bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Interplay between Anxiety, Depression, and Quality of Life Following Pulmonary Embolism
Authors: Rajasekar Bhairavi , Hurley Karen , Cameron Scott J , Tefera Leben 
Published: December 2024

Background
Pulmonary embolism (PE) is the third leading cause of cardiovascular death. It has been shown to be accompanied by significant decreases in quality of life. The prevalence and longitudinal trends of anxiety, depression, and quality of life in PE patients remains largely understudied.
Methods
We conducted a prospective observational study examining 192 PE patients attending a dedicated Pulmonary Embolism Response Team (PERT) Clinic. Participants completed standardized assessments using the Pulmonary Embolism Quality of Life (PEmb-QoL) Questionnaire, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire (PHQ-9) following their PE diagnosis and ensuing treatment.
Results
Our findings revealed noteworthy gender disparities in the psychological impact of PE on survivors. Of the 192 participants, 51% were women and 49% were men. Among women, 42% reported anxiety and 44% reported depression. Through all dimensions evaluated by the PEmb-QoL, women reported a lower quality of life post-PE. Patients with higher levels of anxiety and depression experienced worse quality of life. Younger patients reported worse quality of life in the categories of increased frequency of complaints and emotional complaints. They additionally expressed greater feelings of worry in ceasing anticoagulant medications in comparison to older counterparts.
Conclusion
This study represents one of the largest dedicated prospective studies to date to examine the psychological impact of PE on patients' psyche and quality of life, highlighting the significant psychological toll of PE on patients' recovery. We noted women experienced higher rates of anxiety and depression and lower overall quality of life scores when compared to men. Furthermore, regardless of gender, we observed a decrease in quality of life with the prevalence of anxiety and depression. The results indicated that age influenced a patient's tendency to report worse quality of life. These findings underscore the importance of psychosocial support strategies in addressing the emotional needs of patients in the aftermath of a PE diagnosis.
Learning Objective
Disparities in anxiety and depression prevalence following PE diagnosis and treatment exist. This study highlights the importance of implementing tailored psychosocial support strategies to address the unique emotional needs of PE patients, particularly among women and younger patients.
Targeting CDK16 Abrogates Growth-Factor Mediated TKI Resistance in AML
Authors: Kesarwani Meenu , Kincaid Zachary , Azhar Mohammad , Azam Mohammad 
Published: December 2024

Introduction. Mutations in the Fms-like tyrosine kinase 3 (FLT3) gene are among the most common genetic lesions in AML, associated with poor prognosis and high relapse rates. Targeted TKI therapies against FLT3 have shown promise, yet clinical resistance remains a significant challenge. Using phospho and chemiproteomic analyses of FLT3ITD expressing cells revealed CDK16 drive treatment resistance to chemotherapy during growth factor signaling. Targeting CDK16 in combination with FLT3 tyrosine kinase inhibitor (TKI) or BCL2 inhibitor show synergistic response and significantly prolonged the survival of mice harboring AML.
Result. Using mouse cell lines expressing FLT3ITD treated with gilteritinib with and without growth factors (growth factor signaling confers resistance to TKI) were subjected to whole genome phosphoproteome and total proteome analyses. This analysis revealed significant changes in abundance and phosphorylation of CDK and MAPK family members in resistant cells. Notably, we noted persistent upregulation of CDK2, CDK 12, CDK13 and CDK20 in TKI resistant cells. Using CRISPR-CAS9 mediated knock-out of these target genes revealed that deletion of CDK12, CDK13 and CDK16 confers strong sensitivity to TKI treatment. Our findings demonstrate that CDK16 inhibition significantly reduces cell viability, induces apoptosis, and impairs clonogenic potential in FLT3-mutated AML cells. Mechanistically, CDK16 inhibition disrupts key signaling pathways that stabilizes P53, highlighting its potential to overcome resistance to FLT3-targeted therapies. Moreover, in vivo studies using xenograft models of FLT3-mutated AML revealed that CDK16 inhibition markedly suppresses tumor growth and enhances overall survival. These results suggest that CDK16 inhibitors could serve as a novel therapeutic strategy for FLT3-mutated AML, either as monotherapy or in combination with existing FLT3 inhibitors.
Conclusions. Our research underscores the therapeutic potential of CDK16 inhibition in FLT3-mutated AML, providing a compelling rationale for the clinical evaluation of CDK16 inhibitors in this challenging subset of AML patients. Further studies are warranted to explore the full therapeutic implications and to optimize combination strategies for improved patient outcomes.
Impact of Age on Autologous Stem Cell Transplantation Outcomes for AL Amyloidosis
Authors: Sami Sophiya S , Bashir Qaiser , Saini Neeraj Y. , Aljawai Yosra M. , Hosing Chitra , Popat Uday , Becnel Melody R. , Kaufman Gregory P. , Thomas Sheeba K. , Weber Donna M. , Orlowski Robert Z. , Champlin Richard E. , Shpall Elizabeth J. , Qazilbash Muzaffar H. , Srour Samer A. 
Published: December 2024

