bluuebunny/crossref_metadata_2025_split huggingface dataset:
P20.12.B DNA METHYLATION PROFILING OF ADULT SPINAL GLIAL TUMOURS; RESULTS FROM A LARGE SINGLE CENTRE STUDY
Authors: Clarke M T , Pereira R , Mackay A , Grabovska Y , Cruickshank R , Dutt M , Mariathasan P , Kumar A , Casey A , Merve A , Jaunmuktane Z , Jones C , Brandner S 
Published: September 2023

Abstract

BACKGROUND
Glial tumours can occur in any central nervous system location, including the spinal cord. Although rare, spinal gliomas can represent a significant diagnostic challenge and are recognised as separate tumour types in the WHO classification.

MATERIAL AND METHODS
This study used DNA methylation profiling to characterise adult spinal glial tumours from a large neurosurgical centre, exploring relative frequencies, and the value of this technique in diagnostic workflows. A search in our laboratory information management system (2006-2021) identified 116 tumours, from patients aged 17.2-79.2 years. Diagnoses included ependymomas (all grades/subtypes) and other high- or low-grade gliomas (HGG/LGG). Extrinsic tumours (metastases, meningiomas, schwannomas) were excluded. DNA underwent methylation profiling (Illumina EPIC BeadArrays, n=116). iDat files were processed using the brain tumour classifier (MNP v12.5 R package), classifying cases against a reference cohort (n=2,800). Longitudinal (n=8) and poor QC cases (n=3) were excluded.

RESULTS
83% (n=87) classified as an ependymoma (myxopapillary ependymoma (EPN_MPE, n=44), spinal ependymoma (n=43), spinal subependymoma (n=1)). We identified HGGs that were not diagnosed histologically (diffuse midline glioma, H3 K27-altered (n=2), high-grade astrocytoma with piloid features (n=1)) and 41% of cases (n=18/44) diagnosed histologically as an ependymoma, CNS WHO grade 2, classified as EPN_MPE. LGGs were less frequent (pilocytic astrocytoma (n=3), pleomorphic xanthoastrocytoma (n=1), rosette-forming glioneuronal tumour (n=1)). 9% (n=9) did not classify with existing methylation classes. Copy number analysis revealed subtype-specific changes, including prognostic alterations.

CONCLUSION
In conclusion, this single-centre study highlights the crucial role of DNA methylation profiling as part of diagnostic workflows for spinal glial tumours.
P20.15.A DESCRIPTIVE ANALYSIS OF A SERIES OF H3 K27-ALTERED DIFFUSE MIDLINE GLIOMAS IN CHILDREN AND ADULT POPULATION
Authors: Salva de Torres C , Lopez Valbuena D , Gonzalez M , Vieito M 
Published: September 2023

Abstract

BACKGROUND
Molecular biomarkers have gained importance in providing diagnostic information for brain and spinal cord tumors. Diffuse midline gliomas (DMG) are now defined as H3 K27-altered. H3 K27M mutations were first described in pediatric diffuse pontine gliomas but can also be encountered in adult gliomas. The H3 K27M mutation often co-occurs with mutations in TP53, PDGFR, or ACVR1 and is mutually exclusive to IDH1/2 mutations and 1p/19q co-deletion. Surgical resection is often not feasible for its localization and the benefit of temozolomide (TMZ) is not clear as they are MGMT unmethylated; all of it conferring a poor prognosis. It has been suggested that pediatric patients (pts) have worse outcomes. Our aim was to describe pts with H3 K27-altered gliomas to better understand the characteristics of this population.

MATERIAL AND METHODS
We analyzed clinical, histological and molecular features of 6 adults and 10 pediatric pts diagnosed with H3 K27M-mutant gliomas between May 2016 and January 2021 in a tertiary hospital in Barcelona.

RESULTS
For adults, mean age at diagnosis was 34.6 years (range = 20 - 55 years). For children, mean age was 11.2 years (range = 4 - 17 years). Male-to-female ratio was 1:1. Tumors involved thalamus (adult = 3; pediatric = 3), pons (adult = 1; pediatric = 6), and pineal region (n = 1). Ki67 range was 2-60% (pediatric mean 32%, adult mean 20%). A molecular panel was analyzed in 8 pediatric pts and 1 adult. No EGFR amplifications were detected.Three of them had TP53 mutations and 2 had PDGFRA amplification. Only 2 pediatric pts had MGMT methylation. Regarding treatment, 9 pediatric and 4 adult pts underwent radiotherapy and TMZ as first-line, with a mean time to intervention of 5.6 months. One child went through palliative care. As a second-line treatment, re-irradiation was used in 3 pediatric pts and irinotecan-bevacizumab was used in 2 adults. One adult received up to 4 different treatments (TMZ chemoradiotherapy followed by adjuvant TMZ, irinotecan-bevacizumab, lomustine and metronomic TMZ).All 9 pediatric pts died, with a mean OS of 12.0 months. Among adults, 2 pts died, 10.5 and 31.2 months after diagnosis, 1 has progressed to first-line and is receiving PCV as second-line treatment, and 1 has completed Stupp regimen with stable disease as best response.

