bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Web-Based Mind-Body Intervention (Mindful Steps) for Promoting Walking in Chronic Cardiopulmonary Disease: Insights From a Qualitative Study
Authors: Kraemer Kristen M. , Kilgore Karen , Litrownik Daniel , Jean-Laurent Brianna , Wayne Peter M. , Richardson Caroline R. , Moy Marilyn L. , Yeh Gloria Y. 
Published: December 2023

Background Given the deleterious effects of physical inactivity in persons with chronic obstructive pulmonary disease (COPD) and/or heart failure (HF), interventions that promote long-term daily physical activity are needed. Mindful Steps, designed to promote walking behaviors in COPD and HF, is a multicomponent intervention that integrates mind-body content with other self-regulatory components. The aim of the current qualitative study was to characterize participants’ experiences with Mindful Steps and understand the perceived influence of the intervention on walking and health. Method In the context of a pilot randomized controlled feasibility trial comparing the year-long Mindful Steps program to usual care among individuals with COPD and HF, semi-structured qualitative interviews were administered at 6- and 12-months. Interviews were audio recorded and transcribed. The constant comparative method was used to code transcripts, identify categories, and develop interrelated themes. Results Nineteen participants (63% female; M age = 70.2 years, SD = 6.95) who were randomized to the intervention group completed the 6-month interview and 17 completed the 12-month interview. The pedometer with feedback, live group classes, and mind-body videos were described as the most helpful intervention components. Participants learned several strategies that helped their walking (e.g., breathing regulation and awareness, body awareness, mind-body techniques, pacing), described walking as enjoyable, and identified internal reasons for walking (e.g., to feel good). They also reported several physical and mental health benefits of the intervention. Some participants reported limited influence of the intervention on walking or health. Many participants continued to use the strategies they learned in the first half of the intervention at 12-months. Conclusions The mind-body content of Mindful Steps appeared to positively influence walking behaviors. Participants’ experiences with the intervention helped to identify areas for future intervention refinement. Future quantitative work is needed to corroborate these qualitative findings and assess the efficacy of the intervention on long-term physical activity engagement. Trial Registration This trial is registered in Clinical Trials.gov, ID number NCT01551953.
Enhancing Therapeutic Efficacy: Harnessing the Synergy of Histone Deacetylase and BCL6 Inhibition in DLBCL
Authors: Zhuang Wenzhuo , Li Qi , Zhang Yuchen , Li Bingzong 
Published: December 2023

Background
Diffuse large B-cell lymphoma (DLBCL) is characterized by its aggressive nature and resistance to standard chemotherapy, necessitating the development of new therapeutic approaches. Histone acetylation, a crucial epigenetic modification, is globally decreased in DLBCL. Chidamide, a histone deacetylase (HDACs) inhibitor, has shown promise in certain lymphomas but its effectiveness in DLBCL remains under investigation.
Methods
RNA-seq and gene enrichment analysis were performed to identify chidamide's impact on the biological processes in DLBCL. The key factor influencing chidamide sensitivity was determined through correlation analysis, utilizing gene expression levels from the Cancer Cell Line Encyclopedia and IC50 values of four HDAC inhibitors across multiple cancer cell lines sourced from the Genomics of Drug Sensitivity database. Histone acetylation levels, HAT and HDAC enzyme activity analysis, and co-immunoprecipitation were performed to investigate the underlying mechanism through which BCL6 influences chidamide sensitivity. A search among small molecule drugs in clinical investigation aimed to find drugs inhibiting BCL6 to enhance DLBCL sensitivity to chidamide. Synergy between HDAC and BCL6 inhibition was explored through synergistic effects, ubiquitination, and proteasomal degradation analysis. DLBCL mouse models were utilized to evaluate the therapeutic potential of combining chidamide and lenalidomide in vivo. Additionally, chidamide's effects on macrophage polarization were investigated through RNA-seq analysis of M1, M2, and chidamide-treated M2 macrophages.
