bluuebunny/crossref_metadata_2025_split huggingface dataset:
P13.19 Bi-modular G-quadruplex DNA-crypto-aptamers diminish viability of glioma primary cell cultures of patients
Authors: Kopylov A M , Samoylenkova N , Bizayeva A , Arutyunyan A , Tashlitsky V , Golbin D , Usachev D , Pavlova G 
Published: September 2021

Abstract

BACKGROUND
G-quadruplex oligonucleotides (GQs) exhibit specific anti-survival activity in human cancer cell lines; they can selectively inhibit the viability/proliferation. The most studied, AS1411, had been in clinical trials. This anti-proliferative ability of GQs could be translated into glioma, which currently has poor prognosis and low-efficiency therapeutic treatments for glioblastoma multiform (GBM). Set of GQs have been designed, synthesized, and tested: they have different amount of Q-quartets, they have dimers of different GQ modules: either covalent dimers or non-covalent ones; all of them could be coined as ‘twins’.

MATERIAL AND METHODS
Folding of synthetic DNA oligonucleotides into GQs and thermal stability have been studied by circular dichroism, melting with unfolding-folding regimes, oligomerization was followed by original SE-HPLC. Conventional human cell lines U87 and fibroblasts from human embryo (HEF) were provided from the collection of the Centre of Neurosurgery (Moscow, Russia). GBM primary cell cultures N1, G11, Sus/fP2, G22, G23, and G01 were developed in Burdenko National Medical Research Centre of Neurosurgery (NMRCN) from the surgery samples of patients (PCC_SSP). All samples had WT IDH1. This study was approved by the Ethics Committee of Burdenko NMRCN, Russian Academy of Medical Sciences (№_12/2020, 15.12.2020). All subjects gave written informed consent in accordance with the guidelines of Declaration of Helsinki. Cell viability was tested by conventional MTT-test.

RESULTS
Novel bi-modular GQ, bi-(AID-1-T), twin of three-quartet AID-1-T, was designed by covalent conjugation of two AID-1-Ts via three thymidine link, TTT; and linking did not interfere with its GQ structure. Comparison of bi-(AID-1-T) with mono-modular AID-1-T, mono-modular two-quartet HD1, bi-modular bi-HD1, and two-quartet AS1411, was made. Among five GQs, bi-(AID-1-T) had the highest anti-survival activity for U87, while not affecting the control, HEF. GQs, for the first time, were tested on several PCC_SSP. Sensitivity of PCC_SSP toward GQs varied, with apparent IC50 of less than 1 μM for bi-(AID-1-T) toward the most sensitive G11 (glioma, Grade III).

CONCLUSION
GQs as anti-proliferative crypto-aptamers with moderate activity due to restricted functioning of apparent GQ-binding proteins could be applied toward real glioma PCC_SSP. Variety of effects reflects glioma inter-tumor heterogeneity.Research was funded by Ministry of Education and Science of Russia, grant number № 075-15-2020-809 (13.1902.21.0030) and by Russian Foundation for Basic Research, grants number №18-29-01047
P14.01 Incidence and impact of venous thromboembolism and major bleeding in patients with glioblastoma
Authors: Kaptein F H J , Stals M A M , Klaase E , Kapteijn M Y , Cannegieter S C , Taphoorn M J B , Dirven L , Huisman M V , Koekkoek J A F , Klok F A 
Published: September 2021

Abstract

BACKGROUND
Patients with glioblastoma are considered to be at high risk of venous thromboembolism (VTE) and major bleeding (MB), although reliable incidence estimates are lacking. The aim of this study was to assess the cumulative incidence, risk factors and prognostic impact of VTE and MB in a large cohort of glioblastoma patients.

MATERIAL AND METHODS
Patients diagnosed with glioblastoma between 2004–2020 from the Leiden University Medical Center and Haaglanden Medical Center were included and followed from 6 months before date of histopathological glioblastoma diagnosis up to two years after, or until an outcome of interest (VTE and MB) or death occurred. Cumulative incidences were estimated using Kaplan-Meier and cumulative incidence competing risk methods. Outcome predictors were determined with multivariable (time-dependent) Cox models.

