bluuebunny/crossref_metadata_2025_split huggingface dataset:
P15.10.A USE OF DUAL TRACERS PET AS A PREDICTIVE BIOMARKER OF THE SITE OF RECURRENCE IN HIGH GRADE GLIOMA
Authors: Alfaifi B , Agushi E , Hinz R , Jackson A , Lewis D , Coope D 
Published: September 2023

Abstract

BACKGROUND
High grade glioma has poor survival rate and tumour recurrence occurs despite current treatments. Positron emission tomography (PET) with [11C](R)PK11195 can evaluate translocator protein (TSPO) and [11C]methionine can assess amino acid transport. PET imaging might have the potential to detect tumour regions at baseline that will later develop as the site of recurrence. We compare TSPO measured using [11C](R)PK11195 and amino acid transport using [11C]methionine at baseline and investigate to what extend the two tracers can predict the site of tumour recurrence.

MATERIAL AND METHODS
Twelve patients with newly diagnosed high grade glioma underwent multimodal imaging studies. Preoperative MRI, [11C](R)PK11195 PET, [11C]methionine PET and postoperative (follow-up) MRI were co-registered. [11C](R)PK11195 binding potential (BPND) maps were generated using the simplified reference tissue model with grey matter cerebellar time-activity curve as tissue input function. [11C]methionine uptake was calculated as tumour to background ratio (TBR). Contrast enhancing volumes of interest (VOI) were defined on T1W post contrast. The VOI of [11C]methionine high uptake was standardized as TBR&gt;1.7. For [11C](R)PK11195 VOI, the mean BPND + SD of grey matter voxels was calculated from individual maps of healthy control (HC; n = 50). Afterward, 95% confidence interval threshold (HC mean + 1.96 × SD) was used to describe high voxel activity in tumour (BPND&gt;0.35). Tumour recurrence VOI was defined as contrast enhancement on the follow-up images.

RESULTS
The mean percentage overlap between high [11C](R)PK11195 BPND and [11C]methionine uptake was 48±17%. The mean percentage of each VOI showing exclusively high [11C](R)PK11195 BPND or exclusively high [11C]methionine was 25±21 or 27±22 respectively. The mean percentage overlap between high [11C](R)PK11195 and contrast enhancement is 36±14. The mean percentage of exclusively hight [11C](R)PK11195 or exclusively contrast enhancement were 38±18 or 26±25 respectively. The mean percentage overlap between high [11C]methionine and contrast enhancement were 47±12. The mean percentage of exclusively [11C]methionine or contrast enhancement were 36±20 or 17±17 respectively. The percentage volume overlap between contrast enhancing regions at recurrence and baseline [11C](R)PK11195 or [11C]methionine was 20±13 or 25±13 respectively.

CONCLUSION
The two PET tracers have high overlap although some regions are specific for high TSPO binding without high methionine uptake which could reflect an inflammatory component within the tumour microenvironment. The common regions between methionine and contrast enhancement is larger than TSPO binding which could represent that TSPO binding is less effected by disrupted blood-brain barrier. The mean percentage overlap with VOI representing tumour recurrence were similar.
P17.15.A THANK PHASE I TRIAL OF DNX-2440 ONCOLYTIC ADENOVIRUS IN PATIENTS WITH FIRST OR SECOND RECURRENCE OF GLIOBLASTOMA: PRELIMINARY RESULTS
Authors: Gallego Perez-Larraya J , de la Nava D , González-Huárriz M , García-Moure M , Labiano S , Zalacaín M , Marrodán L , Ausejo I , Laspidea V , Hervás I , Puigdelloses M , Esparragosa I , Giráldez M , Serrano M , Domínguez P , Díez-Valle R , Fueyo J , Gomez-Manzano C , Patiño A , Tejada S , Bejarano B , Alonso M 
Published: September 2023

Abstract

BACKGROUND
Oncolytic immunovirotherapy is emerging as a potential therapeutic approach in neuro-oncology. The oncolytic adenovirus DNX-2401, genetically engineered for selective replication and enhanced infectivity in tumor cells, has shown efficacy in adult patients with recurrent glioblastoma (GBM). In order to overcome the immunosuppressive brain-tumor microenvironment and thus enhance its antiglioma effect, DNX-2440 is a new armed virus which contains the same modifications but additionally incorporates OX40 ligand to induce the expression of such molecule in tumor cells and so increase the antitumor immune response.

