bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olig2-astrocytes express neutral amino acid transporter SLC7A10 (Asc-1) in the adult brain
Authors: Tatsumi Kouko , Kinugawa Kaoru , Isonishi Ayami , Kitabatake Masahiro , Okuda Hiroaki , Takemura Shoko , Tanaka Tatsuhide , Mori Eiichiro , Wanaka Akio 
Published: November 2021

AbstractWe have reported that the transcription factor Olig2 labels a subpopulation of astrocytes (Olig2-astrocytes), which show distribution patterns different from those of GFAP-expressing astrocytes (GFAP-astrocytes) in the adult brain. Here, to uncover the specific functions of Olig2-astrocytes, we first analyzed public single-cell RNA-seq databases of adult mouse brains. Unbiased classification of gene expression profiles and subsequent gene ontology analyses revealed that the majority of Olig2-astrocytes belonged to an astrocytic cluster that is enriched for transporter-related genes. SLC7A10 (also known as ASC-1) was one of the representative neutral amino acid transporter genes in the cluster. To complement the in silico data analyses, we differentially isolated Olig2- and GFAP-astrocytes from the same frozen section of the lateral globus pallidus using laser microdissection and compared their gene expression by quantitative reverse transcription PCR. We confirmed that Olig2 and GFAP mRNAs were preferentially expressed in the Olig2- and GFAP-astrocytes, respectively, indicating that the laser microdissection method yielded minimal cross-contamination between two types of cells. The Olig2-astrocytes expressed significantly higher levels of SLC7A10 mRNA than the GFAP-astrocytes, corroborating the in silico data. We next localized SLC7A10 protein by immunohistochemistry in the lateral globus pallidus, which was also genetically labeled for Olig2. SLC7A10 co-localized with Olig2-genetic labeling, especially on the fine processes of Olig2-astrocytes. These results are consistent with the recent discovery that SLC7A10 is expressed not only in neurons but also in a subset of astrocytes. Taken together, our findings suggest that SLC7A10 exerts specific functions in Olig2-astrocytes of the adult brain.
C-Myc-activated long non-coding RNA LINC01050 promotes gastric cancer growth and metastasis by sponging miR-7161-3p to regulate SPZ1 expression
Authors: Ji Ziwei , Tang Tianbin , Chen Mengxia , Dong Buyuan , Sun Wenjing , Wu Nan , Chen Hao , Feng Qian , Yang Xingyi , Jin Rong , Jiang Lei 
Published: November 2021

Abstract
Background
Growing evidence shows that long non-coding RNAs (lncRNAs) play significant roles in cancer development. However, the functions of most lncRNAs in human gastric cancer are still not fully understood. Here, we explored the role of a novel c-Myc-activated lncRNA, LINC01050, in gastric cancer progression.

Methods
The expression of LINC01050 in the context of gastric cancer was assessed using The Cancer Genome Atlas datasets. Its functions in gastric cancer were investigated through gain- and loss-of-function experiments combined with the Cell Counting Kit-8 assays, colony-forming assays, Transwell assays, flow cytometry, Western blot analyses, and xenograft tumor and mouse metastasis models. Potential LINC01050 transcription activators were screened via bioinformatics and validated by chromatin immunoprecipitation and luciferase assays. The interaction between LINC01050 and miR-7161-3p and the targets of miR-7161-3p were predicted by bioinformatics analysis and confirmed by a luciferase assay, RNA immunoprecipitation, RNA pull-down, and rescue experiments.

Results
LINC01050 was significantly up-regulated in gastric cancer, and its high expression was positively correlated with a poor prognosis. The transcription factor c-Myc was found to directly bind to the LINC01050 promoter region and activate its transcription. Furthermore, overexpression of LINC01050 was confirmed to promote gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. At the same time, its knockdown inhibited gastric cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition in vitro along with tumor growth and metastasis in vivo. Moreover, mechanistic investigations revealed that LINC01050 functions as a molecular sponge to absorb cytosolic miR-7161-3p, which reduces the miR-7161-3p-mediated translational repression of SPZ1, thus contributing to gastric cancer progression.

