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Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myeloid leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred thirty-six adult patients with Ph + ALL were included in the study and retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. ACAs are observed in 60 cases (44%). ACAs detected in more than 5% of cases were defined as major-route and encompass: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with t(9;22) sole. Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for t(9;22) sole(P = 0.045). The 3-year overall survival (OS) in the - 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with t(9;22) sole(P < 0.05). More importantly, Ph + ALL with - 7 was negatively associated with the rate of 3-year OS(P = 0.012). Thus, ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Anaerobic digestion of food waste can recover carbon in the form of biogas, while the high concentration of ammonia nitrogen in the digestion effluent becomes troublesome. Therefore, some new treatment plants use three-phase centrifugation to separate homogenized food waste into nitrogen-rich fine slag for insect cultivation and carbon-rich liquid for anaerobic digestion. To analyze the effects of the carbon-nitrogen separation, an upgraded plant's material and elementary flows were investigated. The three-phase separation process redistributed carbon and nitrogen, and the biogas slurry was the primary output. The principal endpoint for C was the crude oil, capturing 57.1 ± 13.1 % of the total input; the find slag collected 48.3 ± 6.9 % of the total N input, and the biogas slag accepted 52.9 ± 4.4 % of the P input. The carbon-nitrogen separation strategy can improve digestion efficiency and increase treatment benefits significantly, marking a promising direction for future developments in food waste utilization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Reduced-intensity conditioning (RIC) regimens allogeneic hematopoietic stem cell transplantation (HSCT) was developed for older patients or those with poor functional status. Haploidentical donor was appropriate alternative donor for patients without matched donors or patients with emergency disease state. However, there was few studies report the outcomes of RIC regimen of anti-thymocyte globulin (ATG) based haploidentical HSCT. The selection of the appropriate RIC regimen based on age and comorbidities in ATG-based haploidentical HSCT remains poorly described. To investigate the safety and efficacy of RIC regimen ATG-based haploidentical HSCT in older or unfit patients. Additionally, to explore the potential factors that impact the prognosis of RIC regimen of ATG-based haploidentical HSCT. We included a retrospective cohort of 63 patients with hematologic malignant diseases who underwent their first RIC haploidentical HSCT from November 2016 to June 2022 at our institutions. The conditioning regimen involved fludarabine (Flu) 30 mg/m²/kg 6 days combined with busulfan 3.2 mg/kg 2 days (Bu2) or 3 days (Bu3). ATG-Fresenius (ATG-F) was administered 10 mg/kg in total, ATG-thymoglobulin (ATG-T) was administered 6 mg/kg in total. The median age of patients in the entire cohort was 60 (32-67) years with a median follow-up of 496 (83-2182) days. There were 29 patients with AML, 20 patients with MDS, and 14 patients with ALL. A total of 32 patients underwent Bu2 RIC haplo-HSCT and 31 patients were treated with Bu3 RIC haplo-HSCT. The 2-year overall survival (OS) and 2-year disease-free survival (DFS) in whole cohort were 67.7% (95% confidence interval [CI], 53.8 - 85.1%) and 61.4% (95% CI, 48.8 - 77.3%) respectively. The cumulative incidence rates of grades II to IV and grades III to IV acute graft-versus-host disease (aGVHD) in whole cohort were 15.8% (95% CI, 4.8 - 19.6%) and 9.7% (95% CI, 0.0 - 11.8%) respectively. The 2-year cumulative incidence of chronic GVHD was 34.0% (95% CI, 18.9 - 46.3%). The 2-year cumulative incidence rates of relapse (IR) and non-relapse mortality (NRM) rates in whole cohort were 27.5% (95% CI, 14.5 - 33.7%) and 11.6% (95% CI, 2.2 - 21.9%) respectively. The probability of 2-year OS were 60.2% (95% CI:42.5-85.3%) in Bu2 and 85.5%(95% CI:73.0-100%) in Bu3 group respectively(P = 0.150). The probability of 2-year DFS were 49.7% (95% CI:33.0-74.8%) in Bu2 and 72.6% (95% CI:55.5-95.5%) in Bu3 group respectively (P = 0.045). The 2-year IR of Bu2 group was significantly higher than Bu3 group (P = 0.045). However, the 2-year NRM were not significantly different between Bu2 and Bu3 group(P > 0.05). In multivariable analysis, RIC regimen of Bu3 had superior OS and DFS than Bu2 group respectively [HR 0.42, 95% CI 0.18-0.98; P = 0.044; HR 0.34, 95% CI 0.14-0.86; P = 0.022]. Besides, RIC regimen of Bu3 had lower IR than Bu2 group [HR 0.34, 95% CI 0.13-0.89; P = 0.029]. The RIC regimen of ATG-based haploidentical HSCT is a safe and effective treatment option for patients who are older or have poor functional status. In particular, a relatively high-intensity pre-treatment regimen consisting of Bu achieves significant improvements in OS and DFS, thus providing more favorable post-transplantation clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although the prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) has improved with the introduction of tyrosine kinase inhibitors (TKIs) and stem cell transplantation, prevention of relapse after transplantation remains a concern. The aim of this study was to compare the impact of TKI prophylaxis with imatinib and dasatinib on long-term outcomes after transplantation., Methods: Patients with Ph+ ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) and received TKI prophylaxis after allo-HSCT were included in this retrospective analysis. Two cohorts were established based on the choice of TKI prophylaxis: the imatinib (Ima) and dasatinib (Das) cohorts. The survival and safety outcomes of these cohorts were compared., Results: Ninety-one patients in the Ima cohort and 50 in the Das cohort were included. After a median follow-up of 50.6 months, the 5-year cumulative incidence of relapse, nonrelapse mortality rate, and overall survival in the Ima and Das cohorts were 16.1% and 12.5%, 5.2% and 9.8%, and 86.5% and 77.6%, respectively, with no statistical differences. The cumulative incidence of mild chronic graft-versus-host disease was higher in the Das cohort. The most common adverse event was neutropenia (64.7% vs. 69.5%). The Das cohort had a higher incidence of gastrointestinal bleeding (25.5% vs. 2.3%) and gastrointestinal reaction (48.9% vs. 31.4%) than the Ima cohort. The proportion of patients treated on schedule was significantly lower in the Das cohort than in the Ima cohort, and drug intolerance was the main reason for protocol violation., Conclusions: For patients with Ph+ ALL undergoing allo-HSCT in CR1, imatinib prophylaxis achieved long-term outcomes similar to those of dasatinib., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

