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In this research, the CRDI engine characteristics were analyzed with the aid of exhaust gas recirculation rate (EGR) adoption fueled with ethanol blends. The test fuels were the various blends with ethanol, such as (10% of ethanol + 90% of diesel) E10D90 (20% of ethanol + 80% of diesel), E20D80, and (30% of ethanol + 70% of diesel) E30D70. From the results, it was revealed that performance characteristics were reduced when using a higher concentration of the alcohols mixed with diesel fuel. The blend E30D70 showed that brake thermal efficiency (BTE) without EGR drops by 3.8%, increased by 9.14% of BSFC, a 9.25% decrease in oxides of nitrogen emissions, and slightly decreased CO and HC emissions compared to baseline diesel operation at 60% load condition. The blend E10D90 with 20% EGR shows the highest BTE of 8.87% when compared with base fuel, due to proper fuel mixture taking place in the inlet manifold. The results indicate that the engine runs smoothly, and E30D70 has chosen an optimum blend. A further experiment was performed using E30D70 with different rates of exhaust gas recirculation system. The addition of exhaust gas recirculation with E30D70 in the common rail diesel engine exhibits oxides of nitrogen emission, but in contrast, it was noticed to have inferior performance characteristics and drastically decreased HC and CO emissions. The hydrocarbon emission decreased E10D90, E20D80, and E30D70 at 60% load condition by 21.42%, 37.38%, and 48.76%, respectively. The blends E10D90, E20D80, and E30D70 decreased carbon dioxide by 7.9%, 30.08%, and 31.98%, respectively. The maximum reduction of NOx emission was observed at about 51.06% at an EGR rate of 20% with E30D70.

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Background: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported., Methods: Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided., Results: Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22)., Conclusions: In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel., Competing Interests: Competing interests: BS reports honoraria from Acrotech Biopharma, BeiGene, Gilead Sciences, Janssen, Pharmacyclics, and Spectrum; consulting/advisory role for Adaptive Biotechnologies; Amgen; Celgene/BMS; Kite, a Gilead Company; Novartis; Pfizer; and Precision BioSciences; research funding from Gilead Sciences, Incyte, Jazz Pharmaceuticals, and Kite; and travel support from Celgene, Janssen, Kite, Novartis, Pfizer, Seattle Genetics, and Stemline Therapeutics. RC reports spouse employment with Seagen; stock or other ownership in Seagen; honoraria from Amgen, Autolus (board member), PeproMene Bio (board member), Pfizer, and Kite; consultancy/advisory role for Amgen and Jazz; and research funding from Pfizer, Merck, Amgen, Servier, Kite, and Vanda. JHP reports consulting/advisory role for AstraZeneca, Kite, and Novartis and research funding from Amgen, Genentech, and Juno. RH reports honoraria from ADC therapeutics, Bristol Myers Squibb, Celgene, Gilead Sciences, Janssen, Kite, MSD, Novartis, and Roche; and consulting/advisory role for Kite/Gilead. OOO reports consulting/advisory role for Pfizer, Kite, Gilead, AbbVie, Janssen, TG Therapeutics, ADC, Novartis, Epizyme, Curio Science, Nektar, and Syncopation; research funding from Kite, Pfizer, Daiichi Sankyo, and Allogene; and honoraria from Pfizer and Gilead. ACL reports consulting/advisory role for AbbVie, Bristol Myers Squibb, and Pfizer; research funding from Amgen, Amphivena, Astellas, Autolus, Jazz, Kadmon, Kite, and Pharmacyclics. NB reports honoraria from and consulting/advisory role for Gilead Sciences. TL reports consultancy/advisory role for Amgen and Servier. MRBi reports honoraria from Incyte, Bristol Myers Squibb, Sanofi, and ADC Therapeutics; consulting/advisory role for Novartis, Kite/Gilead, Bristol Myers Squibb, Sana Bio, and CRISPR Therapeutics; and speakers’ bureau participation for Incyte, Bristol Myers Squibb, Sanofi, and ADC Therapeutics. MST reports consulting/advisory role for Amgen, Celgene, Kite, Regeneron, and Roche and research funding from Amgen, Kite, MacroGenics, Regeneron, and Roche. DT reports consulting/advisory role for Bristol Myers Squibb, EUSA, Partner, and Takeda; and research funding from Bristol Myers Squibb. KMO reports consulting/advisory role for Beam Therapeutics. MLA reports consulting/advisory role for Kite and Syndax Pharmaceuticals, Inc. and research funding from Kite (institutional PI). YL reports consulting/advisory role for Kite/Gilead, Celgene/BMS, Juno/BMS, bluebird bio, Janssen, Legend Biotech, Gamida Cell, Novartis, Iovance, Takeda, Fosun Kite, and Pfizer and research funding from Kite/Gilead, Celgene/BMS, bluebird bio, Janssen, Legend Biotech, Merck, Takeda, and Boston Scientific. MRBa reports research funding from AbbVie, Ascentage, Kite, Kura, and Takeda. GJS reports honoraria and research funding from and speakers’ bureau participation for Kite. MS reports consulting/advisory role for Amgen, Celgene/BMS, Gilead Sciences, Janssen, and Novartis; speakers’ bureau participation for Celgene/BMS, Gilead Sciences, Janssen, and Novartis; research funding from Amgen, Gilead Sciences, Miltenyi Biotec, MorphoSys, Roche, and Seattle Genetics; and travel support from Takeda. MA reports stock or other ownership in CytoDyn; consulting/advisory role for Celgene; and speakers’ bureau participation for Celgene, Bristol Myers Squibb, AbbVie, and Kite. MCM reports consulting/advisory role for Gilead Sciences and Janssen-Cilag and speakers’ bureau participation for Janssen-Cilag and Medscape. WW reports consulting/advisory role for Genzyme and Sanofi and research funding from AbbVie, Acerta, Cyclacel, Genentech, Gilead Sciences, GSK, Janssen, Juno, Karyopharm, Loxo Oncology, miRagen, Novartis, Oncternal, Pharmacyclics, Sunesis, and