bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim Analysis and Feasibility of the Effects of Virtual Reality on Pain and Anxiety in Cancer Patients Undergoing Bone Marrow Biopsy
Authors: Wolfson Hannah C , Mohacsi Savannah , Pai Jonathan , Xiong Shigang , Nelson Viva , Konganige Shiran , Ghani Umair , Pinski Jacek K 
Published: December 2024

Introduction/Purpose
We developed a protocol to test the hypothesis that the utility of Virtual Reality (VR) as a companion to bone marrow biopsy (BMBx) procedures will lessen patient experiences of pain and anxiety as indicated by patient-reported pain scores and anxiety surveys. The purpose of the present study was to examine the feasibility of this protocol.
Methods
We conducted a prospective, randomized study of 14 patients (of a planned total enrollment of 30 patients) undergoing BMBx. Patients were randomized 1:1 to the experimental arm (VR) or the control arm (standard of care). Pain surveys and the State Trait Anxiety Inventory (STAI) were completed before and after the BMBx procedure. Pain was rated on a scale from 0-10. The STAI scores were calculated as two sub-scores: State Anxiety Inventory (SAI) score and Trait Anxiety Inventory (TAI) score. Changes in pain and anxiety were calculated as the difference between recorded pain scores (∆Pain) and STAI sub-scores (∆SAI, ∆TAI) pre- minus post-BMBx. In R version 4.3.2, two sample t tests and Mann-Whitney U tests were used to compare changes in pain ratings and STAI sub-scores by experimental group. This was an interim analysis of 14 patients out of a planned 30 planned subjects to examine feasibility of the protocol.
Results
One patient did not complete any pain or STAI surveys and was excluded from analysis. Overall means (SD) for ∆Pain, ∆SAI, and ∆TAI were -0.92 (2.63), 2.46 (9.40), and 2.31 (3.82). Mean ∆Pain in the experimental group (n=8) and the control group (n=5) were -0.75 vs. -1.2, t test p=0.78, respectively. Mean ∆SAI in the experimental group and the control group were 2.875 vs. 1.8, t test p=0.84, respectively. Mean ∆TAI in the experimental group and the control group were 2.875 vs. 1.4, Mann Whitney U test p=0.46, respectively.
Conclusion
Differences were noted in pre- minus post- BMBx scores for pain and STAI sub-scores between the experimental group and the observational group. Although the differences in the means did not reach statistical significance due to the small number of subjects in the study, the results do support the feasibility of the protocol used in this pilot study to be expanded to a larger patient population and to a more diverse set of acutely painful procedures.
Late Effects of Childhood Cancer Among Survivors in Saudi Arabia: A Multicenter Cross-Sectional Study
Authors: Alabbas Fahad , Alharbi Ibrahim , Ahmad Naveed , Alnajashi Khalid , Ballourah Walid , Alsultan Abdulrahman 
Published: December 2024

