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1.
Clin Radiol ; 79(1): e41-e47, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37872026

RESUMO

AIM: To investigate the effect of deep learning on the diagnostic performance of radiologists and radiology residents in detecting breast cancers on computed tomography (CT). MATERIALS AND METHODS: In this retrospective study, patients undergoing contrast-enhanced chest CT between January 2010 and December 2020 using equipment from two vendors were included. Patients with confirmed breast cancer were categorised as the training (n=201) and validation (n=26) group and the testing group (n=30) using processed CT images from either vendor. The trained deep-learning model was applied to test group patients with (30 females; mean age = 59.2 ± 15.8 years) and without (19 males, 21 females; mean age = 64 ± 15.9 years) breast cancer. Image-based diagnostic performance of the deep-learning model was evaluated with the area under the receiver operating characteristic curve (AUC). Two radiologists and three radiology residents were asked to detect malignant lesions by recording a four-point diagnostic confidence score before and after referring to the result from the deep-learning model, and their diagnostic performance was evaluated using jackknife alternative free-response receiver operating characteristic analysis by calculating the figure of merit (FOM). RESULTS: The AUCs of the trained deep-learning model on the validation and test data were 0.976 and 0.967, respectively. After referencing with the result of the deep learning model, the FOMs of readers significantly improved (reader 1/2/3/4/5: from 0.933/0.962/0.883/0.944/0.867 to 0.958/0.968/0.917/0.947/0.900; p=0.038). CONCLUSION: Deep learning can help radiologists and radiology residents detect breast cancer on CT.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Radiologia , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Radiologistas
2.
Phys Rev Lett ; 130(13): 132502, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37067317

RESUMO

The new isotope ^{241}U was synthesized and systematic atomic mass measurements of nineteen neutron-rich Pa-Pu isotopes were performed in the multinucleon transfer reactions of the ^{238}U+^{198}Pt system at the KISS facility. The present experimental results demonstrate the crucial role of the multinucleon transfer reactions for accessing unexplored neutron-rich actinide isotopes toward the N=152 shell gap in this region of nuclides.

3.
Phys Rev Lett ; 130(1): 012501, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36669221

RESUMO

The atomic masses of ^{55}Sc, ^{56,58}Ti, and ^{56-59}V have been determined using the high-precision multireflection time-of-flight technique. The radioisotopes have been produced at RIKEN's Radioactive Isotope Beam Factory (RIBF) and delivered to the novel designed gas cell and multireflection system, which has been recently commissioned downstream of the ZeroDegree spectrometer following the BigRIPS separator. For ^{56,58}Ti and ^{56-59}V, the mass uncertainties have been reduced down to the order of 10 keV, shedding new light on the N=34 shell effect in Ti and V isotopes by the first high-precision mass measurements of the critical species ^{58}Ti and ^{59}V. With the new precision achieved, we reveal the nonexistence of the N=34 empirical two-neutron shell gaps for Ti and V, and the enhanced energy gap above the occupied νp_{3/2} orbit is identified as a feature unique to Ca. We perform new Monte Carlo shell model calculations including the νd_{5/2} and νg_{9/2} orbits and compare the results with conventional shell model calculations, which exclude the νg_{9/2} and the νd_{5/2} orbits. The comparison indicates that the shell gap reduction in Ti is related to a partial occupation of the higher orbitals for the outer two valence neutrons at N=34.


Assuntos
Nêutrons , Titânio
4.
Clin Radiol ; 78(12): e934-e940, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37690975