De novo anti-HLA donor-specific antibodies (DSAs) were rarely reported in stem cell transplantation patients. We present a case of 39-year-old acute myelogenous leukaemia patient who developed de novo DSAs only 16 days after transplantation with the highest mean fluorescence intensity (MFI) of 7406.23, which were associated with poor graft function (PGF). We used plasma exchange (PE) and intravenous immunoglobulin (IVIg) to reduce DSA level. A series of treatment including mesenchymal stem cells and donor cell transfusion were used to help recover graft function. On day 130, the patient achieved a successful engraftment., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prognostic significance of myelofibrosis (MF) grade in patients with myelodysplastic syndrome (MDS) following an allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains elusive., Methods: We retrospectively analyzed data from 153 patients with MDS who underwent allo-HSCT and divided the patients into the MF-0/1 (N = 119) and MF-2/3 (N = 34) cohorts to explore the impact of MF on outcomes of allo-HSCT., Results: The 2-year rates of relapse, non-relapse mortality (NRM), overall survival (OS), and progression-free survival (PFS) were 10.9% (95% confidence interval [CI] 5.9%-17.7%), 16.3% (95% CI 10.2%-23.6%), 76.6% (95% CI 69.0%-85.1%), and 72.8% (95% CI 65.0%-81.5%) in the MF-0/1 cohort, and 16.9% (95% CI 5.8%-32.9%), 14.7% (95% CI 5.3%-28.7%), 71.8% (95% CI 57.6%-89.6%), and 68.4% (95% CI 53.6%-87.2%) in the MF-2/3 cohort, respectively. No significant difference in the outcomes of allo-HSCT was observed between the two cohorts. Both univariate and multivariate analyses confirmed that MF-2/3 in patients with MDS had no effect on the prognosis of transplantation. In addition, major/bidirectional ABO blood type between donors and recipients was an independent risk factor for OS (hazard ratio [HR], 2.55; 95% CI 1.25-5.21; P = 0.010) and PFS (HR, 2.21; 95% CI 1.10-4.42; P = 0.025) in the multivariate analysis. In the subgroup of patients diagnosed with MDS with increased blasts (MDS-IB), it was consistently demonstrated that the clinical outcomes of the MF-2/3 cohort were comparable with those of the MF-0/1 cohort. The risk factors for OS and PFS in patients with MDS-IB were non-complete remission at transplantation and major/bidirectional ABO blood type., Conclusions: In conclusion, MF grade had no significant effect on prognosis of allo-HSCT in patients diagnosed with MDS. Major/bidirectional ABO blood type should be carefully considered in the context of more than one available donor., (© 2024. The Author(s).)

