bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compensation of differential dispersion: application to multiband stellar interferometry
Authors: Pannetier Cyril , Mourard Denis , Cassaing Frédéric , Lagarde Stéphane , Le Bouquin Jean-Baptiste , Monnier John , Sturmann Judit , Ten Brummelaar Theo 
Published: July 2021

ABSTRACT
With the aim of pushing the limiting magnitude of interferometric instruments, the need for wide-band detection channels and for a coordinated operation of different instruments has considerably grown in the field of long-baseline interferometry. For this reason, the Center for High Angular Resolution Astronomy (CHARA), an array of six telescopes, requires a new configuration of longitudinal dispersion compensators to keep the fringe contrast above 95 per cent simultaneously in all spectral bands, while preserving the transmission above 85 per cent. In this paper, we propose a new method for defining the longitudinal dispersion compensators (LDC) suited for multiband observations. A literal approximation of the contrast loss resulting from the dispersion residues enables us to define a general criterion for fringe contrast maximization on several bands simultaneously. The optimization of this criterion leads to a simple solution with only two LDC stages per arm and existing differential delay lines, to the glass choice and a simple linear formula for thickness control of all these media. A refined criterion can also take into account glass transmission. After presenting this criterion, we give the optimal solution (medium, configuration) and its expected performance for the planned observing modes on CHARA.
PIP-SNP: a pipeline for processing SNP data featured as linkage disequilibrium bin mapping, genotype imputing and marker synthesizing
Authors: Zhang Wenchao , Kang Yun , Dai Xinbin , Xu Shizhong , Zhao Patrick X 
Published: July 2021

AbstractGenome-wide association study data analyses often face two significant challenges: (i) high dimensionality of single-nucleotide polymorphism (SNP) genotypes and (ii) imputation of missing values. SNPs are not independent due to physical linkage and natural selection. The correlation of nearby SNPs is known as linkage disequilibrium (LD), which can be used for LD conceptual SNP bin mapping, missing genotype inferencing and SNP dimension reduction. We used a stochastic process to describe the SNP signals and proposed two types of autocorrelations to measure nearby SNPs’ information redundancy. Based on the calculated autocorrelation coefficients, we constructed LD bins. We adopted a k-nearest neighbors algorithm (kNN) to impute the missing genotypes. We proposed several novel methods to find the optimal synthetic marker to represent the SNP bin. We also proposed methods to evaluate the information loss or information conservation between using the original genome-wide markers and using dimension-reduced synthetic markers. Our performance assessments on the real-life SNP data from a rice recombinant inbred line (RIL) population and a rice HapMap project show that the new methods produce satisfactory results. We implemented these functional modules in C/C++ and streamlined them into a web-based pipeline named PIP-SNP (https://bioinfo.noble.org/PIP_SNP/) for processing SNP data.
ECOA-7. Conserved cell-lineage controlled chromatin accessibility in human and mouse glioblastoma stem cells predicts functionally distinct subgroups
Authors: Lu Xi , Maturi Naga Prathyusha , Jarvius Malin , Zhao Linxuan , Xie Yuan , Tan E-Jean , Xing Pengwei , Fryknäs Mårten , Uhrbom Lene , Chen Xingqi 
Published: July 2021

Abstract
There is ample support for developmental control of glioblastoma stem cells (GSCs), and a deeper knowledge of their epigenetic regulation could be central to more efficient glioblastoma (GBM) therapies. For this purpose, we analyzed the chromatin-accessibility landscape of nine mouse GSC cultures of defined cell of origin and 60 patient-derived GSC cultures by assay for transposase-accessible chromatin using sequencing (ATAC-seq). This uncovered an epigenetic variability of both mouse and human GSC cultures that differed from transcriptome clusters. Both mouse and human chromatin accessibility-guided clusters were predominantly determined by distal regulatory elements, displayed unique sets of transcription factor motif enrichment, and exhibited different functional and drug-response properties. Cross-species analysis of distal regulatory element regions in accessible chromatin of mouse and human cultures revealed conserved epigenetic regulation of GSCs.
ECOA-9. Integration of molecular and methylation classifications yields three meningioma groups and suggests chromosome 1p loss may be critical to the aggressive group
Authors: Bayley James , Hadley Caroline , Harmanci Arif , Harmanci Akdes , Klisch Tiemo , Patel Akash 
Published: July 2021

