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INTRODUCTION: Craniofacial morphology and ethnicity may be risk factors for sleep-related breathing disorder (SRBD) in children but have not yet been assessed in an international multicenter study. The objectives of this study were to assess the association among craniofacial features, self-reported ethnicity, and risk of SRBD in children undergoing orthodontic treatment. METHODS: Children aged 5-18 years who presented for orthodontic evaluation were enrolled in the United States, South Africa, South Korea, Saudi Arabia, and Japan. The risk of SRBD was defined as answering ≥0.33 positive responses to the Pediatric Sleep Questionnaire. Craniofacial features included measurements in sagittal and vertical dimensions to evaluate the cranial base, maxillomandibular and dental relationships, and nasopharyngeal airway dimensions. Logistic regression was performed to assess the association among craniofacial features, ethnicity, age, body mass index, and risk of SRBD. RESULTS: Data were obtained from 602 patients from 5 sites. A total of 76 patients (12.6%) had a risk of SRBD. The mean age was 12.5 years. Male gender (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.0-3.4; P = 0.041), Middle Eastern ethnicity (OR, 10.2; 95% CI, 4.1-25.4; P = 0.001), body mass index (OR, 1.1; 95% CI, 1.04-1.10; P = 0.001), gonial angle (OR, 0.91; 95% CI, 0.85-0.98; P = 0.011), and inferiorly positioned hyoid (OR, 1.1; 95% CI, 1.0-1.2; P = 0.002) were significantly associated with the risk of SRBD. CONCLUSIONS: In an ambidirectional cohort study across 5 sites, male gender, Middle Eastern ethnicity, body mass index, gonial angle, and inferiorly positioned hyoid were associated with the risk of SRBD in children undergoing orthodontic treatment.
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Síndromes de la Apnea del Sueño , Humanos , Masculino , Niño , Estados Unidos , Síndromes de la Apnea del Sueño/complicaciones , Estudios de Cohortes , Etnicidad , Sueño , RespiraciónRESUMEN
Design of metal cofactor ligands is essential for controlling the reactivity of metalloenzymes. We investigated a carbene transfer reaction catalyzed by myoglobins containing iron porphyrin cofactors with one and two trifluoromethyl groups at peripheral sites (FePorCF3 and FePor(CF3)2, respectively), native heme and iron porphycene (FePc). These four myoglobins show a wide range of Fe(II)/Fe(III) redox potentials in the protein of +147â mV, +87â mV, +42â mV and -198â mV vs. NHE, respectively. Myoglobin reconstituted with FePor(CF3)2 has a more positive potential, which enhances the reactivity of a carbene intermediate with alkenes, and demonstrates superior cyclopropanation of inert alkenes, such as aliphatic and internal alkenes. In contrast, engineered myoglobin reconstituted with FePc has a more negative redox potential, which accelerates the formation of the intermediate, but has low reactivity for inert alkenes. Mechanistic studies indicate that myoglobin with FePor(CF3)2 generates an undetectable active intermediate with a radical character. In contrast, this reaction catalyzed by myoglobin with FePc includes a detectable iron-carbene species with electrophilic character. This finding highlights the importance of redox-focused design of the iron porphyrinoid cofactor in hemoproteins to tune the reactivity of the carbene transfer reaction.