Objectives: This study aimed to characterize the clinical characteristics, outcomes, and risk factors for coronavirus disease 2019 (COVID-19) in 492 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) during the Omicron wave., Methods: Data were retrospectively collected from patient charts and the electronic medical record systems at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2022 and January 2023., Results: The median follow-up period of the entire cohort was 62 days. Myeloid malignancies (58.5%) and acute lymphocytic leukemia (30.5%) constituted the most common underlying disease. Among the 492 patients, 415, 67, and 10 exhibited mild, moderate, and severe COVID-19, respectively. The incidence of moderate-to-severe COVID-19 was 15.7%. The 60-day overall survival and complete resolution rates were 98.1% and 80.6%, respectively. The risk factors for moderate-to-severe COVID-19 included corticosteroid use within 3 months before diagnosis, <6 months interval between allo-HSCT and COVID-19 diagnosis, and antithymocyte globulin use for graft-versus-host disease prophylaxis., Conclusions: During the Omicron wave, patients with allo-HSCT demonstrated a low COVID-19-related mortality rate and high moderate-to-severe and prolonged disease incidence. Prevention in the early posttransplantation period is critical for allo-HSCT recipients receiving corticosteroids., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: This study investigated the cellular composition of peripheral blood grafts for anti-thymocyte globulin (ATG)-based myeloablative haploidentical haematopoietic stem cell transplantation (haplo-HSCT)., Methods: Clinical characteristics were retrospectively evaluated in a training cohort with ATG-based myeloablative haplo-HSCT between January 2016 and February 2020 and confirmed in a validation cohort between March 2020 and June 2021., Results: A higher dose of graft CD8 + T cells (≥ 0.85 × 10 8  kg -1 ) was significantly improved overall survival (OS; hazard ratio [HR], 1.750; P  = 0.002) and disease-free survival (DFS; HR, 1.751; P  < 0.001) in the training cohort, according to multivariate Cox regression analysis. Higher doses of mononuclear cells (MNCs) demonstrated better OS (HR, 1.517; P  = 0.038) and DFS (HR, 1.532; P  = 0.027). Older patient age (> 46 years), older donor age (≥ 50 years) and a higher refined disease risk index (rDRI) were also related to OS. A graft CD8 + T-cell risk system based on graft CD8 + T-cell dose, donor age and rDRI was constructed using a nomogram model after LASSO Cox regression analysis. It showed acceptable discrimination, with a C-index of 0.62 and 0.63, respectively. Graft CD8 + T-cell dose was negatively correlated with donor age ( P  < 0.001) and positively correlated with a higher lymphocyte percentage in the peripheral blood before mobilisation ( P  < 0.001)., Conclusion: A higher CD8 + T-cell dose in peripheral blood-derived grafts improves patients' survival with ATG-based myeloablative haplo-HSCT. Younger donors with higher lymphocyte percentages improved patients' survival with an intermediate rDRI risk., Competing Interests: The authors have no relevant financial or non‐financial interests to disclose., (© 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)