RESULTS
Of the 967 included patients, 631 died, 101 were diagnosed with VTE and 130 with MB during a median follow-up of 15 months (IQR 9–22). The majority of MBs were intracranially (94%), of which half was within 4 weeks post-surgery (51%). Ambulant patients did not routinely receive pharmacological thromboprophylaxis. The adjusted 2.5-year-cumulative incidence of VTE was 12% (95%CI 10–14) and of MB 16% (95%CI 13–18). One year increase in age (HR 1.03, 95%CI 1.01–1.05), tumor resection (vs. biopsy: HR 0.56, 95%CI 0.35–0.89) and performance status (ECOG &gt;1 vs ≤1: HR 1.8, 95%CI 1.2–2.7) were independent predictors of VTE (a biopsy rather than resection was performed in patients with the worst prognosis). MB and VTE predicted all-cause mortality (adjusted HR 1.7, 95%CI 1.3–2.1 and 1.3, 95%CI 0.99–1.6 respectively).

CONCLUSION
The incidences of VTE and MB in patients with glioblastoma are high, with both complications associated with a poor prognosis. Our observations emphasize the need for prospective studies to determine optimal thromboprophylaxis and VTE treatment strategy in these patients.
P14.04 Detection of circulating tumor cells in cerebrospinal fluid for patients with suspected breast cancer leptomeningeal metastases. A prospective study
Authors: Darlix A , Pouderoux S , Thezenas S , Bievelez A , Jacot W , Cayrefourcq L , Leaha C , Alix-Panabières C 
Published: September 2021

Abstract

BACKGROUND
Breast cancer (BC) is the most frequent cause of leptomeningeal metastases (LM). LM diagnosis is confirmed by the detection of tumor cells in the cerebrospinal fluid (CSF) using conventional cytology (gold standard). However, even with optimal CSF sample volume and time to the analysis, the sensitivity of this technique is low, demanding repeated samples. Here, we aimed to evaluate the value of circulating tumor cell (CTC) detection in CSF using the CellSearch® system for LM diagnosis.

MATERIAL AND METHODS
This prospective, monocentric study included adult BC patients with suspected LM (clinical and/or radiological signs). CSF samples from 1–3 lumbar puncture(s) were analyzed: protein level, conventional cytology (60 drops), and CTC detection with the CellSearch® system (60 drops, first lumbar puncture only). Sensitivity (Se) and specificity (Sp) were calculated, using the results of the conventional cytology as the gold-standard.

RESULTS
Forty-nine eligible patients were included (Jan 2017-Jan 2020): median age 51.8, 95.9% women, 20.4% HER2+ BC, 93.8% previously diagnosed with metastatic BC, 89.8% with clinical symptoms. Among them, 40 were evaluable (CTC detection failure: n=8, eligibility criteria failure: n=1). Median sample volume was 3.0 mL for conventional cytology samples (median time to analysis: 22min) and 3.3 mL for CTC samples. Of the 40 evaluable patients, 18 had a positive cytology (on CSF sample n=°1/n°2: n=16/n=2) and were therefore diagnosed with LM using the gold-standard method. Protein level was elevated in 88.2% of these patients, compared with 45.1% of patients with negative CSF cytology (p=0.005). CTCs were detected in these 18 patients (median 5824 CTCs, range 93-45052). CTCs were also detected in 5/22 patients with a negative cytology (median 2 CTCs, range 1–44). Among them, one patient (44 CTCs) was diagnosed with a cytologically-proven LM 9 months later, while there was no further argument for LM in the other 4 patients’ history (1–3 CTC), who died of the extra-cerebral disease after a median time of 5.2 months (range 0.9–25.9). The detection of at least one CTC in CSF was associated with a Se of 100.0% (IC95% 82.4–100) and a Spe of 77.3% (IC95% 64.3–90.3) for the diagnosis of LM.

CONCLUSION
CTCs were detected with the CellSearch® system in all patients diagnosed with a cytologically-proven LM, as well as in a few patients without a cytological confirmation of LM. The prognosis of these patients with CSF cytology-/CTCs+ needs to be further investigated in a larger cohort.
P14.06 Radiomics for the non-invasive determination of the BRAF mutational status in patients with melanoma brain metastases
Authors: Meissner A , Gutsche R , Galldiks N , Kocher M , Juenger S T , Wendl C , Mauch C , Proescholdt M , Grau S , Lohmann P 
Published: September 2021

Abstract

BACKGROUND
The BRAF V600E mutation is present in approximately 50% of patients with melanoma and is an important prerequisite for a response to targeted therapies such as BRAF inhibitors. In the majority of patients, the BRAF mutational status is based on the analysis of tissue samples from the extracranial primary tumor only. Since the extracranial and intracranial BRAF mutational status may be discrepant, the additional information on the BRAF mutational status of melanoma brain metastases would be of clinical value, e.g., for the prediction of response to targeted therapies. Here, we evaluated the potential of structural MRI radiomics for the determination of the intracranial BRAF mutational status in patients with melanoma brain metastases.

