bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives on competency-based feedback for training non-specialists to deliver psychological interventions: multi-site qualitative study of the EQUIP competency-based approach
Authors: Elnasseh Abdelrhman , Mehta Varun S. , Manolova Gergana , Pedersen Gloria A. , Golden Shannon , Eloul Liyam , Gebrekristos Frezgi , Collins Pamela Y. , Mutavi Teresia , Mbwayo Anne W. , Mathai Muthoni , Concepcion Tessa , El Masri Rozane , Steen Frederik , Galea Jerome T. , Contreras Carmen , Akellot Josephine , Kasujja Rosco , Wasereka Samuel , Mutamba Byamah Brian , Tol Wietse A. , Raji Mansurat , Moufarrej Sacha , Schafer Alison , Kohrt Brandon A. 
Published: June 2024

Background
The use of feedback to address gaps and reinforce skills is a key component of successful competency-based mental health and psychosocial support intervention training approaches. Competency-based feedback during training and supervision for personnel delivering psychological interventions is vital for safe and effective care.

Aims
For non-specialists trained in low-resource settings, there is a lack of standardised feedback systems. This study explores perspectives on competency-based feedback, using structured role-plays that are featured on the Ensuring Quality in Psychosocial and Mental Health Care (EQUIP) platform developed by the World Health Organization and United Nations Children’s Fund.

Method
Qualitative data were collected from supervisors, trainers and trainees from multiple EQUIP training sites (Ethiopia, Kenya, Lebanon, Peru and Uganda), from 18 key informant interviews and five focus group discussions (N = 41 participants). Qualitative analysis was conducted in Dedoose, using a codebook with deductively and inductively developed themes.

Results
Four main themes demonstrated how a competency-based structure enhanced the feedback process: (a) competency-based feedback was personalised and goal-specific, (b) competency-based feedback supported a feedback loop, (c) competency-based feedback supported a comfortable and objective feedback environment, and (d) competency-based feedback created greater opportunities for flexibility in training and supervision.

Conclusions
A better understanding of the role of feedback supports the implementation of competency-based training that is systematic and effective for trainers and supervisors, which ultimately benefits the learning process for trainees.
CINSARC score use in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in the Children’s Oncology Group (COG) studies ARST0332 and ARST1321.
Authors: Hurley Rachel M , Guo Lei , Barkauskas Donald A. , Yu Lei , Chen Yen-Lin , Gutstein Lauren , Hawkins Douglas S. , Scharschmidt Thomas , Skapek Stephen X , Spunt Sheri L. , Wang Dian , Weiss Aaron R. , Xu Lin , Laetsch Theodore Willis 
Published: June 2024

10013 Background: Despite genomic and histologic heterogeneity, limited risk stratification is used in the treatment of NRSTS (grade, size, presence of metastases, and extent of surgical resection). Genomic signatures including CINSARC score and Genomic Index (GI), both measures of genomic instability, have been shown to be prognostic in retrospective studies, but are not routinely used clinically. Here we evaluated the association of these scores with EFS and OS on two consecutive, prospective COG NRSTS studies, ARST0332 and ARST1321. Methods: All patients enrolled to ARST0332 or ARST1321 with sufficient banked tumor in the COG biospecimen repository were included in this analysis. Whole exome and transcriptome sequencing was performed on DNA and RNA from banked FFPE and flash frozen specimens. Raw WES reads were mapped to hg38 using BWA. The base qualities of the aligned reads were recalibrated and realigned by GATK. RNAseq data was aligned to hg38 by STAR. Differential expression analysis was performed by DESeq2. Stratified log rank and proportional hazards models were used to evaluate the association of CINSARC score and GI above or below the median with EFS and OS. Results: Tumors from 197 patients yielded sufficient DNA and 166 sufficient RNA, of which 177 and 142, respectively, passed sequencing quality metrics and were included. Demographics of these patients were generally representative of overall trial enrollment with most patients between ages 10-17 years (53%) with localized disease (77-80%). The most common histologic diagnoses were synovial sarcoma (35-37%) and MPNST (9-12%). Median follow-up was 6 years. CINSARC high vs low was associated with worse EFS (5-year 52.1% vs 74.6%, p < 0.01) and OS (5-year 66.2% vs 83.6%, p < 0.01). Accounting for sex and presence of metastatic disease, the hazard ratio for CINSARC high was 2.4 for EFS and 2.7 for OS (p < 0.01). CINSARC maintained the association with EFS among patients with non-metastatic disease (p = 0.017), and with OS among patients with metastatic disease (p = 0.031). GI analysis is ongoing and will be reported. Conclusions: In this analysis from the largest prospective North American pediatric NRSTS studies to date, CINSARC score was prognostic for EFS and OS. Further analysis including additional clinical prognostic factors (tumor size, grade, and extent of resection) is ongoing and will be reported. Use of CINSARC score for risk stratification should be considered on future NRSTS clinical trials. Clinical trial information: NCT00346164 , NCT02180867 .
Interpretable artificial intelligence-based analysis for morphologic classification of neuroblastic tumors.
Authors: Ramesh Siddhi , Pomaville Monica , Doytcheva Kristina , Dolezal James M , Kochanny Sara , TerHaar Rachel , Brewer Jacob , Kusswurm Benjamin , Shimada Hiroyuki , Naranjo Arlene , Pytel Peter , Cohn Susan Lerner , George Rani , Pearson Alexander T. , Applebaum Mark A. 
Published: June 2024

