bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug repositioning as a therapeutic strategy for neurodegenerations associated with OPA1 mutations
Authors: Aleo Serena J , Del Dotto Valentina , Fogazza Mario , Maresca Alessandra , Lodi Tiziana , Goffrini Paola , Ghelli Anna , Rugolo Michela , Carelli Valerio , Baruffini Enrico , Zanna Claudia
Published: November 2020

OPA1 mutations are the major cause of dominant optic atrophy (DOA) and the syndromic form DOA plus, pathologies for which there is no established cure. We used a ‘drug repurposing’ approach to identify FDA-approved molecules able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. We screened two different chemical libraries by using two yeast strains carrying the mgm1I322M and the chim3P646L mutations, identifying 26 drugs able to rescue their oxidative growth phenotype. Six of them, able to reduce the mitochondrial DNA instability in yeast, have been then tested in Opa1 deleted mouse embryonic fibroblasts expressing the human OPA1 isoform 1 bearing the R445H and D603H mutations. Some of these molecules were able to ameliorate the energetic functions and/or the mitochondrial network morphology, depending on the type of OPA1 mutation. The final validation has been performed in patients’ fibroblasts, allowing to select the most effective molecules. Our current results are instrumental to rapidly translating the findings of this drug repurposing approach into clinical trial for DOA and other neurodegenerations caused by OPA1 mutations.
How data shape actor relations in artificial intelligence innovation systems: an empirical observation from China
Authors: Yu Zhen , Liang Zheng , Wu Peiyi
Published: November 2020

With the rise of artificial intelligence (AI), data are widely viewed as the “new oil”. However, data substantially differ from conventional resources in the sense that they are important not only for production but also for knowledge development and public policymaking. This article explores whether and how data reshape government–industry–university relations in the era of AI. Taking China’s AI innovation system as a case, this article investigates the dynamics of actor relations in the business subsystem, knowledge subsystem, and regulatory subsystem. The change of the fundamental input from physical resources to virtual data in AI innovation systems has significantly transformed the relations among industry, state, and academia, and digital platforms are playing an increasingly important role in business value creation, knowledge generation, and regulation formation due to their control of valuable data and frontier expertise in the context of uncertainty.
Repeatedly Measuring Political Interest: Can we Reduce Respondent’ Recall Ability and Memory Effects in Surveys Using Memory Interference Tasks?
Authors: Revilla Melanie , Höhne Jan Karem
Published: November 2020

It is common practice in behavioral and social sciences to repeat questions, such as in pretest–posttest designs. However, if respondents recall their first answer to a repeated question and use it to decide their second answer, this may cause memory effects, affecting empirical findings. So far, only a few studies have investigated respondents’ recall ability and memory effects in surveys. Thus, we conducted an experiment in a probability-based online panel (N = 4,681) where we repeatedly asked a question on political interest. Our results reveal that respondents’ recall ability is high and was not reduced by the implementation of memory interference tasks. Memory effects, in contrast, were low (about 7%). They were also not reduced by memory interference tasks.
DNA Content Variation and SNP Diversity Within a Single Population of Asexual Snails
Authors: Million Kara M , Bhattacharya Amrita , Dinges Zoe M , Montgomery Sarah , Smith Eries , Lively Curtis M
Published: November 2020

A growing body of research suggests that many clonal populations maintain genetic diversity even without occasional sexual reproduction. The purpose of our study was to document variation in single-nucleotide polymorphism (SNP) diversity, DNA content, and pathogen susceptibility in clonal lineages of the New Zealand freshwater snail, Potamopyrgus antipodarum. We studied snails that were collected from multiple field sites around a single lake (Lake Alexandrina), as well as isofemale clonal lineages that had been isolated and maintained in the laboratory. We used the kompetitive allele specific PCR (KASP) method to genotype our samples at 46 nuclear SNP sites, and we used flow cytometry to estimate DNA content. We found high levels of SNP diversity, both in our field samples and in our clonal laboratory lines. We also found evidence of high variation in DNA content among clones, even among clones with identical genotypes across all SNP sites. Controlled pathogen exposures of the laboratory populations revealed variation in susceptibility among distinct clonal genotypes, which was independent of DNA content. Taken together, these results show high levels of diversity among asexual snails, especially for DNA content, and they suggest rapid genome evolution in asexuals.
Conservation Genomics of the Threatened Western Spadefoot,Spea hammondii, in Urbanized Southern California
Authors: Neal Kevin M , Fisher Robert N , Mitrovich Milan J , Shaffer H Bradley
Published: November 2020

