Explore the vast range of titles available.

This study investigated the relationship between the Inflammatory Burden Index (IBI) and risks of all-cause and cancer-specific mortality, focusing on its potential to enhance risk stratification. The research included a cohort of 14,835 participants from the American National Health and Nutrition Examination Survey. IBI was calculated using the formula CRP × (neutrophil / lymphocyte). Cox regression analysis was applied to assess the associations. During 223,719.71 person-years of follow-up, 3483 deaths (23.48%) occurred, including 778 (5.24%) from cancer. Mortality rates were 15.57 (all causes) and 3.48 (cancer) per 1,000 person-years. Kaplan–Meier analysis showed the highest IBI quartile had the lowest survival rates for all-cause and cancer-related mortality (Log-Rank p  < 0.001). Adjusted models revealed a 23.4% higher risk of all-cause mortality and a 14.1% higher cancer-specific mortality per standard deviation increase in IBI. Smooth curve fitting confirmed a proportional relationship between IBI and mortality risk. ROC curve and reclassification analyses supported IBI’s role in improving mortality risk prediction. The findings of this study indicate noteworthy associations between IBI and both all-cause and cancer-specific mortality. Moreover, the results highlight the potential of IBI in enhancing risk stratification for incident all-cause and cancer-specific mortality within the general population.

Chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated a transformative impact in hematologic malignancies and offers a promising strategy to offer new hope for patients with solid tumors who have failed multiple lines of treatment. The clinical application of CAR-T therapy in solid tumors, however, still has challenges, including tumor heterogeneity, an immunosuppressive tumor microenvironment, and safety concerns. These hurdles have mean that CAR-T therapy has become both a focal point and a pivotal trend in contemporary clinical research. The American Society of Clinical Oncology (ASCO) Annual Meeting serves as a premier venue for unveiling groundbreaking clinical data. In this review, we highlight the main phase I clinical trial advances in CAR-T therapy for solid tumors presented at the 2025 ASCO Meeting.

Heterogeneous/multiphase oxidation of SO2 by NO2 on solid or aqueous particles is thought to be a potentially important source of sulfate in the atmosphere, for example, during heavily polluted episodes (haze), but the reaction mechanism and rate are uncertain. In this study, in order to assess the importance of the direct oxidation of SO2 by NO2 we investigated the heterogeneous/multiphase reaction of SO2 with NO2 on individual CaCO3 particles in N2 using Micro-Raman spectroscopy. In the SO2 / NO2 / H2O / N2 gas mixture, the CaCO3 solid particle was first converted to the Ca(NO3)2 droplet by the reaction with NO2 and the deliquescence of Ca(NO3)2, and then NO2 oxidized SO2 in the Ca(NO3)2 droplet forming CaSO4, which appeared as needle-shaped crystals. Sulfate was mainly formed after the complete conversion of CaCO3 to Ca(NO3)2, that is, during the multiphase oxidation of SO2 by NO2. The precipitation of CaSO4 from the droplet solution promoted sulfate formation. The reactive uptake coefficient of SO2 for sulfate formation is on the order of 10-8, and RH enhanced the uptake coefficient. We estimate that the direct multiphase oxidation of SO2 by NO2 is not an important source of sulfate in the ambient atmosphere compared with the SO2 oxidation by OH in the gas phase and is not as important as other aqueous-phase pathways, such as the reactions of SO2 with H2O2, O3, and O2, with or without transition metals.

Vegetation impacts on cloud physical properties and climate. The rapid greening in China in the past two decades, which contributed the most to global greening, may influence clouds in the region. However, due to the influence of a rapid concomitant decline in aerosol levels in China and of global warming, such influence of vegetation change is yet to be clarified. By utilizing observation data from satellite, we explored the impact of vegetation change on summertime low-level cloud cover in China from 2003 to 2022. After excluding the influence of changing aerosol and temperature on clouds, we revealed a significant positive correlation between vegetation changes and low-level cloud cover. Moreover, we explored the underlying mechanisms through which vegetation exerts its influence on clouds. We found that such influence is mediated through enhancing surface water vapor content by vegetation as well as altering net surface radiation and sensible heat flux.

