bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and methodology for a European pooled analysis of postmarketing interventional and observational studies of insulin glargine 300 U/mL in diabetes: protocol of REALI project
Authors: Freemantle Nick , Bonadonna Riccardo C , Gourdy Pierre , Mauricio Didac , Mueller-Wieland Dirk , Bigot Gregory , Ciocca Alice , Mauquoi Celine , Rollot Mélissa , Bonnemaire Mireille
Published: April 2020

Introduction

Type 2 diabetes mellitus (T2DM) is a common and heterogeneous disease. Using advanced analytic approaches to explore real-world data may identify different disease characteristics, responses to treatment and progression patterns. Insulin glargine 300 units/mL (Gla-300) is a second-generation basal insulin analogue with preserved glucose-lowering efficacy but reduced risk of hypoglycaemia. The purpose of the REALI pooled analysis described in this paper is to advance the understanding of the effectiveness and real-world safety of Gla-300 based on a large European patient database of postmarketing interventional and observational studies.

Methods and analysis

In the current round of pooling, REALI will include data from up to 10 000 subjects with diabetes mellitus (mostly T2DM) from 20 European countries. Outcomes of interest include change from baseline to week 24 in haemoglobin A1c, fasting plasma glucose, self-measured plasma glucose, body weight, insulin dose, incidence and rate of any-time-of-the-day and nocturnal hypoglycaemia. The data pool is being investigated using two complementary methodologies: a conventional descriptive, univariate and multivariable prognostic analysis; and a data-mining approach using subgroup discovery to identify phenotypic clusters of patients who are highly associated with the outcome of interest. By mid-2019, deidentified data of 7584 patients were included in the REALI database, with a further expected increase in patient number in 2020 as a result of pooling additional studies.

Ethics and dissemination

The proposed study does not involve collection of primary data. Moreover, all individual study protocols were approved by independent local ethics committees, and all study participants provided written informed consent. Furthermore, patient data is deidentified before inclusion in the REALI database. Hence, there is no requirement for ethical approval. Results will be disseminated via peer-reviewed publications and presentations at international congresses as data are analysed.
Strategies to support HIV literacy in the roll-out of pre-exposure prophylaxis in Scotland: findings from qualitative research with clinical and community practitioners
Authors: Young Ingrid , Valiotis George
Published: April 2020

Objectives

Limited understanding of pre-exposure prophylaxis (PrEP), coupled with negative public discourse, are significant barriers to its introduction. What works to support PrEP awareness and broader HIV literacy among diverse communities in the context of biomedical HIV prevention remains unclear. This article considers how PrEP can be translated across diverse communities and what the HIV literacy challenges might be in the current context of PrEP provision.

Setting

We developed an HIV literacy informed community tool to support the roll-out of PrEP in Scotland. We undertook qualitative research with practitioners in urban and rural settings across nine Scottish health boards.

Primary outcome measure

To examine HIV literacy challenges in the context of PrEP provision.

Participants

Interviews and focus groups with community (n=19) and clinical (n=13) practitioners working with gay and bisexual men and African communities were undertaken between March and October 2017 concerning PrEP support, stigma and HIV literacy.

Results

HIV literacy in the context of PrEP needs to consider more than the provision of individually targeted information. Practitioners identified and responded to stratified communities and social norms of knowledge, which influenced messaging, support and informed how practitioners enabled PrEP engagement and dialogue. Social barriers in HIV literacy, including structural stigmas relating to HIV and homophobia, shaped practitioner concerns and support for community members’ willingness to engage with PrEP.

Conclusion

Critical HIV literacy in the age of PrEP is a complex social practice. Attention needs to be paid tohowinformation is provided and facilitates engagement, rather than simplywhatinformation is given.By exploring practitioner use of the Know about PrEP tool, we have shown how consideration of the patterns of access to services and information, the delivery of and support for engagement with PrEP information and the wider strategies employed to negotiate ongoing structural social barriers can support more equitable and diverse PrEP community conversations.
Adverse events in the paediatric emergency department: a prospective cohort study
Authors: Plint Amy C , Stang Antonia , Newton Amanda S , Dalgleish Dale , Aglipay Mary , Barrowman Nick , Tse Sandy , Neto Gina , Farion Ken , Creery Walter David , Johnson David W , Klassen Terry P , Calder Lisa A
Published: April 2020

Background

Understanding adverse events among children treated in the emergency department (ED) offers an opportunity to improve patient safety by providing evidence of where to focus efforts in a resource-restricted environment.

