bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shock and splash: gas and dark matter halo boundaries around ΛCDM galaxy clusters
Authors: Aung Han , Nagai Daisuke , Lau Erwin T 
Published: September 2021

ABSTRACT
Recent advances in simulations and observations of galaxy clusters suggest that there exists a physical outer boundary of massive cluster-size dark matter (DM) haloes. In this work, we investigate the locations of the outer boundaries of DM and gas around cluster-size DM haloes, by analysing a sample of 65 massive DM haloes extracted from the Omega500 zoom-in hydrodynamical cosmological simulations. We show that the location of accretion shock is offset from that of the DM splashback radius, contrary to the prediction of the self-similar models. The accretion shock radius is larger than all definitions of the splashback radius in the literature by $20-100{{\ \rm per\ cent}}$. The accretion shock radius defined using the steepest drop in the entropy and pressure profiles is approximately 1.89 times larger than the splashback radius defined by the steepest slope in the DM density profile, and it is ≈1.2 times larger than the edge of the DM phase space structure. We discuss implications of our results for multiwavelength studies of galaxy clusters.
Prospects of direct detection of 48V gamma-rays from thermonuclear supernovae
Authors: Panther Fiona H , Seitenzahl Ivo R , Ruiter Ashley J , Siegert Thomas , Sim Stuart , Crocker Roland M 
Published: September 2021

ABSTRACT
Detection of gamma-rays emitted by radioactive isotopes synthesized in stellar explosions can give important insights into the processes that power transients such as supernovae, as well as providing a detailed census of the abundance of different isotope species relevant to the chemical evolution of the Universe. Observations of nearby supernovae have yielded observational proof that 57Co powered the late-time evolution of SN1987A’s light curve, and conclusive evidence that 56Ni and its daughter nuclei power the light curves of Type Ia supernovae. In this paper, we describe the prospects for detecting nuclear decay lines associated with the decay of 48V, the daughter nucleus of 48Cr, which is expected to be synthesized in large quantities – $M_{\mathrm{Cr}}\sim 1.9\times 10^{-2}\, \mathrm{M_\odot }$ – in transients initiated by explosive helium burning (α-capture) of a thick helium shell. We calculate emergent gamma-ray line fluxes for a simulated explosion model of a thermonuclear explosion of carbon–oxygen white dwarf core of mass $0.45\, \mathrm{ M}_{\odot }$ surrounded by a thick helium layer of mass $0.21\, \mathrm{ M}_{\odot }$. We present observational limits on the presence of 48V in nearby SNe Ia 2014J using the INTEGRAL space telescope, excluding a 48Cr production on the surface of more than $0.1\, \mathrm{M_{\odot }}$. We find that the future gamma-ray mission the All-Sky Medium Energy Gamma-Ray Observatory (AMEGO) will have an approximately 5 per cent chance of observing 48V gamma-rays from such events during the currently planned operational lifetime, based on our birthrate predictions of faint thermonuclear transients. We describe the conditions for a 3σ detection by the gamma-ray telescopes INTEGRAL/SPI, Compton Spectrometer and Imager (COSI) , and AMEGO.
Perseus arm – a new perspective on star formation and spiral structure in our home galaxy
Authors: Wienen M , Brunt C M , Dobbs C L , Colombo D 
Published: September 2021

ABSTRACT
Expansion of (sub)millimetre capabilities to high angular resolution offered with interferometers allows to resolve giant molecular clouds (GMCs) in nearby galaxies. This enables us to place the Milky Way in the context of other galaxies to advance our understanding of star formation in our own Galaxy. We, thus, remap 12CO (1–0) data along the Perseus spiral arm in the outer Milky Way to a fixed physical resolution and present the first spiral arm data cube at a common distance as it would be seen by an observer outside the Milky Way. To achieve this goal, we calibrated the longitude–velocity structure of 12CO gas of the outer Perseus arm based on trigonometric distances and maser velocities provided by the BeSSeL survey. The molecular gas data were convolved to the same spatial resolution along the whole spiral arm and regridded on to a linear scale map with the coordinate system transformed to the spiral arm reference frame. We determined the width of the Perseus spiral arm to be 7.8 ± 0.2 km s−1 around the kinematic arm centre. To study the large-scale structure, we derived the 12CO gas mass surface density distribution of velocities, shifted to the kinematic arm centre, and arm length. This yields a variation of the gas mass surface density along the arm length and a compression of molecular gas mass at linear scale. We determined a thickness of ∼63 pc on average for the Perseus spiral arm and a centroid of the molecular layer of 8.7 pc.
Formation and evolution of protostellar accretion discs – II. From 3D simulation to a simple semi-analytic model of Class 0/I discs
Authors: Xu Wenrui , Kunz Matthew W 
Published: September 2021

