bluuebunny/crossref_metadata_2025 huggingface dataset:
IL33 (Interleukin 33)/ST2 (Interleukin 1 Receptor-Like 1) Axis Drives Protective Microglial Responses and Promotes White Matter Integrity After Stroke
Authors: Xie Di , Liu Huan , Xu Fei , Su Wei , Ye Qing , Yu Fang , Austin Taylor J. , Chen Jun , Hu Xiaoming
Published: April 2021

Background and Purpose:

Emerging evidence highlights the importance of IL33 (interleukin 33) and its receptor (ST2 [interleukin 1 receptor-like 1]) in normal brains and neurological disorders. This study explores the function of the IL33/ST2 signaling axis and a transcription factor STAT6 (signal transducer and activator of transcription 6) in white matter integrity and long-term recovery after stroke.

Methods:

Transient middle cerebral artery occlusion was induced in wild type, ST2 knockout, STAT6 knockout, and microglia/macrophage-depleted (by PLX5622 diet) mice. Sensorimotor and cognitive functions were evaluated. White matter integrity was measured by immunofluorescent staining, diffusion tensor imaging, electron microscopy, and electrophysiology. The death of oligodendrocytes and its precursor cells (OPC) and the microglia/macrophage responses were evaluated 3 days after stroke. Primary microglia-oligodendrocyte/OPC cocultures were used for mechanistic studies. Parametric tests (Student
t
test or ANOVA) or nonparametric Mann-Whitney
U
test were used for statistical analysis based on the numbers of groups, types of variables, and the structure of each data set.

Results:

ST2 deficiency exacerbates sensorimotor and cognitive deficits for 28 days after middle cerebral artery occlusion compared with wild-type mice, which was accompanied by deteriorated structural damages and impaired conduction of compound action potentials in white matter. ST2 knockout mice displayed increased death of oligodendrocytes and OPCs, and a concomitant exacerbation in neuroinflammation 3 days after stroke. Using microglia/macrophage-depleted mice and microglia-oligodendrocyte/OPC cocultures, we showed that IL33 protected oligodendrocytes and OPCs against ischemic injury in a microglia/macrophage dependent manner. Further mechanistic studies identified STAT6 as a molecule that mediates the protective effects of IL33/ST2 on oligodendrocytes in the ischemic brain. IL33 treatment failed to rescue oligodendrocytes and OPCs after stroke in STAT6 knockout mice.

Conclusions:

These results shed light on the IL33/ST2/STAT6 signaling as a potential immune regulatory mechanism to modulate microglia/macrophage activity, improve white matter integrity, and restore long-term neurological functions after stroke.
Molecular phylogeny of the Austrolebias adloffi group (Cyprinodontiformes, Rivulidae), with description of two new endangered and highly endemic species of annual killifishes from the Laguna dos Patos system, southern Brazil
Authors: VOLCAN MATHEUS VIEIRA , BARBOSA CRISLAINE , ROBE LIZANDRA JAQUELINE , LANÉS LUIS ESTEBAN KRAUSE
Published: April 2021

The Austrolebias adloffi species group encompasses a diverse lineage of annual killifishes that occurs along the Laguna dos Patos/Lagoa Mirim system, in both Brazilian and Uruguayan territories. We herein employ an integrative taxonomy approach to describe two new species of the group, inferring their phylogenetic relationships and evaluating their conservation status. Austrolebias cheffei sp. nov. and Austrolebias lourenciano sp. nov. are herein described from the western portion of the Laguna dos Patos system. Austrolebias cheffei is distinguished from the remaining species of the A. adloffi species group by presenting a yellowish green or yellowish blue dorsal fin, with wide black to dark brown bars extending from the base to the middle portion of the dorsal and anal fins in the males. Austrolebias lourenciano is distinguished from the remaining species of the A. adloffi species group by presenting a yellowish green dorsal fin, with light yellow or light bluish bars forming small triangles, interspersed with small dark brown rows of blotches in the dorsal fin base, and greenish blue anal fin, sometimes with lighter elongated yellowish iridescent blotches, limited to the basal region. According to mitochondrial cytb sequences, both species are reciprocally monophyletic relative to other species of the A. adloffi species group, and present positive barcoding gap values. Interestingly, both new species form a grade that is closely related to Austrolebias aff. minuano 1, an undescribed species that occurs at the opposite margin of the Laguna dos Patos. Among the other evaluated species, A. bagual, A. aff. minuano 1, A. nigrofasciatus, A. pelotapes, A. pongondo, A. arachan, and A. viarius also revealed to be reciprocally monophyletic, whereas A. minuano and A. adloffi revealed to be paraphyletic in regard to A. charrua and A. aff. minuano 2, respectively, and A. nachtigalli is subdivided in two clades, one of which including A. reicherti, which points to the need of a taxonomic review of the group. In addition, we discussed the conservation status of the new species, corrected the type locality of A. pongondo, and provided a dichotomous identification key of the A. adloffi species group.
Changes in the Subantarctic Mode Water Properties and Spiciness in the Southern Indian Ocean based on Argo Observations
Authors: ZHANG Ying , DU Yan , QU Tangdong , HONG Yu , DOMINGUES Catia M. , FENG Ming
Published: April 2021