Introduction:
Consolidation with high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with light chain amyloidosis (AL) is associated with deeper responses and improved outcomes. Several factors are known to be associated with worse outcomes. Older patients with AL frequently present with more advanced disease and have generally inferior outcomes compared to younger patients. In this study, we aimed to explore the impact of age on survival outcomes for AL patients who underwent ASCT at our institution.
Methods:
All consecutive patients with AL who underwent their first ASCT between 09/2005 and 11/2021, using a single agent melphalan conditioning regimen, were included. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included non-relapse mortality (NRM).
Results:
One-hundred-and-seventy-nine patients (109 males, 70 females) with a median age of 61 years (range, 27-77) were identified during the study period. Among these 102 (57%) were in the older age group (≥60 years) and 77 (43%) were in the younger age group (&lt;60). Overall, there were no notable differences in baseline patient and disease characteristics between the two age groups, but a higher proportion of patients in the older group had an estimated glomerular filtration rate (eGFR) of &lt;50 (31% vs. 19%, p=0.0765). With a median follow-up of 62 months (range 3.2-167.4), the 5-year PFS and OS for all study patients were 49% and 72%, respectively. The 5-year PFS for patients ≥60 was 44% compared to 55% for patients &lt;60 (p=0.1022). The 5-year OS rate for patients ≥60 was 66% versus 80% for patients age &lt;60 years (p=0.0081). The 1-year NRM was 11% for patients ≥60 compared to 2.6% for patients &lt;60 (p=0.1246). Age and variables with p-value ≤0.15 in univariate analyses were included in multivariable analyses (MVA) for OS (HCT-Comorbidity Index, Beta-2 microglobulin, eGFR, Cardiac Involvement, Revised Mayo Staging). Age ≥60 (HR: 3.075; 95% CI: 1.374-6.884; p=0.0063) and Revised Mayo Stage III/IV (HR: 2.576, 95% CI: 1.145-5.796; p=0.0221) were significantly associated with inferior OS in MVA. In a subgroup analysis stratifying patients by their age and Revised Mayo Staging, patients age ≥60 with Mayo Stage III/IV had significantly inferior 5-year PFS/OS of 27%/37% vs 53%/77% vs. those in the same age group but with Mayo Stage I/II (p=0.02 for PFS; p=0.0012 for OS).
Conclusions:
For AL patients undergoing ASCT, our findings suggest that older patients with Mayo Stage I/II age have excellent long-term outcomes. Revised Mayo stage III/IV combined with age ≥60 years were predictive of poor outcomes, which warrants alternative treatment strategies for these patients.
Combined Coagulation Factor XI and Factor XII Deficiencies in an Asymptomatic Black Female
Authors: Rupani Karishma Vijay , Hawkins Katherine A. , Walsh Christopher 
Published: December 2024

Background: While there are multiple studies describing combined coagulation factor deficiencies, their genetic defects and clinical significance remain largely unknown. We present the case of an asymptomatic Black female with deficiencies of both coagulation factor XI and factor XII. To our knowledge, the combination of coagulation factor XI and XII deficiencies has not previously been reported in a Black individual.
Case Report: In April 2024, a healthy 29 year old Black female from Honduras without personal or family history of bleeding or bruising, presented with a prolonged activated partial thromboplastin time (aPTT) that was incidentally found during a routine pre-operative evaluation for elective cosmetic surgery. Her prothrombin time (PT) was normal. Her aPTT was prolonged to 43.4 seconds (reference interval 25.4 - 34.9 seconds) and normalized with 1:1 mixing studies of patient and normal plasma. She was therefore evaluated for deficiencies in factors VIII, IX, and XI, as well as for the presence of a lupus anticoagulant. Her factor VIII and IX levels were normal. No lupus anticoagulant was detected. Her factor XI levels were decreased: 47% in April 2024, 56% in June 2024, and 58% in July 2024 (reference range 60 - 150%). Her factor XII levels were also decreased at 39% in April 2024 and borderline normal at 51% in July 2024 (reference range 50 - 150%). She has no past medical history and has never had excessive bleeding. She has been pregnant once and delivered a healthy baby via an uncomplicated spontaneous vaginal delivery at full term.
Conclusion: Although detection and identification of combinations of coagulation factor deficiencies is readily available, their underlying genetic defects and clinical significance requires ongoing investigation.
Outcomes and Associations in Hospitalized Patients with Concomitant Helicobacter Pylori Infection and Idiopathic Thrombocytopenic Purpura(ITP)
Authors: Olusoji Rahman , Abbey Enoch , Akpoigbe Kesiena , Genao Alvaro , Ahluwalia Meena 
Published: December 2024

