bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying and Addressing Knowledge and Confidence Gaps Regarding the Management of Patients with Sickle Cell Disease Via Engaging Continuing Medical Education
Authors: Robinson Katie , Esgro Robert A. , Cooper Simon , LoPresti Michael , Carson Benjamin 
Published: December 2023

Introduction: While there have been recent advances in therapeutic options for the management of patients with sickle cells disease (SCD), hematology providers remain challenged by how to deliver an individualized approach to care, negatively impacting patient outcomes. To address this practice gap and identify drivers that underlie persisting challenges, an interactive continuing medical education (CME) activity was developed and implemented.
Methods: Vindico Medical Education provided an interactive web-based CME activity on CME.Healio.com that was available for credit for one year starting August 31, 2022. The activity included opportunities for interaction with the content to encourage engagement, transfer knowledge, improve confidence, and encourage appropriate practice patterns. Impact of education was measured by comparing paired pre- and post-test responses.
Results: As of July 2023, 221 hematology/oncology providers, including 116 MDs and advanced practice providers (APPs) and 105 nurses, who each see an average of 4 patients with SCD per month participated in the education. At baseline, scores on questions related to the latest evidence regarding new SCD therapies were low in both professional cohorts - an average 30% for MD/APPs and 16% for nurses. Moreover, 95% of HCPs in both cohorts lacked confidence in their knowledge of these agents and their appropriate use. This lack of knowledge and confidence translated into practice gaps. Specifically, 48% of those involved in treatment decisions indicated in the pre-test that they had never used a newer option for SCD management, and only 17% reported that they always consider the latest evidence when individualizing treatment for patients. On a post-test, however, the MD/APP and nurse cohorts scored an average of 81% and 84%, respectively, indicative of a robust impact of the education on clinician knowledge. Similarly, there was a 41% absolute increase in clinician confidence in understanding the latest evidence. These gains in knowledge and confidence translated into post-education planned practice improvements, with completers 22% more likely to apply this knowledge to clinical decision-making.
Conclusion: Hematology/oncology providers lack knowledge and confidence regarding the latest evidence in SCD treatment. While the use of interactive CME led to robust gains in knowledge and confidence, follow-up case-based education is needed to facilitate the application of knowledge to practice while continuing to improve clinician confidence.
Clinical Characteristics and Prognosis of Primary Plasma Cell Leukemia and Newly Diagnosed Multiple Myeloma Under the New IMWG Definition Criteria
Authors: Guan Jiaheng , Chen Bao-An 
Published: December 2023

Background: Recently, the International Myeloma Working Group (IMWG) has recommended new primary plasma cell leukemia (pPCL) definition criteria, which require the presence of ≥ 5% circulating plasma cells in peripheral blood smears. The objective of this study was to investigate the clinical characteristics and prognosis of new-defined pPCL and newly diagnosed multiple myeloma (NDMM).
Methods: This was a single-center, retrospective study including patients diagnosed with new-defined pPCL or NDMM at Zhongda Hospital, China, between January 2010 and December 2022.
Results: There were 23 pPCL patients and 264 NDMM patients in our cohort. Generally, pPCL patients were younger than NDMM patients (median diagnostic age: 63 vs. 67 years old, p=0.018). The 1q21+ aberration was predominantly found in NDMM (p= 0.038) whereas t(11;14) dominated in pPCL (p= 0.017). Notably, pPCL exhibited a lower platelet level (p&lt; 0.001) and a higher frequency of non-hyperdiploid karyotypes (p= 0.03) in contrast to NDMM. The median overall survival (OS) and progression-free survival (PFS) in NDMM were notably superior to those observed in pPCL (HR: 0.41, p= 0.001, HR: 0.38, p&lt; 0.001, respectively). Interestingly, the OS in NDMM was 3 times longer than that in pPCL in females (p&lt; 0.01) while no difference was found between NDMM and pPCL in males (p= 0.078). Moreover, NDMM patients treated with proteasome inhibitor (PI)-based treatment showed a significantly better prognosis than pPCL patients receiving the same treatment (OS: p&lt; 0.01, PFS: p&lt; 0.01, respectively). Similar findings were observed for patients undergoing either autologous stem cell transplantation (ASCT) or CD38 antibody treatment, both presenting a favorable prognosis in NDMM. However, no significant difference emerged between the two groups in terms of immunomodulatory drugs (IMiDs)-based or PI+IMiDs-based regimens. Multivariate analysis indicated elevated lactate dehydrogenase (LDH) was an independent predictor of adverse prognosis in NDMM (HR: 3.12, p&lt;0.01).
Conclusion: Our study revealed the clinical features and prognosis of pPCL and NDMM patients according to the new diagnostic criteria. The findings highlighted a generally improved prognosis in NDMM compared to pPCL, especially among female patients or those treated with PI-based regimens. It is important to note that our study had a limited sample size, potentially introducing some bias. We hope well-designed and long-term follow-up studies can be conducted to provide more reliable results.
Gender Disparities in Outcomes of Autoimmune Hemolytic Anemia Admissions: An Analysis of the National Inpatient Sample
Authors: Abdelhay Ali , Jain Tripti , Srivastava Arnav , Avalos Sugastti Eduardo , Mostafa Mariam , Reghis Mouna , Kharel Himal , Orakzai Abdullah 
Published: December 2023

