Trends in Volumes and Survival After Hematopoietic Cell Transplantation in Racial/Ethnic Minorities.

There has been an increase in volume as well as improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have impacted racial/ethnic minorities equally. In this observational study from Center for International Blood and Marrow Transplant Research of 79,904 autologous (auto) and 65,662 allogeneic (allo) HCTs, we examined the volume and rates of change of auto HCT and allo HCT over time and trends in OS in 4 racial/ethnic groups: Non-Hispanic Whites (NHWs), Non-Hispanic African Americans (NHAAs), Hispanics across five 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs. NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (HR 1.13; 95% CI 1.04-1.22; p=0.004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; p<0.001 had a higher risk of mortality after alloHCT compared to NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT.Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics compared to NHWs. Survival after autoHCT and alloHCT improved over time, however NHAAs have worse OS after alloHCT which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Real-World and Clinical Trial Outcomes in Large B-cell Lymphoma with Axicabtagene Ciloleucel Across Race and Ethnicity.

Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Despite extensive data supporting the use of axi-cel in patients with LBCL, outcomes stratified by race and ethnicity groups are limited. Here, we report clinical outcomes with axi-cel in patients with R/R LBCL by race and ethnicity in both real-world and clinical trial settings. In the real-world setting, 1290 patients with R/R LBCL who received axi-cel between 2017-2020 were identified from the Center for International Blood and Marrow Transplant Research database; 106 and 169 patients were included from the ZUMA-1 and ZUMA-7 clinical trials, respectively. Adjusted odds ratio (OR) and hazard ratio (HR) for race and ethnicity groups are reported. Overall survival was consistent across race/ethnicity groups. However, non-Hispanic (NH) Black patients had lower overall response rate (OR, 0.37, [95% CI, 0.22-0.63]) and lower complete response rate (OR, 0.57, [95% CI, 0.33-0.97]) than NH-white patients. NH-Black patients also had a shorter progression-free survival versus NH-white (HR, 1.41, [95% CI, 1.04-1.90]) and NH-Asian patients (HR, 1.67, [95% CI, 1.08-2.59]). NH-Asian patients had a longer duration of response compared with NH-white (HR, 0.56, [95% CI, 0.33-0.94]) and Hispanic patients (HR, 0.54, [95% CI, 0.30-0.97]). There was no difference in cytokine release syndrome by race/ethnicity; however, higher rates of any-grade ICANS were observed in NH-white patients compared with other patients. These results provide important context when treating patients with R/R LBCL with axi-cel across different racial and ethnic groups. ZUMA-1 (NCT02348216) and ZUMA-7 (NCT03391466), both registered on ClinicalTrials.gov.

The 3-component mixture of power distributions under Bayesian paradigm with application of life span of fatigue fracture.

Mixture distributions are naturally extra attractive to model the heterogeneous environment of processes in reliability analysis than simple probability models. This focus of the study is to develop and Bayesian inference on the 3-component mixture of power distributions. Under symmetric and asymmetric loss functions, the Bayes estimators and posterior risk using priors are derived. The presentation of Bayes estimators for various sample sizes and test termination time (a fact of time after that test is terminated) is examined in this article. To assess the performance of Bayes estimators in terms of posterior risks, a Monte Carlo simulation along with real data study is presented.

Proceeding of catalytic water splitting on Cu/Ce@g-C3N4 photocatalysts: an exceptional approach for sunlight-driven hydrogen generation.

Increasing energy demands and environmental problems require carbon-free and renewable energy generation systems. For this purpose, we have synthesized efficient photocatalysts (i.e., g-C3N4, Cu@g-C3N4, Ce@g-C3N4 and Cu/Ce@g-C3N4) for H2 evolution from water splitting. Their optical, structural and electrochemical properties were investigated by UV-Vis-DRS, PL, XRD, FTIR, Raman and EIS methods. Their surface morphologies were evaluated by AFM and SEM analyses. Their chemical characteristics, compositions and stability were assessed using XPS, EDX and TGA techniques. Photoreactions were performed in a quartz reactor (150 mL/Velp-UK), whereas hydrogen generation activities were monitored using a GC-TCD (Shimadzu-2014/Japan). The results depicted that Cu/Ce@g-C3N4 catalysts are the most active catalysts that deliver 23.94 mmol g-1 h-1 of H2. The higher rate of H2 evolution was attributed to the active synergism between Ce and Cu metals and the impact of surface plasmon electrons (SPEs) of Cu that were produced during the photoreaction. The rate of H2 production was optimized by controlling various factors, including the catalyst amount, light intensity, pH, and temperature of the reaction mixture. It has been concluded that the current study holds promise to replace the conventional and costly catalysts used for hydrogen generation technologies.