RESUMO

AIM: To develop a model using radiomics features extracted from magnetic resonance imaging (MRI) images of Gamma Knife radiosurgery (GKRS) to predict the BRAF mutation in patients with melanoma brain metastases (MBM). MATERIALS AND METHODS: Data of 220 tumours were classified into two groups. One was a group whose BRAF mutation was identified, and the other group whose BRAF mutation was not identified. We extracted 1,962 radiomics features from gadolinium contrast-enhanced T1-weighted MRI treatment-planning images. Synthetic Minority Over-sampling TEchnique (SMOTE) was performed to address the unbalanced data-related issues. A single-layer neural network (NN) was used to build predictive models with radiomics features. The sensitivity, specificity, accuracy, and the area under the curve (AUC) were evaluated to assess the model performance. RESULTS: The prediction performance for the final evaluation without the SMOTE had an accuracy of 77.14%, a specificity of 82.44%, a sensitivity of 81.85%, and an AUC of 0.79. The application of SMOTE improved the prediction model to an accuracy of 83.1%, a specificity of 87.07%, a sensitivity of 78.82%, and an AUC of 0.82. CONCLUSION: The current study showed the feasibility of generating a highly accurate NN model for the BRAF mutation prediction. The prediction performance improved with SMOTE. The model assists physicians to obtain more accurate expectations of the treatment outcome without a genetic test.


Assuntos
Neoplasias Encefálicas , Melanoma , Radiocirurgia , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Radiocirurgia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Melanoma/diagnóstico por imagem , Melanoma/genética , Melanoma/radioterapia , Mutação/genética , Estudos Retrospectivos
5.
Zygote ; 31(2): 173-179, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36804925

RESUMO

Carvacrol (C10H14O), an efficient phenolic antioxidant substance for several cell types, may become a useful antioxidant for female germ cells and embryo culture. This study investigates the effects of carvacrol supplementation on bovine oocytes in in vitro maturation (IVM) and embryo production. In total, 1222 cumulus-oocyte complexes were cultured in TCM-199+ alone (control treatment) or supplemented with carvacrol at the concentrations of 3 µM (Carv-3), 12.5 µM (Carv-12.5), or 25 µM (Carv-25). After IVM, the oocytes were subjected to in vitro fertilization and embryo production, and the spent medium post-IVM was used for evaluating the levels of reactive oxygen species and the antioxidant capacity (2,2-diphenyl-1-picryl-hydrazyl-hydrate and 2,2'-azinobis-3-ethyl-benzothiozoline-6-sulphonic acid quantification). A greater (P < 0.05) antioxidant potential was observed in the spent medium of all carvacrol-treated groups compared with the control medium. Moreover, the addition of carvacrol to the maturation medium did not affect (P > 0.05) blastocyst production on days 7 and 10 of culture; however, the total number of cells per blastocyst was reduced (P < 0.05) in two carvacrol-treated groups (Carv-3 and Carv-25). In conclusion, carvacrol demonstrated a high antioxidant capacity in the spent medium after oocyte maturation; however, although embryo production was not affected, in general, carvacrol addition to IVM medium reduced the total number of cells per blastocyst. Therefore, due to the high antioxidant capacity of carvacrol, new experiments are warranted to investigate the beneficial effects of lower concentrations of carvacrol on embryo production in cattle and other species.


Assuntos
Antioxidantes , Técnicas de Maturação in Vitro de Oócitos , Bovinos , Feminino , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Oogênese , Oócitos , Fertilização in vitro/veterinária , Blastocisto
6.
Tech Coloproctol ; 26(2): 109-115, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34761314

RESUMO

BACKGROUND: Placing a transanal endoscopic rectal purse-string suture (taEPS) is the crucial first component of transanal total mesorectal excision (taTME). However, no structured training is available to improve the procedure-specific skills for taEPS. The aim of this study was to create a performance rubric to improve taEPS skills and provide preliminary evidence for its validity. METHODS: A performance rubric was created based on technical considerations for taEPS, identified by consulting with taTME surgical and performance assessment experts. Ten independent, blinded raters assessed 10 videotaped taEPS procedures of consecutive taTME cases, at National Cancer Center Hospital East (NCCHE), Chiba, Japan, in January 2018-March 2019 using the rubric and the Global Operative Assessment of Laparoscopic Skills (GOALS). Internal consistency and inter-rater reliabilities were calculated. Videotaped taEPS procedures were timed and assessed by the rubric. Correlation between rubric scores and suturing times were analyzed. RESULTS: The rubric consists of four items: loading the needle (LN), atraumatic needle passage (AP), planned suture path (PS), and overall performance (OA). Videotaped performances were graded on a 3-point Likert scale; scores were calculated as sums of the points. Cronbach's α for internal consistency was 0.713. Inter-rater reliabilities were LN: 0.73, AP: 0.76, PS: 0.71, and OA: 0.70. Rubric and GOALS scores were strongly correlated (r = 0.964, p < 0.001). In 112 consecutive taEPS performances, rubric scores were strongly correlated with suturing time (r = - 0.69, p < 0.001). Surgeons' experience with taTME was associated with rubric scores and suturing time. CONCLUSIONS: This study provides preliminary validation for the taEPS skill performance rubric. The rubric's structured training may facilitate skill acquisition by providing trainees with critical clinical considerations.


