bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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 &gt; Topology &gt; Fold) with two new levels (Clan &gt; 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

Abstract
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

Abstract
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

Abstract

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

Abstract

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

AbstractCadmium (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

Abstract

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

Abstract

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

AbstractThis 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

Abstract
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

Abstract
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.