bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response of Parasitic Wasp Cotesia glomerata L. (Hymenoptera: Braconidae) to Cabbage Plants of Two Varieties: Olfactory Spectra of Males and Females
Authors: Blažytė-Čereškienė Laima , Aleknavičius Dominykas , Apšegaitė Violeta , Būda Vincas 
Published: September 2022

Abstract
The parasitoid Cotesia glomerata L. (Hymenoptera: Braconidae) oviposits in larvae of the large cabbage white butterfly (Pieris brassicae L.). Many parasitoids are attracted by volatile organic compounds (VOCs) emitted by the plant that the host insects feed on. The objectives of the study were to identify the VOCs in leaves of two varieties of cabbage (white cabbage, Brassica oleracea var. capitata f. alba and cauliflower, B. oleracea var. botrytis) damaged by P. brassicae caterpillars which elicit antennal responses of C. glomerata, and characterize the olfactory spectra of females and males. Leaf extracts were analyzed by using gas chromatography equipped with an electroantennographic detector (GC–EAD) and GC–mass spectrometry. In total, 32 olfactory-active compounds for C. glomerata in cauliflower and 24 in white cabbage were revealed. The females perceived more compounds than males. Hexan-1-ol, (E)-3-hexen-1-ol, (E)-2-octenal, benzylcianide, tetradecanal, and two unidentified compounds elicited EAG responses in females but not in males. Females were more sensitive to (E)-3-hexenal, (Z)-3-hexenal, and pentadecenal, whereas males showed higher sensitivity to (Z)-3-hexenyl butanoate, heptanal, (Δ)-2-pentenal, (E)-2-hexenol, and octanal. The olfactory spectrum of C. glomerata was expanded from 18 to 41 VOCs emitted by different varieties of cabbage damaged by P. brassicae caterpillars. Eight EAG-active VOCs were common for all cabbage varieties. In tritrophic interactions, benzylcyanide can serve as an important signal for C. glomerata females indicating damage of cabbage caused by P. brassicae caterpillars. The data are useful for development of a push–pull strategy for P. brassicae control, based on parasitoid behavior regulation by VOCs.
Staged surgical repair of severe pulmonary stenosis post radiofrequency ablation
Authors: Murray Lewis William , Gopal Rakesh , Gimpel Damian , Szpytma Malgorzata (Maggie) , Crouch Gareth 
Published: September 2022

Abstract
We present a case of a 68-year-old man who presents with worsening cough and dyspnoea 12 months after undergoing radiofrequency ablation therapy for atrial fibrillation. Investigation revealed complete occlusion of the left lower pulmonary vein and partial stenosis of the left upper pulmonary vein. He underwent a stage surgical resection with the first stage being a left lower lobectomy for the non-viable lobe followed by a repair of the left upper pulmonary vein via anastomosis with the left atrial appendage. This staged procedure yielded excellent results and avoided the need for a left-sided pneumonectomy.
Small bowel obstruction caused by hemorrhagic metastatic melanoma: case report and literature review
Authors: Wu Fanyi , Lee M Sung , Kim Daniel E 
Published: September 2022

Abstract
Melanoma is one of the most common cancers and causes of death from skin cancer. It is also one of the most common malignancies to metastasize to the gastrointestinal tract. However, the incidence of gastrointestinal metastases from unknown primary cutaneous melanoma is reported to be 4–9%. Despite advances in diagnostic techniques, only 1.5–4.4% of metastases to the gastrointestinal tract are detected before death. We report a patient with no prior history of melanoma who presented with both gastrointestinal hemorrhage and small bowel obstruction. Diagnostic laparoscopy, followed by small bowel resection, was performed after a red blood cell radionuclide scan showed active hemorrhage. Pathologic examination confirmed metastatic melanoma of the jejunum. Additional small bowel resections were required for recurrent gastrointestinal bleeding, confirming two additional metastases. A review of the literature on small intestinal melanoma causing hemorrhage and obstruction is discussed.
The financial aspects of offshore decommissioning and Brazilian regulatory system in the light of the transnational legal order
Authors: Braga Luciana , Pinto Helder 
Published: September 2022