Conclusions
Taken together, our results identified a novel gastric cancer-associated lncRNA, LINC01050, which is activated by c-Myc. LINC01050 may be considered a potential therapeutic target for gastric cancer.
Constructing germline research cohorts from the discarded reads of clinical tumor sequences
Authors: Gusev Alexander , Groha Stefan , Taraszka Kodi , Semenov Yevgeniy R. , Zaitlen Noah 
Published: November 2021

Abstract
Background
Hundreds of thousands of cancer patients have had targeted (panel) tumor sequencing to identify clinically meaningful mutations. In addition to improving patient outcomes, this activity has led to significant discoveries in basic and translational domains. However, the targeted nature of clinical tumor sequencing has a limited scope, especially for germline genetics. In this work, we assess the utility of discarded, off-target reads from tumor-only panel sequencing for the recovery of genome-wide germline genotypes through imputation.

Methods
We developed a framework for inference of germline variants from tumor panel sequencing, including imputation, quality control, inference of genetic ancestry, germline polygenic risk scores, and HLA alleles. We benchmarked our framework on 833 individuals with tumor sequencing and matched germline SNP array data. We then applied our approach to a prospectively collected panel sequencing cohort of 25,889 tumors.

Results
We demonstrate high to moderate accuracy of each inferred feature relative to direct germline SNP array genotyping: individual common variants were imputed with a mean accuracy (correlation) of 0.86, genetic ancestry was inferred with a correlation of > 0.98, polygenic risk scores were inferred with a correlation of > 0.90, and individual HLA alleles were inferred with a correlation of > 0.80. We demonstrate a minimal influence on the accuracy of somatic copy number alterations and other tumor features. We showcase the feasibility and utility of our framework by analyzing 25,889 tumors and identifying the relationships between genetic ancestry, polygenic risk, and tumor characteristics that could not be studied with conventional on-target tumor data.

Conclusions
We conclude that targeted tumor sequencing can be leveraged to build rich germline research cohorts from existing data and make our analysis pipeline publicly available to facilitate this effort.
Insights into diastolic function analyses using cardiac magnetic resonance imaging: impact of trabeculae and papillary muscles
Authors: Schoennagel Bjoern P. , Müllerleile Kai , Tahir Enver , Starekova Jitka , Grosse Regine , Yamamura Jin , Bannas Peter , Adam Gerhard , Fischer Roland 
Published: November 2021

Abstract
Background
This cardiovascular magnetic resonance (CMR) study investigates the impact of trabeculae and papillary muscles (TPM) on diastolic function parameters by differentiation of the time-volume curve. Differentiation causes additional problems, which is overcome by standardization.

Methods
Cine steady-state free-precession imaging at 1.5 T was performed in 40 healthy volunteers stratified for age (age range 7–78y). LV time-volume curves were assessed by software-assisted delineation of endocardial contours from short axis slices applying two different methods: (1) inclusion of TPM into the myocardium and (2) inclusion of TPM into the LV cavity blood volume. Diastolic function was assessed from the differentiated time-volume curves defining the early and atrial peaks, their filling rates, filling volumes, and further dedicated diastolic measures, respectively.

Results
Only inclusion of TPM into the myocardium allowed precise assessment of early and atrial peak filling rates (EPFR, APFR) with clear distinction of EPFR and APFR expressed by the minimum between the early and atrial peak (EAmin) (100% vs. 36% for EAmin < 0.8). Prediction of peak filling rate ratios (PFRR) and filling volume ratios (FVR) by age was superior with inclusion of TPM into the myocardium compared to inclusion into the blood pool (r2 = 0.85 vs. r2 = 0.56 and r2 = 0.89 vs. r2 = 0.66). Standardization problems were overcome by the introduction of a third phase (mid-diastole, apart from diastole and systole) and fitting of the early and atrial peaks in the differentiated time-volume curve.

Conclusions
Only LV volumetry with inclusion of TPM into the myocardium allows precise determination of diastolic measures and prevents methodological artifacts.
Association of baseline neutrophil-to-eosinophil ratio with response to nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma
Authors: Tucker Matthew D. , Brown Landon C. , Chen Yu-Wei , Kao Chester , Hirshman Nathan , Kinsey Emily N. , Ancell Kristin K. , Beckermann Kathryn E. , Davis Nancy B. , McAlister Renee , Schaffer Kerry , Armstrong Andrew J. , Harrison Michael R. , George Daniel J. , Rathmell W. Kimryn , Rini Brian I. , Zhang Tian 
Published: November 2021

Abstract
Background
The identification of biomarkers to select patients with metastatic renal cell carcinoma (mRCC) most likely to respond to combination immunotherapy (IO) is needed. We sought to investigate an association of the baseline neutrophil-to-eosinophil ratio (NER) with outcomes to nivolumab plus ipilimumab for patients with mRCC.