Structural performance of FRP composite bars reinforced rubberized concrete compressive members: Tests and numerical modeling.

Waste tyre rubber has become an environmental and health concern that needs to be sustainably managed to avoid fire hazards and save natural resources. This research work aims to study the structural behavior of glass fiber reinforced polymer (glass-FRP) reinforced rubberized concrete (GRC) compressive elements under monotonic axial compression loads. Nine GRC circular compressive elements with different axial and crosswise reinforcement ratios were fabricated. All the elements were 300 mm in diameter and 1200 mm in height. A 3D nonlinear finite element equation (FEM) was suggested for the GRC compressive elements using a commercial package ABAQUS. A parametric study has been done to examine the effect of various parameters of GRC elements. The test outcomes revealed that the ductility of GRC elements ameliorated with the lessening in the spaces of glass-FRP ties. The addition of rubberized concrete improved the ductility of GRC elements. The damage to GRC elements occurred due to the vertical cracking along the height of the elements. The estimates of FEM were in close agreement with the test outcomes. The suggested empirical equation depending on the 600 test elements, which considered the lateral confinement effect of FRP ties, presented higher accuracy than previous equations.

Efficacy of SARS-CoV-2 Vaccine Doses in Allogeneic Hemopoietic Stem Cell Recipients: A Systematic Review and Meta-Analysis.

OBJECTIVE: Recipients of allogeneic hematopoietic cell transplantation (alloHCT) are at increased risk of morbidity and mortality due to COVID-19. Immune responses to SARS-CoV-2 vaccines are blunted in these profoundly immunocompromised patients. As a result, novel strategies for protection, such as additional vaccine doses (boosters), are being explored. However, data regarding the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients are limited and conflicting. METHODS: In this systematic review and meta-analysis, we investigated the efficacy of a third dose of SARS-CoV-2 vaccine in alloHCT recipients. The review was conducted following PRISMA guidelines, and 7 studies with 385 alloHCT recipients who received 3 vaccine doses were included. The primary outcomes assessed were the rate of seroconversion following the third dose of vaccine and the rate of seroconversion in patients who did not respond to the initial 2-dose vaccination series. RESULTS: The pooled humoral response rate after 3 doses of SARS-CoV-2 vaccine in alloHCT recipients was 74%. In a subgroup analysis of patients who did not respond to the initial 2-dose series, the seroconversion rate following the third vaccine dose was 49%. Notably, male patients and those with a shorter interval between alloHCT and the first vaccine dose were more likely to not respond to the third dose. CONCLUSION: In conclusion, the pooled humoral response rate of 74% following three doses of SARS-CoV-2 vaccine in alloHCT recipients highlights the potential for protection in this immunosuppressed population. Additionally, encouraging responses in nearly half of the patients who did not seroconvert with the initial 2-dose series suggest the continued utilization of additional vaccine doses until results from large prospective studies become available. These findings are critical for informing vaccination strategies in alloHCT recipients to mitigate the high mortality risk associated with COVID-19.

Integrative analysis of RNA expression data unveils distinct cancer types through machine learning techniques.

Cancer is a highly complex and heterogeneous disease. Traditional methods of cancer classification based on histopathology have limitations in guiding personalized prognosis and therapy. Gene expression profiling provides a powerful approach to unraveling molecular intricacies and better-stratifying cancer subtypes. In this study, we performed an integrative analysis of RNA sequencing data from five cancer types - BRCA, KIRC, COAD, LUAD, and PRAD. A machine learning workflow consisting of dataset identification, normalization, feature selection, dimensionality reduction, clustering, and classification was implemented. The k-means algorithm was applied to categorize samples into distinct clusters based solely on gene expression patterns. Five unique clusters emerged from the unsupervised machine learning based analysis, significantly correlating with the known cancer types. BRCA aligned predominantly with one cluster, while COAD spanned three clusters. KIRC was represented within two main clusters. LUAD is associated strongly with a single cluster and PRAD with another cluster. This demonstrates the ability of machine learning approaches to unravel complex signatures within transcriptomic profiles that can delineate cancer subtypes. The proposed study highlights the potential of integrative analytics to derive meaningful biological insights from high-dimensional omics datasets. Molecular subtyping through machine learning clustering enhances our understanding of the intrinsic heterogeneities and pathways dysregulated in different cancers. Overall, this study exemplifies a powerful computational framework to classify gene expressions of patients having different types of cancers and guide personalized therapeutic decisions. Finally, Wide Neural Network demonstrates a significantly higher accuracy, achieving 99.834% on the validation set and an even more impressive 99.995% on the test set.

