bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of miRNA–disease associations via deep forest ensemble learning based on autoencoder
Authors: Liu Wei , Lin Hui , Huang Li , Peng Li , Tang Ting , Zhao Qi , Yang Li 
Published: March 2022

AbstractIncreasing evidences show that the occurrence of human complex diseases is closely related to microRNA (miRNA) variation and imbalance. For this reason, predicting disease-related miRNAs is essential for the diagnosis and treatment of complex human diseases. Although some current computational methods can effectively predict potential disease-related miRNAs, the accuracy of prediction should be further improved. In our study, a new computational method via deep forest ensemble learning based on autoencoder (DFELMDA) is proposed to predict miRNA–disease associations. Specifically, a new feature representation strategy is proposed to obtain different types of feature representations (from miRNA and disease) for each miRNA–disease association. Then, two types of low-dimensional feature representations are extracted by two deep autoencoders for predicting miRNA–disease associations. Finally, two prediction scores of the miRNA–disease associations are obtained by the deep random forest and combined to determine the final results. DFELMDA is compared with several classical methods on the The Human microRNA Disease Database (HMDD) dataset. Results reveal that the performance of this method is superior. The area under receiver operating characteristic curve (AUC) values obtained by DFELMDA through 5-fold and 10-fold cross-validation are 0.9552 and 0.9560, respectively. In addition, case studies on colon, breast and lung tumors of different disease types further demonstrate the excellent ability of DFELMDA to predict disease-associated miRNA–disease. Performance analysis shows that DFELMDA can be used as an effective computational tool for predicting miRNA–disease associations.
Characterizing the stabilization effects of stabilizers in protein–protein systems with end-point binding free energy calculations
Authors: Tang Rongfan , Chen Pengcheng , Wang Zhe , Wang Lingling , Hao Haiping , Hou Tingjun , Sun Huiyong 
Published: March 2022

AbstractDrug design targeting protein–protein interactions (PPIs) associated with the development of diseases has been one of the most important therapeutic strategies. Besides interrupting the PPIs with PPI inhibitors/blockers, increasing evidence shows that stabilizing the interaction between two interacting proteins may also benefit the therapy, such as the development of various types of molecular glues/stabilizers that mostly work by stabilizing the two interacting proteins to regulate the downstream biological effects. However, characterizing the stabilization effect of a stabilizer is usually hard or too complicated for traditional experiments since it involves ternary interactions [protein–protein–stabilizer (PPS) interaction]. Thus, developing reliable computational strategies will facilitate the discovery/design of molecular glues or PPI stabilizers. Here, by fully analyzing the energetic features of the binary interactions in the PPS ternary complex, we systematically investigated the performance of molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) methods on characterizing the stabilization effects of stabilizers in 14-3-3 systems. The results show that both MM/PBSA and MM/GBSA are powerful tools in distinguishing the stabilizers from the decoys (with area under the curves of 0.90–0.93 for all tested cases) and are reasonable for ranking protein–peptide interactions in the presence or absence of stabilizers as well (with the average Pearson correlation coefficient of ~0.6 at a relatively high dielectric constant for both methods). Moreover, to give a detailed picture of the stabilization effects, the stabilization mechanism is also analyzed from the structural and energetic points of view for individual systems containing strong or weak stabilizers. This study demonstrates a potential strategy to accelerate the discovery of PPI stabilizers.
In vitro investigation of mammalian peri-implantation embryogenesis
Authors: Quan Yujun , Wang Xiaoxiao , Li Lei 
Published: March 2022

Abstract
The embryos attach and invade the uterus, establishing the connection with their mother in peri-implantation development. During this period, the pluripotent epiblast cells of the embryo undergo symmetry breaking, cell lineage allocation, and morphogenetic remodeling, accompanied by the dramatic changes of transcriptomic, epigenomic, and signaling pathways, and preparing the stage for their differentiation and gastrulation. The progress in mouse genetics and stem cell biology has advanced the knowledge of these transformations, which are still largely hindered by the hard accessibility of natural embryos. To gain insight into mammalian peri-implantation development, much effort has been made in the field. Recently, advances in the prolonged in vitro culture of blastocysts, the derivation of multiple pluripotent stem cells, and the construction of stem cell-based embryo-like models have opened novel avenues to investigate peri-implantation development in mammals, especially humans. Combining with other emerging new technologies, these new models will substantially promote the comprehension of mammalian peri-implantation development, thus accelerating the progress of reproductive and regenerative medicine.
Various tests of left neglect are associated with distinct territories of hypoperfusion in acute stroke
Authors: Stein Colin , Bunker Lisa , Chu Brian , Leigh Richard , Faria Andreia , Hillis Argye E. 
Published: March 2022

