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BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Femenino , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/efectos adversos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/radioterapia , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Oxaliplatino/efectos adversos , Quimioradioterapia/métodos , Quimioradioterapia/mortalidad , Quimioradioterapia/efectos adversos , Capecitabina/administración & dosificación , Capecitabina/efectos adversosRESUMEN
Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) be light enough for use in mice; (3) allow reuse of the probes after explantation. Here, we present the "Apollo Implant", an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a "payload" module that is attached to the probe and is recoverable, and a "docking" module that is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across seven labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.
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We present an erratum to our Letter [Opt. Lett.40, 4249 (2015)OPLEDP0146-959210.1364/OL.40.004249]. This erratum corrects the nuclear Lande factor gI in Eq. (2). After correcting the error, the final ground-state hyperfine splitting frequency of the 113Cd+ ion is determined to be 15199862855.0287(10) Hz.
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A series of sulfonamide derivatives were synthesized, and the enzyme inhibitory activity of the synthesized compounds on carbonic anhydrase II was evaluated. Through molecular docking studies, it was found that compounds 1b, 1e, 2a, 2b, 3a have a strong binding affinity to carbonic anhydrase II. The IC50 values of the four compounds 1e, 2b, 3a, and 3b were lower than that of the positive control drug acetazolamide. What's more, the compounds had a high inhibitory activity for A549 lung cancer cell growth, among them, 1e and 3a could inhibit both carbonic anhydrase II and lung cancer cell proliferation.
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Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica , Acetazolamida/farmacología , Anhidrasa Carbónica II/química , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Sulfonamidas/química , Sulfonamidas/farmacologíaRESUMEN
The aim of this study was to analyze the clinical features of a Rubinstein-Taybi syndrome (RSTS) case with neonatal glaucoma. We also wanted to explore the manifestation of the disease in combination with genotype-phenotype correlation. For DNA extraction we used 2 ml peripheral blood, collected from the child and parents. The extracted genomic DNA was used for clinical exome sequencing. A 38-day old baby boy was diagnosed with congenital glaucoma on the third day after birth with symptoms, including choking milk, feeding difficulties and slow weight gain. He was admitted to the neonatology department because of lung infection. The clinical exome sequencing showed that the child has a c.2368C>T heterozygous mutation in exome 13 in CREBBP (cAMP responsive element binding protein) while his parents have no such mutation. Combining genetic data with the clinical features, this infant was diagnosed with RSTS. This is the first report of RSTS caused by a c. 2368C>T mutation in CREBBP. RSTS is an extremely rare disease with extensive clinical manifestations. It is highly overlapped with other syndromes which makes the diagnosis difficult. RSTS is easy to be missed or misdiagnosed due to the lack of specific clinical manifestations during the neonatal period. Neonatal specialists need to enhance their awareness and recognition of this condition, and use genetic testing as an effective tool in order to finalize their diagnosis.
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Pruebas Genéticas , Glaucoma/genética , Síndrome de Rubinstein-Taybi/genética , Glaucoma/diagnóstico , Humanos , Lactante , Masculino , Mutación , Síndrome de Rubinstein-Taybi/diagnósticoRESUMEN
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ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad , Tuberculosis Pulmonar/genética , Adulto , Pueblo Asiatico , Estudios de Casos y Controles , China/epidemiología , Femenino , Dosificación de Gen , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Tuberculosis Pulmonar/epidemiologíaRESUMEN
In this study, structures and behaviours of acoustic cavitation bubbles induced by a high-intensity focused ultrasound (HIFU) transducer, operating at its resonance frequency of 250kHz, are experimentally explored with corresponding observations captured by a high-speed video camera system. The experiments were conducted in an open-top Perspex water tank with deionized water, and illumination was provided by a LED spotlight which is placed beside the water tank throughout the whole experiment. Experimental results show that the structure of ultrasonically generated bubbles forms in a conical shape with several concentric bubble rings above the transducer. The distance between the adjacent rings with equal spacing as determined by the driving frequency of the HIFU transducer is experimentally measured and compared with the theoretical value. Then, the distribution of acoustic pressure in the acoustically driven liquid is further studied to investigate the behaviours of cavitation bubbles generated in a HIFU field. Additionally, the analysis of Bjerknes forces on the bubble surface which are induced by the gradient of acoustic pressure and the adjacent oscillating bubbles is quantitatively carried out, and the radius and velocity of a typical larger bubble are measured to characterize the behaviours of ultrasonically induced bubbles. Particularly, the physical phenomena of large bubbles including the coalescence, attraction or repulsion between adjacent bubbles, as well as the jumping of an acoustic bubble from the lower concentric ring level to the higher level, are analysed. The moving trajectory of the bubble is next obtained, and some conclusions are summarized to provide a greater understanding of the complex behaviours of the ultrasonically generated bubbles.