The Subantarctic Mode Water (SAMW) plays an essential role in the global heat, freshwater, carbon, and nutrient budgets. In this study, decadal changes in the SAMW properties in the Southern Indian Ocean (SIO) and associated thermodynamic and dynamic processes are investigated during the Argo era. Both temperature and salinity of the SAMW in the SIO show increasing trends during 2004-2018. A two-layer structure of the SAMW trend, with more warm and salty light SAMW but less cool and fresh dense SAMW, is identified. The heaving and spiciness processes are important but have opposite contributions to the temperature and salinity trends of the SAMW. A significant deepening of isopycnals (heaving), peaking atσθ=26.7-26.8 kg m−3in the middle layer of the SAMW, expands the warm and salty light SAMW and compresses the cool and fresh dense SAMW corresponding to the change in subduction rate during 2004-2018. The change in the SAMW subduction rate is dominated by the change in the mixed layer depth, controlled by the changes in wind stress curl and surface buoyancy loss. An increase in the mixed-layer temperature due to weakening northward Ekman transport of cool water leads to a lighter surface density in the SAMW formation region. Consequently, density outcropping lines in the SAMW formation region shift southward and favor the intrusion and entrainment of the cooler and fresher Antarctic surface water from the south, contributing to the cooling/freshening trend of isopycnals (spiciness). Subsequently, the cooler and fresher SAMW spiciness anomalies spread in the SIO via the subtropical gyre.
On the Performance of Airborne Meteorological Observations Against Other In-situ Measurements
Authors: Wagner Timothy J. , Petersen Ralph A.
Published: April 2021

Routine in situ observations of the atmosphere taken in flight by commercial aircraft provide atmospheric profiles with greater temporal density and, in many parts of the country, at more locations than the operational radiosonde network. Thousands of daily temperature and wind observations are provided by largely complementary systems, the Airborne Meteorological Data Relay (AMDAR) and the Tropospheric Airborne Meteorological Data Reporting (TAMDAR). All TAMDAR aircraft also measure relative humidity while a subset of AMDAR aircraft are equipped with the Water Vapor Sensing System (WVSS) measure specific humidity.

One year of AMDAR/WVSS and TAMDAR observations are evaluated against operational National Weather Service (NWS) radiosondes to characterize the performance of these systems in similar environments. For all observed variables, AMDAR reports showed both smaller average differences and less random differences with respect to radiosondes than the corresponding TAMDAR observations. Observed differences were not necessarily consistent with known radiosonde biases. Since the systems measure different humidity variables, moisture is evaluated in both specific and relative humidity using both aircraft and radiosonde temperatures to derive corresponding moisture variables. Derived moisture performance is improved when aircraft-based temperatures are corrected prior to conversion. AMDAR observations also show greater consistency between different aircraft than TAMDAR observations do. The small variability in coincident WVSS humidity observations indicates that they may prove more reliable than humidity observations from NWS radiosondes.
Suicide crisis calls to emergency services: Cohort profile and findings from a data linkage study in Queensland, Australia
Authors: Meurk Carla , Wittenhagen Lisa , Bosley Emma , Steele Megan L , Bunting Denise , Waterson Elissa , Edwards Bronwen , Martain Ben , Heffernan Ed
Published: April 2021

Background and Aims:

Police and paramedics play a crucial role in responding to suicide crises in the community. However, little is known about the nature, extent, precipitating factors, pathways and outcomes of a suicide-related call to emergency services and what responses will most effectively and compassionately meet the needs of those in crisis. Partners in Prevention: Understanding and Enhancing First Responses to Suicide Crisis Situations (PiP) was established to address these knowledge gaps.

Methods:

This article describes (1) the methodology used to construct the PiP dataset, a population-wide linked dataset that investigates the characteristics and health pathways of individuals in Queensland who were the subject of a suicide-related call to police or paramedics; and (2) preliminary findings on service demand, demographics and health services utilisation.

Results:

We identified 219,164 suicide-related calls to Queensland Police Service or Queensland Ambulance Service that were made over the 3-year period 1 February 2014 to 31 January 2017. A total of 70,893 individuals were identifiable via records linkage. The cohort linked to more than 7,000,000 health records. We estimated that police or paramedics in Queensland received on average 209 calls per day, with increases year on year over the study period. Analysis of demographic data highlighted the heterogeneous nature of this cohort and important demographic variations between individuals in contact with police versus ambulance services.

Discussion:

The PiP dataset provides a strong foundation for a multi-modal dataset that can be built on over time, both cross-sectionally and longitudinally. Further linkages to Medicare Benefits Schedule, Pharmaceutical Benefits Scheme and social care datasets are planned.