Assuntos
Laparoscopia , Protectomia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Laparoscopia/métodos , Complicações Pós-Operatórias/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgia , Suturas , Cirurgia Endoscópica Transanal/métodos
7.
Pharmazie ; 76(12): 594-601, 2021 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986955

RESUMO

Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC50 value of PLC/PRF/5 cells from 13.0±0.8 µM in normoxia to 21.3±1.1 µM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore, in-silico analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Fibronectinas/genética , Fibronectinas/uso terapêutico , Humanos , Hipóxia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Compostos de Fenilureia , Quinolinas
8.
Phys Rev Lett ; 124(8): 084802, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32167312

RESUMO

Acceleration of particles from the interaction of ultraintense laser pulses up to 5×10^{21} W cm^{-2} with thin foils is investigated experimentally. The electron beam parameters varied with decreasing spot size, not just laser intensity, resulting in reduced temperatures and divergence. In particular, the temperature saturated due to insufficient acceleration length in the tightly focused spot. These dependencies affected the sheath-accelerated protons, which showed poorer spot-size scaling than widely used scaling laws. It is therefore shown that maximizing laser intensity by using very small foci has reducing returns for some applications.

9.
Clin Exp Immunol ; 195(2): 167-178, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30368780

RESUMO

Autoantibodies characteristic for anti-phospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are anti-ß2 -glycoprotein I (ß2 GPI) antibodies and anti-DNA antibodies, respectively, and almost half of APS cases occur in SLE. Anti-ß2 GPI antibodies are recognized to play a pivotal role in inducing a prothrombotic state, but the precise mechanism has not been fully elucidated. In a widely accepted view, binding of anti-ß2 GPI antibodies to cell surface ß2 GPI in monocytes and endothelial cells triggers the Toll-like receptor 4-myeloid differentiation primary response 88 (TLR)-4-MyD88) signaling pathway which leads to activation of p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase kinase 1/extracellular signal-regulated kinases (MEK-1/ERK) and/or nuclear factor kappa B (NF-κB) and expression of tissue factor (TF). However, resting cells do not express substantial amounts of TLR-4. Previously, we generated a mouse monoclonal anti-ß2 GPI antibody WB-6 and showed that it induced a prothrombotic state - including TF expression on circulating monocytes - in normal mice. In the current study, we aimed to clarify the mechanism of interaction between WB-6 and resting monocytes, and found that WB-6 exhibits binding activity to DNA and enters living monocytes or a monocytic cell line and, to a lesser extent, vascular endothelial cells. Treatment of the cells with DNase I reduced the internalization, suggesting the involvement of cell surface DNA in this phenomenon. Monocytes harboring internalized WB-6 expressed TF and tumor necrosis factor (TNF)-α which, in turn, stimulated endothelial cells to express intercellular adhesion molecule 1 (ICAM-I) and vascular cell adhesion molecule 1 (VCAM-I). These results suggest the possibility that a subset of anti-ß2 GPI antibodies with dual reactivity to DNA possesses ability to stimulate DNA sensors in the cytoplasm, in addition to the cell surface receptor-mediated pathways, leading to produce proinflammatory and prothrombotic states.