Biological control of tomato early blight in Pakistan using local rhizobacteria.

BACKGROUND: The biocontrol potential of soil microbes can reduce the extensive use of hazardous synthetic fungicides. This study was designed to find a strain of rhizobacteria indigenous to Pakistan with potential biocontrol against early blight of tomato caused by Alternaria solani and to characterize its biocontrol mechanisms. RESULTS: Among 88 strains tested for antagonism against A. solani on agar media, S27, Dt10 and 423, identified by 16S rRNA sequencing as strains of Bacillus amyloliquefaciens, B. cereus and Stenotrophomonas rhizophila, respectively, were the most inhibitory. When applied to detached tomato leaflets in Petri dish assays, the strains reduced lesion development by over 30% compared to the control. In greenhouse pot trials, the bacterial strains reduced early blight severity by over 50%. In three field trials, all three strains applied to tomato foliage slowed early blight disease progress and reduced disease severity, with B. amyloliquefaciens S27 reducing the area under the disease progress curve by up to 70%. All three strains showed protease, catalase and oxidase activities in vitro, but none produced ß-1,3-glucanase and only B. cereus Dt10 showed slight chitinase activity. In a greenhouse experiment in which the bacteria were applied to tomato foliage prior to pathogen inoculation, bacteria-treated leaves had higher ß-1,3-glucanase and chitinase levels than leaves inoculated only with the pathogen, indicating priming induction of response. CONCLUSION: Three rhizobacteria strains have the potential to control early blight of tomato under Pakistan's growing conditions, with B. amyloliquefaciens S27 being the most promising candidate for commercial development. Antagonism and induction of the priming response may be mechanisms of biocontrol by the bacterial strains. © 2023 Society of Chemical Industry.

Efficacy of Multiple SARS-CoV-2 Vaccine Doses in Patients with B Cell Hematologic Malignancies Receiving Chimeric Antigen Receptor T Cell Therapy: A Contemporary Cohort Analysis.

The mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approaches 40% in recipients of chimeric antigen receptor (CAR) T cell therapy (CAR-T). The efficacy of repeated vaccine doses, including bivalent boosters, remains unknown. We examined the efficacy of repeated vaccine doses among CAR-T recipients who received at least 2 or more vaccine doses after T cell infusion. This single-center retrospective study included adults age >18 years receiving CAR-T for relapsed/refractory (R/R) B cell hematologic malignancies targeting CD19, BCMA, or CD19 and CD20 between September 2018 through March 2022 and were alive beyond 2021 to receive incremental SARS-CoV-2 vaccine doses with available seroconversion data. Multivariable analyses were performed using the design-adjusted Cox regression and logistic regression approaches with stratification. In multivariable analysis, seroconversion rates were significantly greater with a total of 4 or more vaccine doses (odds ratio [OR], 8.22; P = .008). CAR-T recipients with other B cell hematologic malignancies had significantly lower seroconversion rates and diminished Ab titers compared to those with R/R multiple myeloma (OR, .07; P = .003). One patient died due to COVID-19 in this vaccinated study cohort, accounting for a COVID-19-attributable mortality rate of 1.7%. The results provide baseline vaccine response data in a contemporary cohort including patients with diverse group of SARS-COV2 variants and support the latest Centers for Disease Control and Prevention guidelines for repeated vaccinations directed against the prevalent variant of concern.

Management of Complications after Levator Resection for Ptosis.

