bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between IL-6 and severe disease and mortality in COVID-19 disease: a systematic review and meta-analysis
Authors: Liu Xiaohui , Wang Hongwei , Shi Si , Xiao Jinling 
Published: June 2021

AbstractBackgroundSo far, SARS-CoV-2 is the seventh coronavirus found to infect humans and cause disease with quite a strong infectivity. Patients diagnosed as severe or critical cases are prone to multiple organ dysfunction syndrome, acute respiratory distress syndrome and even death. Proinflammatory cytokine IL-6 has been reported to be associated with the severity of disease and mortality in patients with COVID-19.ObjectiveThis systematic review and meta-analysis were carried out to evaluate the association between IL-6 and severe disease and mortality in COVID-19 disease.MethodsA systematic literature search using China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, Chinese Biomedical Literature, Embase, PubMed and Cochrane Central Register of Controlled Trials was performed from inception until 16 January 2021.Results12 studies reported the value of IL-6 for predicting the severe disease in patients with COVID-19. The pooled area under the curve (AUC) was 0.85 (95% CI 0.821 to 0.931). 5 studies elaborated the predictive value of IL-6 on mortality. The pooled sensitivity, specificity and AUC were 0.15 (95% CI 0.13 to 0.17, I2=98.9%), 0.73 (95% CI 0.65 to 0.79, I2=91.8%) and 0.531 (95% CI 0.451 to 0.612), respectively. Meta-regression analysis showed that country, technique used, cut-off, sample, study design and detection time did not contribute to the heterogeneity of mortality.ConclusionIL-6 is an adequate predictor of severe disease in patients infected with the COVID-19. The finding of current study may guide clinicians and healthcare providers in identifying potentially severe or critical patients with COVID-19 at the initial stage of the disease. Moreover, we found that only monitoring IL-6 levels does not seem to predict mortality and was not associated with COVID-19’s mortality.PROSPERO registration numberCRD42021233649.
Evaluation of a survey for acute care programme directors on the utilisation of point-of-care ultrasound
Authors: Wang Annie , McCabe Melissa , Gow-Lee Esther , James Stephanie , Austin Briahnna , Wailes Dustin , Dinh Vi , Ramsingh Davinder 
Published: June 2021

AbstractPurposePoint-of-care ultrasound (POCUS) is ultrasound brought to the patient's bedside and performed in ‘real time’ by the healthcare provider. The utility of POCUS to facilitate management of the acutely ill patient has been demonstrated for multiple pathologies. However, the integration of ultrasonography and echocardiography training into residency curriculum varies across the acute care specialties.Study designAfter an institutional review board approval, anaesthesiology, emergency medicine, family medicine, internal medicine, paediatrics and general surgery programme directors (PDs) were surveyed. The survey consisted of 11 questions evaluating the primary bedside assessment tool for common acute care situations, POCUS topics that the PDs were comfortable practising and topics that the PDs felt were useful for their specialty. Barriers to POCUS use, certification and documentation were also surveyed.ResultsOverall, 270 PD surveys were completed. The preferred primary assessment tool for common acute care situations varied with specialty; emergency medicine PDs consistently responded that POCUS was the diagnostic modality of choice (p&lt;0.0001). The majority of the PDs reported lack of educational opportunities as the primary barrier to learning POCUS (64%). Most PDs indicated that POCUS examinations should be documented (95.7%), and 39% reported that departmental certification would be sufficient.ConclusionsThis study is the first to evaluate differences in the preferred initial bedside assessment tool between the acute care specialties. Although POCUS is a superior tool for evaluating acute pathologies, disconnect between education and utilisation remains. This study highlights the need to incorporate POCUS into the acute care specialty curriculum.
Competition-driven modeling of temporal networks
Authors: Zhu Kaijie , Fletcher George , Yakovets Nikolay 
Published: June 2021