Results
Chidamide exhibited potent suppression of DLBCL both in vitro and in vivo (Figure 1A), exerting a significant impact on diverse biological processes in DLBCL. BCL6 inhibited chidamide-induced histone acetylation by recruiting HDACs, leading to drug resistance in DLBCL cells. Lenalidomide could target BCL6 degradation through the ubiquitination pathway and restored the sensitivity of drug-resistant DLBCL to chidamide (Figure 1B). Additionally, chidamide had an impact on the tumor microenvironment. Chidamide inhibited the activity of M2-like tumor-associated macrophages and redirected the polarization of macrophages toward the M1 phenotype. Moreover, we conducted a single-arm multicenter clinical trial to evaluate the safety and efficacy of chidamide in combination with lenalidomide in DLBCL.
Conclusions
These findings highlighted HDACs as a viable therapeutic strategy for DLBCL, providing valuable insights into chidamide's global impact on the disease. Furthermore, BCL6 was a pivotal determinant of chidamide sensitivity and a reliable biomarker for treatment response. Integrating HDAC and BCL6 inhibition held potential for personalized and effective DLBCL treatments.
The Treatment of Burkitt Lymphoma with the Berlin-Frankfurt-Münster Protocol with Rituximab and Autologous Transplantation
Authors: Broccoli Alessandro , Bagnato Gianmarco , Argnani Lisa , Casadei Beatrice , Cantelli Martina , Pellegrini Cinzia , Zoli Sabrina , Sutto Emanuele , Coppola Paolo Elia , Gentilini Marianna , Morigi Alice , Carella Matteo , Gugliotta Gabriele , Nanni Laura , Stefoni Vittorio , Zinzani Pier Luigi 
Published: December 2023

Intensive treatment approaches are required for adult Burkitt lymphoma (BL), although a univocal standard of care still does not exist. The use of frontline autologous transplantation is debated.
Between 2004 and 2020, 50 HIV-negative BL patients were treated with the Berlin-Frankfurt-Münster (BFM) protocol at our institution. Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, cytarabine), B (vincristine, cyclophosphamide, methotrexate, doxorubicin) and C (vindesine, methotrexate, etoposide, cytarabine), each repeated twice, every 28 days. Patients elder than 60 years did not receive block C, thus blocks A and B were repeated 3 times. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. Autologous stem cells were reinfused (ASCT) at the end of the 6-blocks after BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning, when feasible.
Median age at onset was 38 years (range 16-72); 38 patients were male and 12 female. Stage III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Two patients did not receive rituximab because of adverse reaction and early death. Intrathecal prophylaxis was given in 96% of patients. Stem cell harvest was performed in 70% of patients, who all received a subsequent ASCT. The full 6-blocks treatment was completed in 70% of the patients; 8% received 5 cycles and 22% received ≤ 3 cycles. Early treatment interruption occurred because of disease progression (12%), toxicity (8%), death (4%) or other causes (4%).
The overall response rate was 74%, with a complete response rate of 60%. Three patients could not be evaluated because of early progression/death. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, with both curves exhibiting a plateau (Figure). Ten-year disease-free survival was 80.3%. Eight patients had died because of disease progression (3 patients), infection or sepsis (4 patients) or cardiac arrest (1 patient). Grade 3-4 neutropenia, thrombocytopenia, anemia and mucositis were seen in 96%, 60%, 32% and 24% of patients. Infections occurred in 60% of patients; grade 4 and fatal sepsis in 14% and 8% of cases.
Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe and highly effective in adult patients with BL, as confirmed by long-term survival rates.
Earliest Possible Detection and Intervention for Synovitis in Hemophilia- Results from a Single Center Retrospective Cohort Study
Authors: Halimeh Susan , Daoud Mohamad Ayman , Siebert Manuela , Zappek Jennifer , Rosenthal Marc 
Published: December 2023

Introduction
There is scientific evidence to suggest that the most serious health problems for hemophilic patients arise from joint damage, which in turn results from joint bleeding, which is overlooked and therefore not treated. The ankle joint was affected the earliest in most hemophilic patients. Strategies for detecting and treating bleeding in hemophilic patients need to be further developed and made more widely known by clinicians.
