bluuebunny/crossref_metadata_2025_split huggingface dataset:
GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region
Authors: Xu Rui-Gang , Gauer Julia S. , Baker Stephen R. , Slater Alexandre , Martin Eleyna M. , McPherson Helen R. , Duval Cédric , Manfield Iain W. , Bonna Arkadiusz M. , Watson Steve P. , Ariëns Robert A.S. 
Published: January 2021

Objective:
GPVI (glycoprotein VI) is a key molecular player in collagen-induced platelet signaling and aggregation. Recent evidence indicates that it also plays important role in platelet aggregation and thrombus growth through interaction with fibrin(ogen). However, there are discrepancies in the literature regarding whether the monomeric or dimeric form of GPVI binds to fibrinogen at high affinity. The mechanisms of interaction are also not clear, including which region of fibrinogen is responsible for GPVI binding. We aimed to gain further understanding of the mechanisms of interaction at molecular level and to identify the regions on fibrinogen important for GPVI binding.

Approach and Results:
Using multiple surface- and solution-based protein-protein interaction methods, we observe that dimeric GPVI binds to fibrinogen with much higher affinity and has a slower dissociation rate constant than the monomer due to avidity effects. Moreover, our data show that the highest affinity interaction of GPVI is with the αC-region of fibrinogen. We further show that GPVI interacts with immobilized fibrinogen and fibrin variants at a similar level, including a nonpolymerizing fibrin variant, suggesting that GPVI binding is independent of fibrin polymerization.

Conclusions:
Based on the above findings, we conclude that the higher affinity of dimeric GPVI over the monomer for fibrinogen interaction is achieved by avidity. The αC-region of fibrinogen appears essential for GPVI binding. We propose that fibrin polymerization into fibers during coagulation will cluster GPVI through its αC-region, leading to downstream signaling, further activation of platelets, and potentially stimulating clot growth.

Graphic Abstract:
A graphic abstract is available for this article.
Identification of Celastrol as a Novel Therapeutic Agent for Pulmonary Arterial Hypertension and Right Ventricular Failure Through Suppression of Bsg (Basigin)/CyPA (Cyclophilin A)
Authors: Kurosawa Ryo , Satoh Kimio , Nakata Takashi , Shindo Tomohiko , Kikuchi Nobuhiro , Satoh Taijyu , Siddique Mohammad A.H. , Omura Junichi , Sunamura Shinichiro , Nogi Masamichi , Takeuchi Yutaro , Miyata Satoshi , Shimokawa Hiroaki 
Published: January 2021

Objective:
Pulmonary arterial hypertension is characterized by abnormal proliferation of pulmonary artery smooth muscle cells and vascular remodeling, which leads to right ventricular (RV) failure. Bsg (Basigin) is a transmembrane glycoprotein that promotes myofibroblast differentiation, cell proliferation, and matrix metalloproteinase activation. CyPA (cyclophilin A) binds to its receptor Bsg and promotes pulmonary artery smooth muscle cell proliferation and inflammatory cell recruitment. We previously reported that Bsg promotes cardiac fibrosis and failure in the left ventricle in response to pressure-overload in mice. However, the roles of Bsg and CyPA in RV failure remain to be elucidated.

Approach and Results:
First, we found that protein levels of Bsg and CyPA were upregulated in the heart of hypoxia-induced pulmonary hypertension (PH) in mice and monocrotaline-induced PH in rats. Furthermore, cardiomyocyte-specific Bsg-overexpressing mice showed exacerbated RV hypertrophy, fibrosis, and dysfunction compared with their littermates under chronic hypoxia and pulmonary artery banding. Treatment with celastrol, which we identified as a suppressor of Bsg and CyPA by drug screening, decreased proliferation, reactive oxygen species, and inflammatory cytokines in pulmonary artery smooth muscle cells. Furthermore, celastrol treatment ameliorated RV systolic pressure, hypertrophy, fibrosis, and dysfunction in hypoxia-induced PH in mice and SU5416/hypoxia-induced PH in rats with reduced Bsg, CyPA, and inflammatory cytokines in the hearts and lungs.