10023 Background: Rapid and accurate identification of morphologic features of neuroblastic tumors (NTs) is critical for risk stratification and therapeutic decision making. The prognostic value of features like neuroblast differentiation, mitosis-karyorrhexis index (MKI), and Schwannian stromal presence is well established. Deep learning permits objective histopathological analysis, streamlining workflows for pathologists, notably in rare cancers. In rare cancers, our method minimizes bias and optimizes limited data using transfer and self-supervised learning (SSL) for feature extraction, with improved explainability. Here, we used an artificial intelligence-based model to morphologically classify NT tumors and MYCN-amplification. Methods: Annotated H&E-stained slides of diagnostic NT tumor biopsies from the University of Chicago and the Children’s Oncology Group were digitalized. Pathologists defined three binarized measures including diagnostic category (ganglioneuroblastoma/neuroblastoma), grade (differentiating/poorly differentiating), and MKI (low and intermediate/high). MYCN status was abstracted from patient records (amplified/non-amplified). Using Slideflow, our open-source pipeline, we developed an attention-based multiple instance learning model with features extracted by CTransPath, a SSL model pretrained on pan-cancer images from The Cancer Genome Atlas. For each measure, model performance was evaluated using 5-fold cross validation by aggregating k-fold model predictions across multiple metrics. Patients were excluded from a model if the measure of interest was unknown. Feature significance was assessed visually using Class Activation Mapping (Grad-CAM). Results: The mean age of the study cohort (n = 172) was 3.66 years. Of patients with clinical information, 84 of 138 (60.2%) had metastatic disease and 94 of 133 (70.7%) were high-risk. Of the 148 tumors with a diagnostic category of neuroblastoma, 93.2% were poorly differentiated and 25% had high MKI. Of the 135 tumors with known MYCN status, 40 were amplified (29.6%). The final models excelled across all outcomes, performing best for diagnostic category, grade, and MYCN status (Table 1). Physician review of the attention-based heatmaps for all measures highlighted biologically relevant regions such as neuropil. Conclusions: We created a deep learning pipeline for auto-characterization of digitized H&E-stained NT pathology slides. Our approach may also aid in identifying molecular features including MYCN-amplification. Review of heatmaps showed pertinent biological tissue, boosting model reliability.[Table: see text]
Phase I trial of chidamide, an oral HDAC inhibitor, in combination with oral etoposide in patients with refractory/recurrent neuroblastoma.
Authors: Sun Feifei , Zhen Zijun , Lu Suying , Zhu Jia , Wang Juan , Huang Junting , Que Yi , Zhang Yizhuo 
Published: June 2024

