bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model development and analysis of coal permeability based on the equivalent characteristics of dual-porosity structure
Authors: Guo Haijun , Wang Kai , Cheng Yuanping , Yuan Liang , Xu Chao 
Published: December 2019

Abstract
Mining is a dynamic fracture process of coal and/or rock. The structural failure of coal bodies will change the coal matrix-fracture characteristics and then affect the distribution characteristics of the coalbed methane (CBM). Because of the structural complexity of coal, the coal matrices and fractures will be assumed to the geometries with rule shapes when the gas seepage characteristics in coals are analyzed. The size of the simplified geometries is the equivalent scale of dual-porosity coal structures (i.e. the equivalent fracture width and equivalent matrix scale). In this paper, according to the reasonable assumptions with regarding to dual-porosity coal structures, a new coal permeability evolution model based on the equivalent characteristics of dual-porosity structure (ECDP model) was built and the effect of the equivalent characteristics of dual-porosity structure on the coal permeability evolution law was analyzed. It is observed that if the initial fracture porosity is constant and the equivalent matrix scale increases, the range in which the permeability of coal rises with rising gas pressure increases; if the equivalent fracture width decreases and the equivalent matrix scale is constant, the range in which the permeability of coal rises with rising gas pressure decreases. The ECDP model is more suitable for revealing the evolution law of the coal permeability when large deformations occur in the coal bodies and/or the coal structure is damaged irreversibly, especially during enhancing CBM recovery.
Development of a Novel Orthotopic Primary Human Chordoma Xenograft Model: A Relevant Support for Future Research on Chordoma
Authors: Salle Henri , Pocard Marc , Lehmann-Che Jacqueline , Bourthoumieu Sylvie , Labrousse François , Pimpie Cynthia , Lemnos Leslie , Guichard Jean-Pierre , Froelich Sebastien , Adle-Biassette Homa 
Published: December 2019

Abstract
Chordomas are slow-growing rare malignant neoplasms. The aim of this study was to establish a primary model of chordoma in the lumbosacral orthotopic area, to compare the growth rate to the subcutaneous site, and to show that this new graft site optimizes tumor growth and bony invasion. Eleven chordoma samples were transplanted subcutaneously in the flank and/or in contact with the lumbosacral region and grown into nude mice. Engraftment rate was significantly more successful in the lumbosacral environment compared with the flank at P0. Two xenografts from 2 patients showed bone invasion. One tumor was maintained through multiple rounds of serial transplantation, creating a model for study. Histological and immunostaining analysis confirmed that tumor grafts recapitulated the primary tumor from which they were derived, consisting of a myxoid chordoma expressing brachyury, cytokeratin AE1, EMA, and VEGF. Clear destruction of the bone by the tumor cells could be demonstrated. Molecular studies revealed PIK3CA and PTEN mutations involved in PI3K signaling pathway and most of the frequently reported chromosomal alterations. We present a novel orthotopic primary xenograft model of chordoma implanted for the first time in the lumbosacral area showing bone invasion, PIK3CA, and PTEN mutations that will facilitate preclinical studies.
Social Practices of Rule-Making for International Law in the Cyber Domain
Authors: Raymond Mark 
Published: December 2019

Abstract
In 2013, despite deteriorating relations between Russia and the United States and increased global contention over cybersecurity issues, participating states in the First Committee of the United Nations General Assembly agreed on a landmark report endorsing the applicability of existing international law to state military use of information technology. Given these conditions, the timing of this agreement was surprising. In this article I argue that state representatives engaged in a rule-governed social practice of applying old rules to new cases, and that the procedural rules governing this practice help to explain the existence, timing, and form of the agreement. They also help to explain further agreements expressed in a follow-on report issued in 2015. The findings of the case study presented here demonstrate that social practices of rule-making are simultaneously rule-governed and politically contested, and that outcomes of these processes have been shaped by specialized rules for making, interpreting, and applying rules. The effectiveness of procedural rules in shaping the outcome of a contentious, complex global security issue suggests that such rules are likely to matter even more in simpler cases dealing with less contentious issues.
Using Selection by Nonantibiotic Stressors to Sensitize Bacteria to Antibiotics
Authors: Maltas Jeff , Krasnick Brian , Wood Kevin B 
Published: December 2019