AbstractWe study the problem of modeling temporal networks constrained by the size of a concurrent set, a characteristic of temporal networks shown to be important in many application areas, e.g., in transportation, social, process, and other networks. We propose a competition-driven model for the generation of such constrained networks. Our method carries out turns of competitions along the timeline where each node in a network is labeled with a probability to gain outgoing edges in competitions. We present a thorough theoretical analysis to investigate the cardinality and degree distributions of the generated networks. Our experimental results demonstrate that our model simulates real-world networks well and generates networks efficiently and at scale.
Aging and CNS Myeloid Cell Depletion Attenuate Breast Cancer Brain Metastasis
Authors: Wu Alex Man Lai , Gossa Selamawit , Samala Ramakrishna , Chung Monika A. , Gril Brunilde , Yang Howard H. , Thorsheim Helen R. , Tran Andy D. , Wei Debbie , Taner Esra , Isanogle Kristine , Yang Yuan , Dolan Emma L. , Robinson Christina , Difilippantonio Simone , Lee Maxwell P. , Khan Imran , Smith Quentin R. , McGavern Dorian B. , Wakefield Lalage M. , Steeg Patricia S. 
Published: June 2021

Abstract

Purpose:
Breast cancer diagnosed in young patients is often aggressive. Because primary breast tumors from young and older patients have similar mutational patterns, we hypothesized that the young host microenvironment promotes more aggressive metastatic disease.

Experimental Design:
Triple-negative or luminal B breast cancer cell lines were injected into young and older mice side-by-side to quantify lung, liver, and brain metastases. Young and older mouse brains, metastatic and naïve, were analyzed by flow cytometry. Immune populations were depleted using antibodies or a colony-stimulating factor-1 receptor (CSF-1R) inhibitor, and brain metastasis assays were conducted. Effects on myeloid populations, astrogliosis, and the neuroinflammatory response were determined.

Results:
Brain metastases were 2- to 4-fold higher in young as compared with older mouse hosts in four models of triple-negative or luminal B breast cancer; no age effect was observed on liver or lung metastases. Aged brains, naïve or metastatic, contained fewer resident CNS myeloid cells. Use of a CSF-1R inhibitor to deplete myeloid cells, including both microglia and infiltrating macrophages, preferentially reduced brain metastasis burden in young mice. Downstream effects of CSF-1R inhibition in young mice resembled that of an aged brain in terms of myeloid numbers, induction of astrogliosis, and Semaphorin 3A secretion within the neuroinflammatory response.

Conclusions:
Host microenvironmental factors contribute to the aggressiveness of triple-negative and luminal B breast cancer brain metastasis. CSF-1R inhibitors may hold promise for young brain metastasis patients.
Repertoire Remodeling through CD4+ T-cell Depletion
Authors: Yao Winnie , Satpathy Ansuman T. 
Published: June 2021

Abstract
Understanding the cellular regulation of tumor-specific CD8+ T-cell responses is critical to designing improved clinical strategies for cancer immunotherapy. In this issue, Aoki and colleagues deepen our knowledge of this topic by demonstrating that transient depletion of CD4+ T cells in patients with gastrointestinal cancer induces remodeling of the T-cell repertoire, including clonal replacement and expansion of CD8+ T-cell clones shared between the blood and tumor.
See article by Aoki et al., p. 624
Design of utility functions for game-based channel allocation in cognitive radio wireless sensor network
Authors: Rai Prativa , Kanti Ghose Mrinal , Kumar Deva Sarma Hiren 
Published: June 2021

Cognitive radio enabled wireless sensor network is capable of reducing the spectrum scarcity problem of the wireless networks. Looking at the scarcity of available bandwidth, and the high growth in the number of communication devices in recent times, cognitive radio technology has proven to be a promising technology for the days to come. The application of Game Theory in cognitive radio networks has been visible in recent research works. However, only limited literature is available in which possibilities of applying the game-theory based approaches for the challenging task of channel assignment in cognitive radio wireless sensor are available in the literature. It is understood that the crux of the solution to the problem of scheming games for allocation of the channel is centered on the selection of the utility function in order to increase the efficiency of the channel allocation algorithm. Accordingly, the study regarding the influence of several utility functions on the performance of the corresponding channel allocation algorithm is important. Such a study enables designers to arrive at the optimal utility function to be used in game-theory based channel allocation algorithms, and the same is explored to the best extent, in this paper. The detailed procedure of allocating channels to all the contending nodes through game-based channel allocation has been discussed in this paper. Moreover, the performance of six different utility functions proposed which can be used for channel allocation using game theory has been evaluated for respective performances through MATLAB-based simulations.
Dynamic composition components based on machine learning: architecture design and process
Authors: Zouani Younes , Abdali Abdelmounaim , Ait Zaouiat Charafeddine 
Published: June 2021

