bluuebunny/crossref_metadata_2025_split huggingface dataset:
OTHR-29. A SINGLE INSTITUTION REVIEW REGARDING TRENDS IN THE MOLECULAR ANALYSIS OF PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS AND GERMLINE ANALYSIS BETWEEN 2019 – 2023, EMPHASIZING THE IMPORTANCE OF EASY ACCESS TO COMPREHENSIVE TESTING
Authors: Bendel Anne E , Skrypek Mary M , Galkowski Allison M , Pond Dinel A , Olson Damon R , Roiko Samuel A 
Published: June 2024

Abstract

BACKGROUND
Molecular characterization of pediatric CNS tumors improves diagnostic accuracy and guides treatment. Germline analysis is also important to uncover cancer predisposition syndromes, which influence the approach to treatment and tumor surveillance. The options for molecular assessment are influenced by availability, including access through a trial or insurance approval.

METHODS
A retrospective review of the molecular workup performed on all CNS tumors biopsied/resected at Children’s Minnesota from 2019 – 2023 was undertaken to look at trends in the specific tests performed over time and how the molecular results guided treatment.

RESULTS
Between 2019 – 2023, 220 patients at Children’s Minnesota were diagnosed with a CNS tumor. A total of 191 underwent surgery and 162 (85%) had sufficient tissue for molecular analysis. There was no apparent difference in the percentage of patients who underwent IHC/FISH/NGS between 2019 - 2023, but methylation profiling frequency increased over time (2019 2%, 2020 and 2021 10%, 2022 58% and 2023 71%). Frequency of germline analysis also increased (2019-2021 29%, 2022-52% and 2023-63%). Easy availability of comprehensive molecular and germline analysis for patients enrolled on COG-APEC14B1 is credited for these improving trends. Molecular analysis confirmed (59%) or supported (36%) the diagnosis, and guided treatment in 30% of cases (stratification of treatment in 89% of medulloblastoma and targeted treatment in 63% of high-grade glioma, 9% of medulloblastoma and 6% of low-grade glioma). Methylation profiling alone accurately diagnosed 79% of cases, including subtyping tumors. Germline analysis detected a pathogenic germline alteration in 14% of CNS tumor patients (NF1 5%; TP53 and BRIP1 1%; PALB1, NF2, TS2, SMARCB1, biallelic PMS2, CHEK2, FANCA, ORICH1 and SDHA 0.5%).

CONCLUSION
These findings demonstrate the importance of easy access to comprehensive molecular and germline analysis with quick turnaround time to provide the best diagnosis, prognosis and treatment options for pediatric CNS tumor patients.
PATH-01. ACCURATE AND RAPID PAEDIATRIC BRAIN TUMOR CLASSIFICATION (PBT) BY METHYLATION PROFILING USING NOVEL NATIVE REAL TIME OXFORD NANOPORE TECHNOLOGY SEQUENCING TECHNOLOGY
Authors: Feinberg Galina , Grunwald Assaf , Mark Nurit Gal , Maman Lena Shinderman , Shihrur Keren , Hameiri-Grossman Michal , Toledano Helen , Michaeli Orly , Fichman Suzanna , Izraeli Shai , Birger Yehudit 
Published: June 2024

Abstract

BACKGROUND
Pediatric brain tumors (PBTs) pose a significant challenge being the leading cause of cancer related mortality in children. The existing classification process is time-consuming and fails to capture the heterogeneity of PBTs. Urgent advancements in diagnostic and therapeutic approaches are needed. The WHO classification 5th edition for CNS tumors introduced DNA methylation analysis into the diagnostic process, especially for difficult-to-diagnose cases. However, the currently available DNA methylation array-based methods are laborious, costly, &require large amounts of DNA

METHODS
Nanopore methylation analysis is rapid, accurate, and inexpensive & requires minimal tissue. We applied this technology on 24 PBT samples that were classified into ten molecular subgroups.

