bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collaborating with cancer patients and informal caregivers in a European study on quality of life: protocol to embed patient and public involvement within the EUonQoL project
Authors: Engelaar Merel , Bos Nanne , van Schelven Femke , Lorenzo i Sunyer Nora , Couespel Norbert , Apolone Giovanni , Brunelli Cinzia , Caraceni Augusto , Ferrer Montse , Groenvold Mogens , Kaasa Stein , Ciliberto Gennaro , Lombardo Claudio , Pietrobon Ricardo , Pravettoni Gabriella , Sirven Aude , Vachon Hugo , Gilbert Alexandra , Rademakers Jany 
Published: June 2024

Abstract
Background
Patient and public involvement (PPI) has become an essential part of health research. There is a need for genuine involvement in order to ensure that research is relevant to patients. This can then improve the quality, relevance, and impact of health research, while at the same time reducing wasted research and in doing so bringing science and society closer together. Despite the increasing attention for this involvement, it is not yet common practice to report on proposed activities. An article reporting planned PPI could provide guidance and inspiration for the wider academic community in future activities. Therefore, this current article aims to describe the way in which PPI principles are incorporated in the research project called “Quality of Life in Oncology: measuring what matters for cancer patients and survivors in Europe (EUonQoL).” This project aims to develop a new set of questionnaires to enable cancer patients to assess their quality of life, entitled the EUonQoL-Kit.

Methods
The first step is to recruit cancer patients and their informal caregivers as co-researchers in order to train them to collaborate with the researchers. Based on their skills and preferences, they are then assigned to several of the project’s work packages. Their individual roles, tasks, and responsibilities regarding the work packages, to which they have been assigned, are evaluated and adapted when necessary. The impact of their involvement is evaluated by both the researchers and co-researchers.

Discussion
PPI is a complex and dynamic process. As such, the overall structure of the research may be defined while at the same time leaving room for certain aspects to be filled in later. Our research is, we believe, relevant as co-researcher involvement in such a large European project as EUonQoL is a new development.
The complete mitochondrial genomes of five critical phytopathogenic Bipolaris species: features, evolution, and phylogeny
Authors: Song Xinzheng , Geng Yuehua , Xu Chao , Li Jiaxin , Guo Yashuang , Shi Yan , Ma Qingzhou , Li Qiang , Zhang Meng 
Published: June 2024

AbstractIn the present study, three mitogenomes from the Bipolaris genus (Bipolaris maydis, B. zeicola, and B. oryzae) were assembled and compared with the other two reported Bipolaris mitogenomes (B. oryzae and B. sorokiniana). The five mitogenomes were all circular DNA molecules, with lengths ranging from 106,403 bp to 135,790 bp. The mitogenomes of the five Bipolaris species mainly comprised the same set of 13 core protein-coding genes (PCGs), two rRNAs, and a certain number of tRNAs and unidentified open reading frames (ORFs). The PCG length, AT skew and GC skew showed large variability among the 13 PCGs in the five mitogenomes. Across the 13 core PCGs tested, nad6 had the least genetic distance among the 16 Pleosporales species we investigated, indicating that this gene was highly conserved. In addition, the Ka/Ks values for all 12 core PCGs (excluding rps3) were < 1, suggesting that these genes were subject to purifying selection. Comparative mitogenomic analyses indicate that introns were the main factor contributing to the size variation of Bipolaris mitogenomes. The introns of the cox1 gene experienced frequent gain/loss events in Pleosporales species. The gene arrangement and collinearity in the mitogenomes of the five Bipolaris species were almost highly conserved within the genus. Phylogenetic analysis based on combined mitochondrial gene datasets showed that the five Bipolaris species formed well-supported topologies. This study is the first report on the mitogenomes of B. maydis and B. zeicola, as well as the first comparison of mitogenomes among Bipolaris species. The findings of this study will further advance investigations into the population genetics, evolution, and genomics of Bipolaris species.
Myopericarditis revealing a systemic sclerosis-systemic lupus erythematosus overlap syndrome complicated by fatal cytomegalovirus infection: a case report
Authors: Bennani Ghali , Zahri Soukaina , Boulahnach Anas , Drighil Abdenasser , Habbal Rachida 
Published: June 2024

