bluuebunny/crossref_metadata_2025 huggingface dataset:
Conceptual considerations for using EHR-based activity logs to measure clinician burnout and its effects
Authors: Kannampallil Thomas , Abraham Joanna , Lou Sunny S , Payne Philip R.O
Published: November 2020

Electronic health records (EHR) use is often considered a significant contributor to clinician burnout. Informatics researchers often measure clinical workload using EHR-derived audit logs and use it for quantifying the contribution of EHR use to clinician burnout. However, translating clinician workload measured using EHR-based audit logs into a meaningful burnout metric requires an alignment with the conceptual and theoretical principles of burnout. In this perspective, we describe a systems-oriented conceptual framework to achieve such an alignment and describe the pragmatic realization of this conceptual framework using 3 key dimensions: standardizing the measurement of EHR-based clinical work activities, implementing complementary measurements, and using appropriate instruments to assess burnout and its downstream outcomes. We discuss how careful considerations of such dimensions can help in augmenting EHR-based audit logs to measure factors that contribute to burnout and for meaningfully assessing downstream patient safety outcomes.
A High-Resolution Melting Analysis with an Unlabeled Probe for CRISPR/Cas9-Induced ZBED6 Knockout Pigs Detection
Authors: Liu Xiaofei , Qiu Songyin , Mei Lin , Jing Hongli , Lin Xiangmei , Wang Qin
Published: November 2020

Background

The zinc finger BED-type containing six knockout (ZBED6-KO) pigs were created to improve economic traits by increasing the expression of insulin-like growth factor 2. They were generated by CRISPR/CRISPR-associated protein 9 (Cas9) technology and a single-base deletion of ZBED6 was found. An efficient and rapid method was needed to detect this type of pig.

Objective

This study aimed to develop a high-resolution melting (HRM) method to detect ZBED6-KO pigs.

Methods

An unlabeled probe and two primers were designed to develop the HRM method. The limit of detection, specificity, and accuracy of the established method were tested by the constructed plasmid and DNA extracts of tissue specimens.

Results

The limit of detection by the established method was 102 copies/µL. The HRM method with an unlabeled probe showed good specificity and high accuracy.

Conclusions

The established HRM analysis with an unlabeled probe showed it to be a highly effective, rapid, and reliable method to distinguish ZBED6-KO pigs from wild-type pigs.

Highlights

It is the first time that HRM analysis with an unlabeled probe has been used in the detection of genome editing pigs by the CRISPR/Cas9 technology.
Edible Fruit Plant Species in the Amazon Forest Rely Mostly on Bees and Beetles as Pollinators
Authors: Paz Fabricia Sousa , Pinto Carlos Eduardo , de Brito Rafael Melo , Imperatriz-Fonseca Vera Lucia , Giannini Tereza Cristina
Published: November 2020

Edible fruit plants of tropical forests are important for the subsistence of traditional communities. Understanding the most important pollinators related to fruit and seed production of these plants is a necessary step to protect their pollination service and assure the food security of these communities. However, there are many important knowledge gaps related to floral biology and pollination in megadiverse tropical rainforests, such as the Amazon Forest, due mainly to the high number of plant species. Our study aims to indicate the main pollinators of edible plants (mainly fruits) of the Amazon forest. For this, we adopted a threefold strategy: we built a list of edible plant species, determined the pollination syndrome of each species, and performed a review on the scientific literature searching for their pollinator/visitors. The list of plant species was determined from two specialized publications on Amazon fruit plants, totaling 188 species. The pollination syndrome was determined for 161 species. The syndromes most frequently found among the analyzed species were melittophily (bee pollination), which was found in 101 of the analyzed plant species (54%) and cantharophily (beetle pollination; 26 species; 14%). We also found 238 pollinator/visitor taxa quoted for 52 (28%) plant species in previous publications, with 124 taxa belonging to Apidae family (bees; 52%), mainly from Meliponini tribe (58 taxa; 47%). Knowledge about pollinators is an important step to help on preserving their ecosystem services and maintaining the productivity of fruit trees in the Amazon.
Repetitive Traumatic Brain Injury Is Associated With TDP-43 Alterations, Neurodegeneration, and Glial Activation in Mice
Authors: Rajič Bumber Jelena , Pilipović Kristina , Janković Tamara , Dolenec Petra , Gržeta Nika , Križ Jasna , Župan Gordana
Published: November 2020

Increasing evidence points to a relationship between repetitive mild traumatic brain injury (mTBI), the Tar DNA binding protein 43 (TDP-43) pathology and some neurodegenerative diseases, but the underlying pathophysiological mechanisms are still unknown. We examined TDP-43 regulation, neurodegeneration, and glial responses following repetitive mTBI in nontransgenic mice and in animals with overexpression of human mutant TDP-43 protein (TDP-43G348C). In the frontal cortices of the injured nontransgenic animals, early TDP-43 cytoplasmatic translocation and overexpression of the protein and its pathological forms were detected. In the injured animals of both genotypes, neurodegeneration and pronounced glial activity were detected in the optic tract. In TDP-43G348C mice, these changes were significantly higher at day 7 after the last mTBI compared with the values in the nontransgenic animals. Results of this study suggest that the changes in the TDP-43 regulation in the frontal cortices of the nontransgenic animals were a transient stress response to the brain injury. Repetitive mTBI did not produce additional TDP-43 dysregulation or neurodegeneration or pronounced gliosis in the frontal cortex of TDP-43G348C mice. Our research also suggests that overexpression of mutated human TDP-43 possibly predisposes the brain to more intense neurodegeneration and glial activation in the optic tract after repetitive mTBI.
Combining Hypothermia and Oleuropein Subacutely Protects Subcortical White Matter in a Swine Model of Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Lee Jennifer K , Santos Polan T , Chen May W , O’Brien Caitlin E , Kulikowicz Ewa , Adams Shawn , Hardart Henry , Koehler Raymond C , Martin Lee J
Published: November 2020