Conclusion:

Detailed population-level analysis that data linkage can provide is critical to improving understanding and responses to suicide crisis situations. The PiP study is a world first and provides a unique opportunity to improve responses to this public health problem.
Numerical investigation of blowing ratio, density ratio and axial position of film holes on the vane endwall film cooling effectiveness with upstream step
Authors: Xu Qingzong , Du Qiang , Wang Pei , Xiao Xiangtao , Liu Jun
Published: April 2021

The aerothermal performance of interrupted slot and film holes was numerically investigated. Previous study indicates that the interrupted slot performs better compared to the conventional slot. In the meanwhile, the step formed along with the interrupted slot affects the film cooling characteristics. In this article, a row of film holes is arranged downstream of the step, and the mass flow rate for the interrupted slot is constant at 1%. Blowing ratio (BR) from 0.5 to 1.5 and density ratio from 1 to 2 were studied for the film holes. Endwall film cooling effectiveness distribution indicates that film cooling is easily affected by the secondary flow inside passage and the upstream step. Coolant traces are split into two parts due to the effects of step vortex and transverse flow. For different density ratios, increasing BR shows a different trend of film cooling effectiveness due to the variation of coolant momentum. The coolant jet is easily affected by the secondary flow when its momentum is low, but tends to liftoff when its momentum is too high. As a result, it is better to position the film holes far away from the upstream step. The total pressure loss coefficient distribution at the passage exit indicates that the coolant injection increases the total pressure loss. But density ratio has smaller effect on the loss variation. Besides, two axial positions of cooling holes were studied to improve the endwall cooling performance. Without the effect of step vortex, the film effectiveness of cooling holes is improved.
Public Diplomacy in Strengthening India: Vietnam Relations
Authors: Nga Le Thi Hang , Quang Trieu Hong
Published: April 2021

It is noticeable that India–Vietnam relations have remained stable and had signs of development despite the new challenges in the global and regional environment due to COVID-19 pandemic. The authors of this article are of the view that one of the factors that help maintain the stability and development of bilateral relations in the current context is public diplomacy. Since the beginning of the twenty-first century, India has invested a huge amount of resources in public diplomacy to leverage India’s soft power. A dedicated public diplomacy division within the Ministry of External Affairs was set up in May 2006, many new schemes were designed to engage domestic and foreign public opinion and a series of high-profile dialogues with foreign think tanks were organised. By utilising both traditional and new approaches of public diplomacy, India is actively seeking new audiences within and outside India. India’s foreign policymaking process has become more open and democratic with the contribution of communities outside the New Delhi political and diplomatic elite. New media has also been utilised to reach its various target audiences. Vietnam considers public diplomacy an important pillar of the comprehensive diplomacy of the country. Public diplomacy helps Vietnam succeed in implementing comprehensive and effective foreign policies. It contributes important part in building cooperative, peaceful and friendly relations between Vietnam and international partners. The importance that both India and Vietnam attach to public diplomacy has many implications for strengthening Vietnam–India relations in the current context. This article focuses on India and Vietnam’s public diplomacy as an instrument of strengthening bilateral relations, and thereby proposes suggestions for both sides to enhance cooperation in the future.
Natural vibration of imperfect sandwich plates considering the effects of transverse stretching
Authors: Hao YX , Wang MX , Zhang W , Liu LT , Yang SW
Published: April 2021

In this article, the natural vibration investigation of a functionally graded material sandwich plate with initial geometrical imperfection of the exponential function is conducted. Two face sheets of the sandwich plate are composited by functionally graded material. Their material coefficients are affected by temperature and vary in the direction of thickness following the power law. The core layer is only the metal. With the aid of Reddy’s displacement fields, a quasi-three-dimensional model is used, in which the effects of transverse stretching on natural vibration are considered. The natural frequencies and model shapes of the system are calculated on the basis of Rayleigh–Ritz method and Chebyshev polynomials. A comparison of these results with those of the existing three-dimensional theory results shows the validity and computability of present method. The influences of various parameters on the natural frequencies are researched in detail.
Artificial neural network (ANN) assisted prediction of transient NOx emissions from a high-speed direct injection (HSDI) diesel engine
Authors: Fang XiaoHang , Zhong Fengyu , Papaioannou Nick , Davy Martin H , Leach Felix CP
Published: April 2021

