bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bistability in cell signalling and its significance in identifying potential drug-targets
Authors: Halder Suvankar , Ghosh Sumana , Chattopadhyay Joydev , Chatterjee Samrat 
Published: May 2021

Abstract

Motivation
Bistability is one of the salient dynamical features in various all-or-none kinds of decision-making processes. The presence of bistability in a cell signalling network plays a key role in input–output (I/O) relation. Our study is aiming to capture and emphasize the role of motif structure influencing the I/O relation between two nodes in the context of bistability. Here, a model-based analysis is made to investigate the critical conditions responsible for the emergence of different bistable protein–protein interaction (PPI) motifs and their possible applications to find the potential drug-targets.

Results
The global sensitivity analysis is used to identify sensitive parameters and their role in maintaining the bistability. Additionally, the bistable switching through hysteresis is explored to develop an understanding of the underlying mechanisms involved in the cell signalling processes, when significant motifs exhibiting bistability have emerged. Further, we elaborate the application of the results by the implication of the emerged PPI motifs to identify potential drug-targets in three cancer networks, which is validated with existing databases. The influence of stochastic perturbations that could hinder desired functionality of any signalling networks is also described here.

Supplementary information
Supplementary data are available at Bioinformatics online.
Ring-like late gadolinium enhancement for predicting ventricular tachyarrhythmias in non-ischaemic dilated cardiomyopathy
Authors: Chen Wensu , Qian Wen , Zhang Xinwei , Li Dongcheng , Qian Zhiyong , Xu Hai , Liao Shengen , Chen Xing , Wang Yao , Hou Xiaofeng , Patel Amit R , Xu Yi , Zou Jiangang 
Published: May 2021

AbstractAimsMyocardial fibrosis is associated with clinical ventricular tachyarrhythmia (VTA) events in patients with non-ischaemic dilated cardiomyopathy (DCM). Subepicardial or mid-wall ring-like late gadolinium enhancement (LGE) has received increasing attention in recent years. The aim of this study was to investigate the relationship between ring-like LGE and VTAs in DCM.Methods and resultsPatients diagnosed with non-ischaemic DCM who underwent cardiac magnetic resonance with LGE imaging at baseline were investigated. The composite outcome was the occurrence of VTAs defined as sustained ventricular tachycardia, ventricular fibrillation/flutter, aborted sudden cardiac death (SCD), SCD, and appropriate implantable cardioverter-defibrillator intervention. The final cohort comprised 157 patients, including 36 (22.9%) in no LGE group, 48 (30.6%) in focal LGE group, 40 (25.5%) in multi-focal LGE group, and 33 (21%) in ring-like LGE group. Ring-like LGE group patients were younger compared to focal and multi-focal LGE group (P &lt; 0.001) with higher left ventricular ejection fraction (33.0% vs. 24.4% vs. 22.1%, P &lt; 0.001). After a median of 13 ± 7 months follow-up, compared to patients with no LGE, the hazard ratios (HRs) with 95% confidence intervals (CIs) for VTAs were 2.90 (0.56–15.06), 5.55 (1.21–25.44), and 11.75 (2.66–51.92) for patients with focal LGE, multi-focal LGE, and ring-like LGE, respectively. After multivariable adjustment, ring-like LGE group remained associated with increased risk of VTAs (adjusted HR 10.00, 95% CI 1.54–64.98; P = 0.016) independent of the global LGE burdenConclusionThe ring-like pattern of LGE is independently associated with an increased risk of VTAs in patients with non-ischaemic DCM.
The Atlantic salmon’s stress- and immune-related transcriptional responses to moderate hypoxia, an incremental temperature increase, and these challenges combined
Authors: Beemelmanns Anne , Zanuzzo Fábio S , Sandrelli Rebeccah M , Rise Matthew L , Gamperl A Kurt 
Published: May 2021