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Mioglobina , Oxidación-Reducción , Mioglobina/química , Mioglobina/metabolismo , Ingeniería de Proteínas , Ciclopropanos/química , Metaloporfirinas/química , Metano/química , Metano/análogos & derivadosRESUMEN
BACKGROUND: Circulatory failure is classified into four types of shock (obstructive, cardiogenic, distributive, and hypovolemic) that must be distinguished as each requires a different treatment. Point-of-care ultrasound (POCUS) is widely used in clinical practice for acute conditions, and several diagnostic protocols using POCUS for shock have been developed. This study aimed to evaluate the diagnostic accuracy of POCUS in identifying the etiology of shock. METHODS: We conducted a systematic literature search of MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Web of Science, Clinicaltrial.gov, European Union Clinical Trials Register, WHO International Clinical Trials Registry Platform, and University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) until June 15, 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-analysis was conducted to pool the diagnostic accuracy of POCUS for each type of shock. The study protocol was prospectively registered in UMIN-CTR (UMIN 000048025). RESULTS: Of the 1553 studies identified, 36 studies were full-text reviewed, and 12 studies with 1132 patients were included in the meta-analysis. Pooled sensitivity and specificity were 0.82 [95% confidence interval (CI) 0.68-0.91] and 0.98 [95% CI 0.92-0.99] for obstructive shock, 0.78 [95% CI 0.56-0.91] and 0.96 [95% CI 0.92-0.98] for cardiogenic shock, 0.90 [95% CI 0.84-0.94] and 0.92 [95% CI 0.88-0.95] for hypovolemic shock, and 0.79 [95% CI 0.71-0.85] and 0.96 [95% CI 0.91-0.98] for distributive shock, respectively. The area under the receiver operating characteristic curve for each type of shock was approximately 0.95. The positive likelihood ratios for each type of shock were all greater than 10, especially 40 [95% CI 11-105] for obstructive shock. The negative likelihood ratio for each type of shock was approximately 0.2. CONCLUSIONS: The identification of the etiology for each type of shock using POCUS was characterized by high sensitivity and positive likelihood ratios, especially for obstructive shock.
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Sistemas de Atención de Punto , Choque , Humanos , Ultrasonografía/métodos , Pruebas en el Punto de Atención , Choque/diagnóstico por imagen , Sensibilidad y EspecificidadRESUMEN
Experimental characterization of the nanostructure of metastable functional materials has attracted significant attention with recent advances in computational materials discovery. However, since metastable glass-ceramics are easily damaged by irradiation, damage-free nanoimaging has not been realized thus far. Herein, we propose novel high-contrast coherent diffractive imaging that quantitatively analyzes the intact internal nanostructure of metastable glass-ceramics using femtosecond X-ray pulses. The immersion of sample particles in a solvent helps enhance the reconstructed image contrast and allows us to distinguish an â¼7% electron density difference between an amorphous form and crystals. Furthermore, morphological operations with a band-pass filter quantitatively elucidate the depth information. The evaluated volume ratio of the amorphous to crystalline phases is â¼2.5:1 for the measured metastable (Li2S)70-(P2S5)30 glass-ceramic particle. Sulfide glass-ceramics are used as electrolytes for all-solid-state batteries, which are indispensable for reducing the carbon footprint. Our results will facilitate structural studies on fragile metastable materials with important scientific and industrial implications.
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Heme binds selectively to the 3'-terminal G-quartet of all parallel G-quadruplex DNAs to form stable heme-DNA complexes. Interestingly, the heme-DNA complexes exhibit various spectroscopic and functional properties similar to those of hemoproteins. Since the nature of the axial ligands is crucial in determining the physicochemical properties of heme, identification and characterization of the axial ligands in a heme-DNA complex are essential to elucidate the structure-function relationship in the complex. NMR studies of a complex possessing a low-spin ferric heme with a water molecule (H2O) and cyanide ion (CN-) as the axial ligands allowed detailed characterization of the physicochemical nature of the axial H2O ligand. We found that the in-plane asymmetry of the heme electronic structure of the complex is not largely affected by the axial H2O coordination, indicating that the H2O confined in the hydrophobic interface between the heme and G-quartet planes of the complex rotates about the coordination bond with respect to the heme. The effect of the hydrogen(H)/deuterium(D) isotope replacement of the axial H2O on the heme electronic structure was manifested in the isotope shifts of paramagnetically shifted heme methyl proton signals of the complex in such a manner that three resolved peaks associated with axial H2O, HDO, and D2O were observed for each of the heme methyl proton signals. These findings provide not only the basis for an understanding of the nature of the unique axial H2O but also an insight into the molecular mechanism responsible for the control of the heme reactivity in the heme-DNA complex.