Background
Studies have shown that H. pylori infection could be associated with Idiopathic Thrombocytopenic (ITP) in some patients. Multiple studies have also reported improvement and resolution of ITP after H. pylori eradication therapy in these patients. This study explores adverse outcomes in hospitalized patients with ITP and H pylori infection, explicitly focusing on mortality rates and length of stay in affected patients.
Methods
This retrospective cohort study utilized the 2018 to 2020 National Inpatient Sample (NIS) database. The inclusion criteria included adults aged 18 and above diagnosed with idiopathic thrombocytopenic purpura during hospitalization, with or without H pylori infection. We defined ITP and H. pylori infection using ICD-10 codes. We analyzed the demographic data of these patients and their correlation with hospital outcomes, including length of stay, hospitalization costs, and mortality rates. Using univariate and multivariate logistics regression models, we measured mortality as the primary outcome.
Result
We identified 149,780 patients with ITP, among whom 350 (0.2%) had concomitant diagnosis of H. pylori infection. ITP patients were primarily female and white, with a mean age of 61. Patients with concomitant H. pylori infection had a significantly more extended stay of nine vs. seven days, p=0.02. Individuals with H. pylori infection exhibited lower odds of death on univariable and after multivariable regression. However, this fails to meet statistical significance [0.32, 95% CI (0.04-2.30)] and [0.30, 95% CI (0.04-2.16)], likely underpowered by the rarity of co-existing pathology.
Conclusion
Our study shows that the mortality odds among individuals with idiopathic thrombocytopenic purpura were lower in patients with concurrent H. pylori infection than those without H pylori. Though limited by statistical power, it gives credence to previous studies showing that treating co-existing H pylori infections may permanently lead to platelet recovery and possible resolution of their ITP.
Agent Orange Exposure and Myelodysplastic Syndrome: A Single VA Medical Center Experience
Authors: Domb Chaim , O'Brien Timothy 
Published: December 2024

Background:
Agent Orange (AO) exposure may be linked to the development of myeloid malignancies, including myelodysplastic syndrome (MDS). This is not yet definitive, though, and, unlike several other malignancies, MDS is not yet a service-connected diagnosis for AO exposed veterans. Although recent studies have not revealed AO associated specific mutations in MDS, clinical and pathological potential differences have not been well studied. In addition, determination of AO exposure is often not reported.
Methods:
All veterans diagnosed with MDS at the Cleveland VAMC from 2012-2023 were identified. Prior AO exposure was determined by Military Exposure tab in the EMR and confirmed with direct patient contact. Data collected included age and IPSS-R score at diagnosis; ring sideroblast percentage; mutations (on NGS); progression to AML and overall survival (OS).
Results:
129 veterans were identified, 48 of whom had AO exposure. The mean age was 70.7 years in the AO group and 73.3 in the non-AO group (p=0.098); average IPSS-R score was 3.14 in AO and 2.75 in non-AO group (p= 0.32). 8 (6%) of pts had high risk IPSS-R (4 in each group); 29 (22%) pts had intermed risk (13 AO and 10 non-AO exposed) and 92 pts (71%) were low risk (31 AO and 61 non-AO). In the AO group 4/48 (8.3%) progressed to AML vs 10/81 (12.3%) in the non-AO group; median OS was 39 months in AO vs 33 months in non-AO group (p=0.93). The most common mutations seen were TP53 (17%), SF3B1 (21%), SRSF2 (23%), DNMT (10%), ASXL1 (11%), and U2AF1 (11%), with no differences between the 2 groups. 50% of those in the AO group had 2 or more genetic mutations vs. 61% for the non-AO group. Average variant allele frequency (VAF) was 40.2% in the AO group vs. 44% in the non-AO group. 9/48 (19%) of pts in the AO group met criteria for MDS-RS vs 12/81 (15%) in the non-AO group (p= 0.74). The average ring sideroblasts seen was 6% for the AO group compared to 5.7% for the non-AO group, p = 0.89.
Conclusion:
This small retrospective study did not reveal statistically significant differences between AO vs non-AO exposed veterans with MDS, in terms of age at diagnosis, IPSS-R score, RS %, mutations (type, number or VAF load), progression to AML or OS. There were trends for AO exposed veterans presenting at a younger age and having a lower rate of progression to AML. Although we did not find any phenotypic or genotypic differences this was not a study of causality and does not exclude AO being associated with increased risk for MDS.
Hypoalbuminemia Increases Clot Fibrin Network Density and Reduces Fibrinolytic Susceptibility through a Paraoxonase 1 Dependent Mechanism
Authors: Waller Amanda , Wolfgang Katelyn , Stevenson Zachary , Kerlin Bryce 
Published: December 2024

