bluuebunny/crossref_metadata_2025_split huggingface dataset:
SIGNORApp: a Cytoscape 3 application to access SIGNOR data
Authors: De Marinis Ilaria , Lo Surdo Prisca , Cesareni Gianni , Perfetto Livia 
Published: December 2021

Abstract

Summary
SIGNORApp is a Cytoscape 3 (3.8 and later) application that provides access to causal interactions annotated in the SIGNOR resource. The application builds networks that can be represented as weighted, signed, directed graphs, where nodes are interacting biological entities and edges represent causal interactions captured by expert curators from experiments reported in peer reviewed journals. Users can query the SIGNOR dataset with (i) single or multiple entity name(s) or identifier(s) and optionally they may require to include in the output network their interacting partners, (ii) browse pathways that are annotated in the SIGNOR resource and (iii) extract the entire causal interactome. The app offers two visualizations modes: one only displaying entity interactions and a second emphasizing the post-translational modifications occurring as a consequence of the interaction. In addition, users can click on nodes and edges to access entity and interaction annotations. Causal information is available for three model organisms: Homo sapiens, Mus musculus and Rattus norvegicus.

Availability and implementation
SIGNORApp has been developed for Cytoscape 3 (3.8 and later) in the Java programming language. The latest source code and the plugin can be found at: https://github.com/SIGNORcysAPP/signor-app and https://apps.cytoscape.org/apps/signorapp, respectively.

Supplementary information
Supplementary data are available at Bioinformatics online.
Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis
Authors: Cabrera-Serrano Macarena , Caccavelli Laure , Savarese Marco , Vihola Anna , Jokela Manu , Johari Mridul , Capiod Thierry , Madrange Marine , Bugiardini Enrico , Brady Stefen , Quinlivan Rosaline , Merve Ashirwad , Scalco Renata , Hilton-Jones David , Houlden Henry , Aydin Halil Ibrahim , Ceylaner Serdar , Drewes Sarah , Vockley Jerry , Taylor Rhonda L , Folland Chiara , Kelly Aasta , Goullee Hayley , Ylikallio Emil , Auranen Mari , Tyynismaa Henna , Udd Bjarne , Forrest Alistair R R , Davis Mark R , Bratkovic Drago , Manton Nicholas , Robertson Thomas , O’Gorman Cullen , McCombe Pamela , Laing Nigel G , Phillips Liza , de Lonlay Pascale , Ravenscroft Gianina 
Published: December 2021

Abstract
Rhabdomyolysis is the acute breakdown of skeletal myofibres in response to an initiating factor, most commonly toxins and over exertion. A variety of genetic disorders predispose to rhabdomyolysis through different pathogenic mechanisms, particularly in patients with recurrent episodes. However, most cases remain without a genetic diagnosis.
Here we present six patients who presented with severe and recurrent rhabdomyolysis, usually with onset in the teenage years; other features included a history of myalgia and muscle cramps. We identified 10 bi-allelic loss-of-function variants in the gene encoding obscurin (OBSCN) predisposing individuals to recurrent rhabdomyolysis. We show reduced expression of OBSCN and loss of obscurin protein in patient muscle. Obscurin is proposed to be involved in sarcoplasmic reticulum function and Ca2+ handling. Patient cultured myoblasts appear more susceptible to starvation as evidenced by a greater decreased in sarcoplasmic reticulum Ca2+ content compared to control myoblasts. This likely reflects a lower efficiency when pumping Ca2+ back into the sarcoplasmic reticulum and/or a decrease in Ca2+ sarcoplasmic reticulum storage ability when metabolism is diminished. OSBCN variants have previously been associated with cardiomyopathies. None of the patients presented with a cardiomyopathy and cardiac examinations were normal in all cases in which cardiac function was assessed. There was also no history of cardiomyopathy in first degree relatives, in particular in any of the carrier parents.
This cohort is relatively young, thus follow-up studies and the identification of additional cases with bi-allelic null OBSCN variants will further delineate OBSCN-related disease and the clinical course of disease.
Weight Gain of Spodoptera frugiperda Larvae (Lepidoptera: Noctuidae) on Leaf and Floral Tissues of Silphium integrifolium (Asterales: Asteraceae) Differs by Plant Genotype
Authors: Peterson Kelsey , Cheremond Edy , Brandvain Yaniv , Van Tassel David , Murrell Ebony 
Published: December 2021