Conclusions:
These results indicate that elevated Bsg in pressure-overloaded RV exacerbates RV dysfunction and that celastrol ameliorates RV dysfunction in PH model animals by suppressing Bsg and its ligand CyPA. Thus, celastrol can be a novel drug for PH and RV failure that targets Bsg and CyPA.

Graphic Abstract:
A graphic abstract is available for this article.
Resolvin D1 Enhances Necroptotic Cell Clearance Through Promoting Macrophage Fatty Acid Oxidation and Oxidative Phosphorylation
Authors: Hosseini Zeinab , Marinello Michael , Decker Christa , Sansbury Brian E. , Sadhu Sudeshna , Gerlach Brennan D. , Bossardi Ramos Ramon , Adam Alejandro P. , Spite Matthew , Fredman Gabrielle 
Published: January 2021

Objective:
Plaque necrosis is a key feature of defective resolution in atherosclerosis. Recent evidence suggests that necroptosis promotes plaque necrosis; therefore, we sought to determine how necroptotic cells (NCs) impact resolution programs in plaques.

Approach and Results:

To investigate the role(s) of necroptosis in advanced atherosclerosis, we used mice deficient of
Mlkl
, an effector of necroptosis.
Mlkl
−/−
mice that were injected with a gain-of-function mutant PCSK9 (AAV8-gof-PCSK9) and fed a Western diet for 16 weeks, showed significantly less plaque necrosis, increased fibrous caps and improved efferocytosis compared with AAV8-gof-PCSK9 injected wt controls. Additionally, hypercholesterolemic
Mlkl
−/−
mice had a significant increase in proresolving mediators including resolvin D1 (RvD1) and a decrease in prostanoids including thromboxane in plaques and in vitro. We found that exuberant thromboxane released by NCs impaired the clearance of both apoptotic cells and NCs through disruption of oxidative phosphorylation in macrophages. Moreover, we found that NCs did not readily synthesize RvD1 and that exogenous administration of RvD1 to macrophages rescued NC-induced defective efferocytosis. RvD1 also enhanced the uptake of NCs via the activation of p-AMPK (AMP-activated protein kinase), increased fatty acid oxidation, and enhanced oxidative phosphorylation in macrophages.

Conclusions:
These results suggest that NCs derange resolution by limiting key SPMs and impairing the efferocytic repertoire of macrophages. Moreover, these findings provide a molecular mechanism for RvD1 in directing proresolving metabolic programs in macrophages and further suggests RvD1 as a potential therapeutic strategy to limit NCs in tissues.

Graphic Abstract:
A graphic abstract is available for this article.
The dominance of big teams in China’s scientific
output
Authors: Liu Linlin , Yu Jianfei , Huang Junming , Xia Feng , Jia Tao 
Published: January 2021

Abstract
Modern science is dominated by scientific productions from teams. A recent finding shows that teams of both large and small sizes are essential in research, prompting us to analyze the extent to which a country’s scientific work is carried out by big or small teams. Here, using over 26 million publications from Web of Science, we find that China’s research output is more dominated by big teams than the rest of the world, which is particularly the case in fields of natural science. Despite the global trend that more papers are written by big teams, China’s drop in small team output is much steeper. As teams in China shift from small to large size, the team diversity that is essential for innovative work does not increase as much as that in other countries. Using the national average as the baseline, we find that the National Natural Science Foundation of China (NSFC) supports fewer small teams than the National Science Foundation (NSF) of the United States does, implying that big teams are preferred by grant agencies in China. Our finding provides new insights into the concern of originality and innovation in China, which indicates a need to balance small and big teams.
Profiling and predicting the problem-solving patterns in
China’s research systems: A methodology of intelligent bibliometrics and
empirical insights
Authors: Zhang Yi , Wu Mengjia , Hu Zhengyin , Ward Robert , Zhang Xue , Porter Alan 
Published: January 2021