RESULTS
Our results were compatible with those obtained through Heidelberg methylation analysis, standard histopathological examination, and molecular tests and were in concordance with the final neuro-pathological diagnosis. Moreover, for five prospective cases, that would have challenged standard methods, Nanopore yielded same-day results, guiding additional tests and providing a significant diagnostic advantage. In one case, a 2.2-year-old male, with a large left parieto-temporal tumor and a suprasellar lesioninitially treated elsewhere with upfront chemotherapy without biopsy, developed clinical deterioration. We resected the temporal lesion and frozen tissue diagnosis suggested low-grade glioma. However, same day Nanopore sequencing analysis indicated a high score for ‘Meningioma’. Final pathology examination 10 days later confirmed ‘‘Atypical meningioma, WHO grade 2” – an extremely rare diagnosis in this age group. Visual deterioration prompted immediate resection of the second lesion before final pathological confirmation. Thus, early Nanopore classification played a vital role in diagnosis and management.

CONCLUSIONS
Our preliminary results underscore the potential of Nanopore potential for accurate and rapid PBT classification from small brain biopsies, with DNA input as low as 100 nanograms. This cutting-edge technology promises to substantially reduce time to diagnosis, shaping future neurosurgical strategies for individualized PBT patient management.
LMIC-13. ENCOURAGING EXPERIENCE OF CONCURRENT CARBOPLATIN DURING CRANIOSPINAL IRRADIATION USING IMAGE GUIDED INTENSITY MODULATED PROTON BEAM (IMPT) IN HIGH-RISK EMBRYONAL TUMORS: FIRST REPORT FROM A LOW MIDDLE-INCOME COUNTRY
Authors: K Vasudeva Bhat , Uppuluri Ramya , Krishna Uday , Das Anindita , KC Ganapathy , S Preethi , VS Venkateswaran , R Adithyan , Patil Sushma , Jalali Rakesh 
Published: June 2024

Abstract

BACKGROUND
Concurrent carboplatin during craniospinal irradiation (CSI) using photon radiotherapy in High risk (HR) embryonal tumors has been shown to improve the event free survival in select subgroup of patients. Experience of using concurrent carboplatin during CSI using proton therapy is limited.

METHOD
A retrospective audit was done in Children &lt;18 years from January 2018 to December 2023 diagnosed with HR embryonal tumors who received image guided pencil beam intensity modulated proton beam therapy-based CSI (35Gy/21#) along with concurrent carboplatin 35mg/m2 at least for 15 fractions. The patient demographics, pathological diagnosis, treatment related toxicities and date of follow-up were recorded in predesigned proforma using electronic medical record.

RESULTS
Twenty children with HR embryonal tumors with median age at diagnosis 5 years (Range: 1-15 years) with M: F ratio of 3:1 were included in the study. Fifteen (75%) of the patients had HR medulloblastoma defined by spinal metastases or HR molecular subtype of which 5 patients had group 3 medulloblastoma (3- leptomeningeal disease at baseline, 2- MYC amplification) while rest had embryonal tumors (3-NOS, 1-Pinealoblastoma and 1-ETMR). Carboplatin was well tolerated, however 12 (60%) patients developed neutropenia requiring daily G-CSF for an average of 5 days. Average time to complete radiotherapy was 45 days with median interruption of 4 days (Range 1-7). Radiotherapy induced toxicities included Grade 3 skin toxicity in 6 (30%) and grade 2 weight loss in 3 (15%). At a median follow up of 14 months (Range: 4-58), the PFS was 80% in the whole cohort while in the Group 3 Medulloblastoma the PFS was only 20% which was statistically significant(p=0.004).

CONCLUSIONS
Carboplatin along with proton CSI is well tolerated in children with HR embryonal tumors without significant adversities. Experience is encouraging especially in non-group 3 medulloblastoma patients in our cohort of children with HR embryonal tumors.
MODL-15. CHARACTERIZATION OF SPONTANEOUS CANINE HIGH-GRADE GLIOMA MODELS AS CLINICALLY-RELEVANT SURROGATES OF PEDIATRIC HIGH-GRADE GLIOMA
Authors: Link Gabrielle , Garey Simon , DeSisto John , Antonakakis Markos , McGrath Stephanie , Chow Lyndah , Slade Mathew , Dow Steven , Green Adam L 
Published: June 2024

Abstract

BACKGROUND
High-grade glioma (HGG) occurring spontaneously in canines shows histological and genetic resemblance to pediatric high-grade glioma (PHGG). Both canine HGG and PHGG are treated with combinations of surgical resection, radiation therapy, and/or chemotherapy, but outcomes for both groups are poor. Studying canine HGG both serves companion dogs and provides an orthogonal preclinical model of PHGG.

