bluuebunny/crossref_metadata_2025 huggingface dataset:
(075) THE USE OF ONLINE EDUCATIONAL MODULES TO REDUCE FEMALE SEXUAL DYSFUNCTION
Authors: Suarez R , Shah M , Lynn M
Published: June 2024

Introduction

Sex is fundamental to overall health, well-being, and quality of life yet, the prevalence of female sexual dysfunction is alarmingly high. This could be attributed to multiple factors such as an overall dearth of evidence-based information detailing female anatomy, arousal, orgasm, and sexual disorders. In addition, many women face numerous obstacles that limit their access to a comprehensive sexual and reproductive health education. The unavailability and inaccessibility of knowledge regarding the female sexual experience can prevent many women from truly appreciating and understanding their bodies. This can lead to a variety of negative outcomes, including depression, anxiety, low self-esteem, and decreased well-being.

Objective

Several of these outcomes are most prevalent in young women; thus, it is critical that we educate this age group using delivery methods best suited for a young demographic.

Methods

In this study, we created a brief online educational module for women between the ages of 18 and 29 years old, which explained various aspects of the female sexual experience including female anatomy, orgasm responses, and masturbation. The module also shared resources women may use if they are experiencing issues regarding sex or pleasure. We expected to see greater female sexual literacy among women who completed the module (intervention) compared to those who did not (control). 13 women between the ages of 18 and 29 years old who were attending their annual gynecologic well-visit were recruited and randomly assigned to the intervention or control group.

Results

Although all participants from both groups rated sex education as important (N=13), less than half (N=5) reported having received formal sex education including female sexual functioning. Furthermore, only half (N=6) correctly disagreed when asked if the outer part of the female reproductive system was called “vagina.” However, post-test surveys showed no significant difference in knowledge between those who watched the module and those who did not. We attribute this to the sample size being too small, to the age range being too wide, and to the information presented in the module being too basic for this age group.

Conclusions

It is imperative that we not only continue to explore the female sexual experience, but that we also continue to improve ways to deliver that information. Further research on the use of online modules for sex education should consider its population’s degree of knowledge, limit their sample’s age range, and focus on issues its population commonly inquires about.

Disclosure

No.
(111) PLATELET-RICH PLASMA FOR IMPROVEMENT OF SEXUAL DYSFUNCTION: A PILOT STUDY
Authors: Kim S E
Published: June 2024

Introduction

Platelet-rich plasma has been widely used in various field of medicine. Some studies have shown that PRP helps improving sexual function, but most studies were conducted on men. There are also studies showing that it helps women’s sexual function, but it is very limited.

Objective

This study conducted to determine whether PRP was effective for women complaining of sexual dysfunction.

Methods

This retrospective study included 34 women who underwent PRP for improving sexual function from December 2022 to September 2023. Patients underwent a total of three procedures on schedules 0, 1, and 4 months. Before performing each procedure, a survey was conducted on questionnaire related to sexual dysfunction. The results of a total of 22 questions were analyzed by dividing them into sexual desire or sexual interest, sexual excitement, lubrication, orgasm, satisfaction with sexual life, pain during intercourse, and urinary incontinence.

Results

In the categories of sexual desire or sexual interest, sexual excitement, and satisfaction with sexual life scores showed a significant increase after PRP treatment (p < 0.001, p < 0.001, and p < 0.003, respectively). There was a significant increase in orgasm between the first and third treatments (p < 0.021), but it was not statistically significant overall. Symptoms related with lubrication, pain, and urinary incontinence all improved, but did not show statistical significance.

Conclusions

This study demonstrated that PRP improved some categories of sexual dysfunction.

Disclosure

No.
(116) SUBJECTIVE AND GENITAL SEXUAL RESPONSE IN FEMALE BREAST CANCER SURVIVORS: RESULTS FROM A PSYCHOPHYSIOLOGY STUDY
Authors: Grosse-Rueschkamp M S , Dörfler C , Tissen-Diabaté T , Kronthaler S , Beier K M , Hatzler L
Published: June 2024

Introduction

Sexual dysfunction is a prevalent concern affecting more than 70% of female breast cancer survivors, casting a substantial shadow on their quality of life. Beyond the physical impact of cancer and its treatments, the emotional and psychological toll of sexual dysfunction introduces additional challenges, amplifying stress levels and undermining overall well-being. Acknowledging the profound implications of sexual dysfunction in this group and the absence of therapies, there is an urgent need to delve deeper into the intricacies of its manifestations.

Objective

This study aimed to gather preliminary data on psychophysiological aspects of sexual function in premenopausal breast cancer patients undergoing antihormonal therapy and compare them with a healthy control group. Exploring sexual arousal in breast cancer patients may unveil potential targets for innovative treatment strategies to address sexual dysfunction in this population.

Methods

Participants were prescreened during a telephone interview. We included 40 premenopausal breast cancer survivors with an age range of 29 to 57 years (M = 43.5, SD = 6.36) on current hormonal treatment and 20 healthy controls with an age range of 22 to 35 (M = 27.55, SD = 3.19). Physiological measures (VPA and HRV), subjective sexual arousal (SSA) and self-reported orgasm were assessed in response to audiovisual stimuli and vibrotactile clitoral stimulation sexual stimuli in breast cancer survivors and healthy controls. Self-reported measures like the Female Sexual Function Index (FSFI), the Sexual Self-Esteem Inventory (SSEI) und the PROMIS29 were incorporated. Data were analyzed using 2-level mixed effect models.

Results

No significant differences in VPA scores were observed between healthy controls and breast cancer survivors. Both groups exhibited a greater genital response to clitoral vibrator use than to visual stimuli. Group differences emerged in SSA and HRV, with higher SSA and lower HRV being detected. Breast cancer survivors climaxed less frequently than healthy controls and had significantly lower self-reported sexual function.

