bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTHR-01. SUCCESSFUL DEVELOPMENT OF A LOCAL-REGIONAL POST-MORTEM BRAIN TUMOR DONATION PROGRAM
Authors: Mark Melissa , Sowell Kelsey , Zapata Deborah 
Published: June 2023

Abstract
Patient tumor tissue is vital to development of therapeutic interventions in the setting of refractory CNS tumors. Patients and families who participate in tumor donation (TD) report meaning making and improved bereavement outcomes. Provider discomfort is a significant barrier to autopsy participation. Families who are not approached for tumor donation report distress or a feeling of a missed opportunity. Our center developed a process to offer all patients who died from their disease the option to participate in TD as a standard of care. Discussions around TD are best done in the context of a multidisciplinary team well known to the patient and family lead by the treating oncologist. Opportunities to discuss TD present themselves at predictable time points in the disease trajectory: day one talk, treatment discussion, time of recurrence, clinical deterioration, advance care planning discussions, end of life, and immediately-post mortem. Our practice is in the setting of a free-standing children’s hospital. We are not a phase one site. In 2022 seven patients in our neuro-oncology program died from progressive disease. Seven of seven chose to participate in TD. We partnered with a regional phase one center and SWIFTY foundation to coordinate logistics and enrollment. All tumor procurements occurred off site at the funeral home selected by each family. To facilitate family comfort with TD a local team member was present at the time of harvest and kept family updated in process in real time via phone call at the following time points: time of harvest, completion of harvest, tissue arrival at research site. Future directions include offering structured post-mortem visits with families to review research findings with primary treating oncologist in conjunction with the research team and conducting prospective studies with bereaved families to better understand the impact of TD on bereavement.
OTHR-09. A RETROSPECTIVE COHORT STUDY EXAMINING RADIOLOGIC AND CLINICAL CHARACTERISTICS OF CHILDREN AND ADOLESCENTS WITH ATYPICAL/COMPLEX PINEAL CYSTS
Authors: Tahbaz Meghan , Malvar Jemily , Khan Sara , Tamrazi Benita , Chi Yueh-Yun , Robison Nathan 
Published: June 2023

Abstract

INTRODUCTION
The significance of atypical or complex pineal cysts (CPC) on magnetic resonance imaging (MRI) is often unclear, and the appropriate management has not been well defined. We conducted a retrospective cohort study of children and adolescents (0-18 years of age) with complex pineal cysts noted on brain MRIs obtained at Children’s Hospital Los Angeles (CHLA) prior to 05/31/2022.

METHODS
We retrospectively reviewed electronic medical records at CHLA to identify patients &lt;18 years of age who were diagnosed with CPC upon MRI between January 1, 2010 and May 31, 2022. CPC were defined as cysts that are multi-cystic, enhancing, ≥1 cm in size, have a solid component, or exhibit restricted diffusion. Patients were identified by an automated Boolean search of a radiology report database; individual reports were then reviewed for eligibility. Patients with normal pineal glands or simple (&lt;1 cm) pineal cysts were excluded. Electronic medical records were evaluated for patient chief complaint, initial clinical and radiographic symptoms, tumor markers (beta-human chorionic gonadotropin and alpha-fetoprotein), and final diagnosis.

RESULTS
We identified a cohort of 175 patients; 106 (61%) were female. Mean age at initial MRI was 8.36 years of age (SD 5.36). Tumor markers were measured in 52 patients (30%). The most common presenting symptoms for patients were headache (34%), seizures (26%), nausea/vomiting (19%), weakness/fatigue (17%), and dizziness (12%). Additional presenting symptoms included ataxia, sensory changes, and anxiety. Pineal malignancies were identified in 4 patients (2.2%), which consisted of a pituitary pure germinoma, a pineal region parenchymal tumor, and two pineoblastomas. The remaining 98% of patients (171 patients) either had a benign pineal cyst or were categorized as unknown.

CONCLUSION
Most CPC are not associated with malignant neoplasms and represent incidental findings with scant clinical significance.
OTHR-13. IDENTIFYING INDIVIDUALS WITH PRIMARY CENTRAL NERVOUS SYSTEM TUMORS AT RISK FOR HEREDITARY CANCER SYNDROMES USING A STATEWIDE CANCER REGISTRY
Authors: Whipple Nicholas , Yu David Zhe , Cheshier Samuel , Schiffman Joshua , Curtin Karen , Kohlmann Wendy 
Published: June 2023

Abstract

INTRODUCTION
Central Nervous System (CNS) tumors are associated with hereditary cancer syndromes (HCS), especially among pediatric and AYA populations. Using population-based resources, we evaluated the proportion of patients meeting HCS testing criteria.