Abstract
Background
Systemic sclerosis (SSc)-systemic lupus erythematosus (SLE) overlap syndrome is rarely described in the literature, and its morbidity and mortality remain high after the early onset of pulmonary arterial hypertension (PAH), which determines its severity. The epidemiology of SSc-SLE overlap syndrome is not well known. It is characterized by high clinical polymorphism, making its diagnosis difficult. Through this case, we underline the difficulty and delay in the diagnosis of this syndrome in a country with limited resources, as well as the difficulty of its management given the specificity of the treatment for each pathology and the risk of infections, which could limit their use.

Case presentation
We report the case of a 49-year-old North African female patient, initially followed for SSc for 8 years, whose diversity of symptoms masked the distinct disease. Indeed, her initial clinical presentation was in favor of SSc, but the discovery of a pericardial effusion stimulated us to carry out more investigations and correct the initial diagnosis. The involvement of the myocardium and pericardium, as well as the positive antibody serology tests, make it possible to retain the diagnosis of SSc-SLE overlap syndrome. Despite the introduction of treatment, the patient unfortunately died a month later after developing a multi organ failure following an opportunistic infection.

Conclusions
The management of SSc-SLE overlap syndrome can be complex, requiring good knowledge of these two pathologies, especially in immunocompromised patients with complications. Treatments based on corticosteroids and immunosuppressants may differ from one case to another, making their use difficult in a patient developing a cytomegalovirus (CMV) infection. These patients require urgent treatment before the onset of complications, at the risk of worsening the prognosis, with close collaboration between a cardiologist and an internist, given the multisystem involvement.
Long-term efficacy of high-dose imatinib in Hispanic patients without access to second-generation tyrosine kinase inhibitors treated in LATAM centers.
Authors: Dorsey Trevino Edgar , Cantu-Rodriguez Olga Graciela , Osorno-Rodriguez Karen Lorena , Gutierrez-Aguirre Cesar Homero , Jaime-Perez Jose Carlos , Gomez-Villarreal Juan Pablo , Rios-Rodelo Miguel Ricardo , Gonzalez-Cantu Graciela Alejandra , Contreras-Arce Alan , Gomez-Almaguer David 
Published: June 2024

6512 Background: Treatment for patients with chronic myeloid leukemia (CML) had a benchmark with the introduction of imatinib, a tyrosine kinase inhibitor (TKI). Nevertheless, resistance due to genetic mutations in the BCR::ABL1 kinase receptor remains relatively common for many patients, leading to failure, lack of response, or suboptimal response. Ideally, to bypass genetic resistance, guidelines recommend switching to a second-generation TKI, but for many developing countries, socioeconomic barriers hinder the possibility of switching medication. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. Methods: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to standard-dose imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights and depicted the survival curves and median using the Kaplan-Meier estimator. Our primary outcome was overall survival (OS) at 150 months, defined as the number of deaths once patients had reached treatment response based on parameters of the European Leukemia Net Guidelines for CML. Our secondary outcomes were disease-free survival (DFS) at 150 months, defined as the number of months after patients achieved either major molecular response or deep molecular response, and adverse events that included gastrointestinal, dermatologic, hematologic, and others. Results: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. While we found no difference in the 150-month risk in both OS and DFS (Table), patients receiving second-generation TKI had an increase in median survival of OS ( p-value = 0.009). No difference was found in the median survival of DFS ( p-value = 0.55). No difference was found in either hematologic, gastrointestinal, dermatologic, or other adverse events (p-values of 0.39, 0.94, 0.24, and 0.33, respectively). Conclusions: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. However, If impossible, our findings suggest that patients treated with high-dose imatinib have a similar OS and DFS prognosis to those receiving a second-generation TKI. [Table: see text]
7+3 versus decitabine + venetoclax: A global, propensity-matched study comparing outcomes for both regimens in AML.
Authors: Salimath Varada , Mackey James David , Miles Brittany , Mehta Ankit 
Published: June 2024