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OBJECTIVE: To detect Mycobacterium tuberculosis (MTB) and rifampin resistance of the clinical specimens in children by Xpert MTB DNA and resistance to rifampicin(MTB/RIF) detection system, and evaluate the application value of this method in children with tuberculosis. METHOD: Data of 109 children cases of clinically suspected tuberculosis were collected (including 46 gastric lavage aspirate, 19 sputum, 10 fine needle aspiration biopsy, 4 pus, 14 cerebrospinal fluid, 11 Serous membrance fluid, 1 marrow, 3 stool, 1 urine specimens)between April 2014 and March 2015. All specimens were detected by smear fluorescence staining microscopy, MGIT 960 BACTEC liquid culture, Xpert MTB/RIF assay and T-SPOT.TB test respectively. The sensitivity and specificity of Xpert MTB/RIF assay were analyzed in those clinical specimens. RESULT: The sensitivity and specificity of the Xpert MTB/RIF assay for MTB detection in childhood tuberculosis clinical specimen were 28.6% and 87.5%. The sensitivity of 65 pulmonary tuberculosis(46 gastric lavage aspirate, 19 sputum) which included gastric lavage aspirates and sputum was 33.3% and 57.1%, the specificity of the two was 100.0%. In 44 extrapulmonary tuberculosis, the sensitivity of the pus and the puncture fluid was higher and approached 100.0%. The detection rate of the cerebrospinal fluid and serous cavity effusion was very low. The sensitivity was 100.0% in smear-positive and culture-positive samples and only 30.8% to 50.0% in smear-negative and culture-positive samples. The sensitivity and specificity of Xpert MTB/RIF assay to detect rifampin resistance were 100.0%. In clinical samples, the sensitivity of Xpert MTB/RIF assay was higher than that of smear fluorescence staining microscopy, but the difference was not statistically significant (χ(2)=0, P>0.05). The result was equivalent to that of MGIT 960 BACTEC liquid culture (28.6% vs. 27.3%, χ(2)=2.50, P>0.05), and far below that of T-SPOT.TB(28.6% vs 59.7%, χ(2)=13.92, P<0.05). CONCLUSION: Xpert MTB/RIF assay did not show obvious advantage in childhood tuberculosis, especially in serous cavity effusion and cerebrospinal fluid, but the advantages of detecting tuberculosis rapidly and resistance to rifampin can provide help for the clinical diagnosis and treatment in childrenhood tuberculosis.
