bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inpatient Outcomes of Laparoscopic Cholecystectomy in Patients with Sickle Cell Disease
Authors: Dave Prashil , Uddin Anwar , Uddin Rahat , Ahad Afgal , Shastri Dipsa , Mahmoud Yasmin , Winer Andrew 
Published: December 2024

Introduction: Cholelithiasis is a common complication in patients with sickle cell disease (SCD), making cholecystectomy one of the most common surgical procedures in this population. Up to 85% of SCD patients develop gallstones by their third decade, and chronic hemolysis caused by the disease can lead to gallstones that block the bile duct. This study aimed to evaluate the outcomes of laparoscopic cholecystectomy in hospitalized patients with SCD using data extracted from a nationwide database.
Methods: The Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) was used to identify adult patients with SCD during 2016 - 2020 using ICD-10-CM codes (D57). ICD-10-PCS codes were used to identify patients who had laparoscopic cholecystectomy procedures. The main outcomes were in-hospital mortality, length of stay (LOS), and hospital costs, and secondary outcomes included acute pancreatitis, chronic pancreatitis, renal cancer, leukemia, lymphoma, Epstein-Barr virus (EBV), gastrointestinal (GI) bleeding, and pancreatic cancer. The association between laparoscopic cholecystectomy and outcomes was evaluated using survey-based multivariate logistic regression models for in-hospital mortality and secondary outcomes, Poisson regression for LOS, and a generalized linear model with gamma distribution and log link for hospitalization cost. Models were adjusted for age, sex, race and ethnicity, primary payer, Charlson comorbidity index, hospital bed size, hospital region, and hospital teaching status.
Results: A total of 899,610 SCD hospitalizations between 2016 and 2020 in the United States were identified, and 4,925 (0.55%) of them had laparoscopic cholecystectomy procedures. Out of 4925, 3620 (74%) patients were &gt;18 years of age, and 3185 (65%) were female. Medicaid was the most common insurance source amongst those who had laparoscopic cholecystectomy (2410, 49%). Inpatient mortality and length of stay were not significantly different in SCD patients with laparoscopic cholecystectomy compared to those without laparoscopic cholecystectomy (inpatient mortality: 0.6% vs 0.6%, adjusted OR: 1.22, 95%CI: 0.55 - 2.72, p = 0.3; length of stay: 4.9 vs 5.1 days, p&lt;0.001). SCD patients with laparoscopic cholecystectomy had an increased cost of hospitalization ($18,673 ± 475 vs $11,789 ± 106, p=0.004). SCD patients with laparoscopic cholecystectomy had increased odds of having acute pancreatitis (13% vs 0.5%, p &lt; 0.001).
Conclusion: This analysis found that inpatient laparoscopic cholecystectomy is infrequent among SCD patients. However, they are associated with higher hospitalization costs and acute pancreatitis diagnoses. Further studies are needed to optimize surgical care in patients with SCD, mainly regarding cost implications, acute complications, and outcomes.
Risk of Depression and Anxiety Post Allogeneic Hematopoietic Stem Cell Transplant in Pediatric Patients with Cancer in a Low-Middle-Income Country (LMIC)
Authors: Boshra Sally , Hafez Hanafy , Hammad Mahmoud , Lehmann Leslie E. , Mohamed Taghreed , Hamdy Nayera , Mosa Ahmed , Elhaddad Alaa 
Published: December 2024

BACKGROUND: Allogeneic Hematopoietic SCT (HSCT) is a potentially curative treatment option in patients with various hematological and lymphatic malignancies. Survival after HSCT has improved over the years but despite the possibility of cure for an otherwise terminal illness, allogeneic HSCT can be accompanied by high levels of morbidity, mortality, and immense psychosocial distress. This is reflected in the significantly increased risk of psychiatric conditions previously described; for example, depression and anxiety following HSCT are reported in 5% to over 40% of patients. However, pediatric patients are not routinely assessed for these complications and the incidence in children is not well understood.
METHODS: Prospective descriptive study assessing pediatric patients undergoing allogeneic HSCT at The Children's Cancer Hospital Egypt for hematologic malignancy from January 2018 to December 2021 and alive at the time of data collection. The primary objective was to assess the prevalence and severity of anxiety and depression post allogeneic HSCT. The secondary objective was to determine potential risk factors related to anxiety and depression.