The reaction of SO2 with NO2 on the surface of aerosol particles has been suggested to be important in sulfate formation during severe air pollution episodes in China. However, we found that the direct oxidation of SO2 by NO2 was slow and might not be the main reason for sulfate formation in ambient air. In this study, we investigated the multiphase reaction of SO2 with an O2 ∕ NO2 mixture on single CaCO3 particles using Micro-Raman spectroscopy. The reaction converted the CaCO3 particle to a Ca(NO3)2 droplet, with CaSO4 ⚫ 2H2O solid particles embedded in it, which constituted a significant fraction of the droplet volume at the end of the reaction. The reactive uptake coefficient of SO2 for sulfate formation was on the order of 10−5, which was higher than that for the multiphase reaction of SO2 directly with NO2 by 2–3 orders of magnitude. According to our observations and the literature, we found that in the multiphase reaction of SO2 with the O2 ∕ NO2 mixture, O2 was the main oxidant of SO2 and was necessary for radical chain propagation. NO2 acted as the initiator of radical formation, but not as the main oxidant. The synergy of NO2 and O2 resulted in much faster sulfate formation than the sum of the reaction rates with NO2 and with O2 alone. We estimated that the multiphase oxidation of SO2 by O2 initiated by NO2 could be an important source of sulfate and a sink of SO2, based on the calculated lifetime of SO2 regarding the loss through the multiphase reaction versus the loss through the gas-phase reaction with OH radicals. Parameterization of the reactive uptake coefficient of the reaction observed in our laboratory for further model simulation is needed, as well as an integrated assessment based on field observations, laboratory study results, and model simulations to evaluate the importance of the reaction in ambient air during severe air pollution episodes, especially in China.

Recent studies have recognised highly oxygenated organic molecules (HOMs) in the atmosphere as important in the formation of secondary organic aerosol (SOA). A large number of studies have focused on HOM formation from oxidation of biogenically emitted monoterpenes. However, HOM formation from anthropogenic vapours has so far received much less attention. Previous studies have identified the importance of aromatic volatile organic compounds (VOCs) for SOA formation. In this study, we investigated several aromatic compounds, benzene (C6H6), toluene (C7H8), and naphthalene (C10H8), for their potential to form HOMs upon reaction with hydroxyl radicals (OH). We performed flow tube experiments with all three VOCs and focused in detail on benzene HOM formation in the Jülich Plant Atmosphere Chamber (JPAC). In JPAC, we also investigated the response of HOMs to NOx and seed aerosol. Using a nitrate-based chemical ionisation mass spectrometer (CI-APi-TOF), we observed the formation of HOMs in the flow reactor oxidation of benzene from the first OH attack. However, in the oxidation of toluene and naphthalene, which were injected at lower concentrations, multi-generation OH oxidation seemed to impact the HOM composition. We tested this in more detail for the benzene system in the JPAC, which allowed for studying longer residence times. The results showed that the apparent molar benzene HOM yield under our experimental conditions varied from 4.1 % to 14.0 %, with a strong dependence on the OH concentration, indicating that the majority of observed HOMs formed through multiple OH-oxidation steps. The composition of the identified HOMs in the mass spectrum also supported this hypothesis. By injecting only phenol into the chamber, we found that phenol oxidation cannot be solely responsible for the observed HOMs in benzene experiments. When NOx was added to the chamber, HOM composition changed and many oxygenated nitrogen-containing products were observed in CI-APi-TOF. Upon seed aerosol injection, the HOM loss rate was higher than predicted by irreversible condensation, suggesting that some undetected oxygenated intermediates also condensed onto seed aerosol, which is in line with the hypothesis that some of the HOMs were formed in multi-generation OH oxidation. Based on our results, we conclude that HOM yield and composition in aromatic systems strongly depend on OH and VOC concentration and more studies are needed to fully understand this effect on the formation of HOMs and, consequently, SOA. We also suggest that the dependence of HOM yield on chamber conditions may explain part of the variability in SOA yields reported in the literature and strongly advise monitoring HOMs in future SOA studies.