METHODS
Canine HGG lines J3T, SDT3G, and G06A were characterized and compared with H3K27M-mutant PHGG lines DIPG7, DIPG13, and BT245 using neurosphere dilution assay and drug screening with all FDA-approved anti-cancer agents. J3T and SDT3G were orthotopically implanted into mice and monitored using MRI and bioluminescence.

RESULTS
Like PHGG, the canine lines J3T and SDT3G were highly sensitive to proteasome and XPO1 inhibition; compared to PHGG, the canine lines were most sensitive to protein translation inhibitors and DNA intercalators. Canine HGG lines were not as sensitive to other targeted inhibitors effective in PHGG. Compared to PHGG cell lines, canine cell lines had greater variance in self-renewal capability. J3T and SDT3G were also injected into the cortex of immunodeficient mice. Bioluminescent signal confirmed J3T engraftment one week post-surgery with rapid tumor growth, while SDT3G presented initial engraftment by MRI two weeks post-surgery but did not exhibit sustained growth.

DISCUSSION
Canine HGG and PHGG showed similar sensitivity to proteasome and XPO1 inhibition; they differed in self-renewal capability and susceptibility to other anti-cancer agents. This could be because canine target proteins often differ from their human counterparts and thus may respond differently to targeted medications designed for humans. Overall, canine HGG provides a novel, primary, immunocompetent surrogate that resembles PHGG and may provide a step for clinical investigation between xenograft models and PHGG trials and/or opportunities for co-clinical trials.
RADT-09. IMMUNE RESPONSE IN DIFFUSE MIDLINE GLIOMA (DMG) FOLLOWING FLASH OR CONVENTIONAL RADIATION
Authors: Minns Hanna E , Padilla Oscar , Wei Hong-Jian , Webster-Carrion Andrea , Gallitto Matthew , Szalontay Luca , Pavisic Jovana , Tan Yuewen , Deoli Naresh , Garty Guy , Garvin James H , Canoll Peter , Vanpouille-Box Claire I , Rabadan Raul , Wu Cheng-Chia , Gartrell Robyn D 
Published: June 2024

Abstract

BACKGROUND
Diffuse Midline Glioma (DMG) is a fatal, unresectable, pediatric brain tumor with limited treatment options and a median survival of 9-15mths. As radiation therapy (RT) can only extend life by 3mths, novel RT techniques are needed, including ultra-high dose rate RT (FLASH). RT can stimulate immune responses in many cancers especially via type 1 interferon (IFN1) but the effect of RT on DMG is understudied as post treatment tissue is not readily available.

METHODS
We evaluated the effect of RT on immune response in an orthotopic syngeneic model of DMG, comparing FLASH, given at 90Gy/second, to conventional dose rate RT (CONV), given at 2Gy/min. We evaluated single-cell RNA sequencing (scRNA-seq) on CD45+ immune cells isolated from tumors 4 days post 15Gy FLASH or CONV RT and compared to unirradiated tumor (SHAM). We also performed flow cytometry on tumors at both day 4 and day 10 post-RT.

RESULTS
We find microglia (MG) are the most abundant immune cell type followed by non-resident myeloid cells including macrophages (MAC) and dendritic cells (DC). While there’s no significant difference in tumor growth or proportion of immune subtypes comparing FLASH, CONV and SHAM, we see similar IFN1 enrichment in MG comparing FLASH and CONV at day 4. Interestingly, at day 10 post-RT we observe higher IFN1 receptor (IFNAR1) by flow in MGs after CONV (p=0.016) and SHAM (p=0.040) compared to FLASH. At day 4 CONV shows higher IFN1 gene set enrichment in MACs and DCs compared to FLASH (both p&lt;0.0001) as well as higher IFNAR1 in DCs comparing CONV to FLASH (p=0.0079), while day 10 post-RT shows equivalent IFNAR1 in MACs and DCs between dose rates.

