bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Imputation with Massive Data: An Application to the Panel Study of Income Dynamics
Authors: Si Yajuan , Heeringa Steve , Johnson David , Little Roderick J A , Liu Wenshuo , Pfeffer Fabian , Raghunathan Trivellore 
Published: September 2021

Abstract
Multiple imputation (MI) is a popular and well-established method for handling missing data in multivariate data sets, but its practicality for use in massive and complex data sets has been questioned. One such data set is the Panel Study of Income Dynamics (PSID), a longstanding and extensive survey of household income and wealth in the United States. Missing data for this survey are currently handled using traditional hot deck methods because of the simple implementation; however, the univariate hot deck results in large random wealth fluctuations. MI is effective but faced with operational challenges. We use a sequential regression/chained-equation approach, using the software IVEware, to multiply impute cross-sectional wealth data in the 2013 PSID, and compare analyses of the resulting imputed data with those from the current hot deck approach. Practical difficulties, such as non-normally distributed variables, skip patterns, categorical variables with many levels, and multicollinearity, are described together with our approaches to overcoming them. We evaluate the imputation quality and validity with internal diagnostics and external benchmarking data. MI produces improvements over the existing hot deck approach by helping preserve correlation structures, such as the associations between PSID wealth components and the relationships between the household net worth and sociodemographic factors, and facilitates completed data analyses with general purposes. MI incorporates highly predictive covariates into imputation models and increases efficiency. We recommend the practical implementation of MI and expect greater gains when the fraction of missing information is large.
‘Blessed is the One who Stands in the Beginning’ (L. 18): Revisiting Protological Eschatology in the Gospel of Thomas
Authors: Joseph Simon J 
Published: September 2021

Abstract
Since its (re)discovery, the Gospel of Thomas has been a central site of debate in the study of Christian origins. Some scholars regard Thomas as a ‘fifth gospel’; others an ‘anti-Jewish’ text dependent on the Synoptics. This article revisits one of Thomas’s most distinctive themes: protological eschatology. This article argues that logion 18 represents a worldview characterized by an Urzeit/Endzeit correlation, a motif relatively common in apocalyptic Judaism, and reminiscent of arguments from creation characteristic of the historical Jesus.
MPK3/MPK6-mediated phosphorylation of ERF72 positively regulates resistance to Botrytis cinerea through directly and indirectly activating the transcription of camalexin biosynthesis enzymes
Authors: Li Yihao , Liu Kun , Tong Ganlu , Xi Chao , Liu Jin , Zhao Heping , Wang Yingdian , Ren Dongtao , Han Shengcheng 
Published: September 2021

Abstract
Ethylene response factor (ERF) Group VII members generally function in regulating plant growth and development, abiotic stress responses, and plant immunity in Arabidopsis; however, the details of the regulatory mechanism by which Group VII ERFs mediate plant immune responses remain elusive. Here, we characterized one such member, ERF72, as a positive regulator that mediates resistance to the necrotrophic pathogen Botrytis cinerea. Compared with the wild-type (WT), the erf72 mutant showed lower camalexin concentration and was more susceptible to B. cinerea, while complementation of ERF72 in erf72 rescued the susceptibility phenotype. Moreover, overexpression of ERF72 in the WT promoted camalexin biosynthesis and increased resistance to B. cinerea. We identified the camalexin-biosynthesis genes PAD3 and CYP71A13 and the transcription factor WRKY33 as target genes of ERF72. We also determined that MPK3 and MPK6 phosphorylated ERF72 at Ser151 and improved its transactivation activity, resulting in increased camalexin concentration and increased resistance to B. cinerea. Thus, ERF72 acts in plant immunity to coordinate camalexin biosynthesis both directly by regulating the expression of biosynthetic genes and indirectly by targeting WRKK33.
The Flowers in The Muses Garland
Authors: Blayney Peter W M 
Published: September 2021

Abstract
A recent publication has laid the groundwork for future studies of printers’ flowers. This paper begins by using the evidence of flowers to show that two seemingly unrelated printed fragments in the Beinecke Library come from a single book. An attempt to identify the printer then reveals the largely unexplored extent to which London printers’ ornaments migrated to Scotland in the 1590s and came back in 1603, and that leads in turn to some new biographical facts about the printer Robert Waldegrave.
An appendix looks at some later copies of Robert Granjon’s best-known six-part combinable flower, which have too often been mistaken for the originals.
The origin of Galactic cosmic rays as revealed by their composition
Authors: Tatischeff Vincent , Raymond John C , Duprat Jean , Gabici Stefano , Recchia Sarah 
Published: September 2021