Methods
We performed a retrospective review of patients with clear cell mRCC treated with nivolumab plus ipilimumab from Vanderbilt-Ingram Cancer Center and Duke Cancer Institute. Patients with prior receipt of immunotherapy and those without available baseline complete blood count with differential were excluded. Patients were divided into groups by the median baseline NER and analyzed for overall survival (OS), progression free survival (PFS), and objective response rate (ORR). Patients were also divided by median baseline neutrophil-to-lymphocyte ratio (NLR) and analyzed for clinical outcome. Further analyses of patients above/below the median NER and NLR were performed in subgroups of IMDC intermediate/poor risk, IMDC favorable risk, and treatment naïve patients.

Results
A total of 110 patients were included: median age was 61 years and 75% were treatment naïve. The median NER (mNER) at baseline was 26.4. The ORR was 40% for patients with <mNER compared to 21.8% among patients with >mNER (OR 2.39, p = 0.04). The median PFS for patients with <mNER was significantly longer at 8.6 months (mo) compared to 3.2 mo for patients with >mNER (HR 0.50, p < 0.01). Median OS was not reached (NR) for patients with <mNER compared with 27.3 mo for patients with >mNER (HR 0.31, p < 0.01). The median NLR (mNLR) was 3.42. While patients with <mNLR showed improvement in OS (HR 0.42, p = 0.02), PFS and ORR did not differ compared with patients in the >mNLR group.

Conclusions
A lower baseline NER was associated with improved clinical outcomes (PFS, OS, and ORR) in patients with mRCC treated with nivolumab plus ipilimumab, and prospective validation of the baseline NER as a predictive biomarker for response to immunotherapy-based combinations in mRCC is warranted.
Claim reserving for insurance contracts in line with the International Financial Reporting Standards 17: a new paid-incurred chain approach to risk adjustments
Authors: Zhao Yixing , Mamon Rogemar , Xiong Heng 
Published: November 2021

AbstractThis study considers the risk management of insurance policies in line with the implementation of the new International Financial Reporting Standards 17. It applies the paid-incurred chain method to model the future unpaid losses by combining the information channels of both the incurred claims and paid losses. We propose the recovery of the empirical distribution of the outstanding claims liabilities associated with a group of contracts via moment-based density approximation. We determine the risk measures and adjustments that are compliant with the new standard using the Monte–Carlo simulation method and approximated distributions. The historical data on the aggregate Ontario automobile insurance claims over a 15-year period are analyzed to examine the appropriateness and accuracy of our approach.
Communicating an Empire and Its Many Worlds: Spanish American Mail, Logistics, and Postal Agents, 1492–1620
Authors: González Martínez Nelson Fernando 
Published: November 2021

AbstractThis article examines the principles underlying Spanish American mail during the government of the first Hapsburgs. I propose that this mail system, in which official and unofficial postal services coexisted, allowed for an intense communicational experience; rather than restricting correspondence, mail circulated at unprecedented levels. To understand this system's rationale I focus on the figure of the correos mayores, who were responsible for the distribution of official information (or information of interest to the crown) within certain Spanish American cities. Using sources in American and European archives, I question the premise that Spanish American communication was chaotic during this period. I also argue that the exceptional circulation of mail within Spanish America and overseas during the sixteenth century is essential for understanding European expansion and the early modern world.
Tecnologías de la memoria: Mapas y padrones en la configuración del territorio guaraní de las misiones
Authors: Wilde Guillermo , Takeda Kazuhisa 
Published: November 2021

AbstractLos mapas y los censos poblacionales o padrones constituyeron dos instrumentos cruciales en el proceso de configuración territorial de las misiones guaraníes. Ambas tecnologías, incorporadas por los jesuitas para el gobierno de la población y el territorio, no solamente sirvieron para representar o describir la situación de las misiones en distintos momentos, sino que fueron dispositivos fundamentales para delimitar el espacio misionero. A su vez, sirvieron como herramientas de la administración misionera apropiadas por la población indígena en la definición de su pertenencia identitaria. De manera similar y complementaria a la escritura narrativa, los mapas y padrones funcionaron como soportes eficaces de la memoria territorial. La primera parte del artículo explora las características de los cacicazgos guaraníes en las misiones y su rol en la organización del territorio. La segunda y tercera partes se adentran en los usos de la cartografía misionera como instrumento de construcción territorial en manos de los religiosos y de las autoridades indígenas de las misiones. La cuarta parte estudia las relaciones entre algunos mapas poco conocidos hasta el momento y los padrones o censos poblacionales como dispositivos complementarios de organización del espacio y la memoria.
Appropriateness of standard cephalometric norms for the assessment of dentofacial characteristics in patients with cleidocranial dysplasia
Authors: Savoldi Fabio , Del Re Francesca , Tonni Ingrid , Gu Min , Dalessandri Domenico , Visconti Luca 
Published: November 2021