Introduction
Hypoalbuminemia is a predictor for thrombotic cardiovascular disease. Albumin is a negative acute phase reactant and may thus be a biomarker for thrombo-inflammation, but some data suggest a mechanistic role for albumin in fibrinolysis. The aim of this study was to investigate the mechanistic role of albumin in fibrinolysis. We hypothesized that albumin modifies clot structure and fibrinolytic susceptibility in two well-established rodent models of hypoalbuminemia and analbuminemia.
Methods
Blood or plasma from a hypoalbuminemic nephrotic syndrome rat model and an albumin knockout rat model were analyzed by thromboelastometry, clot lysis assays, fibrin clot turbidity, fibrin clot density, and plasma clot immunoblotting. Some studies were conducted without vs. with recombinant albumin repletion. We mined albumin and fibrin clot proteome datasets to identify proteins both carried by albumin and incorporated in clots, hypothesizing that albumin delivers proteins that alter fibrinolytic susceptibility to the forming clot.
Results
Albumin levels were proportional to fibrinolysis in a clot lysis assay in both nephrotic and albumin knockout rat plasma. Hypoalbuminemia accelerated fibrin clot formation in nephrotic rat plasma and fibrin clot network density was increased in hypoalbuminemic plasma clots from both nephrotic rats (p&lt;0.01) and albumin knockout rats (p&lt;0.001). Recombinant albumin repletion to healthy control concentrations corrected fibrin network density and fibrinolysis in both nephrotic rat and human plasma as well as in albumin knockout rat plasma (p&lt;0.05). Paraoxonase 1 (PON1) enzyme was identified in both albumin and fibrin clot proteomes. Naringenin, a PON1-specific inhibitor decreased fibrin clot lysis in normal rat plasma in a dose-dependent manner (IC50= 1 uM; p&lt;0.001), but did not alter clot lysis in albumin knockout plasma (p&gt;0.9). Moreover, naringinen ameliorated the ability of recombinant albumin repletion to correct hypofibrinolysis (p&lt;0.001 vs control).
Conclusions
Dense hypoalbuminemic clots demonstrated hypofibrinolysis, and albumin repletion corrected both clot density and hypofibrinolysis. PON1 inhibition decreased clot lysis in plasma with normal albumin levels and ameliorated the ability of albumin repletion to correct fibrinolysis in albumin knockout plasma. Collectively, these data suggest a mechanistic link between hypoalbuminemia and hypofibrinolysis and suggest that albumin indirectly regulates fibrinolysis via its effects on clot density, through a PON1 dependent mechanism.
Effect of Granulocyte Colony Stimulating Factor (GCSF) on Survival in Patients with Acute Myeloid Leukemia (AML)
Authors: Desai Devashish , Sampat Parth , Mammadli Mahinbanu , Ghimire Krishna 
Published: December 2024

