bluuebunny/crossref_metadata_2025_split huggingface dataset:
The whole-genome assembly of an endangered Salicaceae species: Chosenia arbutifolia (Pall.) A. Skv
Authors: He Xudong , Wang Yu , Lian Jinmin , Zheng Jiwei , Zhou Jie , Li Jiang , Jiao Zhongyi , Niu Yongchao , Wang Weiwei , Zhang Jun , Wang Baosong , Zhuge Qiang 
Published: November 2022

Abstract

Background
As a fast-growing tree species, Chosenia arbutifolia has a unique but controversial taxonomic status in the family Salicaceae. Despite its importance as an industrial material, in ecological protection, and in landscaping, C. arbutifolia is seriously endangered in Northeast China because of artificial destruction and its low reproductive capability.

Results
To clarify its phylogenetic relationships with other Salicaceae species, we assembled a high-quality chromosome-level genome of C. arbutifolia using PacBio High-Fidelity reads and Hi-C sequencing data, with a total size of 338.93 Mb and contig N50 of 1.68 Mb. Repetitive sequences, which accounted for 42.34% of the assembly length, were identified. In total, 33,229 protein-coding genes and 11,474 small noncoding RNAs were predicted. Phylogenetic analysis suggested that C. arbutifolia and poplars diverged approximately 15.3 million years ago, and a large interchromosomal recombination between C. arbutifolia and other Salicaceae species was discovered.

Conclusions
Our study provides insights into the genome architecture and systematic evolution of C. arbutifolia, as well as comprehensive information for germplasm protection and future functional genomic studies.
Quality classification and inversion of receiver functions using convolutional neural network
Authors: Gan Lu , Wu Qingju , Huang Qinghua , Tang Rongjiang 
Published: November 2022

SUMMARYConvolutional neural network (CNN) is presented to implement quick quality classification and inversion for teleseismic P-wave receiver functions (RF). For the first case, a CNN is trained using field measured RFs from NE margin of the Tibetan Plateau to efficiently predict the quality of each input waveform. Signal-to-noise ratio and correlation are introduced to quantitatively determine the quality label of RF, avoiding the subjectivity of manual labelling. The trained network reduces the time needed for data processing and has higher accuracy and efficiency than conventional methods. Its good performance is confirmed by comparing it with manually selected data from NE of the Tibetan Plateau. The second case is an example of joint inverting teleseismic P-wave RF and surface wave dispersions for the estimation of earth S-wave structure and associated uncertainties. We train a UNet based on synthetic global Crust 5.1 models and standard earth models, as well as associated perturbed models to ensure enough generalization capacity. We find that the UNet inversion is robust and has a better performance to reconstruct subsurface ${V}_s$ distributions than the damping least-squares method, but at the expense of slightly higher data misfits. The pre-trained network can predict subsurface ${V}_s$ models and associated uncertainties beneath NE of the Tibetan Plateau, which is consistent with the published models.
Micromechanics of rock damage and its recovery in cyclic loading conditions
Authors: Brantut Nicolas , Petit Léo 
Published: November 2022

SUMMARY
Under compressive stress, rock ‘damage’ in the form of tensile microcracks is coupled to internal slip on microscopic interfaces, such as pre-existing cracks and grain boundaries. In order to characterize the contribution of slip to the overall damage process, we conduct triaxial cyclic loading experiments on Westerly granite, and monitor volumetric strain and elastic wave velocity and anisotropy. Cyclic loading tests show large hysteresis in axial stress–strain behaviour that can be explained entirely by slip. Elastic wave velocity variations are observed only past a yield point, and show hysteresis with incomplete reversibility upon unloading. Irrecoverable volumetric strain and elastic wave velocity drop and anisotropy increase with increasing maximum stress, are amplified during hydrostatic decompression, and decrease logarithmically with time during hydrostatic hold periods after deformation cycles. The mechanical data and change in elastic properties are used to determine the proportion of mechanical work required to generate tensile cracks, which increases as the rock approaches failure but remains small, up to around 10 per cent of the net dissipated work per cycle. The pre-rupture deformation behaviour of rocks is qualitatively compatible with the mechanics of wing cracks. While tensile cracks are the source of large changes in rock physical properties, they are not systematically associated with significant energy dissipation and their aperture and growth is primarily controlled by friction, which exerts a dominant control on rock rheology in the brittle regime. Time-dependent friction along pre-existing shear interfaces explains how tensile cracks can close under static conditions and produce recovery of elastic wave velocities over time.
Progress across empire: entanglements between Indian and European reformers before the First World War
Authors: Deroo Florian , Verbruggen Christophe 
Published: November 2022

