bluuebunny/crossref_metadata_2025_split huggingface dataset:
SURG-10. SPECTROSCOPIC MEASUREMENT OF 5-ALA-INDUCED INTRACELLULAR PROTOPORPHYRIN IX IN PEDIATRIC BRAIN TUMORS
Authors: Schwake Michael , Kaneko Sadahiro , Morina Eric Suero , Stummer Walter 
Published: December 2020

Abstract

OBJECTIVE
5-ALA guided resection of glioma in adults enables better delineation between tumor and normal brain, allowing improved resection and improved patients’ outcome. Recently, several reports were published regarding 5-ALA for resection of pediatric brain tumors. The aim of the study was to determine the intracellular fluorescence of PPIX in pediatric brain tumors by hyperspectral imaging and to compare it with visually observed intraoperative fluorescence.

METHODS
5-ALA was administered orally four hours prior to surgery. During tumor resection the surgeon assessed the fluorescence signal to be strong, weak or absent. Subsequently, fluorescence intensity of samples was measured via spectroscopy. In addition, clinical data, imaging and laboratory data were analyzed.

RESULTS
Eleven children (1–16 years) were operated. Tumor entities included: three medulloblastomas, two pilocytic astrocytomas (PA), two anaplastic ependymomas and one diffuse astrocytoma, anaplastic astrocytoma, pilomyxoid astrocytoma and anaplastic pleomorphic xanthoastrocytoma. Strong fluorescence was visible in all anaplastic tumors and one PA; one PA demonstrated weak fluorescence. Visible fluorescence was strongly associated with intracellular fluorescence intensity and PPIX concentration (P&lt;0.05). Within all tumors with visible fluorescence the intracellular PPIX concentration was greater than 4 µg/ml. Except for moderate and transient elevation of liver enzymes, no 5-ALA related adverse events were reported.

CONCLUSION
We demonstrate a strong association between intraoperative observations and spectrometric measurements of PPIX fluorescence in tumor tissue. As in former studies, fluorescence signal was more commonly observed in malignant glial tumors. Further prospective controlled trials should be conducted to investigate the feasibility of 5-ALA guided resection of pediatric brain tumors.
SURG-16. SURGICAL TECHNIQUES TO AVOID COMPLICATIONS DURING REPEAT RESECTIONS FOR PEDIATRIC BRAIN TUMORS
Authors: Shibahara Ichiyo 
Published: December 2020

Abstract
Complications due to repeat resection for recurrent pediatric brain tumors remain unclear. The present study focused on surgical techniques to avoid surgical morbidities during repeat resections for pediatric brain tumors. This study included 57 consecutive repeat resections for 28 pediatric patients under the age of 15 with recurrent brain tumors. Resections were performed 2–14 times for each patient by the senior author (TK). Reviewed factors were wound-related complications, bleeding/ischemic complications, and Eastern Cooperative Oncology Group performance status (PS) before and after surgery. No patients presented any complications to decrease PS, postoperatively. No wound-related complications were worthy of special mention. Surgical techniques to prevent wound-related complications are as follows: 1) shaving the hair around the previous skin incision just before the surgery; 2) washing and disinfecting around the skin incision using chlorhexidine soap and an alcohol swab, followed by Povidone-Iodine solution; 3) after craniotomy, removing all granulation tissues, residual titanium plates, and screws; 4) brushing all surgical fields and a bone flap before opening the dura mater using Povidone-Iodine solution followed by normal saline; 5) maintaining a bone flap in normal saline with antibiotics; 6) changing all the surgical instrument and gloves; 8) closing the dura mater completely to prevent CSF leakage, and 8) using postoperative antibiotics for six days. Meticulous dissecting postsurgical adhesion of brain and dura mater, arteries and nerves; usage of neuronavigation system and neuromonitoring to understand the anatomy radiologically and functionally; applying papaverine hydrochloride for spastic arteries, are important to avoid complications during the intracranial procedure.
SWK-04. A MOBILE AUGMENTED REALITY APP FOR SURGICAL PREPARATION FOR CHILDREN WITH BRAIN TUMORS
Authors: Granville Sharon , Spat-Lemus Jessica , Rice Blakely , Pzena Allison , Stieg Phil , Greenfield Jeffrey , Souweidane Mark 
Published: December 2020

Abstract

BACKGROUND
Children with brain tumors experience significant anxiety secondary to diagnosis and interventions such as surgical management. Preoperative anxiety is known to adversely affect operative outcomes and overall quality of life. Programs that utilize “child-friendly” approaches have been shown to ease anxiety, decrease analgesic requirements, shorten hospital stay, and contribute toward better outcomes. Implementation of these programs is limited due to time, cost, and staffing constraints as well as sociodemographic factors (i.e., language barriers). Therefore, an effective and cost-efficient method could be advantageous. We sought to develop a universally available APP that can assist with these goals and address the current barriers.