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Farmacorresistencia Bacteriana , Técnicas de Diagnóstico Molecular/métodos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis/diagnóstico , Niño , ADN Bacteriano/aislamiento & purificación , Humanos , Mycobacterium tuberculosis/efectos de los fármacos , Rifampin/farmacología , Sensibilidad y Especificidad , Esputo/microbiologíaRESUMEN
OBJECTIVE: To observe the one-year neurologic prognostic outcome of newborns with moderate and severe hypoxic-ischemic encephalopathy (HIE) who received recombinant human erythropoietin (rhuEPO) combined with exogenous monosialotetrahexosylganglioside (GM1) treatment to provide new guidelines for clinical treatment. PATIENTS AND METHODS: Seventy-six newborns with moderate and severe HIE were selected from February 2011 to February 2014 in our hospital. This study received the informed consent of our hospital's Ethics Committee and the newborns' guardians. The newborns were divided to an observation group (n = 34 cases) and a control group (n = 42 cases). All newborns underwent hypothermia and conventional treatment for their conditions. The control group received GMl treatment and observation group received rhuEPO combined with GMl treatment. The curative differences and neural behavior from these two groups were compared. RESULTS: The excellent, efficient proportion and total effective rate of the newborns from the observation group were higher than the control group. The death rate, cerebral palsy and the invalid ratio of the newborns from the observation group were lower than that of the control group. Awareness, muscle tension, primitive reflex and increased intracranial pressure recovery time of the newborns in the observation group were less than those of the control group. The Neonatal Behavior Neurological Assessment (NBNA) score of both groups after the treatment of 7, 14 and 28 days were significantly higher and increased with time (p < 0.05). The MDI, PDI and DQ score of newborns from the two groups all increased after treatment of 3, 6 and 12 months than those of before, which increased with time (p < 0.05). CONCLUSIONS: The rhuEPO + GMl treatment in newborns with HIE improves short-term clinical effects and long-term neurological symptoms.
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Eritropoyetina/administración & dosificación , Hipoxia-Isquemia Encefálica/diagnóstico , Hipoxia-Isquemia Encefálica/tratamiento farmacológico , Proteínas Recombinantes/administración & dosificación , Índice de Severidad de la Enfermedad , Proteínas Activadoras de Esfingolípidos/administración & dosificación , Parálisis Cerebral/diagnóstico , Parálisis Cerebral/tratamiento farmacológico , Quimioterapia Combinada , Femenino , Humanos , Recién Nacido , Masculino , Examen Neurológico/métodos , Pronóstico , Resultado del TratamientoRESUMEN
A bubble initiated near a rigid boundary may be almost in contact with the boundary because of its expansion and migration to the boundary, where a thin layer of water forms between the bubble and the boundary thereafter. This phenomenon is modelled using the weakly compressible theory coupled with the boundary integral method. The wall effects are modelled using the imaging method. The numerical instabilities caused by the near contact of the bubble surface with the boundary are handled by removing a thin layer of water between them and joining the bubble surface with its image to the boundary. Our computations correlate well with experiments for both the first and second cycles of oscillation. The time history of the energy of a bubble system follows a step function, reducing rapidly and significantly because of emission of shock waves at inception of a bubble and at the end of collapse but remaining approximately constant for the rest of the time. The bubble starts being in near contact with the boundary during the first cycle of oscillation when the dimensionless stand-off distance γ = s/R m < 1, where s is the distance of the initial bubble centre from the boundary and R m is the maximum bubble radius. This leads to (i) the direct impact of a high-speed liquid jet on the boundary once it penetrates through the bubble, (ii) the direct contact of the bubble at high temperature and high pressure with the boundary, and (iii) the direct impingement of shock waves on the boundary once emitted. These phenomena have clear potential to damage the boundary, which are believed to be part of the mechanisms of cavitation damage.
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A microwave frequency standard based on laser-cooled (113)Cd(+) ions has been developed in recent years, and the short-term frequency instability is measured to be 6.1×10(-13)/âτ. By comparing the Cd(+) clock to a superior frequency reference, the ground-state hyperfine splitting of (113)Cd(+) is measured precisely to be 15199862855.0192(10) Hz with a fractional precision of 6.6×10(-14). This result is consistent with previous results, and the measurement precision is improved by nearly one order more than the best result reported before.
