bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of Peer Education on the Quality of Life and Self-Management Efficacy in Patients with Lymphoma
Authors: He Yang , Zhu Weiyi , Zhao Weili 
Published: December 2023

Object：
Effect of peer education model on quality of life and self-management efficacy in patients with lymphoma:
Methods:
500 patients with lymphoma were divided into control group (n=250) and observation group (n=250) according to the order of admission. The control group received routine nursing care, while the observation group received peer education on the basis of the control group's nursing interventions, with a nursing duration of 3 months for both groups. A comparison was made between the quality of life before and after intervention and the self-efficacy and self-management levels after intervention in both groups.
Results:
After intervention, the observation group showed significantly higher scores in overall health, physical role limitations, physical functioning, bodily pain, vitality, social functioning, emotional role limitations, and mental health compared to before intervention and the control group after intervention (P&lt;0.05). The observation group also exhibited significantly higher scores in self-efficacy, self-management, treatment compliance, communication with healthcare professionals, and cognitive management compared to the control group (P&lt;0.05).
Conclusion:
The peer education model significantly improves the quality of life in patients receiving chemotherapy for malignant tumors, and significantly enhances self-efficacy and self-management levels.
Gain or Amplification of Chromosome 1q Mediate Multiple Myeloma Resistant to Xpo-1 Inhibitor Selinexor Via Transcription Factor ETV3
Authors: Gu Huiyao , Zhong Yi , Zhang Enfan , Cao Liqin , Cai Zhen , He Jingsong 
Published: December 2023

Background: Gain or amplification of chromosome 1q, which characterized as a poor prognosis indicater, is one of the most frequent cytogenetic abnormalities in multiple myeloma (MM), occurring in nearly 40% of newly diagnosed patients. Though several genes, such as IL6R and CKS1B, have been reported to related to its severity, there still remains a mist for us to explore. So, we further explore the potential mechanism that may illustrate the malignant phenotype of gain or amplification of chromosome 1q in multiple myeloma, and the ETS transcription factors ETV3 may make sense.
Objective：Explore the functions ETV3 played in the malignant phenotype of gain or amplification of chromosome 1q in multiple myeloma.
Methods：Dataset GSE2658 from GEO database was used to analyze the correlation of ETV3 expression and survival of newly diagnosed multiple myeloma (NDMM). Dataset GSE4581 from GEO database was used to investigate the relationship between the number of 1q copies and expression of ETV3. Next, ETV3 expression on different myeloma cell lines was detected by RT-PCR,WB and high ETV3 expression cell lines were selected for further study. Knocking down of ETV3 on these cell lines were performed and CCK-8 was used to detected the proliferation ability. XPO-1 inhibitor selinexor was used with different concentrations (0-300nM) to treat these cells for 24h and 48h, and apoptosis was detected by flow cytometry. Further, RNAseq was performed to explore the related changed genes that might be regulated by ETV3.
Result s : Survival analysis showed MM patients with higher ETV3 expression exhibit worse prognosis according to Dataset GSE2658 (P mini=0.046). As for Dataset GSE4581, 414 patients were included, among which 186 patients carried more than 2 copies of 1q21. We found that along with the increasing of 1q21+ copies, expression of ETV3 increased (p&lt;0.01).
The results of RT-PCR and West-blots showed that all the MM cell lines expressed different level of ETV3, among which H929 and AMO1 were extremely high. Hence, we knocked down ETV3 on these two cell lines (H929 Sh-ETV3 and AMO1 Sh-ETV3) in subsequent experiments. Results showed that after knocking down of ETV3, the proliferation rate of myeloma cells was reduced (p&lt;0.05). Besides, myeloma cells knocked down of ETV3 were more sensitive to selinexor (p&lt;0.01). Based on the above results, we analyzed the genes changed after knocking down of ETV3 by RNAseq, results indicated several genes such as PKN1 might play a part in this process.
Conclusion s : MM patients carrying with higher 1q21+ copies expressed higher level of ETV3 genes, which indicated a worse prognosis. Knocking down ETV3 on myeloma cells reduced their proliferation ability and enhanced their sensitivity to selinexor. PKN1 might involved in this process.
Key words: ETV3, multiple myeloma, Gain or amplification of chromosome 1q, selinexor
The Role of Radiotherapy in Patients with Refractory Hodgkin Lymphoma after Brentuximab Vedotin and -/or Immune Checkpoint Inhibitors
Authors: Liu Ting-Bo , Li Xiaofan , Zhao Rui-Zhi , Shao Han , Shi Gui-Qing , Qiu Yan-Yan , Tang Tian-Lan , Lin Yu-Ping , Chen Si-Lin , Huang Cheng , Liao Si-Qin , Chen Jin-Hua , Fu Hai-Ying , Liu Jian-Zhi , Shen Jian-Zhen , Xu Ben-Hua , Zhang Yu-jing , Yang Yong 
Published: December 2023