Objective: We previously reported an increased expression of microRNA-155 (miR-155) in the blood monocytes of patients with rheumatoid arthritis (RA) that could be responsible for impaired monocyte polarization to anti-inflammatory M2-like macrophages. In this study, we employed two preclinical models of RA, collagen-induced arthritis and K/BxN serum transfer arthritis, to examine the therapeutic potential of antagomiR-155-5p entrapped within PEGylated (polyethylene glycol [PEG]) liposomes in resolution of arthritis and repolarization of monocytes towards the anti-inflammatory M2 phenotype., Methods: AntagomiR-155-5p or antagomiR-control were encapsulated in PEG liposomes of 100 nm in size and -10 mV in zeta potential with high antagomiR loading efficiency (above 80%). Mice were injected intravenously with 1.5 nmol/100 μL PEG liposomes containing antagomiR-155-5p or control after the induction of arthritis., Results: We demonstrated the biodistribution of fluorescently tagged PEG liposomes to inflamed joints one hour after the injection of fluorescently tagged PEG liposomes, as well as the liver's subsequent accumulation after 48 hours, indicative of hepatic clearance, in mice with arthritis. The injection of PEG liposomes containing antagomiR-155-5p decreased arthritis score and paw swelling compared with PEG liposomes containing antagomiR-control or the systemic delivery of free antagomiR-155-5p. Moreover, treatment with PEG liposomes containing antagomiR-155-5p led to the restoration of bone marrow monocyte defects in anti-inflammatory macrophage differentiation without any significant functional change in other immune cells, including splenic B and T cells., Conclusion: The injection of antagomiR-155-5p encapsulated in PEG liposomes allows the delivery of small RNA to monocytes and macrophages and reduces joint inflammation in murine models of RA, providing a promising strategy in human disease., (© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Donor lymphocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely used in preventing post-transplant relapse. We conducted this study to compare the superiority of prophylactic modified DLI (pro-DLI) and preemptive modified DLI (pre-DLI) in patients with high-risk relapse features acute leukemia. Pro-DLI was performed in 95 patients, whereas the pre-DLI cohort included 176 patients. In the pre-DLI cohort, 42 patients relapsed without chance for pre-DLI while 95 patients remained CR without detectable minimal residual disease (MRD). Thirty-nine patients in the pre-DLI cohort became minimal MRD positive/mixed chimerism and received pre-DLI. Pro-DLI cohort had higher 3-year progression-free-survival (PFS) (63.4%vs.53.0%, P = 0.026) and overall survival (OS) (65.2% vs. 57.0%, P = 0.14) compared to the pre-DLI cohort. The 3-year cumulative incidence of relapse (CIR) was 25.3% in the pro-DLI cohort which was significantly lower than 36.7% in the pre-DLI cohort (P = 0.02). The cumulative incidence of grade III-IV aGVHD, cGVHD and non-relapse mortality were comparable between cohorts. Multivariable analysis demonstrated strong protective effect of pro-DLI on OS (hazard ratio (HR) = 0.63, P = 0.04), PFS (HR = 0.54, P = 0.005) and CIR (HR = 0.50, P = 0.005). In high-risk patients with acute leukemia, early scheduled pro-DLI rather than pre-DLI after detectable MRD would reduce post-transplant relapse and improve long-term survival., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported., Methods: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551., Findings: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 10 5 /kg (n = 3) or 2 × 10 6 /kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81-2063). The median age of patients was 31 years (range 21-48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach C max was 9 days (range, 7-11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322-732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively., Interpretation: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles., Funding: Gracell Biotechnologies Inc., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Regularly adding biogas slurry into fermentation reactors is an effective way to enhance hydrogen or methane production. However, how this method affects the production of valuable organic acids and alcohols is still being determined. This study investigated the effects of different addition ratios on semi-continuous fermentation reactors using food waste as a substrate. The results showed that an addition ratio of 0.2 increased lactic acid production by 30% with a yield of 0.38 ± 0.01 g/g VS, while a ratio of 0.4 resulted in mixed acid fermentation dominated by n-butyric acid (0.07 ± 0.01 g/g VS) and n-caproic acid (0.06 ± 0.00 g/g VS). The introduction of Bifidobacteriaceae by biogas slurry played a crucial role in increasing lactic acid production. In contrast, exclusive medium-chain fatty acid producers enhanced the synthesis of caproic acid and heptanoic acid via the reverse β-oxidation pathway. Mechanism analyses suggested that microbial community structure and activity, substrate hydrolysis, and cell membrane transport system and structure changed to varying degrees after adding biogas slurry., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Donor-specific anti-HLA antibodies (DSA) are a major cause of engraftment failure in patients receiving haploidentical haematopoietic stem cell transplantation (Haplo-HSCT). Double filtration plasmapheresis (DFPP) avoids the unnecessary loss of plasma proteins and increases the efficiency of purification. To investigate the effectiveness of the desensitization protocol including DFPP and rituximab, we conducted a nested case-control study. Thirty-three patients who had positive DSA were desensitized by the protocol and 99 patients with negative DSA were randomly matched as control. The median DSA mean fluorescence intensity values before and after DFPP treatment were 7505.88 ± 4424.38 versus 2013.29 ± 4067.22 (p < 0.001). All patients in DSA group achieved haematopoietic reconstitution and the median neutrophils and platelets engraftment times were 13 (10-21) and 13 (10-29) days respectively. Although the cumulative incidence of II-IV aGVHD (41.4% vs. 28.1%) and 3-year moderate to severe cGVHD (16.8% vs. 7.2%) were higher in DSA cohort than in the control, no statistical significance was observed. The 3-year non-relapse mortality and the overall survival were 6.39% and 72.0%, respectively, in the DSA cohort, which were comparable to the negative control. In conclusion, DFPP and rituximab could be effectively used for desensitization and overcome the negative effects of DSA in Haplo-HSCT., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Although many technologies can be applied to sewage sludge (SS) and food waste (FW) treatment, high investment and operational costs, high land occupation, and the "not-in-my-backyard" effect pose many challenges in practice. Thus, it is important to develop and utilize low-carbon or negative-carbon technologies to tackle the carbon problem. This paper proposes a method of anaerobic co-digestion of FW and SS, thermally hydrolyzed sludge (THS), or THS filtrate (THF) to enhance their methane potential. Compared to the co-digestion of SS with FW, the methane yield of the co-digestion of THS and FW was 9.7-69.7% higher, and that of the co-digestion of THF and FW was 11.1-101.1% higher. The synergistic effect was weakened with the addition of THS but enhanced with the addition of THF, potentially owing to the change in humic substances. Filtration removed most humic acids (HAs) from THS but retained fulvic acids (FAs) in THF. Moreover, THF produced 71.4% of the methane yield of THS, although only 25% of the organic matter permeated from THS to THF. This indicated that hardly biodegradable substances remained in the dewatering cake and were removed from anaerobic digestion systems. The results indicate that the co-digestion of THF and FW is an effective way to enhance methane production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Most events that limit life expectancy after allogeneic haematopoietic stem cell transplantation (allo-HSCT) occur within the first 2 years; however, treatment outcomes in long-term survivors who survive for at least 2 years post-HSCT without relapse are yet to be elucidated. To explore the life expectancy trends and late complications and to assess the main mortality-related factors, we investigated the characteristics of patients who received allo-HSCT for haematological malignancies from 2007 to 2019 in our centre and survived in remission for 2 years. A cohort of 831 patients was enrolled; of these, 508 received grafts from haploidentical-related donors (61.1%). The estimated overall survival rate at 10 years was 91.9% (95% confidence interval [CI], 89.8-93.5), which was affected by prior grade III-IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 2.98; 95% CI, 1.47-6.03; p = 0.002) and severe chronic GVHD (HR, 3.60; 95% CI, 1.93-6.71; p < 0.001). The probability of late relapse and non-relapse mortality at 10 years was 8.7% (95% CI, 6.9-10.8) and 3.6% (95% CI, 2.5-5.1) respectively. The top cause of late mortality was relapsed (49.0%). Projected long-term survival in 2-year disease-free survivors following allo-HSCT was excellent. Strategies should be implemented to minimise the late death-specific hazards in recipients., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Based on the annual mean PM 2.5 concentration data of 30 provinces and cities in China from 2006 to 2020, this paper constructs a structural model of manufacturing haze pollution, expounds the main mechanisms affecting haze pollution, then statistically decomposes the main factors affecting the change of pollution emissions, and examines the direct and indirect impact paths of the change of haze pollution emissions in China. The study found that (1) the inhibitory effects of latent variables on manufacturing haze pollution is from strong to weak in order: industrial structure upgrading, environmental regulation, trade opening, productivity improvement, and economic scale expansion, while the optimal path for the indirect effect of exogenous latent variables on haze pollution is to rely on environmental regulation and opening up to achieve the improvement of productivity, so as to achieve the purpose of reducing haze pollution. (2) The analysis based on the PVAR model found that industrial structure adjustment is the key factor of haze decline in both the short and long term. Environmental regulation has an obvious effect on haze control in the short term, but in the long run, it still needs to rely on industrial structure adjustment, production efficiency improvement, and trade opening to achieve the goal of reducing haze. (3) There is an inverted U-shaped nonlinear relationship between output scale and environmental regulation. In addition, trade openness has a long-term effect on productivity. Technology spillovers from opening up can reduce haze pollution in the long run by improving productivity. (4) The environmental regulation policy in the central region is characterized by "race to the bottom," while the eastern region shows the characteristic of "race to the top" in the policy game of improving productivity and optimizing the industrial structure. Therefore, haze control requires an appropriate intensity of environmental regulation to reduce the proportion of high pollution and high energy consumption industries. Make full use of the international cooperation platform of the "the Belt and Road Initiative" and the pilot free trade zone to promote substantive cooperation between Chinese enterprises and developed countries in the field of environmental protection technology, increase investment in research and development of clean equipment and cleaner production technology, improve productivity, help China's green manufacturing, and contribute Chinese wisdom and Chinese solutions to global environmental governance and climate change., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Drawing on teacher interviews, written teacher reflections, teacher research proposals, and research papers, this study explored the outcome and process of teacher learning during their participation in a continuing professional development program. It has been found that the teachers changed their conceptions of research over the course of learning concerning the nature, purpose, and process of research and the relationship between teaching and research. Dialogic exchanges and reading research papers, along with the scaffolding of the teacher educator, enabled the teachers to validate their practices, link others' perspectives up to their own, and re-situate research in light of their current practices. The findings provide insights into the nature of teachers' conceptual change and how learning opportunities can be better built into continuing professional development programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang and Yang.)