The understanding and prediction of NOx emissions formation mechanisms during engine transients are critical to the monitoring of real driving emissions. While many studies focus on the engine out NOx formation and treatment, few studies consider cyclic transient NOx emissions due to the low time resolution of conventional emission analysers. Increased computational power and substantial quantities of accessible engine testing data have made ANN a suitable tool for the prediction of transient NOx emissions. In this study, the transient predictive ability of artificial neural networks where a large number of engine testing data are available has been studied extensively. Significantly, the proposed transient model is trained from steady-state engine testing data. The trained data with 14 input features are provided with transient signals which are available from most engine testing facilities. With the help of a state-of-art high-speed NOx analyser, the predicted transient NOx emissions are compared with crank-angle resolved NOx measurements taken from a high-speed light duty diesel engine at test conditions both with and without EGR. The results show that the ANN model is capable of predicting transient NOx emissions without training from crank-angle resolved data. Significant differences are captured between the predicted transient and the slow-response NOx emissions (which are consistent with the cycle-resolved transient emissions measurements). A particular strength is found for increasing load steps where the instantaneous NOx emissions predicted by the ANN model are well matched to the fast-NOx analyser measurements. The results of this work indicate that ANN modelling could strongly contribute to the understanding of real driving emissions.
The nature of hybrid governance: A case study of a large and well-established European international school
Authors: Holmyard Leila
Published: April 2021

The number of international schools is growing rapidly and existing data points to great diversity of their governance structure. The nature of hybrid governance, in which a board comprises both elected and appointed governors, was investigated through a case study of an international school in western Europe and triangulated with interviews with nine experts in international schooling. Hybrid governance was found to offer the advantages of both elected and appointed boards: elections foster transparency and representation of stakeholders, while appointments allow the board to be populated with particular skills. A model for governance was presented in which the hybrid structure is underpinned by recruitment and training practices that ensure governors complement the existing skillset of the board, have desirable motivations for serving, and understand their role. This model may be useful for informing international school improvement efforts, although its compatibility with the diverse landscape of international schools remains to be determined.
S100A11 Promotes Glioma Cell Proliferation and Predicts Grade-Correlated Unfavorable Prognosis
Authors: Wang Haopeng , Yin Mengyuan , Ye Lei , Gao Peng , Mao Xiang , Tian Xuefeng , Xu Ziao , Dai Xingliang , Cheng Hongwei
Published: April 2021

The prognosis of glioma is significantly correlated with the pathological grades; however, the correlations between the prognostic biomarkers with pathological grades have not been elucidated. S100A11 is involved in a variety of malignant biological processes of tumor, whereas its biological and clinicopathological features on glioma remain unclear. In this study, the S100A11 expression and clinical information were obtained from the public databases (TCGA, GEPIA2) to analyze its correlations with the pathological grade and the prognosis of glioma patients. We then verified the expression of S100A11 by immunohistochemistry staining. The effects of S100A11 on the proliferation of glioma cells were confirmed by cytological function assays (CCK-8, Flow cytometry, Clone formation assay) in vitro, the role of S100A11 in regulation of glioma growth was determined by xenograft model assay. We observed that S100A11 expression positively correlated with the pathological grades, while negatively correlated with the survival time of patients. In cytological analysis, we found the proliferations of glioma cell lines were significantly inhibited in vitro ( P < 0.05) after interfering S100A11 expression via shRNAs. The cell cycle was blocked at G0/G1 stage. The ability of clone formation was significantly decreased, and the tumorigenicity in vivo was weakened ( P < 0.05). In summary, S100A11 was over-expressed in gliomas and positively correlated with the pathological grades. Interfering the expression of S100A11 significantly inhibited the proliferation of glioma in vitro and the tumorigenicity in vivo ( P < 0.05). In conclusion, S100A11 might be considered as a potential biomarker in glioma.
Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats
Authors: Cheng Yu-Ting , Liao Jian , Zhou Qian , Huo Hua , Zellmer Lucas , Tang Zheng-Long , Ma Hong , Hong Wei , Liao Dezhong Joshua
Published: April 2021

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.
3D Modeling of Blood Flow in Simulated Abdominal Aortic Aneurysm
Authors: Gonzalez-Urquijo Mauricio , de Zamacona Raul Garza , Mendoza Ana Karen Martinez , Iribarren Miranda Zamora , Ibarra Erika Garza , Bencomo Marcos David Moya , Fabiani Mario Alejandro
Published: April 2021

Background:

Besides biological factors, abdominal aortic aneurysm rupture is also caused by mechanical parameters, which are constantly affecting the wall’s tissue due to their abnormal values. The ability to evaluate these parameters could vastly improve the clinical treatment of patients with abdominal aortic aneurysms. The objective of this study was to develop and demonstrate a methodology to analyze the fluid dynamics that cause the wall stress distribution in abdominal aortic aneurysms, using accurate 3D geometry and a realistic, nonlinear, elastic biomechanical model using a computer-aided software.

Methods:

The geometry of the abdominal aortic aneurysm; was constructed on a 3D scale using computer-aided software SolidWorks (Dassault Systems SolidWorksCorp., Waltham MA). Due to the complex nature of the abdominal aortic aneurysm geometry, the physiological forces and constraints acting on the abdominal aortic aneurysm wall were measured by using a simulation setup using boundary conditions and initial conditions for different studies such as finite element analysis or computational fluid dynamics.

