bluuebunny/crossref_metadata_2025_split huggingface dataset:
Closing the gap: a new phylogeny and classification of the chemosymbiotic bivalve family Lucinidae with molecular evidence for 73% of living genera
Authors: Taylor John D , Glover Emily A , Yuen Benedict , Williams Suzanne T 
Published: October 2022

AbstractNew molecular phylogenies of the chemosymbiotic bivalve family Lucinidae, using 18S rRNA, 28S rRNA and cytochrome b genes, include species from genera not previously analysed. Notable additions from Myrteinae are sequences from Rostrilucina, Solelucina and Taylorina species, species of Ustalucina, Gonimyrtea from Leucosphaerinae and additional species of Ctena, Codakia, Lucinoma and Divalucina from Codakiinae. New sequences of Lucininae include the type species of Parvilucina (P. tenuisculpta), Liralucina, Falsolucinoma, Easmithia, Jallenia, Radiolucina and Cardiolucina as well as samples of Loripes orbiculatus from multiple localities. Five major clades, defined as subfamilies, are recognized: Pegophyseminae, Myrteinae, Leucosphaerinae, Codakiinae and Lucininae. Two branches, Fimbriinae and Monitilorinae, are represented by single species. Pegophyseminae are an extremely long-branched group with a sister-group relationship to Leucosphaerinae, while Codakiinae are a sister clade to the Lucininae. In various gene trees, the position of Myrteinae is unstable in relation to Pegophyseminae + Leucosphaerinae, Monitilorinae and Fimbriinae. The Myrteinae are not well resolved, with an ambiguous correlation of molecular and morphological characters. Codakiinae now include Divalucina cumingi, shown to be related to Lucinoma rather than Divaricella and Divalinga of the Lucininae. Leucosphaerinae are a well-supported clade but morphologically disparate, with the positions of Gonimyrtea and Callucina unresolved. Several molecularly distinct subclades are recognized within the Lucininae, especially the Lucinisca, Loripes and Parvilucina groups. Parvilucina species are paraphyletic with P. tenuisculpta, the type species, distinct from the western Atlantic species. Codakia, Ctena and Pegophysema have pan-tropical distributions with former connections disrupted by vicariant events of the closure of the eastern Tethyan and Central American Seaways. Species of Radiolucina, Pleurolucina and Lucinisca are present on either side of the Isthmus of Panama. A new classification of the 96 living lucinid genera is presented, providing a framework for future studies of systematics, ecology, biogeography and bacterial symbioses.
Efficacy and safety of anti-TNF multivalent NANOBODY® compound ‘ozoralizumab’ without methotrexate co-administration in patients with active rheumatoid arthritis: A 52-week result of phase III, randomised, open-label trial (NATSUZORA trial)
Authors: Tanaka Yoshiya , Kawanishi Masafumi , Nakanishi Megumi , Yamasaki Hironori , Takeuchi Tsutomu 
Published: October 2022

ABSTRACT

Objectives
The aim is to assess the efficacy and safety of a 52-week subcutaneous ozoralizumab treatment at 30 and 80 mg without methotrexate (MTX) in active rheumatoid arthritis.

Methods
This randomised, open-label, multicentre phase III trial randomly allocated 140 patients in 2:1 ratio as subcutaneous ozoralizumab at 30 or 80 mg every 4 weeks for 52 weeks without MTX.

Results
Both groups administered ozoralizumab at 30 and 80 mg showed good clinical improvement. The American College of Rheumatology response rates were high at Week 24 and maintained through 52 weeks. The ozoralizumab groups also showed good improvement in other end points, and improvements observed from Week 1 were maintained through 52 weeks. Improvements in many efficacy assessments were similar between doses. No deaths were reported, and serious adverse events occurred in a total of 20 patients in the ozoralizumab groups. Increased antidrug antibodies were observed in approximately 40% of patients in the ozoralizumab groups, and 27.7% of the patients in the 30 mg group were neutralising antibody-positive.