Objectives: Cleidocranial dysplasia (CCD) is a rare skeletal syndrome affecting craniofacial and dental development. As a consequence, conventional cephalometric landmarks may not be valid for CCD patients, and the appropriateness of norms used for the general population should be critically discussed. Methods: Five patients 9- to 22-year-old (three females, two males) with CCD were included. Lateral-cephalograms, orthopantomographies, and intra-oral photos were retrospectively analysed. Lateral-cephalograms of 50 normal controls (ten for each CCD patient) matched for age and sex were selected from an online database. Cephalometric measurements of each CCD patients were compared with average values of matched controls using Wilcoxon signed-rank test for paired values (α = 0.05). Results: In CCD patients, a shortening of the cranial base was present (ΔSN = −17.1 mm, p = 0.043). Thus, the mandible (ΔSNPg = +9.5°, p = 0.043) and the maxilla (ΔSNA = +11.2°, p = 0.043) showed protrusion compared to the cranial base, despite a reduced maxillary (ΔCo-A = −15.1 mm, p = 0.043) and mandibular (ΔCo-Gn = −15.2 mm, p = 0.080) length. The mandibular divergence was reduced (ΔSN/GoGn = −6.4°, p = 0.043), a reduced overbite was present (ΔOverbite = −2.9 mm, p = 0.043), and the interincisal angle was increased (ΔInterincisalAngle = +13.7°, p = 0.043), mainly due to retro-inclination of lower incisors. Conclusions: Standard cephalometric norms for the assessment of horizontal jaw position may not be applicable to CCD patients because of a reduced anterior cranial base length compared to normal subjects. Vertical relationships may not be affected, and mandibular hypodivergency was confirmed.
Ground-based corner cube retroreflector optimal design for the geolocation validation of satellite photon counting lidar
Authors: Zhang Qianyin , Zhou Hui , Li Song , Ma Yue 
Published: November 2021

The corner cube retroreflector (CCR) can be applied in the on-orbit geolocation validation of satellite photon counting lidar, which provides insight into the fidelity of laser footprint geolocation on the ground. A novel parameter optimization method, to the best of our knowledge, is proposed to enhance the performance of the CCR. Based on the velocity aberration effect of the satellite and the far-field diffraction pattern (FFDP) of the CCR, a mathematical model with respect to the received energy and design parameters of the CCR, including the aperture, the dihedral angle errors (DAE), and the curvature radius of the front face (CROF), is derived. We can achieve the optimal design parameters of the CCR through searching for the locations of the maximal and uniform FFDP on the circumference of the aberration position. We resolve the optimal aperture, the DAE, and the CROF of the CCR as 14.3 mm, 2.4 in., and 6000 m for the Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) lidar. The received energy derived from the derived parameters has a significant improvement of around 26 times compared with the CCR parameters employed in the ICESat-2. The results demonstrate that the proposed algorithm is effective, and the regression models of the optimal aperture and DAE for different satellite altitudes are conveniently employed in the design of the CCR for the geolocation validation of satellite photon counting lidar.
Test-retest reproducibility of in vivo oscillating gradient and microscopic anisotropy diffusion MRI in mice at 9.4 Tesla
Authors: Rahman Naila , Xu Kathy , Omer Mohammad , Budde Matthew D. , Brown Arthur , Baron Corey A. 
Published: November 2021

Background and purpose
Microstructure imaging with advanced diffusion MRI (dMRI) techniques have shown increased sensitivity and specificity to microstructural changes in various disease and injury models. Oscillating gradient spin echo (OGSE) dMRI, implemented by varying the oscillating gradient frequency, and microscopic anisotropy (μA) dMRI, implemented via tensor valued diffusion encoding, may provide additional insight by increasing sensitivity to smaller spatial scales and disentangling fiber orientation dispersion from true microstructural changes, respectively. The aims of this study were to characterize the test-retest reproducibility of in vivo OGSE and μA dMRI metrics in the mouse brain at 9.4 Tesla and provide estimates of required sample sizes for future investigations.

