bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contracture Severity at Hospital Discharge in Children: A Burn Model System Database Study
Authors: Yelvington Miranda , Godleski Matthew , Lee Austin F , Goverman Jeremy , Parry Ingrid , Herndon David N , Suman Oscar E , Kowalske Karen , Holavanahalli Radha , Gibran Nicole S , Esselman Peter C , Ryan Colleen M , Schneider Jeffrey C 
Published: November 2020

Abstract
Contractures can complicate burn recovery. There are limited studies examining the prevalence of contractures following burns in pediatrics. This study investigates contracture outcomes by location, injury, severity, length of stay, and developmental stage. Data were obtained from the Burn Model System between 1994 and 2003. All patients younger than the age of 18 with at least one joint contracture at hospital discharge were included. Sixteen areas of impaired movement from the shoulder, elbow, wrist, hand, hip, knee, and ankle joints were examined. Analysis of variance was used to assess the association between contracture severity, burn size, and length of stay. Age groupings were evaluated for developmental patterns. A P value of less than .05 was considered statistically significant. Data from 225 patients yielded 1597 contractures (758 in the hand) with a mean of 7.1 contractures (median 4) per patient. Mean contracture severity ranged from 17% (elbow extension) to 41% (ankle plantarflexion) loss of movement. Statistically significant associations were found between active range of motion loss and burn size, length of stay, and age groupings. The data illustrate quantitative assessment of burn contractures in pediatric patients at discharge in a multicenter database. Size of injury correlates with range of motion loss for many joint motions, reflecting the anticipated morbidity of contracture for pediatric burn survivors. These results serve as a potential reference for range of motion outcomes in the pediatric burn population, which could serve as a comparison for local practices, quality improvement measures, and future research.
Thomas Penny and the preservation of Conrad Gessner’s botanical legacy
Authors: Funk Holger 
Published: November 2020

Abstract
The literary legacy of Thomas Penny (c.1532–c.1588) is revealing about the nature of collecting and collections, in that he was lucky enough to find followers (Thomas Muffet and Theodore Mayerne) who mined his entomological research and bundled it into a book. On the other hand, it was unfortunate that nothing of the sort happened to the extensive notes he made during botanical excursions in Switzerland and France with the aim of completing Conrad Gessner’s unfinished ‘Historia plantarum’ of 1565. While we have the benefit of the ‘Insectorum, sive, Minimorum animalium theatrum’ (1634) – a semi-authentic work on insects, on which Penny’s reputation has exclusively rested – yet owing to his failure ultimately to publish either Gessner’s or his own botanical legacy, this aspect of his work has remained little known. Fortunately, much of his preparatory material survives so that we have the authentic, original documents to hand, which remain to be explored. This paper offers an initial contribution to that task by presenting an evaluation of Penny’s botanical notes and by providing his extant letters (as supplementary material) for the first time, both in transcription and in translation, showing Penny as a keen observer of nature amid the political turmoil of his time.
Pairs of giant shock waves (N-waves) in merging galaxy clusters
Authors: Zhang Congyao , Churazov Eugene , Zhuravleva Irina 
Published: November 2020

ABSTRACT
When a subcluster merges with a larger galaxy cluster, a bow shock is driven ahead of the subcluster. At a later merger stage, this bow shock separates from the subcluster, becoming a ‘runaway’ shock that propagates down the steep density gradient through the cluster outskirts and approximately maintains its strength and the Mach number. Such shocks are plausible candidates for producing radio relics in the periphery of clusters. We argue that, during the same merger stage, a secondary shock is formed much closer to the main cluster centre. A close analogue of this structure is known in the usual hydrodynamics as N-waves, where the trailing part of the ‘N’ is the result of the non-linear evolution of a shock. In merging clusters, spherical geometry and stratification could further promote its development. Both the primary and the secondary shocks are the natural outcome of a single merger event and often both components of the pair should be present. However, in the radio band, the leading shock could be more prominent, while the trailing shock might conversely be more easily seen in X-rays. The latter argument implies that for some of the (trailing) shocks found in X-ray data, it might be difficult to identify their ‘partner’ leading shocks or the merging subclusters, which are farther away from the cluster centre. We argue that the Coma cluster and A2744 could be two examples in a post-merger state with such well-separated shock pairs.
Structural dynamics of double-stranded DNA with epigenome modification
Authors: Furukawa Ayako , Walinda Erik , Arita Kyohei , Sugase Kenji 
Published: November 2020

