bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post-acute blood biomarkers and disease progression in traumatic brain injury
Authors: Newcombe Virginia F J , Ashton Nicholas J , Posti Jussi P , Glocker Ben , Manktelow Anne , Chatfield Doris A , Winzeck Stefan , Needham Edward , Correia Marta M , Williams Guy B , Simrén Joel , Takala Riikka S K , Katila Ari J , Maanpää Henna Riikka , Tallus Jussi , Frantzén Janek , Blennow Kaj , Tenovuo Olli , Zetterberg Henrik , Menon David K 
Published: April 2022

Abstract
There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI.
Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and &gt;5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects.
Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to &gt;5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at &gt;5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and &gt;5 years showed higher than predicted brain age and elevated neurofilament light levels.
GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over &gt;5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.
Ubiquitin ligases and a processive proteasome facilitate protein clearance during the oocyte-to-embryo transition inCaenorhabditis elegans
Authors: Spike Caroline A , Tsukamoto Tatsuya , Greenstein David 
Published: April 2022

AbstractThe ubiquitin-mediated degradation of oocyte translational regulatory proteins is a conserved feature of the oocyte-to-embryo transition. In the nematode Caenorhabditis elegans, multiple translational regulatory proteins, including the TRIM-NHL RNA-binding protein LIN-41/Trim71 and the Pumilio-family RNA-binding proteins PUF-3 and PUF-11, are degraded during the oocyte-to-embryo transition. Degradation of each protein requires activation of the M-phase cyclin-dependent kinase CDK-1, is largely complete by the end of the first meiotic division and does not require the anaphase-promoting complex. However, only LIN-41 degradation requires the F-box protein SEL-10/FBW7/Cdc4p, the substrate recognition subunit of an SCF-type E3 ubiquitin ligase. This finding suggests that PUF-3 and PUF-11, which localize to LIN-41-containing ribonucleoprotein particles, are independently degraded through the action of other factors and that the oocyte ribonucleoprotein particles are disassembled in a concerted fashion during the oocyte-to-embryo transition. We develop and test the hypothesis that PUF-3 and PUF-11 are targeted for degradation by the proteasome-associated HECT-type ubiquitin ligase ETC-1/UBE3C/Hul5, which is broadly expressed in C. elegans. We find that several GFP-tagged fusion proteins that are degraded during the oocyte-to-embryo transition, including fusions with PUF-3, PUF-11, LIN-41, IFY-1/Securin, and CYB-1/Cyclin B, are incompletely degraded when ETC-1 function is compromised. However, it is the fused GFP moiety that appears to be the critical determinant of this proteolysis defect. These findings are consistent with a conserved role for ETC-1 in promoting proteasome processivity and suggest that proteasomal processivity is an important element of the oocyte-to-embryo transition during which many key oocyte regulatory proteins are rapidly targeted for degradation.
Chromosome-level genome of the globe skimmer dragonfly (Pantala flavescens)
Authors: Liu Hangwei , Jiang Fan , Wang Sen , Wang Hengchao , Wang Anqi , Zhao Hanbo , Xu Dong , Yang Boyuan , Fan Wei 
Published: April 2022

ABSTRACT

Background
The globe skimmer dragonfly (Pantala flavescens) is a notable Odonata insect distributed in nature fields and farmlands worldwide, and it is commonly recognized as a natural enemy because it preys on agricultural pests and health pests. As one of the sister groups of winged insects, odonatan species are key to understanding the evolution of insect wings.

Findings
We present a high-quality reference genome of P. flavescens, which is the first chromosome-level genome in the Palaeoptera (Odonata and Ephemeroptera). The assembled genome size was 662 Mb, with a contig N50 of 16.2 Mb. Via Hi-C scaffolding, 648 Mb (97.9%) of contig sequences were clustered, ordered, and assembled into 12 large scaffolds, each corresponding to a natural chromosome. The X chromosome was identified by sequence coverage depth. The repetitive sequences and gene density of the X chromosome are similar to those of autosomal sequences, but the X chromosome shows a much lower degree of heterozygosity. Our analysis shows that the effective population size experienced 3 declining events, which may have been caused by climate change and environmental pollution.