Neonatal hypoxia-ischemia (HI) causes white matter injury that is not fully prevented by therapeutic hypothermia. Adjuvant treatments are needed. We compared myelination in different piglet white matter regions. We then tested whether oleuropein (OLE) improves neuroprotection in 2- to 4-day-old piglets randomized to undergo HI or sham procedure and OLE or vehicle administration beginning at 15 minutes. All groups received overnight hypothermia and rewarming. Injury in the subcortical white matter, corpus callosum, internal capsule, putamen, and motor cortex gray matter was assessed 1 day later. At baseline, piglets had greater subcortical myelination than in corpus callosum. Hypothermic HI piglets had scant injury in putamen and cerebral cortex. However, hypothermia alone did not prevent the loss of subcortical myelinating oligodendrocytes or the reduction in subcortical myelin density after HI. Combining OLE with hypothermia improved post-HI subcortical white matter protection by preserving myelinating oligodendrocytes, myelin density, and oligodendrocyte markers. Corpus callosum and internal capsule showed little HI injury after hypothermia, and OLE accordingly had minimal effect. OLE did not affect putamen or motor cortex neuron counts. Thus, OLE combined with hypothermia protected subcortical white matter after HI. As an adjuvant to hypothermia, OLE may subacutely improve regional white matter protection after HI.
Clinical-Pathological, Immunohistochemical, and Genetic Characterization of a Series of Posterior Pituitary Tumors
Authors: Barresi Valeria , Simbolo Michele , Gessi Marco , Rossi Sabrina , Caffo Maria , Eccher Albino , Angileri Filippo Flavio , Cannavò Salvatore , Brunelli Matteo , Scarpa Aldo
Published: November 2020

Posterior pituitary tumors are supposed to represent the morphological spectrum of a single entity. Herein, we report the clinical-pathological, immunohistochemical, and genetic features of 5 spindle cell oncocytomas (SCOs), 3 pituicytomas, and 1 granular cell tumor (GCT). SCOs had the highest local invasiveness and affected older subjects. The 3 histotypes differed in the content of spindle cells (predominant in pituicytoma and absent in GCT), presence of lymphocytic infiltrate (in SCO and GCT, but not in the pituicytoma) and EMA/GFAP staining (negative in GCT; EMA-positive/GFAP-negative in 4/5 SCO and GFAP-positive in 3/3 pituicytomas). Three SCOs and 1 pituicytoma analyzed with next-generation sequencing had no mutations in 409 genes. However, 1 SCO had previously unreported homozygous deletion of CDKN2A/B and another of SMARCA4, SMARCB1, and NF2. All 3 SCOs had loss of heterozygosity of chromosome 1p, while the pituicytoma had chromosome 19 homozygous loss and chromosomes 10, 13q, and 18q loss of heterozygosity. Since 1p and 13q losses were previously reported in 1 pituicytoma and 1 SCO, respectively, our data demonstrate that posterior pituitary tumors share common genetic alterations. The possibility that posterior pituitary tumors are SMARCA4/SMARCB1-deficient should be kept in mind in the differential diagnosis toward other entities.
Acute calcific periarthritis secondary to calcium hydroxyapatite crystal deposition in the wrist: a case report
Authors: Walker Joseph A , McLean Elizabeth R , Anakwe Raymond E
Published: November 2020

Acute calcific periarthritis (ACP) is an unusual cause of monoarticular pain characterised by the deposition of calcium hydroxyapatite in the peri-articular and intra-articular tissues. Although the most commonly affected joint is the shoulder, other joints may be involved, including the wrist. This case report describes a 57-year-old female presenting with wrist pain and swelling associated with amorphous calcification overlying the lunate. The patient improved with the use of non-steroidal anti-inflammatory drugs and splinting. Clinician awareness of the clinical presentation and radiographic features of ACP is important to reduce unnecessary invasive diagnostic procedures such as joint aspiration.
Pott’s puffy tumour in an immunosuppressed adult: case report and systematic review of literature
Authors: Paw Ekta , Ong Chelsea T W , Vangaveti Venkat
Published: November 2020

This case is of a 34-year-old immunocompromised male with Pott’s puffy tumour, which was treated with antibiotics and endoscopic sinus surgery. Pott’s puffy tumour is typically a complication of frontal sinusitis in children and immunocompromise can be a precipitating factor.

A search was conducted of Embase, Medline, CINAHL, Cochrane, Google Scholar, Informit and Scopus of ‘Pott’s Puffy’ and variations of this phrase. Initial 804 records were reviewed by title, abstract and full text.

Of the unique papers identified, 155 only included paediatric patients and 128 included adult patients. After title, abstract and full-text review of 13 papers were identified describing Pott’s puffy tumour in immunocompromised patients.