Abstract
Hemispatial neglect is among the most disabling consequences of right hemisphere stroke. However, there is no consensus on the optimal assessments to identify neglect. We hypothesized that different tests for neglect given the same day (i) detect distinct aspects and types of neglect, (ii) are sensitive to different cognitive functions (beyond spatially specific processing) and (iii) are associated with distinct regions of hypoperfusion. We examined data from 135 participants with acute, right-hemispheric ischaemic stroke who received an MRI and neglect testing within 48 h of acute infarct in a cross-sectional study. The volume of infarct was calculated on diffusion-weighted imaging. We also scored severity and location of fluid-attenuated inversion recovery hyperintense vessels in six areas (anterior cerebral artery territory, posterior cerebral artery territory and four within the middle cerebral artery territory) to estimate the volume and location of hypoperfusion in acute stroke. Neglect tests included gap detection, scene copy, line bisection, line cancellation, oral reading and picture description. We found strong correlations between tests that evaluated viewer-centred processing, as well as strong correlations between tests that evaluated stimulus-centred processing. The error rate on different tests was associated with hypoperfusion in different vascular territories, even after controlling for the volume of an infarct. Our results confirm that it is essential to administer a battery of different tests of hemispatial neglect to capture various deficits in attention and spatially specific processing that underlies neglect. Our results also show the potential usefulness of hyperintense vessel ratings as an indication of dysfunction beyond the infarct, as the ratings (and not infarct volume) were highly associated with many clinical deficits. Finally, results underscore that diverse types of neglect are clinically important in acute stroke, as they reflect different areas of hypoperfused tissue, which may be salvageable in the absence of infarct in those areas. As such, neglect batteries may be useful for detecting patients with cortical hypoperfusion who are candidates for reperfusion therapies.
Mapping cerebral atrophic trajectory from amnestic mild cognitive impairment to Alzheimer’s disease
Authors: Wei Xiaotong , Du Xiaotong , Xie Yingying , Suo Xinjun , He Xiaoxi , Ding Hao , Zhang Yu , Ji Yi , Chai Chao , Liang Meng , Yu Chunshui , Liu Yong , Qin Wen ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2022

AbstractAlzheimer’s disease (AD) patients suffer progressive cerebral atrophy before dementia onset. However, the region-specific atrophic processes and the influences of age and apolipoprotein E (APOE) on atrophic trajectory are still unclear. By mapping the region-specific nonlinear atrophic trajectory of whole cerebrum from amnestic mild cognitive impairment (aMCI) to AD based on longitudinal structural magnetic resonance imaging data from Alzheimer’s disease Neuroimaging Initiative (ADNI) database, we unraveled a quadratic accelerated atrophic trajectory of 68 cerebral regions from aMCI to AD, especially in the superior temporal pole, caudate, and hippocampus. Besides, interaction analyses demonstrated that APOE ε4 carriers had faster atrophic rates than noncarriers in 8 regions, including the caudate, hippocampus, insula, etc.; younger patients progressed faster than older patients in 32 regions, especially for the superior temporal pole, hippocampus, and superior temporal gyrus; and 15 regions demonstrated complex interaction among age, APOE, and disease progression, including the caudate, hippocampus, etc. (P &lt; 0.05/68, Bonferroni correction). Finally, Cox proportional hazards regression model based on the identified region-specific biomarkers could effectively predict the time to AD conversion within 10 years. In summary, cerebral atrophic trajectory mapping could help a comprehensive understanding of AD development and offer potential biomarkers for predicting AD conversion.
Extended, standard, or De-escalation antiplatelet therapy for patients with coronary artery disease undergoing percutaneous coronary intervention? A trial-sequential, bivariate, influential, and network meta-analysis
Authors: Ullah Waqas , Zahid Salman , Sandhyavenu Harigopal , Faisaluddin Mohammed , Khalil Fouad , Pasha Ahmad K , Alraies M Chadi , Cuisset Thomas , Rao Sunil V , Sabouret Pierre , Savage Michael P , Fischman David L 
Published: March 2022

Abstract

Aims
The relative safety and efficacy of de-escalation, extended duration (ED) (&gt;12-months), and standard dual antiplatelet therapy for 12-months (DAPT-12) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial.