Background: Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) had important roles in the treatment of relapse or refractory (R/R) Hodgkin lymphoma (HL). Treatment of refractory disease after BV and -/or ICIs remains a challenge. This study was conducted to evaluate the efficacy and safety of radiotherapy for R/R HL after failure to BV or ICIs.
Patients and methods: We retrospectively analyzed patients in two institutions with R/R HL who had failed after first-line therapy, and were refractory to BV or ICIs, and received radiotherapy (RT) thereafter. The overall response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were analyzed.
Results: A total of 19 patients were enrolled. First-line systemic therapy consisted of ABVD (84.2%), AVD + ICIs (10.5%) and BEACOPP (5.3%), respectively. After first-line therapy, 15 patients (78.9%) were refractory, and 4 patients (21.1%) relapsed. After diagnosis of R/R HL, 8 patients (42.1%) received BV, and 17 patients (89.5%) received ICIs. RT was delivered in all 19 patients who failed after BV or ICIs. In 16 efficacy-evaluable patients, the ORR and CR rate were 100% and 100%. The median DOR was 17.2 months (range, 7.9 to 46.7 months). 3 patients progressed at outside of the radiation field. The in-field-response rate was 100%. The 12-month PFS and OS were 84.4% and 100%, respectively. No patients were reported with sever adverse events.
Conclusion: This study concluded that radiotherapy was effective and safe for refractory HL after BV or ICIs. Further prospective studies were warranted.
KEY WORDS: Radiotherapy; Hodgkin lymphoma; Brentuximab vedotin; Immune checkpoint inhibitors; Refractory; Relapse
The Ratio of Urea Nitrogen to Albumin Is a Better Predictor of OS in MM Patients Than That of Urea Nitrogen Alone
Authors: Dong Mengmeng , Shao Jiaqi , Zhang Enfan , Chen Haoguang , Cai Zhen , Cheng Tao 
Published: December 2023

Background
Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients.
Methods
We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, Kaplan‒Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study.
Results
There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with β2-microglobulin (β2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. β2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost β2-MG and LDH's predictive value and sUAR had a higher predictive value.
Conclusion
This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with β2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.
Key words
Serum urea nitrogen, ratio of serum urea nitrogen to serum albumin, multiple myeloma, overall survival, β2-microglobulin, lactic dehydrogenase
Mutational Changes in Solid Cancer Cells Induce DNA Damage Repair Deficiency in Hematopoietic Cells Leading to a Distinct Spectrum of Clonal Hematopoiesis Independent from Age-Related Clonal Hematopoiesis
Authors: Leitner Theo , Künstner Axel , Kohl Michael , Barmwater Tobias , Ahmed Helal Mohammed , Caliebe Almuth , Dazert-Klebsattel Eva , Fähnrich Anke , Fliedner Stephanie , Gebauer Niklas , Spielmann Malte , Kirfel Jutta , Sailer Verena-Wilbeth , Bastian Lorenz , Von Bubnoff Nikolas , Busch Hauke , Khandanpour Cyrus 
Published: December 2023