6537 Background: In the treatment of AML, 7+3 (seven days of standard-dose cytarabine and three days of anthracycline therapy) has long been the standard for attempted remission induction. Recently published studies have explored the efficacy and tolerability of decitabine and venetoclax as a favorable alternative regimen in older adults with AML. However, there has not yet been a head-to-head study in the literature comparing real world outcomes for both regimens. Here we present a retrospective database analysis comparing remission status and mortality among elderly patients treated with 7+3 versus decitabine and venetoclax. Methods: The TriNetX research network was used for this study. Two patient cohorts were created by utilizing International Classification of Disease 10 (ICD-10) codes and medication codes in the TriNetX platform. Both cohorts had patients age 65 and up with a diagnosis of AML (C92.0) and who started treatment within six weeks of diagnosis. The 7+3 cohort received cytarabine and either idarubicin or daunorubicin, while the other cohort received decitabine and venetoclax. Each cohort was excluded from the other treatment to remove crossover as a confounding factor. The cohorts were balanced for age, race, gender, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm. This resulted in 519 patients in each arm. They were then evaluated for the outcome of AML in remission (C92.01) and for death within 12 months. Results: Patients treated with 7+3 were more likely to obtain remission status (54.5% vs 34.7%, RR 1.57, 95% CI (1.36,1.81), P value < 0.0001). The 7+3 cohort also had a lower rate of mortality at 12 months (37% vs 54%, RR 0.69, 95% CI (0.60,0.79), P value < 0.0001). Conclusions: These results show that among elderly patients with AML, treatment with 7+3 is associated with statistically higher remission rates and lower mortality when compared with decitabine and venetoclax therapy. One limitation of our study was that we were not able to determine the cytogenetics in either arm. These results should be taken into consideration when choosing an induction regimen in this population.
Outpatient blinatumomab with digital monitoring in patients with measurable residual disease positive (MRD+) B-ALL in a phase 4 study.
Authors: Pardee Timothy S. , Varela Juan , Jeyakumar Deepa , Keng Michael Kenneth , Bar-Natan Michal , Gundabolu Krishna , Gayle Arlene , McCann Christopher , Xia Qing , Ganzha Sofia , Mergen Noemi , Zaman Faraz , Gordon Paul R. , Khan Sharif S. 
Published: June 2024

6544 Background: Blinatumomab, a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule, is an effective therapy for patients (pts) with MRD+ B-ALL. Hospitalization is recommended for days (D) 1–3 of cycle (C) 1 and D1–2 of C2 for these pts receiving blinatumomab to monitor for serious adverse events (SAEs). This phase 4 study evaluated the safety and feasibility of outpatient (outpt) digital monitoring to replace hospitalization in pts with MRD+ B-ALL (NCT04506086). Methods: Enrolled adults with MRD+ B-ALL in complete remission received continuous intravenous (cIV) blinatumomab at 28 μg/day. Current Health Wearable Monitoring System (CHWMS) was worn by pts at home for D1–3 (C1) and D1–2 (C2), in the presence of a caregiver, and provided heart rate, respiratory rate, and oxygen saturation; a separate patch monitored temperature. Manual blood pressure measurements were taken every 3-6 hrs. Vital signs (VS) were streamed to a provider smartphone/laptop; changes outside a predetermined threshold generated audible alarms. The primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS), neurotoxicity, or any adverse event (AE) requiring hospitalization during the monitoring period. Results: As of 12/15/2023, 9 pts (median age 43 [20-73] years) received outpt blinatumomab for (completed C1, n=7; C2, n=6). During outpt monitoring, dose interruption was reported in 5 of 9 pts (1 pt had 2 dose interruptions: AE, n=2; dose administration error, n=2; other, n=2). CRS was reported in 2 pts (SAE, n=1; G≥3, n=0; led to interruption, n=1) and neurologic events in 4 pts (SAE, n=0; G≥3, n=0; led to interruption, n=0). Two pts experienced AEs requiring hospitalization (CRS, n=1; fever, n=1). Most VS changes were physiological or from routine pt activity. Median (range) number of alarms triggered/pt was 79 (12-135); among 3 pts, 1.2%, 5.1% and 8.9% of alarms led to therapeutic intervention (Table). Conclusions: To date, outpt administration of cIV blinatumomab in pts with MRD+ B-ALL was feasible and safe with appropriate outpt digital monitoring. Study enrollment is ongoing. Clinical trial information: NCT04506086 . [Table: see text]
TP53 mutation screening for patients at risk of myeloid malignancy.
Authors: Mukherjee Devdeep , Lawal Rialnat A. , Fitzhugh Courtney , Dillon Laura Williams , Hourigan Christopher S. 
Published: June 2024