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OBJECTIVE: To investigate the effect of vascular bradykinin on pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis (SAP). MATERIALS AND METHODS: Ninety male Wistar rats were randomly divided into a blank control group, an SAP group and a vascular bradykinin treatment group. The SAP model was induced by the retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The vascular bradykinin treatment group underwent gastrostomy, with a fine plastic tube placed in the stomach that led out of body through the abdominal wall.Vascular bradykinin was fully dissolved and administered at a dose of 20 U/kg once every 8 h. The pancreatic microcirculatory blood flow volume and velocity, microvascular permeability, hemorheology were evaluated respectively by double-channel laser Doppler flowmetry, the Evans blue leakage test, a blood rheology test instrument. RESULTS: The pancreatic microcirculatory blood flow volume and velocity in the vascular bradykinin treatment group increased gradually after 48 h compared with the SAP group, and the changes were significantly different (p < 0.05). The pancreatic microvascular permeability of the vascular bradykinin treatment group was significantly reduced after 48 h compared with the SAP group (p < 0.05). The low shear rate blood viscosity, hematocrit and erythrocyte aggregation index of the vascular bradykinin treatment group were significantly decreased after 48 h compared with the SAP group (p < 0.05). CONCLUSIONS: Vascular bradykinin can improve pancreatic microcirculation and hemorheology in rats with severe acute pancreatitis.
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Bradiquinina/administración & dosificación , Hemorreología/efectos de los fármacos , Microcirculación/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Animales , Hemorreología/fisiología , Infusiones Parenterales , Masculino , Microcirculación/fisiología , Páncreas/irrigación sanguínea , Pancreatitis/patología , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
Genotyping is a critical step for molecular marker-assisted selection in rice. Rice genomic DNA samples for genotyping are typically isolated from living tissues such as seedlings. This requires the germination of all candidate seeds and extraction of DNA from the seedlings. Currently, an ideal individual is selected from a very large number of plants, which is time- and labor-consuming, requiring several transplantations of materials and sampling processes. In this study, we developed a simplified genomic DNA extraction protocol in rice by using amylase to treat half-seeds. The yields of genomic DNA from a half-seed of Indica and Japonica rice were greater than 203.8 ± 32.5 and 143.2 ± 25.5 ng, respectively, and the 260/280 nm absorbance ratio was 1.75-2.10. The DNA was confirmed to be sufficient for polymerase chain reaction amplification and can be used in a marker-assisted selection program.
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ADN de Plantas/aislamiento & purificación , Genómica , Germinación/genética , Oryza/genética , ADN de Plantas/genética , Genoma de Planta , Genotipo , Plantones/genética , Semillas/genéticaRESUMEN
Recent progress in computational methods for inves-tigating physical and functional gene interactions has provided new insights into the complexity of biological processes. An essential part of these methods is presented visually in the form of gene interaction networks that can be valuable in exploring the mechanisms of disease. Here, a combined network based on gene pairs with an extra layer of re-liability was constructed after converting and combining the gene pair scores using a novel algorithm across multiple approaches. Four groups of kidney cancer data sets from ArrayExpress were downloaded and analyzed to identify differentially expressed genes using a rank prod-ucts analysis tool. Gene co-expression network, protein-protein interac-tion, co-occurrence network and a combined network were constructed using empirical Bayesian meta-analysis approach, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, an odds ratio formula of the cBioPortal for Cancer Genomics and a novel rank algorithm with combined score, respectively. The topological features of these networks were then compared to evaluate their performances. The results indicated that the gene pairs and their relationship rank-ings were not uniform. The values of topological parameters, such as clustering coefficient and the fitting coefficient R(2) of interaction net-work constructed using our ranked based combination score, were much greater than the other networks. The combined network had a classic small world property which transferred information quickly and displayed great resilience to the dysfunction of low-degree hubs with high-clustering and short average path length. It also followed distinct-ly a scale-free network with a higher reliability.
