bluuebunny/crossref_metadata_2025_split huggingface dataset:
Location, Location(s), Location(s+): Moving from Acute to Chronic Pain in SCD Pain in School-Age Children
Authors: Murphy Bridget N , Hood Anna M , Hildenbrand Aimee K. , Shook Lisa M , Quinn Charles T. , Smoot Erin , Sil Soumitri , Crosby Lori E. 
Published: December 2024

Introduction: Sickle cell disease (SCD) pain significantly impairs quality of life for children and adolescents. It is unclear when pain in SCD evolves from acute, episodic pain to chronic pain. Understanding predictors of transition from acute to chronic pain among individuals with SCD is essential to inform prevention efforts for chronic pain. Research indicates that for older adolescents and adults (16+ years), SCD pain location changes with age (localized vs. widespread) and that pain intensity varies based on location. Less is known about differences in pain experiences for those younger than 16. This study aimed to examine the relationship between pain location, pain intensity, and age in a sample of children and adolescents (&lt;16 years) with SCD presenting to the emergency department (ED).
Methods: Data were collected as a part of a larger study examining ED visits for patients living with SCD. Data were extracted from the medical records of patients with SCD ages 8-16 who were seen in the ED at a children's hospital in the Midwest between June 2010 and June 2018. Only patients with data for pain sites and pain intensity documented in the ED notes were included in current analyses (N = 102 patients with N = 313 unique ED visits). Pain location and intensity (0 = no pain, 10 = worst pain) were reported during the ED visit, and we used the first recorded documented location and intensity. We used independent samples t-tests to assess group differences in age and pain intensity between patients who reported one pain site and patients who reported two or more pain sites.
Results: The number of ED visits per patient ranged from one to 22 (M = 3.02, SD = 3.36), with most patients having one (48%), two (17%), or three (10%) ED visits. Average age at first ED visit was 12.06 (SD = 2.65), and Average age at the last ED visit was 13.36 (SD = 2.75). Pain sites ranged from 1 to 4 (M = 1.40, SD = 0.67), with the mode being 1 (69.3%). Patients who reported 2 or more pain sites were significantly older (t(311) = -2.843, p = .005) and had significantly higher pain intensity than those who reported one pain site (t(311) = -2.264, p = .024).
Discussion: Similar to prior research, our findings suggest that the presentation of SCD pain changes with age; this study extends those findings to late childhood and early adolescence. Monitoring the emergence of increasingly multifocal or widespread pain among youth with SCD could facilitate preventive or early intervention for chronic pain, including use of interdisciplinary pain management strategies. Additional research is needed to understand pain trajectories over this developmental period as well as the best ways to support patients through changes to pain presentation.
Community-Engaged Research in Psychological Interventions for Pediatric Sickle Cell Disease: A Scoping Review
Authors: Murphy Bridget N , Durkin Kristine , Williford Desireé N , Blakey Ariel , Musa Chloe , Hood Anna M , Muhammad Malika , Crosby Lori E. 
Published: December 2024

Introduction: Involving those with lived experience in the design and implementation of interventions improves the quality of life and health outcomes and is imperative, as engagement can improve the relevance, reach and effectiveness of interventions. Although there has been a growing call to enhance the use of community-engaged research (CEnR) methods, it remains uncertain how extensively these methods are being adopted and what the quality of the resulting research is.
The aim of this scoping review was to identify and describe the CEnR methods used in the development and evaluation of self-management interventions for pediatric SCD.
Methods: We conducted a systematic search of three databases (PubMed, Scopus, and PsychInfo). All titles, abstracts, and full texts for papers that met criteria were independently reviewed by two members of the research team. Data were extracted from articles that met inclusion criteria: (1) psychological intervention for (2) infants, children, adolescents, and youth adults (3) living with SCD (4) that used CEnR methods.
Results: The search yielded 236 original articles, of which eight met the inclusion criteria. These articles showed varying levels of involvement of community collaborators (patients, families, and community-based organizations) across research phases. Notable gaps in the literature were: 1) few studies reported utilizing CEnR methods, 2) a lack of consensus in language/terms used to describe CEnR methods, 3) limited demographic data about community collaborators, and 4) a lack of description of CEnR frameworks guiding intervention development and evaluation.