MATERIAL AND METHODS
We are conducting a phase I open-label single-center study to investigate the safety and efficacy of a single intratumoral injection of DNX-2440 in patients with first or second recurrence of GBM. This is a dose escalation study, with a 3 + 3 design, evaluating an initial dose of 4x10e9 viral particles (vp) and a target dose of 4x10e10 vp. A single measurable lesion bigger than 10 mm in two perpendicular diameters and smaller than 25 cc is required for inclusion in the study.

RESULTS
To date 16 patients (6 [37.5%] female, 10 [62.5%] male) have been enrolled and treated with DNX-2401. Median age is 55 years (range, 39-80) and median KPS is 80 (range 70-90). As per protocol, surgery consisted of biopsy in all patients followed by intratumoral injection of DNX-2440. No dose limiting toxicity has been registered during the dose escalation phase (first cohort of 3 patients receiving 4x10e9 vp, and second cohort of 3 patients receiving 4x10e10 vp), and the remainder patients have received the target dose of 4x10e10 vp in the dose expansion cohort. Safety profile is acceptable with no serious adverse events related to DNX-2440 reported to date. Clinical benefit with tumor size reduction and prolonged survival have already been confirmed in 3 patients. Correlative analyses evaluating immune response in blood samples are ongoing.

CONCLUSION
Our current data suggest that intratumoral injection of DNX-2440 is feasible and safe, and seems to provide a clinical benefit in some patients with recurrent GBM. Furthermore, this trial illustrates the potential of oncolytic virus platforms to reshape the brain-tumor microenvironment and its interesting role in combination strategies with other immune-oncology agents for treating this disease.
P19.01.A INVESTIGATING THE MORPHOLOGICAL HETEROGENEITY OF GLIOBLASTOMA STEM CELLS AND ITS ROLE IN TUMOUR PROLIFERATION AND INVASIVENESS
Authors: Barelli C , Kaluthantrige Don F , Bertani I , Villa G , Osei I , Iannuzzi R , Vinceti A , Brognaro E , Sottoriva A , Iorio F , Kalebic N 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma is the most common and aggressive primary brain tumour. Cancer hijacks developmental pathways and several studies have identified a stem cell-like population in glioblastoma following neurodevelopmental trajectories. In the foetal neocortex, a type of neural stem cell called basal progenitor is thought to be responsible for neocortical expansion. Basal progenitors exist in different morphotypes, and greater morphological complexity underlies their increased proliferation. We thus propose that cell morphology also plays a role in the proliferation and invasiveness of glioblastoma stem cells.

MATERIAL AND METHODS
We characterise the morphological heterogeneity of glioblastoma stem cells by immunostaining of human primary bulk tumour and peritumoral tissue. To then understand the function of cell morphology in tumour progression, we genetically manipulate morpho-regulatory molecules in 2D glioblastoma stem cells that show a genetic dependency on the target molecules based on cancer dependency maps.

RESULTS
We show that glioblastoma stem cells have a vast morphological heterogeneity in human primary bulk tumour and peritumoral tissue. The morphotypes observed are conserved in 2D glioblastoma stem cells and they are reminiscent of neural progenitors in the developing neocortex. We then test whether the genetic manipulation of those morpho-regulatory molecules which control the proliferation of basal progenitors in the fetal neocortex also affects the proliferation and invasiveness of glioblastoma stem cells.

