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The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1 µm^{-3}, tens of orders of magnitude greater than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and can induce dephasing. Here we show that a dominant mechanism for quasiparticle poisoning is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity of the qubit. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticles. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning.
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BACKGROUND: Aster altaicus var. uchiyamae Kitam is an endemic and endangered species in urgent need of a comprehensive conservation strategy. OBJECTIVE: To develop an efficient cryopreservation protocol using in vitro shoot tips to complement traditional conservation approaches in case seeds are not available or insufficient for conservation programs. METHODS: Shoot tips of in vitro plants were cryopreserved using a droplet-vitrification method following improvement of pre-culture, osmoprotection, vitrification solution (VS), unloading and post-culture treatments. The starting protocol included step-wise pre-culture with 10% and 17.5% sucrose for 55 h and 17 h, respectively, followed by osmoprotection with C4-35% (17.5% glycerol + 17.5% sucrose) for 30 min, and cryoprotection with B5-80% (40% glycerol + 40% sucrose) for 60 min. RESULTS: Shoot tips of A. altaicus were found to be moderately sensitive to the osmotic stress. Pre-culture and osmoprotection were not critical for the regeneration of cryopreserved explants when either of these treatments was applied. Osmoprotection with C4-35% on ice for 60 min followed by cryoprotection with A3-80%, a modified and diluted PVS2, on ice for 60 min resulted in the highest (65.3%) regeneration of cryopreserved shoot tips. Among alternative VSs tested, A3-80% and B5-80% were superior to PVS2 and PVS3 used under the same conditions. Step-wise recovery of shoot tips on ammonium-free medium followed by GA3-containing medium and medium without growth regulators were critical for the normal regeneration of both VS-treated and cryopreserved shoot tips. CONCLUSIONS: Cryopreservation of in vitro shoot tips using droplet-vitrification was developed as a complementary conservation approach for A. altaicus. Adjustment of the composition of regrowth media depending on recovery stage was important for the regeneration of healthy plants from cryopreserved shoot tips.
Assuntos
Aster , Criopreservação/métodos , Espécies em Perigo de Extinção , Brotos de Planta , Vitrificação , Animais , Crioprotetores , SacaroseRESUMO
Interferon gamma release assays (IGRAs) are important tools in identifying prior tuberculosis exposure. The new-generation QuantiFERON-TB Gold Plus (QFT-Plus) assay, recently approved for use in the United States, differs from the current-generation QFT Gold-In-Tube (QFT-GIT) assay with the addition of a second antigen tube that also contains novel CD8+ T-cell-stimulating peptides. The QFT-Plus assay has increased sensitivity in immunocompromised populations, and we sought to assess the specificity of QFT-Plus compared to that of QFT-GIT in low-risk individuals. We enrolled adults without tuberculosis risk factors, including a subgroup with pulmonary nontuberculous mycobacterial (NTM) disease due to Mycobacterium avium complex (MAC) or Mycobacterium abscessus. The primary outcome measures included specificity, interassay concordance, and agreement between the QFT-Plus and QFT-GIT assays. Of 262 participants enrolled, 51 had pulmonary NTM. The median age was 39 years (age range, 18 to 78 years); 73% were female. Among the 262 individuals who were enrolled, 5 (1.9%) individuals had positive QFT-Plus results, and 3 of these individuals also had positive QFT-GIT results. The two individuals with discordant results (QFT-Plus positive/QFT-GIT negative) had only one tube positive in the QFT-Plus assay. The overall specificity of QFT-Plus and QFT-GIT was 98.1% (95% confidence interval [CI], 95.6, 99.4%) and 98.9% (95% CI, 96.7, 99.8%), respectively. The QFT-Plus specificity was similar in both the NTM (98.0% [95% CI, 89.4, 99.9%]) and non-NTM (98.1% [95% CI, 95.2, 99.5%]) groups. QFT-Plus has a high specificity, similar to that of the QFT-GIT assay, including in patients with pulmonary MAC or M. abscessus disease.