Conclusions

Physiological measures of arousal in breast cancer survivors were comparable to healthy controls and only subjective arousal differed. This finding indicates that subjective arousal should be further explored as the focus of intervention and treatment methods for breast cancer patients experiencing sexual dysfunction. Our findings underscore the importance of tailored strategies that resonate with individual narratives, acknowledging the emotional intricacies of post-cancer sexual well-being. This study not only contributes to scientific knowledge but also calls for a compassionate and personalized treatment paradigm, enriching the landscape of survivorship care.

Disclosure

Yes, this is sponsored by industry/sponsor: WOW Tech GmbH

Clarification: No industry support in study design or execution.
(127) TRAUMA INFORMED CARE TO REDUCE ANTEPARTUM COMPLICATIONS IN SURVIVORS OF TRAUMA
Authors: Low A
Published: June 2024

Introduction

Life trauma permeates through society and across cultures. It impacts the individual, community, and society. Trauma may include but is not limited to adverse childhood experiences (ACEs), sexual assault and violence, domestic violence, and interpersonal violence (IPV). In the United States, 1 in 3 women experience physical IPV, 1 in 4 experience sexual assault, and 17% of adults have experienced 4 or more ACEs (CDC 2022, 2023). Experiencing trauma leads to a cascade of effects that infiltrate every aspect of life and causes higher levels of chronic stress. In those who are pregnant or giving birth, a history of trauma, particularly sexual assault, leads to adverse antepartum outcomes.

Objective

After this presentation, the learner will be able to: 1. Define trauma (ACEs, sexual assault, DV, IPV). 2. State the signs and symptoms of trauma. 3. Identify the antepartum complications associated with a history of trauma. 4. Explain the impact that a history of sexual assault has on the birth giver. 5. Define trauma informed care. 6. Identify the components of trauma informed care. 7. State the importance of using trauma informed care as a midwife and WHNP.

Methods

The methods used to address this topic include a literature review and podium style presentation of findings.

Results

Main findings include increased rates of miscarriage, preterm birth, post traumatic stress disorder, placental abruption, premature rupture of membranes, and low birth weight in pregnant survivors of past trauma. Additionally, the dynamic interplay between the Social Determinants of Health and violence experienced during pregnancy must be considered. Low household income, racism, lack of social support, as well as food and housing insecurity increased rates of intimate partner violence experienced during pregnancy. Trauma informed care has been shown to reduce psychological symptom severity and has been integrated into midwifery care to attempt to reduce these outcomes and prevent further traumatization of the client.

Conclusions

As pregnancy and childbirth are intimate and personal in nature, using a trauma informed model of care is crucial to identifying clients with trauma histories and caring for them in a manner that is cognizant of their lived experiences and potential antepartum outcomes. Future providers must receive adequate education and training regarding trauma informed care in an effort to prevent adverse outcomes and prevent re-traumatization of their clients.

Disclosure

No.
The properties of AGN in dwarf galaxies identified via SED fitting
Authors: Bichang’a B , Kaviraj S , Lazar I , Jackson R A , Das S , Smith D J B , Watkins A E , Martin G
Published: June 2024

Given their dominance of the galaxy number density, dwarf galaxies are central to our understanding of galaxy formation. While the incidence of active galactic nuclei (AGN) and their impact on galaxy evolution have been extensively studied in massive galaxies, much less is known about the role of AGN in the evolution of dwarfs. We search for radiatively efficient AGN in the nearby (0.1 < z < 0.3) dwarf (108 M⊙ < M⋆ < 1010 M⊙) population, using spectral energy distribution fitting (via prospector) applied to deep ultraviolet to mid-infrared photometry of 508 dwarf galaxies. Around a third (32 ± 2 per cent) of our dwarfs show signs of AGN activity. We compare the properties of our dwarf AGN to control samples, constructed from non-AGN, which have the same distributions of redshift and stellar mass as their AGN counterparts. Kolmogorov–Smirnov tests between the AGN and control distributions indicate that the AGN do not show differences in their distances to nodes, filaments, and nearby massive galaxies from their control counterparts. This indicates that AGN triggering in the dwarf regime is not strongly correlated with local environment. The fraction of AGN hosts with early-type morphology and those that are interacting are also indistinguishable from the controls within the uncertainties, suggesting that interactions do not play a significant role in inducing AGN activity in our sample. Finally, the star formation activity in dwarf AGN is only slightly lower than that in their control counterparts, suggesting that the presence of radiatively efficient AGN does not lead to significant, prompt quenching of star formation in these systems.
Transition from decaying to decayless kink oscillations of solar coronal loops
Authors: Nakariakov Valery M , Zhong Yu , Kolotkov Dmitrii Y
Published: June 2024

The transition of an impulsively excited kink oscillation of a solar coronal loop to an oscillation with a stationary amplitude, i.e. the damping pattern, is determined using the low-dimensional self-oscillation model. In the model, the decayless kink oscillations are sustained by the interaction of the oscillating loop with an external quasi-steady flow. The analytical solution is based on the assumption that the combined effect of the effective dissipation, for example, by resonant absorption, and interaction with an external flow, is weak. The effect is characterized by a dimensionless coupling parameter. The damping pattern is found to depend upon the initial amplitude and the coupling parameter. The approximate expression shows a good agreement with a numerical solution of the self-oscillation equation. The plausibility of the established damping pattern is demonstrated by an observational example. Notably, the damping pattern is not exponential, and the characteristic decay time is different from the time determined by the traditionally used exponential damping fit. Implications of this finding for seismology of the solar coronal plasmas are discussed. In particular, it is suggested that a very rapid, in less than the oscillation period, decay of the oscillation to the stationary level, achieved for larger values of the coupling parameter, can explain the relative rareness of the kink oscillation events.
WALLABY pilot survey: the Tully–Fisher relation in the NGC 4808, Vela, and NGC 5044 fields
Authors: Mould Jeremy , Jarrett T H , Courtois Hélène , Bosma Albert , Deg Nathan , Dupuy Alexandra , Staveley-Smith Lister , Taylor E N , English Jayanne , Rajohnson S H A , Kraan-Korteweg Renée , Forbes Duncan , Dénes Helga , Lee-Waddell Karen , Shen Austin , Wong O I , Holwerda Benne , Koribalski Bärbel , Leahy Denis , Piña Pavel Mancera , Yu Niankun
Published: June 2024