CONCLUSION
Although the sample size is limited, our cohort data resembles what has been previously reported in terms of clinical and molecular characteristics: diagnosed in young adults and pediatric pts, characterized by a midline location, a low rate of MGMT promoter methylation, frequent TP53 and PDGFR alterations, and poor prognosis. There is currently no consensus on optimal treatment sequence or best treatment for these pts. Collaborative effort and participation in clinical trials are needed to keep advancing in this poor prognosis disease.
P21.02.B THE EFFECT OF SOCIODEMOGRAPHIC FACTORS ON GLIOMA PROGNOSIS
Authors: Söderlund M , Sandström M , Almqvist C , Sjöström O , M Dahlin A , Sjöström S , Numan Hellquist B , Melin B 
Published: September 2023

Abstract

BACKGROUND
Sociodemographic factors are well known to contribute to health disparities for different cancer diagnoses, but they are not extensively studied for glioma patients. In this study socioeconomic status (SES), travel time to health care, cohabitation status, and region (northern Sweden compared to three regions in southern Sweden) were investigated in relation to prognosis for patients with glioma WHO grade I-IV.

MATERIAL AND METHODS
The Swedish National Quality Registry for Brain Tumors was used to identify 1276 patients with glioma WHO grade I-IV, diagnosed 2009-2013. The Swedish population-based database RISK North combines data from several health care and demographic registries through the unique personal identity number. The RISK North was used to study survival in relation to SES, cohabitation status (living alone vs living with another adult person), travel time to the closest regional hospital (i.e. the closest hospital with a neurosurgical unit), and region. Educational level was used as a proxy for SES.

RESULTS
In univariable survival analysis, patients with glioma WHO grade III-IV and high SES had a longer survival compared to patients with low SES (middle school (ref) HR:1, high school HR:0.67 CI[0.56-0.81], university/college HR:0.65 CI[0.53-0.79], p&lt;0.0001). In the multivariable model for the same group, survival was longer for patients with higher SES (middle school (ref) HR:1, high school HR:0.81 CI[0.67-0.98], p=0.033; university/college HR:0.81 CI[0.66-1.00], p=0.048). For patients with glioma WHO grade I-IV, there were no significant differences in survival in relation to travel time, cohabitation status, or region in multivariable survival analysis.

CONCLUSION
Survival was significantly worse in patients with lower SES compared to higher SES for patients with glioma WHO grade III-IV. No significant differences were found in survival in relation to cohabitation status (between those living alone and those living with another adult person), travel time to regional hospital, or between the northern Sweden and three regions in southern Sweden.
P21.03.A CDKN2A/B VERSUS MORPHOLOGY IN DIAGNOSING WHO GRADE 4 IDH MUTATED ASTROCYTOMAS: WHAT IS THE CLINICAL RELEVANCE?
Authors: Lipatnikova A E , Denés A , Olsson Bontell T , Carén H , Ferreyra Vega S , Kling T , Jakola A S 
Published: September 2023

Abstract

BACKGROUND
In the 2021 WHO classification system, the glioma subgroup IDH-mutated astrocytomas grade 4 was introduced, and diagnosis can be based upon molecular or histopathological morphological criteria. We here explore if the reason for a diagnosis of WHO grade 4 IDH mutated astrocytoma influences survival.

MATERIAL AND METHODS
Twenty-five patients with a revised diagnosis of IDH-mutated astrocytoma grade 4 were included. Patients were divided in three groups based upon the; (i) Morphological high grade (necrosis and/or microproliferation in microscopy); (ii) Molecular high grade (homozygous CDKN2A/B homodelation); (iii) Both morphological and molecular high grade. Inclusion period was 2007-2018 for molecular high grade and 2012-2018 for morphological high grade. All patients had potential for at least 5 year follow-up.

RESULTS
The median survival following surgery was 5.2 years (Q1-Q3 2.9-7.0 years). The median age was 42 years (Q1-Q3 33-59). As expected the tumors had the frontal lobe predominance (72%). Seizures were the most common debut symptom, occurring in 48% of patients. There were 12 patients in group (i), nine patients in group (ii), and four patients in group (iii). Group (iii) with both morphological and molecular WHO grade 4 criteria was characterized by a significantly worse prognosis with a median estimated survival of 2.8 years (p = 0.002). There was no substantial difference in overall survival between groups (i) and (ii) (7.3 years vs 5.2 years, p = 0.237).