CONCLUSION
Glioblastoma stem cells display extensive morphological heterogeneity, like basal progenitors in the developing neocortex. Morpho-regulatory molecules do not only control cell shape but may contribute to the proliferation and invasiveness of glioblastoma stem cells. We envision that the identification of morpho-regulatory molecules controlling tumour progression will open new therapeutic windows through pharmacological targeting and drug repurposing.
P20.02.B ELECTRO-CLINICAL, NEUROIMAGING FEATURES AND NEUROPATHOLOGICAL CHARACTERIZATION OF POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG (PLNTY)
Authors: Anghileri E , Didato G , Deleo F , Doniselli F M , Moscatelli M , Rizzi M , Paterra R , de Curtis M , Farinotti M , Freri E , Esposito S , Pollo B , Silvani A , Marucci G 
Published: September 2023

Abstract

BACKGROUND
Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) has been recently recognized by 2021 WHO Central nervous system classification. It is an epileptogenic tumor type, affecting mostly children and young adults, with peculiar radiological, and pathomolecular features. PLNTY is a very rare tumor, described in only 52 cases up to now. Herein, we describe 13 patients with electro-clinical and neuroimaging findings, associated to histopathological and molecular findings.

MATERIAL AND METHODS
We selected PLNTY patients from our Cancer Registry (Apr 2017-Dec 2022), and collected electro-clinical, radiological and histo-molecular data. Minimum follow-up was 6 months. Exams included EEG, long-term scalp video-EEG, pre-surgical brain computer tomography and Magnetic Brain Imaging (MRI). Immunohistochemistry included CD34, IDH1-R132H, GFAP, synaptophysin, ATRX, p53 and FGFR3. IDH1-2, BRAF (V600E) sequencing, Kiaa1549:BRAF, FGFR3:TACC3, FGFR2:kii1598 and FGFR2:CTNNA3 fusion analyses will be performed.

RESULTS
We describe 13 patients, median age 20.6 years (range 12.3-46.4). Most patients showed memory/executive impairment and had epilepsy, with an onset from 5 months-21 years before surgery. The main feature of seizures was a difficult localization and even lateralization, both semiologically and electrographically. Post-surgical seizure control was excellent.The tumors (n=11/13 temporal) presented as solid or solid-cystic cortical mass with no mass effect and unclear hedges. Calcifications were present in 4, and cysts in 6 cases. Microscopically the tumors showed infiltrative growth pattern, oligodendroglial-like cells, strong and often diffuse CD34 immunostaining, and frequent intra-tumoral calcifications. Malformation of cortical development, namely FCD type IIIB, was associated to PLNTY in 2 cases. Proliferation activity (MIB-1 LI) was very low (1%) in all cases except one (MIB-1 LI which reached 3%).

CONCLUSION
This study significantly extends the number of reported PLNTY associated to epilepsy, mostly characterized by bilateral interictal epileptiform discharges and difficult to lateralize seizures.The MRI features were heterogeneous and the differential diagnosis should include also dysplasia and glioneuronal tumors. PLNTY, despite its name, occurs also in adults, and electro-clinical and radiological diagnosis can be challenging. As recently described, PLNTY can show the MAPK pathway activating alterations, that are under investigation in our cohort to eventually clarify their role in the evolution of the disease.

SUPPORT
the study is partially supported by the Health Italian Minister (RC).
P22.01.A PERSON-CENTRED PRACTICE: EXPLORING FAMILY STRENGTH BY USING GENOGRAMS AND ECOMAPS
Authors: Mathiasen M , Suhr Kjærgaard S , Piil K 
Published: September 2023

Abstract

BACKGROUND
Illness of a family member impacts the entire family. Family relationships, roles and tasks often change, and neuro-oncological caregivers experience a high level of burden and distress when playing a vital role in the informal care of the patient. The theory of Family Systems Nursing advises to approach the family rather than merely the patient. Within Family System Nursing the Family Nursing Conversations is an important intervention that focus on the interactions within a family and between the nurse and the family. The Calgary Family Assessment and Intervention Model (CFAM/CFIM) guide clinical practice to be family focused. According to these models, the drawings of genograms and ecomaps are efficient tools to graphicly portray the specific family constellation and social relationships. This presentation shows how genograms and ecograms can be applied to strength the dialogue with a family when implementing family-focused conversations.

MATERIAL AND
Methods In the neuro-oncological outpatient clinic at the University Hospital of Copenhagen we offer family and/or caregiver conversations. At the initial conversation, a genogram and an ecogram are drawn. By visualizing the family structure and interrelationships, the family is illustrated as a unit and the family can see their constellation in relation to each other and to the outside world.