Conclusions
The genome of P. flavescens provides more information on the biology and evolution of insects and will help for the use of this species in pest control.
The Futility of Futility Analyses in Adjuvant Trials in Hormone Receptor–Positive Breast Cancer
Authors: Lohmann Ana Elisa , Ennis Marguerite , Parulekar Wendy R , Chen Bingshu E , Tomlinson George , Goodwin Pamela J 
Published: April 2022

Abstract
An interim analysis is commonly used in phase III superiority trials to compare treatment arms, with the goal of terminating exposure of patients to ineffective or unsafe drugs or to identify highly effective therapies for earlier public disclosure. Traditionally, interim analyses have been designed to identify early evidence of extremely large benefit of the experimental approach, potentially leading to early dissemination of effective treatments. Increasingly, interim analysis has also involved analysis of futility, which may lead to early termination of a trial that will not yield additional useful information. This presents an important challenge in early stage hormone receptor–positive breast cancer, where recurrence often occurs late, with a steady annual event rate up to 20 years. Early analysis of events may miss late treatment effects that can be observed only with longer follow-up. We discuss approaches to futility analysis in adjuvant clinical trials in hormone receptor–positive breast cancer, the role of the Data Safety Monitoring Committee in such analyses, considerations of the potential harms vs benefits of treatment, and the risks of continuing vs early termination of a trial.
Toni Morrison’sTheir Eyes Were Watching God
Authors: Pollak Alec 
Published: April 2022

AbstractI argue that Toni Morrison’s Tar Baby (1981) is a deliberate rewriting of Zora Neale Hurston’s Their Eyes Were Watching God (1937) and was, at the time of its publication, a critical intervention into heated scholarly debates over Janie Crawford’s suitability as a representative of what Jennifer Jordan terms “modern black feminism.” Morrison recasts the early twentieth-century Janie Crawford as the contemporary Jadine Childs and, availing herself of the descriptive and explanatory resources of her post-civil rights moment, renders Jadine’s capacity for self-determination undeniable, thus calling into question contemporaneous critiques of Janie as Hurston’s failed attempt to write, in Hortense J. Spillers’s words, “new” and self-determined “female being.” The novels, read together, reject the foundational paradigm of Black women’s literary succession—built as it has been around models of accretive, intergenerational possibility, wherein each successive generation of Black women characters attains new heights of self-determination—which posits Hurston and her characters as the necessary precursors of but regressive foils to Morrison and her characters’ political and literary self-actualization. Given Janie’s and Jadine’s shared experiences, reactions, and choices across drastically differing sociohistorical contexts, this polarization, Tar Baby suggests, is more a consequence of critics’ entrenched presuppositions than any tangible failings on Janie’s part. As a pair, Tar Baby and Their Eyes Were Watching God exhort readers to forgo the quest for what Jordan calls an “ideologically correct literature” on narrowly contemporary terms and, instead, to pursue recognition of Black women’s agency and truth-telling on malleable terms, even (and especially) amid the historical constraints placed upon these characters’ voices and upon representations thereof.
Phase I/randomized phase II trial of TRC105 plus bevacizumab versus bevacizumab in recurrent glioblastoma: North Central Cancer Treatment Group N1174 (Alliance)
Authors: Galanis Evanthia , Anderson S Keith , Twohy Erin , Butowski Nicholas A , Hormigo Adilia , Schiff David , Omuro Antonio , Jaeckle Kurt A , Kumar Shaji , Kaufmann Timothy J , Geyer Susan , Kumthekar Priya U , Campian Jian , Giannini Caterina , Buckner Jan C , Wen Patrick Y 
Published: April 2022

Abstract

Background
Patients with glioblastoma (GBM) have a poor prognosis and limited effective treatment options. Bevacizumab has been approved for treatment of recurrent GBM, but there is questionable survival benefit. Based on preclinical and early clinical data indicating that CD105 upregulation may represent a mechanism of resistance to bevacizumab, we hypothesized that combining bevacizumab with the anti-CD105 antibody TRC105 may improve efficacy in recurrent GBM.