CONCLUSION
The median survival of IDH-mutated astrocytoma grade 4 is approximately five years, while prognosis seems to be significantly worse for the minority of patients where the tumor fulfills both molecular and morphological criteria. More research into larger cohorts is encouraged.
P21.04.A IMPROVEMENTS IN SURVIVAL FOR GLIOBLASTOMA IN THE POST-STUPP PROTOCOL ERA
Authors: Neff C , Price M , Chavez G , Proescholdt C , Kruchko C , Cioffi G , Waite K , Barnholtz-Sloan J , Ostrom Q T 
Published: September 2023

Abstract

BACKGROUND
The Stupp protocol was accepted as standard of care for glioblastoma in 2005, and has led to significant increases in overall survival. Prior analyses have identified additional survival gains post-Stupp, though the source of these is unknown. In this analysis, we leveraged two large datasets to identify trends in survival and potential treatment factors associated with these improvements.

MATERIAL AND METHODS
Provider-side commercial claims data were obtained from IQVIA for adults (18+ years) diagnosed with malignant brain tumor (ICD-9/ICD-10:191.0-191.9/C71.0-C71.9) from 2015-2021 who received biopsy/resection and temozolomide within 60 days of diagnosis. Treatment patterns were determined using ICD-9/ICD-10 procedure and HCPCS/CPT codes. Death was determined by CPT codes or last claim followed by ≥30 days of no claims. Elixhauser comorbidity score was generated prior to diagnosis. Population-based survival data were obtained from the National Program of Cancer Registries (NPCR) from 2004-2018 for microscopically-confirmed adult (18+ years) glioblastoma cases receiving surgery and radiation. Median survival was estimated using Kaplan-Meier regression, and cox proportional hazards models were used to assess potential prognostic factors. Survival analyses were censored at 36 months.

RESULTS
The IQVIA dataset had 18,883 individuals and NPCR had 92,540 individuals identified as being diagnosed with glioblastoma and meeting treatment criteria. Median survival among IQVIA cases was 13.9 months (95%CI=13.7-14.1), and 14 months (95%CI=14-14) in NPCR. Median survival in NPCR increased from 11 months in 2004-2006, to 14 months in 2016-2018. Within IQVIA, 19% of individuals had ≥1 claim for Bevacizumab and 15.5% had ≥1 claim for tumor treating fields (TTFields). Use of TTFields and/or Bevacizumab in treatment were associated with significantly improved survival after adjustment for age, sex, and comorbidities.

CONCLUSION
s: Survival in glioblastoma continues to improve over time, which may be due to developments in therapeutic approaches. Assessment of population-level survival patterns is essential for understanding the impact of treatment advancements.
P21.06.A TIME IN ONCOLOGY. GLIOBLASTOMA REAL-WORLD DATA
Authors: Macià i Garau M , Lucas Calduch A , García Expósito N 
Published: September 2023

Abstract

BACKGROUND
Time is a crucial component in all diagnostic and therapeutic processes of cancer. Retard in the treatment can have adverse consequences on outcomes. Total treatment delays could be due to patient interval (from the first perceived symptom to the first medical consultation) and system interval (from the first medical consultation to end of treatment). To minimize delays, it is essential to know the time intervals elapsed between each of the steps in the diagnostic and the treatment phase.The purpose of this pilot study is to holistically analyze the total treatment interval of cancer patients as a part of process-oriented total quality management with the ultimate intention of having more useful information for benchmarking and making decisions to improve time in oncology.

MATERIAL AND METHODS
During 2019 in a context of public health-care system all relevant clinical pathway time data from the patient’s perceived first symptom until the end of oncological treatment were collected in a prospective cohort of newly diagnosed glioblastoma patients. Clinical pathway is defined as a description of the current practice in an homogeneous patient group treated by a multidisciplinary team and an inventory of actions defining a diagnostic and therapeutic sequence. This cohort was compared with a serie of glioblastoma patients treated in 2020 (COVID-19-year). We analyzed the mean, median and quartile data of 16-time intervals represented on a time scale

RESULTS
From January 1 to December 31, 2019, we collected data from 59 patients diagnosed and treated for a glioblastoma. There were 24 women and 35 men with a mean age of 60,9 years. We collected 1062 time-points. This group was compared with a COVID-19-year cohort of 49 patients (14 women and 35 men with a mean age of 61,7 years and 630 time-points). The median patient interval time and the system interval time were 6 days (0-210) vs 5 (0-150) and 240 days (81-363) vs 255 (120-482) respectively. Median time from surgery to the start of adjuvancy was 34 days (19-56) vs 34 (17-108). No differences were found in any of the intervals analyzed, in the overall treatment time of radiotherapy or in the dose intensity of chemotherapy.

