bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric MRI texture analysis in prediction of glioma biomarker status: added value of MR diffusion
Authors: Kihira Shingo , Tsankova Nadejda M , Bauer Adam , Sakai Yu , Mahmoudi Keon , Zubizarreta Nicole , Houldsworth Jane , Khan Fahad , Salamon Noriko , Hormigo Adilia , Nael Kambiz 
Published: April 2021

AbstractBackgroundEarly identification of glioma molecular phenotypes can lead to understanding of patient prognosis and treatment guidance. We aimed to develop a multiparametric MRI texture analysis model using a combination of conventional and diffusion MRI to predict a wide range of biomarkers in patients with glioma.MethodsIn this retrospective study, patients were included if they (1) had diagnosis of gliomas with known IDH1, EGFR, MGMT, ATRX, TP53, and PTEN status from surgical pathology and (2) had preoperative MRI including FLAIR, T1c+ and diffusion for radiomic texture analysis. Statistical analysis included logistic regression and receiver-operating characteristic (ROC) curve analysis to determine the optimal model for predicting glioma biomarkers. A comparative analysis between ROCs (conventional only vs conventional + diffusion) was performed.ResultsFrom a total of 111 patients included, 91 (82%) were categorized to training and 20 (18%) to test datasets. Constructed cross-validated model using a combination of texture features from conventional and diffusion MRI resulted in overall AUC/accuracy of 1/79% for IDH1, 0.99/80% for ATRX, 0.79/67% for MGMT, and 0.77/66% for EGFR. The addition of diffusion data to conventional MRI features significantly (P &lt; .05) increased predictive performance for IDH1, MGMT, and ATRX. The overall accuracy of the final model in predicting biomarkers in the test group was 80% (IDH1), 70% (ATRX), 70% (MGMT), and 75% (EGFR).ConclusionAddition of MR diffusion to conventional MRI features provides added diagnostic value in preoperative determination of IDH1, MGMT, and ATRX in patients with glioma.
NBAT1/CASC15-003/USP36 control MYCN expression and its downstream pathway genes in neuroblastoma
Authors: Juvvuna Prasanna Kumar , Mondal Tanmoy , Di Marco Mirco , Kosalai Subazini Thankaswamy , Kanduri Meena , Kanduri Chandrasekhar 
Published: April 2021

Abstract

Background
MYCN has been an attractive therapeutic target in neuroblastoma considering the widespread amplification of the MYCN locus in neuroblastoma, and its established role in neuroblastoma development and progression. Thus, understanding neuroblastoma-specific control of MYCN expression at the transcriptional and post-transcriptional level would lead to identification of novel MYCN-dependent oncogenic pathways and potential therapeutic strategies.

Methods
By performing loss- and gain-of-function experiments of the neuroblastoma hotspot locus 6p22.3 derived lncRNAs CASC15-003 and NBAT1, together with coimmunoprecipitation and immunoblotting of MYCN, we have shown that both lncRNAs post-translationally control the expression of MYCN through regulating a deubiquitinase enzyme USP36. USP36 oncogenic properties were investigated using cancer cell lines and in vivo models. RNA-seq analysis of loss-of-function experiments of CASC15-003/NBAT1/MYCN/USP36 and JQ1-treated neuroblastoma cells uncovered MYCN-dependent oncogenic pathways.

Results
We show that NBAT1/CASC15-003 control the stability of MYCN protein through their common interacting protein partner USP36. USP36 harbors oncogenic properties and its higher expression in neuroblastoma patients correlates with poor prognosis, and its downregulation significantly reduces tumor growth in neuroblastoma cell lines and xenograft models. Unbiased integration of RNA-seq data from CASC15-003, NBAT1, USP36, and MYCN knockdowns and neuroblastoma cells treated with MYCN inhibitor JQ1, identified genes that are jointly regulated by the NBAT1/CASC15-003/USP36/MYCN pathway. Functional experiments on one of the target genes, COL18A1, revealed its role in the NBAT1/CASC15-003-dependent cell adhesion feature in neuroblastoma cells.