The Tully–Fisher Relation (TFR) is a well-known empirical relationship between the luminosity of a spiral galaxy and its circular velocity, allowing us to estimate redshift independent distances. Here we use high signal-to-noise H i 21-cm integrated spectra from the second pilot data release (PDR2, 180 deg2) of the Widefield ASKAP L-band Legacy All-sky Blind surveY (WALLABY). In order to prepare for the full WALLABY survey, we have investigated the TFR in phase 2 of the pilot survey with a further three fields. The data were obtained with wide-field Phased Array Feeds on the Australian Square Kilometre Array Pathfinder (ASKAP) and have an angular resolution of 30 arcsec and a velocity resolution of $\sim$4 km s−1. Galaxy luminosities have been measured from the Wide-field Infrared Survey Explorer, and optical galaxy inclinations from the Dark Energy Camera Legacy Survey. We present TFRs for wavelengths from 0.8 to 3.4 μm. We examine sources of galaxy inclination data and investigate magnitudes from the DECam Local Volume Exploration Survey and DENIS catalogues and the 4HS target catalogue based on the VISTA Hemisphere Survey. We consider the baryonic TFR. These are all of interest for TFR using the full WALLABY survey of 200 000 galaxies. We demonstrate that WALLABY TFR distances can take their place among state-of-the-art studies of the local velocity field.
African, Black, and Western Conceptions of Human Dignity
Authors: Molefe Motsamai
Published: June 2024

The article highlights the potential that African and Black Philosophy can contribute towards the debates on human dignity. It facilitates a three-way philosophical conversation among the Western, African, and Black conceptions of human dignity. It is motivated by the skepticism in the African and Black approaches to ethics that reject the view that some ontological capacity can ground intrinsic value, or human dignity. The article distinguishes the merit-based (the African and Black Philosophy) from the capacity-based approaches (the Western philosophy) to human dignity. In light of the comparisons among the three theories of human dignity, the article identifies three important lessons for moral-political philosophy. First, the Western conception of human dignity needs to explain and justify grounding of value on a descriptive feature. Secondly, the Black conception of dignity is a version of virtue-based account of it, which places a prime on resistance and struggle against domination. Finally, the capacity-based approach seems to have moral-theoretic advantages in dealing with issues in bioethics, environmental ethics, and political philosophy, which the African and Black conceptions of human dignity seems not to have.
ATRT-02. RECAPITULATING THE POST-SURGICAL BRAIN MICROENVIRONMENT OF ATYPICAL TERATOID RHABDOID TUMOURS TO IDENTIFY MEMBRANE PROTEIN CANDIDATES FOR TARGETED THERAPY
Authors: Mistry Shaylen M , Porter Harry , McCorie Phoebe , Snary Anya , Bailey Hannah , Layfield Robert , Rahman Ruman
Published: June 2024

BACKGROUND

Atypical Teratoid Rhabdoid Tumours – (AT/RT) are rare and aggressive tumours primarily arising in the hind brain of children under three, conferring median survival of <12 months. Surgery remains the only standard treatment; however tumours recur from post-surgical residual disease. The utilisation of PolyEthylene Glycol Diacrylate – (PEGDA) hydrogel and decellularised human brain cerebellum extracellular matrix aim to recapitulate AT/RT post-surgery brain microenvironments, where we hypothesise AT/RT plasma membrane proteins represent viable molecular therapy targets.

METHODS

AT/RT and astrocyte membrane protein cellular fractions were extracted and analysed using liquid chromatography-mass spectrometry. Proteomic analyses was integrated to identify differentially expressed AT/RT and astrocyte membrane proteins.

RESULTS

PEGDA and decellularised brain tissue were biocompatible for AT/RT-astrocyte co-cultured spheroid growth. AT/RT and astrocyte KEGG Pathway analysis revealed more specific oncology-based pathway expression in membrane protein than total protein, thus reinforcing membrane proteins as suitable therapeutic targets. Between the top 20 expressed membrane proteins, only ATP1A1 was shared exclusively between all AT/RT cells and astrocytes, suggesting a potential functional role. Membrane proteins showing shared expression when normalised against each AT/RT cell line included ATP1A1, HSPD1, GNA13 and SLC3A2, indicating biological similarities between AT/RT subtypes. Membrane proteins expressed similarly in AT/RT-MYC subtypes include ATP1A1, SLC7A5 and EEF1A1. ATP1A1 network analyses of AT/RT and astrocyte membrane protein pathways displayed strong interactions with ATP1B1, SLC7A5 and SLC3A2, therefore likely to map common expressed shared pathways.