Clonal hematopoiesis (CH) is characterized by the acquisition of defined somatic mutations in hematopoietic stem cells (HSC). It is well known that CH contributes to the development of hematological malignancies but also increases the risk of developing non-malignant conditions such as cardiovascular, pulmonary, and inflammatory liver disease.
However, less is known about the association between clonal hematopoiesis and solid cancer. Reports suggest that patients with solid cancer have a higher incidence of clonal hematopoiesis at an earlier age and an inferior prognosis. To investigate whether the presence of solid cancer itself can drive the development of clonal hematopoiesis, we analyzed 392 paired tumor and blood samples from patients with advanced cancer. In our cohort, all patients had evidence of clonal hematopoiesis based on a variant allele frequency (VAF) of at least 2%. With respect to a defined set of the 20 most frequently CH-associated genes, we discovered an increased CH rate of 23% of all patients (90 cases, median age of 61 years, defined by a VAF from 2% to 30%). The frequency of mutated genes differed greatly from published data from the general population and cancer patients, with the most common mutations being PABPC1 (39%), KMT2C (28%), RUNX1 (18%), and DNMT3A (10%). In addition, we observed a strong correlation between certain mutations in tumor samples and the frequency of CH. The mutational signature of CH was not mainly associated with a typical chemotherapy-dependent mutational signature, but with an impaired DNA repair capacity. For further investigation, we performed additional experiments in mice, which showed that the presence of malignant cells impairs DNA repair capacity in HSC through inflammatory changes in the stroma.
In summary, we were able to show that patients with advanced or recurrent solid tumors have a significantly increased frequency of CH, which is not only the result of prior chemotherapy exposure but the result of diminished DNA repair capacity. This suggests a possible role of solid cancer in promoting the development of CH independent from chemotherapy exposure, which is supported by our additional murine experiments.
Implementation of Clinical Pathways for CAR-T Cell Therapy in a Brazilian Private Healthcare Organization
Authors: Carvalho De Camargo Maria Fernanda FERNANDA , Santos Francisca VANOIDE DE BRITO , Seber Adriana , Rabello Chiattone Ricardo , Bigni Ricardo , Maiolino Angelo , Barroso Fernando , Coelho Erika , Silva Erica FRANCISCO , Chimentao Denise , Lobo Cecilia OLIVEIRA , Santos Elisangela , Lucas Ticiane , Lima Patricia BARROS , Abraao Ligia 
Published: December 2023

Introduction: the treatment with CAR-T cells in Brazil is challenging because it requires a highly qualified multidisciplinary team trained in new clinical pathways to take care of these patients.
Objective: to describe the implementation of the clinical pathways for CAR-T cell therapy, ensuring safety and quality.
Method: this is an experience report study, performed in four private general hospitals of the Americas from São Paulo, Rio de Janeiro and Ceará states, during the year of 2022. The process of implementing the CAR-T Cell clinical pathway included: creation of a medical committee with the main medical references and specialist nurses from each center, for the elaboration of the main clinical protocols and operational procedures, in addition to the discussion of eligibility cases for therapy with CAR-T Cells. Identification of the multidisciplinary reference team in all phases of treatment, training the team involved in the clinical care of the patient, and finally, establishment of patient clinical pathway before, during and after the CAR-T cell therapy. The implementation process lasted seven months between the qualification of centers by the Therapy provider, internal qualification each center and the first cell infusion with CAR-T Cell performed.
Results: In all hospitals, professionals from the multidisciplinary team (pharmacy, nursing, physicians - hematologists, pediatric hematology-oncologists involved in hematopoietic stem cell transplantation, neurologists, pediatric and adult intensive care physicians) were trained. The Multidisciplinary Care Protocol was elaborated including indications, early and late complications. The Standard Operating Procedures addressed the pre and post infusion care, daily screening, criteria to transfer the patients to the intensive care unit, recognition and management of cytokine release syndrome and neurological toxicities. The main challenges of this process were to create the routines for evaluation and systematic monitoring and to identify and involve the multidisciplinary professionals directly involved in patient care.
Conclusions: the implementation of the program brought improvements to the clinical pathway, positively impacting professional satisfaction, the quality and safety of the patients. The CAR-T cell therapy was performed in a safe and integrated environment, uneventful and successful.
Ex-Vivo Testing Platform to Predict Clinical Response and Resistance to Proteosome Inhibitors, IMiDs and Daratumumab in Multiple Myeloma
Authors: Marin Constanza , Nicola Maribel , Andino Diego , Bernaschini Maria Laura , Conrrero Agustina , Ferreira Gimena , Piaggio Marisa , Remaggi Guillermina , Jarchum Maria Sol , Jarchum Gustavo , Meneces Bustillo Rodrigo , Rossi Blanca de los Milagros , García Juan José , Zaki Tarek Ali , Llorens Candelaria , Gatti Gerardo , Arroyo Daniela , Soria Gastón 
Published: December 2023