Abstract
Modification of cytosine plays an important role in epigenetic regulation of gene expression and genome stability. Cytosine is converted to 5-methylcytosine (5mC) by DNA methyltransferase; in turn, 5mC may be oxidized to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation enzyme. The structural flexibility of DNA is known to affect the binding of proteins to methylated DNA. Here, we have carried out a semi-quantitative analysis of the dynamics of double-stranded DNA (dsDNA) containing various epigenetic modifications by combining data from imino 1H exchange and imino 1H R1ρ relaxation dispersion NMR experiments in a complementary way. Using this approach, we characterized the base-opening (kopen) and base-closing (kclose) rates, facilitating a comparison of the base-opening and -closing process of dsDNA containing cytosine in different states of epigenetic modification. A particularly striking result is the increase in the kopen rate of hemi-methylated dsDNA 5mC/C relative to unmodified or fully methylated dsDNA, indicating that the Watson–Crick base pairs undergo selective destabilization in 5mC/C. Collectively, our findings imply that the epigenetic modulation of cytosine dynamics in dsDNA mediates destabilization of the GC Watson–Crick base pair to allow base-flipping in living cells.
Granular Cell Tumor: A Technical Approach for Resection of a Rare Suprasellar Mass
Authors: Schupper Alexander J , Yuk Frank J , Zou Hongyan , Ahuja Sadhna , Tsankova Nadejda M , Hadjipanayis Constantinos G 
Published: November 2020

Abstract

BACKGROUND AND IMPORTANCE
Granular cell tumors (GCTs) of the sellar and suprasellar regions are rare tumors that may be managed surgically by multiple strategies. The technical approaches for these tumors have rarely been described in the literature.

CLINICAL PRESENTATION
We introduce the case of a patient presenting with dizziness and headaches who was found to have a suprasellar and retrochiasmatic mass and eventually underwent surgical resection. We discuss the characteristics of this tumor, and the current state of the literature. Also included are details regarding the surgical approach utilized in this case, and a discussion of the various surgical approaches for this type of tumor.

CONCLUSION
There are several approaches for the surgical resection of suprasellar GCTs, and the approach utilized may depend on patient and/or surgeon considerations. Patient-specific considerations must be made to ensure maximal safe resection of these lesions.
Intracranial Hemorrhage From Dural Arteriovenous Fistulas: Symptoms, Early Rebleed, and Acute Management: A Single-Center 8-Year Experience
Authors: Sorteberg Wilhelm , Sorteberg Angelika , Jacobsen Eva Astrid , Rønning Pål , Eide Per Kristian 
Published: November 2020

Abstract

BACKGROUND
Cerebral dural arteriovenous fistulas (dAVFs) presenting with hemorrhage are so rare that reports on their characteristics and guidelines for their acute management are scarce.

OBJECTIVE
To identify characteristics of the clinical and radiological presentation of hemorrhaging dAVFs, and establish their frequency of early rebleed so that implications for their acute management can be drawn.

METHODS
Retrospective analysis of all patients admitted with intracranial hemorrhage from a dAVF during the years 2011 to 2018.

RESULTS
Twenty patients (14 males) with a median age of 61 yr (27-75 yr) were included. Thunderclap headache was the presenting symptom in 13 (65%) patients. Rebleed prior to treatment occurred in 35% of the patients at median 7.5 h (range 3-96 h) after the ictus. All dAVFs had retrograde venous drainage and a venous aneurysm with a bleb was the source of hemorrhage in 16 (80%) patients, all of them presenting with headache. In contrast, patients bleeding due to diffuse venous hypertension presented with neurological deficits. Endovascular treatment was successful in 2 cases; hence, definite dAVF treatment was surgical in 18 (90%) patients. At median 7 mo (2-29 mo) after the ictus, 13 (65%) patients were in Glasgow Outcome Scale-Extended 7 or 8.

CONCLUSION
The typical presentation of hemorrhage from a cranial dAVF is thunderclap headache. The origin of hemorrhage is often a ruptured venous aneurysm with a bleb. The high frequency of early rebleeds warrants management strategies equivalent to those established for aneurysmal subarachnoid hemorrhage. Overall outcome is favorable.
SS-2 Current status and future perspective of radiomics in glioma imaging
Authors: Kinoshita Manabu , Narita Yoshitaka , Kanemura Yonehiro , Kishima Haruhiko 
Published: November 2020

