bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel, Probe-Based and Instrument-Free Method for Improved Ultrahigh-Throughput Single-Cell Gene Expression Analysis of Peripheral Blood Mononuclear Cells
Authors: Eastburn Dennis , White Kevin , Camiolo Salvatore , Montis Gioele , Martin Nicole , Seligmann Bruce 
Published: December 2023

Single-cell gene expression assays are critical tools for identifying functional subtypes of immune cells, as well as changes within cells resulting from pathology or treatment. However, most current methods are expensive, low in sample throughput, rely on reverse transcription and lack the sensitivity to consistently measure low expressed genes from single cells - preventing measurements of many key immune biomarkers and molecular pathways. Another problem with existing single-cell sequencing methods is that many of the cell-associated reads either fail to map to transcripts or map to uninformative ribosomal and mitochondrial genes. Some methods also require the use of live cells, which means the single-cell assay has to be carried out at the specific time of treatment or when culture is terminated. The aforementioned limitations have contributed to most single-cell sequencing studies being restricted to small numbers of samples and have prevented their wider scale adoption in biopharma, clinical, translational and applied applications.
Here we report on the development and performance of a novel combinatorial split-pool-based workflow, TempO-LINC™, that adds cell-identifying molecular barcodes onto high-sensitivity gene expression probes within fixed cells. Cells can be fixed at the end of a treatment, or when obtained from a patient and stably stored for months until they are ready to be processed with other samples through the TempO-LINC assay. All probes within the same fixed cell receive an identical barcode, enabling the reconstruction of single-cell gene expression profiles across as few as several hundred cells and up to 100,000 cells per run. TempO-LINC simultaneously processes up to 96 fixed cell samples per run, has a simple workflow that is amenable to automation and as we will show, has a higher gene detection rate than existing single-cell platforms. We will also show that TempO-LINC has an observed doublet rate of less than 0.5% for 12,500 cells analyzed. Critically, TempO-LINC reduces sample sequencing costs and although we show the assay accurately profiles the whole transcriptome (23,000 transcripts), it can also be targeted to measure only genes/pathways of interest - dramatically reducing sequencing costs yet further. We applied TempO-LINC to assay PBMCs and a human hepatocyte model for toxicology and demonstrated the ability to correctly identify unique cell states and molecular pathways from these populations. We will also present time course and dose response data from compound treatment of cells. All of these features position TempO-LINC as a potential disruptive technology that hematology researchers, clinicians and drug developers can use for new large-scale applications/studies using single-cell sequencing across thousands of samples while obtaining improved data quality.
Neutrophil-Dependent Immune Response Promotes Joint Damage in Hemophilia
Authors: Kaminski Tomasz Waldemar , Katoch Omika , Ragni Margaret V. , Sundd Prithu 
Published: December 2023

Background: Hemophilic arthropathy (HA) is the predominant pathophysiology resulting from recurrent joint bleeding in individuals with hemophilia and leads to permanent joint damage, chronic pain and reduced quality of life. Although FVIII replacement therapy or FVIII mimetics like HEMLIBRA have significantly improved the disease outcome, joint bleeding continues to occur in severely hemophilic patients (FVIII&lt;1%). HA starts at an early age and develops progressively over time, warranting the need for a therapy that can intervene the progression of HA. Unfortunately, such therapy does not exist and the etiological mechanism of HA remains poorly understood.
Aim: To determine whether neutrophil Gasdermin-D (GSDMD)-dependent generation of neutrophil extracellular traps (NETs) in in the joint promotes HA.
Methods: Knee joints in FVIII-total knockout (F8 TKO) or littermate WT male mice were injured using a needle . Scoring of the bleeding severity and histology of injured joints were conducted to assess the joint injury in mice.Imaging-flow-cytometry and ELISA assays were used to evaluate the number of circulating NETs in the blood samples of patients diagnosed with HA and mice with following knee injury. Neutrophils from HA patients, F8 TKO mice and matched controls were isolated, activation of GSDMD-pathway components was evaluated in neutrophils using qRT-PCR (gene expression) and western blotting (protein levels and cleavage).
