bluuebunny/crossref_metadata_2025_split huggingface dataset:
The perception of HIV self-testing and willingness to use mHealth for HIV prevention among Black men who have sex with men in Iowa, United States: A qualitative study
Authors: Badru Oluwaseun Abdulganiyu , Adeagbo Oluwafemi Atanda 
Published: December 2024

Objective The World Health Organization approved HIV self-test (HIVST) to break the barriers to HIV testing. Black men who have sex with men (Black MSM) in the United States are less likely to test for HIV or link to care due to several factors, such as stigma and distance. We explored Black MSM's knowledge of HIVST and their willingness to use a mobile application (mHealth) to link to HIV care and engage with health providers. Methods Between March and September 2023, we interviewed 12 Black MSM in small urban areas and explored HIVST awareness and willingness to use mHealth. Participants were recruited through purposive and snowball sampling. The data were analyzed inductively. Results The age range was 20–42 years. Participants had mixed knowledge of HIVST. The barriers to HIVST uptake are poor knowledge of HIVST, lack of adequate medical insurance to access HIVST kits, and concerns about the efficacy of HIVST kits. Black MSM were willing to link to care via mHealth but expressed concerns related to safety, confidentiality, and the risk of HIV stigma. Participants recommended wider awareness via social media and that the proposed mobile application has a simple interface for ease of use. Conclusion To encourage uptake among Black MSM, the Iowa Department of Health and Human Services should make HIVST accessible (low-cost or free). The proposed mHealth should be developed with a simple and interactive interface, including images and videos to guide HIVST and linkage to health professionals for assistance.
Development and Implementation of a Clinical Nursing Practice Guideline for Prevention and Management of Increased Intracranial Pressure in Hemorrhagic Stroke Patients
Authors: Sirisaen Kannika , Chaiviboontham Suchira , Phornsuwannapha Surachest 
Published: December 2024

Background Hemorrhagic stroke is a serious condition that leads to high morbidity and mortality rates, particularly within the first 30 days following the stroke. One serious complication is increased intracranial pressure (IICP), which worsens neurological symptoms and can result in death or disability. Purposes To develop and implement a clinical nursing practice guideline (CNPG) for prevention and management of IICP in hemorrhagic stroke patients. Methods This study had two phases: (1) Evidence trigger and support, identifying clinical problems and gathering empirical evidence, and (2) Evidence-observed, where a CNPG was developed and implemented. The CNPG was based on the Nursing Role Effectiveness Model and Soukup's Nursing Practice Development Model, covering preoperative and postoperative care and key nursing activities such as assessment, prevention, and management. The study assessed the CNPG's impact on nurses’ knowledge, practices, and implementation feasibility. Nineteen registered nurses from the Surgical Intensive Care Unit were included and analyzed using descriptive statistics, interquartile range, and the Wilcoxon signed-rank test. Results The findings showed a significant improvement in nurses’ mean knowledge scores after implementing the nursing guideline for preventing IICP in hemorrhagic stroke patients ( p < 0.000). The overall mean knowledge score was high (X̄ = 23.11, SD = 2.54, Mdn = 23, IQR = 5). Additionally, the total mean nursing practice score (X̄ = 122.53, SD = 17.80) and overall mean perceived implementation feasibility score were both high (X̄ = 4.68, SD = .35). Conclusions The findings suggest that integrating nursing practice guidelines and providing training to enhance nurses’ knowledge significantly contribute to positive outcomes in both structure and process. Regarding structure, nurses demonstrated increased knowledge and proficiency in nursing practices. Regarding process outcomes, evidence-based guidelines were effectively utilized, paving the way for practical application in future nursing practice.
Centella asiatica improves cognitive function and alters the hippocampal metabolome of aged Tg2576 and wild-type mice
Authors: Matthews Donald G , Khorani Mona , Bobe Gerd , Caruso Maya , Magana Armando Alcazar , Gray Nora E , Quinn Joseph F , Stevens Jan F , Maier Claudia S , Soumyanath Amala 
Published: December 2024