Abstract
This article argues that the field of social reform was a flourishing sphere of encounter between progressive Indian and European intellectuals in the years leading up to the First World War. By building personal networks, sharing intellectual reference points and exchanging information in internationally oriented journals, reformers could develop the sense that they belonged to a globe-spanning vanguard of like-minded intellectuals who, by identifying and addressing social issues in a local context, were allied to a range of analogous initiatives abroad. The expectation of a mutually beneficial bridging of ‘East’ and ‘West’ stimulated the personal entanglements of these intellectuals, yet they would become harder to maintain after the mechanized violence of the First World War cast doubts on the civilizing offensive.
Decreased cyclic-AMP caused by ATP contributes to fosfomycin heteroresistance in avian Escherichia coli
Authors: Zhao Bing , Han Han , He Kun , Hou Wen-Fei , Liang Yu-Lei , Cui Jun-ling , He Dan-Dan , Hu Gong-Zheng , Liu Jian-Hua , Yuan Li 
Published: November 2022

Abstract

Background
Fosfomycin is an important broad-spectrum bactericidal antibiotic to treat multidrug-resistant bacteria infections. It is generally accepted that heteroresistant bacteria are an intermediate stage in the formation of drug resistance, but there are few studies on the formation mechanism underlying fosfomycin heteroresistance (FHR).

Objectives
To reveal the characteristics and formation mechanisms of FHR in Escherichia coli isolates obtained from chickens.

Methods
We identified the FHR according to the population analysis profile (PAP) test and in vitro time–kill assay. Growth curves for FHR E. coli and their subpopulations were measured. Also, the subpopulations were repeatedly cultured in fosfomycin-free medium for 5–20 overnight incubation periods. The formation mechanisms of FHR in E. coli isolates were identified through accumulation assay, carbohydrate utilization testing, real-time relative quantitative PCR analysis, DNA sequencing, transcriptomic analysis, intracellular ATP and cAMP-level assessment.

Results
Four of six E. coli strains were confirmed to show FHR, with a total of six subpopulations. The subpopulations restored phenotypic susceptibilities to fosfomycin within 5–20 overnight incubation sessions, but four of six subpopulations still maintained FHR characteristics. Differing from their parental isolates, the uptake of fosfomycin in the subpopulations through GlpT was reduced remarkably. Further studies identified that the low expression of glpT was due to the decrease of intracellular cAMP levels in the subpopulations, which was caused by the decreased ATP levels in cells.

Conclusions
Our findings revealed the formation mechanism of E. coli isolates showing FHR obtained from chicken in China and characterized the dynamic change traits in vitro of the subpopulations.
Temperature-dependent Functional Response of the Arboreal Rove Beetle,Oligota flavicornis(Coleoptera: Staphylinidae), a Voracious Predator ofTetranychus urticae(Acarina: Tetranychidae)
Authors: Lin Tao , Chen Yixin , Chen Yong , Lin Shuo , Hu Jinfeng , Zhao Jianwei , Yang Guang , Yang Fenghua , Wei Hui 
Published: November 2022