CONCLUSIONS

AT/RT membrane protein pathways offer novel therapeutic targets directly amenable for drug repurposing. Future work prioritises proteomic analysis utilising 3D AT/RT spheroids and cerebellum brain tissue to maximise accurately recapitulating AT/RT post-surgical microenvironments.
ATRT-08. ATYPICAL TERATOID RHABDOID TUMOR IN AN ADULT PATIENT WITH DOWN SYNDROME
Authors: Judd Dallin , Almefty Kaith K , Vern-Gross Tamara Z , Hoffman Lindsey M , Tiwari Nishant , Vaughn Jennifer A , Mangum Ross
Published: June 2024

BACKGROUND

Atypical teratoid/rhabdoid tumor (ATRT) is a malignant, highly aggressive embryonal tumor of the central nervous system. Long-term survival remains dismal despite aggressive multimodal therapy, including a maximal safe surgical resection and intensive systemic chemotherapy +/- radiation therapy. While these tumors typically present in infancy or early childhood, there are scattered case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports.

CASE REPORT

A 25-year-old female with Down syndrome presented with nausea, vomiting, dysphagia, and facial droop and was found to have an avidly enhancing, left cerebellopontine angle mass. There was initial clinical suspicion for leukemic chloroma given the patient’s Down syndrome status and known association with higher rates of hematologic malignancy concurrent with a dramatic scarcity of solid tumors in the Down syndrome population. However, histology demonstrated sheets of high-grade rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing defined a frameshift mutation in SMARCB1 (p.C298), and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton radiation, followed by chemotherapy on a modified regimen based on the Children’s Oncology Group protocol, ACNS0333. Systemic methotrexate and all consolidative high-dose chemotherapy with stem cell rescue were omitted due to concern for heightened risk of treatment-related toxicity. The patient remains alive and clinically asymptomatic 19 months from diagnosis.

CONCLUSION

This report represents the first known case of ATRT in an adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Adult ATRT is a rare entity without standardized treatment or established prognostic understanding. Further studies are needed to define an appropriate risk-adapted therapeutic approach for this patient population.
ATRT-14. TARGETING ATYPICAL TERATOID RHABDOID TUMORS USING A NOVEL BI-FUNCTIONAL COREST INHIBITOR
Authors: Geethadevi Anupa , Collard Marianne , Findlay Tyler , Fisher Robert , Vaidya Nikhil , Deng Yiming , Eberhart Charles , Cole Philip , Alani Rhoda , Rubens Jeffrey , Raabe Eric
Published: June 2024

BACKGROUND

Atypical teratoid/rhabdoid tumors (ATRT) are deadly infantile brain tumors driven by a loss-of-function mutation of SMARCB1, a critical component of the SWI-SNF chromatin remodeling complex. However, residual SWI-SNF activity inhibits EZH2 at all loci except where CoREST colocalizes with these complexes, specifically contributing to ATRT pathogenesis. This results in hypermethylation and subsequent repression of genes coding for neuronal differentiation and tumor suppressors, accounting for ATRTs’ stem-like state, aggressive growth, and therapy resistance. We functionally inhibited the CoREST complex in ATRT cells by targeting its core enzymes LSD1 and HDAC1/2 using a bi-functional inhibitor, corin.

METHODS

We evaluated the efficacy of corin to target ATRT cells (BT37, CHLA05 and CHLA06) by measuring cell proliferation (BrdU immunofluorescence/IF), apoptosis (CC3 IF, cPARP Western blotting/WB, MUSE Annexin V), histone modifications (WB) and neuronal differentiation (WB, IF). Whole mRNA sequencing and ATAC-Seq were performed to see the global transcriptomic and chromatin changes driven by corin. Further, we examined the long-term survival advantage rendered by corin in an in-vivo orthotopic xenograft model of ATRT.

RESULTS

Corin reprogrammed the chromatin structure in ATRT cells in favor of pathways related to neuronal differentiation, cell differentiation, and axonal development while downregulating pathways related to proliferation and cell cycle (mRNA Seq, ATAC-Seq). Corin inhibited AT/RT cell growth and proliferation (p<0.05), increased apoptosis (p<0.05), increased H3K4me1 and H3K9Ac levels (p < 0.001), and induced neuronal differentiation (IF: Beta-3-tubulin, MAP2, Synaptophysin). Intratumoral delivery of corin increased the median survival of mice bearing aggressive orthotopic CHLA06 tumors from 14 to 35 days compared to control (p=0.02, Log Rank test).

CONCLUSIONS

Targeting the CoREST complex with corin disrupts ATRT’s epigenetic abnormalities, reversing their stem-like state and slowing tumor growth, thus presenting a promising new strategy that may translate into the clinical setting to help improve ATRT’s dismal survival.
ATRT-17. INHIBITING THE MAP KINASE PATHWAY WITH MEK INHIBITOR MIRDAMETINIB SUPPRESSES CANCER GROWTH IN ATYPICAL TERATOID/RHABDOID TUMORS
Authors: Deng Yiming , Malebranche Kristen , Findlay Tyler , Geethadevi Anupa , Eberhart Charles , Rubens Jeffrey , Raabe Eric
Published: June 2024

BACKGROUND

Atypical teratoid/rhabdoid tumors (ATRT) are poor-prognosis infantile brain tumors. Our prior studies examining ATRT primary tissues have shown an increased expression of phospho-ERK, a downstream effector of MEK in the mitogen-activated protein kinase (MAPK) pathway. The elevated MAPK pathway potentially contributes to drug resistance, aggressive cancer growth, and poor treatment outcomes. Mirdametinib is a highly specific MEK1/2 inhibitor reported to have superior blood-brain-barrier penetration compared to other MEK inhibitors. We hypothesized that mirdametinib can suppress ATRT tumor growth and improve overall survival.

METHODS

Mirdametinib effects were assessed through western blot for MAPK markers. Western blot analysis, Muse flow cytometer assays, and immunofluorescence were used for proliferation and apoptosis. Mirdametinib impact on survival was determined in orthotopic xenograft models of ATRT.