Immunosuppression was noted as a risk factor in only a small number of cases, with diabetes mellitus being the most common. A few cases did note immunosuppression due to newer immunomodulatory agents being used for treatment of autoimmune conditions.
The Ursa Major association of galaxies – VI: a relative dearth of gas-rich dwarf galaxies
Authors: Busekool E , Verheijen M A W , van der Hulst J M , Tully R B , Trentham N , Zwaan M A
Published: November 2020

We determined the H i mass function of galaxies in the Ursa Major association of galaxies using a blind Very Large Array (VLA) D-array survey, consisting of 54 pointings in a cross-pattern, covering the centre as well as the outskirts of the Ursa Major volume. The calculated H i mass function has best-fitting Schechter parameters θ* = 0.19 ± 0.11 Mpc−3, log $\mbox{$M^*_{\rm H\,{\small I}}$}\ /\mathrm{ M}_{\odot } = 9.8 \pm 0.8$, and α = −0.92 ± 0.16. The high-mass end is determined by a complementary, targeted Westerbork Synthesis Radio Telescope (WSRT) survey, and the low-mass end is determined by the blind VLA survey. The slope is significantly shallower than the slopes of the H i Parkes All Sky Survey (α = −1.37 ± 0.03 ± 0.05) and Arecibo Legacy Fast Arecibo L-band Feed Array (α = −1.33 ± 0.02) H i mass functions, which are measured over much larger volumes and cover a wider range of cosmic environments: There is a relative lack of low-H i mass galaxies in the Ursa Major region. This difference in the slope strongly hints at an environmental dependence of the H i mass function slope.
Colliding stellar wind modelling of the X-ray emission from WR 140
Authors: Zhekov Svetozar A
Published: November 2020

We modelled the Chandra and Rossi X-ray Timing Explorer X-ray spectra of the massive binary WR 140 in the framework of the standard colliding stellar wind (CSW) picture. Models with partial electron heating at the shock fronts are a better representation of the X-ray data than those with complete temperature equalization. Emission measure of the X-ray plasma in the CSW region exhibits a considerable decrease at orbital phases near periastron. This is equivalent to variable effective mass-loss rates over the binary orbit. At orbital phases near periastron, a considerable X-ray absorption in excess to that from the stellar winds in WR 140 is present. The standard CSW model provides line profiles that in general do not match well the observed line profiles of the strong line features in the X-ray spectrum of WR 140. The variable effective mass-loss rate could be understood qualitatively in CSW picture of clumpy stellar winds where clumps are efficiently dissolved in the CSW region near apastron but not at periastron. However, future development of CSW models with non-spherically symmetric stellar winds might be needed to get a better correspondence between theory and observations.
Are stellar-mass binary black hole mergers isotropically distributed?
Authors: Stiskalek Richard , Veitch John , Messenger Chris
Published: November 2020

The Advanced LIGO and Advanced Virgo gravitational wave detectors have detected a population of binary black hole mergers in their first two observing runs. For each of these events, we have been able to associate a potential sky location region represented as a probability distribution on the sky. Thus, at this point we may begin to ask the question of whether this distribution agrees with the isotropic model of the Universe, or if there is any evidence of anisotropy. We perform Bayesian model selection between an isotropic and a simple anisotropic model, taking into account the anisotropic selection function caused by the underlying antenna patterns and sensitivity of the interferometers over the sidereal day. We find an inconclusive Bayes factor of 1.3: 1, suggesting that the data from the first two observing runs are insufficient to pick a preferred model. However, the first detections were mostly poorly localized in the sky (before the Advanced Virgo joined the network), spanning large portions of the sky and hampering detection of potential anisotropy. It will be appropriate to repeat this analysis with events from the recent third LIGO observational run and a more sophisticated cosmological model.
Multifrequency study of a double–double radio galaxy J0028+0035
Authors: Marecki A , Jamrozy M , Machalski J , Pajdosz-Śmierciak U
Published: November 2020

We report the discovery of a double–double radio source (DDRS) J0028+0035. We observed it with LOFAR, GMRT, and the VLA. By combining our observational data with those from the literature, we gathered an appreciable set of radio flux density measurements covering the range from 74 MHz to 14 GHz. This enabled us to carry out an extensive review of physical properties of the source and its dynamical evolution analysis. In particular, we found that, while the age of the large-scale outer lobes is about 245 Myr, the renewal of the jet activity, which is directly responsible for the double–double structure, took place only about 3.6 Myr ago after about 11 Myr long period of quiescence. Another important property typical for DDRSs and also present here is that the injection spectral indices for the inner and the outer pair of lobes are similar. The jet powers in J0028+0035 are similar too. Both these circumstances support our inference that it is, in fact, a DDRS which was not recognized as such so far because of the presence of a coincident compact object close to the inner double so that the centre of J0028+0035 is apparently a triple.
Intermediate mass black hole formation in compact young massive star clusters
Authors: Rizzuto Francesco Paolo , Naab Thorsten , Spurzem Rainer , Giersz Mirek , Ostriker J P , Stone N C , Wang Long , Berczik Peter , Rampp M
Published: November 2020

