bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid receptor coactivator 3 (SRC-3/AIB1) is enriched and functional in mouse and human Tregs
Authors: Nikolai Bryan C. , Jain Prashi , Cardenas David L. , York Brian , Feng Qin , McKenna Neil J. , Dasgupta Subhamoy , Lonard David M. , O’Malley Bert W. 
Published: February 2021

AbstractA subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.
Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury
Authors: Huie J. R. , Ferguson A. R. , Kyritsis N. , Pan J. Z. , Irvine K.-A. , Nielson J. L. , Schupp P. G. , Oldham M. C. , Gensel J. C. , Lin A. , Segal M. R. , Ratan R. R. , Bresnahan J. C. , Beattie M. S. 
Published: February 2021

AbstractTraumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining five different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis (TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 h after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.
Comparative genomics of a novel clade shed light on the evolution of the genus Erysipelothrix and characterise an emerging species
Authors: Grazziotin Ana Laura , Vidal Newton M. , Hoepers Patricia Giovana , Reis Thais F. M. , Mesa Dany , Caron Luiz Felipe , Ingberman Max , Beirão Breno C. B. , Zuffo João Paulo , Fonseca Belchiolina Beatriz 
Published: February 2021

AbstractErysipelothrix sp. isolates obtained from a deadly outbreak in farmed turkeys were sequenced and compared to representatives of the genus. Phylogenetic trees—supported by digital DNA:DNA hybridization and Average Nucleotide Identity—revealed a novel monophyletic clade comprising isolates from pigs, turkeys, and fish, including isolates previously described as E. sp. Strain 2. Genes coding for the SpaC protein, typically found in E. sp. Strain 2, were detected in all isolates of the clade. Therefore, we confirm E. sp. Strain 2 represents a unique species, that despite its official name “Erysipelothrix piscisicarius” (meaning a killer of fish), may be isolated from a broad host range. Core genome analysis showed that the pathogenic species of this genus, E. rhusiopathiae and the clade E. sp. Strain 2, are enriched in core functionalities related to nutrient uptake and transport, but not necessarily homologous pathways. For instance, whereas the aerobic DctA transporter may uptake C4-dicarboxylates in both species, the anaerobic DcuC transporter is exclusive of the E. sp. Strain 2. Remarkably, the pan-genome analysis uncovered that genes related to transport and metabolism, recombination and repair, translation and transcription in the fish isolate, within the novel clade, have undergone a genomic reduction through pseudogenization. This reflects distinct selective pressures shaping the genome of species and strains within the genus Erysipelothrix while adapting to their respective niches.
Comparison between optical and digital blur using near visual acuity
Authors: Kordek David , Young Laura K. , Kremláček Jan 
Published: February 2021

AbstractIn a low-cost laboratory setup, we compared visual acuity (VA) for stimuli rendered with Zernike aberrations to an equivalent optical dioptric defocus in emmetropic individuals using a relatively short observing distance of 60 cm. The equivalent spherical refractive error of + 1, + 2 or + 4 D, was applied in the rendering of Landolt Rings. Separately, the refractive error was introduced dioptrically in: (1) unchanged Landolt Rings with an added external lens (+ 1, + 2 or + 4 D) at the subject's eye; (2) same as (1) but with an added accommodation and a vertex distance adjustment. To compare all three approaches, we examined VA in 10 healthy men. Stimuli were observed on a PC CRT screen. For all three levels of refractive error, the pairwise comparison did not show a statistically significant difference between digital blur and accommodation-plus-vertex-distance-adjusted dioptric blur (p < 0.204). The best agreement, determined by Bland–Altman analysis, was measured for + 4 D and was in line with test–retest limits for examination in the clinical population. Our results show that even for a near observing distance, it is possible to use digitally rendered defocus to replicate dioptric blur without a significant change in VA in emmetropic subjects.
Histone deacetylase inhibitors suppress ACE2 and ABO simultaneously, suggesting a preventive potential against COVID-19
Authors: Takahashi Yoichiro , Hayakawa Akira , Sano Rie , Fukuda Haruki , Harada Megumi , Kubo Rieko , Okawa Takafumi , Kominato Yoshihiko 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide as a pandemic throughout 2020. Since the virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor for cellular entry, increment of ACE2 would lead to an increased risk of SARS-CoV-2 infection. At the same time, an association of the ABO blood group system with COVID-19 has also been highlighted: there is increasing evidence to suggest that non-O individuals are at higher risk of severe COVID-19 than O individuals. These findings imply that simultaneous suppression of ACE2 and ABO would be a promising approach for prevention or treatment of COVID-19. Notably, we have previously clarified that histone deacetylase inhibitors (HDACIs) are able to suppress ABO expression in vitro. Against this background, we further evaluated the effect of HDACIs on cultured epithelial cell lines, and found that HDACIs suppress both ACE2 and ABO expression simultaneously. Furthermore, the amount of ACE2 protein was shown to be decreased by one of the clinically-used HDACIs, panobinostat, which has been reported to reduce B-antigens on cell surfaces. On the basis of these findings, we conclude that panobinostat could have the potential to serve as a preventive drug against COVID-19.
Construction and validation a nomogram to predict overall survival for colorectal signet ring cell carcinoma
Authors: Diao Jian-dong , Ma Li-xia , Wu Chun-jiao , Liu Xian-hong , Su Xiao-yun , Bi Hong-yu , Bao Bo , Yan Hao-wei , Shi Lei , Yang Yong-jing 
Published: February 2021