Results: F8 TKO but not control mice manifested unresolved joint injury and severe bleeding 5-days post knee injury. Circulating NETs (cNETs) and cNETs markers llike neutrophil elastase or citrulinated histones were significantly elevated in the plasma of hemophilia patients diagnosed with HA and injured F8 TKO mice but not plasma of control humans or injured WT mice or uninjured F8 TKO mice. Major genes (mRNA levels) associated with GSDMD-mediated NETs generation were significantly elevated in neutrophils of HA patients and injured F8 TKO mice compared to matched controls. Finally, western blot analysis revealed activation of GSDMD pathway in neutrophils isolated from HA patients and F8 TKO mice but not matched controls.
Conclusions: These findings are the first to suggest that GSDMD-dependent generation of NETs contributes to the pathogenesis of HA
Association of Hospitalist Care and Outcomes on an Inpatient Elective Anticancer Therapy Service
Authors: Vaughn John L , Merl Man-Yee , Morris Jensa C , Gould Rothberg Bonnie E 
Published: December 2023

Background:
Hospitalist care is becoming increasingly common at cancer centers. Here, we assess the impact of oncology hospitalist care on quality outcomes on an inpatient elective anticancer therapy service for patients with leukemia and lymphoma.
Methods:
On July 26, 2021, the Smilow Cancer Hospital transitioned the elective anticancer therapy team from a hematologic oncologist-led traditional service (TS) to an oncology hospitalist-led service (HS). We compared quality outcomes for patients with leukemia and lymphoma requiring elective anticancer therapy who were admitted during two parallel 18-month periods (TS: July 1, 2018 to December 31, 2019; HS: July 26, 2021 to December 31, 2022). Longitudinal data analysis using mixed linear regression models with random effects for intercept (individual) and slope (time) were used to estimate the association between service and outcome, accounting for patients with multiple admissions reflecting sequential cycles of chemotherapy. The outcomes were length-of-stay (LOS), time from admission to first anticancer therapy administration, and discharge time of day. Models were adjusted for age, sex, race/ethnicity, diagnosis, anticancer therapy type, Severity of Illness index, and total elapsed time since cycle 1/day 1 of the index regimen.
Results:
The study included 161 patients, 59 from the TS and 102 from the HS. There were 65 patients with leukemia and 96 with lymphoma. No significant differences in median age, sex, race/ethnicity, or severity of illness index between services were observed (p&gt;0.05). The most common anticancer regimen was etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) for lymphoma (TS n=16 (27%); HS n=31 (30%)). For anticancer regimens with a fixed number of treatment days, after adjustment, we observed a significant reduction of length of stay that exceeded one full day (TS=6.09 days (95% CI: 6.09, 6.95 days); HS=3.82 days (95% CI:3.48, 4.16 days); p&lt;0.001), the adjusted mean time from admission to first anticancer therapy administration decreased by 4.12 hours (95% CI: 0.66, 7.59 hours; p&lt;0.001), and the adjusted mean discharge time decreased by 66 minutes (95% CI: 9, 211 minutes; p=0.01) ( Table 1). For those regimens that required variable monitoring for post-treatment methotrexate clearance or tumor lysis syndrome, no significant difference in outcomes was noted (p&gt;0.05).
Conclusions:
Hospitalist care on an inpatient elective anticancer therapy service was associated with significant improvements in LOS, time from admission to anticancer therapy administration, and discharge time.
A Retrospective Study of Patient Characteristics, Treatment Patterns and Outcomes in Patients with Primary CNS Lymphoma
Authors: Curley Thomas , Wei Wei , Cordova Christine , Peereboom David , Lobbous Mina , Winter Allison 
Published: December 2023

INTRODUCTION: Primary CNS lymphoma (PCNSL) is a rare lymphoma subtype. Treatment with whole brain radiotherapy (WBRT) resulted in high response rates but poor overall survival and modern therapy typically involves combination chemotherapy regimens that include rituximab and high dose methotrexate and, in some cases, followed by consolidative chemotherapy such as autologous stem cell transplantation (ASCT). However, there is no standard regimen, and the choice is institutional and/or physician preference. We performed a single institution retrospective study evaluating the outcomes of patients with PCNSL with focus on outcome stratified by POD24.