ABSTRACT
Galactic cosmic rays (GCRs) are thought to be accelerated in strong shocks induced by massive star winds and supernova explosions sweeping across the interstellar medium. But the phase of the interstellar medium from which the CRs are extracted has remained elusive until now. Here, we study in detail the GCR source composition deduced from recent measurements by the AMS-02, Voyager 1, and SuperTIGER experiments to obtain information on the composition, ionization state, and dust content of the GCR source reservoirs. We show that the volatile elements of the CR material are mainly accelerated from a plasma of temperature ≳ 2 MK, which is typical of the hot medium found in Galactic superbubbles energized by the activity of massive star winds and supernova explosions. Another GCR component, which is responsible for the overabundance of 22Ne, most likely arises from acceleration of massive star winds in their termination shocks. From the CR-related gamma-ray luminosity of the Milky Way, we estimate that the ion acceleration efficiency in both supernova shocks and wind termination shocks is of the order of 10−5. The GCR source composition also shows evidence for a preferential acceleration of refractory elements contained in interstellar dust. We suggest that the GCR refractories are also produced in superbubbles, from shock acceleration and subsequent sputtering of dust grains continuously incorporated into the hot plasma through thermal evaporation of embedded molecular clouds. Our model explains well the measured abundances of all primary and mostly primary CRs from H to Zr, including the overabundance of 22Ne.
Emission line galaxies in the SHARDS Frontier Fields – I. Candidate selection and the discovery of bursty Hα emitters
Authors: Griffiths Alex , Conselice Christopher J , Ferreira Leonardo , Ceverino Daniel , Rosa-González Daniel , Huertas-Company Marc , Pampliega Belén Alcalde , Pérez-González Pablo G , Sanchez Helena Dominguez , Vega Olga 
Published: September 2021

ABSTRACT
Emission line galaxies provide a crucial tool for the study of galaxy formation and evolution, providing a means to trace a galaxy’s star formation history or metal enrichment, and to identify galaxies at a range of stellar masses. In this paper, we present a study of emission line galaxies in the Survey for High-z Absorption Red and Dead Sources (SHARDS) Frontier Fields (FF) medium-band survey. Through detailed flux calibrations we combine the first results of the SHARDS-FF survey with existing Hubble Frontier Field data to select 1098 candidate emission line galaxies from the Hubble Frontier Filed clusters Abell 370 and MACS J1149.5+2223. Furthermore, we implement this deep medium-band imaging to update photometric redshift estimates and stellar population parameters and discover 38 predominantly low-mass Hα emitters at redshifts 0.24 &lt; z &lt; 0.46. Overall, 27 of these sources have corresponding ultraviolet (UV) data from the Hubble Space Telescope that allow us to distinguish these sources and investigate the burstiness of their star formation histories. We find that more than 50 per cent of our sample shows an enhancement in Hα over UV, suggesting recent bursts in star formation on time-scales of a few to tens of Myr. We investigate these sources and find that they are typically low-mass discy galaxies with normal sizes. Their structures and star formation suggest that they are not undergoing mergers but are bursting due to alternative causes, such as gas accretion.
MetaPlatanus: a metagenome assembler that combines long-range sequence links and species-specific features
Authors: Kajitani Rei , Noguchi Hideki , Gotoh Yasuhiro , Ogura Yoshitoshi , Yoshimura Dai , Okuno Miki , Toyoda Atsushi , Kuwahara Tomomi , Hayashi Tetsuya , Itoh Takehiko 
Published: September 2021