OBJECTIVE: To analyse the complications after external levator resection (ELR) for ptosis, and their management. STUDY DESIGN: Observational Study. Place and Duration of the Study: Mughal Eye Hospital Trust, Lahore, from June 2018 to December 2022. METHODOLOGY: A total of 256 eyes were operated for ptosis cases having good levator function who were treated by ELR. The exclusion criteria was any history of operation of lids or orbits or poor levator function, Marcus Gunn jaw-winking phenomenon, and neurogenic ptosis. The frequency of complications and their management was documented. RESULTS: Age ranged from 6 to 65 years. The follow-up ranged from 8 weeks to 3 years. Eleven (4.3%) cases developed complications. Two cases had mild undercorrection and did not require any treatment. In moderate overcorrection encountered in one eye, pulling the lid down for a few times daily improved lid level in four weeks. Four eyes had severe overcorrection, 2 patients required one operation and the other two patients required two operations each. These included hang-back sutures in two eyes (with 5/O Ethibond in one eye and 6/O Vicryl sutures in another eye) and simple incision in the levator (disinserting it partially from the tarsal plate) in two eyes. Lagophthalmos in two eyes improved with conservative treatment. Notching in two eyes improved with partial disinsertion of levator by cutting one Vicryl suture attaching levator to the tarsal plate and leaving 2 Vicryl sutures connecting levator to the tarsal plate. CONCLUSION: Ptosis correction by ELR is a low-complication procedure with good corrective results. KEY WORDS: Ptosis, Good levator function, Overcorrection after ptosis operation, Hang-back sutures, Partial levator disinsertion.

Decadal oscillation provides skillful multiyear predictions of Antarctic sea ice.

Over the satellite era, Antarctic sea ice exhibited an overall long-term increasing trend, contrary to the Arctic reduction under global warming. However, the drastic decline of Antarctic sea ice in 2014-2018 raises questions about its interannual and decadal-scale variabilities, which are poorly understood and predicted. Here, we identify an Antarctic sea ice decadal oscillation, exhibiting a quasi-period of 8-16 years, that is anticorrelated with the Pacific Quasi-Decadal Oscillation (r = -0.90). By combining observations, Coupled Model Intercomparison Project historical simulations, and pacemaker climate model experiments, we find evidence that the synchrony between the sea ice decadal oscillation and Pacific Quasi-Decadal Oscillation is linked to atmospheric poleward-propagating Rossby wave trains excited by heating in the central tropical Pacific. These waves weaken the Amundsen Sea Low, melting sea ice due to enhanced shortwave radiation and warm advection. A Pacific Quasi-Decadal Oscillation-based regression model shows that this tropical-polar teleconnection carries multi-year predictability.

A High-K+ Affinity Transporter (HKT) from Actinidia valvata Is Involved in Salt Tolerance in Kiwifruit.

Ion transport is crucial for salt tolerance in plants. Under salt stress, the high-affinity K+ transporter (HKT) family is mainly responsible for the long-distance transport of salt ions which help to reduce the deleterious effects of high concentrations of ions accumulated within plants. Kiwifruit is well known for its susceptibility to salt stress. Therefore, a current study was designed to decipher the molecular regulatory role of kiwifruit HKT members in the face of salt stress. The transcriptome data from Actinidia valvata revealed that salt stress significantly induced the expression of AvHKT1. A multiple sequence alignment analysis indicated that the AvHKT1 protein contains three conserved amino acid sites for the HKT family. According to subcellular localization analysis, the protein was primarily present in the cell membrane and nucleus. Additionally, we tested the AvHKT1 overexpression in 'Hongyang' kiwifruit, and the results showed that the transgenic lines exhibited less leaf damage and improved plant growth compared to the control plants. The transgenic lines displayed significantly higher SPAD and Fv/Fm values than the control plants. The MDA contents of transgenic lines were also lower than that of the control plants. Furthermore, the transgenic lines accumulated lower Na+ and K+ contents, proving this protein involvement in the transport of Na+ and K+ and classification as a type II HKT transporter. Further research showed that the peroxidase (POD) activity in the transgenic lines was significantly higher, indicating that the salt-induced overexpression of AvHKT1 also scavenged POD. The promoter of AvHKT1 contained phytohormone and abiotic stress-responsive cis-elements. In a nutshell, AvHKT1 improved kiwifruit tolerance to salinity by facilitating ion transport under salt stress conditions.

Challenges, limitations, and applications of nanofluids in solar thermal collectors-a comprehensive review.