Abstract
Uncovering the driving forces, strategic landscapes, and evolutionary mechanisms of China’s research systems is attracting rising interest around the globe. One topic of interest is to understand the problem-solving patterns in China’s research systems now and in the future. Targeting a set of high-quality research articles published by Chinese researchers between 2009 and 2018, and indexed in the Essential Science Indicators database, we developed an intelligent bibliometrics-based methodology for identifying the problem-solving patterns from scientific documents. Specifically, science overlay maps incorporating link prediction were used to profile China’s disciplinary interactions and predict potential cross-disciplinary innovation at a macro level. We proposed a function incorporating word embedding techniques to represent subjects, actions, and objects (SAO) retrieved from combined titles and abstracts into vectors and constructed a tri-layer SAO network to visualize SAOs and their semantic relationships. Then, at a micro level, we developed network analytics for identifying problems and solutions from the SAO network, and recommending potential solutions for existing problems. Empirical insights derived from this study provide clues to understand China’s research strengths and the science policies underlying them, along with the key research problems and solutions that Chinese researchers are focusing on now and might pursue in the future.
The Role of Surface Heat Fluxes on the Size of Typhoon Megi (2016)
Authors: Shen Li-Zhi , Wu Chun-Chieh , Judt Falko 
Published: January 2021

AbstractThis study attempts to understand how surface heat fluxes in different storm regions affect tropical cyclone (TC) size. The Advanced Research version of the Weather Research and Forecasting (ARW-WRF) Model (version 3.5.1) is used to simulate Typhoon Megi (2016). A series of numerical experiments are carried out, including a control simulation and several sensitivity experiments with surface heat fluxes suppressed in different TC regions [to mimic the reduction of the wind-induced surface heat exchange (WISHE) feedback in the inner and/or outer core]. The results show that with surface heat fluxes suppressed in the entire domain, the TC tends to be smaller. Meanwhile, the TC size is more sensitive to the surface heat flux change in the outer core than to that in the inner core. Suppressing surface heat fluxes can weaken the rainbands around the suppressed area, which in turn slows down the secondary circulation. When the surface heat flux is suppressed in the inner-core region, the weakening of the secondary circulation associated with the diminished inner rainbands is limited to the inner-core region, and only slightly affects the absolute angular momentum import from the outer region, thus having negligible impact on TC size. However, suppression of surface heat fluxes in the outer-core region leads to less active outer rainbands and a more substantial weakening of secondary circulation. This results in less absolute momentum import from the outer region and in turn a smaller TC.
Sibling Transmission of Gang Involvement
Authors: Hashimi Sadaf , Wakefield Sara , Apel Robert 
Published: January 2021

Objectives: The processes driving gang entry and disengagement are central to classic and contemporary criminological research on gang involvement. Yet, the role of delinquent peer friendship networks in contouring gang membership has driven much of criminological research, with little empirical research devoted to understanding sibling influences on the gang career. Method: The study uses the National Longitudinal Survey of Youth 1997 to examine the transmission of gang membership among similar-aged siblings. These data offer the opportunity to use siblings’ self-report of gang involvement as a determinant of focal youths’ self-report of gang involvement while treating gang entry, persistence, and exit (and reentry) as unique transitions with potentially asymmetric determinants. Results: Results from the event history models indicate that gang involved siblings increase the hazard of entry and re-entry into the gang but have little influence on exit decisions. Sibling configurations with respect to sex and age-order further conditions these relations, with brothers and older siblings most influential. Conclusion: Ties to siblings serve as a salient and intimate type of social tie with siblings serving multiplex roles in each other’s lives. Findings lend additional insight on crime concentration in family networks and advance our understanding of continuity and change in gang involvement
Training Structural Awareness with StatHand: A 1 Year Follow-Up
Authors: Allen Peter J. , Fielding Jessica L. , Westermann Annabel H. , Lafratta Amelia M. 
Published: January 2021