RESULTS

Mirdametinib decreased MAPK pathway activity in five ATRT cell lines (western blot: phospho-ERK). Cell lines treated with mirdametinib exhibited lower rates of proliferation (western blot: phospho-Rb; BrdU immunofluorescence staining: CHLA05 p=0.015, CHLA06 p<0.0001, BT37 p<0.0001 compared to DMSO control by t-test). Mirdametinib induced apoptosis in ATRT cells (western blot: cPARP; Muse Annexin V Assay: CHLA04, CHLA05, CHLA06, and BT37, p<0.0001, CHLA266, p<0.01 compared to DMSO control by t-test; cleaved caspase-3 immunofluorescence staining: CHLA05, CHLA06, and BT37, p<0.0001 compared to DMSO control by t-test). Daily oral delivery of mirdametinib treatment significantly extended the survival of mice bearing the very aggressive orthotopic CHLA06 tumors (17 to 24 days, log-rank test p=0.038 compared to vehicle control) and decreased the expression of phospho-ERK (western blot). Testing against additional ATRT orthotopic xenografts is currently underway.

CONCLUSIONS

Mirdametinib inhibits the MAPK pathway both in vitro and in vivo, suppressing proliferation and inducing apoptosis in ATRT. Our studies suggest that pharmacologically inhibiting the MAPK pathway with mirdametinib may be an effective strategy to target ATRT and help extend survival in this deadly disease.
BIOM-01. CARBONIC ANHYDRASE IX INTERPLAY WITH LOCAL AND SYSTEMIC IMMUNE RESPONSE IN PEDIATRIC BRAIN TUMORS
Authors: Kapitancuke Monika , Petroska Donatas , Petrosiute Agne , Luciunaite Asta , Grinceviciene Svitrigaile , Matulis Daumantas , Rocka Saulius , Rinkevicius Dainius , Raugalas Ramunas , Rascon Jelena
Published: June 2024

BACKGROUND

Brain tumors (BT) remain the leading cause of death among childhood cancers. There is an urgent need to identify novel targets in these patients. BT progression depends on the adaptive responses to hypoxia. Carbonic anhydrase IX (CAIX) helps cancer cells survive in a hypoxic environment and can be potentially as a therapeutic target. The role of CAIX in the interplay between the tumor and immune cells requires in-depth investigation to design effective therapies.

METHODS

Fresh BT, blood, and intraoperative cerebrospinal fluid (iCSF) samples were collected prospectively from pediatric patients, who underwent brain tumor surgery at Vilnius University Hospital Santaros Klinikos from March 2022 to December 2023. All tumor types were included. Immunohistochemistry (IHC) and flow cytometry (FC) were performed to analyze the expression of CAIX and selected immunological markers in the fresh tumor, iCSF and peripheral blood mononuclear cells (PBMCs). Soluble CAIX content in serum and iCSF was assessed by ELISA. In addition, a retrospective analysis of previously diagnosed pediatric glioma specimens was performed by IHC.

RESULTS

Twelve patients with heterogeneous BT types have been enrolled prospectively and 17 patients with glioma were reviewed retrospectively. Glioma accounted for 72% (21/29) of all samples. IHC showed that 57% of gliomas were positive for CAIX as well as a moderate correlation between the CAIX score and the expression of CD44, CD206, and CCR2 markers. PD-1/PD-L1 expression was negligible. In the prospective cohort, 83% (10/12) of BT tissue was positive for CAIX by IHC and FC. Soluble CAIX was detectable in 40% of iCSF samples, but not in serum. We found a correlation trend of CAIX expression in the fresh tumor cells and iCSF with increased CCR2 expression on CD45+ PBMCs.

CONCLUSIONS

This interim analysis showed a correlation between CAIX tumor expression and immune biomarkers, prompting further investigation by enrolling more patients.
BIOM-05. THE GUT-MICROBIOTA COMPOSITION IN PEDIATRIC BRAIN TUMORS: AN EMERGING CRUCIAL PLAYER
Authors: Dossena Chiara , Bergamaschi Luca , Rossignoli Federico , Licata Armando G , Oriani Matilde , Marra Manuela , Carollo Maria , Massimino Maura , De Cecco Loris
Published: June 2024

BACKGROUND

Central nervous system (CNS) tumors represent the main cause of cancer-related deaths in children diagnosed at 0–14 years. It has been demonstrated that the bidirectional interaction between gut microbiota and brain, called microbiota-gut-brain axis, has a key role in pathophysiological processes, mediating proliferation of brain tumor cells. The aim of this study was to determine whether the gut microbiota composition of pediatric patients affected by CNS tumors has peculiarities.

METHODS

We included 42 pediatric patients from the clinical study NET-2019-12371188 that were divided in two groups: i) 12 affected by SNC tumors (group 1); ii) 30 affected by other tumor types (group 2), non related to CNS. From their stool samples, microbial DNA was extracted, 16S DNA libraries were generated and sequenced on IONS5xl (ThermoFisher). From the resulting operational taxonomic unit (OTU) tables, the composition of gut-microbiota was analyzed.

RESULTS

To determine the richness of gut microbiota in terms of different taxa, alpha diversity analysis was performed. We applied the number of observed features as data matrix and it was lower in group 1 compared to group 2 (p-value= 0.003); on the other side, the homogeneity of taxonomic groups was determined by Pielou’s evenness index, that was higher in group 1 (p-value=0.018), compared to group 2. Beta-diversity measured with unweighted UniFrac metrics revealed that the taxonomic and phylogenetics composition of gut microbiota is different between group 1 and 2 (p-value= 0.03). Finally, linear discriminant analysis effect size (LEfSe) revealed an increase of genus from RF32 order in group 1, while in group 2 genus Blautia ad genus from Coriobacteriaceaea family increased.