METHODS
Cases of CNS tumors diagnosed in individuals ages 0-39 were identified through the Utah Cancer Registry. Using the Utah Population Database, cases were linked to cancer family history and, when available, to HCS genetic data. A genetic counselor and pediatric neuro-oncologist reviewed family pedigrees containing ≥2 CNS tumors.

RESULTS
We identified 347 CNS tumors in 320 individuals, from 161 families (FSIR P&lt;0.05). The most common tumors were: astrocytoma (n=93), pituitary (n=38), glioma (n=34, 4 optic nerve), glioblastoma (n=32), meningioma (n=31), oligodendroglioma (n=24), and medulloblastoma (n=20). Sixteen individuals had multiple cancers: 9 had ≥ 2 CNS tumors, 7 had CNS and non-CNS tumors. Of those with multiple tumors, 3 met criteria for NF2, 1 for NF1, and 1 for Chompret. 213 individuals (67%) met criteria for HCS testing based on their personal cancer history. Criteria met included glial tumor (&lt; age 40) (n=163), NF2 (n=14), NF1 (n=12), rhabdoid tumor predisposition (n=10), Chompret (n=7), VHL (n=3), medulloblastoma—SHH (n=3), DICER1 (n=1). Germline data were available for 23 individuals, and 14 had a germline mutation (Li Fraumeni Syndrome=8, VHL=3, APC=1, DICER1=1). An additional 12 people met Chompret criteria based on their CNS tumor plus family history. Of these 4 had germline testing, of which 3 had LFS.

CONCLUSIONS
In our cohort, 70% of individuals met criteria for HCS testing. However, this may be an underestimate because many syndromes associated with CNS tumors also predispose to non-CNS tumors, which were not included in the initial query. Research on the actual prevalence of HCS in individuals with CNS tumors requires germline data in a queryable form in the medical record.
XRT-04. THE ROLE OF STEREOTACTIC RADIOSURGERY FOR MENINGIOMAS IN PEDIATRIC PATIENTS
Authors: Shanahan Regan , Wei Zhishuo , Miller Tracy , Deng Hansen , Niranjan Ajay , Dade Lunsford L 
Published: June 2023

Abstract
Despite the generally benign and slow-growing nature, meningiomas in pediatric populations often exhibit more aggressive behavior. Stereotactic radiosurgery (SRS) is a non-invasive modality that is widely used as an upfront or adjuvant treatment for patients with meningiomas. Due to the rarity of meningiomas in pediatric patients, the outcomes of SRS for childhood meningiomas have never been described. From 1987 to 2022, a total of 2,030 patients with meningiomas underwent SRS at the University of Pittsburgh Medical Center. Nine patients (2 female; incidence rate = 0.44%) with a median age of 14.5 years (range, 9—17 years) at SRS were identified. Three patients (33.3%) had a history of total body irradiation. Seven patients (77.8%) were asymptomatic at the time of SRS presentation. Seven patients (77.8%) had a pre-SRS craniotomy; two patients (22.2%) had pre-SRS fractionated radiotherapy. The median cumulative tumor volume was 3.65 cc (range, 0.01—11.84 cc). The median margin dose prescribed was 14 Gy (range, 11—25 Gy). The median follow-up time was 107 months (range, 24—194 months). Five patients (55.6%) experienced tumor progression at a median of 25 months (range, 13—161 months). Local tumor control at 1-, 5-, and 10 years was 100%, 55.56%, and 55.56%, respectively. After local tumor progression, 2 patients received repeat SRS, 2 patients had surgical resection and 1 was placed on hydroxyurea for an unresectable tumor. At the date of the last clinical follow-up, 5 patients (55.6%) were still alive while 4 patients (44.4%) expired due to the progression of intracranial disease. 1-, 5-, and 10-year survival was 100%, 88.89%, and 64.81%, respectively. Childhood meningioma is a rare tumor that exhibits aggressive behaviors. SRS should be considered as an upfront or adjuvant treatment option in the multi-modal management of childhood meningiomas for optimal tumor control and maximal quality of life preservation.
XRT-06. RAPID PTEFB-DEPENDENT TRANSCRIPTIONAL REORGANIZATION UNDERPINS THE GLIOMA ADAPTIVE RESPONSE TO RADIOTHERAPY
Authors: Walker Faye , Sobral Lays Martin , Danis Etienne , Sanford Bridget , Balakrishnan Ilango , Wang Dong , Pierce Angela , Karam Sana , Serkova Natalie , Foreman Nicholas , Venkataraman Sujatha , Dowell Robin , Vibhakar Rajeev , Dahl Nathan 
Published: June 2023