6546 Background: Cellular therapy is a promising approach for many diseases but is associated with a risk of subsequent myelodysplastic syndrome and/or acute myeloid leukemia, also known as therapy-related myeloid neoplasms (tMN). This phenomenon has recently been described with allogeneic hematopoietic cell transplantation (HCT) and gene therapy for sickle cell disease (SCD). Mutation(s) in functional domains of TP53 are often associated with the development of tMN but currently no prospective screening or monitoring technology is available. Methods: A next-generation sequencing (NGS) assay with unique molecular identifiers (UMI) and bioinformatic noise-suppression was designed to discover somatic mutations at a variant allele frequency (VAF) 1% throughout the TP53gene. The background error profile at each base position was calculated using blood genomic DNA from healthy donors. The minimal detectable allele fraction with 95% confidence (MDAF) was calculated for all reported known AML/tMN TP53 hotspots. Orthogonal validation was performed using droplet digital PCR (ddPCR). Results: The median error corrected sequencing depth at 62 known TP53 hotspot regions was 14,512 (95% CI: 14,769 – 15,430) with a theoretical median de novo NGS variant discovery limit of 0.058% (range: 0.037% - 0.13%). Experimental evidence of assay performance characteristics was produced using serial dilutions of 4 missense, 2 splicing, and 1 frameshift TP53 variants with 100% discovery specificity observed (lowest detected VAF range: 0.05 – 0.12%). High correlation was observed in quantification using NGS discovery and ddPCR validation ( r = 0.958, p<0.0001). Pre- and post-HCT clinical samples from 19 patients with SCD, 11 of which had graft failure including 4 who developed tMN, were screened for TP53 mutations. In all tMN cases, the AML-associated TP53 variant was detectable at least 6 months and up to 2.5 years prior to clinical diagnosis of myeloid malignancy. In contrast, no pathogenic TP53 variants were detected in 15 SCD patients who underwent HCT but did not develop tMN. Conclusions: This study provides generalizable evidence that ultra-sensitive discovery of TP53 mutations prior to cellular therapy is possible and could be a potentially valuable clinical tool to screen for tMN risk.
Biomarker testing and adjuvant osimertinib use in patients with resectable EGFR-mutated stage IB–IIIA NSCLC: Physician practices, therapy choice, and barriers among US oncologists.
Authors: Aggarwal Puja , Savill Kristin M. Zimmerman , Jeune-Smith Yolaine , Jennings-Zhang Luke , Bone Robert , Kelly Ronan Joseph , Feinberg Bruce A. 
Published: June 2024