Abstract
Next-generation sequencing has deepened our understanding of meningiomas, particularly those that behave aggressively. Classifications using either DNA methylation profiling or RNA-sequencing predict tumor behavior more reliably than WHO grade, and segregate common meningioma features similarly, implying possible overlap between classifications. In this study, we performed DNA methylation profiling, RNA-sequencing, and whole-exome sequencing on 110 primary meningiomas (90 WHO I, 20 WHO II). Unsupervised non-negative matrix factorization demonstrated three epigenetic types which were highly concordant with our published transcriptional types (87.3% concordance). Two additional classifications (one using 1p/22 loss, the other merlin expression/chromosomal instability) were also highly concordant and an overall meningioma group (MenG) classification was assigned integrating all four together. MenG A and B rarely recur, while MenG C behave aggressively (median recurrence free survival (RFS) of 3.1 years), even after gross total resection (median RFS 4.2 years). MenG A tumors retain Merlin expression (no chromosome loss or NF2 mutation) and harbor mutations in TRAF7, AKT1, or KLF4. Both MenG B and C are merlin-deficient, but MenG B demonstrate low rates of CNV and MenG C high rates of CNV, particularly loss of chromosome 1p. Using partial least squares regression (PLS), we explored how gene expression correlated with promoter methylation and CNV, thereby classifying genes which correlated closely as ‘methylation-driven’ or ‘CNV-driven’. Overall, there were more methylation-driven (5.7%) than CNV-driven (2.9%) genes. Differentially expressed genes (DEGs) were enriched for both methylation- and CNV-driven genes at similar proportions (10.6% and 5.8%), but DEGs unique to MenG C were significantly enriched for CNV-driven (23.7%), but not methylation-driven (4.7%) genes, primarily due many MenG C DEGs on chromosome 1p. Overall, this work suggests three underlying meningioma groups which are identifiable through methylation, transcriptional, or genetic/cytogenetic profiling and warrants exploration of the role of chromosome 1p in group that behaves aggressively.
MOMC-3. Hypermethylation and overexpression of HOX genes are poor prognosticators in Lower-Grade Glioma
Authors: Mamatjan Yasin , Voisin Mathew , Nassiri Farshad , Moraes Fabio , Bunda Severa , Salih Mira , Aldape Kenneth , Zadeh Gelareh 
Published: July 2021

Abstract
Diffuse gliomas represent over 80% of malignant brain tumors ranging from low-grade to aggressive high-grade lesions. Molecular characterization of these tumors led to the development of new classification system comprising specific glioma subtypes. While this provides novel molecular insight into gliomas it does not fully explain the variability in patient outcome. To identify and characterize a predictive signature of outcome in diffuse gliomas, we utilized an integrative molecular analysis (methylation, mRNA, copy number variation (CNV) and mutation data) using multiple molecular platforms, including a total of 310 IDH mutant glioma samples from University Health Network (UHN) and German Cancer Research Center (DKFZ) together with 419 samples from The Cancer Genome Atlas (TCGA). Cox regression analysis of methylation data from the UHN cohort identified CpG-based signatures that split the glioma cohort into two prognostic groups strongly predicting survival (p-value &lt; 0.0001). The CpG-based signatures were reliably validated using two independent datasets from TCGA and DKFZ cohorts (both p-values &lt; 0.0001). The results show that the methylation signatures that predict poor outcome also correlated with G-CIMP low status, elevated CNV instability and hypermethylation of a set of HOX gene probes. Further study in diffuse lower-grade glioma (LGG) using integrated mRNA and methylation (iRM) analyses showed that parallel HOX gene overexpression and hypermethylation in the same direction were significantly associated with increased mutational load, high aneuploidy and worse survival (p-value &lt; 0.0001). Furthermore, this iRM high group was characterized by a 7-HOX gene signature showed significant survival differences not only in IDH mutant LGG but also in IDH wildtype LGG. These results demonstrate the importance of HOX genes in predicting the outcome of diffuse gliomas to identify relevant molecular subtyping independent of histology.
OTEH-1. Alternative RNA splicing modulates composition of ribosomes and determines spatial phenotype of glioblastoma cells
Authors: Pavlyukov Marat , Larionova Tatyana , Bastola Soniya , Shender Victoria , Nakano Ichiro , Shakhparonov Michail 
Published: July 2021