10034 Background: Chidamide, an oral subtype-selective histone deacetylase (HDAC) inhibitor, has been shown to be effective in adult patients with hematological tumors. However, there is no data on its safety and efficacy in pediatric cancer patients. Combination of HDAC inhibitors and etoposide have shown synergistic anti-tumor effects in preclinical studies of neuroblastoma. We conducted a phase I trial in pediatric patients with recurrent or refractory neuroblastoma to determine the maximum tolerable dose (MTD) of chidamide combined with oral etoposide treatment. Methods: Daily oral etoposide 35 mg/m2/dose was administered on days 1–21 in combination with escalating doses of chidamide (14 and 17 mg/m2/d) twice weekly in each 28-day cycle using the standard 3 + 3 design. Patients with response or stable disease after two cycles would maintain treatment until disease progression or unacceptable toxicity occurred. Chidamide pharmacokinetic testing was performed. Results: 31 patients were enrolled in this study. The median age was 7 years (range 3 – 18). 14 patients were included in the dose escalation phase (Ia), 17 patients in the expansion cohort (Ib). The MTD of chidamide was 14 mg/m2/d, with dose limiting neutropenia and thrombocytopenia observed at 17 mg/m2/d. Median number of cycles completed was 2.5 (range 1–11). A total of 19 patients (61.3%) experienced treatment-related grade 3/4 hematologic toxicity, and no grade 3/4 non-hematological toxicity was observed. No objective responses were seen. Conclusions: In children with refractory/recurrent neuroblastoma, chidamide is well-tolerated at 14 mg/m2/d twice weekly when combining with oral etoposide 35 mg/m2/d daily. Prolonged disease stability achieved in patients with minimal residual diseases deserves further investigation. Clinical trial information: NCT05338541 .
Targeted treatment in inflammatory myofibroblastic tumors in children.
Authors: Kebudi Rejin , Yildirim Ulku Miray Miray , Zulfikar Osman Bulent 
Published: June 2024

10046 Background: Inflammatory myofibroblastic tumors (IMTs) and epithelioid inflammatory myofibroblastic sarcoma (EIMS)-a variant of IMT, are rare mesenchymal neoplasms in children. Surgical resection has been the mainstay of treatment, however it may cause morbidities due to the size, location, invasiveness of the tumor. With the identification of targetable molecular alterations, targeted treatment has begun to be used in inoperable/relapsed/refractory cases. Methods: Files of children with IMT diagnosed and treated between 1990-2023 were retrospectively evaluated for demographic, clinical, molecular characteristics, treatment and outcome. Results: The mean age of 8 patients (5 male, 3 female) at diagnosis was 9 years (8 months-17 years). Six had IMT and two EMS. Tumor localization was intestine, retroperitoneum, lower extremity in two patients each; liver and back in one each. None had metastatic at diagnosis. Three of the six patients (one EMS) who underwent only surgical resection had negative surgical margins (one after re-resection) and are under follow-up with no evidence of disease (NED). Molecular analysis was performed in six patients. ALK was positive in the tumor tissue of five patients. One patient with an inoperable local recurrence received chemotherapy, had a life-threatening infection and resistant hypercalcemia. The molecular analysis by next-generation sequencing revealed a YWHAE-ROS fusion and she was treated by ceritinib, after which a significant (>90%) tumor shrinkage occurred and hypercalcemia resolved. She is currently in remission and continuing treatment. The patient with a positive surgical margin experienced local and metastatic (lung, liver) recurrences during follow-up and was treated with chemotherapy containing vincristine, actinomycin-D, and cyclophosphamide, the patient died due to progressive disease. In a patient with an unresectable tumor and ALK positivity, crizotinib treatment was initiated. After a treatment duration of seven months with crizotinib, the tumor completely regressed and treatment was stopped. On follow-up, local recurrence was detected after two months of cessation of crizotinib, crizotinib was restarted, considering the infiltrative appearance of the tumor and possible morbidities if operated. Two months after readministering crizotinib, complete response was achieved once again. The patient is continuing treatment with crizotinib. Thus, 7/8 patients are alive with NED for a median of 99 (9-174) months. Conclusions: Inflammatory myofibroblastic tumor and epithelioid inflammatory myofibroblastic sarcoma are rare in children. Surgery is the mainstay of treatment. The effectiveness of chemotherapy is yet unclear despite its use in inoperable cases. Molecular analysis of tumor tissue is highly recommended as targets such as ALK rearrangements or ROS fusions may enable the use of targeted treatments with fewer side effects.
Overall survival prediction and risk stratification in patients with neuroblastoma through machine learning in the large multi-institutional PRIMAGE cohort.
Authors: Lozano-Montoya Jose , Jiménez Pastor Ana , Weiss Glen J. , Cerdá-Alberich Leonor , Veiga-Canuto Diana , Martínez de Las Heras Blanca , Hero Barbara , Ladenstein Ruth Lydia , Martí-Bonmatí Luis , Alberich-Bayarri Angel 
Published: June 2024