Abstract
This article discusses the financial aspects of offshore decommissioning, highlighting the regulatory challenges to balance public interest protection and investment attraction. The Brazilian regulatory system for offshore decommissioning is chosen to exemplify how Brazil is tackling these issues. To detail this system, this article adopts the Transnational Legal Order approach, by Halliday and Shaffer, which offers an integrated view of the regulatory system, detailing it in three categories of rules: national, international and transnational.
Enriching contextualized semantic representation with textual information transmission for COVID-19 fake news detection: A study on English and Persian
Authors: Ghayoomi Masood 
Published: September 2022

AbstractThe COVID-19 pandemic provided an infodemic situation to face people in the society with a massive amount of information due to accessing social media, such as Twitter and Instagram. These platforms have made the information circulation easy and paved the ground to mix information and misinformation. One solution to prevent an infodemic situation is avoiding false information distribution and filtering the fake news to reduce the negative impact of such news in the society. This article aims at studying the properties of fake news in English and Persian using the textual information transmitted through language in the news. To this end, the properties existed in a text based on information theory, stylometry information from raw texts, readability of the texts, and linguistic information, such as phonology, syntax, and morphology, are studied. In this study, we use the XLM-RoBERTa representation with a convolutional neural network classifier as the basic model to detect English and Persian COVID-19 fake news. In addition, we propose different learning scenarios such that different feature sets are concatenated with the contextualized representation. According to the experimental results, adding any of the textual information to the basic model has improved the performance of the classifier for both English and Persian. Information about readability of the texts and stylometry features have been the most effective features for detecting English fake news and improved the performance by 2.72% based on F-measure. Augmenting this feature setting with the information amount and linguistic morphological information improved the performance of the classifier by 3.79% based on F-measure for Persian.
Synthesis of point-modified mRNA
Authors: Hertler Jasmin , Slama Kaouthar , Schober Benedikt , Özrendeci Zeynep , Marchand Virginie , Motorin Yuri , Helm Mark 
Published: September 2022

Abstract
Synthetic mRNA has recently moved into the focus of therapeutic and vaccination efforts. Incorporation of modified nucleotides during in vitro transcription can improve translation and attenuate immunogenicity, but is limited to triphosphate nucleotides which are accepted by RNA polymerases, and their incorporation is either random or complete. In contrast, site-specific modification, herein termed ‘point modification’ in analogy to point mutations, holds significant technical challenge. We developed fundamental techniques for isolation of long, translatable and internally point-modified mRNAs. Enabling concepts include three-way-one-pot splint ligations, and isolation of mRNA by real-time elution from agarose gels. The use of blue light permitted visualization of mRNA in pre-stained gels without the photochemical damage associated with the use of hard UV-radiation. This allowed visualization of the mRNA through its migration in the agarose gel, which in turn, was a prerequisite for its recovery by electroelution into precast troughs. Co-eluting agarose particles were quantified and found to not be detrimental to mRNA translation in vitro. Translation of EGFP-coding mRNA into functional protein was quantified by incorporation of 35S-labelled methionine and by in-gel EGFP fluorescence. This enabled the functional analysis of point modifications, specifically of ribose methylations in the middle of a 1371 nt long mRNA.
PL01.3.A Radiomic features and DNA methylation attributes in primary CNS lymphoma
Authors: Nenning K , Gesperger J , Nemc A , Roetzer-Pejrimovsky T , Choi S , Preusser M , Nam D , Bock C , Langs G , Woehrer A ,   ABTR-PCNSL study group
Published: September 2022

Abstract

Background
Clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma (PCNSL), but the derived risk models do not fully explain the observed variation in outcome. Here we present an extended framework of phenotype-epigenotype correlations that reveal novel prognostic constellations and enable prioritizing epigenetic therapy.

Material and Methods
In this retrospective discovery and validation study, we leverage radiomic feature-driven analysis of medical images and supervised bioinformatic integration of DNA methylation profiles. We integrate both data modalities synergistically using machine learning-based prediction and cross-domain alignment. Ultimately, we validate the most relevant biological associations in tumor tissues and cell lines.