Abstract
Qualitative imaging, primarily focusing on brain tumors’ genetic alterations, has gained traction since the introduction of molecular-based diagnosis of gliomas. This trend started with fine-tuning MRS for detecting intracellular 2HG in IDH-mutant astrocytomas and further expanded into a novel research field named “radiomics”. Along with the explosive development of machine learning algorithms, radiomics became one of the most competitive research fields in neuro-oncology. However, one should be cautious in interpreting research achievements produced by radiomics as there is no “standard” set in this novel research field. For example, the method used for image feature extraction is different from research to research, and some utilize machine learning for image feature extraction while others do not. Furthermore, the types of images used for input vary among various research. Some restrict data input only for conventional anatomical MRI, while others could include diffusion-weighted or even perfusion-weighted images. Taken together, however, previous reports seem to support the conclusion that IDH mutation status can be predicted with 80 to 90% accuracy for lower-grade gliomas. In contrast, the prediction of MGMT promoter methylation status for glioblastoma is exceptionally challenging. Although we can see sound improvements in radiomics, there is still no clue when the daily clinical practice can incorporate this novel technology. Difficulty in generalizing the acquired prediction model to the external cohort is the major challenge in radiomics. This problem may derive from the fact that radiomics requires normalization of qualitative MR images to semi-quantitative images. Introducing “true” quantitative MR images to radiomics may be a key solution to this inherent problem.
MS-1 Surgical strategy for brain tumor based on molecular and functional connectomics profiles
Authors: Abe Tatsuya 
Published: November 2020

Abstract
It is reported that the development of new perioperative motor deficits was associated with decreased overall survival despite similar extent of resection and adjuvant therapy. The maximum safe resection without any neurological deficits is required to improve overall survival in patients with brain tumor. Surgery is performed with various modalities, such as neuro-monitoring, photodynamic diagnosis, neuro-navigation, awake craniotomy, intraoperative MRI, and so on. Above all, awake craniotomy technique is now the standard procedure to achieve the maximum safe resection in patients with brain tumor. It is well known that before any treatment, gliomas generate globally (and not only focally) altered functional connectomics profiles, with various patterns of neural reorganization allowing different levels of cognitive compensation. Therefore, perioperative cortical mapping and elucidation of functional network, neuroplasticity and reorganization are important for brain tumor surgery. On the other hand, recent studies have proposed several gene signatures as biomarkers for different grades of gliomas from various perspectives. Then, we aimed to identify these biomarkers in pre-operative and/or intra-operative periods, using liquid biopsy, immunostaining and various PCR methods including rapid genotyping assay. In this presentation, we would like to demonstrate our surgical strategy based on molecular and functional connectomics profiles.
MS-2 Minimally invasive glioma surgery with navigation system and tubular retractor
Authors: Kurozumi Kazuhiko 
Published: November 2020

Abstract
Navigation systems are reliable and safe for neurological surgery. Navigation is an attractive and innovative therapeutic option. Recently, endo and exoscopic surgeries have been gradually increasing in neurosurgery. We are currently trialing to use 4K and 8K systems to improve the accuracy and safety of our surgical procedures. Surgeries for deep-seated tumors are challenging because of the difficulty in creating a corridor and observing the interface between lesions and the normal area. In total, 315 patients underwent surgery at Okayama University between 2017 and 2019. Among them, we experienced 92 glioma surgeries using navigation systems. Preoperatively, we performed computed tomography imaging and contrast-enhanced magnetic resonance imaging (MRI) for the neuronavigation system. We experienced Curve(TM) Image Guided Surgery (BrainLab, Munich, Germany). The surgical trajectory was planned with functional MRI and diffusion tensor imaging to protect the eloquent area and critical vasculature of the brain. We used a clear plastic tubular retractor system, the ViewSite Brain Access System, for surgery of deep seated gliomas. We gently inserted and placed the ViewSite using the neuronavigation. The tumor was observed and resected through the ViewSite tubular retractor under a microscope and endoscope. If the tumor was large, we switched the ViewSite tubular retractor to brain spatulas to identify the boundary between the normal brain and lesion. We are currently using the combination of the tubular retractor and brain spatulas using navigation system. Here, we present and analyze our preoperative simulation, surgical procedure, and outcomes.
CBMS-04 Novel xenograft model to clarify tumor progressive mechanism and therapeutic target in primary central nervous system lymphoma
Authors: Tateishi Kensuke , Miyake Yohei , Kawazu Masahito , Nakamura Taishi , Sasaki Nobuyoshi , Sasame Jo , Yoshii Yukie , Wakimoto Hiroaki , Nagane Motoo , Ichimura Koichi , Yamamoto Tetsuya 
Published: November 2020