METHODS: We performed a retrospective analysis of patients with PCNSL at Cleveland Clinic between January 1, 2010 to December 31, 2020, at the Cleveland Clinic. Patients were excluded if there was any evidence of disease outside of the CNS. Progression-free survival (PFS) and overall survival (OS) after diagnosis were estimated using the Kaplan-Meier method and compared by log rank test. OS was estimated for patients with an event within 24 months (POD24) from the time of this event to death or last follow up.
RESULTS: Data from 80 consecutive eligible patients were analyzed with a median follow up of 44 months. The median age at diagnosis was 63 (range 24-87) and 55% were female. Only a small minority of patients were being treated with immunosuppressants at diagnosis (12%). Of the patients receiving induction therapy, 35% received R-MPV, 20% received R-HDMTX, 4% received HD-MTX alone, 4 % received WBRT as a frontline treatment. 16% of patients received no therapy. The overall response rate to induction therapy was 62% (56% CR and 6% PR). The majority of patients did not receive consolidation treatment (59%). Of those who did receive consolidative therapy, non-myeloablative high dose cytarabine was the most frequently used strategy. Thirty-six patients progressed (45%) and of these, the majority (67%) occurred within 24 months of starting therapy. For the entire cohort, the median PFS was 16 months, and the median OS was 32 months. The 1-year and 5-year OS rates were 66% and 34%, respectively. An ECOG performance status of 0 or 1 was associated with significantly improved PFS and OS (p &lt; 0.0001 for both. Median OS after PD for patients with POD24 was 6 months [95% confidence interval (CI) 4-NA] with only 42% alive at 1 year.
CONCLUSION: This large retrospective study evaluating all patients with B-cell NHL PCNSL with extended follow up shows that the majority of progressive events occur within 24 months and is associated with poor outcomes. Rituximab and polychemotherapy regimens are now favored over rituximab and methotrexate alone to improve response rates. Our data show that emphasis on strategies for consolidation such as high dose chemotherapy and autologous transplantation are needed to prevent progression.
The ‘Weekend Effect’ on Immune Cytopenia: Insights from the National Inpatient Sample Database
Authors: Mahmoud Amir , Kharel Himal , Srivastava Arnav , Jain Tripti , Orakzai Abdullah , Mostafa Mariam A , Neupane Niraj , Eltaher Basant , Yassin Heba , Abdelhay Ali 
Published: December 2023

Introduction: Outcomes for weekend versus weekday admissions for immune cytopenias including immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and autoimmune hemolytic anemia (AIHA)/Evan's Syndrome are explored in this abstract.
Methods: A query of the 2012-2019 National Inpatient Sample was performed for primary hospitalizations with immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and autoimmune hemolytic anemia (AIHA)/Evan's Syndrome using ICD-9/10 codes. Demographics, comorbidities, and outcomes were identified. Univariate analysis with t-tests or chi-square performed as appropriate. A 1:1 nearest neighbor propensity score matched cohorts was generated for each of the ITP, TTP and AIHA/Evan's hospitalization dataset. Variables with standardized mean differences &gt;0.1 used in multivariate regression to generate adjusted odds ratios (AOR)/β-coefficients for weekend admission status on outcomes. Significance was set at an alpha level of &lt;0.05. All analysis performed in SPSS versions 26.
Results: 24,325, 2992,and 7,609 hospitalizations were included with 4592, 656, and 1468 weekend admissions in ITP, TTP, and AIHA/Evan's respectively. Propensity matched cohorts were generated adjusting for age, sex, race, median household income and co-morbidities including DM, CHF, CKD/ESRD, and liver disease. The results showed significantly higher, almost two-fold, in-hospital mortality in AIHA for weekend admissions (Odds ratio (OR): 1.85, CI 1.20-2.85, p-value=0.005). In addition, there was significantly higher risk of circulatory shock and mechanical ventilation requirement for weekend admissions in AIHA along with significantly increased length of hospital stay and total hospital charges. TTP patients also showed similar trend towards higher mortality with significantly higher incidence of AKI and increased length of stay for weekend admissions. There was no significant difference seen in ITP. The results are summarized in table 1. These results are partly in agreement with findings of Manadan et al study, which showed lower rate of procedures and higher adjusted mortality for general inpatient admissions in weekends.
Conclusion: Weekend admissions showed poorer outcomes especially in AIHA and TTP. Although the exact reasons are unknown, decreased staffing and procedural availability may be responsible for such findings. Further studies are needed to clarify the steps needed to decrease adverse outcomes for weekend admissions.