MATERIAL AND METHODS
Fifty-nine patients with melanoma brain metastases from two university hospitals (group 1, 45 patients; group 2, 14 patients) underwent surgery with subsequent genetic analysis of the brain metastases tissue to determine the BRAF mutational status. All patients underwent structural MRI preoperatively. Areas of contrast enhancement were manually segmented and analyzed. Group 1 was used for model training and validation, group 2 for model testing. After image preprocessing, 1,316 radiomics features were extracted using the open-source PyRadiomics package. A test-retest analysis was performed to identify robust features prior to feature selection. Finally, the best performing radiomics model was applied to the test data (group 2). Diagnostic performances were evaluated using receiver operating characteristic (ROC) analyses.

RESULTS
Twenty-two patients (49%) in group 1, and 6 patients (43%) in group 2 had an intrametastatic BRAF V600E mutation. Using a six parameter radiomics signature, a linear support vector machine classifier yielded an average area under the ROC curve (AUC) of 0.87 (accuracy, 85%; sensitivity, 78%; specificity, 91%) for prediction of the BRAF mutational status in the training data (group 1). Finally, the classifier achieved an AUC of 0.85 (accuracy, 86%; sensitivity, 83%; specificity, 88%) in the test data (group 2).

CONCLUSION
The developed radiomics classifier allows a non-invasive prediction of the intracranial BRAF V600E mutational status in patients with melanoma brain metastases and may be of value for treatment decisions.
P14.31 Between hospital variation in timings to multidisciplinary glioblastoma care in the Dutch Brain Tumor Registry
Authors: De Swart M E , Ho V K Y , Lagerwaard F J , Brandsma D , Broen M P , French P , Gijtenbeek A , Geurts M , Hanse M C J , Idema B , Klein M , Koekkoek J A F , Polman S K , Samuels C W , Seute T , Sijben A E J , Smits M , Vos M J , Walenkamp A M E , Wesseling P , Kouwenhoven M C M , De Witt Hamer P C 
Published: September 2021

Abstract

BACKGROUND
Delay in cancer care may adversely affect emotional distress, treatment outcome and survival. Optimal timings in multidisciplinary glioblastoma care are a matter of debate and clear national guidelines only exist for time to neurosurgery. We evaluated the between-hospital variation in timings to neurosurgery and adjuvant radiotherapy and chemotherapy in newly diagnosed glioblastoma patients in the Netherlands.

MATERIAL AND METHODS
Data were obtained from the nation-wide Dutch Brain Tumor Registry between 2014 and 2018. All adult patients with glioblastoma were included, covering all 18 neurosurgical hospitals, 28 radiotherapy hospitals, and 33 oncology hospitals. Long time-to-surgery (TTS) was defined as &gt;3 weeks from the date of first brain tumor diagnosis to surgery, long time-to-radiotherapy (TTR) as either &gt;4 or &gt;6 weeks after surgery, and long time-to-chemotherapy (TTC) as either &gt;4 or &gt;6 weeks after completion of radiotherapy. Between-hospital variation in standardized rate of long timings was analyzed in funnel plots after case-mix correction.

RESULTS
A total of 4203 patients were included. Median TTS was 20 days and 52.4% of patients underwent surgery within 3 weeks. Median TTR was 20 days and 24.6% of patients started radiotherapy within 4 weeks and 84.2% within 6 weeks after surgery. Median TTC was 28 days and 62.6% of patients received chemotherapy within 4 weeks and 91.8% within 6 weeks after radiotherapy. After case-mix correction, three (16.7%) neurosurgical hospitals had significantly more patients with longer than expected TTS. Three (10.7%) and one (3.6%) radiotherapy hospitals had significantly more patients with longer than expected TTR for &gt;4 and &gt;6 weeks, respectively. In seven (21.2%) chemotherapy hospitals, significantly less patients with TTC &gt;4 weeks were observed than expected. In four (12.1%) chemotherapy hospitals, significantly more patients with TTC &gt;4 weeks were observed than expected.

CONCLUSION
Between-hospital variation in timings to multidisciplinary treatment was observed in glioblastoma care in the Netherlands. A substantial percentage of patients experienced timings longer than anticipated.
P14.49 Prescription preferences of antiepileptic drugs in brain tumor patients: an international survey
Authors: van der Meer P B , Dirven L , van den Bent M J , Preusser M , Taphoorn M J B , Ruda R , Koekkoek J A F 
Published: September 2021

Abstract

BACKGROUND
This study aimed at investigating antiepileptic drug (AED) prescription preferences in patients with brain tumor-related epilepsy (BTRE) among the European neuro-oncology community, the considerations that play a role when initiating AED treatment, the organization of care, and practices with regard to AED withdrawal.

