Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a ...previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.
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•Sol-gel derived spinel NiMn2O4 is synthesized in pure phase.•The structural analysis has been carried out using Rietveld refinement.•The dependence of EIS on potential is extensively ...demonstrated for first time.•NiMn2O4 electrode exhibits maximum specific capacitance of 875 F g−1.•NiMn2O4 electrode shows excellent ASC device performance.
We report the synthesis of porous spinel-structured binary NiMn2O4 metal oxide nanoparticles and their performance as electrode material for supercapacitors. Spherical NiMn2O4 nanoparticles of ∼8 nm average diameter have been synthesized using inexpensive and simple sol-get method, and characterized by X-ray diffraction, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The electrodes made of this single phase spinel nanoparticles exhibit superior electrochemical performance with excellent rate capability, offering highest specific capacitance value of 875 F g−1 at 2.0 mV s−1 scan rate in 1 M Na2SO4 electrolyte solution. Furthermore, an asymmetric supercapacitor is also assembled and possesses a wide operating voltage window of 1.8 V, exhibiting an energy density of 75.01 W h kg−1 at a power density of 2250.91 W kg−1. The results infer this highly porous binary metal oxide nanostructures are promising candidates for high performance energy storage applications.
Sentiment classification or sentiment analysis has been acknowledged as an open research domain. In recent years, an enormous research work is being performed in these fields by applying numerous ...methodologies. Feature generation and selection are consequent for text mining as the high dimensional feature set can affect the performance of sentiment analysis. This paper investigates the inability of the widely used feature selection method (IG, Chi Square, Gini Index) individually as well as their combined approach on four machine learning classification algorithm. The proposed methods are evaluated on three standard datasets viz. IMDb movie review, electronics and kitchen product review dataset. Initially, select the feature subsets from three different feature selection methods. Thereafter, statistical method UNION, INTERSECTION and revised UNION method are applied to merge these different feature subsets to obtain all top ranked including common selected features. Finally, train the classifier SMO, MNB, RF, and LR (logistic regression) with this feature vector for classification of the review data set. The performance of the algorithm is measured by evaluation methods such as precision, recall, F-measure and ROC curve. Experimental results show that the combined method achieved best accuracy of 92.31 with classifier SMO, which is encouraging and comparable to the related research.
Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and ...adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability <80% (range, 61% to 79%). This first report of tisagenlecleucel in the real-world setting demonstrates outcomes with similar efficacy and improved safety compared with those seen in the pivotal trials.
•Represents the largest set of safety and efficacy data for tisagenlecleucel.•Outcomes in the real-world setting are similar to results in the pivotal trials.
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“Vertically aligned graphene nanosheets” are a type of graphitic carbon nanostructure with an interconnected network of perpendicularly aligned graphene nanosheets. In this study, the thin films of ...this material are deposited on stainless steel substrates using electron cyclotron resonance–based plasma-enhanced chemical vapor deposition. The variation of the electrochemical performance of the vertically aligned graphene nanosheets with the change in surface morphology is analyzed. The samples with different surface geometries offer different values of specific capacitances. The sample with nanopores between the graphene nanosheets of largest diameter and of most open nature delivers the highest specific electrode capacitance of 0.98 mF cm
−2
(11.09 F cm
−3
) at a current density 0.88 mA cm
−2
while the corresponding value for the sample with the smallest gap between nanosheets is of 0.49 mF cm
−2
(6.67 F cm
−3
). The results point out at a direct correlation between surface morphology and electrochemical performance of the material.
Silicon nanowires (SiNWs) are fabricated by Ag assisted chemical etching and are treated with hydrogen plasma created by electron cyclotron resonance (ECR) plasma system at 600 watts microwave power ...for various time durations (0–30 min). The hydrogen plasma exposure on the surface of the SiNWs reduced the surface roughness and increased the crystalline nature. SEM analysis revealed that the diameter of the SiNWs decreased on plasma exposure. The electrical conduction measurements suggested that the hydrogen plasma exposure for 5 min on the SiNW surface enhanced the electrical conductivity when compared to as fabricated SiNW surface. The hydrophobic nature of fabricated SiNWs was transformed to hydrophilic at plasma exposure for lower time duration. On plasma exposure of NWs for 30 min the sample turned hydrophobic. Study of different properties of the SiNWs before and after plasma treatment revealed that there is pronounced effect of plasma on the nature of SiNWs.
Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and ...frequency.IntroductionLymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.MethodsWe retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).ResultsFrom June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.DiscussionAs the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.
Sentiment classification or sentiment analysis has been acknowledged as an open research domain. In recent years, an enormous research work is being performed in these fields by applying various ...numbers of methodologies. Feature generation and selection are consequent for text mining as the high-dimensional feature set can affect the performance of sentiment analysis. This paper investigates the inability or incompetency of the widely used feature selection methods (IG, Chi-square, and Gini Index) with unigram and bigram feature set on four machine learning classification algorithms (MNB, SVM, KNN, and ME). The proposed methods are evaluated on the basis of three standard datasets, namely, IMDb movie review and electronics and kitchen product review dataset. Initially, unigram and bigram features are extracted by applying n-gram method. In addition, we generate a composite features vector CompUniBi (unigram + bigram), which is sent to the feature selection methods Information Gain (IG), Gini Index (GI), and Chi-square (CHI) to get an optimal feature subset by assigning a score to each of the features. These methods offer a ranking to the features depending on their score; thus a prominent feature vector (CompIG, CompGI, and CompCHI) can be generated easily for classification. Finally, the machine learning classifiers SVM, MNB, KNN, and ME used prominent feature vector for classifying the review document into either positive or negative. The performance of the algorithm is measured by evaluation methods such as precision, recall, and F-measure. Experimental results show that the composite feature vector achieved a better performance than unigram feature, which is encouraging as well as comparable to the related research. The best results were obtained from the combination of Information Gain with SVM in terms of highest accuracy.
The escalating demand for video content and streaming services has made it a predominant medium of exchanging information in the modern era. Videos are processed, compressed, and streamed over ...dynamic wireless channels having limited bandwidth. This introduces video impairments that deteriorate the video quality. Humans are the targeted observers of multimedia content. Improving viewing experience requires human intervened subjective assessment of video quality; which is relatively cumbersome and resource intensive. Devising alternatives that can estimate subjective quality scores are essential to evaluate Quality-of-Experience (QoE) in multimedia applications and services. The features (objective quality metrics and impairment factors) provide a measure of artifacts and content characteristics that influence observers viewing experience. We have proposed MO-QoE, a framework to predict video QoE using Multi-Feature Fusion (MFF) based Optimized Learning Models (OLMs). The OLMs are the optimized neural network models designed for QoE prediction. We make use of Adaptive Moment estimation and Batch Gradient Descent algorithms that update the values of weight and biases of the learning models to their optimal values. The inputs to our model is based on MFF scheme, that eliminates distortion specific biased performance of any individual feature. The resultant non-linear regression score from the model is obtained after fusion of scores from multiple features. The QoE prediction using the MFF-based OLMs has been tested on publicly available databases. The prediction performance/accuracy is improved by ≈2 to 3 times as compared to the existing models.
CD4
T-helper subsets drive autoimmune chronic graft-
-host disease, a major complication after allogeneic bone marrow transplantation. However, it remains unclear how specific T-helper subsets ...contribute to chronic graft-
-host disease. T-helper type 1 cells are one of the major disease-mediating T-cell subsets and require interferon-γ signaling and Tbet expression for their function. Regulatory T cells on the other hand can inhibit T-helper type 1 cell-mediated responses. Using an established murine model that isolates the autoimmune component of graft-
-host disease, we hypothesized that T-helper type 1 cells would restrict FoxP3-driven regulatory T cells. Upon transfer into immune-deficient syngeneic hosts, alloreactive
CD4
T cells led to marked increases in FoxP3
cells and reduced clinical evidence of autoimmunity. To evaluate whether peripheral induction contributed to regulatory T-cell predominance, we adoptively transferred
T cells that consisted of fate mapping for FoxP3: recipients of flow-purified effector cells that were Foxp3
and
had enhanced T-regulatory-cell predominance during autoimmune graft-
-host disease. These data directly demonstrated that peripheral T-regulatory-cell induction was inhibited by Tbet. Finally,
T-regulatory cells cross-regulated autoimmune wild-type T-effector-cell cytokine production
The Tbet pathway therefore directly impairs T-regulatory-cell reconstitution and is consequently a feasible target in efforts to prevent autoimmune graft-
-host disease.
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