Assuntos
Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais/imunologia , Autoanticorpos/imunologia , Proteínas de Ligação a DNA/imunologia , Monócitos/metabolismo , beta 2-Glicoproteína I/imunologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Linhagem Celular Tumoral , Desoxirribonuclease I/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/biossíntese , Lúpus Eritematoso Sistêmico/imunologia , MAP Quinase Quinase 1/metabolismo , Proteínas de Membrana/biossíntese , Camundongos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Células THP-1 , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Versicanas/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Water Sci Technol ; 80(6): 1011-1021, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31799945

RESUMO

We investigated the operating conditions of a baffled membrane bioreactor (B-MBR) under which long-term stable operation can be achieved through the continuous operation of a pilot-scale B-MBR. Under appropriate operating conditions, the B-MBR was capable of achieving excellent treated water quality in terms of biochemical oxygen demand and concentration of total nitrogen. Excellent removal of total phosphorus was also achieved. In addition, the degree of membrane fouling was acceptable, indicating that stable continuous operation of a B-MBR is possible under the operating conditions adopted in the present study. Estimation of the specific energy consumption in hypothetical full-scale B-MBRs operated under the conditions recommended by the findings was also performed in this study. The results suggest that energy consumption in full-scale B-MBRs would be in the range of 0.20-0.22 kWh/m3. These results strongly suggest that energy consumption in MBR operation can be significantly reduced by applying the concept of a B-MBR.


Assuntos
Membranas Artificiais , Eliminação de Resíduos Líquidos , Reatores Biológicos , Membranas , Fósforo
11.
BMC Med Genet ; 19(1): 69, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720101

RESUMO

BACKGROUND: Congenital hypothyroidism (CH) has an incidence of approximately 1:3000, but only 15% have mutations in the thyroid hormone synthesis pathways. Genetic analysis allows for the precise diagnosis. CASE PRESENTATION: A 3-week old girl presented with a large goiter, serum TSH > 100 mIU/L (reference range: 0.7-5.9 mIU/L); free T4 < 3.2 pmol/L (reference range: 8.7-16 pmol/L); thyroglobulin (TG) 101 µg/L. Thyroid Tc-99 m scan showed increased radiotracer uptake. One brother had CH and both affected siblings have been clinically and biochemically euthyroid on levothyroxine replacement. Another sibling had normal thyroid function. Both Sudanese parents reported non-consanguinity. Peripheral blood DNA from the proposita was subjected to whole exome sequencing (WES). WES identified a novel homozygous missense mutation of the TG gene: c.7021G > A, p.Gly2322Ser, which was subsequently confirmed by Sanger sequencing and present in one allele of both parents. DNA samples from 354 alleles in four Sudanese ethnic groups (Nilotes, Darfurians, Nuba, and Halfawien) failed to demonstrate the presence of the mutant allele. Haplotyping showed a 1.71 centiMorgans stretch of homozygosity in the TG locus suggesting that this mutation occurred identical by descent and the possibility of common ancestry of the parents. The mutation is located in the cholinesterase-like (ChEL) domain of TG. CONCLUSIONS: A novel rare missense mutation in the TG gene was identified. The ChEL domain is critical for protein folding and patients with CH due to misfolded TG may present without low serum TG despite the TG gene mutations.


Assuntos
Hipotireoidismo Congênito/genética , Sequenciamento do Exoma/métodos , Mutação de Sentido Incorreto , Tireoglobulina/genética , Austrália/etnologia , Hipotireoidismo Congênito/sangue , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Linhagem , Dobramento de Proteína , Sudão , Tireoglobulina/sangue , Tireoglobulina/química
12.
Osteoporos Int ; 29(12): 2791-2801, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30143851

RESUMO

This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism. INTRODUCTION: This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women. METHODS: Participants were 43,652 women aged 40-69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors. RESULTS: During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24-3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01-2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92-0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51-3.73) in all women, 2.25 (1.35-3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499). CONCLUSIONS: Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.


Assuntos
Menstruação/fisiologia , Fraturas por Osteoporose/etiologia , História Reprodutiva , Fraturas da Coluna Vertebral/etiologia , Adulto , Fatores Etários , Idoso , Antropometria/métodos , Feminino , Humanos , Japão/epidemiologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/fisiopatologia
13.
Phys Rev Lett ; 120(15): 152501, 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29756864

RESUMO

The masses of ^{246}Es, ^{251}Fm, and the transfermium nuclei ^{249-252}Md and ^{254}No, produced by hot- and cold-fusion reactions, in the vicinity of the deformed N=152 neutron shell closure, have been directly measured using a multireflection time-of-flight mass spectrograph. The masses of ^{246}Es and ^{249,250,252}Md were measured for the first time. Using the masses of ^{249,250}Md as anchor points for α decay chains, the masses of heavier nuclei, up to ^{261}Bh and ^{266}Mt, were determined. These new masses were compared with theoretical global mass models and demonstrated to be in good agreement with macroscopic-microscopic models in this region. The empirical shell gap parameter δ_{2n} derived from three isotopic masses was updated with the new masses and corroborates the existence of the deformed N=152 neutron shell closure for Md and Lr.