Conclusion
Our data show post-translational regulation of MYCN by NBAT1/CASC15-003/USP36, which represents a new regulatory layer in the complex multilayered gene regulatory network that controls MYCN expression.
Cystathionine-γ-lyase drives antioxidant defense in cysteine-restricted IDH1-mutant astrocytomas
Authors: Cano-Galiano Andrés , Oudin Anais , Fack Fred , Allega Maria-Francesca , Sumpton David , Martinez-Garcia Elena , Dittmar Gunnar , Hau Ann-Christin , De Falco Alfonso , Herold-Mende Christel , Bjerkvig Rolf , Meiser Johannes , Tardito Saverio , Niclou Simone P 
Published: April 2021

Abstract

Background
Mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2) define glioma subtypes and are considered primary events in gliomagenesis, impacting tumor epigenetics and metabolism. IDH enzyme activity is crucial for the generation of reducing potential in normal cells, yet the impact of the mutation on the cellular antioxidant system in glioma is not understood. The aim of this study was to determine how glutathione (GSH), the main antioxidant in the brain, is maintained in IDH1-mutant gliomas, despite an altered NADPH/NADP balance.

Methods
Proteomics, metabolomics, metabolic tracer studies, genetic silencing, and drug targeting approaches in vitro and in vivo were applied. Analyses were done in clinical specimen of different glioma subtypes, in glioma patient-derived cell lines carrying the endogenous IDH1 mutation and corresponding orthotopic xenografts in mice.

Results
We find that cystathionine-γ-lyase (CSE), the enzyme responsible for cysteine production upstream of GSH biosynthesis, is specifically upregulated in IDH1-mutant astrocytomas. CSE inhibition sensitized these cells to cysteine depletion, an effect not observed in IDH1 wild-type gliomas. This correlated with an increase in reactive oxygen species and reduced GSH synthesis. Propargylglycine (PAG), a brain-penetrant drug specifically targeting CSE, led to delayed tumor growth in mice.

Conclusions
We show that IDH1-mutant astrocytic gliomas critically rely on NADPH-independent de novo GSH synthesis via CSE to maintain the antioxidant defense, which highlights a novel metabolic vulnerability that may be therapeutically exploited.
Bintrafusp alfa (M7824), a bifunctional fusion protein targeting TGF-β and PD-L1: results from a phase I expansion cohort in patients with recurrent glioblastoma
Authors: Khasraw Mustafa , Weller Michael , Lorente David , Kolibaba Kathryn , Lee Chee Khoon , Gedye Craig , I. de La Fuente Macarena , Vicente David , Reardon David A , Gan Hui K , Scott Andrew M , Dussault Isabelle , Helwig Christoph , Ojalvo Laureen S , Gourmelon Carole , Groves Morris 
Published: April 2021

Abstract

Background
For patients with recurrent glioblastoma (rGBM), there are few options following treatment failure with radiotherapy plus temozolomide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 antibody blocking PD-L1.

Methods
In this phase I, open-label expansion cohort (NCT02517398), patients with rGBM that progressed after radiotherapy plus temozolomide received bintrafusp alfa 1200 mg Q2W until disease progression, unacceptable toxicity, or trial withdrawal. Response was assessed per RANO criteria. The primary endpoint was disease control rate (DCR); secondary endpoints included safety.

Results
As of August 24, 2018, 35 patients received bintrafusp alfa for a median of 1.8 (range, 0.5–20.7) months. Eight patients (22.9%) experienced disease control as assessed by an independent review committee: 2 had a partial response, 4 had stable disease, and 2 had non-complete response/non-progressive disease. Median progression-free survival (PFS) was 1.4 (95% confidence interval [CI], 1.2–1.6) months; 6- and 12-month PFS rates were 15.1% and 11.3%, respectively. Median overall survival (OS) was 5.3 (95% CI, 2.6–9.4) months; 6- and 12-month OS rates were 44.5% and 30.8%, respectively. The DCR (95% CI) was 66.7% (22.3–95.7%) for patients with IDH-mutant GBM (n = 6) and 13.8% (3.9–31.7%) for patients with IDH–wild-type GBM (n = 29). Disease control was seen regardless of PD-L1 expression. Twenty-five patients (71.4%) experienced treatment-related adverse events (grade ≥3; 17.1% [n = 6]).

