bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Characteristics and Outcomes of Nodular Lymphocyte Predominant Hodgkin Lymphoma at a Safety-Net System Compared to an Academic Comprehensive Cancer Center
Authors: Froessl Luise Josefine , Sottero Theo , Brown L. Steven , Li Hsiao Ching , Kainthla Radhika , Sadeghi Navid 
Published: December 2023

Purpose:
Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that often follows an indolent course although carries a risk of late recurrence and transformation. Given its rarity, there is significant variability in the treatment patterns at various healthcare centers. The aim of this study was to compare the patient characteristics and outcomes of NLPHL treated at a safety-net system compared to those treated at an academic comprehensive cancer center.
Materials and Methods:
Parkland Health (PH) is the safety-net system for uninsured/underinsured patients in Dallas County and is affiliated with the UT Southwestern NCI-designated Harold C. Simmons Comprehensive Cancer Center (SCCC). Electronic records of adult patients (age &gt; 18) diagnosed with NLPHL between January 1st, 2007, and December 31st, 2022, at the two centers were reviewed and data on demographics, disease characteristics, treatments, and outcomes were collected.
Results:
A total of 53 patients were included in the study (25 at PH vs 28 at SCCC). The median age at diagnosis was 42 (IQR 32-54.5) and was not significantly different between the institutions (41.7 at PH vs 46.5 at SCCC). There was a trend towards male predominance at SCCC compared to PH, but this was not statistically significant. PH patients were more likely to belong to racial/ethnic minority groups (Black non-Hispanic 84% at PH vs 32% at SCCC; Hispanic 16% at PH vs 0% at SCCC, p &lt;0.01) and to be uninsured (60% at PH vs 0% at SCCC, p &lt;0.01). Overall, 38% of patients presented at a late stage (stage III-IV) and this was not different based on site of care (11 at PH vs 9 at SCCC; p=0.37). Patients were managed by observation alone (n=4), radiation only (n=11), combination chemotherapy and/or rituximab only (n= 22), or combined modality (n=12). Site of care (PH vs SCCC) or race/ethnicity did not impact the treatment choice. At a median follow up of 60 months (IQR 21-83), 6 recurrences and 5 transformations were noted. Only 3 deaths occurred during the follow up period, for an overall median survival of 62 months (IQR 21.5-84.5).
Conclusion:
Despite health inequities that typically impact safety-net patients, we did not observe any differences in treatment patterns or outcomes of Nodular lymphocyte predominant Hodgkin lymphoma between patients treated at Parkland Health compared to Simmons Comprehensive Cancer Center.
Empowering Global Hematology-Oncology Education: Assessing the Impact of a 1.5-Year Virtual Platform in Combating Miseducation & Inequity
Authors: Leyfman Yan , Van de Kieft Alexandra , Joshi Muskan , Menon Gayathri P. , Balasubramanian Maduri , Heller Elizabeth J. , Smith Keira P. , Hashim Ahmed , Coloma Helena S. , Alves Gabriele , Wilkerson William B. , Park Chandler Howard 
Published: December 2023

Introduction
Social media has revolutionized the global sharing of knowledge, with 77.4% of cancer patients relying on it as their primary medical information resource, especially in resource-limited regions (Ponce et al JCO). However, due to its rapid and unregulated nature, 1/3 of social media posts contain misinformation, with 76.9% of them containing harmful information leading to adverse outcomes. To address this, MedNews Week (MNW), a digital medical education platform dedicated to combating misinformation, was developed to contribute to global hematology-oncology education through its free programming. The Keynote Conference Lecture Series features live virtual presentations from oncology's premier global leaders discussing the latest developments in the field before a mainstream global audience. The aim of this study was to assess the worldwide reach and impact of this virtual oncology education platform.
Methods
From January 2022 to July 2023, MNW hosted 15 global hematology-oncology leaders (Mean H-index = 73.2) as Keynote Speakers. Viewership, impressions, and outreach data were collected from MNW's social media accounts, Symplur and TweepMaps. Data was analyzed to assess MNW's global viewership, reach, and engagement and stratified based on engagement sentiment, gender, age group, and occupation.
Results
In 2022, MNW produced a Healthcare Social Graph Score of 92.77%, placing it in the top 7.33 percentile of global healthcare influencers. Over a 12-month period, MNW generated more than 109,128 Twitter impressions with 4,731 engagements, reaching 1.9 million accounts globally ( Figure 1a). A large proportion of followers (73.44%) were from non-healthcare fields with slightly more males than females. The viewership showed a linear exponential increase from 20,527 (6 months) to 50,707 (1 Year) to 290,532 (1.5 Years) ( Figure 1b). The platform's outreach spanned over 150 cities and 70 countries, with 23 of these countries categorized as low-to-middle socioeconomic regions ( Figure 1c).
Conclusion
Given MNW's performance, it provides a novel model for engaging and disseminating medical information while attracting and sustaining a diverse, global, and growing audience. The platform's ability to spotlight the work of global leaders in the field, free of charge, particularly in lower SE regions, offers a promising approach to combat hematology-oncology educational inequity. Thus, MNW presents an opportunity to inspire audiences worldwide to be proactive, well-informed, and engaged, while narrowing the divide in oncology education.
Prevalence Trends of Anemia Impairment in Adolescents and Young Adults with HIV/AIDS
Authors: Zhang Nan , Li Xinqi , Ma Linlu , Liang Yuxing , Liu Xiaoyan , Zhou Fuling 
Published: December 2023