Abstract
Glioblastoma (GBM) is an extremely heterogeneous tumor and its different regions are populated with phenotypically distinct types of cancer cells. However, it is still unclear how multiple GBM populations arise from the originally homogenous group of tumor precursor cells. Here we showed that GBM cells from the core and edge of the tumor have different composition of ribosomes due to the alternative RNA splicing of multiple ribosomal genes with highest differences observed for RPL22L1. We found that cells at the edge of the tumor express classical isoform of RPL22L1 (RPL22L1a) while core cells have a novel RPL22L1b isoform. RPL22L1b appears due to low pH condition at the core of the tumor. It allows cells to survive during acidosis, promotes more aggressive phenotype in vivo and correlate with worse patient outcome. Mechanistically, RPL22L1b binds to lncRNA MALAT1 in the nucleus and induces its degradation enhancing stemness of GBM cells. On the other hand, RPL22L1a interacts with ribosomes in cytoplasm and upregulates p53 translation favoring less aggressive edge phenotype of GBM. The splicing switch between RPL22L1 isoforms is regulated by SRSF4 proteins. We identified a small molecule compound that inhibits SRSF4 and impairs splicing of RPL22L1, inducing apoptosis of GBM cells and decreasing tumor growth in vivo. Altogether, our data unraveled the mechanism by which less aggressive edge-like GBM cells acquire more malignant core-like phenotype during tumor growth. It may also explain discrepancies between proteome and transcriptome of GBM cell populations. Targeting this pathway may help to decrease tumor heterogeneity and eliminate therapy resistant cells at the tumor core.
Work was supported by the Russian Science Foundation grant 19-44-02027.
OTME-16. Polio virotherapy of murine brain tumors causes microglia/macrophage proliferation and inflammation that is potentiated by immune checkpoint blockade
Authors: Yang Yuanfan , Brown Michael , Stevenson Kevin , López Giselle , Kornahrens William , Zhang Gao , Gromeier Matthias 
Published: July 2021

Abstract
PVSRIPO is a novel viral immunotherapy that has shown evidence of efficacy in a phase I clinical trial for recurrent GBM, resulting in 21% survival rate at 36 months following treatment. To improve clinical response rate, it is critical to resolve the mechanisms of action and therapy resistance in vivo, thereby designing effective combination therapy strategies.
We used immunocompetent mouse models of glioma (CT2A) and metastatic melanoma (B16) to dissect early and late events following virotherapy with PVSRIPO. A blinded systematic review of the pathology from 62 intracranial tumors, collected on different days following PVSRIPO (or control) treatment, was performed. An overall treatment effect, measured by tumor shrinkage, dis-cohesive growth pattern, microglia enrichment, was present in 88% of tumors on day 8, but the tissue response rate fell to 42% on days 10 & 12, and 14% on day 15. The control group showed no treatment effect throughout. RNAseq from the same set of samples showed acute induction of type-I interferon-related inflammation that faded with time in Gene Set Enrichment Analysis. This suggests that sustaining adaptive antitumor immunity elicited by immediate intratumor type-I IFN-dominant inflammation is critical to long term remission. Careful review of the post treatment pathology revealed an early enrichment of both T cells and microglia in the tumor microenvironment with a high Ki-67 proliferation index. We propose that the PVSRIPO therapy effect is dependent on macrophage/microglia mediated cellular immune response, likely in response to direct viral infection. This suggests potential therapeutic interventions, including blockade of the PD1:PD-L1 immune checkpoint, to potentiate antitumor CD8+T cells in response to PVSRIPO therapy. Indeed, combination therapy with αPD-L1 antibody in the CT2A model showed higher long term remission (37%, n=11), compared to either monotherapy; this effect is CD8+T cell- and macrophage-dependent, demonstrated by depletion studies in vivo.
The Effects of Ideological and Ethnoracial Identity on Political (Mis)Information
Authors: Crowder-Meyer Melody , Ferrín Mónica 
Published: July 2021