<p>The dynamic composition of components is an emerging concept that aims to allow a new application to be constructed based on a user’s request. Three main ingredients must be used to achieve the dynamic composition of components: goal, scenario, and context-awareness. These three ingredients must be completed by artificial intelligence (AI) techniques that help process discovery and storage. This paper presents framework architecture for the dynamic composition of components that can extract expressed goals, deduce implicit ones using AI. The goal will be combined with pertinent contextual data, to compose the relevant components that meet the real requirements of the user. The core element of our proposed architecture is the composer component that (i) negotiate user goal, (ii) load the associated scenarios and choose the most suitable one based on user goal and profile, (iii) get binding information of scenario’s actions, (iv) compose the loaded actions, and (v) store the new component as a tree of actions enabled by contextual or process constraint. In our e-learning proven of concept, we consider five components: composer component, reader component, formatter component, matcher component, and executor component. These five components stipulate that a course is the combination of existing/scrapped chapters that have been adapted to a user profile in terms of language, level of difficulty, and prerequisite. The founding result shows that AI is not only an element that enhances system performance in terms of timing response but a crucial ingredient that guides the dynamic composition of components.</p><div style="display: none;"> </div>
Myofibroblast Deficiency of LSD1 Alleviates TAC-Induced Heart Failure
Authors: Huo Jin-Ling , Jiao Lemin , An Qi , Chen Xiuying , Qi Yuruo , Wei Bingfei , Zheng Yichao , Shi Xiaojing , Gao Erhe , Liu Hong-Min , Chen Dong , Wang Cong , Zhao Wen 
Published: June 2021

Rationale:
Histone LSD1 (lysine-specific demethylase 1) is an important epigenetic antitumor drug target, whose inhibitors are currently in phase I/II clinical trials. However, the potential side effects of LSD1 inhibition in the progress of cardiac remodeling to heart failure remain to be investigated.

Objective:
To evaluate the roles of myofibroblast- or cardiomyocyte-specific LSD1 deficiency in pressure overload-induced cardiac remodeling.

Methods and Results:
Adult mouse cardiac fibroblasts, neonatal rat cardiac myocytes, and fibroblasts were isolated, respectively. The myofibroblast-specific and cardiomyocyte-specific LSD1 inducible knockout mice were then generated. We found that LSD1 was increased not only in human dilated cardiomyopathy hearts but also in wild-type mouse heart homogenates and isolated cardiac fibroblasts, following 20 weeks of transverse aortic constriction. The upregulation of LSD1 was also observed in Ang II-treated neonatal rat cardiac fibroblasts, which was reversed by LSD1 silence or its activity inhibition by ORY-1001. These findings suggested a potential involvement of LSD1 in cardiac remodeling. Importantly, myofibroblast-specific LSD1 inducible knockout in vivo significantly alleviated systolic dysfunction, cardiac hypertrophy, and fibrosis, following 6 and 20 weeks of transverse aortic constriction. Mechanistically, through RNA-sequencing and the following Western blot analysis, we found that loss of LSD1 in Ang II-induced myofibroblasts not only inhibited the intracellular upregulation of TGFβ1 (transforming growth factor β1), its downstream effectors Smad2/3 phosphorylation, as well as the phosphorylation of p38, ERK1/2 and JNK, but also reduced the supernatant TGFβ1 secretion, which then decreased myocyte hypertrophy in the indirect coculture model. On the other hand, cardiomyocyte-specific LSD1-inducible knockout in vivo triggered the reprogramming of fetal genes, mild cardiac hypertrophy, and dysfunction under both basal and stressed conditions.

