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Wounding is a trigger for both regeneration and defense in plants, but it is not clear whether the two responses are linked by common activation or regulated as trade-offs. Although plant glutamate-receptor-like proteins (GLRs) are known to mediate defense responses, here, we implicate GLRs in regeneration through dynamic changes in chromatin and transcription in reprogramming cells near wound sites. We show that genetic and pharmacological inhibition of GLR activity increases regeneration efficiency in multiple organ repair systems in Arabidopsis and maize. We show that the GLRs work through salicylic acid (SA) signaling in their effects on regeneration, and mutants in the SA receptor NPR1 are hyper-regenerative and partially resistant to GLR perturbation. These findings reveal a conserved mechanism that regulates a trade-off between defense and regeneration, and they also offer a strategy to improve regeneration in agriculture and conservation.

Transfusion has a recognized immunomodulatory effect, and its role on the outcomes after an ambulatory autologous hematopoietic stem cell transplantation (auto-HSCT) following reduced intensity conditioning (RIC) has not been documented. A study to assess factors associated with the number of packed red blood cells (PRBCs) and platelet units transfused and their impact on survival rates of auto-HSCT recipients after RIC was conducted between 2013 and 2019. Transfusions were recorded from days 0 to 100. Of the 130 patients studied, seventy (53.9%) required transfusion support. The median number of PRBC transfused was 2 (range 1-20), and for platelets, it was also 2 units (range 1-19). Infused CD34 + cells/kg, pre-transplant CMV status, and relapse/progression were significantly associated with the number of PRBC units transfused and sex, infused CD34 + cells/kg, and pre-transplant CMV status with the number of platelet units transfused. In multivariate analysis, a high/very high Disease Risk Index (P = .001) (P = .001) and transfusion of ≥ 5 total blood products (P = .001) (P = .010) were associated with decreased disease-free and overall survival. Two-year cumulative incidence of relapse was 50% for transfused patients vs. 34% for those not transfused (P = .009). These data suggest that the transfusion burden and its interplay with other patient and transplant-related factors could be associated with inferior auto-HSCT outcomes.

Autologous stem cell transplantation (ASCT) is commonly an in-patient procedure. However, outpatient ASCT grows as a cost-effective and feasible option for patients with lymphoma and reports assessing it after reduced-intensity conditioning (RIC) are sparse. We report the outcome of 102 patients with lymphoma who underwent ASCT on a full outpatient basis in a single-center transplant program between 2010 and 2020. Forty-two percent of the cohort required transfusion support, 36.3% experienced a neutropenic fever episode, 25.5% mucositis, and 9.8% developed severe infection. At a median time of 5 days (range 1-28), only 22.5% of the cohort required admission within the first 100 days after the autograft, median length of hospital stay was 0 days (range 0-14) and neutropenic fever was the most common reason for hospitalization. Non-relapse mortality at 1 year was 5%. ASCT in a completely outpatient setting is feasible, safe, and highly effective to treat lymphoma patients.

Wounding is a trigger for both regeneration and defense in plants, but it is not clear if the two responses are linked by common activation or regulated as tradeoffs. While plant glutamate-like receptors (GLRs) are known to mediate defense, here we implicate GLRs in regeneration through dynamic changes in chromatin and transcription in reprogramming cells near wound sites. We show that genetic and pharmacological inhibition of GLR activity increases regeneration efficiency in multiple organ repair systems and plant species. Perturbation of GLR-mediated function speeds cell division and re-specification of the stem cell niche while dampening defense responses. We show that the GLRs work through salicylic acid (SA) signaling in regeneration, with mutants in the SA receptor NPR1 partially resistant to GLR perturbation and hyper regenerative. These findings reveal a conserved mechanism that regulates a tradeoff between defense and regeneration and offer new strategies to improve regeneration in agriculture and conservation.

Ambulatory allogeneic hematopoietic cell transplantation (allo-HCT) after reduced-intensity conditioning (RIC) is a cost-effective option for hematology patients. Data on the impact of transfusion burden in this setting are scarce; we analyzed this retrospectively.A study of 177 HLA-identical and haploidentical allo-HCT recipients on an outpatient basis was conducted between 2013 and 2019. Packed red blood cell (PRBC) and platelet transfusions were documented from days 0-100 after HCT.A total of 121 patients (68.4%) required transfusion while 56 (31.6%) did not. In the multivariate analysis, a lower disease-free (DFS) and overall survival (OS) were documented for patients that received ≥9 total blood products (p = 0.018) (p = 0.014), those who required hospitalization (p = 0.001) (p 0.001), had acute graft-versus-host disease (p = 0.016) (p = 0.004), and a high/very high Disease-Risk-Index (p = 0.002; p = 0.004), respectively. Transfusion of ≥5 PRBC units was associated with a lower OS (p = 0.027). The cumulative incidence of transplant-related mortality at two years for an HLA-identical transplant was 9.5% and for haploidentical, it was 27.1% (p = 0.027); this last group had significantly more transfusion demands than HLA-identical recipients (p = 0.029).Increased blood product utilization is an independent predictor of decreased survival in ambulatory RIC allo-HCT recipients. Further evidence leading to individualized guidelines to transfuse in this complex scenario is needed.

