A patient with refractory multiple myeloma received an infusion of CTL019 cells, a cellular therapy consisting of autologous T cells transduced with an anti-CD19 chimeric antigen receptor, after ...myeloablative chemotherapy (melphalan, 140 mg per square meter of body-surface area) and autologous stem-cell transplantation. Four years earlier, autologous transplantation with a higher melphalan dose (200 mg per square meter) had induced only a partial, transient response. Autologous transplantation followed by treatment with CTL019 cells led to a complete response with no evidence of progression and no measurable serum or urine monoclonal protein at the most recent evaluation, 12 months after treatment. This response was achieved despite the absence of CD19 expression in 99.95% of the patient's neoplastic plasma cells. (Funded by Novartis and others; ClinicalTrials.gov number, NCT02135406.).
Nano-structured silicon is an attractive alternative anode material to conventional graphite in lithium-ion batteries. However, the anode designs with higher silicon concentrations remain to be ...commercialized despite recent remarkable progress. One of the most critical issues is the fundamental understanding of the lithium-silicon Coulombic efficiency. Particularly, this is the key to resolve subtle yet accumulatively significant alterations of Coulombic efficiency by various paths of lithium-silicon processes over cycles. Here, we provide quantitative and qualitative insight into how the irreversible behaviors are altered by the processes under amorphous volume changes and hysteretic amorphous-crystalline phase transformations. Repeated latter transformations over cycles, typically featured as a degradation factor, can govern the reversibility behaviors, improving the irreversibility and eventually minimizing cumulative irreversible lithium consumption. This is clearly different from repeated amorphous volume changes with different lithiation depths. The mechanism behind the correlations is elucidated by electrochemical and structural probing.
The first passage time (FPT) for random walks is a key indicator of how fast information diffuses in a given system. Despite the role of FPT as a fundamental feature in transport phenomena, its ...behavior, particularly in heterogeneous networks, is not yet fully understood. Here, we study, both analytically and numerically, the scaling behavior of the FPT distribution to a given target node, averaged over all starting nodes. We find that random walks arrive quickly at a local hub, and therefore, the FPT distribution shows a crossover with respect to time from fast decay behavior (induced from the attractive effect to the hub) to slow decay behavior (caused by the exploring of the entire system). Moreover, the mean FPT is independent of the degree of the target node in the case of compact exploration. These theoretical results justify the necessity of using a random jump protocol (empirically used in search engines) and provide guidelines for designing an effective network to make information quickly accessible.
A very high hole mobility of 15 cm2 V−1 s−1 along with negligible hysteresis are demonstrated in transistors with an organic–inorganic perovskite semiconductor. This high mobility results from the ...well‐developed perovskite crystallites, improved conversion to perovskite, reduced hole trap density, and improved hole injection by employing a top‐contact/top‐gate structure with surface treatment and MoOx hole‐injection layers.
Abstract The purpose of this study was to evaluate the volumetric change of the upper airway space in 36 Class III patients who had undergone bimaxillary surgery or isolated mandibular setback, and, ...further, to analyse the relation between post-surgical stability and airway change using cone-beam computed tomography (CBCT). A three-dimensional (3D) CBCT examination was performed at three stages: T0 (before surgery), T1 (an average of 4.6 months after surgery), and T2 (an average of 1.4 years after surgery). The results showed that the volumes of the oropharyngeal and hypopharyngeal airways decreased significantly 4.6 months post-surgery in the mandibular setback group ( p < 0.05), and these diminished airways had not recovered 1.4 years post-surgery. In the bimaxillary surgery group, the volume of the oropharyngeal airway also decreased. A Spearman correlation analysis showed that the anteroposterior length of the hypopharyngeal area had a correlation with post-surgical stability in the isolated mandibular surgery group, and that the cross-sectional area of the nasopharynx was correlated with maxillary relapse only in the bimaxillary surgery group ( p < 0.05).
Objective
The present study aimed to analyse the Korean National Health Insurance Service (NHIS) cohort data to examine the safety of acupuncture therapy during pregnancy.
Design
Retrospective ...cohort.
Setting
Korea.
Population or sample
Women with confirmed pregnancy between 2003 and 2012 from the 2002–13 NHIS sample cohort (n = 20 799).
Methods
Women with confirmed pregnancy were identified and divided into acupuncture or control group for comparison of their outcomes. Differences in other factors such as age, and rate of high‐risk pregnancy and multiple pregnancy were examined. In the acupuncture group, the most frequent acupuncture diagnosis codes and the timing of treatment were also investigated.
Main outcome measures
Incidence of full‐term delivery, preterm delivery and stillbirth by pregnancy duration and among the high‐risk and multiple pregnancy groups.
Results
Of 20 799 pregnant women analysed, 1030 (4.95%) and 19 749 were in the acupuncture and control groups, respectively. Both overall (odds ratio OR 1.23; 95% CI 0.98–1.54), and in the stratified analysis of high‐risk pregnancies (OR 1.09; 95% CI 0.73–1.64), there was no significant difference between acupuncture and control groups in preterm deliveries. No stillbirths occurred in the acupuncture group and 0.035% of pregnancies resulted in stillbirths in the control group.
Conclusion
No significant difference in delivery outcomes (preterm delivery and stillbirth) was observed between confirmed pregnancies in the acupuncture and control groups. Therefore, in pregnancy, acupuncture therapy may be a safe therapeutic modality for relieving discomfort without an adverse delivery outcome.