Populations of the western spadefoot (Spea hammondii) in southern California occur in one of the most urbanized and fragmented landscapes on the planet and have lost up to 80% of their native habitat. Orange County is one of the last strongholds for this pond-breeding amphibian in the region, and ongoing restoration efforts targeting S. hammondii have involved habitat protection and the construction of artificial breeding ponds. These efforts have successfully increased breeding activity, but genetic characterization of the populations, including estimates of effective population size and admixture between the gene pools of constructed artificial and natural ponds, has never been undertaken. Using thousands of genome-wide single-nucleotide polymorphisms, we characterized the population structure, genetic diversity, and genetic connectivity of spadefoots in Orange County to guide ongoing and future management efforts. We identified at least 2, and possibly 3 major genetic clusters, with additional substructure within clusters indicating that individual ponds are often genetically distinct. Estimates of landscape resistance suggest that ponds on either side of the Los Angeles Basin were likely interconnected historically, but intense urban development has rendered them essentially isolated, and the resulting risk of interruption to natural metapopulation dynamics appears to be high. Resistance surfaces show that the existing artificial ponds were well-placed and connected to natural populations by low-resistance corridors. Toad samples from all ponds (natural and artificial) returned extremely low estimates of effective population size, possibly due to a bottleneck caused by a recent multi-year drought. Management efforts should focus on maintaining gene flow among natural and artificial ponds by both assisted migration and construction of new ponds to bolster the existing pond network in the region.
The variance and covariance of counts-in-cells probabilities
Authors: Repp Andrew , Szapudi István
Published: November 2020

Counts-in-cells (CIC) measurements contain a wealth of cosmological information, yet are seldom used to constrain theories. Although we can predict the shape of the distribution for a given cosmology, to fit a model to the observed CIC probabilities requires the covariance matrix – both the variance of counts in one probability bin and the covariance between counts in different bins. To date, there have been no general expressions for these variances. Here, we show that correlations of particular levels, or ‘slices’, of the density field determine the variance and covariance of CIC probabilities. We derive explicit formulae that accurately predict the variance and covariance among subvolumes of a simulated galaxy catalogue, opening the door to the use of CIC measurements for cosmological parameter estimation.
Power spectrum of halo intrinsic alignments in simulations
Authors: Kurita Toshiki , Takada Masahiro , Nishimichi Takahiro , Takahashi Ryuichi , Osato Ken , Kobayashi Yosuke
Published: November 2020

We use a suite of N-body simulations to study intrinsic alignments (IA) of halo shapes with the surrounding large-scale structure in the ΛCDM model. For this purpose, we develop a novel method to measure multipole moments of the three-dimensional power spectrum of the E-mode field of halo shapes with the matter/halo distribution, $P_{\delta E}^{(\ell)}(k)$ (or $P^{(\ell)}_{{\rm h}E}$), and those of the auto-power spectrum of the E-mode, $P^{(\ell)}_{EE}(k)$, based on the E/B-mode decomposition. The IA power spectra have non-vanishing amplitudes over the linear to non-linear scales, and the large-scale amplitudes at k ≲ 0.1 h−1 Mpc are related to the matter power spectrum via a constant coefficient (AIA), similar to the linear bias parameter of galaxy or halo density field. We find that the cross- and auto-power spectra PδE and PEE at non-linear scales, k ≳ 0.1 h−1 Mpc, show different k-dependences relative to the matter power spectrum, suggesting a violation of the non-linear alignment model commonly used to model contaminations of cosmic shear signals. The IA power spectra exhibit baryon acoustic oscillations, and vary with halo samples of different masses, redshifts, and cosmological parameters (Ωm, S8). The cumulative signal-to-noise ratio for the IA power spectra is about 60 per cent of that for the halo density power spectrum, where the super-sample covariance is found to give a significant contribution to the total covariance. Thus our results demonstrate that the IA power spectra of galaxy shapes, measured from imaging and spectroscopic surveys for an overlapping area of the sky, can be used to probe the underlying matter power spectrum, the primordial curvature perturbations, and cosmological parameters, in addition to the standard galaxy density power spectrum.
Small-scale primordial fluctuations in the 21 cm Dark Ages signal
Authors: Cole Philippa S , Silk Joseph
Published: November 2020

Primordial black hole production in the mass range $10\!-\!10^4 \, {\rm M_\odot}$ is motivated respectively by interpretations of the LIGO/Virgo observations of binary black hole mergers and by their ability to seed intermediate black holes that would account for the presence of supermassive black holes at very high redshift. Their existence would imply a boost in the primordial power spectrum if they were produced by overdensities reentering the horizon and collapsing after single-field inflation. This, together with their associated Poisson fluctuations would cause a boost in the matter power spectrum on small scales. The extra power could become potentially observable in the 21 cm power spectrum on scales around $k\sim 0.1\!-\!50\, {\rm Mpc^{-1}}$ with the new generation of filled low-frequency interferometers. We explicitly include the contribution from primordial fluctuations in our prediction of the 21 cm signal that has been previously neglected, by constructing primordial power spectra motivated by single-field models of inflation that would produce extra power on small scales. We find that depending on the mass and abundance of primordial black holes, it is important to include this contribution from the primordial fluctuations, so as not to underestimate the 21 cm signal. Evidently our predictions of detectability, which lack any modelling of foregrounds, are unrealistic, but we hope that they will motivate improved cleaning algorithms that can enable us to access this intriguing corner of primordial black hole-motivated parameter space.
A survey of CH2DOH towards starless and pre-stellar cores in the Taurus molecular cloud
Authors: Ambrose Hannah E , Shirley Yancy L , Scibelli Samantha
Published: November 2020