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Técnicas Bacteriológicas/normas , Testes de Liberação de Interferon-gama/normas , Mycobacterium tuberculosis/isolamento & purificação , Kit de Reagentes para Diagnóstico , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Feminino , Humanos , Interferon gama/análise , Tuberculose Latente/diagnóstico , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Sensibilidade e Especificidade , Adulto JovemRESUMO
Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.
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Carcinoma/genética , Transformação Celular Neoplásica/genética , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Feminino , Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hibridização in Situ Fluorescente , Masculino , Proteínas de Ligação a RNA/genética , Fatores de Transcrição , TranscriptomaRESUMO
The rarity of primary small cell carcinoma of the esophagus (PSCE) has limited the clinical feature and survival analysis with large sample size. Tissue chromogranin A (CgA) protein expression has been reported to be a useful biomarker for diagnosing PSCE. Interestingly, recent studies have indicated tissue CgA as a significant prognostic marker in multiple human cancers, but without PSCE. The present study, thus, was undertaken to characterize the clinicopathological changes and to evaluate the associations of tissue CgA expression with clinical response on Chinese PSCE patients. All the 125 PSCE patients were enrolled from our 500,000 esophageal and gastric cardia carcinoma databases (1973-2015), constructed by the cooperative team from more than 700 hospitals in China and established by Henan Key Laboratory for Esophageal Cancer Research in Henan, China. Immunostaining for CgA showed that CgA was mainly located in cytoplasm of tumor cells with a positive detection rate of 44.6%. The CgA positive expression rate in PSCE at lower segment of the esophagus (72.2%) was higher than that at middle segment (41.5%) (P = 0.001). However, CgA protein expression did not correlated with lymph node metastasis (P = 0.767), TNM staging (P = 0.740), tumor invasion (P = 0.253), gender (P = 0.262), and age (P = 0.250). Multivariate survival analysis showed that the patients with higher CgA protein expression had a superior long survival than those without CgA expression (P = 0.037). The clinicopathological analysis showed that PSCE occurred predominantly in male (M:F = 1.9:1) at the middle segment (68%) of the esophagus. Histologically, 89.6% were pure PSCE and 10.4% were mixed type with either squamous cell carcinoma (8%) or adenocarcinoma (2.4%). It was noteworthy that, with the in-depth invasion from T1 to T2 and T3, the positive lymph node metastasis rate increased dramatically from 38%, 56% to 74%, respectively. The survival rates of 1-, 2-, 3-, and 5-year were 64%, 35%, 18%, and 7%, respectively. The Kaplan-Meier survival analysis showed that the young patients (≤60 years) had longer survival than the elderly (P = 0.011). Interestingly, multivariate survival analysis revealed that the patients with mixed PSCE had a significantly better survival than those with pure PSCE (P = 0.015). Furthermore, the median survival time for the patients with and without lymph node metastasis was 1.16 and 2.03 years, respectively. But, the difference was not significant (P = 0.143). Univariate analysis did not show any survival influence by gender, tumor location, tumor invasion depth, and TNM staging. It was noteworthy that, of the 13 early PSCE patients (T1N0M0), only one patient had more than 5 year survival, the others died with less than one or two year (65%). The present study indicates that the PSCE is of badly worsen prognosis, even in the pathological early stage. Tissue CgA protein expression is a promising maker not only for diagnosis and also for prognosis. Further assessment is needed to establish specific PSCE pathological staging system and to clarify the mechanisms of CgA protein in PSCE progression and prognosis.
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Carcinoma de Células Pequenas/patologia , Cromogranina A/análise , Neoplasias Esofágicas/patologia , Esôfago/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , China , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Coloração e Rotulagem/métodosRESUMO
Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.