Background
Anemia is a common complication of HIV/AIDS, particularly in adolescents and young adults. However, little is known about the changing prevalence trends of anemia impairment in this population over time.
Methods
Data on anemia in adolescents and young adults with HIV/AIDS from 1990 to 2019 were collected globally. Prevalence was calculated by gender, region, and country for individuals aged 10-24, and trends were measured using estimating annual percentage changes (EAPC).
Results
Globally, the prevalence of adolescents and young adults with HIV/AIDS increased from 103.95 per 100,000 population in 1990 to 203.78 in 2019. However, anemia impairment has decreased over the past three decades, with a global percentage decreasing from 70.6% in 1990 to 34.7% in 2019, mainly presenting as mild to moderate anemia and significantly higher in females than males. The largest decreases were observed in Central Sub-Saharan Africa, High-income North America, and Eastern Sub-Saharan Africa, with EAPCs of -2.8, -2.34, and -2.17, respectively. Tajikistan (78.76%) and Madagascar (74.65%) had the highest anemia impairment percentage in 2019, while China (16.61%) and Iceland (13.73%) had the lowest. Anemia impairment was closely related to sociodemographic index (SDI) levels, with a high proportion of impairment in low SDI regions but a stable decreasing trend (EAPC=-0.37). Hence, anemia impairment in HIV/AIDS-infected individuals varies by region, sex, and age group.
Conclusion
Continued anemia monitoring and management are crucial for HIV/AIDS patients, especially in high-prevalence regions and among females. Public health policies and interventions can improve the quality of life and reduce morbidity and mortality.
Keywords : Adolescents; Human immunodeficiency virus; Anemia; Prevalence; Global Burden of Diseases
Impact of Immunosuppression Intensified Conditioning Regimen for Patients with Strong Positive Pre-Transplantation Donor Specific Anti-HLA Antibodies (DSAs) Undergoing Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Liu Huixia , Wei Daolin , Shao Shan , Jiang Ying , Li Su , Zhu JUN , Wang Chun , Zhao Chuxian 
Published: December 2023

Objective: Immunosuppression intensified conditioning regimen has been applied for 10 patients with strong positive pre-transplantation Donor specific Anti-HLA Antibodies (DSAs) undergoing Haploidentical Hematopoietic Stem Cell Transplantation (HSCT), its effects on engraftment of hematopoietic stem cell were examined.
Methods: Characteristics of 10 consecutive patients with strong positive pre-transplantation DSAs were retrospectively analyzed, including gender, age, diagnosis, disease status pre-transplantation, presence of DSA, conditioning regimens, engraftment, graft versus host disease (GVHD) incidence and survival.
Results: Ten patients [3 males vs 7 females, median age 53.5(36-64)] received immunosuppression intensified conditioning regimen: Fludarabine plus busulfan (FluBu) combining total body irradiation and cyclophosphamide (TBI-Cy). DSA levels gradually decreased in all patients after preparative conditioning, and the mean fluorescence intensity (MFI) values dropped significantly (P＜0.003). The average MFI values dropped 40% at day 7 post-HSCT, 8 cases acquired hematopoietic reconstitution, the median time of neutrophil engraftment was 15.6(10-16) days, and 19(13-22) days for platelet engraftment. One case had primary graft failure and another one had poor graft function. After a median follow-up of 12.5(1.5-27) months, 7 cases remained in disease remission state with negative DSA assay, including 2 cases with MFI values higher than 20000 pre-transplantation.
Conclusions：Immunosuppression intensified conditioning regimen can efficiently decrease the Donor specific Anti-HLA Antibodies (DSA) level, which leads to lowered chances of primary graft failure.
A Feasibility Study Evaluating Von Willebrand Factor in Patients with Gastrointestinal Angiodysplasia
Authors: Chornenki Nicholas L.J. , Grabell Julie , Bowman Mackenzie L , Good David , Hookey Lawrence , James Paula 
Published: December 2023