Background: Allen, Fielding, East, et al. demonstrated experimentally that structural awareness, or the ability to disregard a research problem’s topic and instead focus on its structural features, can be trained using StatHand ( https://stathand.net ). Most training benefits persisted for 1 week. Objective: The objective was to assess the longer-term effects of training. Method: One year after training (or control activities), 54 participants were re-administered 5 measures of structural awareness and 1 statistic selection measure. Results: Trained participants continued to reliably out-perform control participants on 4 measures of structural awareness, though no longer on the 5th. Over the year, decrements in trained participants’ performance on the 5 structural awareness measures were mostly small. However, 1 year after training, the trained participants’ statistic selection advantage had largely disappeared. Conclusion: Brief structural awareness training can have long-term benefits, though selecting an appropriate statistical test for common research scenarios without assistance remains a difficult task. Teaching Implications: Structural awareness can be trained. However, even structurally aware students cannot reliably select appropriate statistics without assistance. Training plus easy access to a decision-making aid should maximize statistic selection accuracy. Our evidence-based training methods and materials, including StatHand, can be freely used and adapted for these purposes.
Geriatric Depression and Cognitive Impairment—An Update
Authors: Mukku Shiva Shanker Reddy , Dahale Ajit Bhalchandra , Muniswamy Nagalakshmi Rajavoor , Muliyala Krishna Prasad , Sivakumar Palanimuthu Thangaraju , Varghese Mathew 
Published: January 2021

Background: Depression and cognitive impairment often coexist in older adults. The relation between depression and cognitive impairment is complex. The objective of this article is to review recent literature on cognitive impairment in older adults with depression and provide clinicians an update. Methods: We searched PubMed, Google Scholar, Science Direct, and Psych Info for the articles published in the English language related to late-life depression (LLD)/geriatric depression and cognitive impairment. We considered original research articles, relevant systematic reviews, chapters, and important conceptual articles published in the last 9 years (2011–2019). We selected relevant articles for this narrative review. Conclusion: The concept pseudodementia, indicating depression with cognitive impairment mimicking dementia, is now seen only as a historical concept. The current literature strongly agrees with fact that cognitive deficits often exist in LLD. The cognitive deficits in depression were initially seen as trait marker; however, some recent studies suggest that cognitive deficits persist even in the remission phase. There is heterogeneity among the studies in terms of the nature of the cognitive deficits, but higher number of studies reported impairment in attention and executive function. LLD with cognitive deficits is at a higher risk of progression to dementia. In older adults, depression with cognitive impairments requires a comprehensive evaluation. Electroencephalography, event-related potentials, fluorodeoxyglucose–positron emission tomography, amyloid positron emission tomography, and CSF amyloid will supplement clinical evaluation in differentiating functional depressive disorder with cognitive impairment from depression with an underlying degenerative condition.
Use of non-contact infrared thermometers in rehabilitation patients: a randomized controlled study
Authors: Chen Zhen , Wang Hui , Wang Yi , Lin Hongmei , Zhu Xiuping , Wang Yaqin 
Published: January 2021

Objective In this randomized controlled study, we aimed to determine whether non-contact infrared thermometers (NCITs) are more time-efficient and create less patient distress than mercury axillary thermometers (MATs) and infrared tympanic thermometers (ITTs). Methods Forty-five rehabilitation inpatients were randomly assigned to one of three groups (NCIT, MAT, and ITT). Time required to measure body temperature with an NCIT, MAT, and ITT was recorded. We examined associations between time required to take patients’ temperature and measuring device used. Patient distress experienced during temperature measurement using the three thermometers was recorded. Results A significantly longer average time was required to measure temperatures using the MAT (mean 43.17, standard deviation [SD] 8.39) than the ITT (mean 13.74, SD 1.63) and NCIT (mean 12.13, SD 1.18). The thermometer used influenced the time required to measure body temperature (t = 33.99). There were significant differences among groups (NCIT vs. ITT, NCIT vs. MAT, and ITT vs. MAT) regarding patient distress among the different thermometers. Most distress arose owing to needing help from others, sleep disruption, and boredom. Conclusion The NCIT has clinically relevant advantages over the ITT and MAT in measuring body temperature among rehabilitation patients, including saving nurses’ time and avoiding unnecessary patient distress. Clinical trial registration number ( http://www.chictr.org.cn ): ChiCTR1800019756.
Prevalence of pre-cluster symptoms in episodic cluster headache: Is it possible to predict an upcoming bout?
Authors: Pedersen Adam Sebastian , Snoer Agneta , Barloese Mads , Petersen Anja , Jensen Rigmor Højland 
Published: January 2021

