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The dualistic model of passion has been linked to several psychological constructs related to well-being in runners. Evidence suggests that investigating the interaction of passion subtypes might increase our understanding of the relationship between passion and indices of well-being. This study used both person- and variable-centered analyses to investigate the relationship between passion, multidimensional well-being, and psychological distress in 219 adult marathon runners. We performed a canonical correlation multivariate analysis to determine the relationship between passion types and psychological outcomes, as well as a multivariate analysis of variance to compare passion sub-types to indices of well-being. Results indicated that harmonious passion was significantly and positively related to multidimensional well-being and negatively related to psychological distress, while obsessive passion was significantly and positively related to psychological distress. Minor differences in well-being and distress between passion subtype clusters were also noted. A discussion of these findings includes the potential benefit of considering the harmonious and obsessive passion subtype interaction when examining these measures of well-being in marathon runners. Keywords: passion; well-being; cluster analysis; marathon running; psychological distress, Many anecdotes exist that suggest following one's passion will reap benefits and improve a person's quality of life. This idea that passion is associated with positive outcomes has become more [...]

PURPOSE: Long-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance. PATIENTS AND METHODS: NMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m2 twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on MYCN, and additional sensitivity analyses. RESULTS: DFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; P = .008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; P = .007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses. CONCLUSION: The externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.

Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Childrens Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTN's 32 member institutions utilize a shared regulatory governance architecture at the Children's Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4700 subjects, over 1500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1000 tumors and germline material are currently available with data generation for > 5000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

BACKGROUND: Survival for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapies. AIMS: To study the feasibility and safety of incorporating a genomic-based targeted agent to induction therapy for HRNB as well as the feasibility and safety of adding difluoromethylornithine (DFMO) to anti-GD2 immunotherapy. METHODS: Twenty newly diagnosed HRNB patients were treated on this multicenter pilot trial. Molecular tumor boards selected one of six targeted agents based on tumor-normal whole exome sequencing and tumor RNA-sequencing results. Treatment followed standard upfront HRNB chemotherapy with the addition of the selected targeted agent to cycles 3-6 of induction. Following consolidation, DFMO (750 mg/m2 twice daily) was added to maintenance with dinutuximab and isotretinoin, followed by continuation of DFMO alone for 2 years. DNA methylation analysis was performed retrospectively and compared to RNA expression. RESULTS: Of the 20 subjects enrolled, 19 started targeted therapy during cycle 3 and 1 started during cycle 5. Eighty-five percent of subjects met feasibility criteria (receiving 75% of targeted agent doses). Addition of targeted agents did not result in toxicities requiring dose reduction of chemotherapy or permanent discontinuation of targeted agent. Following standard consolidation, 15 subjects continued onto immunotherapy with DFMO. This combination was well-tolerated and resulted in no unexpected adverse events related to DFMO. CONCLUSION: This study demonstrates the safety and feasibility of adding targeted agents to standard induction therapy and adding DFMO to immunotherapy for HRNB. This treatment regimen has been expanded to a Phase II trial to evaluate efficacy.

PurposePlacental growth factor (PlGF) and its receptor neuropilin 1 are elevated in malignant embryonal tumors and mediate tumor progression by promoting cell proliferation, survival, and metastasis. TB-403 is a blocking monoclonal antibody against PlGF that inhibits tumor growth and increases survival in orthotopic medulloblastoma models.Patients and methodsWe conducted a phase I, open-label, multicenter, dose-escalation study of TB-403 in pediatric subjects with relapsed or refractory cancers. The study involved four dose levels (20 mg/kg, 50 mg/kg, 100 mg/kg, 175 mg/kg) using a 3 + 3 dose-escalation scheme. Subjects received two doses of TB-403 (days 1 and 15) per cycle. After cycle 1, temozolomide or etoposide could be added. The primary objective was to determine the maximum tolerated dose (MTD) of TB-403 monotherapy during a dose-limiting toxicity assessment period. The secondary and exploratory objectives included efficacy, drug pharmacokinetics, and detection of pharmacodynamic biomarkers.ResultsFifteen subjects were treated in four dose levels. All subjects received two doses of TB-403 in cycle 1. Five serious treatment-emergent adverse events were reported in 3 subjects, but MTD was not reached. While no complete nor partial responses were observed, 7 of 11 relapsed subjects with medulloblastoma experienced stable disease, which persisted for more than 100 days in 4 of 7 subjects.ConclusionsTB-403 was safe and well tolerated at all dose levels. No MTD was reached. The results look encouraging and therefore warrant further evaluation of efficacy in pediatric subjects with medulloblastoma.

Introduction: Physical disability represents a major burden to health and lifespan, particularly as the proportion of older adults within the United States is expected to grow. Prevention efforts for physical disability targets methods and strategies to decrease modifiable risk factors. Potential challenges for health professionals may exist in synthesizing and interpreting this broad spectrum of literature due to the discipline-specific nuance of language used, practice type or specialty, and lack of interdisciplinary resources. This scoping review will map and synthesize the literature across healthcare disciplines to identify modifiable risk factors and the evidence related to their ability to predict physical disability. We will also draw attention to the possibility of modifiable risk factors for physical disability being operationalized as pre-disability in order to strengthen primary and secondary prevention efforts. Methods: A planned search strategy using physical disability terminology will be searched in English across MEDLINE, CINAHL, Health Source, PEDro, and REHABDATA by two reviewers in line with our review objectives and inclusion criteria. Eligibility for inclusion include peer-reviewed primary research published in the English language and have established a relationship between a person-level measurable characteristic that is modifiable by changes in lifestyle behaviors and any of the commonly accepted terms used to categorize or describe physical disability. Expected results: Presentation of results will be using the PRISMA flowchart, with additional mapping and synthesis of evidence for modifiable risk factors for physical disability to clarify divergent terms used in classifying and measuring these factors and their potential for prediction of physical disability. Expected conclusion: It is anticipated that this scoping review will identify and highlight a variety of modifiable risk factors for physical disability that may aid primary and secondary prevention efforts for health professionals. [ABSTRACT FROM AUTHOR]

Structure reflects a variety of practices teachers use with the intent to guide students' behavior and increase academic success. A research synthesis was conducted on the role of classroom structure in the academic engagement, disengagement, competence beliefs, and achievement of preschool through high school students. A meta-analysis of 191 samples from 165 correlational studies revealed statistically significant correlations with achievement (.11), engagement (.28), and competence beliefs (.22), and a statistically non-significant relationship with disengagement (–.08). A meta-analysis of 71 samples from 46 structure intervention studies revealed a positive statistically significant average effect (g) on achievement (0.33), engagement (0.46), and disengagement (–0.34), but a statistically non-significant effect for competence beliefs (0.26). Consistent with a dual process model of engagement, associations were stronger for engagement than disengagement. Results related to variation suggested some universality, particularly across grade levels, and underscored the importance of emphasizing anticipatory strategies, minimizing the controlling aspects of structure, and considering the broader context, including the country context, income background of students, or whether structure is paired with other psychological supports. Methodological features also explained variation, highlighting the importance of using methods that center teachers' and students' experiences and align with the nature of the focal outcome. [ABSTRACT FROM AUTHOR]