AbstractThe marine environment is predicted to become warmer, and more hypoxic, and these conditions may negatively impact the health and survival of coastal fish species, including wild and farmed Atlantic salmon (Salmo salar). Thus, we examined how: (1) moderate hypoxia (∼70% air saturation) at 12°C for 3 weeks; (2) an incremental temperature increase from 12°C to 20°C (at 1°C week−1) followed by 4 weeks at 20°C; and (3) treatment “2” combined with moderate hypoxia affected transcript expression in the liver of post-smolts as compared to control conditions (normoxia, 12°C). Specifically, we assessed the expression of 45 genes related to the heat shock response, oxidative stress, apoptosis, metabolism and immunity using a high-throughput qPCR approach (Fluidigm Biomark™ HD). The expression profiles of 27 “stress”-related genes indicated that: (i) moderate hypoxia affected the expression of several stress genes at 12°C; (ii) their expression was impacted by 16°C under normoxic conditions, and this effect increased until 20°C; (iii) the effects of moderate hypoxia were not additive to those at temperatures above 16°C; and (iv) long-term (4 weeks) exposure to 20°C, with or without hypoxia, resulted in a limited acclimatory response. In contrast, the expression of 15 immune-related genes was not greatly affected until temperatures reached 20°C, and this effect was particularly evident in fish exposed to the added challenge of hypoxia. These results provide valuable information on how these two important environmental factors affect the “stress” physiology and immunology of Atlantic salmon, and we identify genes that may be useful as hypoxia and/or temperature biomarkers in salmonids and other fishes.
NGSremix: a software tool for estimating pairwise relatedness between admixed individuals from next-generation sequencing data
Authors: Nøhr Anne Krogh , Hanghøj Kristian , Garcia-Erill Genís , Li Zilong , Moltke Ida , Albrechtsen Anders 
Published: May 2021

AbstractEstimation of relatedness between pairs of individuals is important in many genetic research areas. When estimating relatedness, it is important to account for admixture if this is present. However, the methods that can account for admixture are all based on genotype data as input, which is a problem for low-depth next-generation sequencing (NGS) data from which genotypes are called with high uncertainty. Here, we present a software tool, NGSremix, for maximum likelihood estimation of relatedness between pairs of admixed individuals from low-depth NGS data, which takes the uncertainty of the genotypes into account via genotype likelihoods. Using both simulated and real NGS data for admixed individuals with an average depth of 4x or below we show that our method works well and clearly outperforms all the commonly used state-of-the-art relatedness estimation methods PLINK, KING, relateAdmix, and ngsRelate that all perform quite poorly. Hence, NGSremix is a useful new tool for estimating relatedness in admixed populations from low-depth NGS data. NGSremix is implemented in C/C++ in a multi-threaded software and is freely available on Github https://github.com/KHanghoj/NGSremix.
Understanding Community-Dwelling Chinese Older Adults’ Engagement in Physical Activity: A Grounded Theory Study
Authors: Wang Haocen , King Barbara 
Published: May 2021

AbstractBackground and ObjectivesLimited information is available on the process of Chinese older adults’ initiation, engagement, and maintenance of physical activity (PA), thus limiting the development of effective PA promotion programs. The purpose of the study was to investigate Chinese old adults’ perspectives and experiences with PA engagement and to develop a conceptual model illustrating the process of how community-dwelling Chinese older adults engage in PA.Research Design and MethodsThis study used grounded theory methodology. Nineteen community-dwelling Chinese older adults aged older than 60 years participated. We conducted semistructured in-depth interviews with participants. Open, axial, and selective coding, along with constant comparative analysis, was performed to analyze the data.ResultsParticipants described PA engagement as a complex and dynamic process, consisting of 3 stages: Getting started, Participating in PA, and Making PA part of life. The transition from one stage to the next was driven by an increasing internalized motivation toward PA through Seeing benefits. Many participants described that Staying in groups was a key strategy for them to keep physically active. Moreover, Restructuring occurred when Chinese older adults encountered trigger situations.Discussion and ImplicationsThis study identified the stages of how community-dwelling Chinese older adults engage in to perform and maintain PA. The developed conceptual model can inform future interventions for promoting PA among Chinese older adults.
Glucosylceramide and galactosylceramide, small glycosphingolipids with significant impact on health and disease
Authors: Reza Safoura , Ugorski Maciej , Suchański Jarosław 
Published: May 2021