Abstract
Evolutionary adaptation of bacteria to nonantibiotic selective forces, such as osmotic stress, has been previously associated with increased antibiotic resistance, but much less is known about potentially sensitizing effects of nonantibiotic stressors. In this study, we use laboratory evolution to investigate adaptation of Enterococcus faecalis, an opportunistic bacterial pathogen, to a broad collection of environmental agents, ranging from antibiotics and biocides to extreme pH and osmotic stress. We find that nonantibiotic selection frequently leads to increased sensitivity to other conditions, including multiple antibiotics. Using population sequencing and whole-genome sequencing of single isolates from the evolved populations, we identify multiple mutations in genes previously linked with resistance to the selecting conditions, including genes corresponding to known drug targets or multidrug efflux systems previously tied to collateral sensitivity. Finally, we hypothesized based on the measured sensitivity profiles that sequential rounds of antibiotic and nonantibiotic selection may lead to hypersensitive populations by harnessing the orthogonal collateral effects of particular pairs of selective forces. To test this hypothesis, we show experimentally that populations evolved to a sequence of linezolid (an oxazolidinone antibiotic) and sodium benzoate (a common preservative) exhibit increased sensitivity to more stressors than adaptation to either condition alone. The results demonstrate how sequential adaptation to drug and nondrug environments can be used to sensitize bacteria to antibiotics and highlight new potential strategies for exploiting shared constraints governing adaptation to diverse environmental challenges.
A novel use of random priming-based single-strand library preparation for whole genome sequencing of formalin-fixed paraffin-embedded tissue samples
Authors: Saunderson Emily A , Baker Ann-Marie , Williams Marc , Curtius Kit , Jones J Louise , Graham Trevor A , Ficz Gabriella 
Published: December 2019

Abstract
The desire to analyse limited amounts of biological material, historic samples and rare cell populations has collectively driven the need for efficient methods for whole genome sequencing (WGS) of limited amounts of poor quality DNA. Most protocols are designed to recover double-stranded DNA (dsDNA) by ligating sequencing adaptors to dsDNA with or without subsequent polymerase chain reaction amplification of the library. While this is sufficient for many applications, limited DNA requires a method that can recover both single-stranded DNA (ssDNA) and dsDNA. Here, we present a WGS library preparation method, called ‘degraded DNA adaptor tagging’ (DDAT), adapted from a protocol designed for whole genome bisulfite sequencing. This method uses two rounds of random primer extension to recover both ssDNA and dsDNA. We show that by using DDAT we can generate WGS data from formalin-fixed paraffin-embedded (FFPE) samples using as little as 2 ng of highly degraded DNA input. Furthermore, DDAT WGS data quality was higher for all FFPE samples tested compared to data produced using a standard WGS library preparation method. Therefore, the DDAT method has potential to unlock WGS data from DNA previously considered impossible to sequence, broadening opportunities to understand the role of genetics in health and disease.
Laser interstitial thermal therapy
Authors: Holste Katherine G , Orringer Daniel A 
Published: December 2019

Abstract

Background
Laser interstitial thermal therapy (LITT) is becoming an increasingly popular technique for the treatment of brain lesions. More minimally invasive that open craniotomy for lesion resection, LITT may be more appropriate for lesions that are harder to access through an open approach, deeper lesions, and for patients who may not tolerate open surgery.

Methods
A search of the current primary literature on LITT for brain lesions on PubMed was performed. These studies were reviewed and updates on the radiological, pathological, and long-term outcomes after LITT for brain metastases, primary brain tumors, and radiation necrosis as well as common complications are included.

Results
Larger extent of ablation and LITT as frontline treatment were potential predictors of favorable progression-free and overall survival for primary brain tumors. In brain metastases, larger extent of ablation was more significantly associated with survival benefit, whereas tumor size was a possible predictor. The most common complications after LITT are transient and permanent weakness, cerebral edema, hemorrhage, seizures, and hyponatremia.

Conclusions
Although the current literature is limited by small sample sizes and primarily retrospective studies, LITT is a safe and effective treatment for brain lesions in the correct patient population.
CBMS-07 SERINE SYNTHESIS AND ONE-CARBON METABOLISM IN GLIOMA CELLS TO SURVIVE GLUTAMINE STARVATION
Authors: Tanaka Kazuhiro , Sasayama Takashi , Uno Takiko , Fujita Yuichi , Hashiguchi Mitsuru , Irino Yasuhiro , Kohmura Eiji 
Published: December 2019