Recent observations indicate that organic molecules are prevalent towards starless and pre-stellar cores. Deuteration of these molecules has not been well studied during the starless phase. Published observations of singly deuterated methanol, CH2DOH, have only been observed in a couple of well-studied, dense, and evolved pre-stellar cores (e.g. L1544, L183). Since the formation of gas-phase methanol during this cold phase is believed to occur via desorption from the icy grain surfaces, observations of CH2DOH may be useful as a probe of the deuterium fraction in the ice mantles of dust grains. We present a systematic survey of CH2DOH towards 12 starless and pre-stellar cores in the B10 region of the Taurus molecular cloud. Nine of the 12 cores are detected with [CH2DOH]/[CH3OH] ranging from <0.04 to 0.23$^{+0.12}_{-0.06}$ with a median value of 0.11. Sources not detected tend to have larger virial parameters and larger methanol linewidths than detected sources. The results of this survey indicate that deuterium fractionation of organic molecules, such as methanol, during the starless phase may be more easily detectable than previously thought.
Dwarf galaxies without dark matter: constraints on modified gravity
Authors: Khalifeh Ali Rida , Jimenez Raul
Published: November 2020

The discovery of 19 dwarf galaxies without dark matter (DM) provides, counterintuitively, strong support for the ΛCDM standard model of cosmology. Their presence is well accommodated in a scenario where the DM is in the form of cold dark particles. However, it is interesting to explore quantitatively what is needed from modified gravity models to accommodate the presence of these galaxies and what extra degree of freedom is needed in these models. To this end, we derive the dynamics at galaxy scales (Virial theorem) for a general class of modified gravity models. We distinguish between theories that satisfy the Jebsen–Birkhoff theorem, and those that do not. Our aim is to develop tests that can distinguish whether DM is part of the theory of gravity or a particle. The 19 dwarf galaxies discovered provide us with a stringent test for models of modified gravity. Our main finding is that there will always be an extra contribution to the Virial theorem coming from the modification of gravity, even if a certain galaxy shows very small, if not negligible, trace of DM, as has been reported recently. Thus, if these and more galaxies are confirmed as devoid (or negligible) of DM, while other similar galaxies have abundant DM, it seems interesting to find modifications of gravity to describe DM. Our result can be used by future astronomical surveys to put constraints on the parameters of modified gravity models at astrophysical scales where DM is described as such.
RepeatsDB in 2021: improved data and extended classification for protein tandem repeat structures
Authors: Paladin Lisanna , Bevilacqua Martina , Errigo Sara , Piovesan Damiano , Mičetić Ivan , Necci Marco , Monzon Alexander Miguel , Fabre Maria Laura , Lopez Jose Luis , Nilsson Juliet F , Rios Javier , Menna Pablo Lorenzano , Cabrera Maia , Buitron Martin Gonzalez , Kulik Mariane Gonçalves , Fernandez-Alberti Sebastian , Fornasari Maria Silvina , Parisi Gustavo , Lagares Antonio , Hirsh Layla , Andrade-Navarro Miguel A , Kajava Andrey V , Tosatto Silvio C E
Published: November 2020

The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here we present RepeatsDB 3.0, which addresses these challenges and presents an extended classification scheme. The major conceptual change compared to the previous version is the hierarchical classification combining top levels based solely on structural similarity (Class > Topology > Fold) with two new levels (Clan > Family) requiring sequence similarity and describing repeat motifs in collaboration with Pfam. Data growth has been addressed with improved mechanisms for browsing the classification hierarchy. A new UniProt-centric view unifies the increasingly frequent annotation of structures from identical or similar sequences. This update of RepeatsDB aligns with our commitment to develop a resource that extracts, organizes and distributes specialized information on tandem repeat protein structures.
Smart-ORF: a single-molecule method for accessing ribosome dynamics in both upstream and main open reading frames
Authors: Gaba Anthony , Wang Hongyun , Fortune Trinisia , Qu Xiaohui
Published: November 2020

Upstream open reading frame (uORF) translation disrupts scanning 43S flux on mRNA and modulates main open reading frame (mORF) translation efficiency. Current tools, however, have limited access to ribosome dynamics in both upstream and main ORFs of an mRNA. Here, we develop a new two-color in vitro fluorescence assay, Smart-ORF, that monitors individual uORF and mORF translation events in real-time with single-molecule resolution. We demonstrate the utility of Smart-ORF by applying it to uORF-encoded arginine attenuator peptide (AAP)-mediated translational regulation. The method enabled quantification of uORF and mORF initiation efficiencies, 80S dwell time, polysome formation, and the correlation between uORF and mORF translation dynamics. Smart-ORF revealed that AAP-mediated 80S stalling in the uORF stimulates the uORF initiation efficiency and promotes clustering of slower uORF-translating ribosomes. This technology provides a new tool that can reveal previously uncharacterized dynamics of uORF-containing mRNA translation.
Ribosome association primes the stringent factor Rel for tRNA-dependent locking in the A-site and activation of (p)ppGpp synthesis
Authors: Takada Hiraku , Roghanian Mohammad , Caballero-Montes Julien , Van Nerom Katleen , Jimmy Steffi , Kudrin Pavel , Trebini Fabio , Murayama Rikinori , Akanuma Genki , Garcia-Pino Abel , Hauryliuk Vasili
Published: November 2020