Results:

The flow pattern showed an increase velocity at the angular neck, followed by a stagnated flow inside the aneurysm sack. Furthermore, the wall shear stress analysis showed to focalized points of higher stress, the top and bottom of the aneurysm sack, where the flow collides against the wall. An increase of the viscosity showed no significant velocity changed but results in a slight increase in overall pressure and wall shear stress.

Conclusions:

Conducting computational fluid dynamics modeling of the abdominal aortic aneurysm using computer-aided software SolidWorks (Dassault Systems SolidWorksCorp., Waltham MA) proves to be an insightful approach for the clinical setting. The careful consideration of the biomechanics of the abdominal aortic aneurysm may lead to an improved, case-specific prediction of the abdominal aortic aneurysm rupture potential, which could significantly improve the clinical management of these patients.
Fabric defect detection based on deep-handcrafted feature and weighted low-rank matrix representation
Authors: Li Chunlei , Jiang Ban , Liu Zhoufeng , Dong Yan , Tang Shuili , Weng Dawei
Published: April 2021

In the process of textile production, automatic defect detection plays a key role in controlling product quality. Due to the complex texture features of fabric image, the traditional detection methods have poor adaptability, and low detection accuracy. The low rank representation model can divide the image into the low rank background and sparse object, and has proven suitable for fabric defect detection. However, how to further effectively characterize the fabric texture is still problematic in this kind of method. Moreover, most of them adopt nuclear norm optimization algorithm to solve the low rank model, which treat every singular value in the matrix equally. However, in the task of fabric defect detection, different singular values of feature matrix represent different information. In this paper, we proposed a novel fabric defect detection method based on the deep-handcrafted feature and weighted low-rank matrix representation. The feature characterization ability is effectively improved by fusing the global deep feature extracted by VGG network and the handcrafted low-level feature. Moreover, a weighted low-rank representation model is constructed to treat the matrix singular values differently by different weights, thus the most distinguishing feature of fabric texture can be preserved, which can efficiently outstand the defect and suppress the background. Qualitative and quantitative experiments on two public datasets show that our proposed method outperforms the state-of-the-art methods.
The Power of the Media on Peace and Reconciliation Processes: Representing Former Enemy Groups as Moral versus Immoral Matters
Authors: Janković Ana , Čehajić-Clancy Sabina
Published: April 2021

The efforts of peace-building and reconciliation between historical enemies are faced with many structural and psychological obstacles. Scholars have identified mechanisms that can induce improvements in psychological aspects of intergroup relations, such as intergroup contact. However, establishing direct contact with everyone is impossible. Therefore, the mass media represents an important source through which groups learn about each other. Numerous studies have shown that stereotypical and often negative portrayals of specific social groups through the media produce or reinforce negative intergroup outcomes. In this research, the authors report results from an experimental study conducted in a post-conflict society of Bosnia and Herzegovina ( N = 119). It examined the effects of stereotypical and counter-stereotypical representations of former enemy groups (Bosniaks) through the media on intergroup behavior (reported by Bosnian Serbs). More specifically, in this research the authors explored the effects of representing out-group individuals as immoral (the stereotypical condition) and moral (the counter-stereotypical condition) on specific behavioral tendencies toward the historical enemy group. The results indicate that exposure to primarily moral information about the out-group target facilitated important positive intergroup outcomes. This study extends the literature and research on moral exemplars by demonstrating the effects on relevant intergroup outcomes whilst utilizing current (vs. historical) moral exemplar stories.
Adjusting to the canon
Authors: Vincze Orsolya , Jenei Dániel , Pólya Tibor , Erát Dávid
Published: April 2021

The purpose of the present study is to explore the organization of communicative memory among Hungarians. We were also interested in the factors possibly influencing the composition of communicative memory, such as conspiracy beliefs and system justification. The study involved 339 participants who were asked to name the three historical events that have occurred during the lifetime of people they personally knew and had the most significant impact on their country. A latent class analysis was conducted to explore possible associations of event choice with conspiracy beliefs and system justification. The results showed that the most frequently selected events partly corresponded to the Hungarian national historical canon, but progressive events significant on a European scale were also frequently nominated. The latent class analysis revealed two historical profiles. One was characterized by a progressive and Eurocentric view of history, whereas the other showed a canonical historical view with victimhood orientation. The analysis showed that individuals who believe in conspiracy theories were more likely to select events corresponding to the national historical canon, whereas system justification was unrelated to event choice. The results are discussed in terms of the importance of cultural memory and the measured individual constructs in the forming of communicative memory.
Serum-derived exosomes containing NEAT1 promote the occurrence of rheumatoid arthritis through regulation of miR-144-3p/ROCK2 axis
Authors: Liu Rui , Jiang Chunbo , Li Jingjing , Li Xiaoru , Zhao Lin , Yun Haifeng , Xu Weiwei , Fan Weijian , Liu Qiuhong , Dong Hongli
Published: April 2021

Background:

Evidence has demonstrated that non-coding RNAs (ncRNAs) could be delivered efficiently to recipient cells using exosomes as a carrier. Additionally, long ncRNA nuclear enriched abundant transcript 1 (NEAT1) is emerging as a vital regulatory molecule in the progression of rheumatoid arthritis (RA). The aim of this study was to identify the NEAT1/miR-144-3p/Rho-associated protein kinase 2 (ROCK2) functional network regulating the WNT signaling pathway in RA.