Introduction
Autoimmune hemolytic anemia (AIHA) is a condition characterized by the immune destruction of red blood cells, which can necessitate hospitalization in severe cases. The purpose of this study is to compare outcomes of AIHA hospitalizations between genders.
Methods
We utilized the International Classification of Diseases (ICD) codes to identify all hospitalizations with the primary diagnosis of AIHA in the National Inpatient Sample (NIS) from 2002 to 2019. We excluded all pediatric (age &lt; 18 years) and elective hospitalizations. We described the baseline characteristics of both groups including demographics and comorbidities. We fitted multivariable logistic regression models to compare outcomes between males and females while adjusting for age, race, and comorbidities.
Results
A total of 60,529 met the inclusion and exclusion criteria. The majority of these were females (59.1% vs 40.1%, p &lt; 0.001). Males were older (median age 67 vs. 66 years, p &lt; 0.001) and had more white race (73.4% vs. 67.9%, p &lt; 0.001). The distribution of associated comorbidities also differed different between both groups ( (Table 1). On adjusted analysis, males had higher in-hospital mortality rates. They also had higher rates of most secondary outcomes; including rates of circulatory shock, need for mechanical ventilation, bacterial pneumonia, acute myocardial infarction, deep vein thrombosis, hemorrhagic stroke, acute kidney injury, and requiring new hemodialysis. Females had higher rates of urinary tract infections. No significant differences were found in the rates of requiring blood transfusions, sepsis, acute heart failure, pulmonary embolism, ischemic stroke, encephalopathy, and gastrointestinal bleeding (Figure 1). Furthermore, male hospitalizations were associated with higher costs (median [IQR] of $11,400 [6,700-20,500] vs. $10,000 [6,000- 17,200]) despite similar length of stay (median [IQR] of 4 days [3-7] vs. 4 days [3-7]).
Conclusion
Male patients hospitalized with AIHA experience poorer in-hospital compared to females. More research is essential to understand the underlying causes for these disparities and to tailor management to improve outcomes for both male and female AIHA patients.
The Effect of Ciprofloxacin Prophylaxis during Haematopoietic Cell Transplantation on Infection Episodes, Exposure to Treatment Antimicrobials and Antimicrobial Resistance: A Single-Centre Retrospective Cohort Study
Authors: Baltas Ioannis , Kavallieros Konstantinos , Konstantinou Giannis , Koutoumanou Eirini , Gibani Malick M , Gilchrist Mark , Davies Frances , Pavlu Jiri 
Published: December 2023

Objectives
Fluroquinolone prophylaxis during haematopoietic cell transplantation (HCT) remains controversial. We aimed to determine its effectiveness and association with exposure to treatment antimicrobials and antimicrobial resistance.
Methods
All admissions for HCT in a tertiary centre between January 2020 and December 2022 (N=400) were studied. Allogeneic haematopoietic cell transplantation (allo-HCT) recipients had prophylaxis with ciprofloxacin during neutropenia, while autologous haematopoietic cell transplantation (auto-HCT) recipients not.
Results
Allo-HCT was performed for 43.3% (173/400) of patients, auto-HCT for 56.7% (227/400). In multivariable analysis, allo-HCT was associated with 1.01 (95% confidence intervals [CI] 0.62 - 1.40, p&lt;0.001) fewer infection episodes per 100 admission days compared to auto-HCT. In allo-HCT, total exposure to all antimicrobials (+24.8 days of therapy [DOT]/100 admission days, p&lt;0.001) and ciprofloxacin (+40.5 DOT/100 admission days, p&lt;0.001) was higher, while exposure to meropenem (-4.5 DOT/100 admission days, p=0.02), piperacillin-tazobactam (-5.2 DOT/100 admission days, p&lt;0.001), aminoglycosides (-4.5 DOT/100 admission days, p&lt;0.001), glycopeptides (-6.4 DOT/100 admission days, p&lt;0.001), was lower. Enterobacteriaceae isolated during allo-HCT were more likely to be resistant to ciprofloxacin (65.5%, 19/29 versus 6.1%, 2/33, p&lt;0,001), ceftriaxone (65.5%, 19/29 versus 9.1%, 3/33, p&lt;0.001), and other antimicrobial classes. Vancomycin-resistant enterococci were more common in allo-HCT recipients (11%, 19/173 versus 0.9%, 2/227, p&lt;0.001). Inpatient mortality during allo- and auto-HCT was 9.8% (17/173) and 0.4% (1/227) respectively (p&lt;0.001).
Conclusions
Ciprofloxacin prophylaxis in allo-HCT was associated with fewer infection episodes and reduced exposure to treatment antimicrobials compared to auto-HCT. Mortality in auto-HCT remained low. Significant burden of antimicrobial resistance was detected in allo-HCT recipients.
Global Prevalence of Anemia Among Women of Reproductive Age, 2000-2019
Authors: Deloughery Emma P 
Published: December 2023