Background:  Alzheimer's disease (AD) is a growing public health problem in the aging population, with limited treatment options. We previously reported that Centella asiatica herb water extract (CAW) attenuates cognitive decline in murine models of AD and aging. Objective:  To explore changes in the hippocampal metabolome associated with CAW's modulation of cognitive function and amyloid-β (Aβ) plaque load in aged Tg2576 and wild-type (WT) mice. Methods:  We compared cognitive function, hippocampal Aβ plaque burden, and hippocampal metabolite profile in 20-month-old Tg2576 female mice and their WT littermates following 3–5 weeks treatment with CAW (0, 200, or 1000 mg/kg/d p.o.). Cognitive testing included contextual fear response (CFR) and novel object recognition task (NORT). Aβ plaque burden was measured via immunohistochemistry. Metabolomic profiles of mouse hippocampi were obtained using liquid chromatography coupled with high resolution tandem mass spectrometry. Results:  CAW treatment resulted in dose-related improvements in CFR and NORT performance of Tg2576 and WT mice. However, while CFR correlated with neurosignaling and glycosylated ceramide levels, NORT performance correlated with lysophosphatidylcholines and oxidized metabolites, and Aβ accumulation was linked to elevated excitatory and suppressed inhibitory neurotransmission. Only a subset of the metabolite changes induced by CAW in Tg2576 mice represented a reversal of metabolite differences between Tg2576 and WT mice, suggesting the involvement of other pathways in CAW's cognitive effects. Conclusions:  Mechanisms underlying CAW's cognitive effects extend beyond reversing metabolic effects of Aβ accumulation. The data support the potential use of CAW to manage memory challenges in aged individuals with or without AD.
Single-Cell and Spatial Transcriptomics Link Malignant T Cells to Macrophages in the Tumor Immune Microenvironment of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma
Authors: Wang Jinuo , Zhang Zhongmin , Cheng Fei , Wu Wenjun , Wang Zhaoming , Tian Luyi , Cai Zhen 
Published: December 2024

Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and highly aggressive disease that most reported in Asia. However, the specific mechanisms and factors within the tumor microenvironment (TME) that drive this malignant disease remain largely unknown. In this study, we performed a comprehensive analysis of TME in patients with MEITL by single-cell RNA sequencing and spatial transcriptomic, which might help further elucidate the tumor biology and gain an insight to treatments beyond chemotherapy and transplantation.
Methods: A retrospective analysis of the clinical features and pathological data of 20 patients with MEITL treated at the First Affiliated Hospital of Zhejiang University School of Medicine from January 2019 to October 2023 was conducted. Four samples from 4 representative patients were subjected to single-cell RNA sequencing and spatial transcriptomic analysis.
Results: Among the 20 patients with MEITL, there were 13 males and 7 females, with a median age of 55.2 (16-75) years. Nineteen cases (19/20) had lesions located in the jejunum or ileum. Abdominal pain, diarrhea, and fatigue were the main clinical symptoms, with intestinal perforation as the main complication. Immunohistochemistry results showed that most monomorphic epitheliotropic intestinal T-cell lymphoma tumor cells were positive for CD3 (20/20), CD8 (17/20), and CD56 (19/20) expression, while negative for CD5 (19/20) and EBER (18/20) expression. 17 patients died during follow-up due to disesae progression or infection secondary to interstital disease. The estimated one-year OS were 10%. Analysis of single-cell and spatial transcriptomic data revealed that various cells, including MEITL tumor cells, intestinal epithelial cells, and macrophages, were distributed in the intestinal pathological tissue. NK cells were absent among TEM of MEITL. The tumor cells maintain the phenotypes of both T and NK cells. There was a high degree of spatial correlation between tumor cells and macrophages. Further differential gene enrichment analysis of macrophages revealed a positive spatial correlation between tumor cells and M1 macrophages, while the numbers of M1 macrophages under high power field were also related to patients' survival.
Conclusions: Monomorphic epitheliotropic intestinal T-cell lymphoma has an insidious onset, often presenting with acute abdomen, and has a very poor prognosis. According to single-cell sequencing and spatial transcriptomic results, the TME of MEITL is complex with various cells while in absence of NK cells. The high spatial correlation between tumor cells and macrophages suggests the underlying interactions of these two cells during the pathogenesis of MEITL.
Complications of Modern Immunotherapy (CAR-T and BsAb), a Single Centre Experience
Authors: Sokolova Tereza , Zavrelova Alzbeta , Belada David , Zak Pavel , Radocha Jakub 
Published: December 2024