CONCLUSION
The routine measurement of the intervals between the different diagnostic and therapeutic actions is essential to monitor the time of clinical processes in terms of quality and benchmarking. It is also essential to standardize in a holistic way the distressing temporality in oncology.
P22.02.B RELATIVE REPRESENTATIVES IN RESEARCH: HOW TO APPLY PATIENT AND PUBLIC INVOLVEMENT IN THE DEVELOPMENT OF AN INTERVENTION FACILITATING RELATIVE’S INVOLVEMENT IN THE PATIENT’S CARE AND DISEASE TRAJECTORY
Authors: Guldager R , Smedegaard P S , Nordentoft S 
Published: September 2023

Abstract

BACKGROUND
The importance of engaging patients and the public in health research is gaining growing recognition. However, robust evidence of the process seems to be lacking. This study aims to apply Patient and Public Involvement as a panel of relatives from the development to implementation of a clinical tool, to systematically involve relatives of patients with acquired brain injury and a malignant brain tumor in the patient’s care and disease trajectory.

MATERIAL AND METHODS
This is a descriptive study in the initial phase of applying Patient and Public Involvement in a current research project. Two national patient associations Brain Injury Association and Brain Tumor Association were contacted to recruit relatives of patients within these populations. An informational text with the aim of the overall project and purpose of the research panel was formulated and posted on the home page of- and by the patient associations on behalf of the research group. To enable a broad representation of the whole country, TEAMS was chosen as a communication platform. Preliminary interviews were conducted individually with the relatives and two researchers to align expectations and examine the motivation to participate in the panel.

RESULTS
Six relatives replied and were considered eligible by the research team, able to express both their own experiences, and representing relatives in general. The relative representatives comprised relatives of patients with acquired brain injury (n=3) and malignant brain tumor (n=3). The relatives were all women between the age of 44 to 66, all partners to the patients, and geographically representing four of the five regions in Denmark. Ethical considerations regarding the relatives were taken into account throughout the process. Two-panel meetings have until now been conducted where the relative representatives have been presented for and discussing findings from two scoping reviews. A pivotal finding is a perceived lack of involvement and systematic support for the children and young adults of the patients.

CONCLUSION
By including the relatives in the early stage of the research process, they can validate and nuance the research findings by applying their lived experiences and ensuring relevance to a national context. The perspectives and knowledge from the panel are an important foundation before the development of an intervention facilitating the relative’s involvement in the patient’s care and disease trajectory.
P22.03.A FEASIBILITY OF AND COMPLIANCE TO ELECTRONIC PATIENT-REPORTED OUTCOME ASSESSMENT IN THE MOLECULAR TUMOR BOARD IN (NEURO-)ONCOLOGICAL PATIENTS UNDER TARGETED THERAPY (TRACE)
Authors: Renovanz M , Stange F , Dörner L , Bombach P , Grosse L , Rieger J , Skardelly M , Rieger D , Hille H , Kurz S , Hippler M , Paulsen F , Öner Ö , Ruhm K , Beha J , Sundberg Malek H , Möller Y , Tatagiba M , Wallwiener M , Escher P , Pfeiffer N , Forschner A , Bauer A , Zips D , Bitzer M , Malek N , Gani C , Tabatabai G 
Published: September 2023

Abstract

BACKGROUND
Comprehensive genomic profiling and biomarker-based therapies are increasingly used in clinical trials and in innovative health care systems including the center for personalized medicine network. Systematic assessments of patient-reported outcomes (PRO) are warranted to gain insight into the perspective of patients during biomarker-based therapies. In the present study, we focused on the feasibility of and compliance to an electronic PRO assessment in patients treated at our center.

MATERIAL AND METHODS
Based on a retrospective evaluation of symptom burden in 265 neurooncology patients in the Molecular Tumor Board (MTB), we developed an app by 14 expert rounds including validated assessments of health-related quality of life (HRQoL), burden of symptoms und psychological stress, and tested it in a pilot study. After informed consent, patients were introduced to the app by study staff and completed subsequently patient-reported outcomes at several time points (weekly, monthly, and quarterly). We conducted a structured interview with health care personnel and the patients as users after 3 months to assess the app’s usability and feasibility. The interview was transcribed and analyzed according to Mayring´s qualitative content analysis regarding handling, feasibility and applicability in daily routine.Furthermore, we assessed compliance and descriptive data of the ePROs.