Conclusions
Ozoralizumab, at 30 and 80 mg, demonstrated significant therapeutic effects without MTX, and the efficacy was maintained for 52 weeks with active rheumatoid arthritis. Ozoralizumab showed an acceptable tolerability profile over 52 weeks.
CovInter: interaction data between coronavirus RNAs and host proteins
Authors: Amahong Kuerbannisha , Zhang Wei , Zhou Ying , Zhang Song , Yin Jiayi , Li Fengcheng , Xu Hongquan , Yan Tianci , Yue Zixuan , Liu Yuhong , Hou Tingjun , Qiu Yunqing , Tao Lin , Han Lianyi , Zhu Feng 
Published: October 2022

Abstract
Coronavirus has brought about three massive outbreaks in the past two decades. Each step of its life cycle invariably depends on the interactions among virus and host molecules. The interaction between virus RNA and host protein (IVRHP) is unique compared to other virus–host molecular interactions and represents not only an attempt by viruses to promote their translation/replication, but also the host's endeavor to combat viral pathogenicity. In other words, there is an urgent need to develop a database for providing such IVRHP data. In this study, a new database was therefore constructed to describe the interactions between coronavirus RNAs and host proteins (CovInter). This database is unique in (a) unambiguously characterizing the interactions between virus RNA and host protein, (b) comprehensively providing experimentally validated biological function for hundreds of host proteins key in viral infection and (c) systematically quantifying the differential expression patterns (before and after infection) of these key proteins. Given the devastating and persistent threat of coronaviruses, CovInter is highly expected to fill the gap in the whole process of the ‘molecular arms race’ between viruses and their hosts, which will then aid in the discovery of new antiviral therapies. It's now free and publicly accessible at: https://idrblab.org/covinter/
DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci
Authors: Bader Aldo S , Luessing Janna , Hawley Ben R , Skalka George L , Lu Wei-Ting , Lowndes Noel F , Bushell Martin 
Published: October 2022

Abstract
Proteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair. We found DDX17 to be required for both cell survival and DNA repair in response to numerous agents that induce DSBs. Analysis of DSB repair factor recruitment to damage sites suggested a role for DDX17 early in the DSB ubiquitin cascade. Genome-wide mapping of R-loops revealed that while DDX17 promotes the formation of DNA:RNA-hybrids around DSB sites, this role is specific to loci that have low levels of pre-existing hybrids. We propose that DDX17 facilitates DSB repair at loci that are inefficient at forming DNA:RNA-hybrids by catalysing the formation of DSB-induced hybrids, thereby allowing propagation of the damage response.
TFSyntax: a database of transcription factors binding syntax in mammalian genomes
Authors: Zhao Yongbing 
Published: October 2022

Abstract
In mammals, transcriptional factors (TFs) drive gene expression by binding to regulatory elements in a cooperative manner. Deciphering the rules of such cooperation is crucial to obtain a full understanding of cellular homeostasis and development. Although this is a long-standing topic, there is no comprehensive database for biologists to access the syntax of TF binding sites. Here we present TFSyntax (https://tfsyntax.zhaopage.com), a database focusing on the arrangement of TF binding sites. TFSyntax maps the binding motif of 1299 human TFs and 890 mouse TFs across 382 cells and tissues, representing the most comprehensive TF binding map to date. In addition to location, TFSyntax defines motif positional preference, density and colocalization within accessible elements. Powered by a series of functional modules based on web interface, users can freely search, browse, analyze, and download data of interest. With comprehensive characterization of TF binding syntax across distinct tissues and cell types, TFSyntax represents a valuable resource and platform for studying the mechanism of transcriptional regulation and exploring how regulatory DNA variants cause disease.
Implementation of Telemedicine Infectious Diseases Consultation in a Rural Hospital Using the Active Implementation Framework
Authors: Burnham Jason P , Fritz Stephanie A , Colditz Graham A 
Published: October 2022

Abstract
In this pilot study, guided by the Active Implementation Framework, telemedicine infectious diseases consultation was provided to hospitalized inpatients at a rural Missouri hospital. Measured outcomes included the implementation outcomes of feasibility, acceptability, appropriateness, and fidelity, as well as clinical outcomes of readmissions and death.
The Value of Phenotypic Precision Medicine in Prostate Cancer
Authors: Hawkey Nathan M , Broderick Amanda , George Daniel J , Sartor Oliver , Armstrong Andrew J 
Published: October 2022