AbstractTo construct and validate a nomogram to predict the overall survival (OS) of colorectal signet ring cell carcinoma (SRCC). The potentially eligible cases were obtained against the SEER database from 2004 to 2015. Log-rank test and Cox analysis were conducted to identify the independent prognostic factors for predicting OS. The identified prognostic factors were later integrated for the construction of an OS prediction nomogram. Altogether 2904 eligible cases were identified, and the median survival time was 18 (range: 0–155) months. As suggested by multivariate analysis, age, primary site, grade, tumor size, T stage, N stage, M stage, surgery, lymph node dissection and chemotherapy were identified as the independent factors for predicting OS. Afterwards, the above variables were incorporated into the nomogram. The C-index indicated better discriminatory ability of the nomogram than AJCC 8th TNM staging and SEER summary stage systems (both P < 0.001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The time independent area under the curves (tAUCs) for 3-year and 5-year OS in nomogram were larger than AJCC and SEER summary stage system. The constructed nomogram could potentially predict the survival of colorectal SRCC individuals.
Considering serum alanine aminotransferase and gamma-glutamyltransferase levels together strengthen the prediction of impaired fasting glucose risk: a cross-sectional and longitudinal study
Authors: Jeong Ji Hye , Jung Susie , Kim Kyu-Nam 
Published: February 2021

AbstractEmerging data suggest that an increase in serum alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as biomarkers of oxidative stress are associated with increased risk of impaired fasting glucose (IFG). The present study was an investigation of whether an increase in serum ALT and GGT had a combined effect on increasing IFG risk through cross-sectional and longitudinal studies. In the cross-sectional study, data were analyzed from 9937 subjects without diabetes who underwent health check-ups between 1999 and 2001 (baseline data). In the longitudinal study, 6390 subjects were analyzed who had been rechecked between 2009 and 2014, excluding IFG patients from baseline data. In cross-sectional analysis, adjusted odds ratio (OR) of IFG in the fourth quartile of both ALT and GGT was 1.829 (95% confidence interval [CI] 1.545–2.164) compared with the reference group (1st and 2nd quartiles of ALT and GGT). In longitudinal analysis, IFG probability increased gradually with an increase in the circulating levels of ALT and GGT. Adjusted hazard ratios for developing IFG in the fourth quartile of both ALT and GGT was 1.625 (95% CI 1.263–2.091) compared with the reference group (1st and 2nd quartiles). Increased serum ALT and GGT levels are well associated with IFG after potential confounders are adjusted for, and elevated ALT and GGT at the same time can have a combined effect in predicting the development of IFG.
Pangenome analysis reveals genetic isolation in Campylobacter hyointestinalis subspecies adapted to different mammalian hosts
Authors: Costa Daniela , Lévesque Simon , Kumar Nitin , Fresia Pablo , Ferrés Ignacio , Lawley Trevor D. , Iraola Gregorio 
Published: February 2021