In the Gram-positive Firmicute bacterium Bacillus subtilis, amino acid starvation induces synthesis of the alarmone (p)ppGpp by the RelA/SpoT Homolog factor Rel. This bifunctional enzyme is capable of both synthesizing and hydrolysing (p)ppGpp. To detect amino acid deficiency, Rel monitors the aminoacylation status of the ribosomal A-site tRNA by directly inspecting the tRNA’s CCA end. Here we dissect the molecular mechanism of B. subtilis Rel. Off the ribosome, Rel predominantly assumes a ‘closed’ conformation with dominant (p)ppGpp hydrolysis activity. This state does not specifically select deacylated tRNA since the interaction is only moderately affected by tRNA aminoacylation. Once bound to the vacant ribosomal A-site, Rel assumes an ‘open’ conformation, which primes its TGS and Helical domains for specific recognition and stabilization of cognate deacylated tRNA on the ribosome. The tRNA locks Rel on the ribosome in a hyperactivated state that processively synthesises (p)ppGpp while the hydrolysis is suppressed. In stark contrast to non-specific tRNA interactions off the ribosome, tRNA-dependent Rel locking on the ribosome and activation of (p)ppGpp synthesis are highly specific and completely abrogated by tRNA aminoacylation. Binding pppGpp to a dedicated allosteric site located in the N-terminal catalytic domain region of the enzyme further enhances its synthetase activity.
Tobacco Withdrawal Symptoms Before and After Nicotine Deprivation in Veteran Smokers with Posttraumatic Stress Disorder and with Major Depressive Disorder
Authors: Kaye Jesse T , Baker Timothy B , Beckham Jean C , Cook Jessica W
Published: November 2020

Introduction

The high smoking prevalence amongst individuals with psychiatric disorders constitutes a major public health disparity. Negative reinforcement models of addiction posit that severe tobacco withdrawal symptoms, related to the affective vulnerabilities of these smokers, may thwart their quitting smoking successfully. However, relatively few studies have prospectively examined the effects of nicotine deprivation on withdrawal symptoms in these groups.

Methods

This study compared the level of withdrawal symptoms both before and after nicotine deprivation in those diagnosed with posttraumatic stress disorder (PTSD) or major depressive disorder (MDD) and in those without psychiatric diagnoses. Participants were US veterans who smoked (≥10 cigarettes/day) and met diagnostic criteria for PTSD (n = 38), MDD (n = 43), or no psychiatric diagnosis (“controls” n = 44). Participants attended study visits before and during 48-hour nicotine deprivation to report tobacco withdrawal symptoms. Analyses evaluated withdrawal symptom levels (baseline and during nicotine deprivation) and the change in symptoms related to nicotine deprivation and compared (1) participants with a psychiatric diagnosis versus controls, and (2) participants with PTSD versus MDD.

Results

Contrary to hypotheses, nicotine deprivation produced greater increases in most withdrawal symptoms amongst controls than in those with psychiatric diagnoses. Compared with controls, those with PTSD or MDD reported elevated symptom levels both before and after tobacco deprivation for most withdrawal symptoms.

Conclusions

These findings suggest that chronically high levels of distress and craving, rather than acute increases in withdrawal symptoms because of nicotine deprivation, may account for the quitting difficulties of those with comorbid conditions such as PTSD and MDD.

Implications

Severe tobacco withdrawal may account for the higher quitting difficulties of smokers with either posttraumatic stress disorder (PTSD) or major depressive disorder (MDD). Paradoxically, this study showed that individuals with no psychiatric diagnosis had greater increases in tobacco withdrawal severity because of nicotine deprivation than did those with either PTSD or MDD. Those with either PTSD or MDD showed high stable levels of withdrawal symptom severity both before and during two days of abstinence, suggesting that their quitting difficulties may be related to their chronically high levels of distress rather than nicotine deprivation per se.
Do Young Adults Attend to Health Warnings in the First IQOS Advertisement in the U.S.? An Eye-Tracking Approach
Authors: Liu Jiaying , Phua Joe , Krugman Dean , Xu Linjia , Nowak Glen , Popova Lucy
Published: November 2020

Introduction

In October 2019, a heated tobacco product (HTP) IQOS debuted in the United States. This study examined young adults' attention and cognitions in response to an IQOS ad that carried two mandated textual health warnings (Surgeon General's warning and nicotine warning), and how their vaping and smoking status may interact with attention patterns to affect attitude and intention to use IQOS.

Methods

In November 2019, college students (N = 164) viewed IQOS' first U.S. magazine ad and two distractor ads. Viewing patterns were recorded with eye-tracking. Masked recall and aided recognition, attitude and intention towards IQOS use were later assessed with self-report. Ordinary Least Squares (OLS) regressions and moderated mediation analyses examined the associations between visual attention and viewers' cognitions about IQOS use.