10054 Background: Neuroblastoma (NB) is the most prevalent solid cancer in childhood in which imaging plays a pivotal role at every step of the patient's journey. This investigation aimed to develop a machine learning model using clinical, molecular (MycN amplification), and magnetic resonance (MR) radiomics features at diagnosis to predict patient’s overall survival (OS) and improve their risk stratification. Methods: A database comprising clinical, molecular, and International Neuroblastoma Risk Group (INRG) staging on 513 patients with accessible MR imaging (discovery cohort) was employed for model training, validation, and testing. An additional 22 patients from non-discovery cohort hospitals served as an external validation group. Tumor segmentations of NB were manually and semi-automatically performed on corresponding T2-weighted MR images by an experienced radiologist. In total, 107 radiomics features were extracted and harmonized across MR scan manufacturers and magnetic field strengths using the nested ComBat methodology to correct both batch effects. These radiomics features, combined with clinical and molecular data, were utilized as input for the models. A nested cross-validation approach was employed for model development to determine the optimal preprocessing, machine learning algorithm, and model configuration. Results: The discovery cohort yielded a C-index of 0.788 ± 0.049 in the test partitions, with a random survival forest (RSF) exhibiting the best performance. In the validation cohort, a C-index of 0.934 was achieved. Interpretability analysis identified lesion heterogeneity, size, and molecular variables as crucial factors in OS prediction. The model demonstrated superior predictive performance and patient stratification compared to conventional staging systems in both cohorts. Conclusions: The RSF predictive model exhibited high performance, emphasizing the significant contribution of radiomics features and alignment with established clinical and molecular variables. The model stratified NB patients into low-, intermediate-, and high-risk categories and suggests that radiomics features potentially could improve current risk stratification systems. Additional external validation is warranted as this may present new evidence for enhancing patient care and clinical decision-making for NB patients.
PP2A activation as a new therapeutic strategy in neuroblastoma: Making sense out of senescence.
Authors: Nazam Nazia , Shaikh Maryam G. , Butey Swatika , Erwin Michael H , Stewart Jerry E. , Ohlmeyer Michael , Beierle Elizabeth A 
Published: June 2024

10055 Background: Neuroblastoma (NBL) is the most common extracranial solid tumor in children, accounting for 15% of all pediatric cancer deaths. The five-year survival rate for children with high-risk disease is less than 50%, with the primary reasons for mortality being refractory and relapsed disease. One hypothesis for the poor response to therapy and propensity for recurrent disease in high-risk patients is treatment-induced senescence (TIS). Protein phosphatase 2A (PP2A) is a known tumor suppressor that is downregulated in NBL. PP2A activation has been shown to reverse cellular senescence in non-cancerous pathologies, therefore we hypothesized that reactivation of PP2A using novel small molecule activators would function as a novel senotherapeutic in NBL. Methods: We employed MYCNamplified, SK-N-BE(2), and non-amplified, SK-N-AS, established human NBL cell lines. Topotecan, a common NBL chemotherapeutic, known to induce senescence, and ATUX-1215, a small molecule PP2A activator, were utilized. NBL cells were treated with topotecan and ATUX-1215 alone, as well as in combination. Colorimetric assays detected cell viability and proliferation. Immunoblotting identified proteins of interest including γ-H2AX and CCL2. TIS was detected by S-β galactosidase (Sβgal) assay. Results: We found increased expression of the senescence marker, histone γ-H2AX, and increased Sβgal-positive tumor cells supporting the ability of topotecan to generate TIS in NBL. Following treatment with PP2A activator in combination with topotecan, markers of TIS are decreased in both MYCN amplified and non-amplified NBL cells. Further, and importantly, PP2A activation reversed the effects of topotecan TIS and acted in a synergistic fashion to decrease NBL cell viability. Conclusions: Activation of PP2A with a novel small molecule ameliorates topotecan-induced TIS in NBL cells irrespective of MYCN status. These results are promising, providing a potential novel therapeutic adjunct to children who are most in need of innovative interventions.
Intravitreal chemotherapy (IVC) in retinoblastoma: A study of clinical variables and ocular preservation outcomes.
Authors: Epelman Sidnei , Mutran Thamires MJ , Teixeira Luiz Fernando , Gorender Ethel Fernandes , Carvalho Filho Neviçolino Pereira de 
Published: June 2024