Anxiety was assessed with the Spence Children's Anxiety Scale and Beck Anxiety Inventory, while Depression was assessed with the Child Depression Inventory and Beck's Depression Inventory. Anxiety and depression were categorized into 2 categories: Non-significant with scores in the normal to mild range and not requiring medical intervention or psychotherapy and Significant with scores in the moderate to severe range and needing medical intervention and /or psychotherapy.
RESULTS: A total of 100 patients were included. The prevalence of Significant anxiety was 35% and significant depression 60%. 27% of patients had both significant anxiety and depression. Among the whole cohort, age (as a continuous variable) was the only significant predictor of anxiety, with increasing likelihood of anxiety as age decreased.
The association with gender, stem cell source, presence of GVHD and time from transplant to test were evaluated and the primary diagnosis was the only significant predictor of depression identified with AML patients having a higher risk, likely due to intensive treatment pre-transplant therapy and long admission periods.
CONCLUSION: The high prevalence of anxiety and depression post allogeneic HSCT in pediatric patients transplanted for hematologic malignancy highlights the need for routine psychological assessment as an essential component of long-term follow-up, particularly in those treated at a younger age and those with a diagnosis of AML.
KEYWORDS: Anxiety, Depression, Allogeneic Hematopoietic SCT, LMICs
Single-Cell Multi-Omics Reveals Immune Characteristics of T Cells in Patients with Relapsed/Refractory Leukemia after Haplo+Cord HSCT
Authors: Li Nainong , Li Hua , Zhang Zheyang , Zhu Ming , Li Xiaofan , Chen Ping , Chen Fei , Chen Xianling , Yang Yiding , Yuan Xiaohong , Tang Ronghan , Zhu Zhijuan , Lin Hongli , Lin Ting , Tong Mengsha , Chen Tao , Zhong Chen , Huang Jialiang 
Published: December 2024

Single-cell multi-omics reveals immune characteristics of T cells in patients with relapsed/refractory leukemia after haplo+cord HSCT
Background:
The treatment of relapsed/refractory leukaemia (R/R) is a significant challenge in medical oncology. Allogeneic haematopoietic stem cell transplantation has been demonstrated as the only cure method ; however, long-term survival rates for patients with R/R leukaemia remain low. Our current study's findings indicate that sequential transplantation of haploidentical stem cell and umbilical cord blood (haplo+cord HSCT) may result in enhanced survival outcomes for patients with R/R leukemia. Nevertheless, the underlying mechanisms remain largely unexplored.
Methods:
A comparative analysis of single-cell gene expression and chromatin accessibility was conducted in bone marrow samples from 16 patients who had undergone haplo+cord or single cord HSCT. Furthermore, flow cytometry was conducted to substantiate our findings.
Results:
Distinct compositions and functions of global immune landscapes were observed, with haplo+cord HSCT exhibiting effective anti-tumour and anti-viral immunity, mediated by type I interferon signalling. The analysis of T cells revealed the presence of a group of CD8+ T cells expressing GNLY and CX3CR1, which were observed to be enriched in recipients of haplo+cord HSCT. This finding was subsequently confirmed by flow cytometry. It is noteworthy that gene signature scoring indicates that haplo+cord-enriched CD8+ T cells possess a dual effector and memory property, which may provide long-term protection. Ultimately, an integrated single-cell multi-omics analysis elucidated the regulatory networks governing lineage-specific gene expression following transplantation. To illustrate, the expression of GNLY in CD8+ T cells enriched in haplo+cord transplants was found to be regulated by an enhancer network situated within a CTCF-mediated chromatin loop.
Conclusions: The collective findings of the single-cell multi-omics analyses demonstrate that CX3CR1+GNLY+ CD8+ T cells, which exhibit effector and memory properties, contributed to the enhanced survival of patients with R/R leukaemia who underwent haplo+cord HSCT.