Results

Promotional content attracted significantly more attention compared to the warnings. Attention to the Surgeon General's warning but not to the nicotine warning was associated with recall and recognition of the warning's content. For ever-vapers, greater attention allocation to the promotional content in the IQOS ad was associated with more favorable attitude toward IQOS use, which was in turn positively associated with intention to use IQOS. Attention allocation to the warnings did not affect attitude or intentions, regardless of tobacco use status.

Conclusions

The results revealed the effects of IQOS promotional content overshadowed the two health warnings in influencing young people's attitude and intention to use IQOS. Young adults who vaped were more vulnerable to HTP advertising with respect to future use and vaping may be a gateway to HTP use.

Implications

This is the first eye-tracking study examining attention and cognitions associated with the new IQOS ad exposure among young adults. Promotional content in the ad attracted significantly more attention than the two warnings combined. Attention to the Surgeon General's warning but not to the nicotine warning was associated with recall and recognition of the warning's content. Greater attention allocation to the promotional content led to a more favorable attitude toward IQOS use which was associated with increased intention to use IQOS for ever-vapers. However, greater attention allocation to the warnings did not affect attitude or intentions to use IQOS.
Cadmium Inhibits Lateral Root Emergence in Rice by Disrupting OsPIN-Mediated Auxin Distribution and the Protective Effect of OsHMA3
Authors: Wang Han-Qing , Xuan Wei , Huang Xin-Yuan , Mao Chuanzao , Zhao Fang-Jie
Published: November 2020

Cadmium (Cd) strongly inhibits root growth, especially the formation of lateral roots (LRs). The mechanism of Cd inhibition on LR formation in rice (Oryza sativa) remains unclear. In this study, we found that LR emergence in rice was inhibited significantly by 1 �M Cd and almost completely arrested by 5 �M Cd. Cd suppressed both the formation and subsequent development of the lateral root primordium (LRP). By using transgenic rice expressing the auxin response reporters DR5::GUS and DR5rev::VENUS, we found that Cd markedly reduced the auxin levels in the stele and LRP. Cd rapidly downregulated the expression of the auxin efflux transporter genes OsPIN1b, OsPIN1c and OsPIN9 in the stele and LRP. The emergence of LRs in a rice cultivar with a null allele of OsHMA3 (Heavy Metal ATPase 3) was more sensitive to Cd than cultivars with functional alleles. Overexpression of functional OsHMA3 in rice greatly alleviated the inhibitory effect of Cd, but the protective effect of OsHMA3 was abolished by the auxin polar transport inhibitor 1-N-naphthylphthalamic acid. The results suggest that Cd inhibits LR development in rice by disrupting OsPIN-mediated auxin distribution to LRP and OsHMA3 protects against Cd toxicity by sequestering Cd into the vacuoles.
Prevalence, incidence and cause-specific mortality of rheumatoid arthritis–associated interstitial lung disease among older rheumatoid arthritis patients
Authors: Sparks Jeffrey A , Jin Yinzhu , Cho Soo-Kyung , Vine Seanna , Desai Rishi , Doyle Tracy J , Kim Seoyoung C
Published: November 2020

Objective

We aimed to investigate the prevalence, incidence and cause-specific mortality of RA-associated interstitial lung disease (RA-ILD) among older US patients with RA.

Methods

We performed a nationwide cohort study using Medicare claims data (parts A, B and D for 2008–2017). RA was identified with a validated algorithm using RA diagnosis codes and DMARD prescription. RA-ILD was identified with a validated algorithm using ILD diagnosis codes by a rheumatologist/pulmonologist. RA-ILD was categorized as prevalent or incident relative to the initial RA observation (baseline/index date). We compared the total mortality of RA-ILD to RA without ILD using multivariable Cox regression, adjusting for baseline covariates. For cause-specific mortality, Fine and Gray subdistribution hazard ratios (sdHRs) were estimated to handle competing risks of alternative mortality causes.

Results

Among 509 787 RA patients (mean age 72.6 years, 76.2% female), 10 306 (2.0%) had prevalent RA-ILD at baseline. After baseline, 13 372 (2.6%) developed RA-ILD during 1 873 127 person-years of follow-up (median 3.0 years/person). During follow-up, 38.7% of RA-ILD patients died compared with 20.7% of RA patients without ILD. After multivariable adjustment, RA-ILD had an HR of 1.66 (95% CI 1.60, 1.72) for total mortality. Accounting for competing risk of other causes of death, RA-ILD had an sdHR of 4.39 (95% CI 4.13, 4.67) for respiratory mortality and an sdHR of 1.56 (95% CI 1.43, 1.71) for cancer mortality compared with RA without ILD.