14.
Phys Rev Lett ; 121(24): 242501, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-30608744

RESUMO

The isospin character of p-n pairs at large relative momentum has been observed for the first time in the ^{16}O ground state. A strong population of the J,T=1,0 state and a very weak population of the J,T=0,1 state were observed in the neutron pickup domain of ^{16}O(p,pd) at 392 MeV. This strong isospin dependence at large momentum transfer is not reproduced by the distorted-wave impulse approximation calculations with known spectroscopic amplitudes. The results indicate the presence of high-momentum protons and neutrons induced by the tensor interactions in the ground state of ^{16}O.

15.
Phys Rev Lett ; 120(15): 152505, 2018 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-29756883

RESUMO

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

16.
Mol Psychiatry ; 22(3): 430-440, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27240532

RESUMO

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.


Assuntos
Esquizofrenia/genética , Adulto , Estudos de Casos e Controles , Hibridização Genômica Comparativa/métodos , Variações do Número de Cópias de DNA/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Japão , Masculino , Polimorfismo de Nucleotídeo Único/genética
17.
Neoplasma ; 65(1): 132-139, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29322797

RESUMO

Malignant pleural effusion (MPE) is a common complication occurring in cancer patients, and its management affects the prognosis of these patients. Preclinical and clinical studies have reported that treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin (CBDCA) is effective against intraperitoneal malignant tumors. To investigate the effectiveness of nab-paclitaxel plus CBDCA therapy for MPEs arising in patients with non-small cell lung cancer (NSCLC), we retrospectively analyzed the clinicopathological characteristics of 40 patients with stage IIIb or IV NSCLC who were treated with nab-paclitaxel plus CBDCA from 2013 to 2016. Out of 26 patients with MPEs who were treated with nab-paclitaxel plus CBDCA in this study, 21 patients (80.8%) had effective responses in MPEs; 6 of 21 patients exhibited complete responses (23.1%) and 15 of 21 had partial responses (57.7%). Kaplan-Meier survival curves and log-rank tests to evaluate the effectiveness of nab-paclitaxel plus CBDCA therapy against MPEs showed longer median progression-free survival (323 days vs. 26 days; p=0.009) and overall survival (not reached vs. 199 days; p=0.047) in patients with complete responses compared with those who achieved no response. There were no statistical differences between therapeutic effects on MPEs and those on systemic lesions. Nab-paclitaxel plus CBDCA therapy may be a preferred therapeutic option for patients with NSCLC who experience MPEs, and its effectiveness in treatment of MPEs may need to be evaluated separately from its therapeutic responses in systemic lesions.


Assuntos
Albuminas/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Nanopartículas , Estudos Retrospectivos , Resultado do Tratamento
18.
BMC Pulm Med ; 18(1): 23, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29378571

RESUMO

BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor effects against various types of malignant tumors. However, its administration is complicated by immune-related adverse events (irAEs), including pneumonitis. CASE PRESENTATION: We present a case series of four patients with malignant melanoma, non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated pneumonitis induced by nivolumab, and further review clinicopathological characteristics of these patients in comparison with those of previously reported patients with nivolumab-induced pneumonitis. In our series, 20% of patients who were treated with nivolumab developed pneumonitis, all of which occurred approximately 2 weeks after the initiation of nivolumab treatment. Prompt recognition of the nivolumab-induced pneumonitis allowed for successful resolution. Computed tomography scan images of the patients demonstrated predominantly cryptogenic organizing pneumonia patterns. All patients were males, who had been heavily treated with antitumor drugs prior to nivolumab. CONCLUSIONS: Our case series showed that nivolumab had a high incidence of drug-induced pneumonitis with early onset, supporting the need for renewed attention to nivolumab-induced pneumonitis, particularly in patients with a history of heavy antitumor treatments.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Hipofaríngeas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Pneumonia/induzido quimicamente , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Idoso , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/epidemiologia , Tomografia Computadorizada por Raios X
19.
J Oral Rehabil ; 45(1): 9-16, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29090477