Treatment of Multiple Myeloma (MM) relies on Standard of Care (SoC) schemes that include immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) in combination with dexamethasone (Dexa). More recently, monoclonal antibodies such as Daratumumab (Dara) have become complementary therapeutic strategies to treat newly diagnosed and relapsed MM patients. Despite the multiple therapeutic schemes available, MM remains an incurable disease in which patients transit intermittent cycles of relapse and remission that ultimately lead to multi-drug resistance. It has therefore become clear that novel tools for personalized therapy selection are necessary to improve outcomes and reduce trial and error, particularly when selecting later lines of treatment.
At OncoPrecision, we have developed a personalized ex-vivo platform that mimics the tumor microenvironment and promotes the survival of Patient-Derived Cells (PDCs), with the goal to predict the performance of the complete array of FDA-approved drugs, as well as experimental treatments, within 7 days. This technology, which we have named Patient Micro Avatars (PMAs), consists of the co-culture of PDCs with engineered neoplastic (System Control) and stromal (Tox Control) heterologous cells in combination with a multi-tagging approach coupled to high-throughput flow cytometry (Figure: Upper Panel). Our PMAs not only enable us to rank the activity of all approved treatments, but also unveil potential unspecific toxicities of novel treatments on non-tumoral cells, thus unlocking unique insights for early drug development programs.
In this work, we introduce our PMA technology for MM by presenting differential response between patients in a Clinical Study performed in collaboration with two healthcare centers which, through approved IRBs, have provided MM patient samples from bone marrow aspiration. We present ex-vivo profiling results with a comprehensive MM drug matrix which includes SoC treatments used in several lines of therapy. We illustrate the potential of PMAs to identify differential activity from individual agents and synergistic drugs combinations in 13 patients (Figure: Lower Panel). By anticipating vulnerability/resistance to SoC treatments, our platform has the potential to become a first-in-class phenotypic biomarker to serve as a decision-support tool for Physicians to select optimal therapeutic regimes, as well as to elucidate valuable pre-clinical patient-derived insights for the development of innovative therapies for MM.
Rational Combinatorial Targeting By Adapter CAR T Cells (AdCAR-T) Prevents Antigen Escape in Acute Myeloid Leukemia (AML)
Authors: Atar Daniel , Ruoff Lara , Mast Anna-Sophia , Krost Simon , Moustafa-Oglou Moustafa , Scheuermann Sophia , Kristmann Beate , Feige Maximilian , Canak Aysegül , Wolsing Katrin , Schilbach Karin , Zekri Latifa , Ebinger Martin , Nixdorf Daniel , Subklewe Marion , Schulte Johannes , Lengerke Claudia , Werchau Niels , Mittelstaet Joerg , Lang Peter , Handgretinger Rupert , Schlegel Patrick , Seitz Christian Martin 
Published: December 2023