ABO incompatibility is common in hematopoietic stem cell transplantation (HSCT); however, the impact of donor-recipient ABO compatibility on transplantation outcomes in different HSCT settings is controversial. Moreover, haploidentical stem cell transplantation (haplo-SCT) with peripheral blood stem cell (PBSC)-derived grafts has not been well investigated. The present study aimed to investigate the impact of ABO incompatibility on post-transplantation outcomes, engraftment kinetics, blood product requirements, transfusion independence, and the incidence of poor graft function (PGF) in antithymocyte globulin (ATG)-based haplo-SCT with PBSC grafts during long-term follow-up. We prospectively evaluated 510 patients with hematologic malignancies who underwent haplo-SCT after myeloablative conditioning (MAC). The primary endpoint was overall survival (OS), and secondary endpoints were nonrelapse mortality (NRM), graft-versus-host disease (GVHD), relapse, neutrophil and platelet engraftment, blood transfusion requirements, transfusion independence, and the incidence of PGF. There was no significant association between ABO matching and OS, disease-free survival (DFS), relapse, NRM, grade II-IV acute GVHD, grade III-IV acute GVHD, and moderate and severe chronic GVHD. There were also no significant differences in neutrophil and platelet engraftment, blood transfusion independence, and transfusion requirements at 30, 60, 90, 180, and 365 days post-transplantation among patients with ABO matching and those with minor, major, or bidirectional ABO incompatibility. Donor-recipient ABO matching did not differ significantly according to graft function (good versus poor). ABO incompatibility status has no major impact on patient outcomes in patients with hematologic malignancies undergoing ATG-based MAC haplo-SCT with PBSC-derived grafts., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

It is promising to recover lactic acid (LA) from fermentation of food waste (FW). In this study, pH and temperatures were investigated comprehensively to find their effects on LA fermentation, and microbial analyses were used to take insight to the variation of LA production. The results showed that mesophilic fermentation benefited hydrolysis and acidification, leading to a high yield of LA, while thermophilic conditions restricted other producers at low pH, leading to a high purity of LA. Lactobacillus amylolyticus was the main LA producer under thermophilic conditions, but Thermoanaerobacterium thermosaccharolyticum boomed at pH 5.0-6.0 and it converted LA partly to butyric acid. Simultaneously, Bacillus coagulans also increased and improved the optical purity (OP) of L-LA. From a series of this study, an operational condition of pH 5.5 and temperature of 52 °C would be potentially suitable for lactate fermentation of FW with high purity of 89%, while a stable LA production with an OP of 68% was achieved at 55 °C and pH 6.0., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Donor lymphocyte infusion (DLI) is a key strategy for the treatment of AML relapse after allogeneic hematopoietic cell transplantation (allo-HCT) and has been used for either prophylactic, pre-emptive, or therapeutic purposes. However, the prognosis of these patients remains dismal even after DLI infusion (2-year overall survival, ~25%), and the efficacy is achieved at the cost of toxicities such as graft-versus-host (GVH) disease. Attempts to optimize DLI efficacy and safety, such as dose/timing modification and the use of cytoreduction, before DLI have been performed previously. Recently, a great number of novel targeted and immunomodulatory agents have emerged. Some of them, such as hypomethylating agents, FLT3 and Bcl-2 inhibitors, have been used in combination with DLI, aiming to enhance the graft-versus-leukemia effect. Moreover, manipulation of the DLI graft through cell selection ( e . g ., donor NK cells) or cell engineering (donor CAR-T cells) has shown potentially superior anti-tumor effects but less GVH effect than conventional DLI in clinical trials. This review summarizes the recent advances on the use of DLI for the prophylaxis/treatment of AML relapse and discusses future strategies which may further improve the treatment efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Yang, Yuan, Huang and Luo.)