Abstract
Cancer cells optimize nutrient utilization to supply energetic and biosynthetic pathways. These metabolic processes also include redox maintenance and epigenetic regulation through nucleic acid and protein methylation, enhancing tumorigenicity and clinical resistance. But less is known about how cancer cells exhibit metabolic flexibility to sustain cell growth and survival from nutrient starvation. Here, we identify a key role for serine availability and one-carbon metabolism in the survival of glioma cells from glutamine deprivation. To identify metabolic response to glutamine deprivation in glioma cells, we analyzed metabolites using gas chromatography and mass spectroscopy (GC/MS) in glioma cells cultured in glutamine-deprived medium and examined gene expression of key enzymes for one-carbon units using RT-PCR and western blotting methods. These expressions were also confirmed by immunohistochemical staining in glioma clinical samples Metabolome studies indicated serine, cysteine, and methionine as key differentiating amino acids between control and glutamine-deprived groups. Serine synthesis was mediated through autophagy rather than glycolysis. Gene expression analysis identified upregulation of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) to regulate serine synthesis and one-carbon metabolism. Importantly, suppression of this metabolite impaired glioma cell survival in glutamine deprivation. In human glioma samples. MTHFD2 expressions were highest in poorly nutrient regions around “pseudopalisading necrosis”. Serine-dependent one-carbon metabolism has a key role for glioma cells to survive glutamine starvation. These results may suggest the new therapeutic strategies targeting critical glioma cells adapting the tumor microenvironment.
SPDR-01 INHIBITION OF HOMOLOGOUS RECOMBINATION, PARP INHIBITOR, OR DIANHYDROGALACTITOL OVERCOMES TEMOZOLOMIDE-RESISTANCE IN GLIOMA CELLS
Authors: Ohba Shigeo , Hirose Yuichi 
Published: December 2019

Abstract
Glioblastoma is one of the most aggressive tumors, with 5-year survival rates of less than 10%. The standard therapy for glioblastomas is maximal safe resection, followed by radiation therapy and chemotherapy with temozolomide (TMZ). The poor prognosis is partially contributed to the acquisition of resistance to TMZ and intratumoral heterogeneity. The mechanisms of resistance to TMZ are various due to tumor heterogeneity. TMZ is a DNA-methylating agent, delivering a methyl group to DNA (O6-guanine, N7-guanine and N3-adenine). The primary cytotoxic lesion, O6-methylguanine, mispairs with thymine, leading to futile DNA mismatch repair (MMR), formation of double strand breaks (DSBs) and eventual cell death, when O6-methylguanine DNA methyltransferase (MGMT) is absent. N7-methylguanine and N3-methyladenine are repaired by base excision repair (BER). The object of the study was to reveal the mechanisms of resistance to TMZ and to find the way to overcome the resistance in glioma. Several clones of TMZ-resistant U251 or U87 were obtained and analyzed. Increased homologous recombination (HR) and deficiency of MMR system, not MGMT were revealed to be contributed to the resistance to TMZ. Inhibition of HR resensitized cells with high HR to TMZ, but it could not resensitize cells with deficient MMR. For the cells with deficient MMR, Inhibition of BER by PARP inhibitor was revealed to potentiate the TMZ-induced cytotoxicity. PARP inhibitors also potentiate the cytotoxicity of TMZ to cells with expressed MGMT. Dianhydrogalactitol (DAG) is a bifunctional DNA-targeting agent, forming N7 alkylguanine and inter-strand DNA crosslinks. DAG reduced the proliferation of cells independent of MGMT and MMR, inducing DNA DSBs, G2/M arrest, and apoptosis in TMZ-resistant glioma cells. Inhibition of chk1, or HR could enhance the cytotoxicity of DAG, increasing apoptosis cells. By selecting the appropriate treatments to the types of resistant mechanisms, these new treatments have the potential to improve the prognosis of glioblastoma.
TB-09 MRNA-SEQ FOR PERICYTES FROM IN VITRO BRAIN METASTASIS AND BLOOD-BRAIN BARRIER MODEL
Authors: Ujifuku Kenta , Fujimoto Takashi , Sato Kei , Morofuji Yoichi , Muto Hideki , Masumoto Hiroshi , Nakagawa Shinsuke , Niwa Masami , Matsuo Takayuki 
Published: December 2019

Abstract

BACKGROUND
Metastatic brain tumors associated with poor prognosis and limited treatment options. The blood-brain barrier (BBB) is supposed to play a major role in brain metastasis. However, little is known about the role of pericytes in brain metastasis formation. This study aimed to reveal the expression profile of interaction between pericytes, endothelial cells, and cancer cells.