Objective

To estimate the risk of adverse events, their type, preventability and severity, for children seen in a paediatric ED.

Methods

This prospective cohort study examined outcomes of patients presenting to a paediatric ED over a 1-year period. The primary outcome was the proportion of patients with an adverse event (harm to patient related to healthcare received) related to ED care within 3 weeks of their visit. We conducted structured telephone interviews with all patients and families over a 3-week period following their visit to identify flagged outcomes (such as repeat ED visits, worsening symptoms) and screened admitted patients’ health records with a validated trigger tool. For patients with flagged outcomes or triggers, three ED physicians independently determined whether an adverse event occurred.

Results

Of 1567 eligible patients, 1367 (87.2%) were enrolled and 1319 (96.5%) reached in follow-up. Median patient age was 4.34 years (IQR 1.5 to 10.57 years) and most (n=1281; 93.7%) were discharged. Among those with follow-up, 33 (2.5%, 95% CI 1.8% to 3.5%) suffered an adverse event related to ED care. None experienced more than one event. Twenty-nine adverse events (87.9%, 95% CI 72.7% to 95.2%) were deemed preventable. The most common types of adverse events (not mutually exclusive) were management issues (51.5%), diagnostic issues (45.5%) and suboptimal follow-up (15.2%).

Conclusion

One in 40 children suffered adverse events related to ED care. A high proportion of events were preventable. Management and diagnostic issues warrant further study.
Finding the missing link: when community-based outreach in public space is key to engage migrants in health prevention programmes in Paris, France
Authors: Gosselin Anne , Coulibaly Karna , Ravalihasy Andrainolo , Carillon Séverine , Ridde Valéry , Derche Nicolas , Mbiribindi Romain , Desgrées du Loû Annabel
Published: April 2020

Background

One of the classic challenges for prevention programmes is reaching the populations they serve. In France, a substantial number of African migrants living with HIV acquired their infection after migrating. The aim of this paper is to better understand the characteristics of the population reached by a community-based outreach approach.

Methods

We compared sociodemographic characteristics across three different groups in the Paris greater area: (1) the general African migrant population (Population census), (2) the African migrant population using either the regular healthcare system or the system for vulnerable populations (PARCOURS Survey) and (3) the African migrant population reached through a community-based mobile unit (Afrique Avenir). Comparisons were conducted according to sex, age, region of origin, duration of residence and occupational and legal statuses using χ2tests.

Results

The migrants reached by the mobile unit were mostly men (69%), 52% of whom were younger than 35 years old. They more often lived in precarious situations than did the general sub-Saharan population (49% vs 35% were unemployed, respectively, p<0.001) and the ones accessing the regular healthcare system. Fewer of them lived in precarious situations than did migrants seeking healthcare consultations for vulnerable populations (42% in the mobile unit vs 54% in healthcare consultations were undocumented, p<0.028).

Conclusion

Our study shows that the outreach approach can constitute a missing link in the prevention chain among sub-Saharan African migrants, reaching a group that differs from the general migrant population and from the migrant population in healthcare services—not only the newly arrived migrants who live in more precarious situations but also those who have been in France for several years and are still affected by social hardship.
Incomplete Freund’s adjuvant reduces arginase and enhances Th1 dominance, TLR signaling and CD40 ligand expression in the vaccine site microenvironment
Authors: Pollack Karlyn E , Meneveau Max O , Melssen Marit M , Lynch Kevin T , Koeppel Alexander F , Young Samuel J , Turner Stephen , Kumar Pankaj , Sol-Church Katia , Mauldin Ileana S , Slingluff Jr Craig L
Published: April 2020

Background

Immunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME.

Methods

Biopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq.

Results

VSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p<0.01), CD40 and CD40L (p<0.0001) over normal skin; these effects were significantly enhanced for SSV with peptides+IFA. Vaccines containing pICLC increased expression of TBX21 (T-bet) but did not decrease GATA3 over normal skin, whereas SSV with peptides in IFA dramatically enhanced TBX21 and decreased GATA3, with high expression of IFNγ and STAT1. SSV with peptides in IFA also reduced arginase-1 (ARG1) expression and enhanced expression of TLR adapter molecules TICAM-1 (TRIF) and MYD88. Furthermore, SSV with IFA and peptides also enhanced expression of chemokines associated with TLS formation.