Abstract
Background: With the advancement of childhood cancer therapy, long-term survivors are on therise. Reports of late effects of childhood cancer are limited. This study aims to assess the spectrum and burden of late effectsamong survivors of childhood cancer in Saudi Arabia.
Methods: This observational cross-sectional retrospective study was conducted at multiple cancer centers in Saudi Arabia. Survivors were enrolled consecutively, provided they completed at least 5 years after cancer therapy that was diagnosed before 14 years of age. Details of primary cancer diagnosis, treatment received, and current health status of the last 2 visits were assessed from electronic health records. The primary outcome was to estimate the prevalence of chronic health conditions (CHC) among survivors, while the secondary outcome included the impact of the primary diagnosis and various cancer therapies on the occurrence of CHC.
Results: 305 survivors met the inclusion criteria, with a minimum of 5 years of follow-up after completing cancer therapy as of July 2022. Female participants constituted 46% of the cohort. The median follow-up duration was 8.5 (range 5-21) years,with median ages at diagnosis and evaluation of 4 (range 0.16-14) and 14 (range 5-28) years, respectively. Hematological malignancies comprised 65.9%, with leukemia being the most prevalent (49.2%), followed by lymphoma (16.7%), and solid tumors (15.7%). Chemotherapy was administered to 287 survivors (94.1%), while radiotherapy and surgery were used in 29.2% and 22.3%, respectively. Nine patients (3%) required hematopoietic stem cell transplant. Cancer relapse and secondary malignancy were reported in 5.2% and 0.7%, respectively.Approximately 78% of the cohort experienced at least one CHC, with 31.1% and 14.2% having 2 and 3 CHC, respectively. A multivariate logistic regression analysis identified a statistically significant association between CHC and solid tumors compared to hematological malignancies (OR 2.2; 95% CI: 1.1-4.3; p=.023).Growth impairment was the most common CHC, followed by endocrine dysfunction. History of radiotherapy was significantly associated with short stature (95% CI: 1.2-3.6; p=.008).Among the subgroup analysis of 77 survivors, 39 (67.2%) had grade I (mild) disability,19% had grade II (moderate) disability, and 13.8% had grade III (severe) disability.
Conclusion: The estimation oflate effects of childhood cancer among survivors has revealed a prevalent concern. However, the majority of CHC were mild in severity. To optimize health outcomes for survivors, it is essential to minimize cancer therapy without compromising survival rates, implement well-structured and long-term follow-up tailored to individual risk profiles, utilize cost-effective screening methods, and promote prospective clinical research and establishment of a registry.
The LSD1 Inhibitor RN1 Rescues Congenital Dyserythropoietic Anemia Type II
Authors: Yu Lei , Wang Yu , King Richard , Myers Greggory , McGee Beth , Friedman Ann , Balbin-Cuesta Ginette , Lin Zesen , Drysdale Claire , Liu Xiaofang , Kerpet Claire , Deng Kaiwen , Robida Aaron , Engel James , Khoriaty Rami 
Published: December 2024

Congenital dyserythropoietic anemia type II (CDAII) is an autosomal recessive disease resulting from loss-of-function mutations in SEC23B, which encodes a component of coat complex protein II (COPII) vesicles. Mammals express two paralogous genes for SEC23, SEC23A and SEC23B, which encode proteins with ~85% amino acid sequence identity. We have previously shown that the SEC23 paralogs have identical interactomes and that SEC23A overlaps in function with SEC23B. Since the SEC23B/SEC23A expression ratio is disproportionately high in human erythroid cells, we reasoned that the endogenous SEC23A expression level is not sufficiently elevated to compensate for loss of SEC23B in CDAII erythroid cells. Indeed, we demonstrated that increasing SEC23A expression, using CRISPR activation or cDNA expression, completely rescues the SEC23B-null erythroid defect.
In this study, we generated a human erythroid cell line that expresses eGFP from the endogenous genomic locus of SEC23A and performed a small molecule screen to identify compounds that increase the SEC23A-eGFP level. The top compound passing all filters was an LSD1 inhibitor. We validated that LSD1 inhibition dramatically increased SEC23A mRNA and protein levels in primary erythroid cells derived from CD34+ human hematopoietic stem and progenitor cells (HSPCs), at doses that do not impair erythroid cell growth or differentiation. We also showed that LSD1 inhibition rescues the erythroid differentiation defect resulting from SEC23B deletion in primary human erythroid cells.
We validated LSD1 as the target of RN1 by showing that genetic downregulation of LSD1 also led to a profound induction of SEC23A mRNA levels in HPSC-derived erythroid cells. Subsequently, we validated our findings in vivo. We first demonstrated that deletion of Lsd1 in mouse erythroid cells results in increased Sec23a expression. Subsequently, we generated CDAII mice, with inducible deletion of both Sec23b alleles and haploinsufficiency for Sec23a. We showed that RN1 treatment of CDAII mice rescues the erythroid defect observed in these mice. Finally, using CUT&RUN, we found that LSD1 occupies a sequence in the SEC23A promoter, which when mutated, results in increased SEC23A expression and rescue of CDAII.
Taken together, these finding suggest that LSD1 occupies the SEC23A promoter, repressing SEC23A transcription and that in the setting of LSD1 inhibition, SEC23A expression is de-repressed, resulting in CDAII rescue. Therefore, using an unbiased screen, we have identified and validated a novel promising therapeutic strategy for CDAII, using a compound that inhibit LSD1 or a genetic approach based on deleting the SEC23A promoter sequence that is occupied by LSD1.
Cohort Comparison of Therapy-Related Myeloid Neoplasms after CAR T-Cell Therapy, Autologous Stem Cell Transplant, and Standard Cancer Therapies
Authors: Roman Diaz Jaime , Dahiya Saurabh , Sillito Francesca Emily , O'Reilly Maeve , Rejeski Kai , Buecklein Veit L. , Subklewe Marion , Iacoboni Gloria , Barba Pere , Roddie Claire , Locke Frederick , Spiegel Jay Y. , Al Ali Najla H. , Thompson Zachary , Kim Jongphil , Komrokji Rami S. , Jain Michael D. 
Published: December 2024