Methods and results
Online databases were queried to identify relevant randomized control trials (RCTs). ED-DAPT, high-potency (HP) DAPT, shorter duration (SD) DAPT, and low-dose (LD) DAPT were compared with DAPT-12. A trial sequential, bivariate, influential, and frequentist network meta-analysis (NMA) was performed to determine the pooled estimates. A total of 30 RCTs comprising 81 208 (40 839 experimental, 40 369 control arm) patients with CAD were included in the quantitative analysis. On NMA, compared with DAPT-12, all types of de-escalation, HP-DAPT-12, and ED-DAPT strategies had a statistically non-significant difference in the incidence of MACE at a median follow-up of 1-year. Similarly, there was no significant difference in the incidence of stroke, stent thrombosis, target lesion revascularization (TLR), target vessel revascularization (TVR), and all-cause mortality between DAPT-12 and all other strategies. The network estimates showed a significantly lower incidence of major bleeding with DAPT for 3-months followed by P2Y12-inhibitor monotherapy (RR 0.62, 95% CI 0.45–0.84), while a higher risk of bleeding with HP-DAPT for 12 months (RR 1.55, 95% CI 1.16–2.06). The net clinical benefit and rankograms also favoured DAPT-3 (P2Y12) and discouraged the use of HP-DAPT-12 and ED-DAPT. A subgroup analysis of 19 RCTs restricted to patients who presented with acute coronary syndrome (ACS) mirrored the findings of pooled analysis. A sensitivity analysis revealed no influence of any individual study or individual strategy on net ischemic estimates. The trial sequential analysis (TSA) illustrated a consistently non-significant difference at the interim analysis of trials, reaching the futility area for MACE, while the cumulative Z-values line surpassed the monitoring boundary as well as the required information size for major bleeding favouring de-escalation strategy.

Conclusion
DAPT for three months followed by ticagrelor-only and use of aspirin + clopidogrel after a short period of high potency DAPT appears to be a safe strategy for treating post-PCI patients. However, given the methodological limitations and inclusion of a small number of trials in novel de-escalation strategies, these findings need validation by future large scale RCTs.
Social Class and (Un)Ethical Behaviour: Causal and Correlational Evidence
Authors: Gsottbauer Elisabeth , Müller Daniel , Müller Samuel , Trautmann Stefan T , Zudenkova Galina 
Published: March 2022

Abstract
Are individuals of higher socio-economic status less ethical than those of lower status? Highly popularised research findings claim that this is the case. This paper provides evidence against this claim, based on data from two large survey experiments with more than 11,000 participants. We prime social status in two heterogeneous samples of the German population and then elicit ethical behaviour in an incentivised experimental task. Thus, our data allows us to study both correlation (using demographic data) and causality (using the priming). Our study rejects the claim that higher social status individuals are less ethical on both accounts.
Co-creating with families and healthcare professionals: shaping a context-sensitive health promotion intervention ‘Face-it’
Authors: Timm Anne , Maindal Helle Terkildsen , Hillersdal Line 
Published: March 2022