AbstractThere is much concern today about the spread of fake news and the misinformation it can produce among the public. In this article, we investigate how the American public interprets accurate and inaccurate statements from the news. Moving beyond partisanship, we theorize that ideological and ethnoracial identities also shape individuals’ interpretations of the news. We argue that people have incentives to interpret information they encounter in ways that favor their ideological and ethnoracial ingroups and that these incentives are particularly strong when ideological and ethnoracial identities align. Using a survey that asks respondents to classify statements from news stories as facts or opinions, we find support for these hypotheses. Liberals and conservatives, and white, Black, and Hispanic respondents, more often classify as factual statements that favor their ingroup’s interests while classifying information opposing their ingroup’s interests as opinions. Holding cross-cutting ethnoracial and ideological identities diminishes these effects, while identities that align produce stronger ingroup biases in information processing, particularly among whites. Our study reveals that it is not only partisanship but also ideological and ethnoracial identities that shape how Americans interpret the news, and therefore how informed, or misinformed, they are.
Inpatient Treatment of People With Schizophrenia: Quantifying Clinical Change Using the Health of the Nation Outcome Scales
Authors: Lay Barbara , Roser Patrik , Kawohl Wolfram 
Published: July 2021

Abstract
Schizophrenia can require hospital inpatient care in crisis periods or times of severe symptoms, although the length of hospital stays has been considerably reduced in the last few decades. Evidence on individual outcomes under routine psychiatric practice conditions is sparse. This study aims to evaluate the outcomes of inpatient treatment in patients with schizophrenia using the reliable and clinically significant change approach. We used routinely collected Health of the Nation Outcome Scales (HoNOS) data to assess the extent to which and the areas where symptomatic and functional improvement was achieved. Data from 1783 schizophrenia patients admitted to a large psychiatric centre in Switzerland were examined.
Mean HoNOS total score dropped from 17.9 to 11.7 (effect size 0.8) during treatment; the greatest improvements were achieved regarding symptomatic problems and aggressive, agitated behavior. According to the reliable change index formula, 24.5% of patients were to be considered improved, 73.3% unchanged and 2.2% deteriorated. In total, 56.6% were discharged from the hospital in a subclinical or mild functional state. The degree of individual improvement and time to achieve maximum symptom reduction varied considerably, depending on the patients’ functional state at admission, as did the length of hospital stay (median 28 days). Rates of readmission within 28 days (17.8%) were significantly lower in patients with clinically significant improvement, discharged in better clinical condition. These findings support reconsidering (length of) inpatient treatment within the overall framework of meaningful clinical change and subsequent treatment needs in patients with schizophrenia.
Reduced concentrations of limestone and monocalcium phosphate in diets without or with microbial phytase did not influence gastric pH, fecal score, or growth performance, but reduced bone ash and serum albumin in weanling pigs
Authors: Lagos L Vanessa , Lee Su A , Bedford Mike R , Stein Hans H 
Published: July 2021

AbstractAn experiment was conducted to test the hypothesis that reducing limestone and monocalcium phosphate in diets for weanling pigs by lowering the concentration of Ca and P or by including microbial phytase in the diet will reduce stomach pH and fecal score and will improve growth performance of pigs. A total of 160 weanling pigs (5.75 ± 1.04 kg) were allotted to four corn-soybean meal-based diets in a completely randomized design with five pigs per pen. Diets for phase 1 (d 1 to 15) were formulated using a 2 × 2 factorial design with 2 concentrations of Ca and P (adequate or deficient levels of total Ca and digestible P) and 2 inclusion levels of phytase (0 or 2,000 units/kg feed). Phytase was assumed to release 0.16% total Ca and 0.11% digestible P. Common diets were fed in phases 2 (d 16 to 21) and 3 (d 22 to 35). Fecal scores were recorded in phase 1 and on d 15, gastric pH was measured and a blood sample and the right femur were collected from one pig per pen. Growth performance data were recorded within each phase. Results indicated that in phase 1, at deficient dietary Ca and P, pigs fed the diet with phytase had greater (P &lt; 0.05) average daily gain (ADG) and gain to feed (G:F) compared with pigs fed the diet without phytase, but in diets with adequate levels of Ca and P, no effect of phytase inclusion was observed (interaction, P &lt; 0.05). Without phytase, pigs fed the diet with deficient Ca and P had reduced (P &lt; 0.05) G:F compared with pigs fed the diet with adequate Ca and P, but if phytase was included, there was no effect of Ca and P on G:F (interaction, P &lt; 0.05). For phases 2 and 3, and from d 1 to 35, no differences among dietary treatments were observed for ADG or G:F. Bone ash was greater (P &lt; 0.05) in pigs fed diets with adequate Ca and P than in pigs fed diets with deficient Ca and P, but no effect of phytase inclusion was observed on bone ash. Concentrations of Ca and P did not affect stomach pH or fecal score, but pigs fed diets with phytase tended (P &lt; 0.10) to have reduced stomach pH and fecal score compared with pigs fed diets without phytase. Pigs fed diets with adequate Ca and P had greater (P &lt; 0.05) albumin in serum than pigs fed the Ca- and P-deficient diets. In conclusion, phytase inclusion in phase 1 diets may reduce diarrhea, but lowering Ca and P does not reduce stomach pH or fecal score and decreases bone ash, although growth performance during the entire weanling period is not affected.
Ethnography and user-centered design to inform context-driven implementation
Authors: Haines Emily R , Kirk M Alexis , Lux Lauren , Smitherman Andrew B , Powell Byron J , Dopp Alex , Stover Angela M , Birken Sarah A 
Published: July 2021