Young dense massive star clusters are promising environments for the formation of intermediate mass black holes (IMBHs) through collisions. We present a set of 80 simulations carried out with nbody6++gpu of 10 models of compact $\sim 7 \times 10^4 \, \mathrm{M}_{\odot }$ star clusters with half-mass radii Rh ≲ 1 pc, central densities $\rho _\mathrm{core} \gtrsim 10^5 \, \mathrm{M}_\odot \, \mathrm{pc}^{-3}$, and resolved stellar populations with 10 per cent primordial binaries. Very massive stars (VMSs) up to $\sim 400 \, \mathrm{M}_\odot$ grow rapidly by binary exchange and three-body scattering with stars in hard binaries. Assuming that in VMS–stellar black hole (BH) collisions all stellar material is accreted on to the BH, IMBHs with masses up to $M_\mathrm{BH} \sim 350 \, \mathrm{M}_\odot$ can form on time-scales of ≲15 Myr, as qualitatively predicted from Monte Carlo mocca simulations. One model forms an IMBH of 140 $\mathrm{M_{\odot }}$ by three BH mergers with masses of 17:28, 25:45, and 68:70 $\mathrm{M_{\odot }}$ within ∼90 Myr. Despite the stochastic nature of the process, formation efficiencies are higher in more compact clusters. Lower accretion fractions of 0.5 also result in IMBH formation. The process might fail for values as low as 0.1. The IMBHs can merge with stellar mass BHs in intermediate mass ratio inspiral events on a 100 Myr time-scale. With 105 stars, 10 per cent binaries, stellar evolution, all relevant dynamical processes, and 300 Myr simulation time, our large suite of 80 simulations indicate another rapid IMBH formation channel in young and compact massive star clusters.
Multi-frequency temporal and spectral variability study of blazar PKS 1424−418
Authors: Abhir J , Joseph J , Patel S R , Bose D
Published: November 2020

A study of blazar PKS 1424−418 was carried out using multi-waveband data collected by the Fermi Large Area Telescope (Fermi-LAT), Swift X-Ray Telescope (Swift-XRT), Swift UltraViolet and Optical Telescope (Swift-UVOT), and Small and Moderate Aperture Research Telescope System (SMARTS) between MJD 56000 and MJD 56600 (2012 March 14–2013 November 4). Two flaring episodes were identified by analysing the gamma-ray light curve. Simultaneous multi-waveband spectral energy distributions (SEDs) were obtained for those two flaring periods. A cross-correlation analysis of infrared (IR)–optical and γ-ray data suggested that the emission originated from the same region. We have set a lower limit for the Doppler factor using the highest energy photon observed from this source during the flaring periods, which should be >12. The broad-band emission mechanism was studied by modelling the SED using the leptonic emission mechanism.
The SALT survey of helium-rich hot subdwarfs: methods, classification, and coarse analysis
Authors: Jeffery C S , Miszalski B , Snowdon E
Published: November 2020

A medium- and high-resolution spectroscopic survey of helium-rich hot subdwarfs is being carried out using the Southern African Large Telescope (SALT). Objectives include the discovery of exotic hot subdwarfs and of sequences connecting chemically peculiar subdwarfs of different types. The first phase consists of medium-resolution spectroscopy of over 100 stars selected from low-resolution surveys. This paper describes the selection criteria, and the observing, classification, and analysis methods. It presents 107 spectral classifications on the MK-like Drilling system and 106 coarse analyses (${T_{\rm eff}}, \log g, \log y$) based on a hybrid grid of zero-metal non-LTE and line-blanketed LTE model atmospheres. For 75 stars, atmospheric parameters have been derived for the first time. The sample may be divided into six distinct groups including the classical ‘helium-rich’ sdO stars with spectral types (Sp) sdO6.5–sdB1 (74) comprising carbon-rich (35) and carbon-weak (39) stars, very hot He-sdO’s with Sp ≲ sdO6 (13), extreme helium stars with luminosity class ≲5 (5), intermediate helium-rich subdwarfs with helium class 25–35 (8), and intermediate helium-rich subdwarfs with helium class 10–25 (6). The last covers a narrow spectral range (sdB0–sdB1) including two known and four candidate heavy-metal subdwarfs. Within other groups are several stars of individual interest, including an extremely metal-poor helium star, candidate double-helium subdwarf binaries, and a candidate low-gravity He-sdO star.
Species cycling and the enhancement of ammonia in pre-stellar cores
Authors: von Procházka Azrael A , Millar T J
Published: November 2020

The quantity of NH3 produced on grain surfaces in the pre-stellar core is thought to be one of the determining factors regarding the chemical complexity achievable at later stages of stellar birth. In order to investigate how this quantity might be influenced by the gas–grain cycling of molecular material within the cloud, we employ a modified rates gas–grain chemical code and follow the time-dependent chemistry of NH3 as the system evolves. Our models incorporate an updated version of the most recent UDfA network of reaction rate coefficients, desorption from the grains through standard thermal and non-thermal processes, and physisorbed and chemisorbed binding of atomic and molecular hydrogen to a population of carbonaceous and siliceous grains. We find that (1) observable abundances of NH3 can exist in the gas phase of our models at early times when the N atom is derived from CN via an efficient early-time hydrocarbon chemistry, (2) a time-dependent gradient exists in the observational agreement between different species classes in our models, consistent with possible physical substructures within the TMC-1 Cyanopolyyne Peak, and (3) the gaseous and solid-state abundances of NH3 are sensitive to the presence of gas–grain cycling within the system. Our results suggest that the degree of chemical complexity achievable at later stages of the cloud’s chemical evolution is indeed influenced by the manner in which the gas–grain cycling occurs.
The Gaia spectrophotometric standard stars survey – IV. Results of the absolute photometry campaign
Authors: Altavilla G , Marinoni S , Pancino E , Galleti S , Bellazzini M , Sanna N , Rainer M , Tessicini G , Carrasco J M , Bragaglia A , Schuster W J , Cocozza G , Gebran M , Voss H , Federici L , Masana E , Jordi C , Monguió M , Castro A , Peña-Guerrero M A , Pérez-Villegas A
Published: November 2020