Introduction: A common disease with significant impacts on health and quality of life, anemia is particularly prevalent in women of reproductive age due to blood losses during menstruation and pregnancy. Data from the World Health Organization (WHO) was analyzed to compare trends in prevalence of anemia in women aged 15-49 among countries and over time with the goal of identifying regions both successful and in need of assistance in combatting anemia.
Methods: Publicly available data was obtained from the WHO on the prevalence of anemia among women aged 15-49 from 194 countries from 2000-2019, data being reported as percentages. Anemia was defined as hemoglobin &lt; 12 g/dL for non-pregnant women and &lt; 11 g/dL for pregnant women, with severe anemia being defined as hemoglobin &lt; 8 g/dL for non-pregnant women and &lt; 7 g/dL for pregnant women. WHO data was from both individual-level and summary statistics sources and hemoglobin was adjusted for altitude. Human development index (HDI) data and categories (low, medium, high, and very high) were obtained from the United Nations. Data was analyzed based on year, country, geographic region, and HDI, with ANOVA and Tukey HSD tests being used to analyze the relationship between HDI and anemia.
Results: Worldwide from 2000 to 2013 the prevalence of anemia decreased, and then increased from 2013 to 2019 though remained lower than at 2000 levels; severe anemia decreased throughout the world from 2000 to 2019. Throughout all years, African countries had the highest prevalence of anemia and severe anemia while American and European countries had the lowest (Figure 1). When analyzed by HDI category, there was a significant difference among HDI categories with both total and severe anemia ( P &lt; 0.001 for both). With each decrease in HDI category (very high to high, etc.) there was a significant increase in prevalence of total anemia (Table 1, P &lt; 0.001 for all). For severe anemia, there was a significant difference in prevalence of anemia between all HDI levels except very high and high ( P = 0.09).
Discussion: This data suggests that although the prevalence of anemia among reproductive age women has decreased over time there is still much work remaining, particularly in low HDI countries, where the prevalence of anemia was over twice that of very high HDI countries in 2019, and the prevalence of severe anemia was over three times as high. More research is needed into the relationship of anemia and socioeconomic status as well as preventing, recognizing and treating anemia.
Do We Still Need to Perform Bone Marrow Examination in All Subjects Suspected of MDS? Evaluation and Validation of Non-Invasive (Web-Based) Algorithm
Authors: Oster Howard S , Polakow Ariel M , Goldschmidt Noa , Mittelman Moshe 
Published: December 2023