Summary
Participatory methodologies have become imperative when developing health promotion programmes. However, the concrete adoption of co-creation and its implications for intervention development are less reported. This article aims to convey how fidelity and adaptation were balanced in a structured intervention design by co-creating intervention components with various stakeholders. The intervention was part of the Face-it programme, which was initiated to prevent diabetes and increase the quality of life in women with prior diabetes during pregnancy by supporting the entire family’s health practices. We relied on participatory methods, e.g. workshops using design games, role play and family interviews, as well as ethnographic fieldwork. Stakeholders comprised women with prior gestational diabetes mellitus and their families as intervention receivers and healthcare professionals, e.g. obstetricians, midwives and health visitors as potential intervention deliverers to shape intervention content. We used Bammer’s stakeholder participation spectrum in research to describe how different stakeholders were engaged and with what implications for the intervention components. This article shows how an iterative co-creation process was (i) achieved through diverse involvement practices across stakeholder groups; and (ii) upheld both premises of the structured design (fidelity) and flexibility (adaptation) in developing intervention content and delivery. When adopting co-creation as a strategy for intervention development, we recommend using various engagement practices according to the role of stakeholders in the intervention and available resources to create ownership and sustainable intervention content.
Sugar signal mediates flavonoid biosynthesis in tea leaves
Authors: Lv Yi-Qing , Li Da , Wu Liang-Yu , Zhu Yu-Meng , Ye Ying , Zheng Xin-Qiang , Lu Jian-Liang , Liang Yue-Rong , Li Qing-Sheng , Ye Jian-Hui 
Published: March 2022

Abstract
Sugar metabolism and flavonoid biosynthesis vary with the development of tea leaves. In order to understand the regulatory mechanisms underlying the associations between them, a comprehensive transcriptomic analysis of naturally growing tea leaves at different stages of maturity was carried out. Based on weighted gene coexpression network analysis, the key gene modules (Modules 2 and 3) related to the varying relationship between sugar metabolism and flavonoid biosynthesis as well as the corresponding hub genes were obtained. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that the transcription factors (TFs) in Modules 2 and 3 were mainly enriched in the pathway of plant hormone signal transduction. An in vitro study showed that the transcriptional levels of ERF1B-like TF for hexokinase inhibitor and sucrose treatments were upregulated, being respectively 28.1- and 30.2-fold higher than in the control, suggesting that ERF1B-like TFs participate in the sugar-induced regulation of flavonoid biosynthesis. The results of yeast one-hybrid and dual-luciferase assays demonstrated that CsF3′H, encoding flavonoid 3′-hydroxylase, was the target flavonoid biosynthetic gene for CsERF1B-like TF. Our study identified the potential key regulators participating in the metabolism of sugars and flavonoids, providing new insights into the crosstalk between sugar metabolism and flavonoid biosynthesis in tea plants.
Role of female-predominant MYB39-bHLH13 complex in sexually dimorphic accumulation of taxol in Taxus media
Authors: Yu Chunna , Huang Jiefang , Wu Qicong , Zhang Chengchao , Li Xiao-lin , Xu Xinyun , Feng Shangguo , Zhan Xiaori , Chen Zhehao , Wang Huizhong , Shen Chenjia 
Published: March 2022

Abstract
Taxus trees are major natural sources for the extraction of taxol, an anti-cancer agent used worldwide. Taxus media is a dioecious woody tree with high taxol yield. However, the sexually dimorphic accumulation of taxoids in T. media is largely unknown. Our study revealed high accumulation of taxoids in female T. media trees using a UPLC–MS/MS method. Thereafter, many differential metabolites and genes between female and male T. media trees were identified using metabolomic and transcriptomic analyses, respectively. Most of the taxol-related genes were predominantly expressed in female trees. A female-specific R2R3-MYB transcription factor gene, TmMYB39, was identified. Furthermore, bimolecular fluorescence complementation and yeast two-hybrid assays suggested the potential interaction between TmMYB39 and TmbHLH13. Several taxol biosynthesis-related promoter sequences were isolated and used for the screening of MYB recognition elements. The electrophoretic mobility shift assay indicated that TmMYB39 could bind to the promoters of the GGPPS, T10OH, T13OH, and TBT genes. Interaction between TmMYB39 and TmbHLH13 transactivated the expression of the GGPPS and T10OH genes. TmMYB39 might function in the transcriptional regulation of taxol biosynthesis through an MYB-bHLH module. Our results give a potential explanation for the sexually dimorphic biosynthesis of taxol in T. media.
Molecular mechanisms underlying multi-level defense responses of horticultural crops to fungal pathogens
Authors: Xu Xiaodi , Chen Yong , Li Boqiang , Zhang Zhanquan , Qin Guozheng , Chen Tong , Tian Shiping 
Published: March 2022