We present Johnson–Kron–Cousins BVRI photometry of 228 candidate spectrophotometric standard stars for the external (absolute) flux calibration of Gaia data. The data were gathered as part of a 10-yr observing campaign with the goal of building the external grid of flux standards for Gaia and we obtained absolute photometry, relative photometry for constancy monitoring, and spectrophotometry. Preliminary releases of the flux tables were used to calibrate the first two Gaia releases. This paper focuses on the imaging frames observed in good sky conditions (about 9100). The photometry will be used to validate the ground-based flux tables of the Gaia spectrophotometric standard stars and to correct the spectra obtained in non-perfectly photometric observing conditions for small zero-point variations. The absolute photometry presented here is tied to the Landolt standard stars system to ≃1 per cent or better, depending on the photometric band. Extensive comparisons with various literature sources show an overall ≃1 per cent agreement, which appears to be the current limit in the accuracy of flux calibrations across various samples and techniques in the literature. The Gaia photometric precision is presently of the order of 0.1 per cent or better, thus various ideas for the improvement of photometric calibration accuracy are discussed.
Origins and Long-Term Patterns of Copy-Number Variation in Rhesus Macaques
Authors: Thomas Gregg W C , Wang Richard J , Nguyen Jelena , Alan Harris R , Raveendran Muthuswamy , Rogers Jeffrey , Hahn Matthew W
Published: November 2020

Mutations play a key role in the development of disease in an individual and the evolution of traits within species. Recent work in humans and other primates has clarified the origins and patterns of single-nucleotide variants, showing that most arise in the father’s germline during spermatogenesis. It remains unknown whether larger mutations, such as deletions and duplications of hundreds or thousands of nucleotides, follow similar patterns. Such mutations lead to copy-number variation (CNV) within and between species, and can have profound effects by deleting or duplicating genes. Here, we analyze patterns of CNV mutations in 32 rhesus macaque individuals from 14 parent–offspring trios. We find the rate of CNV mutations per generation is low (less than one per genome) and we observe no correlation between parental age and the number of CNVs that are passed on to offspring. We also examine segregating CNVs within the rhesus macaque sample and compare them to a similar data set from humans, finding that both species have far more segregating deletions than duplications. We contrast this with long-term patterns of gene copy-number evolution between 17 mammals, where the proportion of deletions that become fixed along the macaque lineage is much smaller than the proportion of segregating deletions. These results suggest purifying selection acting on deletions, such that the majority of them are removed from the population over time. Rhesus macaques are an important biomedical model organism, so these results will aid in our understanding of this species and the disease models it supports.
Photoreceptor Diversification Accompanies the Evolution of Anthozoa
Authors: Gornik Sebastian G , Bergheim Bruno Gideon , Morel Benoit , Stamatakis Alexandros , Foulkes Nicholas S , Guse Annika
Published: November 2020

Anthozoan corals are an ecologically important group of cnidarians, which power the productivity of reef ecosystems. They are sessile, inhabit shallow, tropical oceans and are highly dependent on sun- and moonlight to regulate sexual reproduction, phototaxis, and photosymbiosis. However, their exposure to high levels of sunlight also imposes an increased risk of UV-induced DNA damage. How have these challenging photic environments influenced photoreceptor evolution and function in these animals? To address this question, we initially screened the cnidarian photoreceptor repertoire for Anthozoa-specific signatures by a broad-scale evolutionary analysis. We compared transcriptomic data of more than 36 cnidarian species and revealed a more diverse photoreceptor repertoire in the anthozoan subphylum than in the subphylum Medusozoa. We classified the three principle opsin classes into distinct subtypes and showed that Anthozoa retained all three classes, which diversified into at least six subtypes. In contrast, in Medusozoa, only one class with a single subtype persists. Similarly, in Anthozoa, we documented three photolyase classes and two cryptochrome (CRY) classes, whereas CRYs are entirely absent in Medusozoa. Interestingly, we also identified one anthozoan CRY class, which exhibited unique tandem duplications of the core functional domains. We next explored the functionality of anthozoan photoreceptors in the model species Exaiptasia diaphana (Aiptasia), which recapitulates key photo-behaviors of corals. We show that the diverse opsin genes are differentially expressed in important life stages common to reef-building corals and Aiptasia and that CRY expression is light regulated. We thereby provide important clues linking coral evolution with photoreceptor diversification.
Design of experimental food patches to measure foraging intensity for octopus: a case study with the giant Pacific octopusEnteroctopus dofleini
Authors: Chancellor Stephanie , Scheel David , Brown Joel S
Published: November 2020

In a study of the foraging behaviour of the giant Pacific octopus Enteroctopus dofleini, we designed two types of experimental food patches to measure habitat preferences and perceptions of predation risk. The first patch successfully measured giving-up densities (GUDs), confirmed by octopus prey presence and higher foraging at sites with historically greater octopus presence. However, nontarget foragers also foraged on these experimental food patches. Our second floating patch design successfully excluded nontarget species from subtidal patches, and from intertidal patches at high tide, but allowed for foraging by E. dofleini. The second design successfully measured GUDs and suggested that octopus preferred foraging in a subtidal habitat compared to an intertidal habitat. We ascribe the higher GUD in the intertidal habitat to its higher predation risk relative to the subtidal habitat. The second patch design seems well suited for E. dofleini and, in conjunction with a camera system, could be used to provide behavioural indicators of the octopus's abundance, perceptions of habitat quality and predation risk.
VEZF1–guanine quadruplex DNA interaction regulates alternative polyadenylation and detyrosinase activity of VASH1
Authors: Li Lin , Williams Preston , Gao Zi , Wang Yinsheng
Published: November 2020