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Antivirais/farmacocinética , Ribavirina/farmacocinética , Suínos/metabolismo , Animais , Antivirais/efeitos adversos , Humanos , Injeções Intramusculares/veterinária , Ribavirina/efeitos adversosRESUMO
BACKGROUND: Systemic inflammatory response (SIR) is important in the relationship between the tumour, the host, and outcome in cancer patients. However, limited data exist regarding the prognostic significance of SIR in bladder cancer. We investigate the utility of pretreatment SIR in patients with urothelial carcinoma undergoing radical cystectomy. METHODS: The study cohort consisted of 419 patients with a median follow-up of 37.7 months. The SIRs used for each described prognostic nomogram are consistent with previously published data: C-reactive protein, albumin, white cell count, neutrophil count, lymphocyte count, and platelet count. Primary end point was disease-specific survival (DSS) and overall survival (OS) after surgery. Cox regression models were used to determine the time to disease-specific and overall mortality. Multivariate regression coefficients of the predictors were used to develop nomograms for predicting 5-year DSS and OS probability. RESULTS: Multivariate Cox regression analyses revealed that albumin, lymphocyte count, and platelet count were significantly associated with a significantly increased risk for death from bladder cancer. The nomograms including each index were developed to predict the probability of 5-year DSS and OS after radical cystectomy. The C statistics were 77.8% and 77.3%, respectively, and exceeded the 2002 AJCC (72.0% and 70.3%, respectively). In the decision curve analyses, the nomograms including SIR demonstrated higher net benefit gains compared with the models without SIR. CONCLUSIONS: Cellular components of SIR have better prognostic values compared with acute-phase protein in patients undergoing radical cystectomy for bladder cancer.
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Carcinoma/diagnóstico , Carcinoma/cirurgia , Cistectomia , Inflamação/diagnóstico , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/cirurgia , Idoso , Carcinoma/mortalidade , Carcinoma/patologia , Cistectomia/métodos , Feminino , Humanos , Inflamação/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
To evaluate the diagnostic values of using autoantibodies in sera to a panel of eight tumor-associated antigens (TAAs) of P53, Koc, P62, C-myc, IMP1, Survivn, P16 and Cyclin B1 full-length recombinant proteins for early detection of patients with gastric cardia adenocarcinoma (GCA) and high-risk subjects screening. Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 383 sera samples from four groups, including 140 subjects with normal gastric cardia epithelia (NOR), 76 patients with chronic atrophic gastritis (CAG), 79 patients with gastric cardia dysplasia (DYS) and 88 patients with GCA. In addition, the expression of the eight antigens was analyzed in gastric cardia tissues by immunohistochemical method. The individual autoantibodies to six TAAs (P53, P62, IMP1, Survivn P16 and Cyclin B1) were significantly higher in sera from patients with GCA than that in normal subjects (P < 0.05). When autoantibody assay successively accumulated to seven TAAs (P53, Koc, P62, C-myc, IMP1, Survivn and P16), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (13% in NOR, 39% in CAG, 46% in DYS, and 64% in GCA, respectively), the risks to CAG, DYS and GCA steadily increased about 4.4-, 5.7- and 12.0-fold. The sensitivity and the specificity for autoantibodies against the seven TAAs in diagnosing GCA reached up to 64% and 87%, respectively. The area under the receiver operating characteristic curve for the seven anti-TAA autoantibodies was 0.73 (95%CI: 0.68-0.78) No more increase in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might be helpful to distinguish GCA patients from normal subjects and the patients with gastric cardia precancerous lesions. In addition, further studies in patients with GCA and precancerous lesions using enlarged TAA panels might improve the sensitivity and specificity of cancer detection and high-risk subjects screening.