Background:
GCSF is a hematopoietic growth factor used in patients receiving chemotherapy, which is commonly used to prevent chemotherapy-induced neutropenia and neutropenic fever. There is concern that use of GCSF can enhance proliferation of myeloid blasts. Our goal was to analyze the effect of GCSF on survival with patients with AML.
Methods:
TrinetX, a global federated research network, provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients with AML. The population was further divided into two groups, based on the receipt of GCSF (filgrastim, pegfilgrastim, lenograstim, eflapegrastim) within 6 months of diagnosis. Further, propensity score matching (PSM) was carried out to match age, sex, race, and severe sepsis. Descriptive analysis was used for demographic data. Kaplan Meier analysis using log-rank test was used for overall survival (OS), and Cox regression used for hazard ratio (HR).
Results:
99,756 patients were identified with AML, out of whom 21.34% (21,293) received GCSF. It was seen that patients who received GCSF were significantly younger (56.2 ± 16.3 vs. 60.5 ± 18.7, p &lt;0.0001). Males were predominant gender in both groups and were significantly higher in receiving GCSF (54% vs. 52%, p &lt;0.0001). Looking into Race, Caucasians (67% vs. 49%, p &lt;0.0001) were predominant race in both groups. African Americans (8% vs. 7%, p&lt;0.0001) and Asians (5% vs. 3%, p &lt;0.0001) were significantly more in the GCSF group, while Unknown races were more in no GCSF group (16% vs. 37%, p &lt;0.0001). Patients who received GCSF were found to have more severe sepsis with or without shock (11% vs. 2%, p&lt;0.0001). Median follow-up was 549 days and 202 days for patients in the GCSF group and not in the GCSF group, respectively. Relapse of AML was significantly more in the GCSF group (25.41% (4,512) vs. 7.26% (5,107), p &lt;0.0001; OR - 4.35 (4.162,4.547)). 47.14% patients died in GCSF group compared to 32.07% in non-GCSF group (p&lt;0.0001). Kaplan Meier curve showed significant separation of curve with median OS shorter in patients who received GCSF (1,079 vs. 2,339 days, p&lt;0.0001; Hazard Ratio - 1.132 (1.106-1.159)). After PSM, 25.50% patients who received GCSF had relapse (25.50 vs. 9.0%, p&lt;0.0001; OR - 3.461 (3.259,3.675)) and 46.48% died (46.48% vs. 33.38%, p&lt;0.0001; HR - 1.263 (1.224,1.304)).
Conclusion:
Our study shows real world data, where use of GCSF in patients with AML has increased risk for relapse as well as death. Overall survival was also shorter for patients who received GCSF. GCSF should be used very diligently in AML cases.
Selective Reversal of ADAR1 Splicing Prevents Leukemia Stem Cell Maintenance In Vivo
Authors: Ma Wenxue , Jamieson Catriona , Pham Jessica , Klacking Emma E , Katragadda Neha , Ruiz Antonio W , Frias Thomas P , La Clair James J. , Morris Sheldon , Kulidjian Anna , Whisenant Thomas 
Published: December 2024

Introduction
Acute myeloid leukemia (AML) is characterized by a clonal proliferation of myeloid progenitors with a reduced capacity to differentiate into more mature cellular elements. Adenosine deaminase acting on RNA 1 (ADAR1) is an enzyme that is involved in the editing of messenger RNA (mRNA) transcripts (A-to-I RNA editing), which can alter the function of the resulting protein. ADAR1 drives cancer stem cell (CSC) generation and therapeutic resistance in many types of malignancies. As a potent small molecule splicing modulator, Rebecsinib inhibits splicing of ADAR1 into the ADAR1p150 isoform while Fedratinib inhibits JAK/STAT3 mediated activation of ADAR1p150 transcription1, 2.
Methods
To assess the relative ADAR1 inhibitory capacity of Rebecsinib and Fedratinib, humanized sAML mouse models were established with immunomagnetic bead-selected CD34+ cells from primary AML patient samples. Engrafted mice treated with Rebecsinib survived significantly longer compared to those treated with vehicle (p = 0.0003, log-rank test), Fedratinib (p = 0.016, log-rank test), and the combination of Rebecsinib and Fedratinib (p= 0.0002, log-rank test). In comparison, humanized aged normal bone marrow stem cell mouse models established by intravenous transplantation of CD34+ cells (obtained according to IRB-approved protocols from the bone marrow of patients undergoing hip replacement surgery), into NSG-SGM3 mice demonstrated increased human CD34+ cells engraftment in the bone marrow.
Conclusions
The results suggest that inhibition of ADAR1 splice isoform switching may provide a competitive advantage for normal hematopoietic stem cells compared with leukemia stem cells in the bone marrow niche and lay the foundation for developing clinical ADAR1p150 inhibitory strategies.
References1. Crews L, Balaian L, Delos Santos, NP et al. RNA Splicing Modulation Selectively Impairs Leukemia Stem Cell Maintenance in Secondary Human AML. Cell Stem Cell. 2016; 19: 599-612, PMID: 275700672. Crews L, Ma W, Ladel L, et al. Reversal of Malignant ADAR1 Splice Isoform Switching with Rebecsinib. Cell Stem Cell. 2023.