Introduction: immunotherapy represents a revolutionary therapeutic approach in the current era of malignant disease treatment. However, this therapy has its own pitfalls and risks, including immune complications such as Cytokine Release Syndrome (CRS), Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), immunosuppression and subsequent infections.
Aim: The analysis aimed to evaluate the incidence of infectious and immune complications (CRS, ICANS) in patients treated with modern immunotherapy (Chimeric Antigen Receptor T-Cell Therapy (CAR-T) and bispecific antibodies (BsAb) of the antiCD20 and antiBCMA/GPRC5D groups), to compare the findings across agents and to detect IgG antibody levels along with the incidence of infectious complications.
Methods. This was a retrospective analysis of all incomers treated with BsABs and CAR-T. Data were extracted from the hospital information system.
Results. Eighteen patients were treated with CAR-T (here (14/18) 77.8% with a diagnosis of non-Hodgkin's lymphoma (NHL), (4/18) 22.2% with a diagnosis of multiple myeloma (MM)) and 63 patients were treated with BsAb (here (38/63) 60.3% with a diagnosis of NHL, (25/63) 39.7% with a diagnosis of MM). The target antigen was BCMA/GPRC5D in 35.8%, CD20 in 46.9% and CD19 in 17.3%. The overall incidence of CRS was 63%, with a maximum severity of grade 2, in 21% of patients, and with the most significant prevalence in CAR-T, 94.5%. The incidence of ICANS was observed in 38.9% of patients, exclusively with CAR-T therapy for B-NHL. Infectious complications were observed in 74.1% of patients overall, with a median incidence of 79 days after therapy. The most common type of infection, given the epidemiological situation, was COVID-19 (44%), followed by respiratory infections (30%), urinary infections (3%), sepsis (8%), aspergillosis (2%), and unspecified infections (13%). Any grade infection was observed in both BsAb groups (antiBCMA/GPRC5D and antiCD20) with an overall proportion of infectious complications (88% vs. 81.6%) and a similar proportion of each grade (grades 3-5: 32% vs. 31.6%). The median IgG concentration at 3 months post-treatment was 3.65 g/L in the antiBCMA/GPRC5D BsAb group, 3.13 g/L in the CAR-T group and 5.15 g/l in the antiCD20 BsAB gourp. Percentage of patients indicated for substitution across immunotherapy groups; antiBCMA/GPRC5D BsAb (76%), CAR-T (38.9%), antiCD20 BsAb (21.1%).
Conclusion: Infectious complications remain a significant source of morbidity and mortality in patients treated with modern immunotherapy. Patients treated with antiCD20 and antiBCMA/GPRC5D showed different levels of IgG antibodies, but the observed incidence of infectious complications was similar in both types.
Study on Clinical and Laboratory Characteristics of Acute Erythroid Leukemia with EPOR Amplification
Authors: Fu Wenjing , Zhang Qiguo , Gong Wenyu , Bao Wenqiang , Xu Shiyun , Ling Chun , Jin Qichuan , Chen Bing 
Published: December 2024

Objective: To enhance the understanding of acute erythroid leukemia (AEL) with erythropoietin receptor (EPOR) amplification and to improve its precise diagnosis and individualized treatment strategies.
Methods: A thorough analysis of the clinical and laboratory characteristics of two cases of de novo acute erythroid leukemia were performed and literatures were reviewed.
Results: Case 1: A 57-year-old male presented with dizziness and fatigue for one week. The proportion of erythroblasts in bone marrow aspirations was 3.2%, 40.5%, and 55% in three separate punctures, with proerythroblasts accounting for 18.4%, 23.5%, and 41% respectively. Bone marrow biopsy showed extremely hypercellular areas, with up to 80% erythroblasts in focal areas, predominantly proerythroblasts. Flow cytometry revealed that approximately 14.72% of cells were erythroblasts expressing CD36, CD117, CD33, and partially CD13. The granulocyte proportion was relatively normal. Chromosome analysis revealed a complex karyotype, and only a TP53 gene c.559+2T&gt;G splice site mutation was detected using myeloid neoplasm-related gene mutation panel, with a VAF of 35.0%. FISH analysis showed no deletion of the TP53 gene. The diagnosis of acute erythroid leukemia was made, and the patient received two courses of decitabine plus arsenic trioxide and decitabine alone. However, bone marrow examination showed no remission, and the patient had a complex karyotype with clonal evolution, resulting in a survival of 3 months.
Case 2: An 80-year-old male presented with chest tightness, dyspnea, and fatigue for 10 days. Bone marrow aspiration showed hypercellular marrow, with 94% erythroblasts, including 35% proerythroblasts, 52% basophilic erythroblasts, 5.5% polychromatophilic erythroblasts, and 1.5% orthochromatic erythroblasts. Flow cytometry revealed that approximately 11.69% of nucleated cells were blast/early erythroid cells expressing CD33, CD117, CD36, CD71, and CD105. Chromosome analysis showed a complex karyotype. Myeloid neoplasm-related gene mutation panel showed TET2 mutation (+), TPMT mutation (+), and a TP53 p.K132E missense mutation with a VAF of 59.4%. Copy number variation (CNV) analysis revealed EPOR amplification and IKZF gene deletion. The patient survived for 7 days.
Conclusion: The proportion of erythroblasts in bone marrow smears of acute erythroid leukemia can be underestimated due to aspiration dilution, emphasizing the importance of bone marrow biopsy pathology combined with immunohistochemistry. Acute erythroid leukemia with EPOR amplification exhibits more significant erythroblast proliferation and a more aggressive clinical course.
FLAG/IDA/Venetoclax Induction in Patients with FLT3+ Acute Myeloid Leukemia
Authors: Abdelmessieh Peter , Ridgway Forrest , Shestovska Yuliya , Khanal Rashmi , Styler Michael , Ojala Anne , Ballas Brittany , Sorrentino Michele , Varshavsky-Yanovsky Asya , Fung Henry C. 
Published: December 2024