Abstract
Dynamic regulation of gene expression is fundamental for cellular adaptation to exogenous stressors. PTEFb-mediated pause-release of RNA polymerase II (Pol II) is a conserved regulatory mechanism for synchronous transcriptional induction in response to heat shock, but this pro-survival role has not been examined in the applied context of cancer therapy. Using a combination of ChIP-, ATAC-, and RNA-seq in model systems of diffuse intrinsic pontine glioma and other pediatric high-grade gliomas, we observe a rapid genome-wide reorganization of active chromatin within hours of exposure to therapeutic ionizing radiation. This redistribution facilitates PTEFb-mediated pause-release of Pol II to drive nascent transcriptional induction of canonical DNA damage response programs. Concurrent inhibition of PTEFb imparts a transcription elongation defect, disrupting this chromatin reorganization and blunting transcriptional induction. Functionally, concurrent PTEFb inhibition abrogates key adaptive programs such as DNA repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival. These studies reveal a central role for PTEFb underpinning the early adaptive response to radiotherapy, opening new avenues for combinatorial treatment in these lethal malignancies.
TRLS-02. FEASIBILITY OF EVALUATING ABEMACICLIB NEUROPHARMACOKINETICS OF DIFFUSE MIDLINE GLIOMA USING INTRATUMORAL MICRODIALYSIS
Authors: Jackson Sadhana , Glod John , Peer Cody , Figg William , Dalmage Mahalia , Brown Desmond 
Published: June 2023

Abstract

BACKGROUND
Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates &lt;10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment response.

METHODS
This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are &gt;10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression.

DISCUSSION
The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options.
TRIAL REGISTRATION: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis; https://clinicaltrials.gov/ct2/show/NCT05413304?term=22c0003&draw=2&rank=1
TRLS-08. EXPERIENCE WITH THE SELECTIVE FIBROBLAST GROWTH FACTOR INHIBITOR ERDAFITINIB IN THREE PEDIATRIC PATIENTS WITH CNS TUMORS
Authors: Stepien Natalia , Mayr Lisa , Hedrich Cora , Lippolis Maria Aliotti , Schned Hannah , Baumgartner Alicia , Raimann Adalbert , Schmook Maria-Theresa , Traub-Weidinger Tatjana , Dorfer Christian , Hartmann Gabriele , Senfter Daniel , Madlener Sibylle , Peyrl Andreas , Azizi Amedeo A , Haberler Christine , Müllauer Leonhard , Gojo Johannes 
Published: June 2023

Abstract
Activation of FGF signaling has been described for at least 3% of pediatric solid tumors including pediatric gliomas. Therapeutic actionability of FGF signaling activations, however, remains challenging. Here, we report on three patients with FGFR activation treated with erdafitinib, originally approved for the treatment of FGFR3 or FGFR2 mutated urothelial carcinoma. Our patients were treated for posterior fossa group A ependymoma (patient (Pat) 1&2) and glioma NOS °II-III (Pat3). Dose of erdafitinib at initiation of therapy was 5,2mg/kg/d; 3,8mg/kg/d and 2,8mg/kg/d for Pat1-3 respectively. Rationale for treatment with erdafitinib was increased FGFR3 expression in tumor tissue (TT) of Pat1, increased FGFR1 expression in TT of Pat2, and in Pat3 an activating FGFR1 internal tandem duplication (ITD). Both ependymoma patients received erdafitinib as a fourth line treatment and progressed rapidly under therapy. Treatment was discontinued after 2 weeks (Pat2) and 3 months (Pat1) due to progressive disease. Pat3, with the FGFR1 ITD, responded very well to therapy with a decrease in tumor size and reduced contrast-enhancement after 3&6 months. Therapy was discontinued after six months due to dystrophic nail changes. During treatment, our patients reported on diarrhea, abdominal pain, pain in the lower extremities, dysgeusia, hypersensitivity of the oral mucosa, dry skin and dystrophic nail changes. Additionally, we observed a distinct increase in longitudinal growth (Pat1&3), increased serum phosphate levels, LFPs, alpha-amylase, cholinesterase, alkaline phosphatase and LDH. Summing up, treatment with erdafitinib has high potential for a selected cohort of pediatric CNS tumor patients, as demonstrated by the treatment response of Pat3 with the FGFR1 IDT. However, further defining the exact molecular alterations that predict the individual patient’s response as well as side effects in the pediatric population are imperative to elucidate the further role of erdafitinib in treatment of pediatric CNS tumors.
TRLS-14. TARGETING REPLICATIVE STRESS IN BRAIN TUMORS BY COMBINING ATR AND PARP INHIBITION
Authors: Sarvode Supriya , Refaat Alaa , DeVries Rebekah , Pal Anasuya , Tinkle Christopher , Shelat Anang 
Published: June 2023