Targeting AML by chimeric antigen receptor T cells (CAR-T) has been challenging due to promiscuous expression of AML-associated antigens on healthy hematopoietic stem and progenitor cells as well as a high degree of inter- and intratumoral heterogeneity. Consequently, we did not yet see the dramatic clinical successes as in B-phenotypic malignancies treated with CD19 or BCMA directed CAR-T.
In the present study, we analyzed inter- and intratumoral heterogeneity of AML-associated antigens in 30 primary pediatric AML samples at single cell resolution. We identified CD33, CD38, CD371, IL1RAP and CD123 to be most frequently expressed. Notably, high variability was not only observed across the different patient samples, but also among leukemic cells of the same patient, which indicates that multiplexed targeting approaches will be required to target all leukemic cells. To address this need, we utilized our modular Adapter CAR (AdCAR) platform enabling precise qualitative and quantitative control over CAR-T function. We show highly efficient and target specific activity for newly generated adapter molecules (AMs) against CD33, CD38, CD123, CD135 and CD371, both in vitro and in vivo. Importantly, we prove that inherent intratumoral heterogeneity in antigen expression translates into antigen escape and therapy failure to mono-targeted CAR-T therapy. For the first time, we demonstrate in a PDX model that rational combinatorial targeting by AdCAR-T can cure heterogenic disease.
In conclusion, we elucidate the clinical relevance of heterogeneity in antigen expression in pediatric AML and present a novel concept for precision immunotherapy by combinatorial targeting, utilizing the AdCAR platform.
A Complex Relationship between Clostridium Difficile Infection and Graft Versus Hoste Disease: Fundeni Clinical Institute Experience
Authors: Lipan Lavinia Eugenia , Enache Alexandra Oana , Colita Anca , Craciun Oana , Stefan Laura Diana , Tanase Alina Daniela 
Published: December 2023

Introduction: Clostridium difficile infection (CDI) is a common complication in patients who have undergone hematopoietic stem cell transplantation (HSCT) due to prolonged hospitalization, prolonged neutropenia, use of broad-spectrum antibiotics, mucosal damage, changes in gut microbiota and compromised immunity. The incidence of CDI in patients undergoing allogeneic HSCT varies between 12 and 34% in the literature and has gradually increased in recent years in Europe North America due to the NAP1 strain. In the patient who has experienced allogeneic HSCT, diagnostic testing for CDI should include both nucleic acid amplification test (NAAT) and enzyme immunoassays (EIA) for toxins A and B, because detection of toxins A and B tests have a sensitivity of 75-80%. 5 In HSCT patients, CDI appears to be strongly associated with graft versus host disease (GVHD), gut GVHD and/or severe GVHD, but this has not been universally demonstrated.
The aim: For this reason, we wanted to see whether patients who developed a CDI between day 0 and day 100 were at higher risk for gut GVHD or for severe GVHD.
Results: Between January 2017 and August 2022, we performed 290 of allogeneic hematopoietic stem cell transplant procedures, in the Fundeni Clinical Institute. 50/290 developed CDI within the first 100 days after HSCT and before the diagnosis of intestinal GVHD, and 240/290 did not develop CDI. 16/50 (32%) of those with CDI developed acute GVHD, respectively 402/240 (43%) of those without CDI. From these 13/16, respectively 50/102 hade gut involvement. Of the 118 patients with acute GVHD, 13/16 in the group with CDI, respectively 30/102 in the group without CDI were assigned to severe acute GVDH (grade III and IV). Mortality due to gut GVHD in the group with CDI was 46%, respectively 14% in the group without CDI.
In conclusion: CDI is not a risk factor for GVHD, but gut damage is usually associated. CDI infection is associated with severe forms of GVHD, and the implication of the digestive tract in these patients increases mortality. Also, often in the patient with digestive GVHD, CDI can coexist, making them difficult to treat.