AbstractThe functional responses of Oligota flavicornis (Boisduval & Lacordaire) (Coleoptera: Staphylinidae) preying on the eggs of Tetranychus urticae Koch (Acarina: Tetranychidae) were examined at seven constant temperature settings (12, 15, 18, 22, 25, 30, and 32°C) to elucidate the predator–prey interactions between them. Logistic regression showed that O. flavicornis exhibited type II functional responses to T. urticae eggs at different temperatures. The reciprocal of handling time declined exponentially with warming, and the search rate presented a single hump-shaped relationship with temperature. For the search rate, the lower temperature thresholds were 9.1°C (linear) and 8.7°C (Briere). The optimal temperature and upper temperature threshold were 29.1 and 37.8°C for Logan and 29.7 and 35.8°C for Briere, respectively. The predation threshold window of O. flavicornis reached 27.1°C with a range of 8.7–35.8°C. The predator could consume 244.7–388.4 T. urticae eggs in a day in the optimal temperature range (18–32°C). The voracious predatory behavior of O. flavicornis against T. urticae eggs over a broad temperature range indicates that the predator shows promise as a potential biological control agent and that temperature-dependent predation could be a basis for formulating strategies to control tetranychid mites.
Serotype 19A and 6C Account for One-Third of Pneumococcal Carriage Among Belgian Day-Care Children Four Years After a Shift to a Lower-Valent PCV
Authors: Ekinci Esra , Van Heirstraeten Liesbet , Willen Laura , Desmet Stefanie , Wouters Ine , Vermeulen Helene , Lammens Christine , Goossens Herman , Van Damme Pierre , Verhaegen Jan , Beutels Philippe , Theeten Heidi , Malhotra-Kumar Surbhi ,   NP Carriage Study Group
Published: November 2022

Abstract

Background
Pneumococcal conjugate vaccines (PCVs) effectively reduce infection and asymptomatic carriage of Streptococcus pneumoniae vaccine serotypes. In 2016, Belgium replaced its infant PCV13 program by a 4-year period of PCV10. Concomitantly, S. pneumoniae serotype carriage was monitored together with the carriage of other nasopharyngeal pathogens in children attending day-care centers.

Methods
From 2016 to 2019, a total of 3459 nasopharyngeal swabs were obtained from children aged 6–30 months. Culture and qPCR were used for the identification of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and for serotyping and antimicrobial susceptibility assessment of S. pneumoniae strains.

Results
S. pneumoniae colonization was frequent and stable over the study years. H. influenzae and M. catarrhalis were more frequently carried (P &lt; .001) than S. pneumoniae, by, respectively, 92.3% and 91.0% of children. Prevalence of all PCV13 serotypes together increased significantly over time from 5.8% to 19.6% (P &lt; .001) and was attributable to the increasing prevalence of serotype 19A. Coincidently, non-vaccine serotype 6C increased (P &lt; .001) and the overall pneumococcal non-susceptibility to tetracycline and erythromycin. Non-susceptibility to cotrimoxazole decreased (P &lt; .001).

Conclusions
The switch to a PCV program no longer covering serotypes 19A, 6A, and 3 was associated with a sustained increase of serotypes 19A and 6C in healthy children, similarly as in invasive pneumococcal disease. This resulted in a re-introduction of the 13-valent conjugate vaccine during the summer of 2019.
Distinct chromosomal “niches” in the genome ofSaccharomyces cerevisiaeprovide the background for genomic innovation and shape the fate of gene duplicates
Authors: Stavropoulou Athanasia , Tassios Emilios , Kalyva Maria , Georgoulopoulos Michalis , Vakirlis Nikolaos , Iliopoulos Ioannis , Nikolaou Christoforos 
Published: November 2022