Teacher written feedback (TWF) has long been regarded as a necessary pedagogical tool for improving the writing proficiency of ESL/EFL learners, while student responses to this feedback can often reflect its effectiveness. This paper reviews 64 articles appearing in high-ranking journals during 2010-2021 in terms of research methodology, theoretical framework and main findings. Analysis of these articles reveals few studies adopted any theoretical frameworks to examine learner responses to TWF and suggests a need for longitudinal naturalistic studies adopting mixed methods and some theoretical framework such as sociocultural theory of mind (SCT) to better explain learners' dynamic engagement in response to TWF. The main findings of these previous studies reveal the diverse responses among learners at different language proficiency levels and in various sociocultural contexts. The results of the review indicate that future research could take classroom-based mixed-method research design to investigate learner variables., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yu and Yang.)

It is a promising method to recover lactic acid from food waste (FW) fermentation, but the bottleneck problem is the low yield when using mixed inoculation. In this study, laboratorial biogas slurry (LBS) and industrial biogas slurry (IBS) were used as the additive in semi-continuous FW fermentation, aiming to promote the production of lactic acid. According to the research results, the addition of LBS or IBS promoted the production of lactic acid significantly from FW, especially carbohydrate, because it increased the pH values, maintained low OPR levels, and increased microbial number and diversity in the fermentation systems. IBS performed better than LBS because of higher pH, more diverse microbial community and more functional microorganisms. The best ratio of IBS to feedstock was 0.2, and the lactic acid yield reached 0.42 g/gVS added . An excessively high dose would alter the fermentation pathways, reduce the ratio of lactic acid., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The transplant outcomes of non-first-degree (NFD) related donors in haploidentical haematopoietic stem cell transplantation (haplo-HSCT) remain unclear. This multi-centre analysis compared NFD and first-degree (FD) related donors in haplo-HSCT using a low-dose anti-T-lymphocyte globulin/G-CSF-mobilised peripheral blood stem cell graft-based regimen. Ninety-nine patients (33 NFD; 66 FD) were included. All patients achieved myeloid and platelet engraftment. The 100-day cumulative incidence (CI) of aGVHD, 2-year CIs of relapse, cGVHD, and NRM, and 2-year probabilities of OS and GRFS were comparable between the two cohorts. In multivariate analysis, donor type (NFD vs. FD) had no impact on OS, PFS, GRFS, incidences of relapse, grade II-IV aGVHD or moderate-severe cGVHD. Older donor age was associated with a higher incidence of grade II-IV aGVHD (HR, 1.64, p = 0.03), moderate-severe cGVHD (HR, 1.92, p = 0.01) and worse GRFS (HR, 1.40, p = 0.02). A lower level of donor-recipient HLA matching was associated with a higher incidence of moderate-severe cGVHD (HR, 4.07, p = 0.02), and disease at complete remission was associated with better OS (HR, 0.21, p = 0.01) and PFS (HR, 0.3, p = 0.03). In conclusion, NFD donors may serve as feasible alternatives when FD donors are not available for haplo-HSCT., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Chimeric antigen receptor T cell (CAR-T) therapy is successful in improving treatment outcomes for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, toxicities associated with CAR-T therapy are being increasingly identified. Pancytopenia is one of the most common complications after CAR-T therapy, and platelet transfusions are an essential part of its supportive care. Study Design and Methods: This study aimed to assess the effectiveness of platelet transfusions for R/R ALL patients at our single center and identify associated risk factors. Overall, 44 R/R ALL patients were enrolled in this study, of whom 26 received CAR-T therapy and 18 received salvage chemotherapy. Result: Patients in the CAR-T group had a higher incidence of platelet transfusion refractoriness (PTR) (15/26, 57.7%) than those in the chemotherapy group (3/18, 16.7%) ( p = 0.007). For patients receiving CAR-T therapy, multivariate analysis showed that the grade of cytokine release syndrome (CRS) was the only independent risk factor associated with PTR ( p = 0.007). Moreover, higher peak serum IL-6 and IFN-γ levels suggested a higher risk of PTR ( p = 0.024 and 0.009, respectively). Patients with PTR received more platelet infusion doses than those without PTR ( p = 0.0426). Patients with PTR had more grade 3-4 bleeding events than those without PTR (21.4 vs. 0%, p = 0.230), and the cumulative incidence of grade 3-4 bleeding event was different ( p = 0.023). Conclusion: We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Liang, Liu, Wei, Wu, Yang, Yang, Huang, Xie and Hu.)