Background : The gold standard of diagnosing myelodysplastic syndromes (MDS) still requires a bone marrow examination (BME), an old invasive procedure, with possible associated pain and bleeding, and subjective interpretation with 20-25% inter-observer variability. We first developed a logistic regression formula [Oster HS et al., Leuk Res 2018], and then a non-invasive web-based diagnostic algorithm [Oster HS et al., Bld Adv 2021]. The app requires input of 10 readily available clinical and laboratory parameters (age, gender, Hb, MCV, WBC, ANC, monocytes, PLT, glucose, creatinine), resulting in diagnosing or excluding MDS, perhaps obviating the BME (Figure). Here, we performed external validation of the model, using data of MDS patients and non-MDS controls, who had not been included in the development of the model.
Methods: The BM registry of Tel Aviv Sourasky Medical Center (1/2017-12/2021) was reviewed. Inclusion criteria for the MDS group were BME diagnosis, and for the controls, age &gt;50yr, and unexplained anemia requiring BME. We excluded patients with other causes of anemia (renal failure; B12/folic acid or iron deficiency), active malignancy and other hematologic diseases.
The relevant parameters were entered into the online model (at https://shiny.york.ac.uk/mds/) and the results of both groups were compared. In a sub-analysis, the model performance was tested in patients with lower risk (LR, IPSS-R&lt;3.5) and higher risk (HR, IPSS-R≥3.5) MDS.
Results: In total, 204 patients were included and compared, 103 with MDS, and 101 anemic non-MDS control patients, all with BME. The analysis of model performance (Table, upper portion) showed a sensitivity of 85.6%, specificity of 92.3%, positive predictive value (PPV) of 90.3% and a negative predictive value (NPV) of 88.4%. The algorithm was indeterminate in 26.2% of patients with MDS (BME proven), compared with 9.9% in the control group.
In the sub-analysis (Table, lower portion), the model performance in the patients with LR-MDS (n=61) demonstrated sensitivity 85.1%, specificity 92.3%, PPV 90.3% and NPV 88.1%. The performance in HR-MDS (n=32), was 89.3%, 92.3%, 90.6% and 91.1%, respectively.
Conclusions : This study validates the potential role of this non-invasive, easy-to-use model to assist in diagnosis, and mainly exclusion of MDS, perhaps allowing to avoid bone marrow examination in some patients. This might be especially relevant for patients suspected to have LR-MDS. Emerging technologies with data generated from peripheral blood (genetics, morphometrics) may be incorporated in the model in the future.
Pre-Existing Chromatin States Regulate KLF4 Binding to Eliminate Leukemia Stem Cells
Authors: Lu Ting , Yang Shangda , Chen Cong , Liu Shan , Sun Guohuan , Cheng Hui , Cheng Tao , Yen Kuangyu 
Published: December 2023

Transcription factors collaborate with chromatin's epigenetic states to regulate cell fate decisions. While recent in vitro work using cryo-EM (Sinha et al., Nature, 2023) suggested that histone modifications could regulate the activity of pioneer transcription factors, it was not clear whether these findings applied in vivo, or if chromatin states could influence transcription factor binding to affect cell fate. Our previous work (Liu et al., Leukemia,2014; Wang et al., Nat Commun,2019) showed that reprogramming factors (Oct4, Sox2, Klf4, and cMyc, collectively known as OSKM) selectively eliminated leukemia cells in vivo, with minimal impact on normal Hematopoietic Stem and Progenitor Cells (HSPCs). This suggested that cell fates induced by OSKM could be influenced by pre-existing chromatin states.
Building on this hypothesis, we profiled the pre-existing chromatin states of leukemia cells and HSPCs using MNase-ChIP-seq, ATAC-seq, and WGBS-seq. In our Tet-on-induced models, Klf4 activation resulted in the targeting of distinct gene sets and exhibited similar dynamic changes in chromatin accessibility, despite these regions sharing the same active chromatin state. Using machine learning algorithms, we identified H3K18ac –a feature of the active chromatin states preferred by Klf4– as a dominant factor influencing Klf4's genomic binding. We then altered H3K18ac through an enzymatically deficient SIRT7, which is an H3K18ac deacetylase, and examined where Klf4 binds. We observed an increase in Klf4 binding at sites where H3K18ac levels were elevated. This result suggested that Klf4 binding was influenced by changes in H3K18ac. We exposed human CD34+ cells, several leukemia cell lines, and samples from leukemia patients to ATPO-253. This small molecule, currently in phase 1 clinical trials, has been found to enhance the levels of the KLF4 protein. This treatment led to an increase in KLF4 protein levels and we observed activation of apoptosis genes in the tested leukemia cell lines that possessed high pre-existing H3K18ac levels. In addition, we observed a decline across all tested leukemia samples, while the population of CD34+ cells essentially remained stable.
In conclusion, our work demonstrated that pre-existing chromatin states, such as H3K18ac, regulate Klf4's genomic binding, thereby influencing distinct cell fates in leukemia cells and HSPCs. This opens potential avenues for clinical applications in targeted leukemia cell clearance using KLF4 or ATPO-253.
Anti-Hemojuvelin Monoclonal Antibody DISC-0974 Elicits a Durable and Consistent Response with Repeated Dosing in Cynomolgus Monkeys
Authors: Reisman Scott A , Savage William , Liu Guowen , Yang Hua 
Published: December 2023