AbstractNearly one third of Saccharomyces cerevisiae protein coding sequences correspond to duplicate genes, equally split between small-scale duplicates (SSD) and whole-genome duplicates (WGD). While duplicate genes have distinct properties compared to singletons, to date, there has been no systematic analysis of their positional preferences. In this work, we show that SSD and WGD genes are organized in distinct gene clusters that occupy different genomic regions, with SSD being more peripheral and WGD more centrally positioned close to centromeric chromatin. Duplicate gene clusters differ from the rest of the genome in terms of gene size and spacing, gene expression variability and regulatory complexity, properties that are also shared by singleton genes residing within them. Singletons within duplicate gene clusters have longer promoters, more complex structure and a higher number of protein–protein interactions. Particular chromatin architectures appear to be important for gene evolution, as we find SSD gene-pair co-expression to be strongly associated with the similarity of nucleosome positioning patterns. We propose that specific regions of the yeast genome provide a favourable environment for the generation and maintenance of small-scale gene duplicates, segregating them from WGD-enriched genomic domains. Our findings provide a valuable framework linking genomic innovation with positional genomic preferences.
MODL-15. BRINGING PRECISION MEDICINE TO GLIOBLASTOMA PATIENTS BY MODELING MOLECULAR TUMOR SUBTYPES IN IMMUNOCOMPETENT SWINE FOR THERAPEUTIC AND BIOMARKER DEVELOPMENT
Authors: Watson Adrienne , Korpela Derek , Koes Nicholas , Taisto Mandy , Corbiere Stanislas , Tschida Barbara 
Published: November 2022

Abstract
Glioblastoma (GBM) is an aggressive primary brain tumor with no effective cure. Standard of care treatment offers dismal prognoses for patients with a median survival time of only 15.6 months, and no new drugs have been approved in 15 years. Contributing factors include tumor heterogeneity, high mutation rates, infiltrative growth, a complex tumor-immune microenvironment, and the blood-brain barrier, all of which are obstacles clinicians and researchers must overcome to improve patient outcomes. Research to identify novel therapeutic strategies are ongoing, but treatments that show promise in preclinical studies often do not pass Phase 2 and 3 clinical trials. These costly failures are attributable to a lack of predictive preclinical models that translate to human application, low patient availability for numerous and robust clinical trials, and an “all-comer” approach to clinical trial design where patients are enrolled based on disease presence and not molecular features of the tumor. To advance treatments for GBM, Recombinetics has pioneered somatic gene-editing technologies to the same genetic changes seen in patient tumors in GBM-initiating cells in an immune-competent swine model. These models rapidly and reproducibly develop GBM tumors that resemble human GBMs genetically, clinically and histologically. In addition to the physiological, immunological, and metabolic parallels between swine and humans, the molecular data collected from our swine mesenchymal and classical subtypes of GBM validate accurate disease modeling and we are pursuing additional GBM subtypes. Using RNA-sequencing, we are characterizing molecular profiles of these tumors, as well as identifying and validating drug targets. Studies are ongoing to characterize the tumor immune microenvironment of our models for improved immune-oncology therapeutic development. These large animal models of GBM will usher in a new era of pre-clinical testing that predicts the efficacy of a variety of therapeutic approaches, using precision medicine to bring novel, safe, and effective therapies to patients.
CTIM-07. PHASE II RANDOMIZED, BLINDED, PLACEBO-CONTROLLED TRIAL TESTING PP65 CMV MRNA DENDRITIC CELL VACCINE AND TETANUS-DIPHTHERIA TOXOID FOR NEWLY DIAGNOSED GBM (ATTAC II, NCT02465268)
Authors: Rahman Maryam , Ghiaseddin Ashley , Deleyrolle Phuong , Peters Katherine B , Archer Gary , Sampson John , Mitchell Duane 
Published: November 2022

Abstract

INTRODUCTION
Immunotherapy is limited in efficacy for glioblastoma (GBM). The objective of this study was to evaluate the efficacy and immune effects of the pp65 mRNA dendritic cell (DC) vaccine with the use of lysosomal-associated membrane protein (LAMP) in two different formulations (full-length (fl) and short-length (sh).