The daily increase in the demand for energy consumption is partly caused by the global population explosion and advancements in technology. Humanity relies on energy to fulfil its daily routines, such as electricity for lighting, heating, cooling, and running electronic devices. There are continuous attempts by researchers and industry experts to optimize and enhance the efficiency of various sustainable energy generation devices. Solar collectors play a critical role in the renewable energy sector, which is vital in helping the world achieve a clean, green, and sustainable environment. Over the last two decades, researchers have made significant efforts to explore various techniques for enhancing the effectiveness of solar thermal collectors. Their effort has been centered around improving the fluid thermal properties, which act as the heat transfer medium in solar collectors. The discovery of nanofluids will help resolve some of the challenges associated with conventional fluid used in solar collectors. Enhancement through nanofluids is influenced by several factors, which include nanoparticle types, nanoparticle concentration, base fluid, and the purpose of its application. This review provides a technical summary of the application of nanofluids in the two main types of collectors: non-concentrating and concentrated thermal collectors. Findings from this study showed that TiO2 + Cu hybrid nanofluids with a mass fraction of 0.03 augment heat transfer coefficient by 21% in parabolic trough collectors. The merits of employing nanofluids as heat transfer fluids in solar collectors are examined, while also outlining the obstacles and areas where further research is needed.

Advances in the application of functional nanomaterial and cold plasma for the fresh-keeping active packaging of meat.

The most recent advancements in food science and technology include cold sterilization of food and fresh-keeping packaging. Active packaging technology has received much interest due to the photocatalytic activity (PCA) of functional nanoparticles, including titanium dioxide (TiO2) and ferric oxide (Fe2O3). However, there are still significant concerns about the toxicity and safety of these functional nanoparticles. This review emphasizes the bacteriostatic and fresh-keeping properties of functional nanoparticles as well as their packaging strategies using the ultraviolet photo-catalysis effect. High-voltage electric field cold plasma (HVEF-CP) is the most innovative method of cold-sterilizing food. HVEF-CP sterilizes by producing photoelectrons, ions, and active free radicals on food media, which come into contact with the bacteria's surface and destroy their cells. Next, this review also assesses the photocatalytic activity and bacteriostasis kinetics of nanosized TiO2 and Fe2O3 in poultry, beef, and lamb. In addition, this review also emphasizes the importance of exploiting the complex interaction processes between TiO2 and Fe2O3, along with dietary components and their utilization in the fresh meat industry.

Genome-wide identification of the heat shock transcription factor gene family in two kiwifruit species.

High temperatures have a significant impact on plant growth and metabolism. In recent years, the fruit industry has faced a serious threat due to high-temperature stress on fruit plants caused by global warming. In the present study, we explored the molecular regulatory mechanisms that contribute to high-temperature tolerance in kiwifruit. A total of 36 Hsf genes were identified in the A. chinensis (Ac) genome, while 41 Hsf genes were found in the A. eriantha (Ae) genome. Phylogenetic analysis revealed the clustering of kiwifruit Hsfs into three distinct groups (groups A, B, and C). Synteny analysis indicated that the expansion of the Hsf gene family in the Ac and Ae genomes was primarily driven by whole genome duplication (WGD). Analysis of the gene expression profiles revealed a close relationship between the expression levels of Hsf genes and various plant tissues and stress treatments throughout fruit ripening. Subcellular localization analysis demonstrated that GFP-AcHsfA2a/AcHsfA7b and AcHsfA2a/AcHsfA7b -GFP were localized in the nucleus, while GFP-AcHsfA2a was also observed in the cytoplasm of Arabidopsis protoplasts. The results of real-time quantitative polymerase chain reaction (RT-qPCR) and dual-luciferase reporter assay revealed that the majority of Hsf genes, especially AcHsfA2a, were expressed under high-temperature conditions. In conclusion, our findings establish a theoretical foundation for analyzing the potential role of Hsfs in high-temperature stress tolerance in kiwifruit. This study also offers valuable information to aid plant breeders in the development of heat-stress-resistant plant materials.

Allogeneic hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: a CIBMTR analysis.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a poor prognosis and considered incurable with conventional chemotherapy. Small observational studies reported allogeneic hematopoietic cell transplantation (allo-HCT) offers durable remissions in patients with BPDCN. We report an analysis of patients with BPDCN who received an allo-HCT, using data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We identified 164 patients with BPDCN from 78 centers who underwent allo-HCT between 2007 and 2018. The 5-year overall survival (OS), disease-free survival (DFS), relapse, and nonrelapse mortality (NRM) rates were 51.2% (95% confidence interval [CI], 42.5-59.8), 44.4% (95% CI, 36.2-52.8), 32.2% (95% CI, 24.7-40.3), and 23.3% (95% CI, 16.9-30.4), respectively. Disease relapse was the most common cause of death. On multivariate analyses, age of ≥60 years was predictive for inferior OS (hazard ratio [HR], 2.16; 95% CI, 1.35-3.46; P = .001), and higher NRM (HR, 2.19; 95% CI, 1.13-4.22; P = .02). Remission status at time of allo-HCT (CR2/primary induction failure/relapse vs CR1) was predictive of inferior OS (HR, 1.87; 95% CI, 1.14-3.06; P = .01) and DFS (HR, 1.75; 95% CI, 1.11-2.76; P = .02). Use of myeloablative conditioning with total body irradiation (MAC-TBI) was predictive of improved DFS and reduced relapse risk. Allo-HCT is effective in providing durable remissions and long-term survival in BPDCN. Younger age and allo-HCT in CR1 predicted for improved survival, whereas MAC-TBI predicted for less relapse and improved DFS. Novel strategies incorporating allo-HCT are needed to further improve outcomes.