AbstractNumerous clinical observations and exploitation of cellular and animal models indicate that glucosylceramide (GlcCer) and galactosylceramide (GalCer) are involved in many physiological and pathological phenomena. In many cases, the biological importance of these monohexosylcermides has been shown indirectly as the result of studies on enzymes involved in their synthesis and degradation. Under physiological conditions, GalCer plays a key role in the maintenance of proper structure and stability of myelin and differentiation of oligodendrocytes. On the other hand, GlcCer is necessary for the proper functions of epidermis. Such an important lysosomal storage disease as Gaucher disease (GD) and a neurodegenerative disorder as Parkinson’s disease are characterized by mutations in the GBA1 gene, decreased activity of lysosomal GBA1 glucosylceramidase and accumulation of GlcCer. In contrast, another lysosomal disease, Krabbe disease, is associated with mutations in the GALC gene, resulting in deficiency or decreased activity of lysosomal galactosylceramidase and accumulation of GalCer and galactosylsphingosine. Little is known about the role of both monohexosylceramides in tumor progression; however, numerous studies indicate that GlcCer and GalCer play important roles in the development of multidrug-resistance by cancer cells. It was shown that GlcCer is able to provoke immune reaction and acts as a self-antigen in GD. On the other hand, GalCer was recognized as an important cellular receptor for HIV-1. Altogether, these two molecules are excellent examples of how slight differences in chemical composition and molecular conformation contribute to profound differences in their physicochemical properties and biological functions.
Multiple Switches From the Originator Infliximab to Biosimilars Is Effective and Safe in Inflammatory Bowel Disease: A Prospective Multicenter Cohort Study
Authors: Hanzel Jurij , Jansen Jeroen M , ter Steege Rinze W F , Gecse Krisztina B , D’Haens Geert R 
Published: May 2021

Abstract

Background
Though a single nonmedical switch from the originator infliximab (IFX) to a biosimilar is considered effective and safe for most patients with inflammatory bowel disease (IBD), very limited data are available on multiple successive switches.

Methods
We performed a prospective multicenter cohort study of adult IBD patients who underwent 2 switches from the originator IFX to CT-P13 to SB2 (group 1), 1 switch from CT-P13 to SB2 (group 2), and 1 switch from the originator IFX to CT-P13 (group 3). Patients were assessed at 4 and 12 months since the most recent switch for remission using clinical (physician’s assessment) and biochemical (C-reactive protein [CRP], and fecal calprotectin [FC]) measures. Patients discontinuing treatment for ineffectiveness or adverse events before month 12 were imputed as nonremitters.

Results
One hundred seventy-six patients (Crohn’s disease 71%, ulcerative colitis 27.8%, IBD unclassified 1.2%; group 1, 69; group 2, 80; group 3, 27) were included. At 12 months after the most recent switch 76.9% (40 of 52, group 1), 65.7% (46 of 70, group 2) and 76.9% (20 of 26, group 3) of patients were in clinical remission. Treatment persistence at 12 months was 85.0%, 87.0%, and 70.1%, respectively. There were no significant differences in the rate of clinical, CRP, FC remission, or treatment persistence at 12 months between the 3 groups. Infusion reactions occurred in 1.7% of patients (3/176), all in patients with antidrug antibodies from group 2.

Conclusions
Multiple successive switching and switching between biosimilars of IFX seemed to be effective and safe.
Intestinal Ultrasound in Pediatric Inflammatory Bowel Disease: Promising, but Work in Progress
Authors: van Wassenaer Elsa A , Benninga Marc A , van Limbergen Johan L , D’Haens Geert R , Griffiths Anne M , Koot Bart G P 
Published: May 2021

Abstract
Intestinal ultrasound (IUS) is increasingly used and promulgated as a noninvasive monitoring tool for children with inflammatory bowel disease because other diagnostic modalities such as colonoscopy and magnetic resonance imaging cause significant stress in the pediatric population. The most important parameters of inflammation that can be assessed using IUS are bowel wall thickness and hyperemia of the bowel wall. Research has shown that IUS has the potential to be a valuable additional point-of-care tool to guide treatment choice and to monitor and predict treatment response, although evidence of its accuracy and value in clinical practice is still limited. This review gives an update and overview of the current evidence on the use and accuracy of IUS in children with inflammatory bowel disease.
Perspectives on Community STEM: Learning from Partnerships between Scientists, Researchers, and Youth
Authors: Nation Jasmine McBeath , Hansen Alexandria Killian 
Published: May 2021