Abstract
Pediatric brain tumors like MYC-amplified Medulloblastomas (MB) and Atypical Teratoid and Rhabdoid Tumors (AT/RT) continue to have poor survival rates despite recent advances in understanding tumor biology. MYC is an oncogenic transcription factor often expressed in MB and AT/RT at high levels. While direct inhibition of MYC by small molecules is an active area of research, such approaches lack clinical validation and are not yet actionable. Strategies to target MYC-driven brain tumors that are immediately translatable are urgently needed. Replication stress has been identified as a prominent source of tumorigenesis over the past decade and is a potential target for cancer therapy. Specific oncogenes induce elevated levels of replicative stress through aberrant activation of transcription and dysregulation of DNA replication. In these instances, replicative stress could be rescued by either metabolic supplementation or MYC expression. The activation of ATR and PARP are critical events in response to replicative stress. PARP inhibitors stall replication forks and promote the generation of single-strand DNA, which activates ATR. Genetic and pharmacological evidence suggests the sensitization of MYC-induced tumors to PARP inhibitors. Preclinical studies in diverse tumor backgrounds have demonstrated that the combination of ATR and PARP inhibition is synergistic and leads to premature entry into mitosis, enhanced replicative stress and cell death, and tumor regression. Additionally, a reduction in ATR activity can be lethal in oncogene-induced replication stress. Using high throughput drug screening across MB and AT/RT cell lines, we found that the CNS penetrant PARP inhibitor AZD9754 significantly potentiated the cytotoxicity of ATR inhibition. This emerging synergistic combination therapy reveals new therapeutic targets in MYC-driven replicative stress. Studies are ongoing to validate in vitro findings in vivo.
Cell-specific RNA profiling reveals host genes expressed in Arabidopsis cells haustoriated by downy mildew
Authors: Asai Shuta , Cevik Volkan , Jones Jonathan D G , Shirasu Ken 
Published: June 2023

Abstract
The downy mildew oomycete Hyaloperonospora arabidopsidis, an obligate filamentous pathogen, infects Arabidopsis (Arabidopsis thaliana) by forming structures called haustoria inside host cells. Previous transcriptome analyses have revealed that host genes are specifically induced during infection; however, RNA profiling from whole-infected tissues may fail to capture key transcriptional events occurring exclusively in haustoriated host cells, where the pathogen injects virulence effectors to modulate host immunity. To determine interactions between Arabidopsis and H. arabidopsidis at the cellular level, we devised a translating ribosome affinity purification system using 2 high-affinity binding proteins, colicin E9 and Im9 (immunity protein of colicin E9), applicable to pathogen-responsive promoters, thus enabling haustoriated cell-specific RNA profiling. Among the host genes specifically expressed in H. arabidopsidis–haustoriated cells, we found genes that promote either susceptibility or resistance to the pathogen, providing insights into the Arabidopsis–downy mildew interaction. We propose that our protocol for profiling cell-specific transcripts will apply to several stimulus-specific contexts and other plant–pathogen interactions.
Whole-genome assembly of A02 bacteria involved in nitrogen fixation within cassava leaves
Authors: Huang Danping , Ren Jie , Chen Xi , Akhtar Kashif , Liang Qiongyue , Ye Congyu , Xiong Caiyi , He Huahong , He Bing 
Published: June 2023