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Adenocarcinoma/diagnóstico , Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Cárdia , Neoplasias Gástricas/diagnóstico , Adenocarcinoma/sangue , Adenocarcinoma/imunologia , Adulto , Idoso , Cárdia/patologia , Detecção Precoce de Câncer/métodos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/imunologia , Sensibilidade e Especificidade , Neoplasias Gástricas/sangue , Neoplasias Gástricas/imunologiaRESUMO
The aim of this study was to evaluate the diagnostic values by detecting sera autoantibodies to eight tumor-associated antigens (TAAs) of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn and Koc full-length recombinant proteins for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma (ESCC). Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 567 sera samples from four groups, including 200 individuals with normal esophageal epithelia (NOR), 214 patients with esophageal basal cell hyperplasia (BCH), 65 patients with esophageal dysplasia (DYS), and 88 patients with ESCC. In addition, the expression of the eight antigens in esophageal tissues was analyzed by immunohistochemistry. Statistically significant distribution differences were identified among the four groups for each of the individual autoantibodies to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc); the detection rates of antoantibodies were positively correlated with the progression of ESCC. When autoantibody assay successively accumulated to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (6% in NOR, 18% in BCH, 38% in DYS, and 64% in ESCC, respectively), the risks to BHC, DYS, and ESCC steadily increased about 3-, 9-, and 27-folds. The sensitivity and the specificity for autoantibodies against the six TAAs in diagnosing ESCC reached up to 64% and 94%, respectively. The area under the receiver operating characteristic curve for the six anti-TAA autoantibodies was 0.78 (95% confidence interval 0.74-0.83). No more increasing in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might distinguish ESCC patients from normal individuals and the patients with esophageal precancerous lesions.
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Antígenos de Neoplasias/imunologia , Autoanticorpos/sangue , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Esofágicas/diagnóstico , Adulto , Idoso , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/metabolismo , Ciclina B1/imunologia , Ciclina B1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Diagnóstico Precoce , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Proteínas Inibidoras de Apoptose/imunologia , Proteínas Inibidoras de Apoptose/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/metabolismo , Survivina , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/imunologia , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort. METHODS: The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan-Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis. RESULTS: The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan-Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis. CONCLUSION: The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.
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Técnicas de Apoio para a Decisão , Nefrectomia , Nomogramas , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Interpretação Estatística de Dados , Feminino , Humanos , Internet , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Sobrevida , Ureter/patologia , Ureter/cirurgia , Urotélio/patologia , Adulto JovemRESUMO
BACKGROUND: Middle meningeal artery embolization is an emerging treatment option for chronic subdural hematomas. PURPOSE: Our aim was to assess outcomes following middle meningeal artery embolization by different techniques, including in comparison with traditional surgical methods. DATA SOURCES: We searched the literature databases from inception to March 2022. DATA SELECTION: We selected studies reporting outcomes after middle meningeal artery embolization as a primary or adjunctive treatment for chronic subdural hematoma. DATA ANALYSIS: We analyzed the risk of recurrence of chronic subdural hematoma, reoperation for recurrence or residual hematoma, complications, and radiologic and clinical outcomes using random effects modeling. Additional analyses were performed on the basis of whether middle meningeal artery embolization was used as the primary or adjunct treatment and by embolic agent type. DATA SYNTHESIS: Twenty-two studies were included with 382 patients with middle meningeal artery embolization and 1373 surgical patients. The rate of subdural hematoma recurrence was 4.1%. Fifty (4.2%) patients underwent a reoperation for a recurrent or residual subdural hematoma. Thirty-six (2.6%) experienced postoperative complications. The rates of good radiologic and clinical outcomes were 83.1% and 73.3%, respectively. Middle meningeal artery embolization was significantly associated with decreased odds of subdural hematoma reoperation (OR = 0.48; 95% CI, 23.4-99.1; P = .047) compared with surgery. The lowest rates of subdural hematoma radiologic recurrence, reoperation, and complications were observed among patients receiving embolization with Onyx, whereas good overall clinical outcome occurred most commonly with combined polyvinyl alcohol and coils. LIMITATIONS: A limitation was the retrospective design of studies included. CONCLUSIONS: Middle meningeal artery embolization is safe and effective, either as a primary or adjunctive treatment. Treatment using Onyx seems to yield lower rates of recurrence, rescue operation, and complications whereas particles and coils produce good overall clinical outcomes.