Vascular endothelial zinc finger 1 (VEZF1) plays important roles in endothelial lineage definition and angiogenesis. Vasohibins 1 and 2 (VASH1 and VASH2) can form heterodimers with small vasohibin-binding protein (SVBP) and were recently shown to regulate angiogenesis by acting as tubulin detyrosinases. Here, we showed that VEZF1 binds directly with DNA guanine quadruplex (G quadruplex, G4) structures in vitro and in cells, which modulates the levels of the two isoforms of VASH1 mRNA. Disruption of this interaction, through genetic depletion of VEZF1 or treatment of cells with G4-stabilizing small molecules, led to increased production of the long over short isoform of VASH1 (i.e. VASH1A and VASH1B, respectively) mRNA and elevated tubulin detyrosinase activity in cells. Moreover, disruption of VEZF1-G4 interactions in human umbilical vein endothelial cells resulted in diminished angiogenesis. These results suggest that the interaction between VEZF1 and G4 structures assumes a crucial role in angiogenesis, which occurs through regulating the relative levels of the two isoforms of VASH1 mRNA and the detyrosinase activity of the VASH1-SVBP complex. Together, our work revealed VEZF1 as a G4-binding protein, identified a novel regulatory mechanism for tubulin detyrosinase, and illustrated that the VEZF1- and VASH1-mediated angiogenesis pathways are functionally connected.
NGS-based identification and tracing of microsatellite instability from minute amounts DNA using inter-Alu-PCR
Authors: Yu Fangyan , Leong Ka Wai , Makrigiorgos Alexander , Adalsteinsson Viktor A , Ladas Ioannis , Ng Kimmie , Mamon Harvey , Makrigiorgos G Mike
Published: November 2020

Sensitive detection of microsatellite instability (MSI) in tissue or liquid biopsies using next generation sequencing (NGS) has growing prognostic and predictive applications in cancer. However, the complexities of NGS make it cumbersome as compared to established multiplex-PCR detection of MSI. We present a new approach to detect MSI using inter-Alu-PCR followed by targeted NGS, that combines the practical advantages of multiplexed-PCR with the breadth of information provided by NGS. Inter-Alu-PCR employs poly-adenine repeats of variable length present in every Alu element and provides a massively-parallel, rapid approach to capture poly-A-rich genomic fractions within short 80–150bp amplicons generated from adjacent Alu-sequences. A custom-made software analysis tool, MSI-tracer, enables Alu-associated MSI detection from tissue biopsies or MSI-tracing at low-levels in circulating-DNA. MSI-associated indels at somatic-indel frequencies of 0.05–1.5% can be detected depending on the availability of matching normal tissue and the extent of instability. Due to the high Alu copy-number in human genomes, a single inter-Alu-PCR retrieves enough information for identification of MSI-associated-indels from ∼100 pg circulating-DNA, reducing current limits by ∼2-orders of magnitude and equivalent to circulating-DNA obtained from finger-sticks. The combined practical and informational advantages of inter-Alu-PCR make it a powerful tool for identifying tissue-MSI-status or tracing MSI-associated-indels in liquid biopsies.
Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast
Authors: Rubio Angela , Ghosh Sanjay , Mülleder Michael , Ralser Markus , Mata Juan
Published: November 2020

Translational control is essential in response to stress. We investigated the translational programmes launched by the fission yeast Schizosaccharomyces pombe upon five environmental stresses. We also explored the contribution of defence pathways to these programmes: The Integrated Stress Response (ISR), which regulates translation initiation, and the stress-response MAPK pathway. We performed ribosome profiling of cells subjected to each stress, in wild type cells and in cells with the defence pathways inactivated. The transcription factor Fil1, a functional homologue of the yeast Gcn4 and the mammalian Atf4 proteins, was translationally upregulated and required for the response to most stresses. Moreover, many mRNAs encoding proteins required for ribosome biogenesis were translationally downregulated. Thus, several stresses trigger a universal translational response, including reduced ribosome production and a Fil1-mediated transcriptional programme. Surprisingly, ribosomes stalled on tryptophan codons upon oxidative stress, likely due to a decrease in charged tRNA-Tryptophan. Stalling caused ribosome accumulation upstream of tryptophan codons (ribosome queuing/collisions), demonstrating that stalled ribosomes affect translation elongation by other ribosomes. Consistently, tryptophan codon stalling led to reduced translation elongation and contributed to the ISR-mediated inhibition of initiation. We show that different stresses elicit common and specific translational responses, revealing a novel role in Tryptophan-tRNA availability.
Nucleotide resolution profiling of m3C RNA modification by HAC-seq
Authors: Cui Jia , Liu Qi , Sendinc Erdem , Shi Yang , Gregory Richard I
Published: November 2020