Abstract
De novo metagenome assembly is effective in assembling multiple draft genomes, including those of uncultured organisms. However, heterogeneity in the metagenome hinders assembly and introduces interspecies misassembly deleterious for downstream analysis. For this purpose, we developed a hybrid metagenome assembler, MetaPlatanus. First, as a characteristic function, it assembles the basic contigs from accurate short reads and then iteratively utilizes long-range sequence links, species-specific sequence compositions, and coverage depth. The binning information was also used to improve contiguity. Benchmarking using mock datasets consisting of known bacteria with long reads or mate pairs revealed the high contiguity MetaPlatanus with a few interspecies misassemblies. For published human gut data with nanopore reads from potable sequencers, MetaPlatanus assembled many biologically important elements, such as coding genes, gene clusters, viral sequences, and over-half bacterial genomes. In the benchmark with published human saliva data with high-throughput nanopore reads, the superiority of MetaPlatanus was considerably more evident. We found that some high-abundance bacterial genomes were assembled only by MetaPlatanus as near-complete. Furthermore, MetaPlatanus can circumvent the limitations of highly fragmented assemblies and frequent interspecies misassembles obtained by the other tools. Overall, the study demonstrates that MetaPlatanus could be an effective approach for exploring large-scale structures in metagenomes.
PL03.1.A Surgery for glioblastomas in the elderly: an ANOCEF trial (CSA)
Authors: Laigle-Donadey F , Metellus P , Guyotat J , Menei P , Proust F , Dufour H , Chinot O , Honnorat J , Faillot T , Paquis P , Peruzzi P , Emery E , Guillamo J S , Carpentier A , Wager M , Lebbah S , Hajage D , Delattre J Y , Cornu P 
Published: September 2021

Abstract

BACKGROUND
The role of surgery for the treatment of malignant gliomas in patients 70 years of age or older is unsettled. We conducted a randomized trial that compared surgical resection of the tumor and biopsy only, both followed by standard therapy, in such patients.

MATERIAL AND METHODS
Patients aged 70 years and older, with a KPS of at least 50, presenting with a radiological suspicion of an operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the adjunction of concomitant and adjuvant temozolomide when this regimen became standard (2017–2019). The primary end point was survival; secondary endpoints were progression free survival (PFS), cognitive status (MMS), autonomy (KPS), quality of life (EORTC QLQ C30 and BN20), and perioperative morbidity/ mortality.

RESULTS
From 2008 to 2019, 107 patients from 9 centers were enrolled in the study, of whom 101 were evaluable for analysis because the diagnosis of GBM was histologically confirmed (50 patients in the “surgery” arm and 51 patients in the “biopsy” arm). There was no statistically significant difference of median survival between the “surgery” arm (9.37 mo) and the “biopsy” arms (8.96 mo, p=0.36). However, the surgery group had increased PFS (5.06 mo vs 4.02 mo; p=0.034; p=0.002 on multivariate analysis) and better QOL (e.g. physical and cognitive functioning, motor dysfunction, fatigue) and KPS score evolution as compared to the “biopsy” group. Surgery was not associated with increased mortality or morbidity.

CONCLUSION
This study suggests that optimal debulking surgery does not provide a significant survival benefit in elderly patients suffering from newly diagnosed malignant glioma, but resection improves QOL and autonomy with a significant though modest improvement of PFS.
PL03.2.A Radiotherapy is associated with a deletion signature that contributes to poor outcomes in glioma patients
Authors: Kocakavuk E , Anderson K J , Varn F S , Johnson K C , Amin S B , Sulman E P , Lolkema M P , Barthel F P , Verhaak R G W 
Published: September 2021

Abstract

BACKGROUND
Diffuse gliomas are highly aggressive brain tumors that invariably relapse despite treatment with chemo- and radiotherapy. Treatment with alkylating chemotherapy can drive tumors to develop a hypermutator phenotype. In contrast, the genomic effects of radiation therapy (RT) remain largely unknown.

MATERIAL AND METHODS
We analyzed the mutational spectra following treatment with RT in whole genome or exome sequencing data from 190 paired primary-recurrent gliomas from the Glioma Longitudinal Analysis (GLASS) dataset and 3693 post-treatment metastatic tumors from the Hartwig Medical Foundation (HMF).

RESULTS
We identified a significant increase in the burden of small deletions following radiation therapy that was independent of other factors (P = 3e-03, multivariable log-linear regression). These novel deletions demonstrated distinct characteristics when compared to pre-existing deletions present prior to RT-treatment and deletions in RT-untreated tumors. Radiation therapy-acquired deletions were characterized by a larger deletion size (GLASS and HMF, P = 1.5e-04 and P = 6e-16, respectively; Mann-Whitney U test), an increased distance to repetitive DNA elements (P &lt; 2.2e-16, Kolmogorov-Smirnov test) and a lack of microhomology at breakpoints (P = 6.6e-05, paired Wilcoxon signed-rank test). Furthermore, mutational signature analysis confirmed the distinct genomic characteristics of RT-associated deletions when compared to deletions arising via homologous recombination deficiency or microsatellite instability.
These observations suggested that canonical non-homologous end joining (c-NHEJ) was the preferred pathway for DNA double strand break repair of RT-induced DNA damage. Furthermore, RT resulted in frequent chromosomal deletions and significantly increased frequencies of CDKN2A homozygous deletions in IDHmut glioma (P= 1.9e-05, Fisher’s exact test). Finally, a high burden of RT-associated deletions was associated with worse clinical outcomes (GLASS and HMF, P = 3.4e-02 and P &lt; 1e-04, respectively; log-rank test).