Introduction
Induction chemotherapy (IC) in acute myeloid leukemia (AML) in younger and fit patients has combined an anthracycline (i.e., daunorubicin or idarubicin) with the antimetabolite, cytarabine. This is termed the 7 + 3 regimen. Response rates with this standard regimen approach 70-80%, but 30-40% of patients eventually relapse. Patients with FLT3 mutations have had poorer outcomes, however, the RATIFY trial, and more recently the QuANTUM-FIRST study, have shown that adding a targeted FLT3 inhibitor to the standard back bone of the 7+ 3 regimen improved response rates and overall survival. MD Anderson published a phase II study in which venetoclax was added to the standard anthracycline/cytarabine induction regimen of fludarabine, cytarabine, G-CSF, and idarubicin (FLAG-IDA/venetoclax). Results from this study showed an impressive 96% response rate for newly diagnosed (ND) AML patients. Based on these results, Fox Chase Cancer Center adopted this approach. Although this phase II study did include patients with FLT3, no studies have looked at outcomes with this protocol in patients with FLT3 mutations.
Methods
Patients between 2020 and 2024 who were treated with induction FLAG-IDA/venetoclax for AML, based on ELN 2022 criteria, were retrospective reviewed. Patients that had FLT3-ITD or TKD mutations were included in this review. All patients after induction either proceeded directly to allogenic stem cell transplant or proceeded to receive consolidation that included a FLT3 inhibitor.
Results
Overall, 9 patients were included in this study. Induction with FLAG-IDA/venetoclax lead to a 100% (N = 9/9) complete response rate on recovery marrow results per IWG criteria and FLT3 PCR negativity. MRD testing was not performed. There were no patient deaths during induction. Twenty-two percent (N=2/9) of patients relapsed despite receiving FLT3 directed therapy during the consolidation phase of their treatment. Data on long-term survival will require longer followup however thus far only 2 patients have had relapse. All patients were able to complete their induction course with no grade 3 or 4 cardiac events.
Conclusions
Based on our small review, FLAG-IDA/venetoclax appears to be an effective induction therapy for FLT3+ AML. Although the current standard of care for FLT3+ AML should include targeted therapy with FLT3 directed agents, this review shows it is not necessarily needed with induction. This is not surprising considering the combination of hypomethylating agents and venetoclax also showed excellent response rates. Adding FLT3+ inhibition to FLAG-IDA/venetoclax would be a promising study to explore in a phase I setting.
Multiple Supratherapeutic Doses of Iptacopan 400 Mg Twice Daily Are Well Tolerated in Healthy Participants: Safety Findings from a Randomized, Participant-Blinded, Placebo-Controlled, Phase I Study
Authors: Schmouder Robert L , Hackling Melissa , Shah Bharti , Bellibas S. Eralp , Kulmatycki Kenneth 
Published: December 2024