RESULTS
Based upon the genograms and ecograms, a dialogue takes place. They have shown to be important tools to visualize the structure, with strengths and challenges within a family system. Further, they provide a good starting point for a family-focused communication. However, to implement these tools, training is required. Therefore, we have prepared teaching material to healthcare professionals. This material has been tested in family-focused conversations.

CONCLUSION
The use of genograms and ecomaps have proven to be efficient for a family-focused approach in a neuro-oncological outpatient clinic. They facilitate a good starting point for a family to identify their relationships and resources. During the conversations the family/caregivers often gain new insights and management strategies for coping.
Systematic review of hearing loss in dental professionals
Authors: Hartland J C , Tejada G , Riedel E J , Chen A H-L , Mascarenhas O , Kroon J 
Published: September 2023

Abstract

Background
Hearing loss leads to increased irritability and disengagement in social activities and conversations, which may impact quality of life. Dental professionals are at risk of developing hearing loss through daily exposure to noise from a wide range of equipment that produces significantly high decibels and noise frequencies.

Aims
The aim of this systematic review was to investigate the risk of hearing loss in dental professionals, including dentists, dental specialists, dental hygienists and dental assistants.

Methods
This review was conducted following the Cochrane Handbook for Systematic Reviews. PubMed, Scopus, Embase, Cochrane, Science Direct, Google Scholar and ProQuest were searched up to March 2023. Seventeen of 416 studies met the inclusion criteria. Quality assessment was performed according to the Newcastle–Ottawa Scale for cohort and case–control studies, and a modified version of this tool for cross-sectional studies.

Results
The majority of included studies (82%) found a positive association with hearing loss for dentists and dental specialists, with years of clinical experience identified as a prominent risk factor. Dental hygienists and dental assistants were less commonly reported in the literature. Difference between the left and right ears was found in 71% of studies, with the left ear more affected in both dentists and dental assistants due to proximity to the noise-inducing equipment.

Conclusions
Dental professionals are at risk of hearing loss in their workplace, especially linked to years of clinical experience, which highlights the need for prevention and appropriate ear-protective devices.
Population-level annotation of lncRNAs in Arabidopsis reveals extensive expression variation associated with transposable element–like silencing
Authors: Kornienko Aleksandra E , Nizhynska Viktoria , Molla Morales Almudena , Pisupati Rahul , Nordborg Magnus 
Published: September 2023

Abstract
Long noncoding RNAs (lncRNAs) are understudied and underannotated in plants. In mammals, lncRNA loci are nearly as ubiquitous as protein-coding genes, and their expression is highly variable between individuals of the same species. Using Arabidopsis thaliana as a model, we aimed to elucidate the true scope of lncRNA transcription across plants from different regions and study its natural variation. We used transcriptome deep sequencing data sets spanning hundreds of natural accessions and several developmental stages to create a population-wide annotation of lncRNAs, revealing thousands of previously unannotated lncRNA loci. While lncRNA transcription is ubiquitous in the genome, most loci appear to be actively silenced and their expression is extremely variable between natural accessions. This high expression variability is largely caused by the high variability of repressive chromatin levels at lncRNA loci. High variability was particularly common for intergenic lncRNAs (lincRNAs), where pieces of transposable elements (TEs) present in 50% of these lincRNA loci are associated with increased silencing and variation, and such lncRNAs tend to be targeted by the TE silencing machinery. We created a population-wide lncRNA annotation in Arabidopsis and improve our understanding of plant lncRNA genome biology, raising fundamental questions about what causes transcription and silencing across the genome.
Evaluation of apple (Malus domestica) cider vinegar and garlic (Allium sativum) extract as phytogenic substitutes for growth-promoting dietary antibiotics in sexed broiler chickens
Authors: Chabalala Oscar , Bhebhe Evison , Fushai Felix 
Published: September 2023