BACKGROUND
Myeloid neoplasms (TMNs), such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), are an important cause of non-relapse mortality after CAR T-cell therapy. It is not known whether the characteristics and outcomes of TMNs after CAR T-cell therapy differ from those of TMNs occurring after other types of treatment.

METHODS
We collected a multicenter, international cohort of 51 patients diagnosed with MDS (n=36) or AML (n=15) after CAR T-cell therapy for lymphoma or myeloma. Data was gathered on baseline characteristics, disease type, exposure to chemotherapy, radiation exposure, survival, disease risk, and molecular profiles. The characteristics and mutational profiles of this cohort (CAR T) were compared to historical single-institution cohorts of TMN occurring after autologous stem cell transplant (AUTO, n=96) or other standard anti-cancer therapies (STD=244) such as chemotherapy and/or radiation.

RESULTS
The baseline characteristics for the three cohorts of TMN (post-CAR T, post-AUTO, and post-STD) were similar in terms of age, sex, and ethnicity. The time to onset of TMN was significantly shorter post-CAR T than the other cohorts (CAR T 20 months, AUTO 63.6 months, STD 62.1 months, p&lt;0.001). No significant differences between cohorts were noted in terms of baseline IPSS-R risk categories or the frequency of any specific somatic myeloid mutation. TP53 mutations were the most common somatic mutation in all three cohorts (CAR T 47%, AUTO 47%, STD 39%) but were not more frequent in the CAR T cell cohort. Overall survival from the time of TMN diagnosis was significantly shorter in the post-CAR T cell therapy cohort (median OS months for CAR T=9.2, AUTO=24.4, STD=19.2; log-rank p=0.005).

CONCLUSIONS
The time to onset of TMNs is shorter post-CAR T cell therapy compared to post-AUTO or post-other STD cancer therapies. TMNs occurring after CAR T have a similar cytogenetic risk and mutational profile compared to other TMNs, but shorter overall survival from the time of TMN diagnosis. Additional work is needed to understand risk factors, the shorter time of onset, and the particularly poor prognosis of patients experiencing TMN after CAR T cell therapies.
Discovery of BTC-86, a Novel Second-Generation Menin-MLL Inhibitor to Overcome the Acquired Resistance in MEN1 for R/R Acute Leukemia
Authors: Liu Suxing , Hu Weimin , Yang Dexiao , Han Liang , Tong Minghui , Yan Yuna , Chan Shek Ling , Xi Zhiguo , Shi Xuan , Hu Qiyue 
Published: December 2024

The menin-MLL1 interaction is essential for acute leukemias driven by MLL rearrangements (MLLr) or mutations in the nucleophosmin 1 gene (NPM1c). Menin-MLL inhibitor SNDX-5613 (revumenib) has demonstrated robust clinical responses in the clinical trial. However, somatic MEN1 mutations were found at residues M327, G331 or T349 at the revumenib-menin interface in the patients with acquired resistance to menin inhibition and post a major challenge to the management of acute leukemias driven by MLLr or NPM1c. Therefore, developing second-generation inhibitors that block MLL1 binding while having activity against those MEN1 mutations becomes an important strategy to combat acquired resistance to the first -generation menin-MLL inhibitors.
The MMPT (Matched Molecular Pair Transformation) process is used to develop menin-MLL inhibitors. Fluorescence polarization assay is used to assess the impact of BTC-86 on the binding of MLL to wild-type (WT) or mutated menin proteins. Using the MMPT process, we have discovered a novel second-generation menin-MLL inhibitor BTC-86 that has similar binding activity against wild-type menin protein and MEN1 resistance mutations. SNDX-5613 shows notable steric hinderance in the binding pocket of M327I mutant versus that of wild-type menin. Based on the modeling study, BTC-86 can adopt a novel binding mode, which shows little change in its bound position to M327I mutant compared to that of wild-type menin. BTC-86 is the most potent one in inhibition of menin-MLL1 binding against all the MEN1 acquired mutations among all five clinical molecules, including SNDX-5613, JnJ-75276617, and KO-539.
Furthermore, BTC-86 is a potent and highly selective menin-MLL inhibitor in cell viability of multiple leukemia cell lines. BTC-86 shows anti-tumor efficacies in multiple tumor mouse models carrying MLLr or NPM1c, which are correlated with in vivo on-target activity (inhibition of MEIS1 gene expression) and excellent pharmacokinetic properties.
BTC-86 has lower risk in QTc prolongation (IC50 of hERG greater than 30 µM), and has better human metabolic stability than the first-generation menin-MLL inhibitor. Moreover, it is well tolerated in an exploratory rat toxicology study.
In conclusion,BTC-86 is a potent second-generation menin-MLL inhibitor that blocks MLL1 binding while having similar activity against wild-type and mutant MEN1 proteins. IND-enabling study of BTC-86 is in progress. Further studies in clinical setting are warranted to confirm BTC-86 as a second-generation menin-MLL inhibitor for overcoming acquired resistance in MEN1.
Epidemiology and Prognostic Factors of Angioimmunoblastic T-Cell Lymphoma
Authors: Ali Hassan , Desai Krishna , Bajwa Shammas , Bajwa Umair , Faisal Muhammad Salman , Thirumaran Rajesh 
Published: December 2024