Association between Iron Deficiency Anemia and Thrombosis, a Population Based Study
Authors: Laber Eric Nathan , Laber Damian A 
Published: December 2023

Iron deficiency anemia (IDA) has been associated with thrombosis in children, but this association has not been appropriately studied in other age groups. We hypothesize that IDA is a risk factor for thrombosis in all populations. The aim of our study is to evaluate the association between iron deficiency anemia and different types of thrombosis in all patients.
Methods: We searched the medical records of all patients evaluated at a large hospital and outpatient medical center in Tampa, Florida utilizing the International Classification of Diseases 10th Edition (ICD-10). This coding system assigns standard acronyms to conditions, symptoms, and other factors of disease. We used the codes for iron deficiency anemia of all types, venous embolism and thrombosis, cerebrovascular disease, and retinal vascular occlusion. We then combined the codes in the database search to obtain the total number of patients with these conditions. Finally, we performed simple statistical analysis to compare the number and percentage of patients with thrombosis and IDA to patients with thrombosis and without IDA.
Results: 2,539,231 patients were included in our database between 2010 and July 31st 2023. The age of this population was between 0-102 years-old. IDA was present in 66,693 patients (2.63%), venous embolism and thrombosis was present in 36,523 individuals (1.43%), cerebrovascular thrombosis was present in 14,159 patients (0.56%), and retinal vascular occlusion was present in 1,506 individuals (0.06%). Out of the 66,693 patients with IDA, 7,554 (11.3%) had venous embolism and thrombosis, 14,159 (0.56%) had cerebrovascular thrombosis, and 1,506 (0.06%) had retinal vascular occlusion. Out of the 2,472,538 patients without IDA, 28,969 (1.17%) had venous embolism and thrombosis, 12,172 (0.49%) had cerebrovascular thrombosis, and 1,276 (0.05%) had retinal vascular occlusion. When comparing the percentage of patients with IDA versus no-IDA, venous embolism and thrombosis was 10 times more prevalent, cerebrovascular thrombosis was 6 times more prevalent, and retinal vascular occlusion 6 times more prevalent in patients with IDA than in those without IDA in all age groups combined.
Conclusions: In this population based study, the incidence of thrombosis was 6-10 times greater in patients with IDA compared to no-IDA. Our data suggests that IDA is a risk factor for thrombosis in all patients. Prospective studies might be needed to confirm our findings. Finally, our data suggests that treatment of IDA might decrease the risk of thrombosis.
Survival of Patients with Transformed Marginal Zone Lymphoma in the United States: A Population-Based Cohort Study
Authors: Vaughn John L , Epperla Narendranath 
Published: December 2023

Background: Marginal zone lymphomas (MZLs) are a heterogenous group of indolent non-Hodgkin lymphomas that include extranodal MZL of mucosa-associated lymphoid tissue (EMZL or MALT lymphoma), nodal MZL (NMZL), and splenic (SMZL). All three subtypes can transform to diffuse large B-cell lymphoma (DLBCL). However, the cumulative incidence of histologic transformation (HT) and survival of patients with transformed MZL (t-MZL) in the US population have not been reported to date. Hence, we sought to estimate the risk of HT and relative survival (RS) in patients diagnosed with MZL in USA using a population-based study.
Method: We conducted a population-based cohort study of t-MZL using the Surveillance, Epidemiology, and End Results-17 database. We included adults diagnosed with MZL in the US between 2011-2015. This time period was selected to provide a contemporary estimate of survival and allow for adequate follow-up. We identified patients with t-MZL by following patients with MZL and identifying those patients with subsequent diagnoses of DLBCL. All patients with t-MZL had biopsy-proven HT. We estimated the post-transformation RS of patients with t-MZL using flexible parametric survival models with 5 degrees of freedom for the baseline cumulative hazard. We compared the survival of the different MZL subtypes using multivariable modeling after adjusting for age, year, race, Ann Arbor stage, B symptoms, and geographic location. P values less than 0.05 were considered statistically significant.