Enhanced performance of mixed HWMA-CUSUM charts using auxiliary information.

Quality control (QC) is a systematic approach to ensuring that products and services meet customer requirements. It is an essential part of manufacturing and industry, as it helps to improve product quality, customer satisfaction, and profitability. Quality practitioners generally apply control charts to monitor the industrial process, among many other statistical process control tools, and to detect changes. New developments in control charting schemes for high-quality monitoring are the need of the hour. In this paper, we have enhanced the performance of the mixed homogeneously weighted moving average (HWMA)-cumulative sum (CUSUM) control chart by using the auxiliary information-based (AIB) regression estimator and named it MHCAIB. The proposed MHCAIB chart provided an unbiased and more efficient estimator of the process location. The various measures of the run length are used to judge the performance of the proposed MHCAIB and to compare it with existing AIB charts like CUSUMAIB, EWMAAIB, MECAIB (mixed AIB EWMA-CUSUM), and HWMAAIB. The Run length (RL) based performance comparisons indicate that the MHCAIB chart performs relatively better in monitoring small to moderate shifts over its competitor's charts. It is shown that the chart's performance improves with the increase in correlation between the study variable and the auxiliary variable. An illustrative application of the proposed MHCAIB chart is also provided to show its implementation in practical situations.

Impact of Donor Age on Allogeneic Hematopoietic Cell Transplantation Outcomes in Older Adults with Acute Myeloid Leukemia.

Allogeneic hematopoietic cell transplantation (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit for alloHCT with matched unrelated donors (MUDs), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) versus the best MUD? This retrospective cohort registry study accessed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients with AML age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included nonrelapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival. Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD (median donor age, 60 years), and 2948 underwent alloHCT from a younger MUD (median donor age, 25 years). In multivariable analysis, compared to older MSDs, the use of younger MUDs conferred a decreased relapse risk (hazard ratio [HR], .86; P = .005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% versus 41%; P = .003), but was associated with an increased risk for chronic GVHD (HR, 1.18; 95% confidence interval [CI], 1.08 to 1.29; P = .0002) and greater NRM only in the earlier period of 2011 to 2015 (HR, 1.24; P = .016). The corresponding NRM rates were significantly lower in the more recent period of 2016 to 2018 (HR, .78; P = .017). The adjusted 5-year DFS probability was 44% (95% CI, 42% to 46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38% to 43%) with older MSDs (P = .04). In summary, for older patients with AML undergoing alloHCT, the use of younger MUDs is associated with decreased relapse risk and improved DFS compared with the use of older MSDs.

Functional characterization of DcMYB11, an R2R3 MYB associated with the purple pigmentation of carrot petiole.

MAIN CONCLUSION: DcMYB11, an R2R3 MYB gene associated with petiole anthocyanin pigmentation in carrot, was functionally characterized. A putative enhancer sequence is able to increase DcMYB11 activity. The accumulation of anthocyanin pigments can exhibit different patterns across plant tissues and crop varieties. This variability allowed the investigation of the molecular mechanisms behind the biosynthesis of these pigments in several plant species. Among crops, carrots have a well-defined anthocyanin pigmentation pattern depending on the genic background. In this work, we report on the discovery of DNA structural differences affecting the activity of an R2R3 MYB (encoded by DcMYB11) involved in anthocyanin regulation in carrot petiole. To this end, we first verified the function of DcMYB11 using heterologous systems and identified three different alleles which may explain differences in petiole pigmentation. Characterization of the DcMYB11 alleles at the 5' upstream sequence unveiled a sequence that functions as a putative enhancer. In conclusion, this study provides novel insight into the molecular mechanisms controlling anthocyanin accumulation in carrot. By these outcomes, we expanded our knowledge on the cis-regulatory sequences in plants.