Methods
Twelve adult C57Bl/6 mice were scanned twice (5 days apart). Each imaging session consisted of multifrequency OGSE and μA dMRI protocols. Metrics investigated included μA, linear diffusion kurtosis, isotropic diffusion kurtosis, and the diffusion dispersion rate (Λ), which explores the power-law frequency dependence of mean diffusivity. The dMRI metric maps were analyzed with mean region-of-interest (ROI) and whole brain voxel-wise analysis. Bland-Altman plots and coefficients of variation (CV) were used to assess the reproducibility of OGSE and μA metrics. Furthermore, we estimated sample sizes required to detect a variety of effect sizes.

Results
Bland-Altman plots showed negligible biases between test and retest sessions. ROI-based CVs revealed high reproducibility for most metrics (CVs < 15%). Voxel-wise CV maps revealed high reproducibility for μA (CVs ~ 10%), but low reproducibility for OGSE metrics (CVs ~ 50%).

Conclusion
Most of the μA dMRI metrics are reproducible in both ROI-based and voxel-wise analysis, while the OGSE dMRI metrics are only reproducible in ROI-based analysis. Given feasible sample sizes (10–15), μA metrics and OGSE metrics may provide sensitivity to subtle microstructural changes (4–8%) and moderate changes (> 6%), respectively.
Impact of the sinus node recovery time after termination of atrial fibrillation during catheter ablation on clinical outcomes in patients with persistent atrial fibrillation
Authors: Watanabe Keita , Nagata Yasutoshi , Nitta Giichi , Okata Shinichiro , Nagase Masashi , Miyazaki Ryoichi , Nagamine Sho , Kaneko Masakazu , Lee Tetsumin , Nozato Toshihiro , Ashikaga Takashi , Goya Masahiko , Sasano Tetsuo 
Published: November 2021

Background
Although long sinus arrest is occasionally observed during atrial fibrillation (AF) catheter ablation when the fibrillation was terminated, its meaning and prognosis have not yet been clearly elucidated. We hypothesized that sinus node recovery time (SNRT) after termination of AF (time from termination of AF to the earliest sinus node activation) could reflect the extent of atrial remodeling, influencing the formation of non-pulmonary vein (non-PV) triggers and post-ablation outcomes.

Method
The participants were 157 consecutive patients with persistent AF (male: 77.1%, age: 63.3±11.2 years) who underwent catheter ablation. We recorded SNRT after terminating AF by radiofrequency delivery or electrical cardioversion during the first ablation and evaluated the relationships between SNRT and atrial tachyarrhythmia recurrence and between SNRT and non-PV triggers after repeat ablation.

Results
Forty-five patients (28.7%) experienced recurrence of atrial tachyarrhythmias. Patients with recurrence had longer SNRTs (1738 ms vs. 1394 ms, p = 0.012). In the multivariate logistic regression analysis, only SNRT ≥2128ms was a significant independent predictor of clinical AF recurrence (hazard ratio 7.48; 95% confidence interval 2.94–19.00; P<0.001). Kaplan–Meier estimator showed that the recurrence-free rate was significantly lower if ≥ 2128ms (log-rank, p<0.001). Thirty-five patients (77.8%) underwent a second ablation. Although there was no difference in the rate of pulmonary vein reconnections (78.6% vs. 71.4%, p = 0.712), non-PV triggers were observed more frequently in the longer SNRT group (57.1% vs. 14.3%, p = 0.012).

Conclusions
Patients with a prolonged SNRT had a higher prevalence of AF recurrence after the first ablation and higher inducibility of non-PV triggers. Measuring SNRT might be used for the stratification of patients with persistent AF.
Global TV Horror, Stacey Abbott and Lorna Jowett (eds) (2021)
Authors: Young Nicola 
Published: November 2021

Review of: Global TV Horror, Stacey Abbott and Lorna Jowett (eds) (2021)
Cardiff: University of Wales Press, 272 pp.,
ISBN 978-1-78683-694-6, p/bk, £45
The Two cines con niño: Genre and the Child Protagonist in Over Fifty Years of Spanish Film (1955–2010), Erin Hogan (2018)
Authors: Beaney Rachel 
Published: November 2021

Review of: The Two cines con niño: Genre and the Child Protagonist in Over Fifty Years of Spanish Film (1955–2010), Erin Hogan (2018)
Edinburgh: Edinburgh University Press, 236 pp.,
ISBN 978-1-47443-611-3, h/bk, £75.00 and p/bk, £19.99