Background: Abnormalities of von Willebrand Factor (VWF), such as those found in von Willebrand Disease (VWD) are associated with the development of abnormal blood vessels known as angiodysplasia. Angiodysplasia occurs primarily in the gastrointestinal (GI) tract, particularly the small bowel. Among patients with VWD, angiodysplasia is significantly overrepresented as a cause of GI bleeding and occurs in all VWD subtypes although it is reported more frequently in those with loss of the high molecular weight multimer of VWF. Recent studies have demonstrated more than a third of patients with VWD and GI bleeding have angiodysplasia when systematically assessed with Video Capsule Endoscopy (VCE) to examine the small bowel. Given the relationship between angiodysplasia and VWD our objective was to assess the feasibility of evaluating patients with GI angiodysplasia for abnormalities of VWF.
Methods: We undertook a prospective single center pilot study to assess patients over the age of 18 with GI angiodysplasia for underlying abnormalities of VWF. Patients were identified based on angiodysplasia being present on a VCE study. Patients who consented to enrollment completed a self-administered bleeding assessment tool (BAT) as well as baseline demographic data. VWF testing included VWF antigen (VWF:Ag), VWF functional assay (VWF:GPIbM), Factor VIII coagulant activity (FVIII:C), and VWF pro-peptide (VWFpp) levels.
Results: After reviewing 190 consecutive VCE studies performed at our institution between April 2021 and April 2023, we identified 50 patients who had capsule endoscopies demonstrating angiodysplasia of the GI tract. Thirteen of these patients consented to enrollment in the study. The bleeding histories of included patients are detailed in Table 1 along with their baseline clinical, laboratory, and demographic data. Two patients endorsed lifelong bleeding symptoms and three reported a significant family history of bleeding - all in a female relative. ISTH-BAT scores ranged from 0 to 18 with a median score of 2. Since our population is older than other studies that report on bleeding scores, we considered an abnormal bleeding score to be &gt;6 as recent evidence indicates normal BAT scores increase over time. Five patients (38.6%) in our study had an ISTH-BAT abnormal bleeding score. VWF levels were assessed (Table 1) and one patient aged 88 years old with a significant family and lifelong history of bleeding received a new diagnosis of Type 2A VWD. Severe iron deficiency anemia requiring ongoing IV iron was diagnosed in two patients.
Conclusion: In our feasibility study, we demonstrated a feasible protocol for recruitment of patients with GI angiodysplasia for clinical and laboratory testing of VWF. A significant proportion of our patients (38.6%) had abnormal bleeding scores and one patient had an underlying Type 2A VWD diagnosis.
A Conditioning Regimen of Bendamustine and Melphalan for Autologous Stem Cell Transplantation in Multiple Myeloma: A Phase 2, Single-Arm, Prospective Study
Authors: Zeng Qiang , Li Jian , Dong Tian , Chen Xinchuan , Kuang Pu , Niu Ting , Ji Jie , Liu Zhigang , Liu Ting 
Published: December 2023