ABSTRACT
We use a 3D radiative non-ideal magnetohydrodynamic simulation to investigate the formation and evolution of a young protostellar disc from a magnetized pre-stellar core. The simulation covers the first ${\sim }10\, {\rm kyr}$ after protostar formation and shows a massive, weakly magnetized disc with radius that initially grows and then saturates at ${\sim }30\, {\rm au}$. The disc is gravitationally unstable with prominent large-amplitude spiral arms. We use our simulation results and a series of physical arguments to construct a predictive and quantitative physical picture of Class 0/I protostellar disc evolution from several aspects, including (i) the angular-momentum redistribution in the disc, self-regulated by gravitational instability to make most of the disc marginally unstable; (ii) the thermal profile of the disc, well-approximated by a balance between radiative cooling and accretion heating; and (iii) the magnetic-field strength and magnetic-braking rate inside the disc, regulated by non-ideal magnetic diffusion. Using these physical insights, we build a simple 1D semi-analytic model of disc evolution. We show that this 1D model, when coupled to a computationally inexpensive simulation for the evolution of the surrounding pseudo-disc, can be used reliably to predict disc evolution in the Class 0/I phase. The predicted long-term evolution of disc size, which saturates at ${\sim }30\, {\rm au}$ and eventually shrinks, is consistent with a recent observational survey of Class 0/I discs. Such hierarchical modelling of disc evolution circumvents the computational difficulty of tracing disc evolution through Class 0/I phase with direct, numerically converged simulations.
CLRM-03. BGB-290 AND TEMOZOLOMIDE IN TREATING ISOCITRATE DEHYDROGENASE (IDH)1/2-MUTANT GRADE I-IV GLIOMAS – A NOVEL MODEL OF AYA TRIAL DEVELOPMENT AND DEPLOYMENT
Authors: Marks Asher , Bindra Ranjit 
Published: September 2021

Abstract

DESCRIPTION
The lack of enrollment of AYA patients on clinical trials is well documented and multivariant. Here we present the basic science, examination of its relevance to the AYA population specifically, and the parallel deployment of two international clinical trials via a pediatric neuro-oncology and adult brain tumor consortium.

DISCUSSION
In February of 2017, the laboratory of Ranjit Bindra, MD, PhD, published a manuscript describing the finding that tumors with IDH1/2 mutations induce a BRCAness state leading to PARP inhibitor (PARPi) sensitivity and synergistic interactions with temozolomide chemotherapy [2]. Despite IDH1/2 mutations being rare in the pediatric high-grade glioma population, three independent groups confirmed that the incidence is significantly increased to ~30% in the adolescent and young adult (AYA) population. Upon discovery of a high blood-brain-barrier penetrant, high potency PARPi by BeiGene Pharmaceuticals, an international trial was launched through the Pacific Pediatric Neuro-Oncology Consortium (PNOC) [3] to test this drug in an AYA specific trial recruiting patients ages 13 to 25, with a concurrent trial being run for patients older than 25 years of age through the Adult Brain Tumor Consortium (ABTC) [4].
While most trials that enroll AYA patients are forced to assess them as a unique cohort in post-analysis, if at all, the PNOC trial mentioned above was designed from the ground up with the AYA population in mind. It has allowed us to base initial dosing, recruitment strategies, psychosocial assessments, and outcomes, specifically on the AYA population. Ultimately, we expect their distinctive biology to yield unique results when compared to the ABTC trial.
We propose that this is a model that could potentially be replicated in other disease processes and early phase drugs with the buy-in of the pharmaceutical industry and early phase consortiums.
Acknowledgements: BeiGene Pharmaceuticals, PNOC, ABTC, CureSearch, Gateway Foundation
CLRM-08. TRIAL WORKING GROUPS FOR PAEDIATRIC BRAIN TUMOURS
Authors: Rahman Ruman , Walker David , Campbell Emma , Aquilina Kristian 
Published: September 2021

Abstract

INTRODUCTION
Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the outlook for these children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate these. In addition, custom-built hardware, novel surgical procedures and the testing and licensing of implantable devices add difficulty at the regulatory level.

METHODS
The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium), the CBTDDC and the ITCC (Innovative Therapies for Children with Cancer) brain tumour group launched the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’. This aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for the treatment of paediatric brain tumours.