Results
We leverage a cohort of 191 patients across 9 sites in Austria and an external validation site in South Korea, and use T1-weighted contrast-enhanced magnetic resonance imaging to derive a radiomic risk score that consists of 20 mostly textural features. We determine the risk score as strong and independent predictive factor (multivariate HR=6.56), and confirm its prognostic value in an external validation cohort. Radiomic features align with DNA methylation sites in distinct, biologically meaningful ways, and radiomic risk is predictable from selected DNA methylation sites (AUC=0.78). Ultimately, gene-regulatory differences between radiomically-defined risk groups converge on bcl6 binding activity, which is posed as testable treatment strategy in a subset of patients.

Conclusion
The radiomic risk score is a robust and complementary predictor of survival and is reflected at the level of DNA methylation in PCNSL. Assessing risk and selecting epigenetic treatment based on imaging phenotypes represents a huge step forward, and the ability to define radiomic risk groups provides a concept on which to advance prognostic modeling and precision therapy for this aggressive brain cancer.
PL02.2.A Microglia-specific disruption of sialic acid-Siglec-9/E interactions. A novel immunotherapy against glioblastoma?
Authors: Schmassmann P , Roux J , Martins T A , Ritz M , Shekarian T , McDaid M , Hutter H Läubli G 
Published: September 2022

Abstract

Background
Recently, ‘don’t eat me’-signals like CD47 have emerged as novel innate immune checkpoints, enabling cancer cells to evade clearance by phagocytes such as monocyte-derived macrophages (MdM) or microglia (MG). Here, we aim at defining the role of inhibitory Siglec-9 in human and its mouse homologue Siglec-E in MG-centered immunotherapy against GBM.

Material and Methods
We employed a CT-2A orthotopic GBM mouse model with MG specific (Sall1CreERT2 x Sigleceflox) and whole innate-compartment (Cx3cr1CreERT2 x Sigleceflox) spatio-temporal deletion of Siglece. We applied multi-color flow cytometry, transcriptomics and proteomics analysis to decipher the immune response upon Siglece knockout.

Results
TCGA RNA-sequencing data revealed a significant correlation between high expression of immunoinhibitory SIGLEC9 and poor survival in GBM patients (log-rank p = 0.02). Siglec-E blockade increased murine MG mediated GBM cell in vitro phagocytosis (normalized phagocytosis of 1.00 in isotype vs. 1.76 in anti-Siglec-E antibody, p &lt; 0.001). In the MG specific spatio-temporal deletion of Siglece (Sall1CreERT2 xSigleceflox), we observed high MG-proliferation upon Siglec-E knockout (Ki-67+ MG 14.8% in Cre- vs. 34.9% in Cre+, p &lt; 0.0001) accompanied by an enhanced microglial GBM-cell uptake (5.6% in Cre- vs. 12.3% in Cre+, p &lt; 0.001). By extending the Siglece knockout to the MdM compartment in our glioma mouse model (Cx3cr1CreERT2 x Sigleceflox) we observed a significantly prolonged survival in the Cx3cr1Cre+ population (21d in Cre- vs. 27d post-tumor injection in Cre+, p = 0.018), which could be further promoted by combining Siglece knockout with CD47 blockade (30d post-tumor injection in Cre+ + anti-CD47). Unbiased proteomics analysis revealed increased antigen processing and presentation capabilities of Siglece knockout MdMs which was confirmed by ex-vivo OT-1 cross-presentation assays. This bridging of innate and adaptive responses with increased T cell priming upon MdM Siglece knockout was further promoted by addition of anti-PD1 antibody to the combined Siglece knockout and anti-CD47 treatment arm. Animals harboring CT-2A tumors, exhibited a sustained survival benefit under the triple therapy, with 23% of animals experiencing long-term remission, even after tumor re-challenge into the contra-lateral hemisphere. By genetically targeting sialic acids, the ligand for Siglec receptors, on CT-2A cells (GNE-KO), we observed a strong innate and adaptive immune response with increased GBM-cell phagocytosis by MG and MdMs and less exhausted tumor-infiltrating CD8+ T-cells (14.8% in WT vs. 5.9% in GNE-KO, p = 0.003).