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Embolização Terapêutica , Hematoma Subdural Crônico , Humanos , Hematoma Subdural Crônico/cirurgia , Artérias Meníngeas , Estudos Retrospectivos , Embolização Terapêutica/métodos , ReoperaçãoRESUMO
BACKGROUND AND AIM: Colorectal cancer (CRC) is a multifactorial disease with both environmental and genetic factors contributing to its development. The incidence of CRC is increasing year by year in Japan. Patients with CRC in advanced stages have a poor prognosis, but detection of CRC at earlier stages can improve clinical outcome. Therefore, identification of epidemiologial factors that influence development of CRC would facilitate the prevention or early detection of disease. METHODS: To identify loci associated with CRC risk, we performed a genome-wide association study (GWAS) for CRC and sub-analyses by tumour location using 1583 Japanese CRC cases and 1898 controls. Subsequently, we conducted replication analyses using a total of 4809 CRC cases and 2973 controls including 225 Korean subjects with distal colon cancer and 377 controls. RESULTS: We identified a novel locus on 6q26-q27 region (rs7758229 in SLC22A3, p = 7.92 × 10â»9, OR of 1.28) that was significantly associated with distal colon cancer. We also replicated the association between CRC and SNPs on 8q24 (rs6983267 and rs7837328, p = 1.51 × 10â»8 and 7.44 × 10â»8, ORs of 1.18 and 1.17, respectively). Moreover, we found cumulative effects of three genetic factors (rs7758229, rs6983267, and rs4939827 in SMAD7) and one environmental factor (alcohol drinking) which appear to increase CRC risk approximately twofold. CONCLUSIONS: We found a novel susceptible locus in SLC22A3 that contributes to the risk of distal colon cancer in an Asian population. These findings would further extend our understanding of the role of common genetic variants in the aetiology of CRC.
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Cromossomos Humanos Par 6/genética , Neoplasias Colorretais/genética , Adulto , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Japão/epidemiologia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Quantum error correction can preserve quantum information in the presence of local errors, but correlated errors are fatal. For superconducting qubits, high-energy particle impacts from background radioactivity produce energetic phonons that travel throughout the substrate and create excitations above the superconducting ground state, known as quasiparticles, which can poison all qubits on the chip. We use normal metal reservoirs on the chip back side to downconvert phonons to low energies where they can no longer poison qubits. We introduce a pump-probe scheme involving controlled injection of pair-breaking phonons into the qubit chips. We examine quasiparticle poisoning on chips with and without back-side metallization and demonstrate a reduction in the flux of pair-breaking phonons by over a factor of 20. We use a Ramsey interferometer scheme to simultaneously monitor quasiparticle parity on three qubits for each chip and observe a two-order of magnitude reduction in correlated poisoning due to background radiation.
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OBJECTIVE: This study examined the neural pathophysiology of the theory of mind network by eliciting self-referential processing during an idea of reference evocating situation in patients with schizophrenia. METHOD: Functional MRI was conducted on 14 schizophrenic in-patients with the idea of reference and 15 healthy participants while viewing video vignettes of referential conversations, non-referential conversations or no conversations between two people, which were filmed at varying distances of 1, 5 or 10 m. RESULTS: The patient group did not show normal patterns of superior temporal sulcus activation to conversational context, and reciprocal deactivation and activation of the ventromedial and dorsomedial prefrontal cortex to referential conversational context. Instead, the patient group showed overall greater ventromedial prefrontal activities across different conversational contexts and inverse correlation between superior temporal sulcus activity and delusional severity. Differential activations of the temporal pole and its posterior extension to varying distances were observed in the control group but not in the patient group. CONCLUSION: The present study demonstrates that theory of mind-related responses of the medial prefrontal-superior temporal network are attenuated during the self-referential processing in patients with schizophrenia and that these abnormalities may be related to the formation of their referential or persecutory delusion.