Aim: A registered study to investigate the efficacy and safety of bendamustine plus melphalan conditioning for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) (ChiCTR2100047782).
Method: Bendamustine and melphalan were given to patients at the dose of 150 mg/m 2 on Days -5 and -4 and 70 mg/m 2 on Days -3 and -2, respectively. Progression-free survival (PFS) and overall survival (OS) were used to assess the efficacy and adverse events were used to assess the safety of the conditioning regimen.
Results: A total of 80 patients were included in our study. Of them, 45 patients achieved complete response (CR); 7 patients achieved very good partial response (VGPR), and 28 patients achieved partial response (PR) before ASCT. With a median follow-up period of 16 months, the overall PFS rate was 91%, and the overall OS rate was 95%. Patients with CR pre-transplantation were all in CR until the last follow-up; two patients with VGPR pre-transplantation relapsed and one of them died; four patients with PR pre-transplantation relapsed and one of them died. The median time to neutrophile and platelet engraftment were 11 (9-13) and 13 (10-18) days. Three patients experienced sepsis during ASCT. Vomiting occurred in 45 (57.2%) patients; diarrhea occurred in 27 (34.2%) patients, transaminase elevation was observed in 18 (22.3%) patients; mucositis was found in 16 (18.8%) patients. All these adverse events were grade 1-2, and no grade 3-4 adverse events were observed.
Conclusion: Bendamustine plus melphalan regimen is promising for ASCT in MM patients, and the long-term efficacy and safety remain to be investigated.
Time to Resolution of Iron Deficiency: A 10-Year Single State Retrospective Review
Authors: Cogan Jacob C , Meyer Julia D , Jiang Ziou 
Published: December 2023

Introduction: Iron deficiency can have clinical consequences even without anemia, including fatigue, exercise intolerance and mood disorders. The time from laboratory diagnosis to resolution of iron deficiency has not been previously evaluated.
Methods: In a retrospective review of electronic medical record (EMR) data from a single state health system, we identified patients meeting laboratory criteria for iron deficiency (defined as a ferritin level &lt; 25 ng/mL). Patients with at least one follow-up ferritin level of any value within 3 years were included in the final cohort. Patients with a follow-up ferritin &gt; 50 ng/mL at any time point within 3 years were classified as having resolved iron deficiency. Diagnoses of interest included iron deficiency anemia (IDA), as well as other conditions where iron deficiency is routinely assessed and treated irrespective of anemia, namely heart failure (HF) and restless leg syndrome (RLS). Descriptive statistics and time to event analyses (via Cox proportional hazards regression) were performed to determine time to resolution of iron deficiency in the cohort and characteristics predictive of achieving resolution.
Results: We identified 13,084 patients with iron deficiency detected between 2010 to 2020. The majority of patients were female (86.6%) and White (79.3%); 57.3% had an EMR diagnosis of IDA (Table 1). We found that 5,485 (41.9%) had resolution of iron deficiency within 3 years of diagnosis, while 7,599 (58.1%) had unresolved iron deficiency. Among those with resolved iron deficiency, the median time to resolution was 1.9 years (IQR 0.8, 3.9 years). Factors associated with resolution of iron deficiency included increasing age (aHR 1.42 [95% CI 1.31 - 1.54], p &lt; 0.001 for age &gt; 60), male gender (1.49 [1.39 - 1.59], p &lt; 0.001) and a diagnosis of HF (1.23 [1.11 - 1.36], p &lt; 0.001) (Table 2). Black race (0.75 [0.68 - 0.83], p &lt; 0.001) and absence of an EMR diagnosis of IDA, HF or RLS (0.75 [0.71 - 0.81], p &lt; 0.001) were associated with a lower likelihood of iron deficiency resolution.
Conclusion: Prolonged and unresolved iron deficiency were prevalent in this cohort, with young age, female gender and Black race increasing risk of non-resolution. Interventions are needed to raise awareness of the clinical consequences of non-anemic iron deficiency and of diagnostic ferritin thresholds.
TRIM28 Regulates DHCR7-Mediated Cholesterol Biosynthesis to Promote Survival in B Cell Lymphoma
Authors: Zhang Jiawei , Xin Dijia , Fan Yili , Wang Luyao , Chen Boxiao , Xu Yang 
Published: December 2023