Methods
Phase I dose-escalation/comparative randomized phase II trial in patients with GBM. During phase I, the maximum tolerated dose (MTD) of TRC105 in combination with bevacizumab was determined. In phase II, patients were randomized 1:1 to TRC105 and bevacizumab or bevacizumab monotherapy. Patients received TRC105 (10 mg/kg) weekly and bevacizumab (10 mg/kg) every 2 weeks. Efficacy, as assessed by progression-free survival (PFS), was the primary endpoint; safety, quality of life, and correlative outcomes were also evaluated.

Results
In total, 15 patients were enrolled in phase I and 101 in phase II; 52 patients were randomized to TRC105 with bevacizumab and 49 to bevacizumab monotherapy. The MTD was determined to be 10 mg/kg TRC105 weekly plus bevacizumab 10 mg/kg every 2 weeks. An increased occurrence of grade ≥3 adverse events was seen in the combination arm, including higher incidences of anemia. Median PFS was similar in both treatment arms: 2.9 months for combination versus 3.2 months for bevacizumab monotherapy (HR = 1.16, 95% CI = 0.75–1.78, P = .51). Quality of life scores were similar for both treatment arms.

Conclusions
TRC105 in combination with bevacizumab was well tolerated in patients with recurrent GBM, but no difference in efficacy was observed compared to bevacizumab monotherapy.
The interplay of auxin and brassinosteroid signaling tunes root growth under low and different nitrogen forms
Authors: Devi Loitongbam Lorinda , Pandey Anshika , Gupta Shreya , Singh Amar Pal 
Published: April 2022

Abstract
The coordinated signaling activity of auxin and brassinosteroids (BRs) is critical for optimal plant growth and development. Nutrient-derived signals regulate root growth by modulating the levels and spatial distribution of growth hormones to optimize nutrient uptake and assimilation. However, the effect of the interaction of these two hormones and their signaling on root plasticity during low and differential availability of nitrogen (N) forms (NH4+/NO3-) remains elusive. We demonstrate that root elongation under low N (LN) is an outcome of the interdependent activity of auxin and BR signaling pathways in Arabidopsis (Arabidopsis thaliana). LN promotes root elongation by increasing BR-induced auxin transport activity in the roots. Increased nuclear auxin signaling and its transport efficiency have a distinct impact on root elongation under LN conditions. High auxin levels reversibly inhibit BR signaling via BRI1 KINASE INHIBITOR1. Using the tissue-specific approach, we show that BR signaling from root vasculature (stele) tissues is sufficient to promote cell elongation and, hence, root growth under LN condition. Further, we show that N form-defined root growth attenuation or enhancement depends on the fine balance of BR and auxin signaling activity. NH4+ as a sole N source represses BR signaling and response, which in turn inhibits auxin response and transport, whereas NO3- promotes root elongation in a BR signaling-dependent manner. In this study, we demonstrate the interplay of auxin and BR-derived signals, which are critical for root growth in a heterogeneous N environment and appear essential for root N foraging response and adaptation.
Liquidation Cascade and Anticipatory Trading: Evidence from the Structured Equity Product Market
Authors: Auh Jun Kyung , Cho Wonho 
Published: April 2022

AbstractWe show that structured equity derivatives can cause significant price pressure of the underlying stock upon an event of dramatic payoff change. Moreover, one event causes another: the event cascade amplifies the magnitude of the impact. We find that a single event accounts for a −6.4% return on the event day, and it increases the probability of a subsequent event by 21.3%. Given the negative price impact, traders try to liquidate ahead of each other, exacerbating the degree of price pressure. Our results uncover the chain-reaction and (mis)coordination mechanism in complex derivatives markets that can provoke substantial price shocks. (JEL G12, G14, G24).
Pre-defined gene co-expression modules in rheumatoid arthritis transition towards molecular health following anti-TNF therapy
Authors: Sutcliffe Megan , Nair Nisha , Oliver James , Morgan Ann W , Isaacs John D , Wilson Anthony G , Verstappen Suzanne M M , Viatte Sebastien , Hyrich Kimme L , Morris Andrew P , Barton Anne , Plant Darren 
Published: April 2022

Abstract

Background
No reliable biomarkers to predict response to TNF inhibitors (TNFi) in RA patients currently exist. The aims of this study were to replicate changes in gene co-expression modules that were previously reported in response to TNFi therapy in RA; to test if changes in module expression are specific to TNFi therapy; and to determine whether module expression transitions towards a disease-free state in responding patients.