Background Early symptoms prior to a cluster headache bout have been reported to occur days or weeks before the actual beginning of the cluster headache bouts. This study aimed to describe the prevalence of pre-cluster (premonitory) symptoms and examine the predictability of an upcoming cluster headache bout. Methods 100 patients with episodic cluster headache were included in this retrospective cross-sectional study. All patients underwent a semi-structured interview including 25 questions concerning pre-cluster symptoms. Results Pre-cluster symptoms were reported by 86% of patients with a mean of 6.8 days (interquartile range 3–14) preceding the bout. An ability to predict an upcoming bout was reported by 57% with a mean 4.6 days (interquartile range 2–7) before the bout. Occurrence of shadow attacks was associated with increased predictability (odds ratio: 3.06, confidence interval: 1.19–7.88, p-value = 0.020). In remission periods, 58% of patients reported mild cluster headache symptoms and 53% reported occurrence of single shadow attacks. Conclusions The majority of episodic cluster headache patients experienced pre-cluster symptoms, and more than half could predict an upcoming bout, suggesting the significant potential of early intervention. Furthermore, the experience of mild cluster headache symptoms and infrequent shadow attacks in remission periods is common and suggest an underlying pathophysiology extending beyond the cluster headache bouts.
Clinical Effectiveness of Intraoperative Tranexamic Acid Use in Shoulder Surgery: A Systematic Review and Meta-analysis
Authors: Hartland Alexander W. , Teoh Kar H. , Rashid Mustafa S. 
Published: January 2021

Background: Tranexamic acid (TXA) is widely used across surgical specialties to reduce perioperative bleeding. It has been shown to be effective in spinal surgery and lower limb arthroplasty. Among all languages, there are no systematic reviews or meta-analyses investigating its clinical effectiveness for all types of shoulder surgery. Purpose: To investigate the clinical effectiveness of TXA in all types of shoulder surgery, including open and arthroscopic procedures. To investigate the effect of TXA on bleeding and non–bleeding-related outcomes. Study Design: Systematic review and meta-analysis. Methods: A protocol for the study was designed and registered with PROSPERO (CRD42020185482). The literature search included the MEDLINE, Embase, PsycINFO, and Cochrane Library databases. All randomized controlled trials evaluating the use of TXA against placebo, in all types of shoulder surgery, were included. Assessments were undertaken for risk of bias and certainty of evidence. The primary outcome was total blood loss. Secondary outcomes included those not directly related to bleeding. Data from comparable outcomes were pooled and analyzed quantitatively or descriptively, as appropriate. Results: Eight randomized controlled trials were included in the systematic review, and data from 7 of these studies were pooled in the meta-analysis. Pooled analysis demonstrated a significant reduction in 2 of 3 outcomes measuring perioperative bleeding with TXA compared with controls: estimated total blood loss (mean difference, −209.66 mL; 95% CI, −389.11 to −30.21; P = .02) and postoperative blood loss as measured by drain output (mean difference, −84.8 mL; 95% CI, −140.04 to −29.56; P = .003). Hemoglobin reduction was reduced but not statistically significant (mean difference, –0.33 g/dL; 95% CI −0.69 to 0.03; P = .07). This result became significant with sensitivity analysis excluding arthroscopic procedures. Conclusion: This systematic review and meta-analysis indicated that TXA was effective in reducing blood loss in shoulder surgery. Larger randomized controlled trials with low risk of bias for specific surgical shoulder procedures are required. Clinical Relevance: TXA can be used across shoulder surgery to reduced perioperative blood loss. The use of TXA may have other beneficial features, including reduced postoperative pain and reduced operative time.