Cellular RNAs are subject to a myriad of different chemical modifications that play important roles in controlling RNA expression and function. Dysregulation of certain RNA modifications, the so-called ‘epitranscriptome’, contributes to human disease. One limitation in studying the functional, physiological, and pathological roles of the epitranscriptome is the availability of methods for the precise mapping of individual RNA modifications throughout the transcriptome. 3-Methylcytidine (m3C) modification of certain tRNAs is well established and was also recently detected in mRNA. However, methods for the specific mapping of m3C throughout the transcriptome are lacking. Here, we developed a m3C-specific technique, Hydrazine-Aniline Cleavage sequencing (HAC-seq), to profile the m3C methylome at single-nucleotide resolution. We applied HAC-seq to analyze ribosomal RNA (rRNA)-depleted total RNAs in human cells. We found that tRNAs are the predominant m3C-modified RNA species, with 17 m3C modification sites on 11 cytoplasmic and 2 mitochondrial tRNA isoacceptors in MCF7 cells. We found no evidence for m3C-modification of mRNA or other non-coding RNAs at comparable levels to tRNAs in these cells. HAC-seq provides a novel method for the unbiased, transcriptome-wide identification of m3C RNA modification at single-nucleotide resolution, and could be widely applied to reveal the m3C methylome in different cells and tissues.
Ultrafiltration rate and incident atrial fibrillation among older individuals initiating hemodialysis
Authors: Flythe Jennifer E , Liu Sai , Montez-Rath Maria E , Winkelmayer Wolfgang C , Chang Tara I
Published: November 2020

Background

Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients.

Methods

We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67 years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of delivered UF rate and incident atrial fibrillation.

Results

Among the 15 414 individuals included in the study, 3177 developed atrial fibrillation. In fully adjusted models, a UF rate >13 mL/h/kg (versus ≤13 mL/h/kg) was associated with a higher hazard of incident atrial fibrillation [adjusted HR 1.19 (95% CI 1.07–1.30)]. Analyses using lower UF rate thresholds (≤10 versus >10 mL/h/kg and ≤8 versus >8 mL/h/kg, separately) yielded similar results. Analyses specifying the UF rate as a cubic spline (per 1 mL/h/kg) confirmed an approximately linear dose–response relationship between the UF rate and the risk of incident atrial fibrillation: risk began at UF rates of ~6 mL/h/kg and the magnitude of this risk flattened, but remained elevated, at rates ≥9 mL/h/kg.

Conclusion

In this observational study of older individuals initiating hemodialysis, higher UF rates were associated with higher incidences of atrial fibrillation.
The effect of admission and pre-admission serum creatinine as baseline to assess incidence and outcomes of acute kidney injury in acute medical admissions
Authors: Pickup Luke , Loutradis Charalampos , Law Jonathan P , Arnold Julia J , Dasgupta Indranil , Sarafidis Pantelis , Townend Jonathan N , Cockwell Paul , Ferro Charles J
Published: November 2020

Background

Acute kidney injury (AKI) in hospital-admitted patients is a common complication associated with increased mortality. The diagnosis of AKI relies on the ascertainment of peak increase in serum creatinine (SCr). This study evaluated the incidence of AKI using the increase from mean 7–365 days pre-admission (AKIpre) and admission (AKIadm) SCr levels, and examined the associations of AKI and changes in SCr levels with all-cause mortality.

Methods

A total of 2436 patients admitted to a tertiary hospital were recruited and followed-up for a median of 47.70 (interquartile range 18.20) months. AKI incidence and severity were defined according to the Kidney Disease: Improving Global Outcomes-AKI Guidelines. Follow-up data were collected from the Hospital Episode Statistics and Office of National Statistics. Mortality was evaluated during a short- (30 days), mid- (1 year) and long-term (4 years) period.

Results

No difference in the AKI rates using AKIpre and AKIadm (12.5% versus 12.2%; P = 0.695) or in the AKI severity (P = 0.261) was evident. Agreement between the two definitions was modest (Kappa-statistic = 0.596, P < 0.001). Patients with AKIpre or AKIadm had increased all-cause mortality compared with those without AKI during all follow-up periods. In fully adjusted regression analysis, AKIpre [hazard ratio (HR) = 2.226, 95% confidence interval (CI) 1.140–4.347; P = 0.027] and AKIadm (HR = 2.105, 95% CI 1.090–4.064; P = 0.027) remained associated with 30-day mortality. Results for the 1- and 4-year periods were similar. Increases of >4.00 μmol/L and >6.06% from pre-admission or >6.00 μmol/L and >17.24% from admission SCr levels presented increased mortality risk during follow-up.

Conclusions

Use of admission or pre-admission SCr provides similar incidence rates, but they diagnose different sets of patients. Even minor increases in SCr, below those required for the classification of AKI, were associated with increased mortality. These findings can help the clinicians to identify patients at higher risk for adverse outcomes.
Prospective, Multicenter Clinical Study of Microvascular Decompression for Hemifacial Spasm
Authors: Mizobuchi Yoshifumi , Nagahiro Shinji , Kondo Akinori , Arita Kazunori , Date Isao , Fujii Yukihiko , Fujimaki Takamitsu , Hanaya Ryosuke , Hasegawa Mitsuhiro , Hatayama Toru , Hongo Kazuhiro , Inoue Tooru , Kasuya Hidetoshi , Kobayashi Masahito , Kohmura Eiji , Matsushima Toshio , Masuoka Jun , Morita Akio , Munemoto Shigeru , Nishizawa Shigeru , Okayama Yoshihiro , Sato Kimitoshi , Shigeno Taku , Shimano Hiroshi , Takeshima Hideo , Tanabe Hideki , Yamakami Iwao
Published: November 2020

BACKGROUND

Microvascular decompression (MVD) is the most effective procedure for hemifacial spasm (HFS). MVD results from nonspecialized or low-volume institutes are not always reliable. Most studies on MVD for HFS are retrospective and single centered; to the best of our knowledge, no prospective, multicenter studies exist.