Background: TRIM28, a member of the tripartite motif-containing (TRIM) protein family, is a critical regulator of gene expression, DNA damage response and protein degradation, but little is known about its role in lipid metabolism. Dysregulation of cholesterol metabolism has been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). However, the role of TRIM28 in lymphomagenesis and its clinical relevance remain unclear.
Methods: We searched public databases to characterize the gene expression pattern, clinical parameters, and survival data of TRIM28 in B-cell lymphoma, and immunohistochemistry (IHC) was used to confirm TRIM28 expression. Then, we knocked down TRIM28 by lentiviral shRNA transduction in several B-cell lymphoma lines to determine the effect of TRIM28-KD on cell proliferation, cell cycle progression, apoptosis and drug resistance. In addition, a lymphoma xenograft mouse model was established to test whether TRIM28-KD inhibits lymphoma growth in vivo. Using RNA-seq, we aim to identify novel transcriptional targets and elucidate the mechanisms by which TRIM28 promotes survival in B-cell lymphoma.
Results: Analysis of bioinformatic datasets and clinical samples indicated that TRIM28 expression was significantly upregulated in B-cell lymphoma compared to normal tissues, and high expression of TRIM28 was closely associated with disease progression and poor prognosis in patients with B-cell lymphoma. Knockdown of TRIM28 inhibited lymphoma cell proliferation, induced cell cycle arrest at G0/G1, increased cell apoptosis, and enhanced the sensitivity of lymphoma cells to chemotherapeutic agents. Moreover, TRIM28-KD significantly suppressed lymphoma and prolonged mouse survival in DLBCL xenograft models. The RNA-seq with TRIM28-KD vs. control revealed differentially expressed genes, many of which were enriched in lipid metabolism-related pathways. DHCR7, a critical terminal enzyme in cholesterol biosynthesis, was identified as a potential transcriptional target of TRIM28. TRIM28-KD inhibited DHCR7 expression, which was associated with reduced total cholesterol levels. DHCR7-KD impaired cell proliferation, whereas overexpression of DHCR7 rescued the phenotypes of TRIM28-KD in lymphoma cells.
Conclusions: TRIM28 drives lymphomagenesis through upregulating DHCR7-mediated cholesterol biosynthesis, which may serve as a novel therapeutic target for B-cell lymphoma.
E3 Ubiquitin Ligase TRIM21 Enhances Macrophage-Mediated Bortezomib Resistance By Inducing M2 Polarization in Multiple Myeloma
Authors: Cao Wen , Chen Jing , Zhang Enfan , Cai Zhen 
Published: December 2023

Background: Multiple myeloma (MM) is a malignant plasma cell hematologic tumor with an increasing incidence and has become the second most common hematologic malignancy after non-Hodgkin lymphoma. Macrophage is an abundant component of the MM bone marrow microenvironment and contributes to the enhancement of MM drug resistance. Our previous study found that the expression of the E3 ubiquitin ligase TRIM21 was reduced in MM cells, and MM cells with low expression of TRIM21 showed reduced sensitivity to Bortezomib (Bort). This study aims to investigate the role and mechanism of TRIM21 in macrophage-mediated MM Bort resistance.
Objective ：Explore the effect and mechanism of TRIM21 in mediating multiple myeloma Bortezomib resistance.
Methods ：1. Immunofluorescence to analyze the expression of TRIM21 on macrophages in bone marrow biopsy specimens from patients with MM; 2. QPCR, western blot (WB) and flow cytometry (FCM) to detect the level of macrophage polarization markers after constructing overexpression or knockdown of TRIM21; 3. WB and FCM to detect the sensitivity of MM cells to Bort after co-culture of MM cells and macrophage; 4. Transcriptome sequencing to identify TRIM21-mediated pathway changes in macrophage; 5. QPCR and WB to verify the effect of TRIM21 on macrophage polarization after treatment with pathway inhibitors.
Results:1. Immunofluorescence analysis showed increased expression of TRIM21 in macrophage from relapsed and refractory MM (RRMM) patients compared to newly diagnosed multiple myeloma (NDMM) patients;2. QPCR, WB and FCM results showed that overexpression of TRIM21 in macrophage led to decreased polarization markers of M1 phenotype and increased the polarization markers of M2 phenotype. In contrast, knockdown of TRIM21 increased M1 polarization and decreased M2 polarization; 3. WB and FCM results demonstrated that co-culture of MM cells with TRIM21-overexpressing macrophages significantly enhanced MM cell tolerance to Bortezomib and decreased MM cell apoptosis; 4. Transcriptome sequencing revealed activation of the JAK-STAT3 pathway in macrophages after TRIM21 overexpression; 5. QPCR and WB results showed that the macrophage polarization effect induced by TRIM21 overexpression was reversed after treatment with the STAT3 inhibitor C188-9.
Conclusions: Our study shows that TRIM21 is overexpressed in macrophages in patients with relapsed and refractory MM. In addition, TRIM21 induces M2 polarization by activating the JAK-STAT3 pathway, thereby enhancing the protective effect of macrophage on MM cells. These findings provide a new insight into the role of TRIM21 in MM drug resistance and lay an important theoretical foundation for targeting macrophages in MM.
Key words: TRIM21, Macrophage, Bortezomib, JAK-STAT3