Abstract
Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified recurrent genetic alterations in Primary central nervous system lymphoma (PCNSL). However, lack of clinically representative PCNSL models has diminished our understanding of the pathogenic mechanisms of those genetic events. Here, we established 14 patient-derived orthotopic xenografts (PDOXs). Comprehensive analysis showed that PDOXs faithfully retained the phenotypic, metabolic, and genetic features with 100 % concordance of MYD88 and CD79B mutations present in immuno-competent PCNSL patients. Notably, orthotopic xenograft formation was consistently dependent on deregulated signaling through the RelA/p65-hexokinase 2 (HK-2) axis. MYD88/CD79B mutations and Pin1 activation, or LMP1 and Pin1 activation, converge on the RelA/p65-HK-2 signaling in immunocompetent and EBV-positive PCNSL, respectively. Genetic and pharmacological inhibition of this key signaling axis potently suppressed PCNSL tumor growth in vitro and in vivo. Additionally, our models further offer a platform for predicting clinical chemotherapeutics efficacy. Therefore, our models provide critical insights into pathogenic mechanisms and therapeutic discovery in PCNSL.
CBMS-05 Biological and Pathological meaning of aneuploidy in mouse glioma stem sell
Authors: Negoto Tetsuya , Jo Minji , Sampetrean Oltea , Motohiro Morioka , Saya Hideyuki , Hirota Toru 
Published: November 2020

Abstract
Chromosomal instability (CIN) is a pathological condition where cells continuously mis-segregate chromosomes, producing aneuploid cells. CIN has been recognized as a hallmark of cancer, and its correlation with biological malignancy has been pointed out. Glioma cell line often reveals karyotype aberrations, and a variety of ploidy in the tumor tissue. However, several studies have indicated that aneuploidy is disadvantageous for proliferation or tumorigenesis, and these paradox prompt us to address the role of aneuploid cells in tumor specimens. Here, we adopted mouse glioma stem cell lineages and found that aneuploid population is increased in glioma stem cells in vitro. We also examined Aurora B at centromeres which is crucial for failsafe chromosome segregation and found its reduced activity in glioma stem cells, suggesting that insufficient Aurora B activity plays a causative role in CIN in glioma stem cells. Next, to investigate the tumorigenicity of aneuploid cells, we sorted the glioma stem cells depending on the karyotype pattern, and allografted into mouse brain. We found that the growth rate of diploid glioma stem cells was higher than others in vitro, and the probability of survival after allogeneic transplant was significantly lower in diploid groups. We will discuss the role of ploidy in glioma cells populations.
CBMS-11 PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT CNS NON-GERMINOMATOUS GERM CELL TUMORS
Authors: Tomiyama Arata , Uchida Eita , Kawauchi Daisuke , Wada Kojiro , Ichimura Kouchi 
Published: November 2020

Abstract
Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.
TB-03 Newly Established Meningioma Organoid Model Elucidated an Important Role of FOXM1 in Meningioma Progression
Authors: Yamazaki Shintaro , Ohka Fumiharu , Hirano Masaki , Motomura Kazuya , Tanahashi Kuniaki , Takeuchi Kazuhito , Shiraki Yukihiro , Aoki Kosuke , Kitano Yotaro , Shimizu Hiroyuki , Yamaguchi Junya , Maeda Sachi , Enomoto Atsushi , Wakabayashi Toshihiko , Natsume Atsushi 
Published: November 2020

Abstract
Meningioma is the most frequently occurring intracranial neoplasms in adults. Tumor removal surgery and radiotherapy were the widely accepted standard treatment for meningioma. Most meningioma cases were cured by extended total removal. However, some tumors develop in locations less amenable to resection, resulting in tumor recurrence after incomplete tumor removal followed by radiotherapy. Although several comprehensive studies have revealed frequently found molecular alterations of meningiomas, effective treatment reagents targeting specific molecular alterations have not been identified yet because of limited number of representative research models such as tumor cell lines or animal models of meningiomas. Recently developed 3D culture technologies have led to the development of novel cancer models, termed organoid models, due to their quite high efficiency of establishment. In this study, we established primary organoid culture methods using malignant meningioma cell lines (e.g. HKBMM and IOMM-Lee) and patient-derived meningioma tissues. Using this novel method, we have been able to establish six organoid models (four WHO grade I meningiomas, one WHO grade III one and one solitary fibrous tumor (SFT)) using tumor tissues derived from six consecutive patients with 100% success rate. Histological analyses, whole exome sequencing and copy number analyses revealed that these organoids exhibited consistent histological features and molecular profiling with those of parental tumors. Using public database, we identified upregulated FOXM1 was correlated with increased tumor proliferation. Over-expression of FOXM1 in benign meningioma organoids increased organoid proliferation, while depletion of FOXM1 in malignant ones decreased their proliferation. We revealed that novel organoid model for meningioma enable to shed light on the tumor biology of meningioma.