Targeting YTHDC1 Inhibited the Progression of Mantle Cell Lymphoma By Inhibiting the Expression of MYC Gene through m6A Modification
Authors: Zhou Hui , Wang Li , Yang Ruicheng , Lin Guifeng , Zhang Hailin , Niu Ting 
Published: December 2024

Objective
YTHDC1 (YT521-B homology domain-containing protein 1) is an in vivo nuclear RNA n⁶ -methyladenosine (m6A) reader with YTH domain. At present, YTHDC1 has been found to play an important role in the pathogenesis of various tumors, such as acute myeloid leukemia. However, there are no relevant studies on YTHDC1 in mantle cell lymphoma (MCL). Therefore, this study was to investigate the role and mechanisms of YTHDC1 gene in MCL.
Methods
The expression of YTHDC1 in MCL patients and normal human cells was compared in GEO database. JEKO1 cells with stable knockdown of YTHDC1 were constructed. MTT method, flow cytometry, western blot were used to investigate the effect of YTHDC1 knockdown on proliferation, apoptosis, cell cycle and proteins of apoptosis and G2M phase of cell cycle. MCL subcutaneous tumor model was used to explore the effect of knocking down YTHDC1 in vivo; HE staining and Ki-67 immunohistochemical staining were performed to value the tumor load. RNA-Seq analysis was performed to explore the possible mechanisms of YTHDC1 genes in MCL. MERIP-qPCR and YTHDC1-RIP-qPCR were used to investigate the mRNA level of the target gene of YTHDC1 modified by m6A in MCL. Additionally, qPCR was used to evaluate the mRNA stability of target genes, based on the principle of actinomycin D blocking mRNA synthesis.
Results
The expression of YTHDC1 in MCL was significantly increased compared to normal people. Knocking down YTHDC1 inhibited the proliferation of MCL cells, and promoted cell apoptosis, and leaded the cell cycle arrest at G2M stage, and decreased the expression of apoptosis-related proteins PARP, CASPASE 3 and G2M related proteins CDC25C and CYCLINB 1, while increased the expression of CLEVEAD CASPASE 3. In addition, the tumor growth was decreased and the tumor load was reduced after YTHDC1 was knocked down. There were 3333 differentially expressed genes in sh-YTHDC1 and control cells, including 2178 down-regulated genes and 1155 upregulated genes. The top down-regulated genes included MYC, etc. Enrichment analysis showed that YTHDC1 down-regulated gene may be located in cell membrane, down-regulated cancer pathway, ECM-receptor interaction, etc. Intersection analysis of RNA-Seq data, YTHDC1- iCLIP data and YTHDC1-miCLIP data revealed 174 differentially expressed genes with m6A modification that bind to YTHDC1 in MCL, including MYC. Furthermore, we demonstrated that YTHDC1 regulated the mRNA level of MYC target gene through m6A modification by regulating the stability of MYC mRNA.
Conclusion
The expression of YTHDC1 gene was higher in MCL patients than that in normal people and played a important role in the progression of MCL. Mechanically, YTHDC1 regulated the mRNA level of MYC target gene through m6A modification by regulating the stability of MYC mRNA.
Comparison of the Efficacy and Adverse Effects of Recipient-Derived Versus Donor-Derived CAR-T Cell Therapy for Post-Transplant Relapse in B-ALL
Authors: Liu Lichao , Huang Ruihao , Hu Yongxian , Tu Sanfang , Wang Na , Yi Hai , Gao Qiuying , Zhou Jian , Wang Xiaoqi , Zhang Cheng , Zhang Xi 
Published: December 2024

Background
Chimeric Antigen Receptor T (CAR-T) cells have been demonstrated to be an effective treatment for relapsed acute B-cell lymphoblastic leukemia (B-ALL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells for CAR-T therapy can be derived from the patient's own peripheral blood (recipient) or from the donor's peripheral blood. Despite having identical genomes, the different maturation environments of these T cells can lead to functional differences. This study aims to compare the clinical outcomes of CAR-T cells derived from these two sources.
Methods
This multicenter, retrospective cohort study collected clinical data from 36 patients who experienced B-ALL relapse after allo-HSCT and received CD19 CAR-T cell therapy between January 2016 and October 2023 across seven centers. The primary endpoint was the complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate at 28 days post-CAR-T cell infusion. Secondary endpoints included the 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, incidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and CAR-T cell-related encephalopathy syndrome (CRES).