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Algoritmos , Redes Reguladoras de Genes , Neoplasias Renales/genética , Proteínas de Neoplasias/genética , Mapeo de Interacción de Proteínas/estadística & datos numéricos , Teorema de Bayes , Bases de Datos Genéticas , Epistasis Genética , Perfilación de la Expresión Génica , Humanos , Neoplasias Renales/patología , Proteínas de Neoplasias/metabolismo , Reproducibilidad de los Resultados , Transducción de SeñalRESUMEN
BACKGROUND AND PURPOSE: Treating MS with disease-modifying drugs relies on accurate MR imaging follow-up to determine the treatment effect. We aimed to develop and validate a semiautomated software platform to facilitate detection of new lesions and improved lesions. MATERIALS AND METHODS: We developed VisTarsier to assist manual comparison of volumetric FLAIR sequences by using interstudy registration, resectioning, and color-map overlays that highlight new lesions and improved lesions. Using the software, 2 neuroradiologists retrospectively assessed MR imaging MS comparison study pairs acquired between 2009 and 2011 (161 comparison study pairs met the study inclusion criteria). Lesion detection and reading times were recorded. We tested inter- and intraobserver agreement and comparison with original clinical reports. Feedback was obtained from referring neurologists to assess the potential clinical impact. RESULTS: More comparison study pairs with new lesions (reader 1, n = 60; reader 2, n = 62) and improved lesions (reader 1, n = 28; reader 2, n = 39) were recorded by using the software compared with original radiology reports (new lesions, n = 20; improved lesions, n = 5); the difference reached statistical significance (P < .001). Interobserver lesion number agreement was substantial (≥1 new lesion: κ = 0.87; 95% CI, 0.79-0.95; ≥1 improved lesion: κ = 0.72; 95% CI, 0.59-0.85), and overall interobserver lesion number correlation was good (Spearman ρ: new lesion = 0.910, improved lesion = 0.774). Intraobserver agreement was very good (new lesion: κ = 1.0, improved lesion: κ = 0.94; 95% CI, 0.82-1.00). Mean reporting times were <3 minutes. Neurologists indicated retrospective management alterations in 79% of comparative study pairs with newly detected lesion changes. CONCLUSIONS: Using software that highlights changes between study pairs can improve lesion detection. Neurologist feedback indicated a likely impact on management.
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Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/patología , Neuroimagen/métodos , Programas Informáticos , Adulto , Humanos , Masculino , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
This study aims to investigate the accuracy and value of multislice spiral computed tomography (MSCT) angiography in the evaluation of renal artery variation in living donor kidney transplantation. Two hundred seventy-three kidney transplantation donors underwent preoperative MSCT scanning. Two doctors determined the running direction and variation of the renal artery through joint analysis of the preoperative original MSCT image and the recombination image using the blind reading method, compared the imaging results with the intraoperative results, and evaluated the accuracy and application value of MSCT angiography in the evaluation of renal artery variation in living donor kidney transplantation. CT angiography (CTA) can better show the renal artery and its variation. A total of 52 accessory renal arteries were found in the 273 kidney transplant operations, whereas 55 accessory renal arteries were found in preoperative MSCT. Four accessory renal arteries indicated in the MSCT were not found during the operation, and one accessory renal artery found during the operation was not indicated in the preoperative MSCT. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MSCT in the diagnosis of accessory renal arteries were 98.1, 98.2, 92.7, 99.5, and 98.2%, respectively. MSCT angiography can sensitively and accurately show the renal artery and its variation in living donor kidney transplantation, and has important clinical value for the formulation of the operative scheme before the transplantation.
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Angiografía/métodos , Trasplante de Riñón , Donadores Vivos , Arteria Renal/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Adulto , Anciano , Femenino , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
We report findings of strong anomalies in both mutual inductance and inelastic Raman spectroscopy measurements of single-unit-cell FeSe film grown on Nb-doped SrTiO3, which occur near the temperature where the superconductinglike energy gap opens. Analysis suggests that the anomaly is associated with a broadened ferroelectric transition in a thin layer near the FeSe/SrTiO3 interface. The coincidence of the ferroelectric transition and gap-opening temperatures adds credence to the central role played by the film-substrate interaction on the strong Cooper pairing in this system. We discuss scenarios that could explain such a coincidence.