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G-Cuádruplex , Hemoproteínas , ADN/química , Hemo/química , LigandosRESUMEN
Nondestructive testing of concrete materials is essential in civil engineering to maintain social infrastructure such as buildings or bridges. In this study, we constructed an ultralow-frequency, ultranarrow-bandwidth, coherent terahertz (THz) imaging system based on THz time-domain spectroscopy (THz-TDS). Based on its ultralow-frequency-localized THz wave and coherent detection, the present system achieved a wide dynamic range of THz power over 100 dB at 0.046 THz, which is appropriate to measure the mortar material. The achieved dynamic range of the THz power was 59 dB larger than that of a commercialized THz-TDS system and 49 dB larger than that of an ultralow-frequency noncoherent THz imaging system equipped with a high-power electric THz source. Ultimately, the proposed system could visualize the inner structure of a mortar sample with a thickness of 10 mm, and the present system can investigate a mortar sample with a thickness of over 130 mm. The proposed method is an attractive tool for non-destructive testing of thick concrete structures characterized by non-invasiveness and non-contact remoteness.
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Using a new implantation technique with multielement molecular ions consisting of carbon, hydrogen, and phosphorus, namely, CH2P molecular ions, we developed an epitaxial silicon wafer with proximity gettering sinks under the epitaxial silicon layer to improve the gettering capability for metallic impurities. A complementary metal-oxide-semiconductor (CMOS) image sensor fabricated with this novel epitaxial silicon wafer has a markedly reduced number of white spot defects, as determined by dark current spectroscopy (DCS). In addition, the amount of nickel impurities gettered in the CH2P-molecular-ion-implanted region of this CMOS image sensor is higher than that gettered in the C3H5-molecular-ion-implanted region; and this implanted region is formed by high-density black pointed defects and deactivated phosphorus after epitaxial growth. From the obtained results, the CH2P-molecular-ion-implanted region has two types of complexes acting as gettering sinks. One includes carbon-related complexes such as aggregated C-I, and the other includes phosphorus-related complexes such as P4-V. These complexes have a high binding energy to metallic impurities. Therefore, CH2P-molecular-ion-implanted epitaxial silicon wafers have a high gettering capability for metallic impurities and contribute to improving the device performance of CMOS image sensors. (This manuscript is an extension from a paper presented at the 6th IEEE Electron Devices Technology & Manufacturing Conference (EDTM 2022)).
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Non-alcoholic fatty liver disease (NAFLD) is associated with the chronic progression of fibrosis. In general, the progression of liver fibrosis is determined by a histopathological assessment with a collagen-stained section; however, the ultra-early stage of liver fibrosis is challenging to identify because of the low sensitivity in the collagen-selective staining method. In the present study, we demonstrate the feasibility of second-harmonic generation (SHG) microscopy in the histopathological diagnosis of the liver of NAFLD patients for the quantitative assessment of the ultra-early stage of fibrosis. We investigated four representative NAFLD patients with early stages of fibrosis. SHG microscopy visualised well-matured fibrotic structures and early fibrosis diffusely involving liver tissues, whereas early fibrosis is challenging to be identified by conventional histopathological methods. Furthermore, the SHG emission directionality analysis revealed the maturation of each collagen fibre of each patient. As a result, SHG microscopy is feasible for assessing liver fibrosis on NAFLD patients, including the ultra-early stage of liver fibrosis that is difficult to diagnose by the conventional histopathological method. The assessment method of the ultra-early fibrosis by using SHG microscopy may serve as a crucial means for pathological, clinical, and prognostic diagnosis of NAFLD patients.