AbstractProstate cancer is the most common cancer among men and the second leading cause of cancer-related death. For patients who develop metastatic disease, tissue-based and circulating-tumor–based molecular and genomic biomarkers have emerged as a means of improving outcomes through the application of precision medicine. However, the benefit is limited to a minority of patients. An additional approach to further characterize the biology of advanced prostate cancer is through the use of phenotypic precision medicine, or the identification and targeting of phenotypic features of an individual patient’s cancer. In this review article, we will discuss the background, potential clinical benefits, and limitations of genomic and phenotypic precision medicine in prostate cancer. We will also highlight how the emergence of image-based phenotypic medicine may lead to greater characterization of advanced prostate cancer disease burden and more individualized treatment approaches in patients.
Mutation-Agnostic Detection of Colorectal Cancer Using Liquid Biopsy-Based Methylation-Specific Signatures
Authors: Gouda Mohamed A , Duose Dzifa Y , Lapin Morten , Zalles Stephanie , Huang Helen J , Xi Yuanxin , Zheng Xiaofeng , Aldesoky Amira I , Alhanafy Alshimaa M , Shehata Mohamed A , Wang Jing , Kopetz Scott , Meric-Bernstam Funda , Wistuba Ignacio I , Luthra Rajyalakshmi , Janku Filip 
Published: October 2022

AbstractDetection of methylation patterns in circulating tumor DNA (ctDNA) can offer a novel approach for cancer diagnostics given the unique signature for each tumor type. We developed a next-generation sequencing (NGS)-based assay targeting 32 CpG sites to detect colorectal cancer-specific ctDNA. NGS was performed on bisulfite-converted libraries and status dichotomization was done using median methylation ratios at all targets. We included plasma samples from patients with metastatic colorectal (n = 20) and non-colorectal cancers (n = 8); and healthy volunteers (n = 4). Median methylation ratio was higher in colorectal cancer compared with non-colorectal cancers (P = .001) and normal donors (P = .005). The assay detected ctDNA in 85% of patients with colorectal cancer at a specificity of 92%. Notably, we were able to detect methylated ctDNA in 75% of patients in whom ctDNA was not detected by other methods. Detection of methylated ctDNA was associated with shorter median progression-free survival compared to non-detection (8 weeks versus 54 weeks; P = .027).
Transition to ripening in tomato requires hormone-controlled genetic reprogramming initiated in gel tissue
Authors: Chirinos Ximena , Ying Shiyu , Rodrigues Maria Aurineide , Maza Elie , Djari Anis , Hu Guojian , Liu Mingchun , Purgatto Eduardo , Fournier Sylvie , Regad Farid , Bouzayen Mondher , Pirrello Julien 
Published: October 2022

Abstract
Ripening is the last stage of the developmental program in fleshy fruits. During this phase, fruits become edible and acquire their unique sensory qualities and post-harvest potential. Although our knowledge of the mechanisms that regulate fruit ripening has improved considerably over the past decades, the processes that trigger the transition to ripening remain poorly deciphered. While transcriptomic profiling of tomato (Solanum lycopersicum L.) fruit ripening to date has mainly focused on the changes occurring in pericarp tissues between the Mature Green and Breaker stages, our study addresses the changes between the Early Mature Green and Late Mature Green stages in the gel and pericarp separately. The data showed that the shift from an inability to initiate ripening to the capacity to undergo full ripening requires extensive transcriptomic reprogramming that takes place first in the locular tissues before extending to the pericarp. Genome-wide transcriptomic profiling revealed the wide diversity of transcription factor (TF) families engaged in the global reprogramming of gene expression and identified those specifically regulated at the Mature Green stage in the gel but not in the pericarp, thereby providing potential targets toward deciphering the initial factors and events that trigger the transition to ripening. The study also uncovered an extensive reformed homeostasis for most plant hormones, highlighting the multihormonal control of ripening initiation. Our data unveil the antagonistic roles of ethylene and auxin during the onset of ripening and show that auxin treatment delays fruit ripening via impairing the expression of genes required for System-2 autocatalytic ethylene production that is essential for climacteric ripening. This study unveils the detailed features of the transcriptomic reprogramming associated with the transition to ripening of tomato fruit and shows that the first changes occur in the locular gel before extending to pericarp and that a reformed auxin homeostasis is essential for the ripening to proceed.
Human EWS-FLI protein recapitulates in Drosophila the neomorphic functions that induce Ewing sarcoma tumorigenesis
Authors: Molnar Cristina , Reina Jose , Herrero Anastasia , Heinen Jan Peter , Méndiz Victoria , Bonnal Sophie , Irimia Manuel , Sánchez-Jiménez María , Sánchez-Molina Sara , Mora Jaume , Gonzalez Cayetano 
Published: October 2022