Background:
Peripheral T cell lymphomas (PTCL) constitute only 10-15% of non-Hodgkins lymphoma, and is a heterogenous group of lymphomas. Angioimmunoblastic T-cell (AIB-T) lymphoma is a subset of peripheral T cell lymphomas. It is a highly aggressive malignancy originating from follicular subset of mature CD4+ helper T cell, with a high risk of relapse. AIB-T lymphoma commonly present with generalized lymphadenopathy, hepatosplenomegaly or systemic B symptoms. Diagnosed upon biopsy, AIB-T lymphoma is characterized by polymorphic infiltration of lymph nodes and manifest significant proliferation of follicular dendritic cells and high endothelial venules. Treatment options include chemotherapy (often CHOP with or without etoposide) and autologous hematopoietic stem cell transplant.
Method:
Data was collected from Surveillance, Epidemiology and End Result database Research Plus Data, 17 Registries, Nov 2022 Sub (2000-2020). AIB-T lymphoma cases diagnosed including and after the age of 20 years were extracted from the data base using the ICD Code 9705/3. The data was stratified based on age, sex, race, primary site labelled and chemotherapy, and survival curves were compared using the Log-Rank test (GraphPad Prism).
Results:
Total 2536 cases of angioimmunoblastic T-cell lymphoma were identified, of which ~54.85% were males. The neoplasm was most commonly seen in White (66.68%) patients followed by Hispanic (14.08%), Asians/Pacific Islander (10.92%), Black (7.89%) and Alaskans/Native American (0.28%) patients. The median age of diagnosis was 69 years. The incidence rate (per million population) for the general population is around 0.05 per year. When comparing the survival curves, the data was statistically significant for age, with survival progressively tailing off with increasing age (p value &lt;0.0001). The median of survival (mOS) for males was 17 months and females was 25 months (CI:0.619-0.746, HR: 1.159, p 0.0021). Survival analysis based on race and primary site labelled showed no statistical difference. The mOS calculated for chemotherapy was significant for 28 months (with chemo) vs 4 months (without chemo) (p value &lt;0.0001).
Conclusions:
Angioimmunoblastic T-cell lymphoma is a rarely seen malignancy with only 2536 cases reported in the last two decades in SEER database. It has predilection for males, and majority of the cases were reported in Caucasians. Overall superior survival was observed with younger age groups, female gender and treatment with chemotherapy. Race and primary site of origin showed no association with the median of survival. Given its extremely low incidence, more research and analysis is warranted to understand this lesser known malignancy.
Persistent Thrombocytosis, an Interesting Finding in β-Thalassemia Patients Post-Splenectomy in a Tertiary Referral Center in Jordan
Authors: Aburumman Saif , Alesufi Aisheh , Abu Nasrieh Dima , Banihani Haneen , Al Nawaiseh Maram , Abu Lehyah Naser Aldain , Shersheer Qasem 
Published: December 2024