Abstract
Silflower (Silphium integrifolium (Michaux)) is a native North American relative of sunflower that is undergoing domestication as a perennial oilseed crop. As silflower incurs pest damage from multiple insect species, it is necessary to screen genotypes for their effect on insect performance such that more pest tolerant/resistant accessions can be incorporated into future silflower breeding programs. We present a bioassay protocol for silflower using the generalist herbivore fall armyworm (Spodoptera frugiperda (J. E. Smith)). In this study, fall armyworm larvae were placed on leaf and flower tissue from eleven silflower genotypes, one cup plant (Silphium perfoliatum (L.) (Asterales: Asteraceae)) genotype, and an inbred sunflower line (Helianthus annuus (L.) (Asterales: Asteraceae), HA89). Caterpillar weight gained during a 4-d feeding period significantly differed on leaf and floral tissue from different silflower genotypes, between the Silphium species (silflower and cup plant), and between Silphium genotypes and annual sunflower. Two wild silflower genotypes produced lower larval weight gain on both the floral and leaf tissue than all other genotypes, suggesting these genotypes have either lower nutrition or greater resistance to fall armyworm. However, nonsignificant correlations between larval growth on floral versus leaf tissue across all plant species tested and among all silflower accessions suggest insect performances on these tissue types in silflower are independent. Along with identifying germplasm of interest for silflower breeding programs, we established an easily replicable bioassay protocol using fall armyworm on silflower floral and leaf tissues.
Drosophila centrocortin is dispensable for centriole duplication but contributes to centrosome separation
Authors: Mehta Dipen S , Zein-Sabatto Hala , Ryder Pearl V , Lee Jina , Lerit Dorothy A 
Published: December 2021

Abstract
Centrosomes are microtubule-organizing centers that duplicate exactly once to organize the bipolar mitotic spindle required for error-free mitosis. Prior work indicated that Drosophila centrocortin (cen) is required for normal centrosome separation, although a role in centriole duplication was not closely examined. Through time-lapse recordings of rapid syncytial divisions, we monitored centriole duplication and the kinetics of centrosome separation in control vs cen null embryos. Our data suggest that although cen is dispensable for centriole duplication, it contributes to centrosome separation.
A sensitized genetic screen to identify regulators of Caenorhabditis elegans germline stem cells
Authors: Robinson-Thiewes Sarah , Kershner Aaron M , Shin Heaji , Haupt Kimberly A , Kroll-Connor Peggy , Kimble Judith 
Published: December 2021

Abstract
GLP-1/Notch signaling and a downstream RNA regulatory network maintain germline stem cells in Caenorhabditis elegans. In mutants lacking the GLP-1 receptor, all germline stem cells enter the meiotic cell cycle precociously and differentiate into sperm. This dramatic germline stem cell defect is called the “Glp” phenotype. The lst-1 and sygl-1 genes are direct targets of Notch transcriptional activation and functionally redundant. Whereas single lst-1 and sygl-1 mutants are fertile, lst-1 sygl-1 double mutants are sterile with a Glp phenotype. We set out to identify genes that function redundantly with either lst-1 or sygl-1 to maintain germline stem cells. To this end, we conducted forward genetic screens for mutants with a Glp phenotype in genetic backgrounds lacking functional copies of either lst-1 or sygl-1. The screens generated 9 glp-1 alleles, 2 lst-1 alleles, and 1 allele of pole-1, which encodes the catalytic subunit of DNA polymerase ε. Three glp-1 alleles reside in Ankyrin repeats not previously mutated. pole-1 single mutants have a low penetrance Glp phenotype that is enhanced by loss of sygl-1. Thus, the screen uncovered 1 locus that interacts genetically with sygl-1 and generated useful mutations for further studies of germline stem cell regulation.
Human-Centered Design of an Advance Care Planning Group Visit for Mild Cognitive Impairment
Authors: Daddato Andrea E , Staton Elizabeth W , Bettcher Brianne M , Shanbhag Prajakta , Lum Hillary D 
Published: December 2021

Abstract

Background and Objectives
While advance care planning (ACP) is critical for ensuring optimal end-of-life outcomes among individuals with mild cognitive impairment (MCI), many individuals who may benefit from ACP have not initiated this process. This article aims to describe the iterative design of an MCI group visit-based intervention and evaluate the feasibility and acceptability of the intervention.