CONCLUSIONS

In conclusion, gut microbiota has a peculiar composition in pediatric patients affected by CNS tumors.
CP-14. VOLUMETRIC ANALYSIS OF PAEDIATRIC CRANIOPHARYNGIOMAS: CLINICAL-RADIOLOGICAL CORRELATION STUDY
Authors: Yamaki Vitor Nagai , Sidpra Jai , Peres Bruno Santanna , Massey Flavia , Quianga Catuto Domingos Alexandre , da Borsatto Guilherme Jose Costa , Telles Joao Paulo Mota , Silva Inês Nobrega , Martinez-Barbera Juan Pedro , Biswas Asthik , Mankad Kshitij , Gan Hoong-Wei , Marcus Hani J , Jeelani Noor ul Owase , Hargrave Darren R , Matushita Hamilton , Marie Suely Kazue Nagahashi , Aquilina Kristian
Published: June 2024

BACKGROUND

Craniopharyngioma are heterogeneous hypothalamopituitary tumours with solid and cystic components which have a distinct natural history. Neuroimaging follow-up and the definition of progressive disease is challenging due to unpredictable growth of the inflammatory cystic component.

METHODS

This multicentre retrospective observational study aimed to describe the clinical-radiological correlation of craniopharyngiomas at two paediatric neurosurgery units (GOSH,UK and USP,Brazil). Craniopharyngiomas treated over a 20-year period were identified and standardized clinical outcomes recorded. Baseline MRIs were reviewed and volumetric T1-weighted images segmented by a board-certified paediatric neuroradiologist.

RESULTS

Of 123 patients, 92 baseline MRIs were available for image analysis (USP=32; GOSH=60). No differences between series were identified in either demography (mean age: USP=9.2±4.6; GOSH=8.2±4.1 years) or tumour characteristics, with tumours being predominantly cystic (USP=75%; GOSH=76%), localised to the sellar/suprasellar region (USP=84%; GOSH: 88%), and on pre-chiasmatic (USP=34%; GOSH=22%) or retro-chiasmatic (USP=59%; GOSH=67%) locations. Pre-chiasmatic tumours were associated with an increased prevalence of visual symptoms at presentation (p=0.006) and worse recovery of visual acuity at long-term follow-up (p=0.021). Regarding volumetric analysis, mean volumes were 16.6±25.1cm3 for the cystic component and 38.3±10cm3 for the solid component. Volumes of the solid and cystic components had no correlation with each other. Larger cystic tumour volumes were correlated with a greater prevalence of diabetes insipidus at presentation (p=0.06). Larger solid tumours were significantly related to younger ages (p=0.02) and had worse PFS in our series. In terms of long-term outcomes, high volume cystic tumours were related to worse hypothalamic outcomes. In multivariate analysis (n=92), Paris classification did not predict long-term outcomes.

CONCLUSIONS

Volumetric analysis of craniopharyngiomas showed significant correlation with the onset of diabetes insipidus and hypothalamic long-term outcomes. Larger cystic craniopharyngioma were more common in younger patients. The Paris classification did not predict long-term outcomes in multivariate analysis.
CP-16. PROTEOMIC ANALYSIS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA REVEALS A COMPLEX NETWORK OF ECM REMODELING
Authors: Knox Aaron , Medlin Stephen , Chee Keanu , Staulcup Susan , Prince Eric W , Hankinson Todd C , Mitra Siddhartha
Published: June 2024

BACKGROUND

Adamantinomatous craniopharyngiomas (ACPs) are the most challenging pituitary tumors in children. Despite their histological classification as benign, ACPs exhibit an aggressive clinical demeanor, posing challenges in management and conferring a suboptimal quality of life. The anatomical intricacies of ACPs often preclude complete surgical excision. The greatest morbidity of ACP is associated with damage to the hypothalamus - iatrogenically or through direct invasion, which may be dependent upon extracellular matrix (ECM) remodeling. We endeavored to describe the ECM components of ACPs and the protein milieu that may alter the ECM.

METHODS

High throughput imaging mass cytometry (IMC) alongside conventional histological staining methods. IMC offers unparalleled resolution in detecting ECM constituents, which may play pivotal roles in tumor pathophysiology and could represent novel therapeutic targets. We also employed SomaScan, an innovative, high-throughput, aptamer-based protein quantification platform. SomaScan utilizes Slow Off-Rate Modified Aptamers (SOMAmer Reagents) for the measurement of a broad spectrum of proteins within various biological fluids, including plasma and cyst fluid.

RESULTS

We identified prominent collagen tracts within ACP, which are further interspersed with areas of increased fibrosis surrounding wet keratin, suggestive of focal inflammatory response to cyst fluid. SomaScan identified elevated levels of proteins implicated in neutrophil degranulation. Neutrophil degranulation plays a significant role in ECM remodeling, a process critical to tumor progression and invasion. The association of neutrophils with ECM remodeling in ACPs suggests a potential mechanism through which these tumors might facilitate their own growth and invasion. The elevated protein markers of neutrophil degranulation may also serve as potential biomarkers or therapeutic targets, offering a novel approach to managing these tumors.