AbstractThe horticultural industry helps to enrich and improve the human diet while contributing to growth of the agricultural economy. However, fungal diseases of horticultural crops frequently occur during pre- and postharvest periods, reducing yields and crop quality and causing huge economic losses and wasted food. Outcomes of fungal diseases depend on both horticultural plant defense responses and fungal pathogenicity. Plant defense responses are highly sophisticated and are generally divided into preformed and induced defense responses. Preformed defense responses include both physical barriers and phytochemicals, which are the first line of protection. Induced defense responses, which include innate immunity (pattern-triggered immunity and effector-triggered immunity), local defense responses, and systemic defense signaling, are triggered to counterstrike fungal pathogens. Therefore, to develop regulatory strategies for horticultural plant resistance, a comprehensive understanding of defense responses and their underlying mechanisms is critical. Recently, integrated multi-omics analyses, CRISPR-Cas9-based gene editing, high-throughput sequencing, and data mining have greatly contributed to identification and functional determination of novel phytochemicals, regulatory factors, and signaling molecules and their signaling pathways in plant resistance. In this review, research progress on defense responses of horticultural crops to fungal pathogens and novel regulatory strategies to regulate induction of plant resistance are summarized, and then the problems, challenges, and future research directions are examined.
Large thrombus in transit in a COVID-19 patient
Authors: Bleiziffer Sabine , Zabel Reinhard , Gummert Jan F , Deutsch Marcus-André 
Published: March 2022

AbstractThe course of COVID-19 patients may be complicated by thromboembolic events. We report on a 48-year-old female COVID-19 patient who underwent surgical removal of a large intracardiac thrombus. As per our centre protocol, critically ill COVID-19 patients are anticoagulated by the direct thrombin inhibitor Argatroban with close monitoring of anti-IIa activity. An intra-atrial thrombus formation fixed in a patent foramen ovale but also large mobile portions in both atria was diagnosed 4 days after weaning and removal of the jugular and femoral extracorporeal membrane oxygenation cannulas. The thrombus was removed surgically via median sternotomy and on cardiopulmonary bypass. The thrombus had a bizarre appearance with several finger-like appendices, and histological analysis revealed a mixed picture of acute and chronic thrombus portions. This case highlights the risk of life-threatening thrombus formation in COVID-19 patients despite therapeutic thrombin inhibition.
Street Art, the Discontinuity Thesis, and the Artworld
Authors: Bicknell Jeanette 
Published: March 2022

Abstract
The topic of this article is the relationship of street art to both the street (or “the street”) and the artworld. I take it as significant that philosophers have turned their attention to “street art” and not, say, “urban outdoor art” or “site-specific art in urban settings.” The “street” in street art seems to imply more than a location or geographic modifier. I consider the further significance of the “street” in street art, and the view, argued or assumed, of the street when philosophers discuss street art. My second target in this article is what I have called the “discontinuity thesis.” This is the idea, defended or assumed in some of the most important philosophical writing about street art, that street art represents a radical break with the artworld and is “antithetical” to it. I argue that the discontinuity thesis is mistaken, and that to understand the larger institutional context of street art we must examine the sociology of artworlds. Street art has followed a familiar process and pioneering street artists are best seen as “mavericks” in Howard Becker’s sense. I argue that seeing street artists in this way can help better understand and appreciate their work.
The Fictional Road Not Taken: A Weak Anti-realist Theory of Fiction
Authors: Alward Peter 
Published: March 2022

AbstractNathan Salmon has defended what might be called “weak modal anti-realism”—the view that possible-object names can refer to possible objects that neither exist nor are otherwise real. But rather than adopting a similar view in the fictional case, he instead defends fictional creationism—the view that fictional characters are existent but abstract entities created by authors of fiction. In this paper, I first argue that if weak modal antirealism is defensible then weak fictional antirealism is defensible as well. Second, I argue that there is no reason to prefer fictional creationism over weak fictional antirealism but there is very good reason to prefer the latter over the former. And third, I defend weak fictional antirealism against the charge that it cannot provide a satisfactory account of statements that prima facie involve reference to or quantification over fictional characters.