Conclusions: This scoping review found that most self-management intervention studies for youth with SCD failed to describe CEnR methods in a way that would facilitate reproducibility or evaluation of the quality of the research. Given the increased focus on the use of CEnR methods it will be important to develop reporting standards (e.g., for demographic information, frameworks, steps of CEnR methods) and use common terms/keywords to increase clarity and translatability. By adhering to these recommendations for improving the use and reporting of CEnR methods, we can enhance the effectiveness of patient self-management interventions, ultimately leading to better health outcomes for youth living with SCD.
Characterization of Complement and Immunoglobulin Deposition in Bone Marrow Trephine Biopsies of Patients with Cytopenias
Authors: Fidanza Cecilia Anna , Bortolotti Marta , Croci Giorgio Alberto , Barcellini Wilma , Fattizzo Bruno 
Published: December 2024

Cytopenias can be categorized in “peripheral”, such as autoimmune hemolytic anemias (AIHA), immune thrombocytopenic purpura (ITP), and chronic idiopathic/autoimmune neutropenia (CIN/AIN), and “central”, including disorders such as aplastic anemia (AA) and myelodysplastic neoplasms (MDS). Several overlaps exist between the two forms, with a clear role of the humoral and complement immune response in the former, that is however less known in the latter.
We assessed complement fractions C3 and C4, IgM and IgG deposits by immunohistochemistry on bone marrow biopsies from 162 cytopenic patients diagnosed between 2016 and 2023 at a tertiary hematologic center, reference for immune cytopenias, in Milan, Italy. Deposits were expressed using a semiquantitative scale from 0 to +3 by an expert hemopathologist. The topographical distribution was then evaluated and categorized as serous versus precursors pattern. We collected laboratory data at diagnosis to evaluate a correlation with the immunohistochemical data.
Overall, 28 AIHA, 15 ITP, 58 CIN/AIN, 12 AA, and 49 lower-risk MDS were accrued. A significantly greater deposition of C3 and C4 (≥2+) was found in AA and MDS versus peripheral cytopenias (42% and 33% in AA, 49% and 41% in MDS versus 21% and 14% in all peripheral cytopenias, p=0.004 and p=0.002, respectively). Ig deposition was significantly greater (≥ 3+) in MDS and AA (63% and 42% for IgM and 49% and 33% for IgG, respectively) versus peripheral cytopenias (39% for IgM and 11% for IgG, respectively, p &lt; 0.05); notably, IgM deposition was particularly evident in AIHA, ≥ 3+ in 50% of cases. Topographically, most of C3 and C4 deposition showed a serous pattern, while deposition on precursors was observed in 25% of MDS cases (mainly C3) and 42% of AIHA (mainly C4). IgG/M deposits were equally distributed on serum and precursors in all disease category. Hb and reticulocytes values were negatively correlated with C4 deposits in MDS patients (r= -0.031, p=0.01 for Hb and r= -0.29, p=0.02 for reticulocytes). Bone marrow cellularity negatively correlated with IgM deposits in AA (r= -0.72, p=0.004). Finally, platelet counts negatively correlated with IgM deposits in ITP (r=-0.5, p=0.02).
In conclusion, our data demonstrated a significant deposition of complement and Ig in bone marrow of patients with “peripheral” and “central” cytopenias, more marked in the latter. The correlation with hematological parameters hints for a role of the immune attack against bone marrow precursors in all these conditions and might foster innovative therapeutic approaches.
Comparative Effectiveness of Chatgpt 4.0 and Gemini Advanced in Diagnosing Challenging Hematologic Cases
Authors: Khamees Ibrahim , Wu Xiangni , Qasim Hana , Al-sadi Anas , Abumuhfouz Ma'in , Yacoub Abdulraheem , Li Haoran 
Published: December 2024

Background: In the rapidly evolving field of artificial intelligence (AI), ChatGPT 4.0 and Gemini Advanced have emerged as significant tools with diverse applications, including healthcare. This study evaluates their efficacy in diagnosing hematologic diseases using pathology images, highlighting the potential of AI to augment medical diagnostics.