Conclusions

RA-ILD was present or developed in nearly 5% of patients in this nationwide study of older patients with RA. Compared with RA without ILD, RA-ILD was associated with excess total, respiratory and cancer mortality that was not explained by measured factors.
Slow wave activity moderates the association between new learning and traumatic brain injury severity
Authors: El-Khatib Héjar , Sanchez Erlan , Arbour Caroline , Van Der Maren Solenne , Duclos Catherine , Blais Hélène , Carrier Julie , Simonelli Guido , Hendryckx Charlotte , Paquet Jean , Gosselin Nadia
Published: November 2020

Study Objectives

Sleep–wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep–wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity.

Methods

Forty-two moderate to severe TBI participants, 12–47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance.

Results

We found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI.

Conclusions

This study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.
How Do Adolescent Social Determinants and Social Contexts Shape Adult Sexual Identification?
Authors: Silva Tony , Evans Clare R
Published: November 2020

This study explores the social determinants of exclusively straight sexual identification in a large, nationally representative sample. Using data from the National Longitudinal Study of Adolescent to Adult Health and combining cross-classified multilevel models with social network analysis, we examine how straight identification varies across school, neighborhood, and network community contexts. We also test whether numerous determinants identified by prior ethnographic studies predict straight identification. The use of panel data enables us to establish temporal order, avoiding many of the disadvantages of cross-sectional studies. After controlling for attractions and sexual behaviors, we find persistent clustering of adult sexual identification by adolescent social context, suggesting that these contexts may shape later sexual identification. Religiosity, political conservatism, Black racial identification, migration status, and male identification were strong predictors of straight identification. This study provides the most comprehensive analysis of the social determinants of sexual identification to date as well as evidence on the generalizability of previous findings.
The apple columnar gene candidate MdCoL and the AP2/ERF factor MdDREB2 positively regulate ABA biosynthesis by activating the expression of MdNCED6/9
Authors: Sun Xin , Wen Cuiping , Xu Jihua , Wang Yihe , Zhu Jun , Zhang Yugang
Published: November 2020

MdCoL, which encodes a putative 2OG-Fe(II) oxygenase, is a strong candidate gene for control of the columnar growth phenotype in apple. However, the mechanism by which MdCoL produces the columnar trait is unclear. Here, we show that MdCoL influences abscisic acid (ABA) biosynthesis through its interactions with the MdDREB2 transcription factor. Expression analyses and transgenic tobacco studies have confirmed that MdCoL is likely a candidate for control of the columnar phenotype. Furthermore, the ABA level in columnar apple trees is significantly higher than that in standard apple trees. A protein interaction experiment has showed that MdCoL interacts with MdDREB2. Transient expression and electrophoretic mobility shift assays have demonstrated that MdDREB2 binds directly to the DRE motif in the MdNCED6 and MdNCED9 (MdNCED6/9) gene promoters, thereby activating the transcription of these ABA biosynthesis genes. In addition, a higher ABA content has been detected following co-overexpression of MdCoL–MdDREB2 when compared with the overexpression of MdCoL or MdDREB2 alone. Taken together, our results indicate that an interaction between MdCoL and MdDREB2 promotes the expression of MdNCED6/9 and increases ABA levels, a phenomenon that may underlie the columnar growth phenotype in apple.
Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study
Authors: Kratz Anna L. , Whibley Daniel , Alschuler Kevin N. , Ehde Dawn M. , Williams David A. , Clauw Daniel J. , Braley Tiffany J.
Published: November 2020

Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N = 842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief was reported. Cannabis use for pain was more common, and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAID use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches.
The diagnostic potential of gut microbiome for early hepatitis B virus-related hepatocellular carcinoma
Authors: Tang Yishu , Zhou Hang , Xiang Yu , Cui Fang
Published: November 2020

Background and aims

Gut microbiota is related with hepatocellular carcinoma (HCC). However, the relationship between the gut microbiota and the hepatitis B virus (HBV)-related HCC remains unclear. We aimed to characterize gut microbiome in HBV-related HCC patients and estimate the clinical potential of gut microbiome as biomarkers for HBV-related HCC.

Methods

We collected fecal and plasma samples from 20 health controls, 20 HBV-related cirrhosis and 20 HBV-related HCC in the First Affiliated Hospital of Chongqing Medical University. The fecal samples were subjected to the V3–V4 region of 16S rRNA Miseq sequencing. Plasma samples were calculated for interleukin-6 (IL-6), IL-2, IL-8, IL-10, tumor necrosis factor α (TNF-α), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Then, we analyzed the correlation between the index and the gut microbiota.

Results

We have found that the bacterial richness of the liver cirrhosis group was lower than the HCC group. The bacterial diversities were in consistent with IL-2. The pro-inflammatory bacteria (Veillonella, Escherichia-shigella) have increased in the liver cirrhosis group. The random forest model has achieved an area under the curve value was 94% with 95% CI, 88–100% between the HCC group and the non-HCC group. The results revealed that IL-2 was highly associated with the whole gut bacterial communities of HCC and liver cirrhosis groups. ALT, AST and glutamyl transpeptidase have strongly elevated in liver cirrhosis and HCC groups, which were associated with gut microbiome.