METHODS
Patients who underwent resection of newly diagnosed GBM were enrolled and randomized to one of 3 arms: Arm 1) pp65-shLAMP mRNA DC with GM-CSF, Arm 2) pp65-flLAMP mRNA DC with GM-CSF, Arm 3) Unpulsed peripheral blood mononuclear cells (PBMC). After surgery, patients underwent leukapheresis for PBMC isolation and vaccines generation. Patients were treated with standard radiation and temozolomide followed by dose intensified adjuvant temozolomide at 75-100 mg/m2 x 21 days (aged less than 70) or standard dose at 150-200 mg/m2 x 5 days (patients 70 and older). Immunization started days 22-24 of cycle #1 with vaccines 1-3 delivered at 2 week intervals. All patients received tetanus-toxoid booster prior to vaccine 1. Patients continued to receive monthly vaccines for up to 10 vaccines with tetanus-diphtheria toxoid skin prep prior to vaccines 3, 6 and 9 (arms 1 and 2). Safety, efficacy and immune labs were evaluated.

RESULTS
Overall DC vaccines were well-tolerated with 2 SAEs possibly attributed to DC vaccination that met criteria as DLTs. Of recorded grade 2 or lower AEs, 2 were possibly attributable to DC vaccination. One patient was removed from the study due to failure to produce DC vaccines that met QA/QC release criteria.

CONCLUSION
In a large randomized and blinded patient cohort, delivery of CMV LAMP pp65 mRNA DC vaccines is feasible and safe in a multi-institutional setting. The primary endpoint of survival will be analyzed at the conclusion of the study.
CTIM-24. NUTMEG: A RANDOMIZED PHASE II STUDY OF NIVOLUMAB AND TEMOZOLOMIDE VERSUS TEMOZOLOMIDE ALONE IN NEWLY DIAGNOSED ELDERLY PATIENTS WITH GLIOBLASTOMA
Authors: Sim Hao-Wen , Lwin Zarnie , Barnes Elizabeth , McDonald Kerrie , Yip Sonia , Verhaak Roel , Heimberger Amy , Hall Merryn , Wong Matthew , Jennens Ross , Ashley David , Rosenthal Mark , Hovey Elizabeth , Ellingson Benjamin , Tognela Annette , Gan Hui , Back Michael , Koh Eng-Siew , Long Anne , Cuff Katharine , Begbie Stephen , Gedye Craig , Mislang Anna , Le Hien , Johnson Margaret , Kong Benjamin , Simes John , Khasraw Mustafa 
Published: November 2022

Abstract

BACKGROUND
Nivolumab is a PD-1 inhibitor with known safety profile. An increase in mutations as we age is well documented in glioblastoma and other cancers. Higher mutational load is associated with increased response to nivolumab in extracranial malignancies. NUTMEG examined the activity of nivolumab added to temozolomide in glioblastoma patients aged ≥ 65 years.

METHODS
NUTMEG was an international multicenter phase II trial for newly diagnosed glioblastoma patients aged ≥ 65 years, randomized 2:1 to experimental (40Gy/15 fractions with temozolomide 75mg/m2, then 6 cycles of temozolomide 150-200mg/m2 D1-5 Q28D + nivolumab 240mg D1,15 Q28D C1-4 and 480mg D1 Q28D C5-6) versus standard arm (40Gy/15 fractions with temozolomide 75mg/m2, then 6 cycles of temozolomide alone 150-200mg/m2 D1-5 Q28D), stratified by age, ECOG status, MGMT status and resection extent.

RESULTS
103 patients were enrolled (69 in experimental arm, 34 in standard arm). Median age was 73 years, 36% ECOG 0, 57% MGMT-unmethylated and 51% gross macroscopic resection. Median follow-up is 31 months to date, with 77 deaths (surviving patients to continue follow-up and final results will be presented). Median overall survival was 11.8 months in the experimental arm versus 12.0 months in the standard arm (HR 0.95 95%CI 0.59-1.53 for experimental relative to control). Six-month progression-free survival rate using mRANO was 64% in the experimental arm versus 49% in the standard arm (HR 0.81 95%CI 0.51-1.26). Grade 3/4 adverse events were reported in 46% of experimental arm (7% lung infection, 7% thromboembolic events, 6% fatigue, 6% muscle weakness) and in 29% of control arm (9% fatigue, 6% seizure, 6% thromboembolic events).