AbstractCampylobacter hyointestinalis is an emerging pathogen currently divided in two subspecies: C. hyointestinalis subsp. lawsonii which is predominantly recovered from pigs, and C. hyointestinalis subsp. hyointestinalis which can be found in a much wider range of mammalian hosts. Despite C. hyointestinalis being reported as an emerging pathogen, its evolutionary and host-associated diversification patterns are still vastly unexplored. For this reason, we generated whole-genome sequences of 13 C. hyointestinalis subsp. hyointestinalis strains and performed a comprehensive comparative analysis including publicly available C. hyointestinalis subsp. hyointestinalis and C. hyointestinalis subsp. lawsonii genomes, to gain insight into the genomic variation of these differentially-adapted subspecies. Both subspecies are distinct phylogenetic lineages which present an apparent barrier to homologous recombination, suggesting genetic isolation. This is further supported by accessory gene patterns that recapitulate the core genome phylogeny. Additionally, C. hyointestinalis subsp. hyointestinalis presents a bigger and more diverse accessory genome, which probably reflects its capacity to colonize different mammalian hosts unlike C. hyointestinalis subsp. lawsonii that is presumably host-restricted. This greater plasticity in the accessory genome of C. hyointestinalis subsp. hyointestinalis correlates to a higher incidence of genome-wide recombination events, that may be the underlying mechanism driving its diversification. Concordantly, both subspecies present distinct patterns of gene families involved in genome plasticity and DNA repair like CRISPR-associated proteins and restriction-modification systems. Together, our results provide an overview of the genetic mechanisms shaping the genomes of C. hyointestinalis subspecies, contributing to understand the biology of Campylobacter species that are increasingly recognized as emerging pathogens.
Involvement of bilateral insula in brand extension evaluation: an fMRI study
Authors: Yang Taeyang , Kim Ji-Hyun , Kim Junsuk , Kim Sung-Phil 
Published: February 2021

AbstractThe present study aims to investigate functional involvement of brain areas in consumers’ evaluation of brand extension that refers to the use of well-established brand for launching new offerings. During functional magnetic resonance imaging (fMRI) scanning, participants viewed a beverage brand name followed by an extension goods name selected from the beverage or household appliance categories. They responded acceptability to given brand extension. Both acceptability responses and reaction time revealed a noticeable pattern that participants responded to acceptable stimuli more carefully. General linear model (GLM) analyses revealed the involvement of insular activity in brand extension evaluation. Especially, insular activity was lateralized according to valence. Furthermore, its activity could explain behavioral response in parametric modulation model. According to these results, we speculate that insula activity is relevant to emotional processing. Finally, we divided neural activities during brand extension into separated clusters using a hierarchical clustering-based connectivity analysis. Excluding two of them related to sensorimotor functions for behavioral responses, the remaining cluster, including bilateral insula, was likely to reflect brand extension assessment. Hence, we speculate that consumers’ brand extension evaluation may involve emotional processes, shown as insular activity.
Distinct temporal features of genuine and deliberate facial expressions of surprise
Authors: Namba Shushi , Matsui Hiroshi , Zloteanu Mircea 
Published: February 2021

AbstractThe physical properties of genuine and deliberate facial expressions remain elusive. This study focuses on observable dynamic differences between genuine and deliberate expressions of surprise based on the temporal structure of facial parts during emotional expression. Facial expressions of surprise were elicited using multiple methods and video recorded: senders were filmed as they experienced genuine surprise in response to a jack-in-the-box (Genuine), other senders were asked to produce deliberate surprise with no preparation (Improvised), by mimicking the expression of another (External), or by reproducing the surprised face after having first experienced genuine surprise (Rehearsed). A total of 127 videos were analyzed, and moment-to-moment movements of eyelids and eyebrows were annotated with deep learning-based tracking software. Results showed that all surprise displays were mainly composed of raising eyebrows and eyelids movements. Genuine displays included horizontal movement in the left part of the face, but also showed the weakest movement coupling of all conditions. External displays had faster eyebrow and eyelid movement, while Improvised displays showed the strongest coupling of movements. The findings demonstrate the importance of dynamic information in the encoding of genuine and deliberate expressions of surprise and the importance of the production method employed in research.
Expansion and characterization of bone marrow derived human mesenchymal stromal cells in serum-free conditions
Authors: Bhat Samatha , Viswanathan Pachaiyappan , Chandanala Shashank , Prasanna S. Jyothi , Seetharam Raviraja N. 
Published: February 2021