Methods:

In vivo, a collagen-induced arthritis (CIA) model was established to analyze the effects of blood exosomes on the incidence, clinical score, and bone degradation of RA. In vitro, the CD4+T cells were characterized by flow cytometry and the cell activities were analyzed in the presence of exosome treatment alone or in combination with altered expression of NEAT1, miR-144-3p or Rho-associated protein kinase 2 (ROCK2). The expression of NEAT1, miR-144-3p, ROCK2, and corresponding proteins in the WNT signaling pathway was detected by RT-qPCR and western blot techniques. The binding profile of NEAT1 to miR-144-3p was evaluated via a combination approach of luciferase activity assay, RNA immunoprecipitation, and RNA pull-down experiments.

Results:

Blood exosomes extracted from RA patients increased the incidence of RA and bone destruction significantly. Overexpression of NEAT1 or ROCK2 promoted immune cell (CD4+T cells) proliferation, Th17 cell differentiation, and cell migration in response to stimulus, whereas knockout of the NEAT1 gene induced the expression of miR-144-3p in CD4+T cells. ROCK2 exogenous expression inhibited the expression of miR-144-3p, inducing activation of the WNT signaling pathway.

Conclusion:

A novel regulatory pathway NEAT1/miR-144-3p/ROCK2/WNT in RA was investigated as a potential target for RA therapy.
Effects of an eHealth Intervention on Patient-Provider Interaction and Functional Health Literacy in Adults With Hypertension
Authors: Hickman Ronald L. , Clochesy John M. , Alaamri Marym
Published: April 2021

Introduction

Hypertension is a life-limiting, chronic condition affecting millions of Americans. Modifiable factors, quality of the patient-provider interaction and functional health literacy, have been linked to effective hypertension self-management. However, there has been limited interventional research targeting these modifiable factors. Electronic hypertension self-management interventions, in particular those incorporating virtual simulation, may positively influence the quality of the patient-provider interaction and functional health literacy status of adults with hypertension. Yet there is a dearth of evidence examining the efficacy of eHealth interventions targeting these modifiable factors of hypertension self-management.

Objective

Evaluate the effects of two electronic hypertension self-management interventions on the quality of the patient-provider interaction and functional health literacy in adults with hypertension.

Methods

A convenience sample of community-dwelling adults (>18 years) with hypertension were recruited and randomized to an avatar-based simulation (eSMART-HTN) or a video presentation on hypertension self-management (attention control). Participants were administered questionnaires to capture demographic characteristics, the quality of the patient-provider interaction, and functional health literacy. Questionnaire data were collected at baseline, and then monthly across three months. Two separate repeated measures analysis of covariance models were conducted to assess the effects of the interventions across the time points.

Results

The sample included 109 participants who were predominately middle-aged and older, nonwhite, and female. Scores for the quality of the patient-provider interaction demonstrated significant within-group changes across time. However, there were no significant differences in the quality of the patient-provider interaction or functional health literacy scores between experimental conditions while adjusting for covariates.

Conclusion

An avatar-based simulation (eSMART-HTN) intervention proved to have a positive effect on patient-provider interaction compared to an attention control condition. Although the results are promising, future research is needed to optimize the effectiveness of eSMART-HTN and enhance its efficacy and scalability in a larger cohort of adults with hypertension.
Reopening Oral Health Services during the COVID-19 Pandemic through a Knowledge Exchange Coalition
Authors: McNally M. , Rock L. , Gillis M. , Bryan S. , Boyd C. , Kraglund F. , Cleghorn B.
Published: April 2021

Background:

The COVID-19 novel coronavirus closed oral health care in Nova Scotia (NS) Canada in March 2020. Preparing for a phased reopening, a knowledge exchange coalition (representing government, academia, hospitals, oral health professions, and regulators) developed return-to-work (RTW) guidelines detailing the augmentation of standard practices to ensure safety for patients, oral health care providers (OHPs), and the community. Using online surveys, this study explored the influence of the RTW guidelines and related education on registered NS OHPs during a phased return to work.

Methods:

Dissemination of R2W guidelines included website or email communiques and interdisciplinary education webinars that coincided with 2 RTW phases approved by the government. Aligned with each phase, all registered dentists, dental hygienists, and dental assistants were invited to complete an online survey to gauge the influence of the coalition-sponsored education and RTW guidelines, confidence, preparedness, and personal protective equipment use before and after the pandemic.