OBJECTIVE

To evaluate short- and long-term outcomes and complications in patients who underwent MVD for HFS in specialized Japanese institutions, in this multicenter, prospective, cohort study.

METHODS

Included patients had undergone MVD for HFS in study centers between April 2012 and March 2015. Patients’ postoperative grade of involuntary movements and complications were recorded postoperatively at 7 d (short-term) and at 1 (mid-term) and 3 (long-term) yr.

RESULTS

A total of 486 patients (150 men, 336 women; mean age 53.9 yr with 181 patients over 60 yr) were enrolled during the study period. Neuromonitoring was used in 96.3% of the cases. The complete cure rate of symptom relief, mortality rate, and complication rate at short-term follow-up were 70.6%, 0%, and 15%, respectively. The long-term follow-up was completed by 463 patients (95.3%); the complete cure rate of symptom relief and complication rate were 87.1% and 3.0%, respectively.

CONCLUSION

Our study revealed that under expert guidance and intraoperative neuromonitoring, the long-term curative effect rate of MVD for HFS is high, while complications are uncommon and usually transient. Our results indicate that MVD is an effective and safe treatment for patients with HFS, including elderly patients.
Interferon-related gene expression in response to TNF inhibitor treatment in ankylosing spondylitis patients: a pilot study
Authors: Harrison Stephanie R , Burska Agata N , Emery Paul , Marzo-Ortega Helena , Ponchel Frederique
Published: November 2020

Objective

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis primarily affecting the spine and sacroiliac joints. TNF inhibitor (TNFi) drugs are recommended for patients not responding to NSAIDs; however, there is a significant need for biomarkers of response. IFN-regulated genes (IRGs) and other cytokines/chemokines are linked to autoimmune diseases and have been associated with treatment response. Our objective was to explore whether IRGs and cytokines/chemokines can be associated with response to TNFiagents in AS.

Methods

Peripheral blood mononuclear cells were obtained from 26 AS patients who were to receive a TNFi (I, n = 15) or placebo (P, n = 11) at week 0 and week 22. Response (R)/non-response (NR) was defined as reduction in ASDAS ≥ 1.2 points or reduction in sacroiliac/vertebral MRI lesions. The expression of 96 genes was quantified using TaqMan assays. Finally, ELISA was used to measure IL-6 in serum samples from another 38 AS patients.

Results

Analysis of gene expression in 26 baseline samples segregated patients into four groups defined by a signature of 15 genes (mainly IRGs). ASDAS response was associated with one group independently of treatment received. We then analysed response to the TNFi (n = 15) and identified a 12-gene signature associated with MRI response. A third IRG signature was also associated with a reduction in IRGs expression post-TNFi samples (n = 10 pairs). Finally, decreased circulating IL-6 was associated with BASDAI-R.

Conclusion

This pilot study suggests an association between IRG expression and response to TNFi in AS. These findings require validation in a larger cohort in order to construct predictive algorithms for patient stratification.
The influence of prior intention on joint action: an fNIRS-based hyperscanning study
Authors: Chen Yixin , Zhang Qihan , Yuan Sheng , Zhao Bingjie , Zhang Peng , Bai Xuejun
Published: November 2020

Motor performances of the same action are affected by prior intentions to move unintentionally, cooperatively or competitively. Here, a back-and-forth movement task combined with a motion capture system and functional near-infrared spectroscopy (fNIRS)-based hyperscanning technology was utilized to record both the behavioral and neural data of 18 dyads of participants acting in pairs [joint conditions: no-intention, cooperative (Coop) and competitive (Comp)] or alone (single conditions: self-paced and fast-speed). The results revealed that Coop or Comp intentions in the joint conditions significantly sped up motor performance compared with similar single conditions, e.g. shorter movement times (MTs) in the Coop/Comp condition than the self-paced/fast-speed condition. Hemodynamic response analysis demonstrated that stronger activities for all joint conditions than the single conditions in the premotor and the supplementary motor cortex (Brodmann area 6) were independent of variations of MTs, indicating that they might reflect more complex aspects of action planning rather than simple execution-based processes. The comparisons of joint conditions across distinct prior intentions before acting yielded significant results for both behavioral and neural measures, with the highest activation of the temporo-parietal junction (TPJ) and the shortest MTs in the Comp condition considered to be implications for the top-down influence of prior intentions on joint performance.
Effective science and technology assessment advice for congress: comparing options
Authors: Blair Peter D
Published: November 2020

Effective science and technology (S&T) assessment capabilities providing advice for Congress must be both credible and suitable to congressional needs. To be credible, from the perspective of those who will use the advice, its provision must be (1) authoritative, (2) objective, and (3) independent. To be suitable, the advice must be (4) relevant, (5) useful, and (6) timely. For S&T advice today, Congress draws on many sources but four traditional options stand out as having been used most frequently: (1) The National Research Council, the operating arm of the National Academies of Sciences, Engineering and Medicine, (2) The Congressional Research Service, (3) the former Office of Technology Assessment, and (4) the Government Accountability Office. This article chronicles the evolution of these four organizations and evaluates their relative strengths and weaknesses in terms of the six defined key characteristics for providing effective S&T advice for Congress, drawing conclusions for organizational improvements.