Abstract
The endophytic nitrogen (N)-fixing bacterium A02 belongs to the genus Curtobacterium (Curtobacterium sp.) and is crucial for the N metabolism of cassava ( Manihot esculenta Crantz). We isolated the A02 strain from cassava cultivar SC205 and used the 15N isotope dilution method to study the impacts of A02 on growth and accumulation of N in cassava seedlings. Furthermore, the whole genome was sequenced to determine the N-fixation mechanism of A02. Compared with low N control (T1), inoculation with the A02 strain (T2) showed the highest increase in leaf and root dry weight of cassava seedlings, and 120.3 nmol/(mL·h) was the highest nitrogenase activity recorded in leaves, which were considered the main site for colonization and N-fixation. The genome of A02 was 3,555,568 bp in size and contained a circular chromosome and a plasmid. Comparison with the genomes of other short bacilli revealed that strain A02 showed evolutionary proximity to the endophytic bacterium NS330 (Curtobacterium citreum) isolated from rice (Oryza sativa) in India. The genome of A02 contained 13 nitrogen fixation (nif) genes, including 4 nifB, 1 nifR3, 2 nifH, 1 nifU, 1 nifD, 1 nifK, 1 nifE, 1 nifN, and 1 nifC, and formed a relatively complete N fixation gene cluster 8-kb long that accounted for 0.22% of the whole genome length. The nifHDK of strain A02 (Curtobacterium sp.) is identical to the Frankia alignment. Function prediction showed high copy number of the nifB gene was related to the oxygen protection mechanism. Our findings provide exciting information about the bacterial genome in relation to N support for transcriptomic and functional studies for increasing N use efficiency in cassava.
Monitoring nutrients in plants with genetically encoded sensors: achievements and perspectives
Authors: Sadoine Mayuri , De Michele Roberto , Župunski Milan , Grossmann Guido , Castro-Rodríguez Vanessa 
Published: June 2023

Abstract
Understanding mechanisms of nutrient allocation in organisms requires precise knowledge of the spatiotemporal dynamics of small molecules in vivo. Genetically encoded sensors are powerful tools for studying nutrient distribution and dynamics, as they enable minimally invasive monitoring of nutrient steady-state levels in situ. Numerous types of genetically encoded sensors for nutrients have been designed and applied in mammalian cells and fungi. However, to date, their application for visualizing changing nutrient levels in planta remains limited. Systematic sensor-based approaches could provide the quantitative, kinetic information on tissue-specific, cellular, and subcellular distributions and dynamics of nutrients in situ that is needed for the development of theoretical nutrient flux models that form the basis for future crop engineering. Here, we review various approaches that can be used to measure nutrients in planta with an overview over conventional techniques, as well as genetically encoded sensors currently available for nutrient monitoring, and discuss their strengths and limitations. We provide a list of currently available sensors and summarize approaches for their application at the level of cellular compartments and organelles. When used in combination with bioassays on intact organisms and precise, yet destructive analytical methods, the spatiotemporal resolution of sensors offers the prospect of a holistic understanding of nutrient flux in plants.
Understanding ‘flexing’: the impact on mental health and public trust
Authors: Rachman Ali , Verawati Inuriya , Rusandi M Arli 
Published: June 2023

Abstract

Background
This correspondence explores the rising phenomenon of ‘flexing’ on social media, characterized by flaunting wealth and luxurious lifestyles. This trend is particularly prominent among influencers and some public officials in Indonesia.

Problem
We identify ‘flexing’ as a behavior that potentially harms both mental health and societal trust, creating an environment that contrasts starkly with the beneficial practice of ‘sharenting,’ which promotes sharing parental experiences for mutual support and healing.

Implications
The influence of ‘flexing’ on public mental health and trust in the tax system requires thorough examination.

Conclusion
Given its adverse effects, the correspondence emphasizes the need for comprehensive measures to address this issue.
Managing patients with sex-, race-, or ethnicity-based cardiovascular health inequities
Authors: Luntz Allison , Creary Kashif , Bruessow Diane 
Published: June 2023

ABSTRACT
Cardiovascular health inequities are experienced among cisgender women, gender minorities, Black and Indigenous people, and people with lower socioeconomic status. Early identification and treatment of patients at risk for disparate and adverse cardiac health outcomes are essential.