Assuntos
Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico , Lobo Temporal/fisiopatologia , Adulto , Mapeamento Encefálico/métodos , Emoções/fisiologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Competência Mental , Escalas de Graduação Psiquiátrica , Técnicas Psicológicas/instrumentação , Psicofisiologia , Psicologia do EsquizofrênicoRESUMO
BACKGROUND: Research on the presence of sex-based differences in the outcomes of patients undergoing endovascular thrombectomy for acute ischemic stroke has reached differing conclusions. PURPOSE: This review aimed to determine whether sex influences the outcome of patients with large-vessel occlusion stroke undergoing endovascular thrombectomy. STUDY SELECTION: We performed a systematic review and meta-analysis of endovascular thrombectomy studies with either stratified cohort outcomes according to sex (females versus males) or effect size reported for the consequence of sex versus outcomes. We included 33 articles with 7335 patients. DATA ANALYSIS: We pooled ORs for the 90-day mRS score, 90-day mortality, symptomatic intracranial hemorrhage, and recanalization. DATA SYNTHESIS: Pooled 90-day good outcomes (mRS ≤ 2) were better for men than women (OR = 1.29; 95% CI, 1.09-1.53; P = <.001, I2 = 56.95%). The odds of the other outcomes, recanalization (OR = 0.94; 95% CI, 0.77-1.15; P = .38, I2 = 0%), 90-day mortality (OR = 1.11; 95% CI, 0.89-1.38; P = .093, I2 = 0%), and symptomatic intracranial hemorrhage (OR = 1.40; 95% CI, 0.99-1.99; P = .069, I2 = 0%) were comparable between men and women. LIMITATIONS: Moderate heterogeneity was found. Most studies included were retrospective in nature. In addition, the randomized trials included were not specifically designed to compare outcomes between sexes. CONCLUSIONS: Women undergoing endovascular thrombectomy for large-vessel occlusion have inferior 90-day clinical outcomes. Sex-specific outcomes should be investigated further in future trials as well as pathophysiologic studies.
Assuntos
Procedimentos Endovasculares/métodos , AVC Isquêmico/cirurgia , Trombectomia/métodos , Resultado do Tratamento , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores SexuaisRESUMO
OBJECTIVE: To investigate the potential of our newly developed three-dimensional immersive virtual reality (VR) program modeled on a real street crossing as an assessment tool for extrapersonal neglect in stroke patients. METHODS: Thirty-two patients with right-hemispheric stroke (neglect group, 16; non-neglect group, 16) were enrolled. The deviation angle, reaction time, left-to-right reaction time ratio, visual and auditory cue rates, and failure rate were evaluated during missions to keep a virtual avatar safe from a traffic accident in the VR program. The line bisection test and letter cancellation test were also evaluated. RESULTS: The deviation angle, left-to-right reaction time ratio, left visual and auditory cue rates and left failure rate in the VR program showed significant differences between the two groups (P < 0.05). Depending on the direction of approach of the virtual car, the left parameters were significantly higher than the right parameters in the neglect group (P < 0.05). In the neglect group, the line bisection test correlated significantly with the deviation angle (P < 0.05). None of the other virtual reality parameters significantly correlated with the paper and pencil tests. CONCLUSION: Post-stroke neglect in the extrapersonal space can be easily and safely detected and measured using our three-dimensional immersive virtual street crossing program.
Assuntos
Gráficos por Computador , Transtornos da Percepção/diagnóstico , Espaço Pessoal , Percepção Espacial/fisiologia , Interface Usuário-Computador , Estimulação Acústica/métodos , Idoso , Sinais (Psicologia) , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Transtornos da Percepção/etiologia , Estimulação Luminosa/métodos , Tempo de Reação/fisiologia , Acidente Vascular Cerebral/complicaçõesRESUMO
Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU.