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Enfermedad del Hígado Graso no Alcohólico , Microscopía de Generación del Segundo Armónico , Biopsia/métodos , Colágeno , Fibrosis , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
Extrapulmonary neuroendocrine carcinoma (EPNEC) is a lethal disease with a poor prognosis. Platinum-based chemotherapy is used as the standard first-line treatment for unresectable EPNEC. Several retrospective studies have reported the results of the utilization of temozolomide (TMZ) as a drug for the second-line treatment for EPNEC. Patients with unresectable EPNEC that were resistant to platinum-based combination chemotherapy were recruited for a prospective phase II study of TMZ monotherapy. A 200 mg/m2 dose of TMZ was given from day 1 to day 5, every 4 weeks. Response rate (RR) was evaluated as the primary end-point. The presence of O6 -methylguanine DNA methyltransferase (MGMT) in EPNEC patients was also evaluated as exploratory research. Thirteen patients were enrolled in this study. Primary lesions were pancreas (n = 3), stomach (n = 3), duodenum (n = 1), colon (n = 1), gallbladder (n = 1), liver (n = 1), uterus (n = 1), bladder (n = 1), and primary unknown (n = 1). Each case was defined as pathological poorly differentiated neuroendocrine carcinoma from surgically resected and/or biopsied specimens. The median Ki-67 labeling index was 60% (range, 22%-90%). The RR was 15.4%, progression-free survival was 1.8 months (95% confidence interval [CI], 1.0-2.7), overall survival (OS) was 7.8 months (95% CI, 6.0-9.5), and OS from first-line treatment was 19.2 months (95% CI, 15.1-23.3). No grade 3 or 4 hematological toxicity had occurred and there was one case of grade 3 nausea. One case presented MGMT deficiency and this case showed partial response. Temozolomide monotherapy is a feasible, modestly effective, and safe treatment for patients with unresectable EPNEC following platinum-based chemotherapy, especially those with MGMT deficiency.
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Antineoplásicos Alquilantes/uso terapéutico , Carcinoma Neuroendocrino/tratamiento farmacológico , Temozolomida/uso terapéutico , Adulto , Anciano , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/enzimología , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Esquema de Medicación , Neoplasias Duodenales/tratamiento farmacológico , Neoplasias Duodenales/enzimología , Neoplasias Duodenales/patología , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/enzimología , Neoplasias de la Vesícula Biliar/patología , Humanos , Antígeno Ki-67/análisis , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/enzimología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , O(6)-Metilguanina-ADN Metiltransferasa/análisis , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/enzimología , Neoplasias Pancreáticas/patología , Supervivencia sin Progresión , Estudios Prospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/enzimología , Neoplasias Gástricas/patología , Temozolomida/administración & dosificación , Temozolomida/efectos adversos , Neoplasias Uterinas/tratamiento farmacológico , Neoplasias Uterinas/enzimología , Neoplasias Uterinas/patologíaRESUMEN
The catalytic cycle of a peroxidase-mimicking heme-DNAzyme involves an iron(IV)oxo porphyrin π-cation radical intermediate known as compound I formed through heterolytic O-O bond cleavage of an Fe3+-bound hydroperoxo ligand (Fe-OOH) in compound 0, like that of a heme enzyme such as horseradish peroxidase (HRP). Peroxidase assaying of complexes composed of chemically modified hemes possessing various electron densities of the heme iron atom (ρFe) and parallel-stranded tetrameric G-quadruplex DNAs of oligonucleotides d(TTAGGG), d(TTAGGGT), and d(TTAGGGA) was performed to elucidate the effects of the heme electronic structure and local heme environment on the catalytic activity of the heme-DNAzyme. The study revealed that the DNAzyme activity is enhanced through an increase in the ρFe and general base catalysis of the adenine base adjacent to the heme, which are reminiscent of the "push" and "pull" mechanisms in the catalytic cycle of HRP, respectively, and that the activity of the heme-DNAzyme can be independently controlled through the heme electronic structure and local heme environment. These findings allow a deeper understanding of the structure-function relationship of the peroxidase-mimicking heme-DNAzyme.
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Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo , ADN Catalítico/química , ADN Catalítico/metabolismo , Hemo/química , Hemo/metabolismo , Peroxidasa/metabolismo , Biocatálisis , ElectronesRESUMEN
Mössbauer spectroscopy has been used to characterize oxygenated myoglobins (oxy Mbs) reconstituted with native and chemically modified 57Fe-enriched heme cofactors with different electron densities of the heme Fe atom (ρFe) and to elucidate the effect of a change in the ρFe on the nature of the bond between heme Fe and oxygen (O2), i.e., the Fe-O2 bond, in the protein. Quadrupole splitting (ΔEQ) was found to decrease with decreasing ρFe, and the observed ρFe-dependent ΔEQ confirmed an increase in the contribution of the ferric-superoxide (Fe3+-O2-) form to the resonance hybrid of the Fe-O2 fragment with decreasing ρFe. These observations explicitly accounted for the lowering of O2 affinity of the protein due to an increase in the O2 dissociation rate and a decrease in the autoxidation reaction rate of oxy Mb through decreasing H+ affinity of the bound ligand with decreasing ρFe. Therefore, the present study demonstrated the mechanism underlying the electronic control of O2 affinity and the autoxidation of the protein through the heme electronic structure. Carbon monoxide (CO) adducts of reconstituted Mbs (CO-Mbs) were similarly characterized, and we found that the resonance between the two canonical forms of the Fe-CO fragment was also affected by a change in ρFe. Thus, the nature of the Fe-ligand bond in the protein was found to be affected by the ρFe.