METHODS
In conjunction with a philanthropic resource (Brain Tumor Foundation, New York, NY, USA) a developer was tasked with creating an App for children with brain tumors. The developer integrated published clinical research, multi-specialty input, and patient and family testimonials for possible integration into the tool.

RESULTS
A mobile App was developed that is modifiable for patient-specific features (age, language, and ethnicity). Initial evaluations of the prototype by healthcare providers, appropriately aged children, and their parents have demonstrated positive engagement, appeal, and ease of use.

CONCLUSIONS
The mobile App provides a rapid, affordable, and modifiable platform for assisting children with brain tumors cope with their diagnosis and intervention options. Validation with measurable outcomes is planned. The App is currently being evaluated for purposes of psycho-social clinical research tool.
SWK-05. EDUCATIONAL APPROACH TO GRIEF MANAGEMENT
Authors: DeRosa Veronica , Madrid Nina 
Published: December 2020

Abstract
Pediatric neuro-oncology has a high mortality rate compared to other childhood cancers. This project sought to bring Awareness to the Grief and Trauma that families undergo during treatment through end of life. It also sought to create a pool of parent partners to support families receiving palliative care and to mend the healthcare relationship that is severed when a child passes away. The educational series included Grief Workshops for Bereaved Parents using the ATTEND model, a mindfulness-based bereavement model and seminars with traumatic grief experts for providers. This provided a better understanding on how healthcare workers are influential in the “death story” of a child and how this can dictate the family’s lifelong grief journey. Grief workshops consisted of 2 English and 1 Spanish speaking cohort each with 10–12 bereaved parents. The curriculum provided psychoeducation with the goal of creating a safe space to validate, clarify, and understand the events that happened in their child’s life; support for the parent as they explore emotional awareness; relief of emotional tension; support as the parent expresses their perspective of their new world to others that are in their life; and support as the parent finds meaning in their child’s life and untimely death. At the end of each group surveys showed that parents found that the group provided a safe community, a place to say their child’s name, a place to share their story, and a need to advocate for future oncology parents who undergo this journey.
SWK-06. ANSWERING 900 VOICES: A NATIONAL NONPROFIT ORGANIZATION RESPONDS TO A NATIONWIDE COMMUNITY HEALTH NEEDS ASSESSMENT THAT ELUCIDATED KEY CHALLENGES FACED BY PEDIATRIC BRAIN TUMOR FAMILIES
Authors: Riley Kathy 
Published: December 2020

Abstract
The five-year relative survival rate for childhood primary brain and other central nervous system tumors is nearly 75 percent (Central Brain Tumor Registry of the United States, 2017). Nevertheless, childhood brain tumor survivors often suffer from lifelong side effects caused by their illness or treatments such as surgery, radiation and chemotherapy. To define the nature and extent of problems survivors and their families face, the Pediatric Brain Tumor Foundation (PBTF), the world’s largest nonprofit solely dedicated to children and teens with brain tumors, conducted a 2017 national community health needs assessment in collaboration with the Sol Price Center for Social Innovation at the University of Southern California. The assessment found that pediatric brain tumor patients and their families face key challenges in four general areas: 1) interpersonal and emotional support, 2) logistical and financial support, 3) information and medical education gathering, and 4) educational and vocational anxieties. In 2020, the PBTF’s response to the 900 assessment participants who represent the thousands living with the effects of this disease includes the launch of a national Peer to Peer Mentoring program to meet the ongoing challenges families face; the disbursement of emergency financial assistance to hundreds of families in the throes of treatment; and the distribution of a resource notebook for newly diagnosed families and a comprehensive guidebook for survivors and their families. The results of the needs assessment suggest additional clear, actionable areas for impact not only by the PBTF but by medical professionals, other nonprofit organizations and governmental agencies.
SWK-08. DELAYED DIAGNOSIS OF CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN: PERSPECTIVE FROM THE FRONTLINE
Authors: Jogendran Manisha , Ronsley Rebecca , Goldman Ran D , Cheng Sylvia 
Published: December 2020