Conclusions
The percentage of patients achieving disease control and the manageable safety profile may warrant further investigation of bintrafusp alfa in GBM.
Cancer, cognition, and COVID: delivering direct-to-home teleneuropsychology services to neuro-oncology patients
Authors: Gardner Melissa M , Aslanzadeh Farah J , Zarrella Giuliana V , Braun Sarah E , Loughan Ashlee R , Parsons Michael W 
Published: April 2021

Abstract

Background
The COVID-19 pandemic induced rapid adoption of telemedicine services for neuro-oncology patients at an increased risk of infection. Neuropsychological assessment is important to neuro-oncology care yet challenging to complete outside of a structured testing environment. Teleneuropsychology (TNP) has been explored in limited populations and proven feasible and reliable. Conducting TNP visits directly to patients’ home (DTH) had minimal prior study.

Methods
We used two voluntary surveys to examine acceptance (patients) and feasibility (providers) of DTH-TNP at two regionally diverse medical institutions providing neuropsychological services to neuro-oncology patients from April to September 2020.

Results
A total of 119 patients were scheduled during the study period, 79 of whom completed neuropsychological testing via DTH-TNP. Neuropsychology providers completed surveys on 68 of these encounters (86%). In 98% of cases, neuropsychologists were able to achieve or partially achieve the individually defined goals of their assessment. Common problems reported included patient dysregulation (16%) and slow/unreliable internet (15%). Of the 52 patients who responded, 98% were satisfied with the DTH-TNP experience, and 92% would recommend the virtual visit to others. All respondents felt understood by the examiner (100%) and the majority denied technical difficulties (90%), communication challenges (94%), or privacy concerns (98%). Patients reported reduced risk of infection and saved travel time as favorable aspects of DTH-TNP.

Conclusions
These preliminary results suggest neuro-oncology patients find DTH-TNP acceptable and neuropsychologists find it a feasible practice, while also recognizing its limitations. Results suggest that further study of DTH-TNP (eg, reliability, validity) for neuro-oncology patients is warranted.
Bridging the research-implementation gap in avian conservation with translational ecology
Authors: Saunders Sarah P , Wu Joanna X , Gow Elizabeth A , Adams Evan , Bateman Brooke L , Bayard Trina , Beilke Stephanie , Dayer Ashley A , Fournier Auriel M V , Fox Kara , Heglund Patricia , Lerman Susannah B , Michel Nicole L , Paxton Eben H , Şekercioğlu Çağan H , Smith Melanie A , Thogmartin Wayne , Woodrey Mark S , van Riper Charles 
Published: April 2021

AbstractThe recognized gap between research and implementation in avian conservation can be overcome with translational ecology, an intentional approach in which science producers and users from multiple disciplines work collaboratively to co-develop and deliver ecological research that addresses management and conservation issues. Avian conservation naturally lends itself to translational ecology because birds are well studied, typically widespread, often exhibit migratory behaviors transcending geopolitical boundaries, and necessitate coordinated conservation efforts to accommodate resource and habitat needs across the full annual cycle. In this perspective, we highlight several case studies from bird conservation practitioners and the ornithological and conservation social sciences exemplifying the 6 core translational ecology principles introduced in previous studies: collaboration, engagement, commitment, communication, process, and decision-framing. We demonstrate that following translational approaches can lead to improved conservation decision-making and delivery of outcomes via co-development of research and products that are accessible to broader audiences and applicable to specific management decisions (e.g., policy briefs and decision-support tools). We also identify key challenges faced during scientific producer–user engagement, potential tactics for overcoming these challenges, and lessons learned for overcoming the research-implementation gap. Finally, we recommend strategies for building a stronger translational ecology culture to further improve the integration of these principles into avian conservation decisions. By embracing translational ecology, avian conservationists and ornithologists can be well positioned to ensure that future management decisions are scientifically informed and that scientific research is sufficiently relevant to managers. Ultimately, such teamwork can help close the research-implementation gap in the conservation sciences during a time when environmental issues are threatening avian communities and their habitats at exceptional rates and at broadening spatial scales worldwide.
Particle–particle particle–tree code for planetary system formation with individual cut-off method: GPLUM
Authors: Ishigaki Yota , Kominami Junko , Makino Junichiro , Fujimoto Masaki , Iwasawa Masaki 
Published: April 2021