Abstract
Ewing sarcoma (EwS) is a human malignant tumor typically driven by the Ewing sarcoma-Friend leukemia integration (EWS-FLI) fusion protein. A paucity of genetically modified animal models, partially owed to the high toxicity of EWS-FLI, hinders research on EwS. Here, we report a spontaneous mutant variant, EWS-FLI1FS, that circumvents the toxicity issue in Drosophila. Through proteomic and genomic analyses, we show that human EWS-FLI1FS interacts with the Drosophila homologues of EWS-FLI human protein partners, including core subunits of chromatin remodeling complexes, the transcription machinery, and the spliceosome; brings about a massive dysregulation of transcription that affects a significant fraction of known targets of EWS-FLI in human cells; and modulates splicing. We also show that EWS-FLI1FS performs in Drosophila the two major neomorphic activities that it is known to have in human cells: activation of transcription from GGAA microsatellites and out competition of ETS transcription factors. We conclude that EWS-FLI1FS reproduces in Drosophila the known oncogenic activities of EWS-FLI that drive EwS tumorigenesis in humans. These results open up an unprecedented opportunity to investigate EWS-FLI’s oncogenic pathways in vivo in a genetically tractable organism.
Thinking about the Future: The Psychology of the Mind and Soul in Judgement Day I
Authors: Brooks Deanna 
Published: October 2022

Abstract
The Exeter Book poem Judgement Day I has long been considered by scholars to be an inferior Old English poem, failing to reach the literary heights or vivid drama of Judgement Day II or Christ III. However, this comparison is caused largely by the presuppositions that the modern title imposes, rather than matters of content. This paper argues that Judgement Day I is not meant to warn about the Final Judgement but instead is concerned with the present time of the reader as a way to encourage contemplation of their present actions in order to safeguard their soul’s future. To accomplish this, the poem draws on a psychological model of mind-body-soul primarily identified by Malcolm Godden, Soon-Ai Low, and Leslie Lockett. The presence of this psychological model has been previously noted by scholars in other Exeter Book poems such as The Wanderer, The Seafarer, and Soul and Body II. This study draws Judgement Day I into conversation with some of these poems and argues that its focus on safeguarding the soul for its final journey, or siðfæt, is a motif with which many of the Exeter poems engage. Judgement Day I can thus be read as a poem that engages with the themes of many other Exeter Book texts and participates actively in a larger poetic sequence throughout the manuscript.
Asset Prices and Portfolios with Externalities
Authors: D. Baker Steven , Hollifield Burton , Osambela Emilio 
Published: October 2022

AbstractElementary portfolio theory implies that environmentalists optimally hold more shares of polluting firms than non-environmentalists, and that polluting firms attract more investment capital than otherwise identical non-polluting firms through a hedging channel. Pigouvian taxation can reverse the aggregate investment results, but environmentalists still overweight polluters. We introduce countervailing motives for environmentalists to underweight polluters, comparing the implications when environmentalists coordinate to internalize pollution, or have nonpecuniary disutility from holding polluter stock. With nonpecuniary disutility, introducing a green derivative may dramatically alter who invests most in polluters, but has no impact on aggregate pollution.
Cerebellar Functional Dysconnectivity in Drug-Naïve Patients With First-Episode Schizophrenia
Authors: Cao Hengyi , Wei Xia , Zhang Wenjing , Xiao Yuan , Zeng Jiaxin , Sweeney John A , Gong Qiyong , Lui Su 
Published: October 2022