Conclusions:
Our findings, for the first time, implicate that myofibroblast-specific LSD1 deletion attenuates transverse aortic constriction-induced cardiac remodeling and improves heart function, suggesting that LSD1 is a potential therapeutic target for late-stage heart failure.
Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension
Authors: Bisserier Malik , Mathiyalagan Prabhu , Zhang Shihong , Elmastour Firas , Dorfmüller Peter , Humbert Marc , David Gregory , Tarzami Sima , Weber Thomas , Perros Frederic , Sassi Yassine , Sahoo Susmita , Hadri Lahouaria 
Published: June 2021

Background:
Epigenetic mechanisms are critical in the pathogenesis of pulmonary arterial hypertension (PAH). Previous studies have suggested that hypermethylation of the BMPR2 (bone morphogenetic protein receptor type 2) promoter is associated with BMPR2 downregulation and progression of PAH. Here, we investigated for the first time the role of SIN3a (switch-independent 3a), a transcriptional regulator, in the epigenetic mechanisms underlying hypermethylation of BMPR2 in the pathogenesis of PAH.

Methods:
We used lung samples from PAH patients and non-PAH controls, preclinical mouse and rat PAH models, and human pulmonary arterial smooth muscle cells. Expression of SIN3a was modulated using a lentiviral vector or a siRNA in vitro and a specific adeno-associated virus serotype 1 or a lentivirus encoding for human SIN3a in vivo.

Results:
SIN3a is a known transcriptional regulator; however, its role in cardiovascular diseases, especially PAH, is unknown. It is interesting that we detected a dysregulation of SIN3 expression in patients and in rodent models, which is strongly associated with decreased BMPR2 expression. SIN3a is known to regulate epigenetic changes. Therefore, we tested its role in the regulation of BMPR2 and found that BMPR2 is regulated by SIN3a. It is interesting that SIN3a overexpression inhibited human pulmonary arterial smooth muscle cells proliferation and upregulated BMPR2 expression by preventing the methylation of the BMPR2 promoter region. RNA-sequencing analysis suggested that SIN3a downregulated the expression of DNA and histone methyltransferases such as DNMT1 (DNA methyltransferase 1) and EZH2 (enhancer of zeste 2 polycomb repressive complex 2) while promoting the expression of the DNA demethylase TET1 (ten-eleven translocation methylcytosine dioxygenase 1). Mechanistically, SIN3a promoted BMPR2 expression by decreasing CTCF (CCCTC-binding factor) binding to the BMPR2 promoter. Last, we identified intratracheal delivery of adeno-associated virus serotype human SIN3a to be a beneficial therapeutic approach in PAH by attenuating pulmonary vascular and right ventricle remodeling, decreasing right ventricle systolic pressure and mean pulmonary arterial pressure, and restoring BMPR2 expression in rodent models of PAH.

Conclusions:
All together, our study unveiled the protective and beneficial role of SIN3a in pulmonary hypertension. We also identified a novel and distinct molecular mechanism by which SIN3a regulates BMPR2 in human pulmonary arterial smooth muscle cells. Our study also identified lung-targeted SIN3a gene therapy using adeno-associated virus serotype 1 as a new promising therapeutic strategy for treating patients with PAH.
Humanizing the Enlightened Childhood: Epistolography as Human Formation in Tibetan Buddhism
Authors: Kilby Christina A. 
Published: June 2021

Abstract
This article contributes a Buddhist studies perspective to the question of what it means to be human. By analyzing a collection of letters written to a young Tibetan Buddhist lama, I trace the contours of a humanizing project that grounds the youth within the lived experience of the human life course that his elder has traversed. I also analyze epistolography as a medium for humanistic formation within Tibetan Buddhist monastic education. This textual study, though rooted in the context of a single epistolary relationship in early modern Tibet, illuminates the search for human wisdom that is fundamental to Buddhist childhoods across historical and cultural contexts.
Submesoscale Instability in the Straits of Florida
Authors: Chérubin Laurent M. , Le Paih Nicolas , Carton Xavier 
Published: June 2021