AbstractGiven our rapidly changing world and the pressing challenges of climate change and health care, it is more important than ever for youth and the broader public to learn scientific knowledge and skills. To reach the most people possible and increase diversity in Science, Technology, Engineering, and Mathematics (STEM) fields, we need compelling educational approaches that incorporate the lived experiences of students. Partnerships between researchers, scientists, educators, and community groups can enrich and extend scientists’ research while providing authentic scientific learning experiences for undergraduate and K-12 students, especially from STEM-underrepresented groups. However, more research is needed on equitable long-term partnerships, including how these projects are organized and how partners align their interests and goals. In this article, we present recommendations from research–practice partnership projects that utilize a Community STEM model, an approach that draws from individual and collective strengths, contextualizes science learning, and positions youth as producers of content and artifacts. To situate this work, we review and highlight biology-related citizen and community science projects designed for youth. We characterize projects according to their goals and format, provide illustrative examples of three programs, and provide recommendations for other scientists and researchers. Overall, this article reviews research on all three approaches for partnerships (citizen science, community science, and community STEM) to provide recommendations for scientists who are interested in establishing partnerships within their communities. Limitations of each approach are described as well as areas for further research.
Does the size of pulmonary artery impact on recoarctation of the aorta after the Norwood procedure without patch?
Authors: Kobayashi Yasuyuki , Kotani Yasuhiro , Kawabata Takuya , Kuroko Yosuke , Sano Shunji , Kasahara Shingo 
Published: May 2021

Abstract

OBJECTIVES
This study aimed to evaluate whether recoarctation of the aorta (reCoA) after the Norwood procedure for hypoplastic left heart syndrome correlates with pre- and postoperative anatomic factors.

METHODS
This retrospective study included 48 patients who underwent Norwood procedure with right ventricle-to-pulmonary artery conduit between 2009 and 2017. Anatomical factors such as preoperative length, diameter of the main pulmonary artery (MPA), and postoperative neoaortic arch angle stratified by arch reconstruction technique were analysed using the receiver operating characteristic analysis.

RESULTS
Eleven patients needed surgical intervention for reCoA at stage 2. Out of the 30 patients who underwent direct anastomosis during arch reconstruction, 7 developed reCoA. Seven patients received the full patch augmentation (patch augmentation for both lesser and greater curvatures) and were all spared from reCoA. Among the patients who had direct anastomosis, the preoperative MPA length was correlated with the postoperative arch angle (P = 0.021) and was associated with the occurrence of reCoA (P = 0.002) and the best cutoff value for MPA length was 10 mm. The postoperative arch angle was also correlated with the incidence of reCoA (P &lt; 0.001) and was larger in patients who underwent the full patch augmentation than in patients who had direct anastomosis (126° vs 112°, P = 0.005) despite comparable MPA length.

CONCLUSIONS
ReCoA after the Norwood procedure correlates with MPA length when a direct anastomosis was used. Direct anastomosis can be considered in patients with a longer preoperative MPA. In other cases, the full patch augmentation should be considered for obtaining a large and smooth neoaortic arch.
The Geopolitical Threat Index: A Text-Based Computational Approach to Identifying Foreign Threats
Authors: Trubowitz Peter , Watanabe Kohei 
Published: May 2021

AbstractFew concepts figure more prominently in the study of international politics than threat. Yet scholars do not agree on how to identify and measure threats or systematically incorporate leaders’ perceptions of threat into their models. In this research note, we introduce a text-based strategy and method for identifying and measuring elite assessments of international threat from publicly available sources. Using semi-supervised machine learning models, we show how text sourced from newspaper articles can be parsed to discern arguments that distinguish threatening from non-threatening states, and to measure and track variation in the intensity of foreign threats over time. To demonstrate proof of concept, we use news summaries from The New York Times from 1861 to 2017 to create a geopolitical threat index (GTI) for the United States. We show that the index successfully matches periods in US history that historians identify as high and low threat and correctly identifies countries that have posed a threat to US security at different points in its history. We compare and contrast GTI with traditional indicators of international threat that rely on measures of material capability and interstate behavior.
Deniability in the Nuclear Nonproliferation Regime: The Upside of the Dual-Use Dilemma
Authors: Pauly Reid B C 
Published: May 2021