RESUMO

In a previous study, we used muscle functional magnetic resonance imaging to show that the anterior movement of the occlusal point increased the activity of the superior head of the ipsilateral lateral pterygoid muscle (ipsilateral SHLP) during unilateral single-tooth clenching. The purpose of this study was to verify the hypothesis that the increased activity of the ipsilateral SHLP described above serves to antagonise the occlusal force acting on the condyle. In total, 9 healthy volunteers were requested to perform left unilateral clenching at the first molar or first premolar region for 1 minute at 20% or 40% maximum voluntary clenching force. Changes in the mean proton transverse relaxation time (∆T2) were examined from the magnetic resonance images obtained before and after each clenching act as an index of the activity in all masticatory muscles. Correlation analyses of the mean ΔT2 for each volume of interest were performed with the first molar or premolar clenches to analyse the correlation between the activities in each muscle. A statistically significant correlation was exhibited between the ipsilateral temporal and ipsilateral SHLP (r = .651, P = .003) during first premolar clenching. However, no significant correlations were observed in the ipsilateral SHLP during first molar clenching. The results of this study suggest that the ipsilateral SHLP may contribute to the pulling of the mandibular condyle forward against the occlusal force generated by the ipsilateral temporal muscle.


Assuntos
Dente Pré-Molar/fisiologia , Imageamento por Ressonância Magnética , Côndilo Mandibular/fisiologia , Dente Molar/fisiologia , Contração Muscular/fisiologia , Músculos Pterigoides/fisiologia , Adulto , Dente Pré-Molar/diagnóstico por imagem , Fenômenos Biomecânicos , Força de Mordida , Feminino , Voluntários Saudáveis , Humanos , Masculino , Côndilo Mandibular/diagnóstico por imagem , Dente Molar/diagnóstico por imagem , Músculos Pterigoides/diagnóstico por imagem
20.
J Oral Rehabil ; 45(8): 598-604, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29761827

RESUMO

Clinicians' evaluations of older adults sometimes reveal inconsistencies between objective and subjective dental status. This study investigated which factors contribute both to good objective masticatory function (OMF) and the poor subjective masticatory function (SMF) that often becomes a clinical issue. Study participants included 635 elderly community-dwelling Japanese adults who underwent a comprehensive geriatric health examination in 2012. SMF was assessed with a question from the Kihon Checklist on eating difficulties (poor or good). OMF was assessed by a colour-changing gum (poor or good). Also investigated were age, sex, depressive symptoms, instrumental activities of daily living (I-ADLs), number of people who joined the participant at dinner, grip strength, usual walking speed, number of remaining teeth, number of functional teeth and their occlusal force. The group with good OMF and good SMF, defined as group 1, and the group with good OMF but poor SMF, group 2, were compared. Logistic regression analyses confirmed that the number of remaining and functional teeth participants had was statistically unrelated to differences between OMF and SMF. Instead, differences were related to stronger depressive symptoms (OR = 1.67, CI = 1.14-2.44), less ability to conduct I-ADL activities (OR = 0.73, CI = 0.59-0.91), slower usual walking speeds (OR = 0.18, CI = 0.06-0.58) and less occlusal force (OR = 0.99, CI = 0.99-1.00). Depressive symptoms, I-ADLs, and physical function are shown to be significantly related to divergence between objective and subjective masticatory function in elderly Japanese. This suggests that dissociations between objective and subjective dental evaluations of elderly adults indicate need for assessment of their mental and physical function.


Assuntos
Depressão/epidemiologia , Ingestão de Alimentos/fisiologia , Avaliação Geriátrica , Mastigação/fisiologia , Saúde Bucal/estatística & dados numéricos , Atividades Cotidianas , Idoso , Força de Mordida , Estudos Transversais , Feminino , Força da Mão/fisiologia , Humanos , Vida Independente , Japão , Masculino
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