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Hemo/química , Hierro/química , Mioglobina/química , Oxígeno/química , Monóxido de Carbono/química , Electrones , Estructura Molecular , Espectroscopía de MossbauerRESUMEN
BACKGROUND: High-resolution intravascular ultrasound (HR-IVUS) is the most recently developed IVUS technology, which allows the detailed assessment of intravascular structures. The aim of this study was to evaluate the diagnostic performance of HR-IVUS in the detection of abnormal post-stent findings.MethodsâandâResults:Patients with acute coronary syndrome underwent both HR-IVUS and optical coherence tomography (OCT) for post-stent evaluations. Quantitative measurements for stented segments and qualitative assessments for abnormal post-stent findings (stent edge dissection, intrastent tissue protrusion, and incomplete stent apposition [ISA]) were performed. Forty-seven patients underwent both HR-IVUS and OCT after stent implantation. HR-IVUS identified a larger minimal lumen area and a larger minimal lumen diameter than OCT (6.66±1.98 mm2vs. 5.61±1.79 mm2and 2.87±0.42 mm vs. 2.63±0.43 mm, respectively; both P<0.001). The sensitivity of HR-IVUS for the identification of stent edge dissection, intrastent tissue protrusion, and ISA were 20.0%, 48.9%, and 27.2%, respectively. CONCLUSIONS: In terms of post-stent evaluation, the diagnostic performance of HR-IVUS remains insufficient. Abnormal post-stent findings might be underestimated when performing HR-IVUS due to its low sensitivity.
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Enfermedad de la Arteria Coronaria , Tomografía de Coherencia Óptica , Ultrasonografía Intervencional , Vasos Coronarios/diagnóstico por imagen , Humanos , Stents , Resultado del TratamientoRESUMEN
Although drug-eluting stents have improved clinical outcomes, percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remains a challenging procedure in terms of thrombus management. A new-generation P2Y12 receptor inhibitor, prasugrel, provides more rapid and potent antiplatelet action compared with clopidogrel. Prasugrel achieved significant reduction of ischemic events compared with clopidogrel in ACS. The aim of this optical coherence tomography (OCT) study was to evaluate temporal changes in tissue prolapse after stenting under different antiplatelet regimens (aspirin plus prasugrel or clopidogrel) in ACS patients. A total of 119 ACS patients were randomized to either prasugrel or clopidogrel at the time of PCI. OCT analysis was available in 119 patients at baseline (just after stenting), 77 patients at 2 weeks, and 62 patients at 4 months after stenting. Cross-sectional analysis for every 1 mm was performed at in-stent and adjacent reference segment. Tissue prolapse area was calculated by lumen area minus stent area within the stented segment. Baseline patient and procedural characteristics were not different between the prasugrel and clopidogrel groups. Tissue prolapse area was significantly lower in the prasugrel compared with the clopidogrel group after stenting (0.24 ± 0.23 vs. 0.36 ± 0.23 mm2, p = 0.003) and at 2 weeks (0.11 ± 0.13 vs. 0.19 ± 0.16 mm2, p = 0.005). However, there was no significant difference at 4 months. In conclusion, our study suggests prasugrel was effective in reducing tissue prolapse in the super acute phase in ACS patients compared with clopidogrel. However, the effect of tissue prolapse reduction was not different up to 4 months follow-up.