Abstract
Despite pervasive findings pointing to its inextricable role in intervention implementation, context remains poorly understood in implementation science. Existing approaches for describing context (e.g., surveys, interviews) may be narrow in scope or superficial in their elicitation of contextual data. Thus, in-depth and multilevel approaches are needed to meaningfully describe the contexts into which interventions will be implemented. Moreover, many studies assess context without subsequently using contextual information to enhance implementation. To be useful for improving implementation, though, methods are needed to apply contextual information during implementation. In the case example presented in this paper, we embedded an ethnographic assessment of context within a user-centered design approach to describe implementation context and apply that information to promote implementation. We developed a patient-reported outcome measure-based clinical intervention to assess and address the pervasive unmet needs of young adults with cancer: the Needs Assessment & Service Bridge (NA-SB). In this paper, we describe the user-centered design process that we used to anticipate context modifications needed to deliver NA-SB and implementation strategies needed to facilitate its implementation. Our ethnographic contextual inquiry yielded a rich understanding of local implementation context and contextual variation across potential scale-up contexts. Other methods from user-centered design (i.e., translation tables and a design team prototyping workshop) allowed us to translate that information into specifications for NA-SB delivery and a plan for implementation. Embedding ethnographic methods within a user-centered design approach can help us to tailor interventions and implementation strategies to their contexts of use to promote implementation.
Risk factors for symptomatic hardware removal after plate fixation of olecranon fractures: a retrospective chart review
Authors: Contreras Erik S. , Lynch Daniel J. , Hatef Sarah , Speeckaert Amy L. , Goyal Kanu S. 
Published: July 2021

Background:
Risk factors for removal of symptomatic hardware after plate fixation of olecranon fractures are not well defined. We examined patient, fracture, and surgical characteristics in relation to hardware removal for symptomatic instrumentation after plate and screw fixation of isolated olecranon fractures in adults.

Methods:
Eighty-four patients who underwent open reduction and internal fixation (ORIF) of isolated olecranon fractures with a plate and screw construct were analyzed retrospectively. Those with subsequent hardware removal for symptomatic hardware were identified. Charts and radiographs were reviewed to gather patient, fracture, and surgical characteristics in relation to management of their olecranon fracture. Univariate analysis was performed to test for statistical significance between groups.

Results:
Seventeen of 84 patients (20.2%) underwent hardware removal for symptomatic instrumentation at an average of 326 days after ORIF. Compared to patients who retained hardware, those who underwent removal trended younger (40.0 vs. 49.4 yr, P=0.076), had a higher percentage of one particular plate design (35% vs. 8%, P=0.026), and had their plate fixated an average of 1.3 mm farther from the olecranon tip (3.4 vs. 2.1 mm; P=0.011). There was an 8.2 times increased likelihood of hardware removal for plates that were placed more than 2 mm from the olecranon tip [1.7 to 38.7, 95% confidence interval (CI); P=0.003].

Conclusions:
This study resulted in approximately 20% rate of symptomatic hardware necessitating removal. Patients who request removal tend to be younger. Fixating the plate closer to the olecranon tip may decrease the incidence of symptomatic hardware and need for subsequent removal.

Level of Evidence:
Level III.