RESULTS
On 1 March, 2021, CBTDDC and Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon at Great Ormond Street Hospital) hosted the first steering group meeting, comprising 38 leading brain tumour research scientists and clinicians from the UK, EU and US.

CONCLUSION
The ideas generated during the March meeting are driving the agenda for a Clinical Trials Workshop that will be held in the autumn of 2021. In particular, there was agreed consensus that a ‘Roadmap’ document for pre-clinical to clinical translation needs to be created and shared with the paediatric neuro-oncology research community. We present this abstract to the CNS Clinical Trials Meeting to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.
IMMU-01. TEM-GBM: AN OPEN-LABEL, PHASE I/IIA DOSE-ESCALATION STUDY EVALUATING THE SAFETY AND EFFICACY OF GENETICALLY MODIFIED TIE-2 EXPRESSING MONOCYTES TO DELIVER IFN-A WITHIN GLIOBLASTOMA TUMOR MICROENVIRONMENT
Authors: Finocchiaro Gaetano , Eoli Marica , Gentner Bernhard , Capotondo Alessia , Anghileri Elena , Antonarelli Gabriele , Barcella Matteo , Bruzzone Maria Grazia , Carrabba Matteo , Cuccarini Valeria , D'Alessandris Quintino G , DiMeco Francesco , Farina Francesca , Ferla Valeria , Ferroli Paolo , Gagliardi Filippo , Garramone Mariagrazia , Legnani Federico , Mortini Piero , Naldini Matteo , Olivi Alessandro , Pallini Roberto , Patané Monica , Paterra Rosina , Pollo Bianca , Saini Marco , Snider Silvia , Brambilla Valentina , Magnani Tiziana , Mazzoleni Stefania , Bashir Zahid , Russo Carlo , Naldini Luigi , Ciceri Fabio 
Published: September 2021

Abstract
Temferon is a macrophage-based treatment relying on ex-vivo transduction of autologous HSPCs to express immune-payloads within the TME. Temferon targets the immune-modulatory molecule IFN-a, to a subset of tumor infiltrating macrophages known as Tie-2 expressing macrophages (TEMs) due to the Tie2 promoter and a post-transcriptional regulation layer represented by miRNA-126 target sequences. As of 31st May 2021, 15-patients received Temferon (D+0) with follow-up of 3 – 693 days. After conditioning neutrophil and platelet engraftment occurred at D+13 and D+13.5, respectively. Temferon-derived differentiated cells, as determined be the number of vector copy per genome, were found within 14 days post treatment and persisted albeit at lower levels up to 18-months. Very low concentrations of IFN-a in the plasma (8.7 pg/ml-D+30) and in the CSF (1.6 pg/ml-D+30) were detected, suggesting tight regulation of transgene expression. Five-deaths occurred at D+322, +340, +402, +478 and +646 due to PD, and one at D+60 due to complications following the conditioning regimen. Eight-patients had progressive disease (range: D-11 to +239) as expected for this tumor type. SAEs include GGT elevation (possibly related to Temferon) and infections, venous thromboembolism, brain abscess, hemiparesis, seizures, anemia and general physical condition deterioration, compatible with ASCT, concomitant medications and PD. Four-patients underwent 2ndsurgery. Recurrent tumors had gene-marked cells and increased expression of ISGs compared to first surgery, indicative of local IFNa release by TEMs. In one patient, a stable lesion had a higher proportion of T cells and TEMs within the myeloid infiltrate and an increased ISGs than in the progressing lesion, detected in the same patient. Tumor-associated clones expanded in the periphery. TME characterization by scRNA and TCR-sequencing is ongoing. To date, Temferon is well tolerated, with no DLTs identified. The results provide initial evidence of Temferon potential to activate the immune system of GBM patients, as predicted by preclinical studies.
IMMU-07. A PHASE I STUDY OF MULTIPLE PEPTIDE TUMOR-ASSOCIATED ANTIGEN VACCINES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Batich Kristen , Archer Gary , Norberg Pamela , Ashley David , Sampson John , Khasraw Mustafa 
Published: September 2021

Abstract

INTRODUCTION
Targeting tumor-associated antigens (TAAs) via peptide vaccination has been tested against malignant glioma with minimal success. Poor responses are attributed to relatively low antigen level expression of the TAA and insufficient CD8+ T cell responses. Including a universal class II epitope that provides CD4+ T cell help towards CD8+ responses has been tested with the immunogenic tetanus toxoid epitope P30, but P30 has been employed as a separate peptide in this regard. The current study will employ targeting of three major glioma TAAs: EphA2, pp65 from Cytomegalovirus, and survivin. The ability to induce more potent TAA-specific immune responses will be tested using two novel strategies: P30-linked TAA peptides and a combinatorial vaccination of the linked peptides (P30-EPS).