Conclusions

These findings suggest that SSV with peptides in IFA enhances CD40L expression by CD4 T cells, supports a Th1 microenvironment, with accumulation of activated and mature DC. Increased expression of TLR adaptor proteins after SSV with peptides in IFA might implicate effects of the skin microbiome. Reduced ARG1 may reflect diminished suppressive myeloid activity in the VSME.

Trial registration number

(NCT00705640,NCT01585350).
The right not to know and the obligation to know
Authors: Davies Ben
Published: April 2020

There is significant controversy over whether patients have a ‘right not to know’ information relevant to their health. Some arguments for limiting such a right appeal to potential burdens on others that a patient’s avoidable ignorance might generate. This paper develops this argument by extending it to cases where refusal of relevant information may generate greater demands on a publicly funded healthcare system. In such cases, patients may have an ‘obligation to know’. However, we cannot infer from the fact that a patient has an obligation to know that she does not also have a right not to know. The right not to know is held against medical professionals at a formal institutional level. We have reason to protect patients’ control over the information that they receive, even if in individual instances patients exercise this control in ways that violate obligations.
LINP1 promotes the progression of cervical cancer by scaffolding EZH2, LSD1, and DNMT1 to inhibit the expression of KLF2 and PRSS8
Authors: Wu Liuli , Gong Yuan , Yan Ting , Zhang Huimin
Published: April 2020

There is a growing body of evidence indicating that long non-coding RNAs (lncRNAs) are associated with a variety of cancers. LncRNA LINP1 has been shown to be a key factor in tumor malignancy. However, the role of LINP1 in cervical cancer (CC) it is unclear. In our research, we found that the levels of LINP1 were significantly elevated in CC tissues by comparison with adjacent normal tissue. Further, the expression level of LINP1 was upregulated in CC cells compared with healthy human cervical epithelial cell lines (HUCEC). Surprisingly, we found that downregulation of LINP1 significantly reduced the proliferation of CC cells and promoted apoptosis. Additionally, downregulation of LINP1 significantly decreased CC tumor growth in vivo. Further, we observed that LINP1 recruits EZH2, LSD1, and DNMT1, thereby reducing the expression of KLF2 and PRSS8. The results from our qRT–PCR analyses showed that silencing LINP1 uprgulated the expression of KLF2 and PRSS8 in CC cells. The results from our loss-of-function assays showed that upregulation of KLF2 and PRSS8 inhibits cell proliferation and boosts cell apoptosis in CC. We also found that inhibition of KLF2 and PRSS8 reversed the inhibitory effect on cell proliferation associated with silencing LINP1. In short, LINP1 facilitates the progression of CC by suppressing KLF2 and PRSS8, and thus could provide a promising target for CC therapy.
The Role of Th17/Treg Axis in the Traditional Chinese Medicine Intervention on Immune-Mediated Inflammatory Diseases: A Systematic Review
Authors: Xu Yong-Yue , Wang Dong-Mei , Liang Hua-Sheng , Liu Ze-Hao , Li Jun-Xia , Wang Mao-Jie , Chen Xiu-Min , Balak Deepak M. W. , Radstake Timothy R. D. J. , Huang Run-Yue , Lu Chuan-Jian
Published: April 2020