Abstract
In a standard theory of the formation of the planets in our Solar System, terrestrial planets and cores of gas giants are formed through accretion of kilometer-sized objects (planetesimals) in a protoplanetary disk. Gravitational N-body simulations of a disk system made up of numerous planetesimals are the most direct way to study the accretion process. However, the use of N-body simulations has been limited to idealized models (e.g., perfect accretion) and/or narrow spatial ranges in the radial direction, due to the limited number of simulation runs and particles available. We have developed new N-body simulation code equipped with a particle–particle particle–tree (P3T) scheme for studying the planetary system formation process: GPLUM. For each particle, GPLUM uses the fourth-order Hermite scheme to calculate gravitational interactions with particles within cut-off radii and the Barnes–Hut tree scheme for particles outside the cut-off radii. In existing implementations, P3T schemes use the same cut-off radius for all particles, making a simulation become slower when the mass range of the planetesimal population becomes wider. We have solved this problem by allowing each particle to have an appropriate cut-off radius depending on its mass, its distance from the central star, and the local velocity dispersion of planetesimals. In addition to achieving a significant speed-up, we have also improved the scalability of the code to reach a good strong-scaling performance up to 1024 cores in the case of N = 106.
Variability of Comptonized X-ray spectra of a super-Eddington accretor: Approach using Boltzmann radiation transport
Authors: Ogawa Takumi , Ohsuga Ken , Makino Yoshihiro , Mineshige Shin 
Published: April 2021

Abstract
We investigate the radiation fields around super-Eddington accretion flow, in which multiple inverse-Compton scattering plays a principal role, by using newly developed code describing Boltzmann radiation transfer in the Schwarzschild space-time. We apply this code to post-processing spectral calculations based on general relativistic, radiation magnetohydrodynamic simulation data to obtain X-ray spectra seen from various viewing angles. The radiation fields are distinctively separated into a funnel region with an opening angle of ∼30°, which is full with hot (gas temperature of T &gt; 108 K), tenuous, and high-velocity plasmas, and surrounding cooler (T ∼ 107 K) and optically thick outflow regions. Accordingly, there is a clear tendency that the smaller the viewing angle, the harder the spectra. In particular, hard photons with several tens of keV are observable only by observers at viewing angles less than ∼30°, consistent with past spectral studies based on simulations. Further, we investigate how the spectra are varied by a flare occurring in the innermost region, finding that the variation amplitude grows as the photon energy increases and that the harder photons emerge more quickly than softer photons. The observational implications on long-term spectral variability of ultra-luminous X-ray sources are briefly discussed.
Extracting common signal components from the X-ray and optical light curves of GX 339−4: New view for anti-correlation
Authors: Omama Tomoki , Uemura Makoto , Ikeda Shiro , Morii Mikio 
Published: April 2021

Abstract
Simultaneous X-ray and optical observations of black hole X-ray binaries have shown that the light curves contain multiple correlated and anti-correlated variation components when the objects are in the hard state. In the case of the black hole X-ray binary GX 339−4, the cross correlation function (CCF) of the light curves suggests a positive correlation with an optical lag of 0.15 s and anti-correlations with an optical lag of 1 s and X-ray lag of 4 s. This indicates that the two light curves have some common signal components with different delays. In this study we extracted and reconstructed those signal components from the data for GX 339−4. The results confirmed that correlation and anti-correlation with the optical lag are two common components. However, we found that the reconstructed light curve for the anti-correlated component indicates a positively correlated variation with an X-ray lag of ∼+1 s. In addition, the CCF for this signal component shows anti-correlations not only with the optical lag, but also with the X-ray lag, which is consistent with the CCF for the data. Therefore, our results suggest that the combination of the two positively correlated components, that is, the X-ray preceding signal with the 0.15 s optical lag and the optical preceding signal with the 1 s X-ray lag, can make the observed CCF without anti-correlated signals. The optical preceding signal may be caused by synchrotron emission in a magnetically dominated accretion flow or in a jet, while further study is required to understand the mechanism of the X-ray time lag.
Sexual dimorphism in hemispheric processing of faces in humans: A meta-analysis of 817 cases
Authors: Proverbio Alice M 
Published: April 2021