Aim of our study
The aim of our retrospective, single-center cohort study was to compare the effects of reactive versus preventive joint ultrasound as guidance for adjustments of treatment regimens for patients with severe hemophilia at our Hemophilia Comprehensive Care Center (HCCC) in Duisburg, Germany.
Methods
Before 2020, we used ultrasound according to the German hemophilia-synovitis guidelines in 2018. This meant that we sonographed the ankle joints and knees of most of our patients when they reported discomfort in the joint or when a joint bleeding had occurred. In these cases, prophylactic hemophilia treatment was immediately adjusted to a level at which the bleeding and/or discomfort stopped. If the factor treatment was not sufficient to accomplish this goal, the joints were treated with radiosynoviorthesis (RSO). In 2020, we changed our diagnostic strategy from reactive to preventive measures. Thus, we used ultrasound on every ankle and knee joint of our severely hemophilic patients at least once a year. If we found so called “silent symptoms,” which means touch-sensitive joints, the joints were sonographed once every three months. In cases of signs of joint degradation, we adjusted the prophylactic factor treatment accordingly.
Results
From 2020 to 2022, we examined a total of 1193 joints of 688 patients with hemophilia A or B, as well as with vWD disease type 2 or 3 and other severe coagulation disorders (factor VII deficiency, factor XIII deficiency, afibrinogenemia, and Glanzman disease).
Of these, 103 had severe hemophilia A or B. In this study, we examined 656 joints sonographically. Of these, we examined 281 ankle joints in 80 patients and 175 knees in 64 patients, and adjusted the therapy regimens accordingly in these patients if necessary.
Seven RSOs of the ankle joints and three RSOs of the knees were performed in the cohort up to 2020. After 2020, only two RSOs of the ankle joints were performed in the cohort.
Conclusions
At least for patients at our HCCC in Duisburg, Germany, we were able to show for the period 2020-2022 that closer ultrasound monitoring of ankle joints and knees in patients with severe hemophilia A or B and appropriate adjustment of prophylactic factor therapy was associated with less severe and less frequent joint degradation.
Phase I First-in-Human Study on the Feasibility, Safety, and Antitumor Activity of CD4-Redirected Chimeric Antigen Receptor (CAR) T-Cell Therapy in Patients with CD4+ T-Cell Malignancies (TCM)
Authors: Assi Rita , Hagag Nabil , Farag Sherif , Emmons Robert V.B. , Carter Allie , Czader Magdalena , Abonour Rafat , Apetoh Lionel , Ma Yupo , Salman Huda S. 
Published: December 2023

Background
TCM are aggressive diseases with poor outcomes. Translating the CAR T-cell therapy success from B-cell diseases to TCM has proven challenging. CD4 is an attractive therapeutic target, owing to its restricted expression on normal tissues. In this first-in-human phase I study, we investigate the autologous third generation CD4-redirected CAR T-cell safety, tolerability, manufacturing feasibility, trafficking and preliminary efficacy in patients with R/R CD4+ TCM who failed standard therapies.