Conclusions

It could be helpful to define the potential bacteria linking to pathological mechanisms of HBV-related HCC. The diagnosis potential of gut microbiome for early HBV-related HCC has been estimated.
Microcirculatory changes in the liver of patients with refractory ascites and their relationship with diabetes and alcohol
Authors: Elkrief Laure , Buyse Sophie , Panhard Xavière , Baudry Clotilde , Gault Nathalie , Moreau Richard , Rautou Pierre-Emmanuel , Belghiti Jacques , Durand François , Bedossa Pierre , Paradis Valérie , Valla Dominique
Published: November 2020

Objectives

The determinants of refractory ascites have not been fully characterized. The aims of this study were to assess liver histopathological alterations associated with refractory ascites and their relationship with comorbidities.

Methods

Consecutive patients with cirrhosis who underwent liver transplantation were retrospectively included. Patients’ characteristics at the time of listing were analysed. The native livers were reviewed and lesions associated with refractory ascites were examined.

Results

Out of the 89 patients included, 30 had refractory ascites and 59 did not (including 35 without ascites and 24 with diuretic-sensitive ascites). Patients with and without refractory ascites had a similar amount of fibrous tissue and features of fatty liver disease. By contrast, microvascular changes, namely sinusoidal dilatation (P < 0.001), diffuse perisinusoidal fibrosis (P = 0.001), hepatic venous thromboses (P = 0.004) and vascular proliferation (P = 0.01) were more frequently observed in the livers of patients with refractory ascites. Diabetes (57% vs. 31%, P = 0.02) and alcohol as a causal factor for cirrhosis (80% vs. 42%, P = 0.001) were more frequent in patients with refractory ascites than in those without. By multivariate analysis, refractory ascites was independently associated with diabetes mellitus [odds ratio (OR) (95% confidence interval, CI) 6.15 (1.47–25.71); P = 0.01], alcohol as a causal factor for cirrhosis [OR (95% CI) 4.63 (1.07–20.02); P = 0.04], higher Model For End Stage Liver Diseases [OR (95% CI) 1.21 (1.05–1.38); P = 0.008] and lower serum sodium [OR (95% CI) 0.87 (0.78–0.98); P = 0.03].

Conclusion

Liver microcirculatory changes are associated with refractory ascites. Diabetes and alcohol may explain refractory ascites by causing microangiopathy.
Racial Differences in the Cesarean Section Rates Among Women Veterans Using Department of Veterans Affairs Community Care
Authors: Mattocks Kristin M. , Kroll-Desrosiers Aimee , Kinney Rebecca , Bastian Lori A. , Bean-Mayberry Bevanne , Goldstein Karen M. , Shivakumar Geetha , Copeland Laurel
Published: November 2020

Background:

Racial disparities in maternal morbidity and mortality remain a pressing public health problem. Variations in cesarean section (C-section) rates among racial and ethnic groups have been well documented, though reasons for these variations remain unknown. In the Department of Veterans Affairs (VA), nearly half of all women Veterans are of reproductive age and >40% of these women are racial and ethnic minorities. Because the VA does not provide obstetrical services, all obstetrical care is provided by community obstetrical providers under the auspices of the VA Community Care Network. However, little is known regarding the rates and correlates of C-sections among women Veterans receiving community obstetrical care.

Objective:

To examine predictors of C-section deliveries among a cohort of racially diverse pregnant Veterans enrolled in VA care at 15 VA medical facilities nationwide.

Research Design:

Cross-sectional analysis of a longitudinal, prospective, multisite, observational cohort study of pregnant, and postpartum Veterans receiving community-based obstetrical care.

Results:

Overall, 659 Veterans delivered babies during the study period, and 35% of the deliveries were C-sections. Predictors of C-section receipt included being a woman of color [adjusted odds ratio (AOR), 1.76; 95% confidence interval (CI), 1.19–2.60], having an Edinburgh Postnatal Depression Scale score ≥10 (AOR, 1.71; 95% CI, 1.11–2.65), having a higher body mass indexes (AOR, 1.07; 95% CI, 1.04–1.11), and women who were older (AOR, 1.08; 95% CI, 1.03–1.13). There was a substantial racial variation in C-section rates across our 15 study sites, with C-section rates meeting or exceeding 50% for WOC in 8 study sites.

Conclusions:

There is substantial racial and geographic variation in C-section rates among pregnant Veterans receiving obstetrical care through VA community care providers. Future research should carefully examine variations in C-sections by the hospital, and which providers and hospitals are included in VA contracts. There should also be an increased focus on the types of providers women Veterans have access to for obstetrical care paid for by the VA and the quality of care delivered by those providers.
Increased pain sensitivity and pain-related anxiety in individuals with autism
Authors: Failla Michelle D. , Gerdes Madison B. , Williams Zachary J. , Moore David J. , Cascio Carissa J.
Published: November 2020

Introduction:

Individuals with autism spectrum disorder (ASD) often exhibit differences in pain responsivity. This altered responsivity could be related to ASD-related social communication difficulties, sensory differences, or altered processing of pain stimuli. Previous neuroimaging work suggests altered pain evaluation could contribute to pain-related anxiety in ASD.