Methods: We utilized reference cases from the American Society of Hematology (ASH) Image Bank, which includes peer-reviewed hematologic images and texts for educational purposes. To accommodate AI constraints on image processing, we merged the images for each case into a single file. We replicated all the cases from the ASH reference cases, excluding those with insufficient clinical details, which made it difficult to approach them in two steps. Each case was run in separate chat sessions to prevent the model from applying any “learning” to subsequent cases. We pasted them along with our prompts into the Chat GPT 4.0 and Gemini Advanced models. Initially, a minimal clinical description was provided; if inaccurately diagnosed, a more comprehensive description was used. For each step, we asked the models to give a diagnosis and a list of differential diagnoses based on probability. The aim was to assess and compare the diagnostic accuracy of the two models under varying information conditions.
Results: Of 134 evaluated cases, 29 were excluded due to insufficient data. With case images and limited clinical information (step 1), ChatGPT 4.0 accurately identified the correct diagnosis in 38.1% of cases, compared to 26.6% provided by Gemini Advanced. When provided with detailed clinical information (step 2), ChatGPT 4.0's accuracy improved to 46.1%, compared to 32.4% for Gemini Advanced. ChatGPT 4.0 also demonstrated superior performance in differential diagnosis, correctly including the right diagnosis 82.8% of the time, versus 64.7% for Gemini Advanced. When the correct diagnosis was provided in the differential diagnoses list but not as the top diagnosis, the average rank of the correct diagnosis in step 1 was 3.6 for ChatGPT 4.0 and 2.5 for Gemini Advanced. In contrast, in step 2, it was 2.7 for ChatGPT 4.0 and 2 for Gemini Advanced.
Conclusion: ChatGPT 4.0 outperformed Gemini Advanced in diagnosing complex hematologic cases, both as a primary and differential diagnosis tool. While both models show promise in supporting hematologic diagnostics, their reliability for clinical application requires further investigation and refinement.
Altered Quantity and Function of Follicular T Helper Cell Subsets in Multiple Myeloma and MGUS
Authors: Wang Jinuo , Zhao Duoduo , Zhai Xingyuan , Wu Wenjun , Cai Zhen 
Published: December 2024

Introduction
Almost all Multiple myeloma (MM) cases were progressed from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). So far, the pathogenesis of myeloma is not yet clear. The immune cells, especially T cells in the tumor microenvironment, play an important role in myelomagenesis. Follicular helper T cells (Tfh) primarily assist in plasma cell activation and antibody secretion, potentially contributing to abnormal plasma cell generation. Previous studies showed a significant increase in circulating Tfh cell numbers in MM patients. However, the specific changes in quantity and function, as well as their correlation with disease status, remain unclear. In this study, we performed a comprehensive analysis of Tfh cell subsets in untreated MM patients and individuals with MGUS, which might help further elucidate mechanisms of immune dysfunction during myelomagenesis.
Methods
Our study included 20 MGUS patients and 45 newly diagnosed MM (NDMM) patients. Flow cytometry was applied to determine the proportion of Tfh cell subsets in PB. Flow sorting technology was used to separate Tfh cells and follicular regulatory T cells (Tfr) in MGUS and MM patients. The immune function was indirectly calculated by detecting proliferation rate of plasmablasts differentiated from B cells which were cocultured with Tfh cells. Concentration of IL-10, IL-21 from the culture supernatants of proliferation assay was measured using ELISA.
Results
The proportion of Tfh (CD4+CXCR5+PD-1+) in CD4+ T cells was significantly higher in NDMM patients than healthy controls (P&lt;0.001); there was no difference in the proportion of Tfh between MGUS and healthy adults (P=0.37). The proportion of Tfh1 subset (CD3+CD4+CXCR5+PD-1+CXCR3+CCR6−) in Tfh cells was gradually increased in MGUS, NDMM patients than healthy controls (P=0.012, P&lt;0.001); while the number of Tfh2 subset (CD3+CD4+CXCR5+PD-1+CXCR3-CCR6−) in Tfh cells showed a trend of decrease in MGUS, NDMM patients than healthy controls. The proportions of Tfr cells in CD4+ T cells in MGUS and NDMM patients were no difference from healthy adults.