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In pregnancy, acupuncture therapy may be a safe therapeutic modality for relieving discomfort without an adverse outcome.
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In pregnancy, acupuncture therapy may be a safe therapeutic modality for relieving discomfort without an adverse outcome.
Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular‐related morbidity ...and mortality may reduce life expectancy after LT. It is unknown if the risk of long‐term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow‐up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20–3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long‐term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.
In a retrospective cohort study of 994 liver transplant recipients utilizing adjusted competing risk regression models, sustained posttransplant diabetes mellitus is the only diabetic state associated with a significantly increased risk of long‐term major atherosclerotic cardiac events and cardiac arrest.
Aim
To evaluate the anti‐inflammatory effects of glutamine and the underlying signal pathway mechanisms in lipopolysaccharide (LPS)‐stimulated human dental pulp cells (HDPCs).
Methods
Human dental ...pulp cells were exposed to 10 μg mL−1 LPS and various concentrations of glutamine for 24 h. The production of PGE2 and nitric oxide was determined by enzyme‐linked immunosorbent assay (ELISA) and Griess reagent kit, respectively. Cytokines were examined by ELISA, reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time PCR. iNOS and COX protein expression as well as signal pathways were accessed by Western blot. The data were analysed by anova with Bonferroni's test (α = 0.05).
Results
Glutamine reduced LPS‐induced iNOS and COX‐2 protein expression as well as production of NO and PGE2 in a dose‐dependent fashion. Additionally, glutamine suppressed the production and mRNA expression of inflammatory cytokines including interleukin‐1β (IL‐1β), TNF‐α, and IL‐8. Furthermore, glutamine attenuated phosphorylation of extracellular signal‐regulated kinase (ERK), p38, c‐Jun N‐terminal kinase (JNK) and IκB‐α, and nuclear translocation of NF‐kB p65, but enhanced mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) expression in LPS‐treated HDPCs.
Conclusion
Glutamine exerted an anti‐inflammatory effect via activation of MKP‐1 and inhibition of the NF‐kB and MAPK pathways in LPS‐treated HDPCs.
Melatonin receptors can inhibit breast and prostate cancers; however, little is known regarding their effects on oral squamous cell carcinoma. In this study, we collected specimens from 81 patients ...with oral squamous cell carcinoma and analysed clinicopathological data retrospectively. In addition, the expression of the melatonin receptor was analysed immunohistochemically. Survival rates were calculated using the Kaplan–Meier method and log-rank test. Multivariate analysis was performed based on the Cox proportional-hazards model. Further, an in vitro study was performed using YD15 cells. The cells were transfected with siRNA targeting melatonin receptor 1A and 1B for evaluating the malignancy of melatonin receptors by western blotting, trypan blue-exclusion, colony-forming, wound-healing, and invasion assays. Survival decreased as melatonin receptor expression and clinical and pathological tumour–node–metastasis stages increased. A Cox proportional-hazard model showed that melatonin receptor 1A may serve as a significant predictor of the survival rate of patients with oral squamous cell carcinoma hazard ratio = 1.423, 95% confidence interval (CI) = 1.019–1.988, p = 0.038. Melatonin receptor 1A and 1B knockdown significantly suppressed proliferation, migration ability, and invasion ability of YD15 cells in vitro. Our findings reveal that inhibiting melatonin receptor expression may suppress oral squamous cell carcinoma development.
The relationship between reperfusion and clinical outcome is time-dependent, and the effect of reperfusion on outcome can vary on the basis of the extent of collateral flow. We aimed to identify the ...impact of time-to-reperfusion on outcome relative to baseline angiographic collateral grade in patients successfully treated with endovascular revascularization for acute large-vessel anterior circulation stroke.
Two hundred seven patients were selected for analysis from our prospectively maintained registry. Inclusion criteria were M1 MCA ± ICA occlusions, onset-to-puncture time within 8 hours, and successful endovascular reperfusion. Baseline angiographic collateral grades were independently evaluated and dichotomized into poor (0-1) versus good (2-4). Multivariable analyses were performed to identify the effect of collateral-flow adequacy on favorable outcome on the basis of onset-to-reperfusion time and puncture-to-reperfusion time.
In the poor collateral group, the odds of favorable outcome significantly dropped for patients with onset-to-reperfusion time of >300 minutes or puncture-to-reperfusion time of >60 minutes (onset-to-puncture time: ≤300, 59% versus >300, 32%; OR, 0.24; P = .011; puncture-to-reperfusion time: ≤60, 73% versus >60, 32%; OR, 0.21, P = .011), whereas the probability of favorable outcome in the good collateral group was not significantly influenced by onset-to-reperfusion time or puncture-to-reperfusion time. In the subgroup lesion-volume growth analysis by using DWI, the effect of puncture-to-reperfusion time of >60 minutes was significantly greater compared with the effect of puncture-to-reperfusion time of <60 minutes in the poor collateral group (β = 41.6 cm(3), P = .001).
Time-to-reperfusion including onset-to-reperfusion time and puncture-to-reperfusion time in patients with poor collaterals is an important limiting factor for favorable outcome in a time-dependent fashion. Future trials may benefit from a noninvasive imaging technique to detect poor collaterals along with a strategy for rapid reperfusion.
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