MATERIAL AND METHODS
A digital survey containing 31 questions about prescription preferences of AEDs was set out among members of the European Association of Neuro-Oncology (EANO).

RESULTS
A total of 198 respondents treating patients with BTRE participated of whom 179 completed the entire survey. Levetiracetam was the first choice in patients with BTRE for almost all respondents (90% [162/181]). Levetiracetam was considered the most effective AED in reducing seizure frequency (72% [131/181]) and having the least adverse effects (48% [87/181]). Common alternatives for levetiracetam as equivalent first choice included lacosamide (33% [59/181]), lamotrigine (22% [40/181]), and valproic acid (21% [38/181]). Most crucial factors to choose a specific AED were potential adverse effects (82% [148/181]) and interactions with other antitumor treatments (76% [137/181]). In the majority of patients neuro-oncologists were involved in the treatment of seizures (73% [132/181])). Other relevant findings were that a minority of respondents ever prescribe AEDs in brain tumor patients without epilepsy solely as prophylaxis (29% [53/181]), but a majority routinely consider complete AED withdrawal in seizure free BTRE patients after antitumor treatment (79% [141/179]).

CONCLUSION
Our results show that among European professionals treating patients with BTRE levetiracetam is considered the first choice AED, with the presumed highest efficacy and least adverse effects.
P14.59 Rapid early progression of glioblastoma is not related to cortical/neural stem cells regions
Authors: Kazda T , Lakomy R , Selingerova I , Pospisil P , Hynkova L , Belanova R , Slampa P 
Published: September 2021

Abstract

BACKGROUND
Rapid early progression (REP) of glioblastoma after surgery observed on pre-radiotherapy MRI scan is common. Subventricular zone (SVZ) and hippocampal regions are supposed to harbor astrocyte-like neural stem cells (NSC) with tumors arising from these transformed stem cells threatening of higher risk of REP. REP is defined as a new enhancing tumor or &gt;25% increase in enhancement before radiotherapy. Lim′s classification of initial glioblastoma location related to these NSC regions predicts invasive and multifocal tumor phenotype. Glioblastomas are classified preoperatively into four groups by the spatial relationship of the contrast-enhancing lesion with the SVZ and cortex. The aim of this retrospective single-institutional study is to evaluate the relations of this Lim classification on REP in unselected cohort of glioblastoma patients.

MATERIAL AND METHODS
Patients receiving radiotherapy between 2014–2017 were analyzed, 95 were evaluable. 47 patients (30.5%) were treated with the Stupp regimen. Lim1 classification (contact with cortex as well as SVZ) was presented in 74(48%) patients, Lim2 (contact with SVZ only) in 22(14.3%), Lim3 (contact with cortex only) in 50(32.5%) and Lim4 in 8(5.2%) patients. A total of 52% of patients developed REP.

RESULTS
Significantly better overall survival was with Stupp regimen (23.3 vs. 8.6 months, p&lt;0.001) and without REP (18.5 vs. 10.2 months, p=0.001). There was no significant impact of time to start of radiotherapy. No significant relation between REP and Lim classification was observed.

CONCLUSION
The initial location is not predictive for REP. Patients experiencing REP have significantly worse overall survival and modification of their management represents an urgent unmet clinical need. Molecular and clinical biomarkers indicating an increased risk of REP are needed.Presented will also be an already published analysis of clinical factors associated with REP in glioblastoma and the effect of REP and treatment on survival outcomes. Newly, we will introduce the investigator-initiated prospective academic clinical trial (GlioMET) focused on optimization of glioblastoma radiotherapy by 11C-Methionine PET scan in patients with REP. Supported by Ministry of Health of the Czech Republic AZV, No.18-03-00469 and AZV NU20-03-00148.
P14.71 An assessment of the reporting and methodological quality of meningioma systematic reviews and meta-analyses
Authors: George A M , Gupta S , Keshwara S M , Mustafa M A , Gillespie C S , Richardson G E , Steele A C , Islim A I , Jenkinson M D , Millward C P 
Published: September 2021

Abstract

BACKGROUND
Systematic reviews and meta-analyses constitute the highest level of research evidence and for a disease with limited clinical trial activity, are often relied upon to help inform clinical practice. This review of reviews evaluates both the reporting & methodological quality of meningioma evidence syntheses.