The Th17/Treg axis plays a crucial role in immune-mediated inflammatory diseases (IMID) and might represent an interesting drug target of treatment strategy for these diseases. Accumulating evidence suggests a role for traditional Chinese medicine (TCM) in the modulation of Th17/Treg axis, but a comprehensive overview which summarizes this field hitherto is lacked. This paper performs a systematic literature review of the regulatory effects of TCM on the imbalance of Th17/Treg axis and its potential mechanisms. In addition, the frequency analysis and network pharmacology for the collected TCM herbs from clinical trial data were performed. The studies reported the changes in the ratio of Th17 and/or Treg cells as well as their transcription factor and related cytokines were included. Frequency analysis of composition of the 39 assessed TCM prescriptions showed that Astragalus membranaceus var.mongholicus (5.20%), Glycyrrhiza uralensis (3.67%), Paeonia obovate (3.06%), Salvia digitaloides (3.06%), and Angelica sinensis (2.75%) were the top five herbal components, which were closely associated to the treatment of IMID. Network pharmacology showed that six target proteins (transforming growth factor (TGF)-beta receptor type-1, TGF-beta receptor type-2, retineic-acid-receptor-related orphan nuclear receptor gamma (ROR-gamma), TGFB2, IL-17 and IL-2, respectively) might be involved in the regulatory effects of TCM on Th17/Treg axis. Moreover, there were nine active ingredients (including Oxymatrine, Baicalin, Triptolide, Paeoniflorin, Sinomenine, Celastrol, Emodin, Diosgenin and Chlorogenic acid) originating from TCM reported to have an immunological regulation effect on the Th17/Treg axis. The highlight of this systematic review is to reveal the pharmacological basis of TCM treating IMID and is helpful for supporting future pharmacologic-driven studies. Further research elucidates the immune-modulating mechanisms on Th17/Treg axis by TCM might provide a broader insight for the treatment of IMID.
Muscone Ameliorates LPS-Induced Depressive-Like Behaviors and Inhibits Neuroinflammation in Prefrontal Cortex of Mice
Authors: He Ming-Chao , Shi Zhe , Qin Meng , Sha Nan-Nan , Li Yue , Liao Duan-Fang , Lin Fu-Hui , Shu Bing , Sun Yue-Li , Yuan Ti-Fei , Wang Yong-Jun , Zhang Yan
Published: April 2020

Depression is partially caused by inflammation in the central nervous system. Early study demonstrated that musk, glandular secretion from male musk deer, exerted an antidepressant-like effect. The aim of this study was to investigate if muscone, a bioactive ingredient in musk, could ameliorate neuroinflammation and depressive-like behaviors as well as explore the potential action mechanism. Mice were intraperitoneally (i.p.) injected with muscone for 2 weeks prior to administration of lipopolysaccharides (LPS, 1[Formula: see text]mg/kg, i.p.). Pre-treatment with muscone reversed the LPS-induced decrease in body weight within 24[Formula: see text]h and ameliorated depressive-like behaviors shown by sucrose preference, tail suspension test, and forced swimming test. LPS-induced activation of microglial cells and elevation in expression of inflammatory cytokines including IL-1[Formula: see text], RANTES, and MCP-1 in the prefrontal cortex of mice were effectively abrogated by muscone, which significantly down-regulated expression of TLR4, MyD88, Caspase-1, NLRP3, renin, and Ang II. In addition, treatment of BV2 microglia cells with muscone markedly attenuated the LPS-induced rise in protein expression of TLR4, Ang II, and IL-1[Formula: see text]. This study revealed that muscone could ameliorate LPS-induced depressive-like behaviors by repressing neuroinflammation in the prefrontal cortex of mice caused by its suppression on microglia activation and production of inflammatory cytokines via acting on TLR4 pathway and RAS cascade.
Regression Test Case Prioritization Based on Fixed Size Candidate Set ART Algorithm
Authors: Wang Rongcun , Li Zhengmin , Jiang Shujuan , Tao Chuanqi
Published: April 2020

Regression testing is a very time-consuming and expensive testing activity. Many test case prioritization techniques have been proposed to speed up regression testing. Previous studies show that no one technique is always best. Random strategy, as the simplest strategy, is not always so bad. Particularly, when a test suite has higher fault detection capability, the strategy can generate a better result. Nevertheless, due to the randomness, the strategy is not always as satisfactory as expected. In this context, we present a test case prioritization approach using fixed size candidate set adaptive random testing algorithm to reduce the effect of randomness and improve fault detection effectiveness. The distance between pair-wise test cases is assessed by exclusive OR. We designed and conducted empirical studies on eight C programs to validate the effectiveness of the proposed approach. The experimental results, confirmed by a statistical analysis, indicate that the approach we proposed is more effective than random and the total greedy prioritization techniques in terms of fault detection effectiveness. Although the presented approach has comparable fault detection effectiveness to ART-based and the additional greedy techniques, the time cost is much lower. Consequently, the proposed approach is much more cost-effective.
Towards Generating Realistic and High Coverage Test Data for Constraint-Based Fault Injection
Authors: Qian Ju , Wang Yan , Lin Fusheng , Li Changjian , Zhang Zhiyi , Yan Xuefeng
Published: April 2020