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Síndrome Coronario Agudo/terapia , Vasos Coronarios/diagnóstico por imagen , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tomografía de Coherencia Óptica/métodos , Síndrome Coronario Agudo/diagnóstico , Anciano , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The resting full-cycle ratio (RFR), a novel resting index, is well correlated with and shows good diagnostic accuracy to the fractional flow reserve (FFR). However, discordance results between the RFR and FFR have been observed to occur in about 20% of cases. This study aimed to clarify the prevalence and factors of discordant results between the RFR and FFR through a direct comparison of these values in daily clinical practice. A total of 220 intermediate coronary lesions of 156 consecutive patients with RFR and FFR measurements were allocated to four groups according to RFR and FFR cutoff values. We compared the angiographic, clinical, and hemodynamic variables among the groups. Discordant results between the RFR and FFR were observed in 19.6% of vessels, and the proportion of discordant results was significantly higher in the left main trunk and left anterior descending artery (LM + LAD) than in non-LAD vessels (25.2% vs. 12.3%, p = 0.006). In the multivariable regression analysis, LM + LAD location, hemodialysis, and peripheral artery disease were associated with a low RFR among patients with a high FFR. Conversely, the absence of diabetes mellitus and the presence of higher hemoglobin levels were associated with a higher RFR among patients with a low FFR. Specific angiographic and clinical characteristics such as LM + LAD location, hemodialysis, peripheral artery disease, and absence of diabetes mellitus and anemia can be independent predictors of physiologic discordance between the RFR and FFR.
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Estenosis Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Reserva del Flujo Fraccional Miocárdico/fisiología , Descanso/fisiología , Anciano , Cateterismo Cardíaco , Angiografía Coronaria , Estenosis Coronaria/diagnóstico , Vasos Coronarios/diagnóstico por imagen , Femenino , Estudios de Seguimiento , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
X-ray free-electron lasers (XFELs) opened up a possibility for molecular-scale single particle imaging (SPI) without the need for crystallization. In SPI experiments, the orientation of each particle has to be determined from the measured diffraction pattern. Preparing unidirectionally-aligned particles can facilitate the determination of the sample orientation. Here, we show the design principles of a liquid cell for three-dimensional imaging of unidirectionally-aligned particles in solution with XFELs. The liquid cell was designed so that neither incident X-rays nor diffracted X-rays are blocked by the substrate of the liquid cell even at high tilt angles. As a feasibility evaluation, we performed coherent diffraction measurements using the cells with a 1 µm focused XFEL beam. We successfully measured coherent diffraction patterns of a nano-fabricated metal pattern at 70° tilt angle and obtained the reconstructed image by applying iterative phase retrieval. The liquid cell will be usefully applied to molecular-scale SPI by using more tightly focused XFELs. In particular, imaging of membrane proteins embedded in lipid membranes is expected to have an enormous impact on life science and medicine.
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Imagenología Tridimensional/métodos , Rayos Láser , Electrones , Diseño de Equipo , Oro/química , Imagenología Tridimensional/instrumentaciónRESUMEN
The resting full-cycle ratio (RFR) is a new physiologic index to assess myocardial ischemia. RFR and fractional flow reserve (FFR), the conventionally used index, have not been directly compared in evaluating the entire cardiac cycle. Accordingly, we aimed to compare the diagnostic performance of RFR directly with FFR and clarify the clinical feasibility of RFR as a unique non-hyperemic index in evaluating the cardiac cycle. The diagnostic performance of RFR was compared with FFR using an automated online calculation software. A total of 156 consecutive patients with 220 intermediate lesions were enrolled. RFR showed significant correlation with FFR (r = 0.774, p < 0.001). RFR systole and RFR diastole did also with FFR (r = 0.918, p < 0.001, and r = 0.733, p < 0.001, respectively). With FFR < 0.80 as a reference standard, RFR showed good diagnostic accuracy (DA: 80.5%), similar DA between RFR systole and RFR diastole (79.6% and 87.5%, p = 0.58, respectively), and good DA in any lesion locations, especially in non-left anterior descending coronary artery (LAD) lesions (73.7% and 87.6% for LAD vs. non-LAD, p < 0.05, respectively). RFR is a feasible and reliable non-hyperemic index regardless of the difference in cardiac cycle in evaluating physiological lesion severity in daily practice.