HYPOTHESES
In Evaluation of Tumor Associated P30-Peptide Antigen I (ETAPA-I), P30-EPS is anticipated to have an acceptable toxicity profile. Multi-peptide vaccination is thought to bypass tumor heterogeneity and selection of antigen-negative clones, known as antigen escape. Moreover, the administration of EPS covalently linked to P30 is anticipated to increase the magnitude of antigen-specific immune responses and elicit both CD4- and CD8-mediated immune recognition.

TRIAL DESIGN/OBJECTIVES
A maximum of 24 patients with newly diagnosed, unmethylated WHO grade IV glioma will be treated. Following resection and standard of care chemoradiation, patients will be vaccinated serially during the priming phase (Day 1-22) and booster phase (Day 84 and 140). All P30-EPS vaccines during priming and boosting phases are co-administered with the adjuvant Hiltonol (Oncovir, poly-ICLC), and patients self-administer Hiltonol throughout the booster phase. The primary endpoint will evaluate the safety profile of P30-EPS. Secondary objectives include polyfunctional T-cell responses specific to EphA2, pp65 and survivin, TCR diversity, and survival.

CONCLUSION
We describe a study that employs known TAA targets of malignant glioma with the novel strategy of combinatorial class II-linked peptide vaccination.
NEIM-01. PREDICTION OF RESPONSE TO COMBINATION OF NIVOLUMAB AND BEVACIZUMAB IN PATIENTS WITH RECURRENT GLIOBLASTOMA VIA RADIOMIC ANALYSIS ON CLINICAL MRI SCANS
Authors: Verma Ruchika , Rauf Yasmeen , Yadav Ipsa , Statsevych Volodymyr , Chen Jonathan , Evanoff Wendi , Ahluwalia Manmeet , Tiwari Pallavi 
Published: September 2021

Abstract

PURPOSE
The use of immunotherapy in glioblastoma management is under active investigation. Glioblastomas are “cold” tumors, meaning that they have inactivated or fewer tumor infiltrative lymphocytes in addition to substantial tumor necrosis, attributing to their poor response to immunotherapy. A significant challenge is the apriori identification of Glioblastoma patients who will respond favorably to immunotherapy. In this work, we evaluated the ability of computerized MRI-based quantitative features (radiomics) extracted from the lesion habitat (including enhancing lesion, necrosis, and peritumoral hyperintensities) to predict response and progression-free survival (PFS) in recurrent GBM patients treated with combination of Nivolumab and Bevacizumab.

METHODS
Immunotherapy response assessment in neuro-oncology (iRANO) criteria along with PFS were used to analyze n=50 patients enrolled in a randomized clinical trial where patients received Nivolumab with either standard or low dose Bevacizumab. These patients were assessed to see if they had complete response, partial response, stable disease (i.e. responders, n=31), or disease progression (i.e. non-responders, n=19). Lesion habitat constituting necrotic core, enhancing tumor, and edema were delineated by expert radiologist on Gd-T1w, T2w and FLAIR MRI scans. COLIAGE radiomic features from each of the delineated regions were selected using minimum redundancy maximum relevance (mRMR) via cross-validation, to segregate non-responder patients from responders. A multivariable cox proportional hazard model was used to predict survival (PFS).

RESULTS
CoLlAGe correlation, sum average, and sum variance features (capture local heterogeneity) from the lesion habitat, were found to segregate non-responder patients from responders with an accuracy of 86%, followed by 80% using features from peritumoral hyperintensities and 78% from enhancing tumor. In our survival analysis, C-index of 0.688 was obtained using features from the entire lesion habitat, followed by peritumoral hyperintensities (0.675) and enhancing tumor (0.656).

CONCLUSION
Radiomic features from the lesion habitat may predict response to combination of Nivolumab and Bevacizumab in recurrent Glioblastomas.
SCSS-01. ANTICONVULSANT PROPHYLAXIS IN PATIENTS WITH NEWLY DIAGNOSED BRAIN TUMORS: DOES IT PREVENT FIRST SEIZURES, DOES IT IMPROVE SURVIVAL, AND DO WE BELIEVE THE DATA?
Authors: Brown Timothy , Zoccoli Christina , Mansouri Alireza , Glantz Michael 
Published: September 2021

Abstract

BACKGROUND
Despite an American Academy of Neurology Practice Guideline and ASCO/SNO endorsement against the routine use of anticonvulsant prophylaxis in patients with primary and metastatic brain tumors, there remains widespread variation in practice and several unanswered questions.