e20007 Background: Epidermal Growth Factor Receptor mutations ( EGFRm) are commonly found in patients with resectable and metastatic non-small cell lung cancer (NSCLC). In December 2020, the FDA approved adjuvant osimertinib, for resectable EGFRm NSCLC, based on results of the ADAURA trial which showed significant survival benefit compared to placebo post-resection, further reinforcing need for biomarker testing in NSCLC. In light of publication of Aduara this study aims to understand US oncologists' biomarker testing practices and adjuvant osimertinib use in resectable EGFRm Stage IB–IIIA NSCLC. Methods: Questions related to biomarker testing and adjuvant therapy decision-making for resectable EGFRm Stage IB–IIIA NSCLC were presented to US-based oncologists/hematologists during live meetings in June and July 2023. In addition, questions related to impact of updated overall survival data from ADAURA trial on physicians’ reported treatment preferences were presented.Up to 108 participants responded to questions, though not all participants answered each question. Aggregate responses were summarized using descriptive statistics. Results: Among respondents, 52% identified as medical oncologists and 46% as hematological oncologists, 41% identified as being from an independent community practice and 75% indicated lung cancer was among the 3 solid tumors they most often treat. For patients with newly diagnosed resectable NSCLC patients, respondents indicated that genetic testing was performed before surgery on initial diagnostic biopsy sample (73%), after surgery (44%), and upon progression/relapse (31%). Commonly utilized diagnostic tools reported by respondents included NGS testing of tissue samples (87%), NGS liquid biopsy (42%), and IHC (31%). Barriers impacting molecular testing practices for resectable NSCLC included access to tissue for testing, cost to patient, disease stage, histology, tumor burden, patient age, patient fitness, and prior authorization or time to approval. Half (50%) of respondents reported prescribing adjuvant osimertinib monotherapy for patients with resectable EGFRm NSCLC in the past 6 months. After reviewing the updated ADAURA data, most (83%) respondents indicated they would prescribe adjuvant osimertinib immediately following surgery for resectable EGFRm NSCLC, and 56% would prescribe adjuvant osimertinib with or without adjuvant chemotherapy, 21% would prescribe adjuvant osimertinib with adjuvant chemotherapy, and 17% would prescribe adjuvant osimertinib only. Conclusions: Overall, nearly three-fourths of medical oncologist respondents prefer pre-operative genetic testing and regardless of test timing, when EGFRm identified > 80% will treat adjuvantly with osimertinib. Unfortunately, multiple barriers complicate this pursuit of evidence-based medicine.
Dynamic network biomarker of treg cells differentiation critical state with neoadjuvant treatment in LUSC.
Authors: Meng Yiran , Lin Hai , Zheng Liuqing , Wang Li 
Published: June 2024

e20063 Background: Regulatory T cells (Tregs) suppress immune responses and can promote tumor growth and metastasis during cancer progression. Studies have shown that tumor-infiltrating Tregs upregulate inhibitory gene programs after immune checkpoint blockade therapy. Targeting Tregs is believed to be a valuable approach to enhance the effectiveness of immunotherapy. However, the precise role of Tregs in the tumor microenvironment, their connection to treatment resistance mechanisms, and how changes in their immune activity impact tumor treatment are still not well understood. Methods: Single-cell data and clinical information were obtained from the Gene Expression Omnibus database with the accession number GSE176021 for 4 patients diagnosed with lung squamous cell carcinoma (LUSC) who received neoadjuvant anti-PD-1 therapy, including 2 patients with major pathologic response (MPR) and 2 patients with non-MPR. BioTIP was employed to identify critical transition signals of the Treg cell differentiation trajectory constructed by Monocle2. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set variation analysis were performed to understand biological processes and pathways. Additionally, potential transcription factors were identified using Single-Cell rEgulatory Network Inference and Clustering, and CellChat analysis was conducted to evaluate possible interactions among cell populations. Results: The study constructed a pseudo-temporal differentiation trajectory of Tregs in LUSC patients, and Treg subpopulations during the critical transition period were identified based on the dynamic network biomarker method. Notably, subpopulations of Treg cells clustering MPR or non-MPR samples were located at different ends of the differentiation trajectory, showing variations in Treg-related pathways and transcription factor regulation. The critical transition subpopulation exhibited high expression of glycolysis, TCA cycle, and natural killer cell receptors, along with upregulation of the CEBPB transcription factor activity and downregulation of ARNTL activity. SELPLG-SELL, CD99-CD99, and MHC-II-CD4 were identified as potential key signals that may affect therapeutic effect, primarily influencing cell adhesion, the immune suppressive activity of Treg cells, and T cell response. Conclusions: In conclusion, this study utilized single-cell data analysis to uncover the dynamic regulation of Treg cells in LUSC, identifying critical transition Treg subpopulations. Notably, our findings suggest the involvement of the transcription factors CEBPB and ARNTL in regulating Treg activity. These novel insights shed light on potential strategies for targeted therapies and provide valuable information regarding resistance mechanisms associated with Treg cells.