METHODS
The Institutional review board approved this study. We established an in vitro BBB model with rat primary cultured BBB-related cells (endothelial cells and pericytes) and investigated the gene expression of pericytes under the lung cancer cell’s coculture circumstances. Pericytes showed inhibition of the KNS-62 cell proliferation significantly (p &lt; 0.05). RNA was extracted from the pericytes using miRNeasy mini kit. Complementary DNA library preparation was performed with QuantSeq 3 ‘mRNA-Seq Library Prep Kit. RNA-seq was performed with MiSeq using MiSeq Reagent Kit v3. Sequencing reads were analyzed on the Maser (TopHat2-CuffLinks2-CummeRbund, TopHat2-HTSeq) and TCC-GUI (EdgeR, DESeq, baySeq) platform. Enrichment analysis was performed at Metascape, and the results were analyzed concerning the OMIM and KEGG databases.

RESULT
The RIN value of RNA &lt; 8.0 was confirmed. Data quality was acceptable in Fast QC analysis. In TCC differential expressed gene (DEG) analysis, cluster analysis showed that the influence of pericyte lot difference was stronger than the change between cell lines and control. Therefore, lot-specific DEG analysis was performed; the data were pretreated and re-analyzed to try to identify genes involved in the suppression of cancer cell growth.

DISCUSSION
This study revealed that some expression profiles of brain pericytes implemented in the prevention of metastatic lung cancer cell proliferation in the brain. Pericytes exert an anti-metastatic effect and thus have the potential for the preventive treatment of brain metastasis.
BOT-02 2-METHYLTHIO MODIFICATION OF N6-ISOPENTENYLADENOSINE IN MITOCHONDRIAL TRNAS BY CDK5RAP1 PROMOTES THE MAINTENANCE OF GLIOMA-INITIATING CELLS
Authors: Yamamoto Takahiro , Fujimura Atsushi , Fan-Yan Wei , Kai Keitarou , Takezaki Tatsuya , Ohta Kazutaka , Kuroda Jun-Ichirou , Shinojima Naoki , Tomizawa Kazuhito , Mukasa Akitake 
Published: December 2019

Abstract
2-Methylthio-N6-isopentenyl modification of adenosine (ms2i6A) is an evolutionally conserved modification that is found in mitochondrial (mt)-tRNAs. Cdk5 regulatory subunit-associated protein 1 (CDK5RAP1) specifically converts N6-isopentenyladenosine (i6A) to ms2i6A at position A37 of four mt-DNA-encoded tRNAs, and the modification regulates efficient mitochondrial translation and energy metabolism in mammals. Here, we report that the ms2 conversion mediated by CDK5RAP1 in mt-tRNAs is required to sustain glioma-initiating cell (GIC)-related traits. CDK5RAP1 maintained the self-renewal capacity, undifferentiated state, and tumorigenic potential of GICs. This regulation was not related to the translational control of mt-proteins. CDK5RAP1 abrogated the antitumor effect of i6A by converting i6A to ms2i6A and protected GICs from excessive autophagy triggered by i6A. The elevated activity of CDK5RAP1 contributed to the amelioration of the cytotoxic effect of i6A and promoted GIC maintenance. The hypoxic microenvironment in the tumor core activated CDK5RAP1, whose activity was inversely correlated with the oxygen concentration because of two [4Fe-4S] clusters in the enzyme. This work demonstrates that CDK5RAP1 is crucial for the detoxification of endogenous i6A and that GICs readily utilize this mechanism for survival.
STMO-10 SURGICAL RESECTION FOR PRIMARY MOTOR CORTEX GLIOMA, TWO CASE REPORTS
Authors: Kijima Noriyuki , Kinoshita Manabu , Hirayama Ryuichi , Umehara Tohru , Yokota Chisato , Kagawa Naoki , Kishima Haruhiko 
Published: December 2019

Abstract
Primary motor cortex glioma is usually considered unresectable because of its high risk for motor deficit. However recent reports suggest that surgical resections for primary motor cortex brain tumor is feasible for selected patients. In this case report, we report two cases we can successfully resected primary motor cortex glioma by awake surgery without neurological worsening.
Case1 was 32 year-old woman with right primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got worsening of left hemiparesis which were gradually improved by rehabilitation. The patient underwent 50 Gy of radiation therapy and 6 courses of PCV chemotherapy. 60 months after the initial surgery, the tumor recurred and the she underwent 12 courses of temozolomide chemotherapy, but tumor continued to grow. She underwent second surgery 13 years after the initial biopsy. We resected primary motor cortex tumor by awake surgery without neurological complication.
Case2 was 31 year-old woman with left primary motor cortex oligodendroglioma. We could only perform biopsy at initial surgery, however the patient got mild right hemiparesis which were improved by rehabilitation. The patient underwent 4 courses of PAV chemotherapy and 54 Gy of Intensity Modulated Radiation Therapy (IMRT). 21 months after IMRT, the tumor recurred and the she underwent second surgery. We resected primary motor cortex tumor by awake motor mapping without severe neurological complication.
In conclusion, surgical resections for primary motor cortex glioma is feasible in selected patients without severe neurological complication. Neural plasticity is the reason for this, but careful intraoperative awake mapping is necessary to achieve maximum resections.
NI-11 PATHOLOGICAL ASSESSMENT IN THE IMPACT OF ONE-SHOT BEVACIZUMAB ON UPTAKE OF 11C-METHIONINE
Authors: Beppu Takaaki , Sato Yuichi , Ogasawara Kuniaki 
Published: December 2019

