Anestesia General , Isquemia Encefálica , Frecuencia Cardíaca , Accidente Cerebrovascular , Trombectomía , Humanos , Estudios Retrospectivos , Trombectomía/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVE: Patients undergoing carotid endarterectomy (CEA) have a significant possibility of developing postoperative cognitive decline (POCD). POCD after surgery could be result from cerebral hypotension induced by cross-clamping or postoperative hyperperfusion. Optic nerve sheath diameter (ONSD) exhibits an excellent correlation with invasive intracranial pressure monitoring, Here, the authors explored the risk factors of POCD in patients undergoing CEA, paying close attention to ONSD to test the hypothesis that decrease of coronal ONSD was related to the incidence of POCD. DESIGN: Observational retrospective review. SETTING: Single tertiary academic center. PARTICIPANTS: One hundred sixteen patients undergoing CEA from January 1, 2019 to December 31, 2019. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A multivariate logistic regression, scatter diagrams, and a receiver operating curve were used to evaluate the ability to predict POCD though the change in coronal ONSD. This study ultimately enrolled 84 patients and the incidence of POCD within postoperative two days was 28.6%. Decrease of coronal ONSD (odds ratio [OR], 0.438; 95% confidence interval [CI] 0.217-0.881; pâ¯=â¯0.021) and total intravenous anesthesia (TIVA) (OR, 25.541, 95% CI 2.100-310.614, pâ¯=â¯0.011) were independent risk factors for POCD. Changes in coronal ONSD had an area under the curve to distinguish POCD of 0.716 (95% CI 0.531-0.902). Using a cutoff of 0.05 cm, changes of coronal ONSD had a sensitivity of 66.7% and specificity of 66.7%. CONCLUSIONS: Decrease of coronal ONSD, measured by ultrasonography and TIVA, were associated with POCD. Change in coronal ONSD was a moderate predictor of incidence of POCD.
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Endarterectomía Carotidea , Hipertensión Intracraneal , Complicaciones Cognitivas Postoperatorias , Endarterectomía Carotidea/efectos adversos , Humanos , Presión Intracraneal , Nervio Óptico/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , UltrasonografíaRESUMEN
OBJECTIVES: This study aims to propose a novel and effective throat swab collection method for coronavirus disease 2019 (COVID-19). METHODS: The subjects were randomly divided into two groups. The subjects were asked to open their mouth to make "ah" sound (traditional method) or simulate yawn (improved method) for throat swab collection. The usage of tongue depressor, collection time, adverse reactions and subjective discomfort (VAS score) were compared. The collection time, comprehensive indicators of adverse reactions and VAS score were also compared among three collectors. RESULTS: The tongue depressor was less used in the improved group (χ2 = 40.186, P < 0.01). The average collection time of the traditional group was 5.44 ± 2.97 and that of the improved group was 4.00 ± 2.31 (P < 0.01). The subjects in the improved group had fewer and milder adverse reactions. The VAS score of subjects in the improved group was lower than that in the traditional group (P < 0.01). Among different collectors, the collection time, comprehensive indicators of adverse reactions and VAS were the same as the overall trend. CONCLUSION: Simulating yawn is a safer and faster throat swab collection method.
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COVID-19/diagnóstico , Faringe/virología , Manejo de Especímenes/métodos , Bostezo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Factores de Tiempo , Escala Visual Analógica , Adulto JovenRESUMEN
The orally available novel small molecule drug ZWF is under preclinical development for an anticancer purpose. The present study aimed to assess the viability of developing ZWF as a form of oral formulation for clinical application based on the principles of biopharmaceutics and pharmacokinetics. The crucial physicochemical properties of ZWF were determined by in vitro assays. The in situ gastrointestinal absorption characteristics and in vivo pharmacokinetic behaviors of ZWF in rats were characterized. The solubility of ZWF showed a highly pH-dependent profile, decreasing from 25,392.89 to 20.48 µg/mL as the solution pH increased from 1.0 to 5.8. In PBS with a pH of 1.0 to 5.8, the LogP value of ZWF ranged from -2.35 to 2.20 and was gradually increased as the pH value increased. ZWF was partially absorbed in the stomach, and the favorable absorption sites were the duodenum, jejunum, and ileum. Pharmacokinetic studies showed that the AUC(0-t) and Cmax values of ZWF after its oral administration as a suspension prepared with 0.5% CMC-Na were increased by 18.97% and 40% than that with normal saline, providing a model oral formulation of ZWF with ideal bioavailability and system exposure in rats. From the perspective of oral absorption, ZWF possessed appealing qualities as a drug candidate and could be prepared as an oral preparation for clinical application. The present study has established a fundamental foundation for the development and quality evaluation of the ZWF oral formulations.
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Antineoplásicos , Productos Biológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Administración Oral , Animales , Disponibilidad Biológica , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Absorción Intestinal , Neoplasias Pulmonares/tratamiento farmacológico , Ratas , SolubilidadRESUMEN
OBJECTIVE: To reduce secondary artifactes generated by the current interpolation-based metal artifact reduction (MAR) methods, this study proposes and tests a new Poisson fusion sinogram based metal artifact reduction (FS-MAR) method. METHODS: The proposed FS-MAR method consists of (1) generating the prior image, (2) forward projecting this prior image and applying the Poisson blending technique to seamlessly replace the metal-affected sinogram of the original projection in the metal projection region (MPR) by the prior image projection to get the corrected metal-free sinogram, and (3) performing the filtered back projection (FBP) on the corrected sinogram and filling the metal image back to the metal-free corrected image to get the final artifact reduced image. Simulated images are calculated by taking clinical metal-free CT images as phantoms and inserting metals during the simulated projection process to get the corresponding metal-affected images by the FBP. After the simulated images are processed by the proposed MAR method, two metrics structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) are used to evaluate image quality. Finally, visual evaluation is also performed using several real clinical metal-affected images obtained from the Revision Radiology group. RESULTS: In two testing samples, using FS-MAR method yields the highest SSIM and PSNR of 0.8912 and 30.6693, respectively. Visual evaluation results on both simulated and clinical images also show that using FS-MAR method generates less image artifacts than using the interpolation-based algorithm. CONCLUSIONS: This study demonstrated that with the same prior image, applying the proposed Poisson FS-MAR method can achieve the higher image quality than using the interpolation-based algorithm.
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Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador , Metales , Fantasmas de Imagen , Tomografía Computarizada por Rayos XRESUMEN
The reaction of readily available and bench-stable N-alkoxypyridinium salts with arylboronic and vinylboronic acids afforded δ-aryl and δ-vinyl alcohols, respectively, in the presence of fac-Ir(ppy)3 and Cu(OTf)2 dual catalysts. The reaction takes place through a domino process involving the reductive generation of alkoxyl radicals, 1,5-hydrogen atom transfer (1,5-HAT) and the copper-catalyzed cross-coupling reaction of the resulting translocated carbon radicals with boronic acids. Complementary to the Minisci reaction, this method allows for the arylation of nucleophilic alkyl radicals with both electron-rich and electron-poor arenes under mild reaction conditions.