Abstract
Tightening global regulations on the use of subclinical dietary antibiotics to enhance broiler growth are in response to increasing concern about the risk of resistance and their residues in animal products. The study evaluated the potential of apple cider vinegar (ACV) and garlic extract (GAE) as safer, phytogenic alternatives. A batch of 390 mixed-sex Ross 308-d-old broiler chicks was received into an open, deep litter house, and feather sexed in the second week into 30 experimental units of 13 birds per 2.03 m2 pen. From days 1 to 22, all chicks were on a 200 g/kg crude protein, coccidiostat-treated commercial starter diet. During the grower (16 to 28 days) and finisher (29 to 42 days) phases, chick pens were assigned treatments in a 2 (sex) × 5 (additives) factorial experiment replicated three times. The GAE was a pure extract, while ACV was produced by fermenting 1,000 g fresh apple and 80 g supplementary brown cane sugar in 1.3 liters of water for 4 wk. The five treatments comprised antibiotic (15% granular zinc bacitracin and 12% valinomycin sodium, each at 500 g/tonne) grower (190 g/kg crude protein, 13.0 MJ ME/kg) and finisher (165 g/kg crude protein, 13.2 MJ ME/kg) commercial diets with untreated drinking water as positive controls (PC), antibiotic-free duplicates of the PC diets with untreated drinking water as the negative controls (NC), with 3 mL/L filtered ACV in drinking water (T1), 2 mL/L filtered GAE-treated drinking water (T2), or mixed (3 mL/L ACV + 2mL/L GAE) additive drinking water (T3). Males had higher (P &lt; 0.05) feed intake than females in both growth phases. Birds on the PC gained more (P &lt; 0.05) weight than others. Birds on the PC consumed more feed (P &lt; 0.05) during the finisher phase than T1, T2, and the NC. Birds on the PC had a lower (P &lt; 0.05) grower-phase feed convesion (feed:gain) ratio (FCR) than others, and lower (P &lt; 0.05) FCR during the finisher phase than birds on T1 and T3. Birds on the PC had higher (P &lt; 0.05) percent spleen weight than birds on T1, with smaller proventriculi (P &lt; 0.05) than on NC, T1, T2, and T3, and smaller gizzard weight than birds on the T2 and T3. Birds on the NC exhibited less dressing percentage (P &lt; 0.05) than all other treatments. Meat pH was higher (P &lt; 0.05) in males. In conclusion, in contrast to dietary antibiotics, except for improved dressing percentage, the ACV and GAE did not express phytogenic benefit at the experimental dosage.
Profiling mitochondrial DNA mutations in tumors and circulating extracellular vesicles of triple‐negative breast cancer patients for potential biomarker development
Authors: Vikramdeo Kunwar Somesh , Anand Shashi , Sudan Sarabjeet Kour , Pramanik Paramahansa , Singh Seema , Godwin Andrew K. , Singh Ajay Pratap , Dasgupta Santanu 
Published: September 2023

AbstractEarly detection and recurrence prediction are challenging in triple‐negative breast cancer (TNBC) patients. We aimed to develop mitochondrial DNA (mtDNA)‐based liquid biomarkers to improve TNBC management. Mitochondrial genome (MG) enrichment and next‐generation sequencing mapped the entire MG in 73 samples (64 tissues and 9 extracellular vesicles [EV] samples) from 32 metastatic TNBCs. We measured mtDNA and cardiolipin (CL) contents, NDUFB8, and SDHB protein expression in tumors and in corresponding circulating EVs. We identified 168 nonsynonymous mtDNA mutations, with 73% (123/186) coding and 27% (45/168) noncoding in nature. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) was the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19%–38% TNBCs, which were detectable in the serum‐derived EVs with 82% specificity. Overall, 38% of the metastatic tumor‐signature mtDNA mutations were traceable in the EVs. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI‐specific mtDNA mutational load was higher in women with African compared to European ancestry accompanied by an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p < 0.0001) content was recorded in both tumors and EVs along with an abundance of CL (p = 0.0001) content in the EVs. Aggressive tumor‐signature mtDNA mutation detection and measurement of mtDNA and CL contents in the EVs bear the potential to formulate noninvasive early detection and recurrence prediction strategies.