Abstract
A well-established neuroimaging literature predicts a right-sided asymmetry in the activation of face-devoted areas such as the fusiform gyrus (FG) and its resulting M/N170 response during face processing. However, the face-related response sometimes appears to be bihemispheric. A few studies have argued that bilaterality depended on the sex composition of the sample. To shed light on this matter, two meta-analyses were conducted starting from a large initial database of 250 ERP (Event-related potentials)/MEG (Magnetoencephalography) peer-reviewed scientific articles. Paper coverage was from 1985 to 2020. Thirty-four articles met the inclusion criteria of a sufficiently large and balanced sample size with strictly right-handed and healthy participants aged 18–35 years and N170 measurements in response to neutral front view faces at left and right occipito/temporal sites. The data of 817 male (n = 414) and female (n = 403) healthy adults were subjected to repeated-measures analyses of variance. The results of statistical analyses from the data of 17 independent studies (from Asia, Europe and America) seem to robustly indicate the presence of a sex difference in the way the two cerebral hemispheres process facial information in humans, with a marked right-sided asymmetry of the bioelectrical activity in males and a bilateral or left-sided activity in females.
Molecular detection and genomic characterization of diverse hepaciviruses in African rodents
Authors: Bletsa Magda , Vrancken Bram , Gryseels Sophie , Boonen Ine , Fikatas Antonios , Li Yiqiao , Laudisoit Anne , Lequime Sebastian , Bryja Josef , Makundi Rhodes , Meheretu Yonas , Akaibe Benjamin Dudu , Mbalitini Sylvestre Gambalemoke , Van de Perre Frederik , Van Houtte Natalie , Těšíková Jana , Wollants Elke , Van Ranst Marc , Pybus Oliver G , Drexler Jan Felix , Verheyen Erik , Leirs Herwig , Gouy de Bellocq Joelle , Lemey Philippe 
Published: April 2021

AbstractHepatitis C virus (HCV; genus Hepacivirus) represents a major public health problem, infecting about three per cent of the human population. Because no animal reservoir carrying closely related hepaciviruses has been identified, the zoonotic origins of HCV still remain unresolved. Motivated by recent findings of divergent hepaciviruses in rodents and a plausible African origin of HCV genotypes, we have screened a large collection of small mammals samples from seven sub-Saharan African countries. Out of 4,303 samples screened, eighty were found positive for the presence of hepaciviruses in twenty-nine different host species. We, here, report fifty-six novel genomes that considerably increase the diversity of three divergent rodent hepacivirus lineages. Furthermore, we provide strong evidence for hepacivirus co-infections in rodents, which were exclusively found in four sampled species of brush-furred mice. We also detect evidence of recombination within specific host lineages. Our study expands the available hepacivirus genomic data and contributes insights into the relatively deep evolutionary history of these pathogens in rodents. Overall, our results emphasize the importance of rodents as a potential hepacivirus reservoir and as models for investigating HCV infection dynamics.
MUSCLE MASS AND ESTIMATED RENAL FUNCTION IN ATHLETES
Authors: Yasuda Osamu , Yasuda Hisayo , Ohishi Mitsuru 
Published: April 2021

Objective:
Serum creatinine level is the most common marker used to assess renal function. Because creatinine is a derivative of creatine phosphate, an energy source present in the skeletal muscles, serum creatinine levels are influenced by muscle mass. Elderly people with less muscle mass have low creatinine levels, which may lead to an overestimation of their true renal function. Creatinine levels also tend to be lower in females than males, as females tend to have less muscle mass. Serum cystatin C, a cysteine proteinase inhibitor, is another renal function marker that is produced by every nucleated cell in the body, and thus, unlike creatinine, is thought to be little influenced by muscle mass. Cystatin C level is a sensitive marker of reduction in glomerular filtration rate and suggested to be a better predictive factor for cardiovascular events and death.

Design and method:
Study subjects were 130 male athletes belonging to the National Institute of Fitness and Sports in Kanoya, Japan. A Smedley-type Hand Dynamometer was used to assess grip strength. Serum creatinine and cystatin C levels were measured by enzyme and latex coagulation methods, respectively.

Results:
Muscle mass was significantly correlated with both right and left grip strength, indicating that muscle mass measured in the present study represents skeletal muscle mass. Serum creatinine levels and estimated glomerular filtration rates calculated from creatinine (eGFRcre) showed significant correlations with muscle mass, suggesting that creatinine is influenced by muscle mass and that true renal function may be underestimated in athletes. Cystatin C and estimated glomerular filtration rates calculated from cystatin C (eGFRcys) were also significantly correlated with muscle mass. Serum creatinine levels were significantly correlated with serum cystatin C levels. Consistent with this, eGFRcre was significantly correlated with eGFRcys. This suggests that muscle mass influences the assessment of renal function in athletes when cystatin C is used as a marker.

Conclusions:
The findings in this study suggest that muscle mass of the subject must be considered prior to assessment of renal function using cystatin C in athletes.