Assuntos
Proliferação de Células , Neoplasias do Colo/metabolismo , Galectina 3/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Isoformas de Proteínas/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Sequência de Aminoácidos , Antimetabólitos/metabolismo , Apoptose/fisiologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Regulação para Baixo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fluoruracila/metabolismo , Galectina 3/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Humanos , Dados de Sequência Molecular , Fosfoproteínas/metabolismo , Isoformas de Proteínas/genética , Proteínas Quinases/metabolismo , Proteoma/análise , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TORRESUMO
A dacryolith is a rare finding and can be considered as a complication of a Le Fort I fracture. A case of dacryolith and nasolacrimal duct obstruction after surgery for a Le Fort I fracture is described, and the reasons for and prevention of this condition are discussed.
Assuntos
Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Fraturas Maxilares , Ducto Nasolacrimal , HumanosRESUMO
BACKGROUND AND PURPOSE: Imaging of the cerebral venous sinuses has evolved Substantially during the past 2 decades, and most recently intravascular sinus imaging with sonography has shed light on the pathophysiology of sinus thrombosis and intracranial hypertension. Optical coherence tomography is the highest resolution intravascular imaging technique available but has not been previously used in cerebral sinus imaging. The purpose of this study was to develop a preclinical animal model of endovascular optical coherence tomography cerebral venous sinus imaging and compare optical coherence tomography findings with histology. MATERIALS AND METHODS: Four consecutive Yorkshire swine were selected. The superior sagittal sinus was first catheterized with a microwire, and the optical coherence tomography catheter was delivered via a monorail technique into the sinus. Luminal blood was cleared with a single arterial injection. After structural and Doppler optical coherence tomography imaging, a craniotomy was performed and the sinus and adjacent dura/veins were resected. Bland-Altman analysis was performed to compare optical coherence tomography and histology. RESULTS: Technically successful optical coherence tomography images were obtained in 3 of 4 swine. The luminal environment and visualization of dural arteries and draining cortical veins were characterized. The average maximum diameters of the sinus, dural arteries, and cortical veins were 3.14 mm, 135 µm, and 260 µm, respectively. Bland-Altman analysis demonstrated good agreement between histology and optical coherence tomography images. CONCLUSIONS: Endovascular optical coherence tomography imaging was feasible in this preclinical animal study. Adoption of this imaging technique in the human cerebral venous sinus could aid in the diagnosis, treatment, and understanding of the pathophysiology of various diseases of the sinus. Human safety and feasibility studies are needed.
Assuntos
Cavidades Cranianas , Procedimentos Endovasculares/métodos , Modelos Animais , Neuroimagem/métodos , Tomografia de Coerência Óptica/métodos , Animais , Feminino , Masculino , SuínosRESUMO
One of the causes of erectile dysfunction (ED) is the damaged penile cavernous smooth muscle cells (SMCs) and sinus endothelial cells (ECs). To investigate the feasibility of applying immortalized human mesenchymal stem cells (MSCs) to penile cavernous ECs or SMCs repair in the treatment of ED, the in vivo potential differentiation of the immortalized human MSCs toward penile cavernous endothelial or smooth muscle was investigated. One clone of immortalized human bone marrow mesenchymal stem cell line B10 cells via retroviral vector encoding v-myc were transplanted into the cavernosum of the Sprague-Dawley rats and harvested 2 weeks later. The expression of CD31, von Willebrand factor (vWF), smooth muscle cell actin (SMA), calponin and desmin was determined immunohistochemically in rat penile cavernosum. Multipotency of B10 to adipogenic, osteogenic or chondrogenic differentiation was found. Expression of EC specific markers (CD31 or vWF protein) and expression of SMC specific markers (calponin, SMA or desmin protein) were demonstrated in grafted B10 cells. When human MSCs were transplanted into the penile cavernosum, they have the potential to differentiate toward ECs or SMCs. Human MSCs may be a good candidate in the treatment of penile cavernosum injury.