AbstractBone marrow-derived mesenchymal stromal cells (BM-MSCs) are gaining increasing importance in the field of regenerative medicine. Although therapeutic value of MSCs is now being established through many clinical trials, issues have been raised regarding their expansion as per regulatory guidelines. Fetal bovine serum usage in cell therapy poses difficulties due to its less-defined, highly variable composition and safety issues. Hence, there is a need for transition from serum-based to serum-free media (SFM). Since SFM are cell type-specific, a precise analysis of the properties of MSCs cultured in SFM is required to determine the most suitable one. Six different commercially available low serum/SFM with two different seeding densities were evaluated to explore their ability to support the growth and expansion of BM-MSCs and assess the characteristics of BM-MSCs cultured in these media. Except for one of the SFM, all other media tested supported the growth of BM-MSCs at a low seeding density. No significant differences were observed in the expression of MSC specific markers among the various media tested. In contrary, the population doubling time, cell yield, potency, colony-forming ability, differentiation potential, and immunosuppressive properties of MSCs varied with one another. We show that SFM tested supports the growth and expansion of BM-MSCs even at low seeding density and may serve as possible replacement for animal-derived serum.
Polyglycolic acid sheet covering to prevent recurrence after surgery for spontaneous pneumothorax: a meta-analysis
Authors: Kadomatsu Yuka , Fukui Takayuki , Mori Shoichi , Chen-Yoshikawa Toyofumi Fengshi , Wakai Kenji 
Published: February 2021

AbstractThe coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I2 index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20–0.37, P < 0.001; I2 0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.
Physician requirements for adoption of telehealth following the SARS-CoV-2 pandemic
Authors: Hodgkins Michael , Barron Meg , Jevaji Shireesha , Lloyd Stacy 
Published: February 2021

AbstractIt took the advent of SARS-CoV-2, a “black swan event”, to widely introduce telehealth, remote care, and virtual house calls. Prior to the epidemic (2019), the American Medical Association (AMA) conducted a routine study to compare physicians’ adoption of emerging technologies to a similar survey in 2016. Most notable was a doubling in the adoption of telehealth/virtual technology to 28% and increases in the use of remote monitoring and management for improved care (13–22%). These results may now seem insignificant when compared to the unprecedented surge in telehealth visits because of SARS-CoV-2. Even as this surge levels off and begins to decline, many observers believe we will continue to see a persistent increase in the use of virtual visits compared to face-to-face care. The requirements for adoption communicated by physicians in both the 2016 and 2019 surveys are now more relevant than ever: Is remote care as effective as in-person care and how best to determine when to use these modalities? How do I safeguard my patients and my practice from liability and privacy concerns? How do I optimize using these technologies in my practice and, especially integration with my EHR and workflows to improve efficiency? And how will a mix of virtual and in-person visits affect practice revenue and sustainability? Consumers have also expressed concerns about payment for virtual visits as well as privacy and quality of care. If telehealth and remote care are here to stay, continuing to track their impact during the current public health emergency is critically important to address so that policymakers and insurers will take necessary steps to ensure that the “new normal” will reflect a health care delivery model that can provide comparable or improved results today and into the future.
Country-based rate of emissions reductions should increase by 80% beyond nationally determined contributions to meet the 2 °C target
Authors: Liu Peiran R. , Raftery Adrian E. 
Published: February 2021

AbstractThe 2015 Paris Agreement aims to keep global warming by 2100 to below 2 °C, with 1.5 °C as a target. To that end, countries agreed to reduce their emissions by nationally determined contributions (NDCs). Using a fully statistically based probabilistic framework, we find that the probabilities of meeting their nationally determined contributions for the largest emitters are low, e.g. 2% for the USA and 16% for China. On current trends, the probability of staying below 2 °C of warming is only 5%, but if all countries meet their nationally determined contributions and continue to reduce emissions at the same rate after 2030, it rises to 26%. If the USA alone does not meet its nationally determined contribution, it declines to 18%. To have an even chance of staying below 2 °C, the average rate of decline in emissions would need to increase from the 1% per year needed to meet the nationally determined contributions, to 1.8% per year.