The groundwater quality is essential for high quality of life and social development. Thus, the importance and necessity of the accurate and rigorous requirements for contaminated groundwater assessment has increasingly attracted engineers' and researchers' attentions. In order to improve the precision and robustness of the groundwater quality evaluation of domestic waste landfills, based on the variable fuzzy set (VFS) pair and the optimized N.L. Nemerow index, we develop an optimized fuzzy set pair (OFSP) model for groundwater quality assessment. Then, we devise the OFSP model by five key elements of optimized synthesis operator "C", relative difference[Formula: see text], connection degree"u i ", optimized N.L. Nemerow index "P i ," and pollution load ratio "J i ", which can achieve the reasonable groundwater quality assessment model, the stable groundwater quality evaluation process, and the convincing evaluation results. Finally, a case study on groundwater quality assessment of various domestic landfills in China is conducted to explore the comprehensive impacts of domestic landfills in different regions and types on groundwater pollution from multiple perspectives, and demonstrate the effectiveness of the proposed OFSP model. The groundwater quality assessment results of various domestic landfills indicate that the pollution level of groundwater under unregulated domestic landfills in eastern and southern China is the worst. Based on the assessment results of groundwater quality, we compare the groundwater quality levels obtained by various mainstream methods. In line with precision (0.985), correlation (0.934), robustness (0.953), and rationality (0.946), our designed OFSP model has the best performance. In addition, according to the indexes of discrimination (0.217) and versatility (0.837), the designed OFSP model also has a good ability. Results of experiments well prove that the proposed OFSP model could play a good performance on groundwater quality evaluation in domestic landfills, compared with other mainstream models.

Both haploidentical hematopoietic stem cell transplantation (HSCT) and donor lymphocyte infusion (DLI) exhibit strong graft-versus-leukemia (GVL) effect. However, the role of prophylactic DLI following haploidentical HSCT remains unclear. Here, 34 patients with high-risk acute leukemia who underwent low-dose anti-T-lymphocyte globulin-Fresenius (ATG-F)-based myeloablative haploidentical HSCT and prophylactic modified DLI (pro-DLI) were well-matched with patients without pro-DLI. The 5-year overall survival (OS) (67.8% versus 41.3%, P < 0.01) and leukemia-free survival (LFS) (64.6% versus 33.9%, P < 0.01) of pro-DLI cohort were superior to the control cohort. A slightly higher GVHD-free/relapse-free survival was found in the pro-DLI cohort (32.8% versus 16.3%, P = 0.32). The 5-year cumulative incidence of relapse of the pro-DLI recipients was significantly lower than that of the control cohort (14.7% versus 49.3%, P = 0.01). The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days after pro-DLI was 17.6% and 9.1%, respectively. There was no difference between the two cohorts in terms of the cumulative incidence of chronic GVHD and non-relapse mortality. Data from the multivariate analysis demonstrated that pro-DLI was an independent protective variable for LFS (P = 0.01, hazard ratio {HR} = 0.35), OS (P = 0.01, HR = 0.32), and relapse (P = 0.02, HR = 0.33). Taken together, we demonstrate that pro-DLI after ATG-F-based HSCT effectively decreases the risk of relapse and improves long-term survival of patients with high-risk acute leukemia without increasing treatment toxicity.

Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. With the extensive application of CAR-T therapy in clinical settings, CAR-T-associated toxicities have become increasingly apparent. However, information regarding the associated infections is limited. We aimed to evaluate the incidence of infection during CAR-T therapy and identify the potential risk factors. Especially, we evaluated infections and the associated risk factors in 92 patients. The cohort included patients with acute lymphoblastic leukemia ( n = 58) and non-Hodgkin lymphoma ( n = 34). Fifteen cases of infection (predominantly bacterial) were observed within 28 days of CAR-T therapy, with an infection density of 0.5 infections for every 100 days-at-risk. Neutropenia before CAR-T therapy ( P = .005) and prior infection ( P = .046) were independent risk factors associated with infection within 28 days after CAR-T therapy; corticosteroid treatment during cytokine release syndrome ( P = .013) was an independent risk factor during days 29-180 after CAR-T infusions. Moreover, the 2-year survival duration was significantly shorter in patients with infections than in those without (126 vs 409 days; P = .006). Our results suggested that effective anti-infection therapies may improve prognosis of patients who have a high infection risk. The risk of bacterial infections during the early stages of CAR-T therapy and the subsequent risk of viral infections thereafter should be considered to provide the appropriate treatment and improve patient prognosis.