Research Design and Methods
We used human-centered design, rapid-cycle prototyping, and multiple methods to adapt an ENgaging in Advance Care planning Talks (ENACT) Group Visits intervention. We convened an advisory panel of persons with MCI and care partners (n = 6 dyads) to refine the intervention and conducted a single-arm pilot of 4 MCI ENACT intervention prototypes (n = 13 dyads). We used surveys and interviews to assess outcomes from multiple perspectives.

Results
The advisory panel affirmed that ACP is a priority for individuals with MCI, described the need for ACP in a group setting, and suggested refinements to ACP resources for the MCI ENACT intervention. Feasibility of recruitment was limited. MCI ENACT intervention participants strongly agreed that group discussions provided useful information and recommended the intervention. Themes supporting acceptability included (a) feedback on acceptability of the intervention, (b) previous experiences with ACP, and (c) reasons for participation, including desire for discussions about MCI and how it relates to ACP.

Discussion and Implications
Despite stakeholders’ positive ratings of acceptability of the MCI ENACT intervention, future work is needed to enhance the feasibility of recruitment to support implementation into clinical settings.
Effects of the 2014 Affordable Care Act Medicaid Expansions on Health Care Access and Health Status of Poor Adults Aged 60–64 Years: Evidence From the First 6 Years
Authors: Bin Abdul Baten Redwan , Wehby George L 
Published: December 2021

Abstract

Background and Objectives
Little is known on the effects of the Affordable Care Act (ACA) Medicaid expansions on health care access and health status of adults closest to 65. This study examines the effects of ACA Medicaid expansion on access and health status of poor adults aged 60–64 years.

Research Design and Methods
The study employs a difference-in-differences design comparing states that expanded Medicaid in 2014 under the ACA and nonexpansion states over 6 years postexpansion. The data are from the 2011–2019 Behavioral Risk Factor Surveillance System for individuals aged 60–64 years below the Federal Poverty Level.

Results
Having any health care coverage rate increased by 8.5 percentage points (p &lt; .01), while the rate of forgoing a needed doctor’s visit due to cost declined by 6.6 percentage points (p &lt; .01). Similarly, rates of having a personal doctor/provider and completing a routine checkup increased by 9.1 (p &lt; .01) and 4.8 (p &lt; .1) percentage points, respectively. Moreover, days not in good physical health in the past 30 declined by 1.5 days (p &lt; .05), with suggestive evidence for decline in days not in good mental health and improvement in self-rated health.

Discussion and Implications
The ACA Medicaid expansions have improved health care access and health status of poor adults aged 60–64 years. Expanding Medicaid in the states that have not yet done so would reduce barriers to care and address unmet health needs for this population. Bridging coverage for individuals aged 60–64 years by lowering Medicare eligibility age could have long-term effects on well-being and health services utilization.
Transcriptome-wide association study identifies multiple genes and pathways associated with thyroid function
Authors: Ke Xin , Tian Xin , Yao Shi , Wu Hao , Duan Yuan-Yuan , Wang Nai-Ning , Shi Wei , Yang Tie-Lin , Dong Shan-Shan , Huang Dageng , Guo Yan 
Published: December 2021

Abstract
Thyroid dysfunction is a common endocrine disease measured by thyroid-stimulating hormone (TSH) level. Although &gt;70 genetic loci associated with TSH have been reported through genome-wide association studies (GWASs), the variants can only explain a small fraction of the thyroid function heritability. To identify novel candidate genes for thyroid function, we conducted the first large-scale transcriptome-wide association study (TWAS) for thyroid function using GWAS-summary data for TSH levels in up to 119 715 individuals combined with precomputed gene expression weights of six panels from four tissue types. The candidate genes identified by TWAS were further validated by TWAS replication and gene expression profiles. We identified 74 conditionally independent genes significantly associated with thyroid function, such as PDE8B (P = 1.67 × 10−282), PDE10A (P = 7.61 × 10−119), NR3C2 (P = 1.50 × 10−92) and CAPZB (P = 3.13 × 10−79). After TWAS replication using UKBB datasets, 26 genes were replicated for significant associations with thyroid-relevant diseases/traits. Among them, 16 genes were causal for their associations to thyroid-relevant diseases/traits and further validated in differential expression analyses, including two novel genes (MFSD6 and RBM47) that did not implicate in previous GWASs. Enrichment analyses detected several pathways associated with thyroid function, such as the cAMP signaling pathway (P = 7.27 × 10−4), hemostasis (P = 3.74 × 10−4), and platelet activation, signaling and aggregation (P = 9.98 × 10−4). Our study identified multiple candidate genes and pathways associated with thyroid function, providing novel clues for revealing the genetic mechanisms of thyroid function and disease.
SARS-CoV-2 Infection During Pregnancy and Associated Perinatal Health Outcomes: A National US Cohort Study
Authors: Regan Annette K , Arah Onyebuchi A , Fell Deshayne B , Sullivan Sheena G 
Published: December 2021

Abstract

Background
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with increased risk of adverse perinatal health outcomes, few large-scale, community-based epidemiological studies have been conducted.