The date of acute lymphoblastic leukemia (ALL) diagnosis has been studied regarding potential etiologic roles with contrasting results and the issue remains controversial. The principal aim of this study was to analyze monthly variation of ALL diagnosis in a large homogenous Hispanic Latin American cohort over 15 years; its association with survival rates was also assessed.Clinical files and electronic records of 501 consecutive patients of all ages with ALL in northeastern Mexico over the years of 2004-2018 were scrutinized. Patients were divided into children ≤18 and adults18 years. The Chi-square heterogeneity analysis was used to test for non-uniform variation. The Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using the month of diagnosis as a covariate in a separate model.During the study period 363 children (72.5%) and 138 adults (27.5%) (p 0.001) were diagnosed with ALL. Heterogeneity across the months of diagnosis was confirmed (p = 0.019) and the Poisson regression analysis confirmed a significant monthly variation (p 0.001) (95% CI, 3.024-3.745), a higher annual peak being observed in the month of March (p = 0.002), followed by a second peak in October (p = 0.026). The five-year OS for children was 68.2% (95% CI, 67.64-68.74) and for adults, 43.7% (95% CI, 42.67-44.71) (p 0.001). No significant association between the month of diagnosis and OS was found (p = 0.789).The monthly variation of ALL diagnosis was documented; these results confirm the heterogeneous behavior of the disease and appear to be consistent with an interplay of environmental and biologic factors. Further studies are needed to examine putative candidate agents.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a multisystem autoinflammatory disease due to an underlying plasma cell disorder that lacks a standard treatment strategy because of its rarity. We report a case of relapsed POEMS syndrome successfully treated with a second ambulatory autologous hematopoietic-cell transplantation (AHCT) after a daratumumab desensitization protocol performed during the coronavirus disease (COVID-19) pandemic in a patient with coexisting human immunodeficiency virus (HIV), hepatitis B virus (HBV) and syphilis infections. He is a 37-year old Latin-American male who had been treated with radiation, CyBorD regimen, AHCT and bortezomib therapy before being referred to our service. It was decided to administer daratumumab therapy and subsequently perform the transplant. Placement of central venous access, fluid infusion, conditioning regimen with melphalan and previously cryopreserved autograft infusion were carried out in an outpatient basis. Following second AHCT, the patient demonstrated clinical, VEGF, hematological response and remains SARS-CoV-2 infection-free and in POEMS remission with excellent quality-of-life at last follow up (6 months). We evidenced that thanks to an outpatient transplant program, the best therapeutic modalities can be offered to patients with hematologic malignancies in the context of present or future pandemics. Finally, high-complexity patients with HIV infection should have access to the same treatment strategies as non-infected patients. A second AHCT in the outpatient setting is feasible, safe and highly effective to treat patients with relapsed POEMS syndrome.

To examine the role of the tonoplast in plant salt tolerance and identify proteins involved in the regulation of transporters for vacuolar Na+ sequestration, we exploited a targeted quantitative proteomics approach. Two-dimensional differential in-gel electrophoresis analysis of free flow zonal electrophoresis separated tonoplast fractions from control, and salt-treated Mesembryanthemum crystallinum plants revealed the membrane association of glycolytic enzymes aldolase and enolase, along with subunits of the vacuolar H+-ATPase V-ATPase. Protein blot analysis confirmed coordinated salt regulation of these proteins, and chaotrope treatment indicated a strong tonoplast association. Reciprocal coimmunoprecipitation studies revealed that the glycolytic enzymes interacted with the V-ATPase subunit B VHA-B, and aldolase was shown to stimulate V-ATPase activity in vitro by increasing the affinity for ATP. To investigate a physiological role for this association, the Arabidopsis thaliana cytoplasmic enolase mutant, los2, was characterized. These plants were salt sensitive, and there was a specific reduction in enolase abundance in the tonoplast from salt-treated plants. Moreover, tonoplast isolated from mutant plants showed an impaired ability for aldolase stimulation of V-ATPase hydrolytic activity. The association of glycolytic proteins with the tonoplast may not only channel ATP to the V-ATPase, but also directly upregulate H+-pump activity.

The LC(50) of the organophosphorus pesticides (OPs) diazinon to Nile tilapia (Oreochromis niloticus) was determined, thereafter, hepatic activity, phagocytic index, percentages of active cells, relative spleen weight, total IgM concentration and lymphoproliferation rates were compared between diazinon exposed groups (LC(50) and (1/2)LC(50)) and non-exposed control group. Experimental data show that diazinon is highly toxic for juvenile Nile tilapia (LC(50)=7.830 ppm) and presents immunotoxic properties which affect both the innate and cellular adaptive immune responses of this fish, as revealed by the fact that splenocyte proliferation and phagocytic indices were significantly decreased after acute exposure to the pesticide. However, the hepatic biochemical parameters and the total circulating IgM concentrations were not affected in this experimental model.