CONCLUSIONS

By integrating the data from IMC and SomaScan, our findings reveal a complex interplay between ACPs and the immune system, particularly highlighting the role of neutrophils in the tumor microenvironment.
DIPG-03. VENTRICULAR CEREBROSPINAL FLUID SAMPLING IN PEDIATRIC DIFFUSE MIDLINE GLIOMA PATIENTS: INSTITUTIONAL EXPERIENCE AND REVIEW OF THE LITERATURE
Authors: Li Daphne , Stellpflug Wendy , Romanski Kathy , Speck Stacy , Saratsis Amanda
Published: June 2024

BACKGROUND

Increasing evidence suggests that circulating biomarkers may serve diagnostic and longitudinal monitoring purposes in pediatric neuro-oncology. Mutant tumor DNA is detectable in the cerebrospinal fluid (CSF) of pediatric diffuse midline glioma (DMG) patients and quantity can reflect disease burden. CSF sampling (“liquid biopsy”) via a CSF access device could therefore play a role in DMG management. Therefore, we set to evaluate the incidence of hydrocephalus (HCP) in DMG patients, and to characterize ventricular reservoir placement and access practices.

METHODS

A single institution retrospective review of DMG patients <21-years-old was performed (1984-2019). MEDLINE searches for reports of ventricular reservoir or shunt placement in DMG, and reservoir access for intraventricular chemotherapy (IVC) were performed.

RESULTS

At our institution, 62.6% of DMG patients (67/108) required intervention for HCP: 19.4% provided transient CSF access (ETV alone n=3, EVD n=8, unspecified n=2), and 80.6% permanent CSF access (ETV + reservoir n=13, shunt n=41). Further, 22/34 patients with initially transient CSF devices required conversion to a permanent device. Five devices were revised for malfunction, one for infection. Seventeen articles cited HCP in 22% to 100% of DMG patients. IVC administration was described in 632 patients (seven articles), with 42 infectious and 63 non-infectious complications.

CONCLUSIONS

Management of HCP is often necessary in children with DMG. Given the low rate of clinical risk associated with VAD placement and access, and the potential utility of longitudinal disease monitoring via CSF analysis, VAD placement could be considered in future clinical trials to guide DMG treatment.
DIPG-09. PROGNOSTIC FACTORS IN REIRRADIATED DIFFUSE INTRINSIC PONTINE GLIOMA: CLINICAL AND RADIOMIC ANALYSIS
Authors: Wawrzuta Dominik , Chojnacka Marzanna , Drogosiewicz Monika , Pędziwiatr Katarzyna , Dembowska-Bagińska Bożenna
Published: June 2024

BACKGROUND

Diffuse Intrinsic Pontine Glioma (DIPG) is a lethal pediatric brain tumor. Radiation therapy (RT) is the standard treatment, with reirradiation considered at progression. However, the prognostic factors for reirradiation remain unclear. This study aims to investigate the outcomes of patients with DIPG undergoing reirradiation and to identify radiomic prognostic factors.

METHODS

We analyzed patients with histopathologically proven DIPG who underwent reirradiation at our institution. We delineated pre-reirradiation tumors using 3D Slicer software and extracted radiomic features from FLAIR MRI sequences using the Python package PyRadiomics. Finally, we used the least absolute shrinkage and selection operator (Lasso) for Cox’s proportional hazard model with leave-one-out cross-validation to select optimal prognostic factors for survival after reirradiation. We have also compared the reirradiated group with our cohort of 22 non-reirradiated DIPG patients eligible for reirradiation but whose parents chose only supportive care at progression.

RESULTS

The study included 15 patients who received reirradiation at the first progression, with a total dose of 20 Gy or 24 Gy in 2 Gy fractions. Reirradiation was well tolerated, without grade >2 toxicity. Neurological improvement was observed in 80% of patients. Median survival from the end of the first RT was significantly (p = 0.01) longer in the reirradiated group (68 weeks) compared to the non-reirradiated group (25 weeks). The Cox model demonstrated a concordance of 0.88 (95% CI: 0.83–0.92), revealing that tumor sphericity and structural gray-level heterogeneity in FLAIR MRI images were associated with more prolonged survival in reirradiated patients.

CONCLUSIONS

Reirradiation is a safe and effective approach for patients with DIPG. MRI-based radiomic models could help predict survival after treatment. Our results revealed that tumors with low sphericity and high homogeneity of gray levels are associated with a worse prognosis after reirradiation.
DIPG-11. PRECLINICAL EFFICACY OF B7-H3 CAR T CELLS IN COMBINATION WITH ONC206
Authors: Timpanaro Andrea , Song Edward , Biery Matthew C , Lau Davina , Meechan Michael , Elena-Sanchez Leonel , Vo Linh Thuy , Gustafson Joshua , Koschmann Carl , Dun Matthew D , Foster Jessica B , Jensen Michael C , Vitanza Nicholas A
Published: June 2024

Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric tumor of the pons affecting over 300 children in the U.S. each year. Chimeric antigen receptor (CAR) T cells are a targeted immunotherapy with remarkable clinical success against hematological malignancies and now are being investigated against central nervous system (CNS) tumors. B7-H3 is a surface antigen specifically expressed on nearly all DIPG but not on normal brain providing an attractive therapeutic window. Therefore, Seattle Children’s opened BrainChild-03 (NCT04185038), a first-in-human phase 1 trial of repeatedly dosed intracranial B7-H3 CAR T cells for children with DIPG. We found the highest planned dose (10x107 cells) to be tolerable and observed preliminary signals of efficacy. ONC206 is a small molecule ClpP-agonist and DRD2-antagonist derivative of ONC201 that is currently being evaluated on PNOC-023 (NCT04732065). Here, we set out to evaluate the combinatorial potential of these modalities. ONC206 effectively reduced DIPG tumor cell viability (IC50 = ~300 nM compared to ONC201 ~1400 nM) against four treatment-naïve patient-deriving DIPG models representing a range of molecular subtypes. Using multiple orthogonal systems, apoptosis of DIPG cells was confirmed. We found that ONC206 drives tumor cell mitochondrial dysfunction and upregulation of DR5, a cell-death receptor involved in the TRAIL pathway, whereas levels of B7-H3, DRD2, and ClpP remain constant. We previously published the efficacy of B7-H3 CAR T cells against DIPG, but here - using low effector:tumor (E:T) ratios (e.g. 0.5:1) of activated B7-H3 CAR T cells and low-dose ONC206 (e.g. 200 nM) - we found a significant in vitro combinatorial benefit against DIPG (p<0.01). Supportive biologic studies suggest this could be an additive benefit and in vivo studies are currently ongoing. Based on the clinical translation of B7-H3 CAR T cells and ONC206, we aim to further validate this combinatorial benefit to help future patients.
DIPG-12. ASSESSING THE EFFICACY OF BAY2402234 IN COMBINATION WITH ONC201 IN IMMUNE-COMPETENT MURINE MODELS OF DIFFUSE MIDLINE GLIOMA
Authors: Mizoguchi Sean , Kritzer Bettina , Cerna Steven J , Packer Roger , Yadavilli Sridevi , Phoenix Tim , Nazarian Javad
Published: June 2024