Multiple myeloma (MM) is a hematological malignancy with limited treatment options for patients with relapsed/refractory MM (RRMM). Teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, has shown promising results in clinical trials and real-world studies. PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library, ClinicalTrials.gov, and meeting libraries were searched from inception to 14 November 2024. The assessed outcomes included overall survival (OS), progression-free survival, time to next treatment, duration of response, overall response rate (ORR), ≥complete response (≥CR), ≥very good partial response (≥VGPR), VGPR, partial response, and adverse events. In total, 34 studies involving 4,064 patients were included. In pairwise meta-analysis, teclistamab demonstrated superior OS [hazard ratio (HR) = 0.69, 95% confidence interval (CI): 0.54-0.89; p = 0.037] compared to existing RRMM treatments. Real-world studies showed comparable ORR (62%, 95% CI: 58%-66%) but slightly lower survival outcomes, possibly because of shorter follow-up times and higher-risk populations. Subgroup analyses revealed enhanced efficacy with combination therapies (ORR: 85% vs 62%, p < 0.0001) and notable clinical benefits in the China cohort (≥VGPR: 77%, ≥CR: 58%). Safety profiles indicated manageable cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, though infection risks required vigilant management. Teclistamab continues to be a promising and effective treatment option for RRMM patients, including those previously exposed to BCMA-targeted therapies, and offers new hope for overcoming resistance and achieving better early disease control. Further research is needed to optimize its application in diverse populations, particularly in Asian cohorts. https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42025633838.

Background For CD19-positive relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) after treatment with murine CD19 (mCD19) CAR-T, the reinfusion of mCD19 CAR-T cells may be ineffective due to anti-mouse single-chain variable fragment (scFv) antibody caused by mCD19 CAR. To overcome this immunogenicity, we applied humanized CD19 (hCD19) CAR-T cells to treat r/r B-ALL patients with prior mCD19 CAR-T therapy. Methods Nineteen pediatric and adult patients were included, 16 relapsed after and 3 were primarily resistant to mCD19 CAR-T. All patients presented with more than 5% blasts in bone marrow and/or extramedullary disease, and still showed CD19 antigen expression. Humanized CD19-CARs were lentiviral vectors carrying a second generation CAR with 4–1-BB co-stimulatory and CD3ζ signaling domains. Patient-derived cells were collected for producing CAR-T cells, the median dose of infused hCD19 CAR-T cells was 2.4 × 10 5 /kg (range, 1.0–18.0 × 10 5 /kg). Results hCD19 CAR-T resulted in a complete remission (CR) rate of 68% (13/19). Among 13 remission patients, 11 underwent allogeneic hematopoietic cell transplantation (allo-HCT) (3 were second HCT) and 10 remained in CR; the event-free survival rates at 12–18 months were 91% in 11 patients received following allo-HCT and 69% in all CR patients. Six cases had no response to hCD19 CAR-T, 3 died of disease progression; another 3 received salvage second transplantation, of them, 2 relapsed again (one died). Cytokine release syndrome (CRS) occurred in 95% (18/19) of patients, most CRS events were grade 1 and grade 2 ( n  = 17), there was only one grade 4 CRS. Two cases experienced grade 1 neurotoxicity. Conclusions Humanized CD19 CAR-T cell therapy could be a treatment option for CD19-positive B-ALL patients who relapsed after or resisted prior murine CD19 CAR-T, hCD19 CAR-T followed by allo-HCT provided a longer remission in CR patients. Nevertheless, the prognosis of non-responders to hCD19 CAR-T remained dismal. Trial registration Chinese Clinical Trial Registry/WHO International Clinical Trial Registry ( ChiCTR1900024456 , URL: www.chictr.org.cn ); registered on July 12, 2019.