Xencor. DJD reports consulting or advisory role for Agios, Amgen, Autolus, Blueprint Medicines, Forty Seven, Gilead Sciences, Incyte, Jazz, Novartis, Pfizer, Shire, and Takeda and research funding from AbbVie, Glycomimetics, Novartis, and Blueprint Medicines. PJS reports honoraria from and consulting or advisory role for MorphoSys and CRISPR Therapeutics and research funding from Amgen, Gamida Cell, Pfizer, Karyopharm, Gilead Sciences, Incyte, Seagen, and Cellectar. DJ reports research funding from Jazz Pharmaceuticals and Pfizer. DM has nothing to report. SA reports employment with and stock or other ownership in Kite. LZ reports employment with Kite and ownership of AbbVie RSU or stock in the past 2 years. reports employment with Kite; stock or other ownership in Gilead Sciences; and travel support from Kite and Gilead Sciences. RDK reports employment, stock, or other ownership in Kite. AG reports consulting/advisory role for Amgen, Atara, Bristol Myers Squibb, CRISPR Therapeutics, Kite, and Wugen Inc.; research funding from Amgen, Genentech, and Kite; and honoraria from Kite., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Human herpesvirus 6 (HHV-6) reactivation is common after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with higher mortality and increased transplantation-related complications. We hypothesized that preemptive treatment with a short course of foscarnet at a lower cutpoint of plasma HHV-6 viral load would be effective in treating early HHV-6 reactivation, preventing complications and precluding hospitalization of these patients. We reviewed outcomes of adult patients (age ≥18 years) who received preemptive treatment with once-daily foscarnet 60 to 90 mg/kg for 7 days for HHV-6 reactivation after allo-HSCT at our institution between May 2020 and November 2022. Plasma HHV-6 viral load was monitored by quantitative PCR twice monthly in the first 100 days post-transplantation and twice weekly after reactivation until resolution. Eleven patients with a median age of 46 years (range, 23 to 73 years) were included in the analysis. HSCT was performed with a haploidentical donor in 10 patients and with an HLA-matched related donor in 1 patient. The most common diagnosis was acute leukemia (9 patients). Myeloablative and reduced-intensity conditioning regimens were used in 4 and 7 patients, respectively. Ten of the 11 patients received post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis. The median follow-up was 440 days (range, 174 to 831 days), and the median time to HHV-6 reactivation was 22 days post-transplantation (range, 15 to 89 days). The median viral load at first reactivation was 3,100 copies/mL (range, 210 to 118,000 copies/mL), and the median peak viral load was 11,300 copies/mL (range, 600 to 983,000 copies/mL). All patients received a short course of foscarnet at either 90 mg/kg/day (n = 7) or 60 mg/kg/day (n = 4). In all patients, plasma HHV-6 DNA was undetectable at completion of 1 week of treatment. No HHV-6 encephalitis or pneumonitis occurred. All patients achieved neutrophil and platelet engraftment after a median of 16 days (range, 8 to 22 days) and 26 days (range, 14 to 168 days), respectively, with no secondary graft failure. No complications related to foscarnet administration were noted. One patient with very high HHV-6 viremia had recurrent reactivation and received a second course of foscarnet as an outpatient. A short course of once-daily foscarnet is effective in treating early HHV-6 reactivation post-transplantation and may reduce the incidence of HHV-6-related and treatment-related complications and preclude hospitalization in these patients., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Novel treatment strategies are needed for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in older patients. This trial evaluated the feasibility and outcomes with the anti-CD19 bispecific T-cell-engaging antibody, blinatumomab, in combination with dasatinib and steroids. Patients 65 years of age or older with Ph+ or Ph-like ALL (with dasatinib-sensitive fusions/mutations) were eligible and could be newly diagnosed or relapsed/refractory. Induction therapy consisted of dasatinib/prednisone. Patients not achieving response by day 56 proceeded to blinatumomab reinduction therapy. Patients achieving response with induction or reinduction therapy proceeded to blinatumomab/dasatinib postremission therapy for 3 cycles followed by dasatinib/prednisone maintenance. All patients received central nervous system prophylaxis with intrathecal methotrexate for a total of 8 doses. Response was assessed at days 28, 56, and 84 and at additional time points based on response parameters. Measurable residual disease was assessed centrally by 8-color flow cytometry at day 28. A total of 24 eligible patients with newly diagnosed Ph+ ALL were enrolled with a median age of 73 years (range, 65-87 years). This combination was safe and feasible. With a median of 2.7 years of follow-up, 3-year overall survival and disease-free survival were 87% (95% confidence interval [CI], 64-96) and 77% (95% CI, 54-90), respectively. Although longer follow-up is needed, these results are encouraging, and future trials are building on this backbone regimen. This trial was registered at www.clinicaltrials.gov as #NCT02143414., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care., Methods: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 10 6 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3., Results: After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients (N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 (N = 49) and matched historical controls (N = 40) was 25.4 and 5.5 months, respectively., Conclusions: These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population., Trial Registration: NCT02614066., (© 2022. The Author(s).)