AbstractNuclear technology is often “dual-use,” having both peaceful and military applications. This is widely regarded as a lamentable fact, as states can pursue nuclear weapons under the guise of peaceful intentions. However, this article proposes an upside to the nuclear dual-use dilemma: the deniable nature of dual-use technology makes it more amenable to coercive counterproliferation. Caught proliferators are more likely to come into compliance if they can elude audience costs by denying that they were ever out of compliance. Thus, the dual-use dilemma is both the bane of the nonproliferation regime and a boon to its coercive enforcement. Poor knowledge of past nuclear programs can hamper future verification. Counterintuitively, however, the effectiveness of nonproliferation regime institutions created to promote transparency—the Treaty on the Non-Proliferation of Nuclear Weapons and the International Atomic Energy Agency (IAEA)—may be enhanced by not directly challenging the denial of past nuclear activities. This research uses interviews and archival evidence from the IAEA, US government, and South African apartheid government. At a time when ongoing nuclear disputes revolve around questions of transparency and admissions of guilt, this article contributes to scholarly and policy debates about secrecy, face-saving, counterproliferation strategy, and the role of international institutions in coercive bargaining.
Evaluation of increased fiber, decreased amino acids, or decreased electrolyte balance as dietary approaches to slow finishing pig growth rates
Authors: Helm Emma T , Patience John F , Romoser Matthew R , Johnson Colin D , Ross Jason W , Gabler Nicholas K 
Published: May 2021

Abstract
In swine production, pig movement restrictions or packing plant closures may create the need to slow growth rates of finishing pigs to ensure they remain at a marketable body weight when packing plant access is restored. Although dietary formulations can be successful at slowing pig growth, precision is needed regarding how to best formulate diets to achieve growth rate reductions. Thus, the objective was to evaluate three dietary experimental approaches aimed at slowing growth rates in finishing pigs. These approaches consisted of either increasing neutral detergent fiber (NDF), reducing essential amino acids, or reducing the dietary electrolyte balance through the addition of acidogenic salts. A total of 94 mixed-sex pigs (72.4 ± 11.2 kg BW) across two replicates were individually penned and assigned to 1 of 8 dietary treatments (n = 11–12 pigs/treatment): 1) Control diet representative of a typical corn–soybean meal-based finisher diet (CON); 2) diet containing 15% NDF from soybean hulls (15% NDF); 3) diet containing 20% NDF from soybean hulls (20% NDF); 4) diet containing 25% NDF from soybean hulls (25% NDF); 5) diet formulated as per CON but with 50% of the soybean meal replaced with corn (89% Corn); 6) diet containing 97% corn and no soybean meal or synthetic amino acids (97% Corn); 7) diet containing 2% anhydrous calcium chloride (2% CaCl2); and 8) diet containing 4% anhydrous calcium chloride (4% CaCl2). Over 28 d, pig body weights and performance were recorded weekly. At d 28, all pigs were ultrasound scanned and switched to the CON diet to evaluate compensatory gain from d 28 to 35. Overall, increased NDF did not impact any growth performance parameter (P &gt; 0.05). Amino acid restriction reduced average daily gain (ADG), average daily feed intake (ADFI), and gain:feed (G:F) linearly (linear P &lt; 0.001). Similarly, ADG, ADFI, and G:F were linearly reduced with increased CaCl2 inclusion (linear P &lt; 0.001). ADG differed during the compensatory gain period (P &lt; 0.001), with 4% CaCl2-fed pigs having a 47% increase in ADG compared with CON-fed pigs. Conversely, 15% and 25% NDF-fed pigs had reduced ADG compared with CON-fed pigs during the compensatory gain period. Gain efficiency differed from day 28 to 35 (P &lt; 0.001), with 4% CaCl2-fed pigs having a 36% increase in G:F compared with CON-fed pigs. Altogether, these data demonstrate that both amino acid restriction and CaCl2 inclusion are effective at slowing pig growth, albeit at greater inclusion rates.