Results
Retrospective analysis was performed on 36 patients: 12 in the recipient group and 24 in the donor group. The recipient and donor groups showed no significant differences in CR/CRi rates (83.33% vs. 100%, P=0.105), 2-year EFS rates (50.8% vs. 51.6%, P=0.617), and 2-year OS rates (49.5% vs. 63.6%, P=0.215). Additionally, the incidence of GVHD, CRS, and CRES did not significantly differ between the two groups. Further analysis within the donor group revealed 12 matched sibling donors (MSD) and 12 haploidentical donors (HID). The 2-year EFS rate was significantly higher in the HID group compared to the MSD group (75.0% vs. 30.7%, P=0.043), while no significant differences were observed in CR/CRi rates, 2-year OS, and the incidence of GVHD, CRS, and CRES between these subgroups.
Conclusion
Both recipient-derived and donor-derived CD19 CAR-T cell therapies are effective treatment options for B-ALL relapsed post-allo-HSCT. Haploidentical donor-derived CAR-T cells offer a longer EFS and may be considered the optimal choice.
A Phase I/II Study of AZD0305, a Novel Antibody-Drug Conjugate (ADC) Targeting GPRC5D, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Lim Sueh-Li , Augustson Bradley , Mian Hira S , Stadtmauer Edward A. , Iida Shinsuke , Slade Michael , Hazra Saswati , Chamoun Kamal , Cheung Patricia , Saeh Jamal , Shah Nina , Krishnan Amrita Y 
Published: December 2024

Background and Significance: GPRC5D (G Protein-coupled Receptor, Class C, Group 5, Member D) is a known therapeutic target for multiple myeloma (MM). The GPRC5D bispecific T-cell-engager talquetamab was conditionally approved recently by the FDA and EMA for the treatment of RRMM in adults with at least 4 prior lines of therapy. However, there is still a need to explore additional approaches to target this protein without reliance on immune fitness. AZD0305 is a first-in-class ADC that binds specifically to GPRC5D. AZD0305 has shown preclinical activity against MM and has the potential to be active in patients with RRMM who have exhausted or cannot tolerate standard of care options. In addition to payload-mediated cytotoxicity, AZD0305 can potentially drive the killing of tumor cells through antibody-dependent cellular cytotoxicity.
Study Design and Methods: NCT06106945 is a modular Phase I/II, open-label, multicenter, dose escalation, and dose expansion/optimization study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and preliminary efficacy of AZD0305 in patients with RRMM. Module 1 includes Phase Ia (Dose escalation) and Phase Ib (Dose expansion/optimization). The total enrollment is estimated to be approximately 84.
Patients with RRMM &gt;18 years of age, treated with at least 3 prior lines of treatment including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody are eligible. Patients must have measurable disease by IMWG criteria and an ECOG performance status of ≤2. Patients with peripheral neuropathy Grade ≥2, known COPD, or previous history of interstitial lung disease, uncontrolled cardiovascular disease and primary refractory MM are excluded. Further, patients who previously received anti-GPRC5D or MMAE-containing treatment are excluded. The primary endpoints of the phase I include occurrence of dose-limiting toxicities (dose escalation only) and incidence and severity of adverse events and serious adverse events. Secondary endpoints include but are not limited to objective response rate, duration of response, progression free survival, pharmacokinetics of AZD0305 and immunogenicity of AZD0305. This study is currently recruiting patients for phase I in North America, Europe, Asia and Australia.
An Investigator Initiated Study of RCHOP in Combination with Selinexor (KPT-330) in Diffuse Large B Cell Lymphoma and Richter Transformation
Authors: Modi Dipenkumar , Yang Jay , Kim Seongho , Azmi Asfar , Tolksdorf Emily , Houde Christiane A. , Zonder Jeffrey A. 
Published: December 2024

Background and Significance: Rituximab-containing chemoimmunotherapy remains standard front-line treatment for newly diagnosed diffuse large B cell lymphoma (DLBCL) including Richter transformation (RT). Approximately 70% of patients with DLBCL achieve durable remission with this approach. Patients with RT, however, frequently experience shorter remissions. Therefore, novel strategies are warranted to improve outcomes of these patients. Selinexor is a first in class, slowly reversible, potent and selective inhibitor of nuclear export (SINE) compound that specifically blocks exportin 1 (XPO1) and is approved for relapsed refractory DLBCL after ≥2 prior lines of therapy. We hypothesize that combination of Selinexor and RCHOP may improve outcomes of newly diagnosed DLBCL and RT.