Abstract
Delayed diagnosis of CNS tumors in children is well documented, partially due to challenges in recognizing rare diagnoses. Our objective was to describe Canadian family physicians’ attitudes and confidence in diagnosing and managing pediatric CNS tumors. A standardized questionnaire was administered at a Canadian national family physicians’ conference. Items were based on observations from our institutional study of prediagnostic symptomatic interval in pediatric CNS tumors. 449 surveys were completed. 302/443 (68%) physicians practice in cities. 153/447 (34%) report encountering parents that inquire about their children having brain tumors. 261/449 (58%) have not managed a pediatric brain tumor. 153/447 (34%) report they are not confident, 255/447 (57%) somewhat confident and 39/447 (9%) confident in managing a suspected brain tumor in a stable child. 259/447 (58%) would refer directly to a hospital/specialist. The reported median time for suspicion of a brain tumor was 8–14 days for children with vomiting and/or headache and 1 day for children with seizure and/or ataxia. 410/447 (97%) report not knowing any guidelines to help with management. 235/447 (53%) suggested barriers they experience to include 52/235 (22%) wait times for imaging/specialists, 37/235 (16%) geographical location of the child, 27/235 (12%) knowledge, 25/235 (11%) access to imaging/specialist, and 15/235 (6%) patient-related factors or system barriers, and 8/235 (3%) specialist attitudes. 68/235 (29%) identified no barriers in their practice. This study provides insight into family physicians’ perceived challenges and barriers in diagnosing and managing new suspected pediatric CNS tumors. Educational effort and overcoming systemic perceived barriers may increase physicians’ confidence.
SWK-09. SELF-CARE OUTCOMES AND INTERVENTIONS FOR CHILDREN WHO HAVE HAD A BRAIN TUMOUR: EVIDENCE AND HYPOTHESES. WHAT SHOULD SELF-CARE INTERVENTIONS FOR CHILDREN WITH PAST OR PRESENT BRAIN TUMOUR BE?
Authors: Rowen Elizabeth , Kolehmainen Niina , Bailey Simon 
Published: December 2020

Abstract

OBJECTIVE
To determine the evidence with regards to self-care outcomes and interventions for children who have been treated for a brain tumour and identify when best to intervene.

METHODS
A scoping review of the literature with regards to self-care interventions, outcomes and mechanisms was undertaken. The information from these themes were populated onto a logic model alongside the clinical expertise of the team. The logic model was used to develop hypotheses to inform subsequent research; and identified areas for further patient and public involvement.

RESULTS
Of 27 papers found, 13 were deemed relevant. The literature suggested the diagnosis of a brain tumour can have a long-term negative impact on self-care outcomes whilst evidence with regards to interventions to promote self-care is scarce. The child’s physical and cognitive functions were identified as hypothesised factors influencing self-care, while health related quality of life and participation in other life domains were secondary consequences of self-care. The team expertise was further used to hypothesise that parent factors (emotions, identity, actions), the child’s emotional functions and personal factors as well as peer relationships and norms may influence children’s self-care. These factors were not covered in the existing literature.

CONCLUSIONS
Subsequent research will investigate the hypotheses developed to further specify factors that self-care interventions for children and young people with a brain tumour should target. This will involve specifying when, how and to whom interventions should be targeted.
SWK-11. ASSESSMENT OF THE INDIRECT COSTS ASSOCIATED WITH PROTON THERAPY TREATMENT FOR ALBERTA PATIENTS REFERRED OUT OF COUNTRY
Authors: Black Karina , Middleton Jackie , Ghosh Sunita , Eisenstat David , Patel Samor 
Published: December 2020

Abstract

BACKGROUND
Proton therapy for benign and malignant tumors has dosimetric and clinical advantages over photon therapy. Patients in Alberta, Canada are referred to the United States for proton treatment. The Alberta Heath Care Insurance Plan (AHCIP) pays for the proton treatment and the cost of flights to and from the United States (direct costs). This study aimed to determine the out-of-pocket expenses incurred by patients or their families (indirect costs).