CONCLUSION
Changes in DMG tumor immune microenvironment post-RT differ over time. Though both RT modalities increase IFN1, the timing of this response is dependent on both cell phenotype and dose.
RADT-12. CLINICAL RELEVANCE OF RADIATION-INDUCED CAVERNOUS MALFORMATIONS
Authors: Burnett Lauren A , Cavannaugh Corey , Sato Mariko 
Published: June 2024

Abstract

BACKGROUND
Radiation-induced cavernous malformations (RICMs) are delayed complications of brain irradiation during childhood. The prevalence of cavernomas in the general population was found to be 0.5% in a large prospective study. However, the exact incidence of RICM in children and the mechanisms of the development of RICM remain largely unknown since the cumulative incidence of RICM is underreported. Recent systemic review revealed 113 children with RICM after treatment of brain tumors and leukemias. 67% were asymptomatic and 21% showed signs of hemorrhage. In this review, the average dose of radiation was 50Gy and the mean time to detection was 9.2 years.

METHODS
We conducted a retrospective review of RICM in children who underwent total body irradiation (TBI) for bone marrow transplant. Our study goals were to better understand the incidence and patterns of RICMs and to develop a risk stratification for monitoring. Between 9/2000-1/2023, 161 patients underwent TBI. Of 47 patients who had post-transplant brain MR imaging done, 15 patients had MRIs available for review.

RESULTS
Of 15 reviewed MRIs, 11 (73.3%) had RICMs identified. 6 cases had &gt;5 small (&lt;3mm) RICMs. Most RICMs were in the frontal lobes. MRIs were obtained an average of 64 months from TBI. Radiation doses ranged from 200-2760cGy with an average of 1144cGy. There was 1 case of microhemorrhage due to RICM. None of our patients deceased as a result of their RICM.

CONCLUSIONS
Our cohort showed a high incidence (73.3%) of RICM despite low doses of radiation. Due to their typically small size and lack of clinical symptoms, RICM is often underreported. Although the outcome of cavernous malformation is favorable, it is important to understand the incidence and risk of adverse neurologic outcomes posed by RICMs. By performing regular surveillance, complications related to RICMs may be intervened with preventative procedures such as microsurgery.
Public Support for Tobacco Endgame Policies: A Systematic Review and Meta-Analysis
Authors: Kim Hana , Gartner Coral , Edwards Richard , Puljević Cheneal , Morphett Kylie , Kim Dong Ha , Chun Hae-ryoung , Ekdahl Martin , Kang Heewon 
Published: June 2024

Abstract

Introductions
An increasing number of countries are adopting the tobacco endgame goal. High levels of public support can accelerate momentum towards implementing tobacco endgame policies. We aimed to conduct a systematic review of public support for tobacco endgame policies and to examine the geographical distribution of studies, support among key populations (adolescents and young adults, people who smoke), and the association between survey design and support.

Aims and Methods
We searched Embase, PubMed, Scopus, Web of Science, and Google Scholar for studies published from 2013 onwards. Google was used to search the gray literature. The reference lists of included articles were hand-searched. Studies were included if they reported the proportions of people supporting one or more endgame policies. Risk of bias was assessed using the JBI checklist for prevalence studies.

Results
Forty-seven articles were included. Aotearoa/New Zealand and the United States were the countries with the most studies (n = 11, respectively). Three-level meta-analyses showed the highest support for mandating a very low nicotine content in tobacco products (76%, 95% CI: 61% to 87%). Meta-regressions were performed to assess the associations of population subgroup and survey design with support levels. The level of support was lower among people who smoke compared to the general population (β range: −1.59 to −0.51). Support for some policies was lower when neutral or don’t know response options were included.

Conclusions
Public support for most tobacco endgame policies was high.

Implications
Assessing public support can assist with progressing tobacco endgame policies. Policies that are widely supported by the public may be more politically feasible to implement. Qualitative studies and trial studies can further inform communication and implementation strategies for tobacco endgame policies.
Thinking about the Future
Authors: Brady Henry E. 
Published: June 2024