Conclusion
These data identify the sialic-acid-Siglec-E pathway as an anti-phagocytic signal in a pre-clinical GBM model, and demonstrate its therapeutic potential in GBM immunotherapy.
PL02.4.A International validation study of an EORTC instrument measuring instrumental activities of daily living (IADL) in patients with brain tumours: EORTC IADL-BN32
Authors: Oort Q , Koekkoek J , Aaronson N K , Boele F W , Brannan C , Capela A , Hjermstad M , Klein M , Lips I , Narita Y , Pace A , Petranovic D , Pichler J , Reijneveld J C , Sato H , Seidel C , Shamieh O , Sikkes S A M , Talacchi A , Uitdehaag B M J , Urbanic T , Young T , Taphoorn M J B , Dirven L 
Published: September 2022

Abstract

Background
Brain tumour patients often have neurocognitive deficits which can result in problems with activities in daily living that are cognitively complex. Currently, no valid and reliable brain tumour-specific instrument to measure these instrumental activities of daily living (IADL) is available, but such an instrument is being developed. This study aimed to validate the EORTC IADL-BN32 questionnaire, comprising five multi-item and two single item scales, in a large set of international brain tumour patients.

Material and Methods
This international study was conducted in 10 countries worldwide. Primary and metastatic brain tumour patients and their proxies were requested to complete the EORTC IADL-BN32 and a subjective cognitive questionnaire (MOS COG-R) at multiple time points. Several psychometric properties were evaluated with baseline data, including the structural validity (bi-factor confirmatory factor analysis [CFA]), reliability (internal consistency), construct validity (known groups comparisons) and patient-proxy congruency (intra-class correlation coefficients [ICC], Spearman's correlation).

Results
At baseline, 326 patients ( 30% low-grade glioma, 37% high-grade glioma (HGG) and 33% brain metastases) and 311 proxies completed the EORTC IADL-BN32. The bi-factor CFA was found to have a satisfactory model fit (CFI=0.92 and TLI=0.90), and other parameters indicated a good fit (RMSEA=0.08 and SRMR=0.05), thereby validating the preliminary scale structure, but also an IADL sum score. The multi-item scales showed good (0.9&gt;α≥0.8) to excellent (α≥0.9) internal consistency (range α=0.86-0.97). Known groups comparisons analyses regarding patient’s cognitive status (indications vs. no cognitive impairment), subjective cognitive complaints (MOS COG-R ≤30 vs. &gt;30), basic ADL (Barthel Index &lt;100 vs. 100) and performance status (KPS &lt;70 vs. ≥70) showed significant differences on all IADL outcome measures in line with a priori defined hypotheses. On a group level, patient and proxy ratings had moderate to strong correlations, however, proxies tended to report more problems on all scales. The ICCs showed moderate to good congruency between patients and proxies (range ICC: 0.63-0.81).

Conclusion
The evaluated psychometric properties support the current scale structure of the EORTC IADL-BN32. Additional psychometric properties with longitudinal data are needed, such as test-retest reliability and responsiveness, to further validate the EORTC-IADL BN32 questionnaire.
KS01.5.A Impact of reduced treatment volumes on pattern of tumor recurrence and radiation dose to normal brain parenchyma in glioblastoma
Authors: Minniti G , Giraffa M , Capone L , Raza G , Russo I , Navarria P , Tini P , Romano A , Bozzao A , Paolini S , Esposito V 
Published: September 2022

Abstract

Background
to analyze GBM recurrence pattern after standard chemoradiotherapy according to different target volume delineations. We hypothesized that reduced target volume margins may result in similar pattern of failure.

Material and Methods
207 patients with GBM who recurred after standard chemoradiation were evaluated. According to the Advisory Committee for Radiation Oncology Practice (ACROP) committee of the European Organisation for Research and Treatment of Cancer (EORTC) target volume delineation guideline, the clinical target volume (CTV) used for treatment planning consisted of residual tumor and resection cavity plus 2-cm margin. MRI scans showing tumor recurrences were fused with the planning computed tomography (CT), and the patterns of failure were analyzed dosimetrically using dose-volume histograms. The recurrent lesions were defined as in-field, marginal, or distant if &gt;80%, 20-80%, or &lt;20% of the intersecting volume was included in the 95% isodose line. For each patient a theoretical plan consisting of a reduced CTV using 1-cm margin was created and patterns of failure evaluated.