The immune function of Tfh cells was also altered in MGUS and NDMM patients. The ability of induced differentiation from B cells into plasmablasts (CD19+CD27+CD38hiIgD−) was significantly enhanced in MGUS and NDMM patients compared with healthy controls (P=0.047, P=0.011). The levels of IL-10 and IL-21 secreted by Tfh cells in untreated MM patients was notably higher than that of healthy adults (P&lt;0.001, P=0.001).
Conclusions
There were significant changes in the frequencies of Tfh cell subsets in MGUS and MM patients, suggesting that immunomodulatory abnormality has existed in patients at premalignant stage. The induced differentiation and cytokine secretory functions of Tfh cells in MGUS and NDMM patients were also impaired to promote myeloma cell proliferation and disease progression.
Assessment of Annual Rate Changes of Intraarticular Tissue Measurements in Hemophilic Joints Experiencing Acute Bleeding Using the Joint Activity Damage Exam (JADE) Ultrasound Protocol
Authors: Sheth Parthiv V , Glenzer Michael , Nwi-Mozu Isaac , Aguero Peter , Steiner, DPT, RMSK Bruno U.K. , Bailey Cindy , Quon Doris V. , Kruse-Jarres Rebecca , von Drygalski Annette 
Published: December 2024

Background: The Joint Activity and Damage Exam (JADE) ultrasound protocol has been validated to measure key joint tissues (cartilage thickness, osteochondral alterations, and soft tissue expansion) at sentinel positions in patients with hemophilia. The effect of an acute joint bleed on longitudinal rate changes in these tissues has not been established.
Aims: Determine the effect of acute joint bleeding on annual rate changes of JADE measurements.
Methods: We prospectively evaluated 44 adult patients with hemophilia (A or B) of any severity at three Hemophilia Treatment Centers in the United States. Inclusion criteria required at least one arthropathic joint with Hemophilia Joint Health Score (HJHS) &gt;3. JADE measurements and HJHSs were captured at 3 times points (study entry, ≈12-18 months, and ≈24-36 months). We calculated rates of change in JADE measurements in these joints. Rates of change of joint tissue that experienced an acute bleed confirmed by musculoskeletal ultrasound during the study period were compared to those that did not experience an acute bleed.
Results: Most patients in the cohort had severe hemophilia A and were on regular Factor VIII prophylaxis. The median age was36 [IQR 28,49] years. A total of 264 joints were evaluated longitudinally. Of these joints, 248 (94%) experienced no acute joint bleeds over the study period. While the annual bleed rate was low (&lt;1), 16 joints (4 elbows, 8 ankles, and 4 knees) experienced at least one acute joint bleed. HJHSs remained stable and there was no difference in rate changes of JADE measurements in bleeding joints when compared to non-bleeding joints.
Conclusions: These data suggest that rare joint bleeds may not affect the trajectory of joint health in adult patients who are otherwise well controlled on prophylaxis.
Heavy Menstrual Bleeding (HMB) Is a Common Symptom in Patients with Bleeding Disorder of Unknown Cause (BDUC)
Authors: Monard Amaury , Tegels Sanne , Merry Inge , Derikx Floor , Henskens Yvonne , Beckers Erik AM , Moenen Floor CJI 
Published: December 2024

Background: Patients with an increased bleeding tendency without any abnormalities in laboratory hemostasis tests are classified as having a bleeding disorder of unknown cause (BDUC). The large majority of BDUC patients is female and the most common bleeding symptoms are mucocutaneous, including heavy menstrual bleeding (HMB). Data on HMB and its impact on different aspects of daily life, such as social and work-related activities, in BDUC patients is limited. The aim of this study was to investigate the prevalence of HMB and the HMB-related quality of life in women with BDUC in comparison with patients with known bleeding disorders (BD) and no bleeding disorder (NBD).
Methods: Clinical and laboratory data from a total of 195 female patients from the prospective predictors of bleeding Predictors of Bleeding Evaluation in Adult Hematologic Patients with Bleeding Tendencies cohort (ProBe-AHP study) were used to analyze the prevalence of HMB in patients with an increased bleeding tendency. HMB was defined as a score of ≥1 on the HMB symptoms scoring scale of the International Society of Thrombosis and Hemostasis bleeding assessment tool (ISTH-BAT). Additionally, the Menorrhagia Multi-Attribute Scale (MMAS) was completed. The MMAS entails questions on six domains, including psychological wellbeing and physical health, and provides a score ranging from 0 to 100. Lower scores indicate a poorer HMB-related quality of life. Results from an MMAS population study from Peking was used as a reference group (general population).