Exploring non-platinum group metal (n-PGM) based efficient oxygen reduction reaction (ORR) electro-catalysts is highly important for realizing advancement in sustainable next generation-alkaline anion exchange membrane fuel cells (AAEMFCs). Herein, we demonstrate a new "hierarchical shape tuning approach" for the synthesis of controlled sized and shaped non-PGM based Ag ORR electro-catalysts with surface active nano-islands. Hierarchical shapes ranging from spherical (S-AgNs), worm-in-sphere, sphere-in-worm and vermiform (worm-like) Ag nanostructures (V-AgNs) were obtained by precisely varying the ratios of capping agent to dual reducing agents in water at ambient conditions. Compared to S-AgNs, V-AgNs revealed a higher mass normalized ORR Tafel activity (0.303 A mg Ag -1 at 0.9 V), onset (1.06 V) and half wave (0.78 V) potentials and higher retention of limiting current density (>88%) after 5000 cycles in 0.5 M potassium hydroxide (KOH) solution attributable to their unique worm like morphology with surface active nano-islands and support free-nature enabled better catalyst utilization. In a fully "non-PGM AAEMFC" (n-PAAEMFC), V-AgNs exhibited the highest fuel cell activity of 115.6 mW cm -2 and stable short-term durability (∼240 h) compared to S-AgNs (41.3 mW cm -2 ) and previously reported fully n-PAAEMFCs indicating their potential use in next-generation alkaline fuel cells., Competing Interests: Authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Semi-empirical and ab initio MO methods were used to explore mechanisms for the reduction of carbonyls by alkylaluminum reagents. Two distinct pathways have been observed experimentally, depending on the stoichiometric amounts of the reagents present. The corresponding intermediates and transition structures have been characterized. Alkylaluminum alkoxides are generally less reactive than the analogous alkylaluminum complexes. We suggest that the controlling factor here is not binding of the substrate, but the higher barrier to reaction of the alkoxide.

Quantitative methods to measure human immunodeficiency virus type 1 (HIV-1) integration promise to be important tools in dissecting the mechanisms whereby latent reservoirs of provirus are established, most notably in the resting T cells of patients receiving antiretroviral therapy. Here we describe a fluorescence-monitored, nested PCR assay that is able to quantify the relatively rare integration events that occur within these cells. Following DNA extraction, a nonkinetic preamplification step is performed with primers that bind genomic Alu elements and HIV-1 gag sequences, under conditions where primers, deoxynucleoside triphosphates, and enzyme are not limiting. This is followed by a kinetic PCR that quantitates HIV-1 long terminal repeat sequences. A T-cell-based integration standard which reflects the randomness of HIV-1 integration is also described. The assay is 10 to 100 times more sensitive than previously reported quantitative Alu PCR-based integration assays. It is specific for integration events, since no proviruses are detected in cells infected either in the presence of an integrase inhibitor or with an integrase-deficient virus. This method promises to provide important new insights into the processes underlying the accumulation and persistence of latent HIV-1 reservoirs and may eventually be useful clinically in monitoring the eradication of latent virus by novel therapies.

A detailed study using the cyclic voltammogram was done on the live cells of Aspergillus terreus. The peak current values were obtained for different days of growth and plotted against time. The response of cyclic voltammogram showed the phases of the growth of the fungus. The growth curve obtained matched well with the conventional methodology, which assesses the increase of dry weight of the organisms against time. The electrochemical method is more advantageous because it is easy to assess and consumes less time. Further the electrochemical method clearly shows the decline phase which is generally not very defined in the conventional method of assessment of the growth curve. It was confirmed by further experiments that the metabolites were responsible for the anodic peak and not the biomass. Further work is in progress in order to analyze the metabolite(s) that is/are responsible for the anodic peak.