AbstractThe Florida Current (FC) flows in the Straits of Florida (SoF) and connects the Loop Current in the Gulf of Mexico to the Gulf Stream (GS) in the Western Atlantic Ocean. Its journey through the SoF is at time characterized by the formation and presence of mesoscale but mostly submesoscale frontal eddies on the cyclonic side of the current. The formation of those frontal eddies was investigated in a very high resolution two-way nested simulation using the Regional Oceanic Modeling System (ROMS). Frontal eddies were either locally formed or originated from outside the SoF. The northern front of the incoming eddies was susceptible to superinertial shear instability over the shelf slope when the eddies were pushed up against the slope by the FC. Otherwise, incoming eddies could be advected relatively unaffected by the current, when in the southern part of the straits. In absence of incoming eddies, submesoscale eddies were locally formed by the roll-up of superinertial barotropically unstable vorticity filaments when the FC was pushed up against the shelf slope. The vorticity filaments were intensified by the friction-induced bottom layer vorticity flux as previously demonstrated by Gula et al. (2015b) in the GS. When the FC retreated further south, negative vorticity West Florida Shelf waters overflowed into the SOF and led to the formation of submesocale eddies by baroclinic instability. The instability regimes, hence, the submesoscale frontal eddies formation appear to be controlled by the lateral ‘sloshing’ of the FC in the SoF.
COVID-19 Impact on Buying Behaviour
Authors: Verma Meghna , Naveen B. R. 
Published: June 2021

Executive Summary Pandemics like COVID-19 result in a disruption in the lifestyle and buying pattern of a consumer and adversely impact the global economy. Consumer purchase of country’s own brand and the products manufactured in their own country plays a vital role in the GDP of that country and help in revival of the country’s economy. This study focuses on understanding the factors that influence consumer’s buying behaviour and model these factors to understand the causal relationship using partial least square-structural equation modelling. An online survey which was carried out between 30 March 2020 and 18 April 2020. A total of 367 responses were collected during this period. Findings of the study indicate that economic nationalism, lockdown sentiments and sustainable approach (LSSA), and product-specific ethnocentric behaviour (PSEB) tendency significantly influence the willingness to buy country’s own brands and products. Present study results reveal that during pandemic consumers have realized the importance of hygiene products, environment-friendly products, regional (local) products, and satisfaction beyond shopping; these factors determine their willingness to buy Indian brands (WBIB)/made-in-India products. Further, post lockdown and post COVID era, consumers feel that buying Indian-made products and encouraging others to buy them would impact and revive the Indian economy constructively. It was also found that the influence of factors such as economic nationalism, LSSA, and PSEB on the WBIB is mediated by attitude towards foreign products. The findings of the study can aid marketing managers in planning appropriate promotion strategies to stimulate ethnocentric tendency, and cues can be provided to invoke a sense of economic nationalism in consumers when they buy products or services.
Nationwide evaluation of palliative care (Q-PAC study) provided by specialized palliative care teams using quality indicators : Large variations in quality of care
Authors: Cohen Joachim , Hermans Kirsten , Dupont Charlèss , Van den Block Lieve , Deliens Luc , Leemans Kathleen 
Published: June 2021

Background: Although a number of quality indicators for palliative care have been implemented worldwide, evidence regarding the performance of palliative care teams is scarce. Aim: Evaluating the quality of palliative care using quality indicators; to describe the variation in quality between palliative care teams; and to suggest quality benchmarks for these teams. Design: A repeated cross-sectional study design to collect quality indicator data by means of a validated quality indicator set in 36 Belgian palliative care teams at home and in hospitals. Risk-adjustment procedures, taking into account patient-mix, were applied to suggest benchmarks. Participants: Between 2014 and 2017, five quality measurements with questionnaires were conducted in 982 patients receiving palliative care, 4701 care providers and 1039 family members of deceased patients. Results: A total of 7622 assessments were received. Large risk-adjusted variations between the different palliative care teams were identified in: regularly updating patient files (IQR: 12%–39%), having multidisciplinary consultations about care objectives (IQR: 51%–73%), discussing end-of-life care decisions with patients (IQR: 26%–71%–92%), relieving shortness of breath (IQR: 57%–78%), regularly assessing pain (IQR: 43%–74%) and symptoms by means of validated scales (IQR: 23%–60%), initiating palliative care at least 2 weeks before death (IQR: 30%–50%), and weekly contact with the GP in the last 3 months of life (IQR 16%–43%). Conclusion: The large risk-adjusted variation found across the quality indicator scores suggest that repeated and standardized quality improvement evaluations can allow teams to benchmark themselves to each other to identify areas of their palliative care delivery that need improvement.