CONCLUSION
Our results collectively suggest that effective repair of RT-induced DNA damage is detrimental to patient survival and that inhibiting c-NHEJ may be a viable strategy for improving the cancer-killing effect of radiotherapy. Furthermore, CDKN2A homozygous deletion at recurrence may be leveraged as a promising clinical biomarker of RT-resistance in IDHmut glioma. Taken together, the identified genomic scars as a result of RT reflect a more aggressive tumor with increased levels of resistance to follow up treatments.
OS02.6.A The TeloDIAG: How telomeric parameters can help in glioma rapid diagnosis and liquid biopsies approaches
Authors: Billard P , Guerriau C , Carpentier C , Juillard F , Grandin N , Lomonte P , Kantapareddy P , Barritault M , Rimokh R , Verrelle P , Maucort-Boulch D , Figarella-Branger D , Ducray F , Dehais C , Charbonneau M , Meyronet D , Poncet D A 
Published: September 2021

Abstract

BACKGROUND
The integration of molecular markers into the WHO 2016 classification has clarified the complex diagnosis of gliomas. Among these biomarkers, the TERT promoter mutation and the loss of ATRX (ATRX loss) are mutually exclusive alterations associated with re-activation of telomerase or alternative lengthening of telomeres (ALT), respectively. Strangely, 25% of gliomas display neither or both these alterations, a situation referred to as abnormal telomere maintenance mechanism (aTMM).

MATERIAL AND METHODS
To investigate the TMM actually involved in gliomas, the C-circle (CC) assay was adapted to tumor (FFPE and frozen) samples.

RESULTS
We constructed a CC-based algorithm able to identify the TMM of 284 gliomas with either TERT or ATRX alteration, with a sensitivity of 100% and a specificity of 97.3%, and succeeded in deciphering the TMM involved in 122 aTMM gliomas. Additionally, the combination of the TMM, the mutational status of the Isocitrate dehydrogenase 1/2 (IDH) gene, and the histological grading was used as base for a new classification: TeloDIAG. Six subtypes are defined in this classification: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma, respectively, the last class gathers ALT+ IDHwt glioma. The TeloDIAG diagnosis is 99% concordant with the WHO classification for glioma displaying typical molecular characteristics (N=312). It modified the classification of 38% (N=156) discordant tumors, such as IDHwt Astrocytoma, aTMM tumors, or gliomas with unexpected TMM (e.g. TERTwt oligodendroglioma, ATRX loss GBM). Interestingly, 20% (N=69) of TERTwt, ATRXwt, or IDHwt GBM were actually tAIV, which is remarkable as tAIV-glioma patients’ survival tended to be longer (21.2 months) than tGBM patients’ survival (16.5 months). Importantly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 95% (N = 206).

CONCLUSION
In sum, the TeloDIAG is a new, simple, and efficient tool helping in glioma diagnosis and a promising option for liquid biopsy
OS05.2.A MGMT promoter status in IDH1/2 mutant anaplastic astrocytoma patients assessed by DNA methylation profiling and qMS-PCR: a report from the EORTC Brain Tumor Group
Authors: Tesileanu C M S , French P J , Sanson M , Brandes A A , Wick W , Clement P M , Kros J M , Gorlia T , Golfinopoulos V , van den Bent M J 
Published: September 2021

Abstract

BACKGROUND
Temozolomide (TMZ) efficacy in high-grade glioma is related to O 6-methylguanine DNA methyltransferase promoter (MGMTp) methylation. We compared the prognostic and predictive effect of MGMTp between DNA methylation profiling (the MGMT-STP27 model) and quantitative methylation specific polymerase chain reaction (qMS-PCR) in isocitrate dehydrogenase 1 and 2 (IDH1/2) mutant (mt) anaplastic astrocytoma patients.

MATERIAL AND METHODS
The 2x2 factorial design phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy (RT), RT with concurrent TMZ, RT with 12 cycles of adjuvant TMZ, or RT with concurrent and adjuvant TMZ. MGMTp methylation status was assessed with the MGMT-STP27 model using 850k EPIC data, and qMS-PCR. IDH1/2 mutation status was determined with a next-generation sequencing panel. Overall survival (OS) was measured from date of randomization.