10059 Background: Retinoblastoma, a primary intraocular malignancy, poses unique challenges in preserving life and vision. This retrospective study aims to analyze the impact of IVC in a population of retinoblastoma patients. The primary objective to avoid external radiotherapy, a recognized risk factor for second neoplasms, particularly in germline retinoblastoma cases. Methods: We conducted an analysis of retinoblastoma patients from 2011 to 2024. Clinical variables, including sex, age, laterality, intraocular retinoblastoma staging, and therapies employed, were prospectively documented. Results: The study included 59 patients (37 male; 22 female). Thirty-three percent of patients had unilateral tumors and an average age of 28 months at diagnosis, and 67% had bilateral tumors with an average age of 15 months. Sixty-one eyes were treated and classified at diagnosis as follow: 6 (9.8%) in groups A and B, 10(18%) in group C, 37(64%) in group D, 6(11%) in group E, and 2(3%) without initial information. IVC was administered as part of a multimodal treatment approach. A total of 203 cycles of IVC were performed, averaging 3.4 cycles per patient. Melphalan was used in 39% of cycles, followed by the combination of melphalan and topotecan in 35%, and topotecan alone in 26%. Seven of 61 (11.5%) were enucleated. Three of 61 eyes (4.9%) received radiotherapy. Control of vitreous seeds and vision preservation were achieved in 57/61 eyes (93%). No grade 3 or 4 adverse events occurred. Conclusions: IVC emerges as a crucial component in the management of retinoblastoma, offering a viable alternative to external radiotherapy. The analysis highlights the importance of this approach in preserving ocular integrity, thereby avoiding enucleation and reducing the risk of second neoplasms, particularly in germline retinoblastoma patients.
Racial differences in background parenchymal enhancement, a novel marker of breast cancer.
Authors: Mahmoud Mattia , Ehsan Sarah , Mack Elizabeth , Edmonds Christine E , Kontos Despina , Chen Jinbo , Fayanju Oluwadamilola Motunrayo , McCarthy Anne Marie 
Published: June 2024

10528 Background: Breast density is a risk factor for breast cancer that can guide eligibility for supplemental screening including MRI, but Black women are less likely to qualify for supplemental screening due to having less dense breasts on average despite higher rates of breast cancer mortality. Background parenchymal enhancement (BPE), the enhancement of fibroglandular breast tissue on contrast-enhanced MRI, is a novel biomarker that has been shown to be a superior breast cancer risk marker than breast density. Women with high BPE levels have up to a four-fold increased risk of breast cancer, even after adjusting for density, but no studies have examined BPE exclusively among Black women. Methods: We identified Black and white women ages 40-74 with no prior history of breast cancer who had a mammogram and subsequent MRI as part of a screening or diagnostic work-up from 2016-2022 at our institution. BPE was qualitatively defined according to BI-RADS (Breast Imaging Reporting and Data System), with four ordinal levels of increasing enhancement: minimal, mild, moderate, and marked. We conducted a cross-sectional study to perform a logistic regression with race as the exposure and moderate or marked BPE as the outcome, using minimal and mild BPE as the reference group, adjusted for age and BI-RADS density. Results: We included 1027 Black women and 4834 white women in our analysis. Fewer Black women had extremely dense breasts compared to white women (6% vs 13%, p= 0.04), however, there was a larger proportion of high BPE (moderate or marked) in Black women compared to white women (32% vs 28%, p = 0.03) (Table). There was an inverse association between age and BPE levels (p = 0.03), and a positive association between density and BPE levels regardless of race (p< 0.01) (not shown). Black women were 39% more likely to have high BPE levels (95% CI: 1.39 [1.19, 1.63]), adjusted for age and density. Conclusions: Black women have lower density but higher BPE than white women, suggesting that BPE may improve identification of breast cancer risk for Black women. Participants [Table: see text]