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Cateterismo Cardíaco , Enfermedad de la Arteria Coronaria/diagnóstico , Circulación Coronaria , Estenosis Coronaria/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/fisiopatología , Estudios de Factibilidad , Femenino , Reserva del Flujo Fraccional Miocárdico , Humanos , Hiperemia/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Índice de Severidad de la EnfermedadRESUMEN
Novel mutant alleles related to isoflavone content are useful for breeding programs to improve the disease resistance and nutritional content of soybean. However, identification of mutant alleles from high-density mutant libraries is expensive and time-consuming because soybean has a large, complicated genome. Here, we identified the gene responsible for increased genistein-to-daidzein ratio in seed of the mutant line F333ES017D9. For this purpose, we used a time- and cost-effective approach based on selective genotyping of a small number of F2 plants showing the mutant phenotype with nearest-neighboring-nucleotide substitution-high-resolution melting analysis markers, followed by alignment of short reads obtained by next-generation sequencing analysis with the identified locus. In the mutant line, GmCHR5 harbored a single-base deletion that caused a change in the substrate flow in the isoflavone biosynthetic pathway towards genistein. Mutated GmCHR5 was expressed at a lower level during seed development than wild-type GmCHR5. Ectopic overexpression of GmCHR5 increased the production of daidzein derivatives in both the wild-type and mutant plants. The present strategy will be useful for accelerating identification of mutant alleles responsible for traits of interest in agronomically important crops.
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The impact of hydrocarbon-molecular (C3H6)-ion implantation in an epitaxial layer, which has low oxygen concentration, on the dark characteristics of complementary metal-oxide-semiconductor (CMOS) image sensor pixels was investigated by dark current spectroscopy. It was demonstrated that white spot defects of CMOS image sensor pixels when using a double epitaxial silicon wafer with C3H6-ion implanted in the first epitaxial layer were 40% lower than that when using an epitaxial silicon wafer with C3H6-ion implanted in the Czochralski-grown silicon substrate. This considerable reduction in white spot defects on the C3H6-ion-implanted double epitaxial silicon wafer may be due to the high gettering capability for metallic contamination during the device fabrication process and the suppression effects of oxygen diffusion into the device active layer. In addition, the defects with low internal oxygen concentration were observed in the C3H6-ion-implanted region of the double epitaxial silicon wafer after the device fabrication process. We found that the formation of defects with low internal oxygen concentration is a phenomenon specific to the C3H6-ion-implanted double epitaxial wafer. This finding suggests that the oxygen concentration in the defects being low is a factor in the high gettering capability for metallic impurities, and those defects are considered to directly contribute to the reduction in white spot defects in CMOS image sensor pixels.
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BACKGROUND: The new 60-MHz high-resolution intravascular ultrasound (HR-IVUS) is the next-generation IVUS technology, providing higher image resolution than conventional IVUS. It gives clear images of plaque morphology and can discriminate the underlying mechanism of acute coronary syndrome (ACS). Our study aimed to evaluate the diagnostic performance of 60-MHz HR-IVUS in the detection of plaque rupture in patients with ACS.MethodsâandâResults:Patients with ACS who underwent percutaneous coronary intervention for de novo native coronary artery lesions were enrolled. Both HR-IVUS and optical coherence tomography (OCT) were performed for the culprit lesions prior to interventions other than aspiration thrombectomy. Keeping plaque rupture detected by OCT as the gold standard, the diagnostic performance of HR-IVUS was evaluated. Overall, 70 patients underwent both HR-IVUS and OCT examinations. Of these, imaging assessments by HR-IVUS were available for all 70 patients (100%), and those by OCT were available for 54 patients (77.1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of HR-IVUS for identifying a plaque rupture were 84.8%, 57.1%, 75.7%, 70.6%, and 74.1%, respectively. CONCLUSIONS: HR-IVUS had high sensitivity, but modest specificity for identifying OCT-derived plaque rupture. Compared with results from previous conventional IVUS studies, HR-IVUS might have increased ability to detect OCT-derived plaque rupture, but there is still substantial scope for improvement, especially in the specificity.