Methods
The investigational construct is engineered with a single-chain variable fragment (ScFV) and dual co-stimulators (CD28; 4-1BB), fused to CD3zeta and CD8 leader sequence, packaged in lentivirus and transducer into T-cells. Patients received conditioning therapy with fludarabine and cyclophosphamide. CD4CAR product is administered in a 3+3 dose-escalation scheme. Dose-limiting toxicities (DLT) were monitored during the initial 42-days post-treatment. Treatment-emergent adverse events (AE) were graded by CTCAE v5.0
Results
Three patients with median age of 63 years (range, 18-68) were enrolled and treated at DL1 (2.0x10^5/kg), including 2 (66%) women and 2 (66%) African-American. Median number of prior therapies was 3 (range, 2-4) (Figure). AEs included grade 3-4 hematologic toxicity in 3 (100%) patients, all present before enrollment. There was no protocol defined DLTs. All grade ≥3 lymphopenia reverted to grade 2 by day 30 and no related infections occurred between CAR infusion and hematopoietic stem cell transplantation (HSCT). Since infusion, the CAR T-cells percentage in peripheral blood had continued to expand. CD4CAR T-cells were detectable in all patients for at least 28 days post-infusion, meeting the primary endpoint, and on D111 in one patient. CD4CAR expansion was reflected on by a decrease in CD4/CD8 ratio and flow cytometry using ScFV Fab2 specific antibodies (Figure). Cytokine response analysis CD4CAR was associated with variable but significant production that seems to correlate with clinical responses (Figure; More data at meeting). No cytokine-mediated organ toxicities were observed. Bone marrow and peripheral blood flow cytometry confirmed complete remission (CR) in 2 patients at day 30 (PTCL and T-ALL). Patient 3 (mycosis fungoides) achieved hematological CR with stable skin lesions. Post-treatment day 30 skin biopsy demonstrated persistent disease with marked loss of CD4.
Conclusions
CD4CAR T-cell therapy is feasible in patients with R/R CD4+ TCM. 2/3 patients achieved CR and the third achieved hematological CR with stable skin disease. Toxicities were manageable without DLT upon completion of cohort 1. The cytokine response suggests immune activation and tumor recognition by CD4CAR T-cells. Dose escalation will proceed. NCT03829540
Clinical Analysis of 22 Cases of HIV-Associated Hodgkin Lymphoma in China
Authors: Wang Chaoyu , Liu Jun , Wu Yan , Min Haiyan , Yang Tao , Zhang Wei , Zhou Hui , Liu Yao 
Published: December 2023

Introduction: Knowledge of HIV associated Hodgkin lymphoma mainly comes from case series or retrospective studies. Further,these criteria and guidelines have not been systematically evaluated. To investigate the clinical characteristics, response, and prognosis of HIV associated Hodgkin lymphoma in China.
Methods:A total of twenty-two cases of human immunodeficiency virus infection-related Hodgkin lymphoma patients from 5 Chinese hospitals were enrolled in this study, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed.
Results : The median age at diagnosis was 44(22-60) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man sex with man and twelve cases transmitted through heterosexual transmission. Nine patients were diagnosed with lymphoma and found to be infected with HIV. Five cases were in stage III,and seventeen cases were in stage Ⅳ.After a median follow up of 30.6（4.0～112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with antiretroviral therapy. The 3-year PFS and OS rate were 80.8% and 85.9%,respectively.
Conclusion : HIV associated Hodgkin lymphoma exhibit an invasive process in clinical practice, and standardized treatment can achieve long-term survival.
【Key words】HIV; Hodgkin lymphoma; Therapeutics;Prognostic
The Role of Red Blood Cell Lifespan Testing in the Evaluation of Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Ye Lei , Zhao Xin , Jing Liping , Zhang Fengkui , Zhang Li 
Published: December 2023

Objective To explore the role of red blood cell(RBC) lifespan testing in the evaluation of patients with paroxysmal nocturnal hemoglobinuria (PNH). Methods The endogenous breath carbon monoxide (CO) test was used to detect the RBC lifespan of PNH patient with the treatment of crovalimab（ Roche） or iptacopan（ Novartis.），for comparison of different hemolysis indices in the assessment of patients' condition. Results Nine patients have been enrolled in the study at our centre from June to December 2021, 4 with the treatment of crovalimab and 5 with iptacopan. The median lifespan in the untreated patients was 17 (range 12-38) days, median hemoglobin(Hb) 83(69-94) g/l, median lactic dehydrogenase（LDH）590.8(446.1-935.5)U/L, median PNH clones 96.0(33.2-99.9)%. By 6 months post-treatment, 8 patients achieved hematologic improvement without breakthrough hemolysis. In all patients, LDH levels decreased rapidly and stabilized at lower levels after starting treatment. But the degree of Hb recovery varied，median 60(20-85)g/L. Analyzing the correlation between different hemolytic indices (LDH, RBC lifespan, total bilirubin, indirect bilirubin, etc.) and Hb changes, RBC lifespan showed good correlation（P=0.002，R=0.867）. In the crovalimab group, three patients presented with a positive Coombs test and the negative patient didn't obtain hematologic improvement. No patients with a positive Coombs test were seen in the iptacopan group. Conclusion Different (upstream/downstream) complement inhibitors have different effects on the condition of PNH patients, and different indicators can reflect different results; LDH responds to intravascular hemolysis, and red blood cell lifespan also quantifies extravascular hemolysis, and is applied to monitor hemolysis. The application of RBC lifespan testing can provide an accurate scientific basis for the assessment of PNH conditions.