Results
The median overall survival and progression-free survival were 15.3 months and 7.8 months, respectively, from the date of surgery. Recurrences were in-field in 180 patients, marginal in 5 patients, and distant in 22 patients. Analysis of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status showed different recurrence patterns of GBMs in patients with MGMT methylated compared with patients with MGMT unmethylated status. Recurrences occurred in-field and distant in 75.6% and 18.6% of methylated patients and in 91.8% and 6% of unmethylated patients, respectively (p=0.0046). Patterns of failure were similar between the different treatment plans. Reduced target volumes were associated with significantly lower doses of 20-50 Gy to normal brain and hippocampi (p=0.0001).

Conclusion
Most of patients treated with standard chemioradiotherapy have in-field recurrences; however, an increased risk of distant recurrences occurs in methylated tumors. The use of target delineation using 1-cm CTV margin is associated with smaller volumes of normal brain and hippocampi irradiated to high doses, without significant changes in the pattern of failure. The impact of different target delineation in terms of efficacy and risk of late radiation-induced toxicity should be assessed prospectively.
OS03.5.A Characterization of the inflammatory tumor microenvironment composition in solid cancer patients with brain metastases after progression to immune checkpoint inhibitor therapy
Authors: Starzer A M , Kleinberger M , Feldmann K , Tomasich E , Hatziioannou T , Paiato C , Heller G , Kreminger J , Traint S , Steindl A , Ressler J M , Widhalm G , Gatterbauer B , Dieckmann K , Müllauer L , Preusser M , Berghoff A S 
Published: September 2022

Abstract

Background
Immunotherapy (IO) has changed the treatment landscape of metastatic cancer patients, however, treatment resistance is frequent. We aimed to characterize the inflammatory tumor microenvironment in brain metastases (BM) after IO to gain a deeper understanding of immunologic escape mechanisms.

Material and Methods
Solid cancer patients who had BM resection after IO progression (IO cohort) were retrospectively identified. We analyzed tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) and expression of immune checkpoint molecules (PD-L1, PD-1, LAG-3) by immunohistochemistry. A control cohort of BM tissue samples without prior IO served for comparison (no immunotherapy cohort, NIO).

Results
Twenty-eight IO patients (12/28, 42.9% females; 16/28, 57.1% males; median 61 years; 14/28, 50% lung cancer; 5/28, 17.9% melanoma; 4/28, 14.3% renal cell carcinoma; 1/28, 3.6% breast cancer; 4/28, 14.3% other cancer entities) and 57 NIO patients (28/57, 49.1% females; 29/57, 50.9% males; median 58 years; 35/57, 61.4% lung cancer; 9/57, 15.8% breast cancer; 4/57, 7.0% melanoma; 3/57, 5.3% renal cell carcinoma; 6/57, 10.5% other cancer entities) were included. IO patients had a median of one (range 0-4) systemic therapy line prior to IO. Median time from last IO application until BM resection was 5.6 months (range 0.2-49.8 months). Patients received a median number of 7 (range 1-56) IO applications (14/28, 50% PD-1-targeting IO; 8/28, 28.6% PD-L1; 2/28, 7.1% CTLA4; 4/28, 14.3% CTLA4+PD-1; 3/28, 10.7% IO+chemotherapy). No statistically significant differences in the densities of investigated TILs or PD-L1 expression between the IO and the NIO cohort were observed. Patients of the IO cohort showed higher PD-L1 expression compared to the NIO cohort (57.1 vs. 42.1%, Chi-square, p&gt;0.05). Overall survival (OS) was similar in both cohorts, with a median OS of 11.0 months (range 5.0-17.0) in the IO cohort and 11.0 months (range 5.5-16.5) in the NIO cohort.

Conclusion
Our findings show an upregulation of PD-L1 in BM occurring after prior IO therapy in the absence of other overt changes in the inflammatory microenvironment. Ongoing analyses in this cohort are investigating possible molecular driver of resistance by analyzing DNA methylation profiles of pre-and post-IO tissue samples of the IO cohort to potentially gain insights on inflammatory IO resistance mechanisms in BM patients.