Methods
We conducted a national cohort study using deidentified administrative claims data for 78 283 pregnancies with estimated conception before 30 April 2020 and pregnancy end after 11 March 2020. We identified SARS-CoV-2 infections using diagnostic and laboratory testing data, and compared the risk of pregnancy outcomes using Cox proportional hazard models treating coronavirus disease 2019 (COVID-19) as a time-varying exposure and adjusting for baseline covariates.

Results
Of the pregnancies, 2655 (3.4%) had a documented SARS-CoV-2 infection. COVID-19 during pregnancy was not associated with risk of miscarriage, antepartum hemorrhage, or stillbirth, but was associated with 2–3 fold higher risk of induced abortion (adjusted hazard ratio [aHR], 2.60; 95% confidence interval [CI], 1.17–5.78), cesarean delivery (aHR, 1.99; 95% CI, 1.71–2.31), clinician-initiated preterm birth (aHR, 2.88; 95% CI, 1.93–4.30), spontaneous preterm birth (aHR, 1.79; 95% CI, 1.37–2.34), and fetal growth restriction (aHR, 2.04; 95% CI, 1.72–2.43).

Conclusions
Prenatal SARS-CoV-2 infection was associated with increased risk of adverse pregnancy outcomes. Prevention could have fetal health benefits.
The enforcement of cross-border competition law claims in Asia-pacific and choice of forum agreements: private litigation or arbitration?
Authors: Nishioka Kazuaki 
Published: December 2021

Abstract
A private plaintiff may bring an action against a defendant for the infringement of competition law. In Western countries, it is widely accepted that parties can subject to choice of forum agreements claims seeking private law remedies based on competition law infringements. Accordingly, parties are free to refer those claims to a foreign court or arbitral tribunal for their determination. In contrast, it remains an open question in most Asia-Pacific jurisdictions whether competition-related claims are subject to choice of forum agreements (in particular, an arbitration agreement). If the answer is affirmative, a number of incidental questions will arise. For instance, in what kinds of competition-related claims and under what circumstances will choice of forum agreements be applicable? With focus on international arbitration, this article will look into recent developments around the globe and then propose how states in the Asia-Pacific region should approach those issues.
IGA-PD penalty-based coupling for immersed air-blast fluid–structure interaction: a simple and effective solution for fracture and fragmentation
Authors: Behzadinasab Masoud , Hillman Michael , Bazilevs Yuri 
Published: December 2021

Abstract
We present a novel formulation for the immersed coupling of isogeometric analysis and peridynamics for the simulation of fluid–structure interaction (FSI). We focus on air-blast FSI and address the computational challenges of immersed FSI methods in the simulation of fracture and fragmentation by developing a weakly volume-coupled FSI formulation by means of a simple penalty approach. We show the mathematical formulation and present several numerical examples of inelastic ductile and brittle solids under blast loading that clearly demonstrate the power and robustness of the proposed methodology.
Prospects of discovering subsolar primordial black holes using the stochastic gravitational wave background from third-generation detectors
Authors: Mukherjee Suvodip , Meinema Matthew S P , Silk Joseph 
Published: December 2021

ABSTRACT
Primordial black holes (PBHs) are dark matter candidates that span broad mass ranges from 10−17 M⊙ to ∼100 M⊙. We show that the stochastic gravitational wave background can be a powerful window for the detection of subsolar mass PBHs and shed light on their formation channel via third-generation gravitational wave detectors such as Cosmic Explorer and the Einstein Telescope. By using the mass distribution of the compact objects and the redshift evolution of the merger rates, we can distinguish astrophysical sources from PBHs and will be able to constrain the fraction of subsolar mass PBHs ≤1 M⊙ in the form of dark matter $f_\mathrm{PBH}\le 1{{\ \rm per\ cent}}$ at $68{{\ \rm per\ cent}}$ C.L. even for a pessimistic value of a binary suppression factor. In the absence of any suppression of the merger rate, constraints on fPBH will be less than $0.001{{\ \rm per\ cent}}$. Furthermore, we will be able to measure the redshift evolution of the PBH merger rate with about $1{{\ \rm per\ cent}}$ accuracy, making it possible to uniquely distinguish between the Poisson and clustered PBH scenarios.
Detection of 7Be ii in the Small Magellanic Cloud
Authors: Izzo Luca , Molaro Paolo , Cescutti Gabriele , Aydi Elias , Selvelli Pierluigi , Harvey Eamonn , Agnello Adriano , Bonifacio Piercarlo , Della Valle Massimo , Guido Ernesto , Hernanz Margarita 
Published: December 2021