Results:

Three coalition-sponsored multidisciplinary webinars hosted 3541 attendees prior to RTW. The response to survey 1 was 41% (881/2156) and to survey 2 was 26% (571/2177) of registrants. Survey 1 (82%) and survey 2 (89%) respondents “agreed/strongly agreed” that R2W guidelines were a primary source for guiding return to practice, and most were confident with education received and had the skills needed to effectively treat patients during the COVID-19 pandemic. Confidence and preparedness improved in survey 2. Gowns/lab coat use for aerosol-generating procedures increased from 26% to 93%, and the use of full face shields rose from 6% to 93% during the pandemic.

Conclusions:

A multistakeholder coalition was effective in establishing and communicating comprehensive guidelines and web-based education to ensure unified reintegration of oral health services in NS during a pandemic. This multiorganizational cooperation lay the foundation for responses to subsequent waves of COVID-19 and may serve as an example for collaboratively responding to future public health threats in other settings.

Knowledge Transfer Statement:

The return-to-work strategy that was developed, disseminated, and assessed through this COVID-19 knowledge exchange coalition will benefit oral health practitioners, professional regulators, government policy makers, and researchers in future pandemic planning.
Ankle Arthroscopy as an Adjunct to the Management of Ankle Fractures
Authors: Aziz Hibba , Amirian Aslan , Dabash Sherif , Dunn Warren R. , Bloome David
Published: April 2021

Background:

Ankle fractures are one of the most common injuries managed by orthopedic surgeons. Although the etiology of posttraumatic osteoarthritis in anatomically reduced ankle fractures is not completely known, several studies suggest that undetected intra-articular pathology at the time of injury may play a role. The purpose of this study is to report the operative findings of ankle arthroscopy as an adjunct to ankle fracture open reduction and internal fixation.

Methods:

A retrospective review was performed of all ankle fractures treated consecutively at our institution by a single surgeon from August 2010 to October 2019, which were found using Current Procedural Terminology codes. A total of 84 patients met our inclusion criteria for whom patient demographics and clinical history were collected. Pre- and postoperative diagnoses from every operative report were noted as well as intra-articular intervention made during the time of arthroscopy.

Results:

The study included 49 men (58.3%) and 35 women (41.7%), with a mean age of 39.0 (range, 12-69; SD = 15.0) years. Sixty-three patients (75%) had new diagnoses detected by the addition of ankle arthroscopy. The most common new pathology seen arthroscopically were osteochondral lesions (n = 36, 41.9%) and posterior malleolus fractures (n = 28, 32.6%). Thirty-four patients had a total of 40 additional arthroscopic procedures in conjunction with their fracture management. Complications were noted in 13 patients, with hardware removal (n = 8) being the most common (62%).

Conclusion:

Ankle arthroscopy can act as a significant diagnostic and prognostic tool and can help address intra-articular injuries without adding considerable cost or serious adverse events.

Level of Evidence:

Level IV, retrospective case series.
Carotid artery stenosis – Current evidence and treatment recommendations
Authors: Müller Mandy D , Bonati Leo H
Published: April 2021

Background:

Carotid artery stenosis is an important cause for stroke. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic carotid stenosis and to some extent in patients with asymptomatic carotid stenosis. More than 20 years ago, carotid artery stenting (CAS) emerged as an endovascular treatment alternative to CEA.

Objective and Methods:

This review summarises the available evidence from randomised clinical trials in patients with symptomatic as well as in patients with asymptomatic carotid stenosis.

Results:

CAS is associated with a higher risk of death or any stroke between randomisation and 30 days after treatment than CEA (odds ratio (OR) = 1.74, 95% CI 1.3 to 2.33, p < 0.0001). In a pre-defined subgroup analysis, the OR for stroke or death within 30 days after treatment was 1.11 (95% CI 0.74 to 1.64) in patients <70 years old and 2.23 (95% CI 1.61 to 3.08) in patients ≥70 years old, resulting in a significant interaction between patient age and treatment modality (interaction p = 0.007). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up also favoured CEA (OR = 1.51, 95% CI 1.24 to 1.85, p < 0.0001). In asymptomatic patients, there is a non-significant increase in death or stroke occurring within 30 days of treatment with CAS compared to CEA (OR = 1.72, 95% CI 1.00 to 2.97, p = 0.05). The risk of peri-procedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR = 1.27, 95% CI 0.87 to 1.84, p = 0.22).

Discussion and Conclusion:

In symptomatic patients, randomised evidence has consistently shown CAS to be associated with a higher risk of stroke or death within 30 days of treatment than CEA. This extra risk is mostly attributed to an increase in strokes occurring on the day of the procedure in patients ≥70 years. In asymptomatic patients, there may be a small increase in the risk of stroke or death within 30 days of treatment with CAS compared to CEA, but the currently available evidence is insufficient and further data from ongoing randomised trials are needed.
Effect of the glycine-rich domain in GAREM2 on its unique subcellular localization upon EGF stimulation
Authors: Nishino Tasuku , Oshika Tsuyoshi , Kyan Moriatsu , Konishi Hiroaki
Published: April 2021

Background

In mammals, there are two subtypes of Grb2-associated regulator of Erk/MAPK (GAREM), an adaptor protein that functions downstream of the cell growth factor receptor. GAREM1 is ubiquitously expressed, whereas GAREM2 is mainly expressed in the brain. However, the precise mechanism of the translocation of each GAREM subtype in growth factor-stimulated cells is still unclear.