AbstractBackgroundCerebellar functional dysconnectivity has long been implicated in schizophrenia. However, the detailed dysconnectivity pattern and its underlying biological mechanisms have not been well-charted. This study aimed to conduct an in-depth characterization of cerebellar dysconnectivity maps in early schizophrenia.Study designResting-state fMRI data were processed from 196 drug-naïve patients with first-episode schizophrenia and 167 demographically matched healthy controls. The cerebellum was parcellated into nine functional systems based on a state-of-the-art atlas, and seed-based connectivity for each cerebellar system was examined. The observed connectivity alterations were further associated with schizophrenia risk gene expressions using data from the Allen Human Brain Atlas.Study resultsOverall, we observed significantly increased cerebellar connectivity with the sensorimotor cortex, default-mode regions, ventral part of visual cortex, insula, and striatum. In contrast, decreased connectivity was shown chiefly within the cerebellum, and between the cerebellum and the lateral prefrontal cortex, temporal lobe, and dorsal visual areas. Such dysconnectivity pattern was statistically similar across seeds, with no significant group by seed interactions identified. Moreover, connectivity strengths of hypoconnected but not hyperconnected regions were significantly correlated with schizophrenia risk gene expressions, suggesting potential genetic underpinnings for the observed hypoconnectivity.ConclusionsThese findings suggest a common bidirectional dysconnectivity pattern across different cerebellar subsystems, and imply that such bidirectional alterations may relate to different biological mechanisms.
Neurodegeneration Markers in the Cerebrospinal Fluid of 100 Patients with Schizophrenia Spectrum Disorder
Authors: Runge Kimon , Balla Agnes , Fiebich Bernd L , Maier Simon J , von Zedtwitz Katharina , Nickel Kathrin , Dersch Rick , Domschke Katharina , Tebartz van Elst Ludger , Endres Dominique 
Published: October 2022

AbstractBackgroundSchizophrenia spectrum disorders (SSD) can be associated with neurodegenerative processes causing disruption of neuronal, synaptic, or axonal integrity. Some previous studies have reported alterations of neurodegenerative markers (such as amyloid beta [Aβ], tau, or neurofilaments) in patients with SSD. However, the current state of research remains inconclusive. Therefore, the rationale of this study was to investigate established neurodegenerative markers in the cerebrospinal fluid (CSF) of a large group of patients with SSD.Study DesignMeasurements of Aβ1–40, Aß1–42, phospho- and total-tau in addition to neurofilament light (NFL), medium (NFM), and heavy (NFH) chains were performed in the CSF of 100 patients with SSD (60 F, 40 M; age 33.7 ± 12.0) and 39 controls with idiopathic intracranial hypertension (33 F, 6 M; age 34.6 ± 12.0) using enzyme-linked immunoassays.Study ResultsThe NFM levels were significantly increased in SSD patients (P = .009), whereas phospho-tau levels were lower in comparison to the control group (P = .018). No other significant differences in total-tau, beta-amyloid-quotient (Aβ1–42/Aβ1–40), NFL, and NFH were identified.ConclusionsThe findings argue against a general tauopathy or amyloid pathology in patients with SSD. However, high levels of NFM, which has been linked to regulatory functions in dopaminergic neurotransmission, were associated with SSD. Therefore, NFM could be a promising candidate for further research on SSD.
Risk Factors for Psychotic Relapse After Dose Reduction or Discontinuation of Antipsychotics in Patients With Chronic Schizophrenia. A Meta-Analysis of Randomized Controlled Trials
Authors: Bogers Jan P A M , Hambarian George , Walburgh Schmidt Niels , Vermeulen Jentien M , de Haan Lieuwe 
Published: October 2022

AbstractBackground and hypothesisAlthough maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced.Study DesignWe systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through January 2021 and reviewed randomized controlled trials (RCTs) that reported relapse rates after antipsychotic dose reduction or discontinuation in patients with chronic schizophrenia. We calculated relative risks (RRs) with 95% confidence intervals (CIs) per person-year and sought to identify potential risk factors for relapse. The study is registered with PROSPERO (CRD42017058296).Study ResultsForty-seven RCTs (54 patient cohorts, 1746 person-years) were included. The RR for psychotic relapse with dose reduction/discontinuation versus maintenance treatment was 2.3 per person-year (95% CI: 1.9 to 2.8). The RR was higher with antipsychotic discontinuation, dose reduction to less than 3–5 mg haloperidol equivalent (HE), or relatively rapid dose reduction (&lt;10 weeks). The RR was lower with long-acting injectable agents versus oral antipsychotic dose reduction. Other factors that increased the risk of psychotic relapse were younger age and short follow-up time.ConclusionsClinicians should take several risk factors for psychotic relapse into account when considering dose reduction in patients with chronic schizophrenia. Studies of a relatively fast reduction in antipsychotic dose support a minimum dose of 3–5 mg HE. However, if the dose is tapered more gradually, relapses related to medication withdrawal might be avoided, possibly enabling lower-end doses to be achieved.