Generating faulty data is a key issue in fault injection. The faulty data include not only the ones of extreme values or bad formats, but also the ones which are logically unreasonable. Constraint-based fault injection which negates interface constraints to solve faulty data is effective for logically unreasonable data generation. However, the existing constraint-based approaches just solve brand new data for testing. Such brand new data may easily violate some hidden environment constraints on the test inputs and hence be nonrealistic. Besides, there can be different strategies to negate a constraint in order to derive the constraint-unsatisfied faulty data. What are the possible negation strategies and which strategies are better for high coverage fault injection are still unclear. To these ends, this paper presents a new constraint-based fault injection approach. The approach introduces 10 different strategies for constraint negation and relaxes constraint variables to generate faulty data instead of solving brand new data for fault injection. It can produce faulty data which are closer to the original non-faulty ones and hence likely to be more realistic. We experimentally investigated the effectiveness and cost of the introduced constraint negation strategies. The results provide insights for the application of these strategies in fault injection.
Do Poverty Rates Matter for Trade Openness in Developing Countries?
Authors: Gnangnon Sèna Kimm
Published: April 2020

A voluminous literature has been devoted to the effect of countries’ participation in international trade (for example through trade policy reforms and greater trade openness) on their poverty level, but not on the issue the other way around. The current analysis contributes to filling this gap in the literature by examining the effect of poverty on trade openness in a set of 99 developing countries over the period 1980–2014. Results suggest that while over the full sample poverty exerts a negative effect on trade openness, this effect ultimately depends on countries’ development levels, proxied by their real per capita income level. A rise in poverty levels reduces trade openness in relatively poor countries, but increases it in relatively advanced economies. These findings suggest that enhancing the ability of poor countries to participate in international trade would help promote greater trade openness, which could in turn help reduce poverty. The international community has a key role to play in that respect.
Late Neoproterozoic–Silurian tectonic evolution of the Rödingsfjället Nappe Complex, orogen-scale correlations and implications for the Scandian suture
Authors: Slagstad Trond , Saalmann Kerstin , Kirkland Chris L. , Høyen Anne B. , Storruste Bergliot K. , Coint Nolwenn , Pin Christian , Marker Mogens , Bjerkgård Terje , Krill Allan , Solli Arne , Boyd Rognvald , Angvik Tine Larsen , Larsen Rune B.
Published: April 2020

The Scandinavian Caledonides consist of disparate nappes of Baltican and exotic heritage, thrust southeastwards onto Baltica during the Mid-Silurian Scandian continent–continent collision, with structurally higher nappes inferred to have originated at increasingly distal positions to Baltica. New U–Pb zircon geochronological and whole-rock geochemical and Sm–Nd isotopic data from the Rödingsfjället Nappe Complex reveal 623 Ma high-grade metamorphism followed by continental rifting and emplacement of the Umbukta gabbro at 578 Ma, followed by intermittent magmatic activity at 541, 510, 501, 484 and 465 Ma. Geochemical data from the 501 Ma Mofjellet Group is indicative of arc magmatism at this time. Syntectonic pegmatites document pre-Scandian thrusting at 515 and 475 Ma, and Scandian thrusting at 429 Ma. These results document a tectonic history that is compatible with correlation with peri-Laurentian and/or peri-Gondwanan terranes. The data allow correlation with nappes at higher and lower tectonostratigraphic levels, including at least parts of the Helgeland, Kalak and Seve nappe complexes, implying that they too may be exotic to Baltica. Neoproterozoic fragmentation of the hypothesized Rodinia supercontinent probably resulted in numerous coeval, active margins, producing a variety of peri-continental terranes that can only be distinguished through further combined geological, palaeomagnetic and palaeontological investigations.
Mitigating the Consequences of Subconcussive Head Injuries
Authors: Nauman Eric A. , Talavage Thomas M. , Auerbach Paul S.
Published: April 2020