RESULTS
We identified 444 IDH1/2mt anaplastic astrocytoma patients of which MGMT-STP27 data was available for 440 patients (99.1%), qMS-PCR data for 361 patients (81.3%), and both for 357 patients (80.4%). MGMTp was methylated in 365 patients (83.0%) for the MGMT-STP27 model, and 168 patients (46.5%) for qMS-PCR. The agreement between the MGMT-STP27 model and qMS-PCR is 59.9% with a Cohen’s Kappa score of 0.229. At database lock, 289 patients with MGMT-STP27 data were still alive and 236 patients with qMS-PCR data. The median OS of MGMTp methylated glioma patients was 9.1 yrs [95 % confidence interval (CI) 7.5-not reached] for the MGMT-STP27 model, and not reached [95 % CI 9.1-not reached] for the qMS-PCR data. For MGMTp unmethylated glioma patients, the median OS was 6.9 yrs [95% CI 6.2-not reached] for the MGMT-STP27 model, and 6.8 yrs [95% CI 6.2–9.7] for the qMS-PCR data. The hazard ratio (HR) for OS based on MGMTp methylation was 0.88 [95% CI 0.58–1.31] for the MGMT-STP27 data, and 0.72 [95% CI 0.50–1.03]) for the qMS-PCR data. The HR for OS after RT with any TMZ vs RT alone for the MGMT-STP27 model was 0.53 [95% CI 0.37–0.78] for MGMTp methylated, and 0.54 [95% CI 0.25–1.18] for MGMTp unmethylated glioma patients; and for the MS-PCR data was 0.34 [95% CI 0.19–0.61] for MGMTp methylated, and 0.53 [95% CI 0.33–0.85] for MGMTp unmethylated glioma patients.

CONCLUSION
MGMTp methylation, regardless of assay, was neither prognostic nor predictive for outcome to temozolomide in IDH1/2mt anaplastic astrocytoma patients.
OS05.3.A Temporal muscle thickness as surrogate parameter of sarcopenia in newly diagnosed glioblastoma patients:translational imaging analysis of the CENTRIC EORTC 26071-22072 and CORE trials
Authors: Furtner J , Weller M , Weber M , Gorlia T , Nabors B , Reardon D , Tonn J , Stupp R , Preusser M 
Published: September 2021

Abstract

BACKGROUND
Temporal muscle thickness (TMT) was described as surrogate parameter of skeletal muscle mass. This study aimed to investigate the prognostic relevance of TMT in patients with newly diagnosed glioblastoma.

MATERIAL AND METHODS
TMT was assessed in cranial magnetic resonance images (MRI) of 755 pts enrolled in the CENTRIC EORTC 26071-22072 study (n=508) and CORE study (n=247). Predefined sex-specific TMT cutoff values were used to categorize “patients at risk of sarcopenia” and “patients with normal muscle status” at baseline. Furthermore, patients were categorized according to the extent of TMT loss over time. Cox models adjusted for other explanatory variables were used to evaluate the associations with progression-free survival (PFS) and overall survival (OS).

RESULTS
Overall, 510/755 (67.6%) patients were categorized as “at risk of sarcopenia” and 245/755 (32.4%) patients had normal muscle status at baseline. In both study cohorts patient at risk of sarcopenia at baseline had significantly higher risk of progression and death than patients with normal muscle status (CENTRIC: PFS = HR 0.16, 95% CI: 0.12, 0.21, p&lt;0.001; OS = HR 0.341, 95% CI: 0.27, 0.44, p &lt; 0.001; CORE: PFS = HR 0.29, 95% CI: 0.21, 0.39, p&lt;0.001; OS = HR 0.365, 95% CI: 0.27, 0.49, p&lt;0.001). In multivariate Cox models adjusted for other important prognostic parameters similar results were obtained. In patients at risk for sarcopenia the extent of TMT loss over time showed a significant inverse correlation with median OS times (CENTRIC: p &lt; 0.001, CORE: p = 0.005, log-rank test), but not in patients with normal baseline muscle mass in both study cohorts (CENTRIC: p = 0.538, CORE: p = 0.28, log-rank test).

CONCLUSION
TMT identifies patients with newly diagnosed glioblastoma at risk for progressive sarcopenia and adverse outcomes. Early intervention for muscle mass preservation including exercise and resistance training as well as nutritional support may prevent skeletal muscle loss and improve patient outcome in this group of patients.