Keywords: red blood cell lifespa, paroxysmal nocturnal hemoglobinuria ,red blood cell lifespan,lactic dehydrogenase
Single-Cell Analyses Unveil a Potential Mechanism Promoting Graft-Versus-Leukemia Response in Haploidentical Transplantation Using Peripheral Stem Cells Plus Cord Blood Grafts through Early Immune Reconstruction of CD8+ Infg+ T Cells
Authors: Yu Sijian , Liu Qifa , Xu Xi , Liu Qiong , Qiu Guo 
Published: December 2023

Abstract
Background
Haploidentical donor stem cell transplantation (haplo-SCT) by using G-CSF-primed peripheral stem cells combined with bone marrow grafts (PBSC+BM) represents a widely employed strategy for acute myeloid leukemia (AML). While leukemic relapse is one of the main reasons for the failure of SCT. Surprisingly, our clinical data found that haploidentical peripheral stem cells combined with cord blood (haplo-PBSC+cord) transplantation had significantly lower incidence of relapse than haplo-PBSC+BM transplantation. Nonetheless, the underlying mechanism needs to be explored.
Method
From 2021 to 2022, bone marrow samples at 1 and 3 months post-transplantation from 4 AML patients who underwent haplo-PBSC+cord transplantation and 3 AML patients who received haplo-PBSC+BM transplantation were obtained. We used single-cell RNA-sequence (scRNA-seq) technology for analysis of hematopoietic reconstitution disparity between the PBSC+cord and PBSC+BM groups.
Results
Significant disparities manifest in the initial stages of hematopoietic reconstitution between the PBSC+cord and the PBSC+BM groups. Notably, at 1 month and 3 months post-transplantation, the PBSC+cord group demonstrated conspicuous reconstitution of lymphoid and erythroid cells, with CD8+ T cells exhibiting the most pronounced effect. Differential gene analysis revealed that T cells in the PBSC+cord group display elevated expression of graft-versus-leukemia (GVL)-related cytokines, including IFN-γ, CCL3, and IL1B, when compared to the PBSC+BM group. Furthermore, noteworthy differences in T cell subsets were observed between the two groups. Within 1 month and 3 months post-transplantation, the PBSC+cord group experienced up-regulation of CD8+ effector memory T cells (TEM), characterized by heightened expression of the IFNG gene. Gene Set Variation Analysis (GSVA) unveiled significant enrichment of CD8+ IFNG+ TEM in T cell activation, cytotoxicity, cytokine secretion, and other pathways, suggesting its potential GVL effect. On the contrary, the PBSC+BM group demonstrated a higher proportion of CD4+ T cells, γδT cells, and MAIT cells at 1 month and 3 months post-transplantation. Among CD8+ T cells, the PBSC+BM group showcased a more robust reconstruction of CD8+ TIGIT+ T cell subsets, which highly express exhaustion-related genes like TIGIT, LAG3, PDCD1 (PD-1), HAVCR2 (TIM-3), and exhibited increased apoptosis-related pathway activity.
Conclusion
Our investigation identified a potential mechanism promoting GVL response in the immune reconstitution of haplo-PBSC+cord transplantation.