METHODS
Exhaustive evidence-based literature searches were conducted, and patient-level data from randomized controlled trials (RCTs) were analyzed to answer three questions: does anticonvulsant prophylaxis reduce the risk of first seizures in patients with primary and metastatic brain tumors; does prophylaxis improve one-year overall survival in patients with primary and metastatic brain tumors; and what effect have practice guidelines had on practice patterns.

RESULTS
Five RCTs (n=441 patients) addressed anticonvulsant prophylaxis in patients with brain tumors. Overall, anticonvulsant prophylaxis did not reduce the risk of a first seizure in patients with any brain tumor (RR= 0.95 [0.58-1.55], p= 0.85, anticonvulsant prophylaxis vs. placebo), brain metastasis (RR = 0.96 [0.73-1.25], p=0.77, 5 RCTs) or primary brain tumors (RR= 1.03 [0.19-5.72], p=0.97, 4 RCTs). Eleven RCTs of anticonvulsant prophylaxis (n=3767 patients with CNS tumors) provided data for survival analysis and demonstrated a lower RR of death at one year compared to those who did not receive prophylaxis (0.88 [0.81-0.94] p = 0.0006). Physician-reported practice of prescribing anticonvulsant prophylaxis diminished only negligibly after initial guideline publication (54.9% [1 study] vs. 51.6%, [3 studies] p&lt;0.014).

CONCLUSION
Prophylactic anticonvulsants in patients without a history of seizures does not reduce the risk of first seizures in patients with primary or metastatic brain tumors. Despite this, anticonvulsant prophylaxis provides a small survival benefit at one year, although, this finding may be driven by confounded studies. Rates of anticonvulsant prophylaxis prescription have decreased only minimally and remain very high despite strong evidence against this practice and guideline publication. Evidence-based medicine requires additional mechanisms for encouraging practice change.
SYST-08. A phase II trial of concurrent Sunitinib, Temozolomide and Radiation Therapy followed by adjuvant Temozolomide for newly diagnosed Glioblastoma patients with an unmethylated MGMT gene promoter (A01-M121-11A, McG1132)
Authors: Faye Mame Daro , Sabri Siham , De Robles Paula , Agnihotram Raman , Torres-Vasquez Alexander , Easaw Jacob , Abdulkarim Bassam 
Published: September 2021

Abstract

INTRODUCTION
Despite advances in treatment modalities, the overall prognosis of GBM remains dismal, particularly for patients with unmethylated MGMT promoter. Thus, alternative treatment strategies are warranted. Our group has previously shown that addition of Sunitinib (SU11248) to standard therapy significantly improved the response of unmethylated MGMT cells through decreased angiogenicity and tumorigenicity. In this phase II trial, we tested for the first time the combination of Sunitinib with RT and Temozolomide in newly diagnosed MGMT unmethylated GBM patients.

METHODS
Patients with histologically confirmed WHO Grade IV GBM and MS-PCR confirmed unmethylated MGMT promoter, age 18-70, KPS ≥70, life expectancy ≥6 months were eligible. 41 patients treated between 2012 and 2017 were screened, 37 of which were eligible. Patients received 12.5 mg of daily Sunitinib for 7 days, followed by concurrent RT, Temozolomide and 12.5 mg Sunitinib for 6 weeks, then adjuvant Temozolomide x6 cycles. RT and Temozolomide doses were as per standard of care. Primary objective was PFS as assessed by RANO criteria, secondary objectives were OS and safety.

RESULTS
Median follow-up time was 15 months. Median PFS was 7 months (95%CI, 6.7-7.2) and 6-month PFS was 59.3%. Median OS was 13 months (95%CI, 12.62-13.37) and 2-year OS was 17.8%. Two patients had OS &gt;50 months, with one surviving 71 months. Having received &gt;3 cycles of adjuvant Temozolomide, surgery at progression or age ≤65 significantly predicted for better OS, with hazard ratios of 0.184 (p=0.001), 0.402 (p=0.026) and 10.017 (for age &gt;65, p=0.002) respectively. Grade ≥3 thrombocytopenia occurred in 18.9% of patients, grade ≥3 neutropenia in 10.8% and grade ≥3 thromboembolic events in 13.5%. There were no grade 5 evens.

CONCLUSION
Addition of Sunitinib to RT and Temozolomide was well tolerated and survival outcomes compared favorably to the current standard of care for GBM patients with unmethylated MGMT promoter status.