Objectives:

We hypothesized that individuals with ASD would report increased pain sensitivity and endorse more pain-related anxiety, compared to typically developing controls.

Methods:

We recruited 43 adults (ASD, n = 24; typically developing, n = 19) for 3 heat pain tasks (applied to the calf). We measured heat pain thresholds using a method of limits approach, a pain-rating curve (7 temperatures between 40 and 48°C, 5 seconds, 5 trials each), and a sustained heat pain task with alternating low (42°C) and high (46°C) temperatures (21 seconds, 6 trials each). Individual differences in pain-related anxiety, fear of pain, situational pain catastrophizing, depressive symptoms, and autism-related social communication were assessed by self-report.

Results:

There were no group differences in pain thresholds. For suprathreshold tasks, mean pain ratings were higher in ASD across both the pain-rating curve and the sustained heat pain tasks, but responses in the ASD group were more varied. Pain anxiety (PASS-Total) and pain-related fear (FOP-III-Total) were higher in the ASD group and were positively associated with pain ratings.

Conclusions:

Our results suggest that both sensory and cognitive experiences of pain are heightened and interact reciprocally in adults with ASD. Future studies are needed to evaluate the impact of pain-related anxiety on treatment-seeking and pain behaviors, given higher levels of pain-related anxiety in ASD.
Identification of Patient Characteristics Associated With SARS-CoV-2 Infection and Outcome in Kidney Transplant Patients Using Serological Screening
Authors: Willicombe Michelle , Gleeson Sarah , Clarke Candice , Dor Frank , Prendecki Maria , Lightstone Liz , Lucisano Gaetano , McAdoo Stephen , Thomas David ,   on behalf of the ICHNT Renal COVID Group
Published: November 2020

Background.

From population studies, solid organ transplant recipients are at increased risk of mortality from RT-PCR confirmed COVID-19 infection. The risk factors associated with infection acquisition and mortality in transplant recipients using serological data have not been reported.

Methods.

From 1725 maintenance transplant recipients, 855 consecutive patients were screened for SARS-CoV-2 antibodies. Serological screening utilized assays to detect both the N protein and receptor binding domain antibodies. Thirty-three of 855 (3.9%) of the screened patients had prior infection confirmed with RT-PCR. Twenty-one additional patients from our 1725 maintenance cohort with RT-PCR confirmed infection were included in our analysis.

Results.

Eighty-nine of 855 (10.4%) patients tested positive for SARS-CoV-2 antibodies. Fifty-nine of 89 (66.3%) cases were patients newly identified as exposed, while 30/89 (33.7%) seropositive patients had previous infection confirmed by RT-PCR. A diagnosis of SARS-CoV-2 (RT-PCR or Ab+) was associated with being from a noncaucasoid background, P = 0.015; having a diagnosis of diabetes, P = 0.028 and a history of allograft rejection, P < 0.01. Compared with the RT-PCR+ cohort, patients with serological-proven infection alone were more likely to be receiving tacrolimus monotherapy, P < 0.01, and less likely to have a diagnosis of diabetes, P = 0.012. Seventeen of 113 (15.0%) of all patients with infection (RT-PCR and Ab+) died. Risk factors associated with survival were older age, odds ratio (OR): 1.07 (1.00–1.13), P = 0.041; receiving prednisolone, OR: 5.98 (1.65–21.60), P < 0.01 and the absence of diabetes, OR: 0.27 (0.07–0.99), P = 0.047.

Conclusions.

This study identifies risk factors and outcome for COVID-19 infection incorporating data on serologically defined infection and highlights the important contribution of immunosuppression regimen on outcomes.
Rotational dynamics in motor cortex are consistent with a feedback controller
Authors: Kalidindi Hari Teja , Cross Kevin P. , Lillicrap Timothy P. , Omrani Mohsen , Falotico Egidio , Sabes Philip N. , Scott Stephen H.
Published: November 2020

Recent studies hypothesize that motor cortical (MC) dynamics are generated largely through its recurrent connections based on observations that MC activity exhibits rotational structure. However, behavioural and neurophysiological studies suggest that MC behaves like a feedback controller where continuous sensory feedback and interactions with other brain areas contribute substantially to MC processing. We investigated these apparently conflicting theories by building recurrent neural networks that controlled a model arm and received sensory feedback about the limb. Networks were trained to counteract perturbations to the limb and to reach towards spatial targets. Network activities and sensory feedback signals to the network exhibited rotational structure even when the recurrent connections were removed. Furthermore, neural recordings in monkeys performing similar tasks also exhibited rotational structure not only in MC but also in somatosensory cortex. Our results argue that rotational structure may reflect dynamics throughout voluntary motor circuits involved in online control of motor actions.

Highlights

Neural networks with sensory feedback generate rotational dynamics during simulated posture and reaching tasks

Rotational dynamics are observed even without recurrent connections in the network

Similar dynamics are observed not only in motor cortex, but also in somatosensory cortex of non-huma n primates as well as sensory feedback signals

Results highlight rotational dynamics may reflect internal dynamics, external inputs or any combination of the two.