Hematopoietic stem cell transplantation (HSCT) is increasingly being applied globally. Cases in which healthy HSCT donors are chronically infected with hepatitis B virus (HBV) are relatively common in areas where HBV is endemic. Recipients of stem cells from such hepatitis B surface antigen (HBsAg)-positive donors are at risk of viral infection, and thus may develop HBV-related hepatitis. Given the lack of standardized approach to minimizing the risk of such infections from HBsAg + donors during HSCT, we conducted this study with the aim of developing an efficient strategy to address this challenge. A strategy comprising antiviral treatment for detectable HBV-DNA in HBsAg + donors, hepatitis B immune globulin (HBIG) administration in HBsAg - recipients with passive immunity, and prophylactic antiviral treatment for HBsAg + recipients was developed. The strategy was validated using a case-control study of 40 recipients who received stem cells from HBsAg + donors (group A) and 40 pair-matched controls who received stem cells from HBsAg - donors (group B). The cumulative incidence of HBV-related hepatitis was relatively similar in the 2 groups (group A: 8.5%; 95% confidence interval [CI], -.9% to 17.9%; group B: 7.9%; 95% CI, -.9% to 16.7%; P = .939). In HBsAg - recipients who received passive immunity from HBIG treatment, a significant negative linear correlation was observed between HBsAb titer in vivo and time in the first year after allo-HSCT (R 2  = .23; P < .001). This method was cost-effective, with a median cost of all HBV management of USD 332.1 (range, 172.7 to 1985.3), compared with USD 1464.9 (range 409.9 to 1985.3) for conventional strategies (P < .001). The novel strategy presented in here is robust in preventing HBV-related hepatitis after allo-HSCT with stem cells from HBsAg + donors. This is important for the effective application of allo-HSCT in HBV-endemic areas without precluding the use of HBsAg + donors., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The adoptive transfer of CAR-T cells, which are modified T cells expressing chimeric antigen receptors (CARs), to target B cell maturation antigen (BCMA) has demonstrated impressive results in treating relapsed/refractory multiple myeloma. Although BCMA CAR-T therapy induces certain complications in some patients, idiopathic thrombocytopenic purpura (ITP) has not been reported as one of them. To the best of our knowledge, this is the first report of the successful treatment of ITP that arose in a relapsed/refractory multiple myeloma patient following anti-BCMA CAR-T cell infusion. Herein, we describe this relatively uncommon complication and provide guidance on its treatment., Competing Interests: None., (© 2020 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Treatment of acute lymphoblastic leukemia (ALL) is still a challenge despite years of researching, especially for those of poor prognosis. Zhang and his team recently proved that FLT3 gene mutation was identified in ~5% of ALL and the mutation spectrum is different from AML. Recently, chimeric antigen receptor T cells (CART) therapy presents great efficacy in treating refractory leukemia. We report a case of a refractory ALL patient with FLT3-ITD mutations and unfavorable karyotypes, who failed to respond to chemotherapy and small molecule tyrosine kinase inhibitors, successfully treated by CART therapy. FLT3-ITD mutations were downregulated dramatically into 14.1% positive 3 days after the infusion and remained negative until now. MRD has stayed to be negative from the 10th day. This case suggests that CART-cell therapy might be effective in treating FLT3-ITD positive refractory ALL, implying the possibility to overcome the traditional prognosis scoring system for leukemia and providing a new chance for other leukemia patients with inferior prognosis factors.

Background: Chimeric antigen receptor T cells (CAR-Ts) constitute a novel therapeutic strategy for relapsed/refractory B-cell malignancies. CAR-T therapy has been extensively applied in the clinical setting; however, few systematic studies have evaluated the cost of CAR-T treatment. This study was conducted to evaluate the total cost and cost structure of CAR-T therapy and identify potential risk factors leading to increased costs., Methods: We identified the associated risk factors in 89 patients in a phase 1/2 study. The cohort included patients with acute lymphoblastic leukemia (ALL, n = 55) and non-Hodgkin's lymphoma (NHL, n = 34)., Results: Overall, the treatment of the ALL cohort was costlier than that of the NHL cohort ( P < 0.001). Furthermore, in the ALL cohort, it was costlier to treat patients with a high tumor burden ( P < 0.001), high cytokine release syndrome (CRS) grade ( P < 0.001), and complications of infection after CAR-T cell infusion (CTI) in the whole cohort ( P = 0.013) than patients with a low tumor burden, with low CRS grade, and without infection, respectively. CRS grade and length of stay ( P ≤ 0.005) were independent risk factors associated with the total cost in both the ALL and NHL cohorts during CAR-T therapy. A high tumor burden, duration of fever, and treatment with tocilizumab were independent risk factors associated with the total cost in the ALL cohort ( P < 0.05)., Conclusions: CAR-T treatment should be extended to patients with a low tumor burden or patients in a state of complete remission, and a corticosteroid approach, as opposed to tocilizumab, may reduce costs.

In the case of surface water pollution, it is important and necessary to accurately assess the level of contaminated water and ensure the safety of drinking water for people in disaster areas during floods. However, for the assessment of the strict requirements of drinking water, traditional assessment methods still have some limitations, such as low precision and rationality. In order to overcome these limitations, in the light of the theory of set pair analysis and variable fuzzy set, we propose an improved variable fuzzy set pair analysis method (IVFSPA), which combines the analysis framework of variable fuzzy set and set pair analysis, and has made some improvements to the fusion architecture. Firstly, we present a novel game theory comprehensive weighting method, in which the objective entropy method and the subjective analytic hierarchy process(AHP) method employed to obtain the reasonable weight. Then, based on the Nemerow index method, we improve the arithmetic form of " P i " (Equation P) to replace the fuzzy comprehensive evaluation method. Furthermore, we design a double judgment mode of combining the principle of maximum membership degree with the positive and negative relationship between the standard value and the measured value, which can accurately judge the evaluation level of surface water quality. Finally, to validate and verify the effectiveness of the proposed method, experiments was conducted at the representative river collection sections of Nanking, China, employing water quality data of 14 sampling sections in their rivers in Nanking during the 2017 flood. In terms of performance metcrics of precision and rationality, based on the values of "TP", "NH 3 -N", "Pb", "AS" and "KMnO 4 " of "Ch-lh section/Chuhe gate" are 0.415, 3.77, 0.07, 0.23 and 7.12, respectively, the level of Ch-lh section/Chuhe gate is that the IVFSPA is Class V and the rest are class IV. Results of experiments show that our IVFSPA method can achieve a good performance, compared with other traditional methods.

Following publication of the original article [1], the authors reported that the incorrect Fig. 2A was published in the article. The recovery times required to achieve a normal neutrophil count was omitted. The corrected Fig. 2 is given below.

Background: Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG)., Case Presentation: Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient's general condition remains good., Conclusions: This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case.