METHODS
Invitation letters linked to an electronic survey were mailed to patients treated with protons between 2008 and 2018. Expenses for flights for other family members, accommodations, transportation, food, passports, insurance, and opportunity costs including lost wages and productivity were measured.

RESULTS
Fifty-nine invitation letters were mailed. Seventeen surveys were completed (28.8% response rate). One paper survey was mailed at participant request. Nine respondents were from parent/guardian, 8 from patients. All patients were accompanied to the US by a family member/friend. Considerable variability in costs and reimbursements were reported. Many of the accompanying family/friends had to miss work; only 3 patients themselves reported missed work. Time away from work varied, and varied as to whether it was paid or unpaid time off.

CONCLUSIONS
Respondents incurred indirect monetary and opportunity costs which were not covered by AHCIP when traveling out of country for proton therapy. Prospective studies could help provide current data minimizing recall bias. These data may be helpful for administrators in assessing the societal cost of out-of-country referral of patients for proton therapy.
TBIO-08. BASE-RESOLUTION METHYLOMES OF GLIOMAS BEARING HISTONE H3.3 MUTATIONS REVEAL A G34 MUTANT-SPECIFIC SIGNATURE SHARED WITH BONE TUMORS
Authors: Sangatsuda Yuhei , Miura Fumihito , Araki Hiromitsu , Mizuguchi Masahiro , Hata Nobuhiro , Kuga Daisuke , Hatae Ryusuke , Akagi Yojiro , Amemiya Takeo , Fujioka Yutaka , Arai Yasuhito , Shibata Tatsuhiro , Yoshimoto Koji , Ito Takashi , Iihara Koji 
Published: December 2020

Abstract

BACKGROUND
Two recurrent mutations, K27M and G34R/V, in H3F3A, encoding non-canonical histone H3.3, are reported in pediatric and young adult gliomas, whereas G34W mutation was prevalent in bone tumors. In contrast to K27 mutation, it remains elusive how G34 mutations affect the epigenome. Here we performed whole-genome bisulfite sequencing of four G34R-mutated gliomas and the G34V-mutated glioma cell line KNS-42. Similarly, we analyzed seven and three gliomas harboring K27M and no mutations in H3F3A, respectively. These data were compared with those on bone tumors.

RESULTS
G34R-mutated gliomas exhibited lower global methylation levels, similar CpG island (CGI) methylation levels, and compromised hypermethylation of telomere-proximal CGIs compared with those bearing K27M and no mutations. Hypermethylated regions specific to G34R-mutated gliomas were enriched for CGIs, including those of OLIG1, OLIG2, and canonical histone genes in the HIST1 cluster. These CGIs were hypermethylated in osteosarcomas with, but not without, the G34W mutation. In KNS-42 cells, CGIs with G34V-mutated histone H3.3 exhibited higher methylation levels than those with wild-type histone H3.3. This effect was also observed in the G34R-mutated glioma samples.

CONCLUSIONS
Gliomas bearing G34R/V mutations display characteristic methylomic alterations, some of which are shared by osteosarcomas with the G34W mutation. Deposition of G34 variants may lead to elevated methylation of otherwise hypomethylated, histone H3.3-bearing CGIs.
TBIO-11. DEEP LEARNING-BASED SINGLE-CELL RNA SEQUENCING DIFFERENTIATION IDENTIFIES SIMPLE AND COMPLEX TRANSCRIPTIONAL NETWORKS FOR SUBPOPULATION CLASSIFICATION
Authors: Prince Eric , Hankinson Todd 
Published: December 2020

Abstract

BACKGROUND
Genomic assays capable of cellular resolution (i.e. scRNA-seq) are becoming ubiquitous in biomedical research. Machine learning, and the subtype known as Deep Learning, have broad application within scRNA-seq analytics. However, methods to facilitate the classification of cell populations are lacking. We present the novel computational framework HD Spot, which generates interpretable and robust Deep Learning classifiers that enable unbiased interrogation of linear and non-linear genomic signatures.

METHODS
HD Spot is written in python and relies on Google’s TensorFlow2 deep learning framework. Four datasets of immune cells were obtained from the publicly available Seurat repository, generated using the 10X chromium platform. Data preprocessing used standard Seurat methodology. HD Spot generated optimized classifiers via a custom platform. Network interpretability was achieved using Shapley values. Ontology analysis was performed using Metascape.