CONCLUSIONS
There was insufficient evidence of clinical benefit with nivolumab in this population. No new safety signals were identified. Central imaging review is underway and correlative studies will characterize the immune landscape, including mutational load, neoantigen and other immune markers. NCT04195139.
CTIM-27. AUTOLOGOUS TUMOR LYSATE-LOADED DENDRITIC CELL VACCINATION IMPROVES SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED AND RECURRENT GLIOBLASTOMA: SURVIVAL RESULTS FROM A PHASE 3 TRIAL
Authors: Liau Linda M , Ashkan Keyoumars , Brem Steven , Campian Jian , Trusheim John , Iwamoto Fabio , Tran David , Anstass George , Cobbs Charles , Heth Jason , Salacz Michael , D'Andre Stacy , Aiken Robert , Moshel Yaron , Nam JooYeon , Pillainayagam Clement , Wagner Stephanie , Walter Kevin , Chaudary Rekha , Goldlust Samuel , Lee Ian , Bota Daniela , Elinzano Heinrich , Grewal Jai , Lillehei Kevin , Mikkelsen Tom , Walbert Tobias , Abram Steve , Brenner Andrew , Ewend Matthew , Khagi Simon , Lovick Darren , Portnow Jana , Kim Lyndon , Loudon William , Martinez Nina , Thompson Reid , Avigan David , Fink Karen , Geoffroy Francois , Giglio Pierre , Gligich Oleg , Krex Dietmar , Lindhorst Scott M , Lutzky Jose , Meisel Hans-Joerg , Nadji-Ohl Minou , Sanchin Lhagva , Sloan Andrew , Bosch Marnix 
Published: November 2022

Abstract

BACKGROUND
Standard of care (SOC) and patient survival in glioblastoma have changed little in the past 17 years. We evaluated in a phase 3 trial whether adding an autologous tumor lysate-loaded dendritic cell vaccine (murcidencel) to SOC extends survival. Patients and

METHODS
Newly diagnosed glioblastoma patients were randomized 2:1 to either murcidencel or placebo. Under a crossover design, all patients could receive murcidencel following tumor recurrence. All parties remained blinded regarding treatments before recurrence. Patients thus received murcidencel at new diagnosis (nGBM) or at recurrence (rGBM) following crossover from placebo. The primary and secondary endpoints compare overall survival (OS) with contemporaneous, matched external controls. Four sets of analyses were conducted to ensure rigorous matching of the controls, reduce biases, and confirm the robustness of the results.

RESULTS
331 patients were enrolled. With the crossover, 89% received murcidencel. Median OS (mOS) for nGBM patients (n = 232) was 19.3 months from randomization (22.4 months from surgery) with murcidencel vs. 16.5 months from randomization in the controls (HR = 0.80, p = 0.002). Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%. For rGBM (n = 64), mOS was 13.2 months from relapse vs. 7.8 months in the controls (HR = 0.58, p &lt; 0.001). Survival at 24 months post-recurrence was 20.7% vs. 9.6%, and at 30 months post-recurrence was 11.1% vs 5.1%. In nGBM patients with methylated MGMT (n = 90), mOS was 30.2 months from randomization (33 months from surgery) with murcidencel vs. 21.3 months from randomization in the controls (HR = 0.74, p = 0.027). The treatment was well tolerated, with only 5 serious adverse events deemed at least possibly related to the vaccine.

CONCLUSION
Clinically meaningful and statistically significant survival extension was seen in both nGBM and rGBM patients treated with murcidencel and SOC compared with contemporaneous, matched external controls who received SOC alone.