Abstract

BACKGROUND
This study aimed to clarify how one-time administration of bevacizumab (BEV) changes histological features in glioblastoma, and how histological changes affect the uptake of 11C-methyl-L-methionine (11C-met) as an amino-acid tracer.

MATERIALS AND METHODS
Subjects were 18 patients with newly diagnosed glioblastoma who were assigned to 2 groups: BEV group, single intravenous administration of BEV before surgical tumor removal; and control group, surgical tumor removal alone. After surgery, we compared the densities of tumor cells and microvessels, and microvascular structures including vascular pericytes and L-type amino acid transporter-1 (LAT1), between the BEV and control groups. Correlations between 11C-met uptake on positron emission tomography before surgery, microvascular density, and LAT1 expression were assessed in each group.

RESULTS
BEV induced significant reductions in microvascular density, while tumor cell density and proliferation were retained in the BEV group. Percentages of vessels with pericytes and vascular endothelium with LAT1 expression were lower in the BEV group than in controls. Uptake of 11C-met correlated significantly with microvascular density in the BEV group, but not with LAT1expression.

CONCLUSIONS
The present study showed that even one course of BEV administration induced reductions in microvessels, vascular pericytes, and LAT1 expression in glioblastomas. One course of BEV therapy also reduced 11C-met uptake, which might have been largely attributed to reductions in microvessels rather than reductions in LAT1 expression, in addition to reduction of vascular permeability.
NI-22 IMPROVED DELINEATION OF THE SUPERFICIAL CEREBRAL VENOUS SYSTEM IN BRAIN CT ANGIOGRAPHY BY ULTRAHIGH-RESOLUTION CT FOR ASSISTING BRAIN TUMOR SURGERY
Authors: Koyanagi Masamichi , Suzuki Mitsuru , Kikuyama Satoshi , Nakanishi Akihito , Gomyou Miho , Machida Haruhiko , Yokoyama Kenichi , Tsuchiya Kazuhiro , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo 
Published: December 2019

Abstract

BACKGROUND
In brain CT angiography (CTA) for assisting brain tumor surgery, delineation of the superficial cerebral venous system is critical for selecting the optimal surgical approach. This delineation is, however, limited using conventional CT scanners, including an area-detector CT (ADCT) scanner, due to their insufficient spatial resolution. Since March 2017, a state-of-the-art ultrahigh-resolution CT (UHRCT) scanner has been clinically available to improve in- and through-plane spatial resolution compared with conventional CT scanners, mainly due to smaller slice thickness from 0.5 mm to 0.25 mm, larger channel number from 896 to 1792, and smaller x-ray focus from 0.9 x 0.8 mm to 0.4 x 0.5 mm.PurposeWe assessed usefulness of UHRCT to improve delineation of the superficial cerebral venous system in brain CTA for assisting brain tumor surgery compared with conventional ADCT.

METHODS
We retrospectively enrolled patients with intra- and/or extra-axial brain tumors who underwent preoperative brain CTA for assisting brain tumor surgery by UHRCT or ADCT using our routine technique and generated the CTA to delineate the superficial cerebral venous system using the same technique. Two reviewers by consensus subjectively counted the number of the superficial sylvian veins and the cortical veins draining into these veins and the maximal bifurcation order of the cortical veins draining into the superior sagittal sinus. We compared these numbers and the maximal bifurcation order in the CTA between the UHRCT and ADCT groups using the intraoperative findings as the reference.

RESULTS
The numbers and the maximal bifurcation order in the UHRCT group were significantly greater and more accurate than those in the ADCT group.

CONCLUSIONS
Use of UHRCT can be clinically useful for better delineating the superficial cerebral venous system in brain CTA and assisting brain tumor surgery.