MATERIAL AND METHODS
Potentially eligible meningioma reviews published between 1st January 1990 and 31st December 2020 were identified from eight electronic databases. Inclusion required the study to meet the Cochrane guideline definition of a systematic review or meta-analysis. Reviews concerning neurofibromatosis type 2, spinal and pediatric meningiomas were excluded. The reporting and methodological quality of articles were assessed against the following modified guidelines: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), A MeaSurement Tool to Assess Systematic Reviews (AMSTAR2) and the Risk of Bias in Systematic Reviews (ROBIS) guidelines.

RESULTS
117 systematic reviews were identified, 57 of which included meta-analysis (48.7%). The number of meningioma systematic reviews published each year has increased with 63 studies (53.9%) published between 01/2018 and 12/2020. A median of 17 studies (IQR 9–29) were included per review. Impact factor of journals publishing a systematic review with or without a meta-analysis was similar (median 2.3 vs 1.8, P=0.397). The mean PRISMA scores for systematic reviews with a meta-analysis was 21.11 (SD 4.1, 78% adherence) and without was 13.89 (SD 3.4, 63% adherence). Twenty-nine systematic reviews with meta-analysis (51%) and 11 without meta-analysis (18%) achieved greater than 80% adherence to PRISMA recommendations. Methodological quality assessment using AMSTAR2 revealed one study (0.9%) as high quality whilst 111 (94.8%) studies were graded as critically low. One hundred and two articles (87.2%) did not utilize a comprehensive search strategy as defined by the AMSTAR2 tool. Ninety-nine studies (84.6%) obtained a high level of concern for potential bias as per the ROBIS assessment. One hundred and eight articles (92.3%) failed to present information that a protocol had been established prior to study commencement and 76 articles (65.0%) did not conduct a risk of bias assessment. Across the three tools, domains relating to the establishment of a protocol prior to review commencement and conducting appropriate risk of bias assessments were frequently low scoring.

CONCLUSION
Overall reporting and methodological quality of meningioma systematic reviews was sub-optimal. Established critical appraisal tools and reporting guidelines should be utilized a priori to assist in producing high-quality systematic reviews.
Health-Related Quality of Life as Measured by the 36-Item Short Form Survey Among Adults With Acute Bacterial Skin and Skin Structure Infections who Received Either Omadacycline or Linezolid in a Phase 3 Double-Blind, Double-Dummy Clinical Trial
Authors: Chitra Surya , Hinahara Jordan , Goss Thomas F , Gunter Kyle , LaPensee Kenneth 
Published: September 2021

Abstract
This analysis of data from a Phase 3 study of adults with acute bacterial skin and skin structure infections showed that successful oral treatment with omadacycline (n = 368) or linezolid (n = 367) was associated with improvement in health-related quality of life.
Physiological condition reflects polymorphism at the toll-like receptors in a colonial waterbird
Authors: Podlaszczuk Patrycja , Indykiewicz Piotr , Kamiński Maciej , Minias Piotr 
Published: September 2021

AbstractToll-like receptors (TLRs) are a crucial component of vertebrate innate immune response. Despite their importance, associations of TLR diversity with fitness-related traits have rarely been examined in wild animal populations. Here, we tested for associations of TLR polymorphism with physiological condition in a colonial waterbird, the Black-headed Gull (Chroicocephalus ridibundus). Physiological condition and polymorphism at 4 TLR loci were assessed in 60 gulls from a breeding colony in northern Poland. We found that blood hemoglobin and plasma albumin concentrations were positively associated with TLR diversity across all genotyped loci. Plasma concentrations of albumin and triglycerides were also associated with the presence of specific TLR variants and locus-specific diversity. All significant associations between physiological condition and TLRs were primarily apparent at the level of nucleotide, rather than amino acid allelic variants. Although the exact molecular mechanisms responsible for these associations require further investigation, our study provides strong correlational support for links between TLR diversity and physiological condition in a wild avian population, and it adds to the growing, but still modest, body of evidence for the fitness-related consequences of individual TLR repertoire in wild birds.
The Relationship Between Parenting and Identity Styles Among Adolescents in South Africa
Authors: Roman Nicolette Vanessa , van Heerden Marsha , Davids Eugene Lee , Adonis Kerstin 
Published: September 2021

Abstract
This chapter provides insight into the mother–adolescent relationship in a South African context, focusing on the relationship between identity styles and the mother’s parenting. The findings revealed that maternal involvement predicted adolescent identity style in a sample of non-White South African adolescents. Identity development is an important process in the lives of adolescents, and many changes and much decision-making occur during this phase. Maternal influence, it would seem, is vital in identity development of adolescents. As an understudied area of research in South Africa, this study offers tentative insights into the potential of harnessing the mother–adolescent relationship to enhance positive development of identity style and commitment.