Method
Published transcriptomic data from the whole blood of disease-free controls (n = 10) and RA patients, treated with the TNFi adalimumab (n = 70) or methotrexate (n = 85), were studied. Treatment response was assessed using the EULAR response criteria following 3 or 6 months of treatment. Change in transcript expression between pre- and post-treatment was recorded for previously defined modules. Linear mixed models tested whether modular expression after treatment transitioned towards a disease-free state.

Results
For 25 of the 27 modules, change in expression between pre- and post-treatment in the adalimumab cohort replicated published findings. Of these 25 modules, six transitioned towards a disease-free state by 3 months (P &lt; 0.05), irrespective of clinical response. One module (M3.2), related to inflammation and TNF biology, significantly correlated with response to adalimumab. Similar patterns of modular expression, with reduced magnitude, were observed in the methotrexate cohort.

Conclusion
This study provides independent validation of changes in module expression in response to therapy in RA. However, these effects are not specific to TNFi. Further studies are required to determine whether specific modules could assist molecular classification of therapeutic response.
Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis
Authors: van der Togt Céleste J T , Ten Cate David F , den Broeder Nathan , Rahamat-Langendoen Janette , van den Bemt Bart J F , den Broeder Alfons A 
Published: April 2022

Abstract

Objectives
Humoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients.

Methods
A single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2–6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use.

Results
After two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14–8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39–2.01).

Conclusion
Both increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients.

Trial registration
Netherlands Trial Register, https://www.trialregister.nl/, NL9342.
The impact of disease severity measures on survival in U.S. veterans with rheumatoid arthritis-associated interstitial lung disease
Authors: Brooks Rebecca , Baker Joshua F , Yang Yangyuna , Roul Punyasha , Kerr Gail S , Reimold Andreas M , Kunkel Gary , Wysham Katherine D , Singh Namrata , Lazaro Deana , Monach Paul A , Poole Jill A , Ascherman Dana P , Mikuls Ted R , England Bryant R 
Published: April 2022

AbstractObjectivesTo determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD.MethodsWe studied US veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint DAS [DAS28-ESR]) and functional status (multidimensional HAQ [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications.ResultsWe followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio [aHR] 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment (&lt;80% predicted) was significantly associated with mortality risk. Those with a combination of moderate/high disease activity and FVC &lt;80% predicted had the highest risk of death (aHR 4.43; 95% CI: 1.70, 11.55).ConclusionBoth RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.
Human land use impacts viral diversity and abundance in a New Zealand river
Authors: French Rebecca , Charon Justine , Lay Callum Le , Muller Chris , Holmes Edward C 
Published: April 2022

Abstract
Although water-borne viruses have important implications for the health of humans and other animals, little is known about the impact of human land use on viral diversity and evolution in water systems such as rivers. We used metatranscriptomic sequencing to compare the diversity and abundance of viruses at sampling sites along a single river in New Zealand that differed in human land-use impacts, ranging from pristine to urban. From this, we identified 504 putative virus species, of which 97 per cent were novel. Many of the novel viruses were highly divergent and likely included a new subfamily within the Parvoviridae. We identified at least sixty-three virus species that may infect vertebrates—most likely fish and water birds—from the Astroviridae, Birnaviridae, Parvoviridae, and Picornaviridae. No putative human viruses were detected. Importantly, we observed differences in the composition of viral communities at sites impacted by human land use (farming and urban) compared to native forest sites (pristine). At the viral species level, the urban sites had higher diversity (327 virus species) than the farming (n = 150) and pristine sites (n = 119), and more viruses were shared between the urban and farming sites (n = 76) than between the pristine and farming or urban sites (n = 24). The two farming sites had a lower viral abundance across all host types, while the pristine sites had a higher abundance of viruses associated with animals, plants, and fungi. We also identified viruses linked to agriculture and human impact at the river sampling sites in farming and urban areas that were not present at the native forest sites. Although based on a small sample size, our study suggests that human land use can impact viral communities in rivers, such that further work is needed to reduce the impact of intensive farming and urbanisation on water systems.