Background
β-thalassemia is a common hematological disorder with defective β-globin production. Splenectomy is one of the common modalities of management in its severe forms where blood transfusion requirements are high. However, various post-splenectomy complications, such as thrombocytosis, warrant further exploration.
Methods
This was a retrospective cohort study conducted on 22 patients with β-thalassemia major who had undergone splenectomy at Al-Bashir Hospital, a tertiary referral center in Jordan, from 2019 to 2021. We analyzed demographic data, clinical outcomes (e.g., blood transfusion requirements and intervals), and laboratory values (e.g., hemoglobin and platelets counts) pre- and post-splenectomy. p-values &lt; .05 were considered significant.
Results
All patients with a mean age of 24.71 ± 8.44 years had persistent thrombocytosis post-splenectomy. The average count of platelets peaked at 965.36 ± 413.50 cells/mm³ immediately post-surgery and fell slightly to 843.23 ± 320.08 cells/mm³ one-year post-splenectomy. Transfusion requirements reduced significantly by 42.49% from an average of 295.95 ± 68.24 ml/kg/y to 170.21 ± 54.65 ml/kg/y (p &lt;.001). The average time interval between transfusions has increased by 60.15% from 17.14 ± 4.49 days to 27.45 ± 10.5 days (p &lt;.001). The hemoglobin level showed a significant increase post-splenectomy, with means of 8.47 ± 1.43 g/dL pre-surgery and 9.65 ± 1.49 g/dL post-surgery. Aspirin was recommended to all patients and hydroxyurea was recommended to those with persistent thrombocytosis over 1 million (n=12) but some refused it (n=5).
Conclusions
This study further underscores the persistent thrombocytosis and reduced transfusion needs in β-thalassemia patients following splenectomy. The results of such findings, therefore, indicate that while splenectomy brings very effective control in transfusion requirements, monitoring thrombocytosis and thrombotic events should always be on the lookout. Generally, it brings out the relevance of adopting tailored management strategies to optimize patient outcomes in β-thalassemia care. Future prospective studies involving larger cohorts with a more prolonged duration of follow-up would be required to confirm these observations and define other late complications following splenectomy.
Inconsistent Reporting and Definition of Time-to-Event Endpoints in CAR T Clinical Trials: A Review of the Literature and a Call for Harmonization
Authors: Grady Connor B , Li Yimei , Maude Shannon L. , Hexner Elizabeth O. , Frey Noelle , Porter David L. , Hwang Wei-Ting 
Published: December 2024

Introduction: Clinical trials evaluating chimeric antigen receptor T-cell therapy (CAR T) commonly report time-to-event (TTE) endpoints. However, definitions are not necessarily comparable across studies and variability can lead to misinterpretation of results or inappropriate comparisons across products and studies. Amid the rapidly increasing number of published CAR T trials-many of which were used for regulatory approval-this study aims to summarize the variation in the use and reporting of TTE endpoints in CAR T trials.
Methods: We include CAR T trials published January 2008-January 2023 on PubMed that reported at least one of these TTE endpoints: overall survival (OS), progression-free survival (PFS), duration of response/remission (DOR), disease-free survival, event-free survival (EFS), relapse-free survival (RFS), time to relapse, time to progression, or time to treatment failure. We abstracted and summarized endpoint definitions, including the time origin, events, competing events, and censoring. We assessed the completeness of endpoint reporting, overall and by subgroups such as study phase, publication year, and the journal's impact factor.
Results: We included 116 publications in the analysis. The most frequently reported TTEs were OS (83%,), PFS (56%), DOR (55%), and EFS (23%). Complete reporting of endpoints was poor overall: 32%, 24%, 25%, and 56% for OS, PFS, DOR, and EFS respectively. Complete reporting was lower in articles published before 2018, in lower impact factor journals, and in phase I trials. There was also a large variability in TTE definitions among those reported. For example, among 64 studies reporting DOR, 48% used the date of response as the time origin while 20% used the date of infusion, and 31% did not report a time origin.
Conclusion: There is substantial heterogeneity and incompleteness of TTE endpoint definitions in CAR T trials reported in the existing literature that could impact the interpretation of the study results. Improving and harmonizing reporting is required to ensure valid assessment of clinical benefit and cross-trial comparison. Complete reporting should include all the following components: time origin, event(s) of interest, competing event(s) if any, and censoring. Recommended definitions for the common TTEs and the rationales will be presented at the meeting.