BACKGROUND

Radiation therapy remains the sole standard-of-care treatment for Diffuse Midline Glioma (DMG), an aggressive and lethal brain tumor. Despite numerous clinical trials, median overall survival has not improved. Therefore, precise preclinical modeling is essential to guide clinical trials toward positive patient outcomes. ONC201, a ClpP antagonist, has demonstrated efficacy in treating DMG (NCT05580562, NCT05476939). However, efficacy is short-term and acquired resistance necessitates combination therapies. Therefore, we assessed the efficacy of BAY2402234, a potent and selective Dihydroorotate Dehydrogenase (DHODH) inhibitor, in combination with ONC201 in a murine model of DMG.

METHODS

Forty 6-week-old C57/B6 mice underwent pontine orthotopic injection with isogenic DMG cells via stereotactic surgery. The cell line used, 24B-7, has a mutational profile (PDGFRA+p53+H3.3K27M) and growth morphology representative of pontine DMGs. In our previous work, untreated mice injected with these cells had a median survival of 58 days. Upon confirmation of tumor growth using IVIS, mice were assigned to treatment groups based on BLI signal, and treatment was initiated. When mice showed signs of tumor burden or >20% weight loss they were euthanized. At euthanasia, the brain was collected, sectioned sagittally, and divided between fixation and freezing. These samples will evaluate tumor growth, morphology, and characterization compared between treatment groups by both immunohistochemistry and western blot.

RESULTS

As expected, ONC201 treated mice demonstrated an increase in median survival compared to the untreated group. While well-tolerated, neither BAY2402234 nor the combination of BAY2402234 and ONC201 exhibited a statistically significant increase in median survival after statistical correction. (Vehicle: 55 days, ONC201: 62 days, p=0.0026; BAY2402234: 58.5 days, p=0.0403; Combination: 57 days, p=0.1491). Ongoing efforts include target validation and tumor analysis through western blot and immunohistochemistry. ONC201 treatment will be evaluated by investigating ATF4, DR5, and CHOP. BAY2402234 treatment will be evaluated by investigating phosphor-gH2AX and gH2AX.

CONCLUSIONS

Pending tumor analysis.
DIPG-14. METABOLIC REPROGRAMMING AS A RESISTANCE MECHANISM IN DIFFUSE MIDLINE GLIOMA
Authors: Neyazi Sina , Gowda Pruthvi , Frederico Stephen C , Nguyen Cuong M , Trissal Maria C , Portero Erika P , Haley-Read John-Paul , Anderson Emily P , Thomas Craig J , Danial Nika N , Filbin Mariella G
Published: June 2024

BACKGROUND

Diffuse midline gliomas (DMG) are uniformly fatal pediatric brain cancers, refractory to current standards of care. Based on genomic and transcriptomic profiling data, we previously proposed that platelet-derived growth factor receptor alpha (PDGFRA) is crucial to the tumorigenic potential and maintenance of stem-like DMG cells and that targeting PDGFRA is an important therapeutic avenue in DMG. In comprehensive pre-clinical studies, we identified avapritinib, an FDA-approved PDGFRA inhibitor, to be highly effective in patient-derived xenograft (PDX) DMG models. We further reported the first clinical experience using avapritinib in recurrent DMG and demonstrated preliminary safety, tolerability, and efficacy of the drug in this population. While a subset of patients experienced a strong clinical response from avapritinib, tumor progression was eventually observed in all patients.

METHODS

Here, we investigated the molecular mechanisms that DMG cells upregulate following avapritinib treatment, with the aim to exploit them therapeutically. To uncover these mechanisms, we performed transcriptomic, metabolic and functional assays along with a combinatorial drug screening.

RESULTS

Transcriptional analysis of patient-derived DMG cell lines revealed an upregulation of genes associated with fatty acid metabolism and oxidative phosphorylation (OXPHOS) following treatment with avapritinib. Functional assays confirmed elevated OXPHOS in avapritinib-treated cells with significant (i) increase in mitochondrial energy transduction, (ii) increase in palmitate- (a product of fatty acid metabolism) driven oxygen consumption rate and (iii) greater incorporation of palmitate-derived carbons into the tricarboxylic acid cycle. To determine which therapies could target this dependency on OXPHOS and fatty acid metabolism, we performed a metabolic drug screening in patient-derived DMG cell lines and identified two metabolic drugs to have synergistic cytotoxic effects with avapritinib.

CONCLUSION

We revealed distinct metabolic reprogramming in avapritinib-treated DMG cells and showed that targeting these metabolic vulnerabilities might further increase the clinical benefit of PDGFRA inhibitor avapritinib.