Background: Iptacopan, the first oral proximal complement inhibitor that targets factor B to selectively inhibit the alternative pathway of the complement system, is approved as a monotherapy for adults with paroxysmal nocturnal hemoglobinuria and is being investigated in diseases such as immunoglobulin A nephropathy, C3 glomerulopathy and atypical hemolytic uremic syndrome. Iptacopan is administered at a therapeutic dose of 200 mg twice daily (bid). A Phase I, randomized, participant-blinded, placebo-controlled study (A2109) is being conducted to assess the safety, pharmacokinetics and pharmacodynamics of multiple supratherapeutic oral doses of iptacopan (400 mg and 800 mg bid) in healthy volunteers.
Aim: To report the safety findings from the completed Cohort 1 of the ongoing A2109 study, in which healthy participants received multiple 400 mg bid supratherapeutic doses of iptacopan or placebo.
Methods: Healthy individuals aged between 18 and 55 years were enrolled into Cohort 1 and were randomized 2:1 to receive iptacopan 400 mg bid or matching placebo. There was a 28-day screening period, a 14-day treatment period and a 5-day post-treatment washout period. The primary endpoint was safety, including adverse event (AE) reportings, vital signs, electrocardiogram (ECG) assessments and safety laboratory evaluations. Pre-dose safety data were collected at screening and baseline. On treatment, safety laboratory evaluations were performed on Days 2, 3, 7, 10, 14, 15, 16, 18 and 19; vital signs were measured daily; and ECG assessments were done on Days 1, 4, 7, 10, 14 and 19.
Results: Twelve healthy volunteers were enrolled into Cohort 1; 8 received iptacopan 400 mg bid and 4 received placebo.Two participants in the iptacopan arm had AEs during the treatment period; 1 had moderate headache and the other had a mild AE of elevated amylase levels. These 2 AEs were considered related to iptacopan; however, both resolved without the need for additional treatment. No participants discontinued iptacopan. One individual receiving placebo had 5 mild AEs during the treatment period (chills, bilateral hand pain, sensation of feeling flushed, headache and bilateral sclera erythema), which resolved without the need to discontinue treatment. The other 3 participants who received placebo had no AEs. During iptacopan treatment, there was no evidence of an effect on any laboratory parameter (including red or white blood cell count), ECG parameter or vital sign (including heart rate and blood pressure), and there was no adverse impact on liver, kidney or thyroid function.
Conclusions: Multiple supratherapeutic doses of iptacopan 400 mg bid for 14 days were well tolerated in healthy individuals. Based on these results, the study will progress to assess iptacopan 800 mg bid in Cohort 2.
Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Prediction of Allogeneic Hematopoietic Stem Cell Transplantation Outcomes of Patients with Hematologic Malignancies
Authors: Thammahong Arsa , Wudhikarn Kitsada , Bunworasate Udomsak , Chanswangphuwana Chantiya 
Published: December 2024

Background: Myeloid-derived suppressor cells (MDSCs), which include polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs), are known to suppress immune responses. Research on MDSCs following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological malignancies is limited. This study aimed to characterize MDSCs and their pattern of immune reconstitution, as well as to explore the association between MDSCs and allo-HSCT outcomes in patients with hematologic malignancies.
Methods: Forty-one patients who underwent allo-HSCT at King Chulalongkorn Memorial Hospital from 2021 to 2023 were included. MDSCs were identified in whole blood using immunophenotyping with flow cytometry. Signature cytokines were measured using the Luminex assay. The percentage of MDSCs among total CD45 positive cells and cytokine levels were analyzed in relation to transplantation outcomes.
Results: Among the 41 patients, the median age was 44 years (range: 18-62), and they were diagnosed with acute myeloid leukemia (41.46%), acute lymphoid leukemia (36.59%), myelodysplastic syndrome (7.32%), myeloproliferative neoplasm (12.20%), and lymphoma (2.44%). Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (82.93%) and haploidentical donors (17.07%). Thirty-seven patients (90.24%) received myeloablative conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitors plus methotrexate (68.29%) and post-transplant cyclophosphamide (31.71%). The median follow-up time was 188 days. Acute GVHD (aGVHD) occurred in 9 (21.95%) patients with a median onset time of 31 days, with only two patients experiencing grade II-IV aGVHD. The percentage of PMN-MDSC at day+14 and day+28 was significantly lower in aGVHD patients compared to non-GVHD patients (day+14: 0.0052% vs. 0.193%, p=0.003; day+28: 0.061% vs. 0.197%, p=0.018). Similarly, the CXCL2 level (a PMN-MDSC cytokine) was significantly lower in aGVHD patients. M-MDSC percentage and interleukin-10 (an M-MDSC cytokine) at day+28 were also significantly lower in aGVHD patients compared to non-GVHD patients (0.143% vs. 0.431%, p=0.023; 15.45 pg/ml vs. 25.07 pg/ml, p=0.011). Cytomegalovirus (CMV) reactivation was observed in 48.78% of patients, associated with increased M-MDSC at day+14 and decreased PMN-MDSC at day+14. For GVHD-free, relapse-free survival (GRFS) analysis, patients with high PMN-MDSC (≥0.15%) at day+14 had better outcomes than those with low PMN-MDSC (&lt;0.15%) (95% CI: 1.102-9.706, p=0.030).
Conclusion: Delayed reconstitution of MDSCs at day+14 and day+28 post-allo-HSCT is associated with aGVHD occurrence. MDSCs could serve as potential surrogate markers for predicting aGVHD and CMV reactivation.