ABSTRACT
We analyse high-resolution spectra of two classical novae that exploded in the Small Magellanic Cloud (SMC). 7Be ii resonance transitions are detected in both ASASSN-19qv and ASASSN-20ni novae. This is the first detection outside the Galaxy and confirms that thermo-nuclear runaway reactions, leading to the 7Be formation, are effective also in the low-metallicity regime, characteristic of the SMC. Derived yields are of N(7Be = 7Li)/N(H) = (5.3 ± 0.2) × 10−6 which are a factor 4 lower than the typical values of the Galaxy. Inspection of two historical novae in the Large Magellanic Cloud observed with IUE in 1991 and 1992 showed also the possible presence of 7Be and similar yields. For an ejecta of MH, ej = 10−5 M⊙, the amount of 7Li produced is of $M_{^7 Li} = (3.7 \pm 0.6) \times 10^{-10}$ M⊙ per nova event. Detailed chemical evolutionary model for the SMC shows that novae could have made an amount of lithium in the SMC corresponding to a fractional abundance of A(Li) ≈ 2.6. Therefore, it is argued that a comparison with the abundance of Li in the SMC, as measured by its interstellar medium, could effectively constrain the amount of the initial abundance of primordial Li, which is currently controversial.
Optical solution to spot elongation in laser guide stars wavefront sensors for Extremely Large Telescopes
Authors: Lombini Matteo , Schreiber Laura , Diolaiti Emiliano , Cortecchia Fausto 
Published: December 2021

ABSTRACTLaser guide stars have been proposed to overcome a widely recognized limitation of adaptive optics: the need for bright reference sources for wavefront sensing nearby the scientific field of interest. The laser guide stars foreseen for the future Extremely Large Telescopes are based on the resonant back-scattering of a laser beam by the Sodium atoms concentrated in a ∼13 km thick layer at about 90 km above the ground. Such an artificial source, observed from a position laterally offset from the laser projector, appears elongated due to the finite thickness of the Sodium layer: on a 40-m class telescope with laser projector located on the primary mirror edge the image elongation may exceed 13 arcsec. In a Shack–Hartmann wavefront sensor, the elongated spots require the use of large detectors to avoid spot truncation and impose demanding requirements in terms of photon flux return with respect to smaller telescopes. We propose an alternative wavefront sensor concept intrinsically insensitive to the spot elongation, measuring the local wavefront slope in the direction orthogonal to the elongation itself; the full 2D slope measurements are retrieved by combining the signals from different laser guide stars, projected from different positions at the edge of the telescope. The performance of the new wavefront sensor is analysed in the framework of a ground-layer adaptive optics application. A possible extension to multiconjugate adaptive optics is also qualitatively described.
Effects of pebble accretion on the growth and composition of planetesimals in the inner Solar system
Authors: Mah J , Brasser R , Bouvier A , Mojzsis S J 
Published: December 2021

ABSTRACT
Recent work has shown that aside from the classical view of collisions by increasingly massive planetesimals, the accretion of mm to m-sized ‘pebbles’ can also reproduce the mass–orbit distribution of the terrestrial planets. Here, we perform N-body simulations to study the effects of pebble accretion on to growing planetesimals of different diameters located in the inner Solar system. The simulations are run to occur during the lifetime of the gas disc while also simultaneously taking Jupiter’s growth into account. We find that pebble accretion can increase the mass in the solid disc by at least a few times its initial mass with reasonable assumptions that pebbles fragment to smaller sized grains at the snow line and that gas-disc-induced orbital migration effects are in force. Such a large contribution in mass by pebbles would seem to imply that the isotopic composition of the inner Solar system should be similar to the pebble source (i.e. outer Solar system). This implication appears to violate the observed nucleosynthetic isotopic dichotomy of the sampled Solar system. Thus, pebble accretion played little or no role in terrestrial planet formation.