Introduction
DISC-0974 is a monoclonal antibody (mAB) targeting hemojuvelin and is currently in clinical trials evaluating effects on anemia in patients with myelofibrosis or chronic kidney disease. Inhibition of hemojuvelin (HJV) results in decreased hepcidin and reduction in ferroportin degradation, enabling more iron to be exported out of cells and into the bloodstream for transport to other cells and tissues.
Methods
A study was conducted in healthy, naïve cynomolgus monkeys to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of DISC-0974 following once-monthly dosing for 6 months. Male and female cynomolgus monkeys (n=6/sex/dose group) were intravenously administered DISC-0974 at doses of 0, 0.3, 1, or 6 mg/kg on Days 1, 29, 57, 85, 113, and 141. An additional IV dose was administered on Day 165 for males and Day 166 for females. Dose levels were selected where the high dose would maximally mobilize iron for sustained periods over the treatment regimen, with lower doses selected to provide a dose-response. Male and female monkeys (n=4/sex/group) were euthanized on Day 168 and 169, respectively, and subgroups were monitored for an additional 6 months (n=2/sex/group) to evaluate reversibility of any effects. PK was evaluated after the 1 st, 3 rd, and 6 th dose in all monkeys, as well as during the 6-month period after the final dose in the remaining monkeys. PD effects (i.e., serum iron and transferrin saturation [TSAT]) were monitored at the same timepoints as those collected for PK.
Results
DISC-0974 was well tolerated, and no DISC-0974-related adverse effects were observed. Systemic exposure, based on area under the curve (AUC) and maximum plasma concentrations (C max), increased with dose. Systemic exposures were achieved that reached and exceeded those observed in clinical trials. The high dose of 6 mg/kg achieved systemic exposures, based on AUC, that were &gt;15-fold those observed in humans. Half-lives were consistent with an mAb, and repeated exposure did not result in accumulation with monthly dosing. Increases in serum iron (up to approximately 3-fold baseline) (Figure 1) and TSAT (&gt;90%), representative of PD activity, correlated with systemic exposures of DISC-0974, with similar activity maintained after each of the 7 monthly doses.
Conclusion
Overall, these data demonstrate that DISC-0974 is well tolerated after repeated monthly exposure in cynomolgus monkeys, and an appropriate and durable PK/PD profile was observed, supporting clinical development of chronic once-monthly dosing.
Study on the Changes of Immune Cells in the Evolution of Myelodysplastic Syndromes
Authors: Wang Jing , Zhang Xiaoyuan , Zhao Yue , Zhang Jingjing , Zhou Yibin , Hou Li 
Published: December 2023

ABSTRACT Objective: To analyze the differences of peripheral blood immune cells in healthy people, and patients with myelodysplastic syndromes (MDS) patients or acute myeloid leukemia (AML), and to investigate their correlations with International Prostate Symptom Score(IPSS), blasts and other factors in MDS patients. Methods: 55 patients with MDS(MDS group), 67 patients with AML(AML group) and 25 heathy people(healthy group) were selected as research objects from Dongzhimen Hospital Affiliated with Beijing University of Chinese Medicine from January, 2012 to April, 2022 for this retrospective analysis. By comparing peripheral blood lymphocyte subsets count and peripheral blood lymphocyte subsets percentage, we studied the expression of T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+, CD3+CD4+CD25+FoxP3+), B cells (CD19+) and NK cells (CD3-CD16+CD56+). The correlations between the different indexes and IPSS and blasts were analyzed. Results: (1) Peripheral blood lymphocyte subsets count: There were differences among the three groups. Through pairwise comparison, MDS group had lower peripheral blood lymphocyte subsets count(P＜0.025), probably owing to the low peripheral blood lymphocyte count. (2)Peripheral blood lymphocyte subsets percentage: The percentages of Treg cells, B cells and T cells varied among the three groups. Compared with the healthy group, the percentages of T cells ( P＜0.025) and Treg cells ( P＞0.025) in MDS group were higher, and the percentage of B cells ( P＜0.025) was lower. Compared with MDS group, the percentage of Treg cells ( P＜0.025) in AML group was higher and the proportion of B cells was lower ( P＜0.025). (3)Correlations with IPSS and blasts: The percentage of Treg cells was positively correlated with IPSS and blasts. Conclusion: Treg cells showed an increasing trend in turn by healthy people group, MDS group and AML group. The high expression of Treg cells may have great significance in prognosis and progression of MDS.
Key words: Acute myeloid leukemia; Blasts; Immune cells; Myelodysplastic syndromes.