RESULTS
So far, 14 patients and caregivers have been enrolled, (9 female, 5 male). Median age was 50 years (range 28 -79), 3 out of 14 patients dropped out due to death. A total of 4 study staff members, 9 patients and one caregiver were interviewed regarding usability /feasibility. Both evaluated as good (study staff members in total n=40 quotes, patients/caregivers n=112 quotes). Main advantages were the possibility to complete questionnaires at home and the easy implementation in daily life. Compliance to questionnaires was high, e.g., 91% of weekly distributed NCCN Distress Thermometer were answered in time (range 65-100%, assessment duration 5-56 weeks, 262 answers), we observed a median Distress score of 4 (range 0-9, n=262, weekly assessed) and a median Global health score of 66.7 (range 16.7-100, n=69, EORTC QLQ-C30, question 29 and 30, monthly assessed, compliance 94%).

CONCLUSION
This pilot study proved feasibility and acceptance of the app and might enable PRO assessment during biomarker-guided therapies.
Caenorhabditis elegansLIN‐24, a homolog of bacterial pore‐forming toxin, protects the host from microbial infection
Authors: Zhang Huijie , Zeng Weirong , Zhao Ming‐Ming , Wang Jiali , Wang Qiquan , Chen Ting , Zhang Yuyan , Lee Wenhui , Chen Shenghan , Zhang Yun , Lan Xinqiang , Xiang Yang 
Published: September 2023

AbstractAerolysin‐like pore‐forming protein (af‐PFP) superfamily members are double‐edge swords that assist the bacterial infection but shied bacteria from the host by various mechanisms in some species including the toad Bombina maxima and zebrafish. While members of this family are widely expressed in all kingdoms, especially non‐bacteria species, it remains unclear whether their anti‐bacterial function is conserved. LIN‐24 is an af‐PFP that is constitutively expressed throughout the Caenorhabditis elegans lifespan. Here, we observed that LIN‐24 knockdown reduced the maximum lifespan of worms. RNA‐seq analysis identified 323 differentially expressed genes (DEGs) post‐LIN‐24 knockdown that were enriched in “immune response” and “lysosome pathway,” suggesting a possible role for LIN‐24 in resisting microbial infection. In line with this, we found that Pseudomonas aeruginosa 14 (PA14) infection induced LIN‐24 expression, and that survival after PA14 infection was significantly reduced by LIN‐24 knockdown. In contrast, LIN‐24 overexpression (LIN‐24‐OE) conferred protection against PA14 infection, with worms showing longer survival time and reduced bacterial load. Weighted gene co‐expression network analysis of LIN‐24‐OE worms showed that the highest correlation module was enriched in factors related to immunity and the defense response. Finally, by predicting transcription factors from RNA‐seq data and knocking down candidate transcription factors in LIN‐24‐OE worms, we revealed that LIN‐24 may protect worms against bacterial infection by stimulating DAF‐16‐mediated immune responses. These findings agree with our previous studies showing an anti‐microbial role for the amphibian‐derived af‐PFP complex βγ‐CAT, suggesting that af‐PFPs may play a conserved role in combatting microbial infections. Further research is needed to determine the roles this protein family plays in other physio‐pathological processes, such as metabolism, longevity, and aging.
Dermal white adipose tissue development and metabolism: The role of transcription factor Foxn1
Authors: Walendzik Katarzyna , Kopcewicz Marta , Wiśniewska Joanna , Opyd Paulina , Machcińska‐Zielińska Sylwia , Gawrońska‐Kozak Barbara 
Published: September 2023

AbstractIntradermal adipocytes form dermal white adipose tissue (dWAT), a unique fat depot localized in the lower layer of the dermis. However, recognition of molecular factors regulating dWAT development, homeostasis, and bioactivity is limited. Using Foxn1−/− and Foxn1+/+ mice, we demonstrated that epidermally expressed Foxn1 regulates dWAT development and defines the adipogenic capacity of dermal fibroblasts. In intact and post‐wounded skin, Foxn1 contributes to the initial stimulation of dWAT adipogenesis and participates in the modulation of lipid metabolism processes. Furthermore, Foxn1 activity strengthens adipogenic processes through Bmp2 and Igf2 signaling and regulates lipid metabolism in differentiated dermal fibroblasts. The results reveal the contribution of Foxn1 to dWAT metabolism, thus identifying possible targets for modulation and regulation of dWAT in physiological and pathological processes in the skin.