Study Design and Methods: This was a phase I/II investigator-initiated dose escalation/dose-expansion study to evaluate the safety and tolerability of selinexor when combined with RCHOP. Phase I cohort included B-non-Hodgkin lymphoma and the RP2D of selinexor was determined to be 60 mg weekly (Seymour et al, 2021). Currently phase II expansion cohorts are enrolling. Key eligibility criteria for phase II expansion include patients ≥18 years of age with newly diagnosed advanced stage III-IV DLBCL (Group A) or RT (Group B), ECOG PS £1, and FDG avid measurable disease by PET. Patients with RT could receive prior non-anthracycline-based CLL treatment. All patients will receive selinexor orally on days 1, 8, 15 during each 21-day cycle for a total of 6 cycles along with standard dosing of RCHOP. Patients with response (partial or complete remission) at the end of 6 cycles will receive optional maintenance selinexor for 1 year. Maintenance selinexor will be given once a week on days 1, 8, 15, 22 in a 4-week cycle (1 cycle=28 days).
The primary objective of phase II expansion is to estimate 2-year progression-free survival (PFS) for group A, and overall response rate (ORR) for group B. Exploratory objective will evaluate association of baseline XPO-1 expression with response and outcomes after therapy. For group A, we expect to enroll 31 participants with DLBCL in the phase II expansion cohort. This design will provide 80% statistical power and a one-sided 5% type I error to assess a 2-year PFS greater than 55%. For group B, we will enroll 7 participants per the Simon's first stage of the study. If ³ 4 participants have an ORR by 12 weeks, an additional 13 participants will be enrolled for a total of 20. If at least 12 of 20 have an ORR by 12 weeks, it will be concluded that there is sufficient evidence of efficacy, that the ORR is at least 40%. The study is currently enrolling. The clinicalTrials.gov ID is NCT03147885.
Efficacy and Safety of Mesenchymal Stem Cells in Improving Thrombocytopenia after Chemotherapy in Malignant Tumors
Authors: Guo Bingling , Li Jieping , Liu Yao 
Published: December 2024

INTRODUCTION
Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cytotoxic chemotherapy and targeted therapies, which always contributes to morbidity and poor overall survival. There are limited therapies to prevent or treat CIT. Mesenchymal stem cells (MSC) are immunogenic multipotent stem cells derived from the mesoderm with self-renewal and multi-directional differentiation potential. They have the ability of self-replication and multi-directional differentiation potential. They not only provide mechanical support for hematopoietic stem cells in the bone marrow, but also can secrete a variety of growth factors to support hematopoietic function. It has long-term hematopoietic support function. We have explored the application of MSC to patients with CIT to improve platelet levels and reduce bleeding-related complications.
METHODS
We screened out 25 patients who met the CIT criteria and whose platelet count was lower than 50×10^9/L. We recorded the age, gender, tumor type, stage, whether there was combined bone marrow invasion, the number and efficacy of previous treatment lines, the condition of bone marrow hyperplasia before chemotherapy, whether CIT occurred previously, and the lowest platelet count during previous chemotherapy.We conducted a therapy for CIT patients with mesenchymal stem cells to evaluate the efficacy and safety. Patients received therapies: mesenchymal stem cells（1×10^6/u, once a week, continuous for 4 weeks as a course）.
RESULTS
27 patients（F:M=13:14）with CIT had received MSC at least once, 18 of which were solid tumors, and 9 hematologic neoplasms. The median age of the patients was 58 years (24-80y). The lowest platelet level was 1×10^12/L. With MSC therapy, median treatment cycles were 1.75 cycles（7 times）. After MSC therapy, platelet levels increased in 23 patients（85%）, and the mean increase of platelet levels was 32×10^12/L. No treatment-relevant adverse reactions.
CONCLUSIONS
Our results show that MSC is a safe and effective method for CIT patients both in solid tumors and hematologic tumors. It indicates that the achieve efficient effectively improves the platelet level of patients with CIT, reduces the risk of bleeding and the frequency of blood transfusion, and without significantly increasing toxicity.