Methods

In this study, immunofluorescence staining with specific antibodies against each GAREM subtype and time-lapse analysis using GFP fusion proteins were used to analyze the subcellular localization of each GAREM subtype in a cell growth stimulus-dependent manner. We also biochemically analyzed the correlation between its subcellular localization and tyrosine phosphorylation of GAREM2.

Results

We found that endogenously and exogenously expressed GAREM2 specifically aggregated and formed granules in NGF-stimulated PC-12 cells and in EGF-stimulated COS-7 cells. Based on the observed subcellular localizations of chimeric GAREM1 and GAREM2 proteins, a glycine-rich region, which is present only in GAREM2, is required for the observed granule formation. This region also regulates the degree of EGF-stimulation-dependent tyrosine phosphorylation of GAREM2.

Conclusions

Our results, showing that aggregation of GAREM2 in response to EGF stimulation is dependent on a glycine-rich region, suggest that GAREM2 aggregation may be involved in neurodegenerative diseases.
Genome-wide variant-based study of genetic effects with the largest neuroanatomic coverage
Authors: Li Jin , Liu Wenjie , Li Huang , Chen Feng , Luo Haoran , Bao Peihua , Li Yanzhao , Jiang Hailong , Gao Yue , Liang Hong , Fang Shiaofen
Published: April 2021

Background

Brain image genetics provides enormous opportunities for examining the effects of genetic variations on the brain. Many studies have shown that the structure, function, and abnormality (e.g., those related to Alzheimer’s disease) of the brain are heritable. However, which genetic variations contribute to these phenotypic changes is not completely clear. Advances in neuroimaging and genetics have led us to obtain detailed brain anatomy and genome-wide information. These data offer us new opportunities to identify genetic variations such as single nucleotide polymorphisms (SNPs) that affect brain structure. In this paper, we perform a genome-wide variant-based study, and aim to identify top SNPs or SNP sets which have genetic effects with the largest neuroanotomic coverage at both voxel and region-of-interest (ROI) levels. Based on the voxelwise genome-wide association study (GWAS) results, we used the exhaustive search to find the top SNPs or SNP sets that have the largest voxel-based or ROI-based neuroanatomic coverage. For SNP sets with >2 SNPs, we proposed an efficient genetic algorithm to identify top SNP sets that can cover all ROIs or a specific ROI.

Results

We identified an ensemble of top SNPs, SNP-pairs and SNP-sets, whose effects have the largest neuroanatomic coverage. Experimental results on real imaging genetics data show that the proposed genetic algorithm is superior to the exhaustive search in terms of computational time for identifying top SNP-sets.

Conclusions

We proposed and applied an informatics strategy to identify top SNPs, SNP-pairs and SNP-sets that have genetic effects with the largest neuroanatomic coverage. The proposed genetic algorithm offers an efficient solution to accomplish the task, especially for identifying top SNP-sets.
Uncarboxylated osteocalcin alleviates the inhibitory effect of high glucose on osteogenic differentiation of mouse bone marrow–derived mesenchymal stem cells by regulating TP63
Authors: Gong Fangzi , Gao Le , Ma Luyao , Li Guangxin , Yang Jianhong
Published: April 2021

Background

Progressive population aging has contributed to the increased global prevalence of diabetes and osteoporosis. Inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by hyperglycemia is a potential pathogenetic mechanism of osteoporosis in diabetic patients. Uncarboxylated osteocalcin (GluOC), a protein secreted by mature osteoblasts, regulates bone development as well as glucose and lipid metabolism. In our previous studies, GluOC was shown to promote osteoblastic differentiation of BMSCs; however, the underlying mechanisms are not well characterized. Tumor protein 63 (TP63), as a  transcription factor, is closely related to bone development and glucose metabolism.

Results

In this study, we verified that high glucose suppressed osteogenesis and upregulated adipogenesis in BMSCs, while GluOC alleviated this phenomenon. In addition, high glucose enhanced TP63 expression while GluOC diminished it. Knock-down of TP63 by siRNA transfection restored the inhibitory effect of high glucose on osteogenic differentiation. Furthermore, we detected the downstream signaling pathway PTEN/Akt/GSK3β. We found that diminishing TP63 decreased PTEN expression and promoted the phosphorylation of Akt and GSK3β. We then applied the activator and inhibitor of Akt, and concluded that PTEN/Akt/GSK3β participated in regulating the differentiation of BMSCs.

Conclusions

Our results indicate that GluOC reduces the inhibitory effect of high glucose on osteoblast differentiation by regulating the TP63/PTEN/Akt/GSK3β pathway. TP63 is a potential novel target for the prevention and treatment of diabetic osteoporosis.