Results: A total of 5372 patients with MZL were included in the study. There were 3446 (64.2%) patients with EMZL, 1485 (27.6%) with NMZL, and 441 with SMZL (8.2%). Among the 5372 patients, 121 (2.3%) had biopsy-proven HT after a median follow-up of 6.2 years (95% confidence interval (CI), 6.1-6.3). HT was associated with decreased survival for patients with MZL ( Figure 1A). Among the MZL subtypes, SMZL was the most likely to develop HT (24/441, 5.4%), followed by NMZL (49/1436, 3.3%) and EMZL (48/3398, 1.4%) ( P &lt; 0.001) despite similar follow-up between groups. The 5-year post-transformation RS was highest for t-EMZL (61%) followed by t-NMZL (51%) and t-SMZL (46%) (Figure 1B). On multivariable analysis, however, the subtype of MZL was not a significant predictor of RS. In addition, there were no significant predictors of RS identified among the study covariates.
Conclusion: This is the first population-based study to date reporting outcomes associated with t-MZL in the USA. The risk of HT in MZL may vary depending on the subtype of MZL with cumulative incidence of 1.4-5.4% observed after 6 years of follow-up in the contemporary era. HT was associated with increased mortality irrespective of MZL subtype. Among the MZL subtypes, SMZL was most likely to develop HT and had the lowest estimated 5-year RS. Additional studies are needed to better understand factors associated with prognosis in t-MZL.
Statewide Burden and Trends of Acute Myeloid Leukemia in the United States between 1990-2019: A Benchmarking Analysis for the Global Burden of Disease Study 2019
Authors: Gadhiya Dhruvkumar , Bhatt Parjanya , Christian Cleris , Singh Gauravdeep , Dhawan Arushi , Amin Vishrant , Patel Juhi , Desai Hardik Dineshbhai 
Published: December 2023

Background: Acute myeloid leukemia (AML) ranks as the 15th leading cause of death, accounting for 1.75% of all cancer-related deaths in the United States of America (USA) in 2019, following Myeloma. Despite its significance, statewide disparities in AML burden have not been previously studied. Thus, this research aimed to assess the burden and trends of AML across the USA over the last three decades, spanning from 1990 to 2019.
Method: Employing the Global Burden of Disease methodology, we evaluated AML prevalence, incidence, mortality, and disability-adjusted life years (DALYs) using standardized approaches and statistical modeling. The results were presented in absolute counts and age-standardized rates (per 100,000 person-years).
Results: The total number of AML prevalence cases rose from 10,124 (95% uncertainty interval (UI): 9,259-11,482) in 1990 to 21,370 (95% UI: 17,759-24,830) in 2019. Correspondingly, deaths increased from 6,849 (95% UI: 6,301-7,724) in 1990 to 13,620 (95% UI: 11,632-14,664) in 2019, while DALYs increased from 185,960 (95% UI: 171,985-210,122) in 1990 to 301,526 (95% UI: 268,606-323,608) in 2019. The age-standardized incidence rate (ASIR) rose from 2.75 (95% UI: 2.52-3.09) to 3.23 (95% UI: 2.71-3.73) cases per 100,000 from 1990 to 2019. Similarly, the age-standardized mortality rate (ASMR) increased from 2.20 (95% UI: 2.03-2.48) to 2.54 (95% UI: 2.19-2.72) cases per 100,000 during the same period. In 2019, the greatest AML incidence was observed in California (1,677), followed by Florida (1,268) and Texas (1,155), while the lowest incidence was observed in the District of Columbia (24). Regarding the annual percentage of change (APC), the highest percentage increase in deaths was observed in Nevada (328%), followed by Alaska (224%), while the District of Columbia had the lowest APC (6%) from 1990 to 2019. In terms of incidence, Nevada (332%) and Arizona (227%) had the highest APC during the same period. The age group of 70-74 years had the highest number of deaths (2,264) and incidence (2,665), as well as DALYs (43,918) in 2019. Notably, the older age groups exhibited the highest APC in deaths and incidence. Males had a higher burden of AML compared to females.
Conclusion: Our study underscores significant disparities in AML burden across different states in the USA from 1990 to 2019. We have also identified that males and elderly individuals face a higher likelihood of AML burden. Consequently, policymakers must prioritize enhancing healthcare systems, advancing early diagnosis and treatment approaches, and promoting health education to reduce individual exposures to relevant risk factors.