RESULTS
HD Spot identified meaningful ontologic signatures across all tested datasets. In the binary case of control versus IFN-B stimulated CD4+ T cells, gene ontologies reflected Th0 and Th2 T cell populations, congruent with T cell activation. In the 9-class case of PBMCs, HD Spot identified meaningful gene networks characteristic of the ground-truth populations using raw feature counts alone. When feature counts are processed into expression values, HD Spot demonstrates increased specificity of top genes and respective ontologies between subpopulations.

CONCLUSION
This work introduces a broadly applicable computational tool for the advanced bioinformatician to decipher complex cellular heterogeneity (e.g., tumors) in an unbiased way. Additionally, HD Spot lowers the barrier for novice bioinformaticists to derive actionable insights from their data.
TBIO-24. USING MOLECULAR GUIDED THERAPY IN PEDIATRIC NEURO ONCOLOGY PATIENTS: THE SUCCESS AND BARRIERS
Authors: Armstrong Beth , Schmitt Morgan , VonBergen Jayne 
Published: December 2020

Abstract
Remarkable advances have been made in pediatric brain tumor treatments, however many of these children suffer significant side effects from standard chemotherapy-based treatment. Recent advances in precision medicine offer great hope to pediatric patients in terms of improved therapeutic precision, safety, and efficacy. However, there are barriers to implementing precision medicine that are best approached from a multi-disciplinary perspective. The goals of the Riley Hospital for Children at Indiana University Health Precision Genomics Neuro Oncology program are to optimize the treatment of children by assessing children’s cancers for actionable molecular targets and finding available, affordable therapies that treat those actionable targets. Children are referred to the Riley Precision Genomics Neuro Oncology program at the time of diagnosis or with relapse. Tumor tissue is tested for somatic and germline findings. Riley’s Precision Genomics Neuro Oncology program has received 55 patient referrals. Of these 55 patients, 46 (84%) had molecular analysis completed, and the results of 40 (87%) patients indicated actionable targets. Of the 40 patients with results, 23 (58%) patients went on to receive genomics guided therapy. Limited availability of tissue has accounted for 6 (13%) patients’ lack of results. Many guided therapy options are oral medications, which positively impact patient’s quality of life. The learner will increase their knowledge of how molecular guided therapy is now innovatively being used to treat children with cancer, and the challenges involved.
THER-01. AWAKING THE IMMUNE SYSTEM WITH AN IMMUNO-ONCOLYTIC VIRUS AS A THERAPEUTIC STRATEGY FOR DIPGs
Authors: Laspidea Virginia , Puigdelloses Montse , Ausejo-Mauleon Iker , Hambardzumyan Dolores , Chen Zhihong , Martinez-Velez Naiara , Zalacain Marta , de Larraya Jaime Gallego Perez , Becher Oren , Fueyo Juan , Gomez-Manzano Candelaria , Alonso Marta M 
Published: December 2020

Abstract
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour, being the leading cause of paediatric death caused by cancer. Despite all the advances made regarding effective therapies, the survival is dismal. Our lab has engineered the oncolytic virus Delta-24-ACT armed with the costimulatory ligand 41BBL in order to increase the antitumoral effect of the adenovirus. 41BB is a costimulatory receptor which promotes the expansion of activated T cells and the generation and maintenance of CD8 T memory cells. Therefore, we propose the use of Delta-24-ACT as a therapeutic approach for DIPG tumours. We observed that Delta-24-ACT is able to infect and replicate in NP53 and PDGFB-driven, two DIPG murine cell lines. Furthermore, 41BBL is expressed in the membranes of the infected cells and results with immunogenic cell death as shown by the different DAMPs. Injection of Delta-24-ACT in DIPG model was safe, showed no sign of toxicity and led to a significantly increase in the median overall survival, generating anti-glioma memory in long-term survivors. Mechanistic experiments, showed an increase of T cell infiltration (mainly CD8), decrease of proliferating cells and a reduction of the number of vessels in FFPE brain samples in the treated mice. We are currently performing nanostring analyses to assess the changes in the transcriptional immune phenotype of treated versus control mice. In summary, our data suggest that Delta-24-ACT is safe and induces a potent antitumor immune response in DIPG models mainly based in the activation of CD8 lymphocytes recruited by the viral activity.