The prognosis for patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) is dismal. Recurrence in R/R DLBCL is mostly determined by antigen loss or mutation and the limited survival of chimeric antigen receptor (CAR) T cells. A 38-year-old female patient was diagnosed with left breast DLBCL in March 2018. After undergoing immunochemotherapy, autologous stem cell transplantation, and radiotherapy, she relapsed in May 2019. The peripheral blood (PB) morphology showed that 36% of cells were classified as unknown. The bone marrow (BM) smear showed 71% of abnormal lymphocytes. BM flow cytometric (FCM) analysis revealed 70.24% abnormal phenotype of mature B lymphocytes. The patient's abnormal karyotype was complex, and the 17th chromosome was missing. The p53 gene deletion (which accounted for approximately 82%) was revealed by fluorescence hybridization (FISH) investigation. Autologous CD19 CAR T cells were infused after lymphodepletion chemotherapy with cyclophosphamide and fludarabine. The patient experienced Grade I cytokine release syndrome (CRS) and achieved complete remission (CR). The genetic susceptibility gene test results suggested that the patient had potential susceptibility gene mutations for hematological tumors; therefore, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as consolidation therapy. Unfortunately, the patient relapsed 5 months after allo-HSCT. Then, the patient received sequential pseudoallogeneic CAR20/22/19 T-cell therapy. The patient is currently at 4 years after allo-CAR-T treatment with BM morphology CR, negative minimal residual disease, complete donor chimerism, and no graft versus host disease (GVHD). Our findings suggest that pseudoallogeneic CAR-T therapy was safe and effective in patients with DLBCL who experienced relapse after allo-HSCT. Sequential administration of CAR20/22/19 T cells may have reduced the antigen escape relapse in DLBCL. For patients with DLBCL relapse after allo-HSCT, larger trials are required to validate the safety and effectiveness of pseudoallogeneic CAR-T therapy as well as its ability to lower the rate of antigen escape relapse.

Post-stroke anxiety (PSA) has caused wide public concern in recent years, and the study on risk factors analysis and prediction is still an open issue. With the deepening of the research, machine learning has been widely applied to various scenarios and make great achievements increasingly, which brings new approaches to this field. In this paper, 395 patients with acute ischemic stroke are collected and evaluated by anxiety scales (i.e., HADS-A, HAMA, and SAS), hence the patients are divided into anxiety group and non-anxiety group. Afterward, the results of demographic data and general laboratory examination between the two groups are compared to identify the risk factors with statistical differences accordingly. Then the factors with statistical differences are incorporated into a multivariate logistic regression to obtain risk factors and protective factors of PSA. Statistical analysis shows great differences in gender, age, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level between PSA group and non-anxiety group with HADS-A and HAMA evaluation. Meanwhile, as evaluated by SAS scale, gender, serious stroke, hypertension, diabetes mellitus, drinking, and HDL-C level differ in the PSA group and the non-anxiety group. Multivariate logistic regression analysis of HADS-A, HAMA, and SAS scales suggest that hypertension, diabetes mellitus, drinking, high NIHSS score, and low serum HDL-C level are related to PSA. In other words, gender, age, disability, hypertension, diabetes mellitus, HDL-C, and drinking are closely related to anxiety during the acute stage of ischemic stroke. Hypertension, diabetes mellitus, drinking, and disability increased the risk of PSA, and higher serum HDL-C level decreased the risk of PSA. Several machine learning methods are employed to predict PSA according to HADS-A, HAMA, and SAS scores, respectively. The experimental results indicate that random forest outperforms the competitive methods in PSA prediction, which contributes to early intervention for clinical treatment.