Results: From the 195 included patients, 68 were diagnosed with a BD, 81 were diagnosed with BDUC and 46 were classified as NBD. The prevalence of HMB was 69% in BD, 83% in BDUC and 41% in NBD, which was a statistically significant difference between the three groups (p&lt;0.001). A total of 53 MMAS questionnaires were completed and returned (BD n=21, BDUC n=21 and NBD n=9). MMAS score was lowest in the BD group (median [IQR]: 44 [ 39-95]), followed by the BDUC group (median [IQR]: 69 [43-86]) and the NBD group (median [IQR]: 69 [ 33-74]). Compared to data from the general population (mean ± SD: 95 ± 10), MMAS score was significantly lower in BDUC patients and BD patients.
Conclusion: HMB is a highly prevalent symptom in women with BD and with BDUC. Menstruation related quality of life was impaired in BDUC patients and even more in BD patients compared to the general population.
High-Dose Cytarabine with Idarubicin Versus High-Dose Cytarabine within First Consolidation for Acute Myeloid Leukemia in First Complete Remission: An Open-Label, Multicenter, Randomized, Phase 3 Trial
Authors: Feng Zinan , Zhang Yu , Liu Hui , Yu Sijian , Liu Qifa , Xuan Li 
Published: December 2024

Backgrounds ：
Whether adding anthracycline to intermediate- or high-dose cytarabine as consolidation is beneficial remains unclear in acute myeloid leukemia (AML). We investigated the efficacy and safety of high-dose cytarabine with idarubicin as consolidation for AML in first complete remission (CR1).
Methods:
We performed the open-label, randomized phase 3 trial at 16 hospitals in China. Eligible AML patients in CR1 were randomly assigned (1:1) to receive either high-dose cytarabine with idarubicin (IA3+3) (idarubicin 10mg/m2, d1-3 and cytarabine 2g/m2, q12h, d1-3) or high-dose cytarabine (HDAC) (cytarabine 3g/m2, q12h, d1-3) regimens as first consolidation. The primary endpoint was the rate of measurable residual disease negativity (MRD-) after first consolidation. Secondary endpoints included cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS), treatment-related mortality (TRM) and adverse events (AEs).
Results
Between November 2018 and December 2021, a total of 407 eligible patients were enrolled and randomly assigned to IA3+3(n=204) or HDAC(n=203) groups. The MRD- rates for IA3+3 and HDAC groups were 65.2% (95%CI: 58.6%-71.8%) and 53.2% (46.3%-60.1%) (RR=1.23, 95%CI:1.04-1.44, P =0.01). Median follow-up time was 37.3 months, the 3-year CIR, DFS, OS and TRM were 22.6% (95%CI :16.8%-29.0%) and 34.0% (27.1%-41.1%) (P=0.01), 68.4% (95%CI :61.5%-75.3%) and 52.9% (45.4%-60.5%) (P=0.003), 75.5% (95% CI :69.0%-82.1%) and 69.6% (62.4%-76.7%) (P=0.18), 8.8% (95%CI :5.2%-13.6%) and 13.0% (8.5%-18.5%) (P=0.23) in two groups, respectively. Ultimately, the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) were 87 and 114 cases, respectively (P=0.006). Within 28 days after first consolidation, the most common grade 3 or higher AEs were thrombocytopenia (196[96%]vs 196[97%]), neutropenia (195[96%] vs 185[91%]), anemia (165[81%] vs 152[75%]), febrile neutropenia (146[72%] vs 128[63%]) and infections (104[51%] vs 83[41%]). One patient died from infection in IA3+3 group.
Conclusions
IA3+3 resulted in deeper remissions, reduced relapse and was well-tolerated compared to HDAC. This deeper remission improved DFS and translated into treatment advantage, with fewer patients undergoing allo-HSCT. This regimen may be an appropriate consolidation option for AML in CR1.