Abstract
The five projective inference methods of statistical forecasting and modeling, technological forecasting, constructing future scenarios, configurative analysis, and robust decision-making (RDM) evaluate the possibility, attainability, and sustainability of plans or projections about the future such as a new constitution for a fledgling democratic republic in 1787–89, a transcontinental railroad in the 1860s, and a California Global Warming Solutions Act (AB 32) in 2006. This chapter considers these five approaches to the projective inference problem of portraying causal relationships leading to future outcomes. The first two (statistical and technological forecasting) ask what is likely and focus on determining the probabilities of relationships and outcomes. The second two (scenario and configurative analysis) ask what is possible and best and focus on the values embedded in outcomes. The last one (RDM) asks what must be avoided or can be adventitiously exploited and focuses on robust actions and decision-rules to produce acceptable and sustainable outcomes. These different questions and emphases lead to different methods and procedures—all of which constitute legitimate forms of projective inference based upon modern understandings of scientific method reviewed in the last part of the paper. Because projective inference is important and because it poses special problems, political methodologists should pay more attention to it and develop better methods and standards for doing it.
E3 ligase DECREASED GRAIN SIZE 1 promotes degradation of a G-protein subunit and positively regulates grain size in rice
Authors: Hao Qixian , Zhu Xingjie , Huang Yunshuai , Song Jiawei , Mou Changling , Zhang Fulin , Miao Rong , Ma Tengfei , Wang Ping , Zhu Ziyan , Chen Cheng , Tong Qikai , Hu Chen , Chen Yingying , Dong Hui , Liu Xi , Jiang Ling , Wan Jianmin 
Published: June 2024

Abstract
Grain size is one of the most important traits determining crop yield. However, the mechanism controlling grain size remains unclear. Here, we confirmed the E3 ligase activity of DECREASED GRAIN SIZE 1 (DGS1) in positive regulation of grain size in rice (Oryza sativa) suggested in a previous study. Rice G-protein subunit gamma 2 (RGG2), which negatively regulates grain size, was identified as an interacting protein of DGS1. Biochemical analysis suggested that DGS1 specifically interacts with canonical Gγ subunits (rice G-protein subunit gamma 1 [RGG1] and rice G-protein subunit gamma 2 [RGG2]) rather than non-canonical Gγ subunits (DENSE AND ERECT PANICLE 1 [DEP1], rice G-protein gamma subunit type C 2 [GCC2], GRAIN SIZE 3 [GS3]). We also identified the necessary domains for interaction between DGS1 and RGG2. As an E3 ligase, DGS1 ubiquitinated and degraded RGG2 via a proteasome pathway in several experiments. DGS1 also ubiquitinated RGG2 by its K140, K145, and S147 residues. Thus, this work identified a substrate of the E3 ligase DGS1 and elucidated the post-transcriptional regulatory mechanism of the G-protein signaling pathway in the control of grain size.
CBP60b clade proteins are prototypical transcription factors mediating immunity
Authors: Li Lu-Shen , Yang Yan-Yan , Chen Yun-Xia , Yu Fei , Hao Guang-Jiu , Yin Gui-Min , Dou Yan , Zhi Jing-Yu , Ma Lin , Wang Jing-Fan , Feng Qiang-Nang , Zhang Yan , Li Sha 
Published: June 2024

Abstract
Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, systemic acquired resistance deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c–f, 4 uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is interchangeable with CBP60b, suggesting clade-specific functionalization. We further show that the function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b–like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest that CBP60b clade TFs are functionally conserved in evolution and positively mediate immunity.
Soundness arguments for consistency and their epistemic value: A critical note
Authors: Zicchetti Matteo 
Published: June 2024

Abstract
Soundness Arguments for the consistency of a (mathematical) theory S aim to show that S is consistent by first showing or employing the fact that S is sound, i.e., that all theorems of S are true. Although soundness arguments are virtually unanimously accepted as valid and sound for most of our accepted theories, philosophers disagree about their epistemic value, i.e., about whether such arguments can be employed to improve our epistemic situation concerning questions of consistency. This article provides a (partial) negative answer to this question and argues that soundness arguments cannot be employed to justify their conclusion. Additionally, soundness arguments are unconvincing; they cannot be employed to overcome reasonable open-mindedness about their conclusion.
United States: Tax classification and treatment of non-U.S. private foundations
Authors: Georgiev Lyubomir , Noked Noam , Desrosiers Christiana 
Published: June 2024

Abstract
This article discusses a U.S. Court of Appeals decision from August 2022 regarding the proper classification of a Liechtenstein Stiftung foundation for U.S. federal tax purposes. It also discusses at a high level the implications of different classifications. Founders (including non-U.S. persons) and their advisers should consider these implications when establishing foundations, particularly when the foundations’ beneficiaries are U.S. persons or if the foundations hold U.S. situs assets.