Subconcussive head injury represents a pathophysiology that spans the expertise of both clinical neurology and biomechanical engineering. From both viewpoints, the terms injury and damage, presented without qualifiers, are synonymously taken to mean a tissue alteration that may be recoverable. For clinicians, concussion is evolving from a purely clinical diagnosis to one that requires objective measurement, to be achieved by biomedical engineers. Subconcussive injury is defined as subclinical pathophysiology in which underlying cellular- or tissue-level damage (here, to the brain) is not severe enough to present readily observable symptoms. Our concern is not whether an individual has a (clinically diagnosed) concussion, but rather, how much accumulative damage an individual can tolerate before they will experience long-term deficit(s) in neurological health. This concern leads us to look for the history of damage-inducing events, while evaluating multiple approaches for avoiding injury through reduction or prevention of the associated mechanically induced damage.
My Life in Words and Numbers
Authors: Preston Samuel H.
Published: April 2020

George Orwell reportedly said that “Autobiography is only to be trusted when it reveals something disgraceful.” I've done my best to eliminate any disgraceful episodes from the following account, thereby compromising its trustworthiness. What's left is a record of someone lucky enough to ( a) find a career as a demographer that was ideally suited to his affinity for writing and math and ( b) find institutions and individuals who vigorously and uncompromisingly supported the search for a better understanding of our social world. I can only hope that I have been equally supportive of students, colleagues, and institutions whose pathways I have crossed.
Tracking US Social Change Over a Half-Century: The General Social Survey at Fifty
Authors: Marsden Peter V. , Smith Tom W. , Hout Michael
Published: April 2020

In the five decades since its inception in 1971, the General Social Survey (GSS) project has prospectively recorded the current characteristics, backgrounds, behaviors, and attitudes of representative cross sections of American adults covering more than two generations and more than a century of birth cohorts. A foundational resource for contemporary social science, the data it produces and disseminates enable social scientists to develop broad and deep understandings into the changing fabric of US society, and aid legions of instructors and students in teaching and learning. It facilitates internationally comparative survey research and places the United States in the context of other societies through the International Social Survey Program, which it cofounded. This article first recounts the GSS's origins, design, and development. It then surveys contributions based on GSS data to studies of stratification and inequality, religion, sociopolitical trends, intergroup relations, social capital and social networks, health and well-being, culture, and methodology.
Extracellular vesicles as signaling mediators in type 2 diabetes mellitus
Authors: Noren Hooten Nicole , Evans Michele K.
Published: April 2020

Diabetes mellitus type 2, a chronic metabolic disease, has globally increased in incidence and prevalence throughout the lifespan due to the rise in obesity and sedentary lifestyle. The end-organ cardiovascular and cerebrovascular effects of diabetes mellitus result in significant morbidity and mortality that increases with age. Thus, it is crucial to fully understand how molecular mechanisms are influenced by diabetes mellitus and may influence the development of end-organ complications. Circulating factors are known to play important physiological and pathological roles in diabetes. Recent data have implicated extracellular vesicles (EVs) as being circulating mediators in type 2 diabetes. These small lipid-bound vesicles are released by cells into the circulation and can carry functional cargo, including lipids, proteins, and nucleic acids, to neighboring cells or between tissues. In this review, we will summarize the current evidence for EVs as promising diagnostic and prognostic factors in diabetes, the mechanisms that drive EV alterations with diabetes, and the role EVs play in the pathology associated with diabetes.
Muscle metaboreflex-induced increases in effective arterial elastance: effect of heart failure
Authors: Mannozzi Joseph , Kaur Jasdeep , Spranger Marty D. , Al-Hassan Mohamed-Hussein , Lessanework Beruk , Alvarez Alberto , Chung Charles S. , O’Leary Donal S.
Published: April 2020

Dynamic exercise elicits robust increases in sympathetic activity in part due to muscle metaboreflex activation (MMA), a pressor response triggered by activation of skeletal muscle afferents. MMA during dynamic exercise increases arterial pressure by increasing cardiac output via increases in heart rate, ventricular contractility, and central blood volume mobilization. In heart failure, ventricular function is compromised, and MMA elicits peripheral vasoconstriction. Ventricular-vascular coupling reflects the efficiency of energy transfer from the left ventricle to the systemic circulation and is calculated as the ratio of effective arterial elastance ( Ea) to left ventricular maximal elastance ( Emax). The effect of MMA on Ea in normal subjects is unknown. Furthermore, whether muscle metaboreflex control of Ea is altered in heart failure has not been investigated. We utilized two previously published methods of evaluating Ea [end-systolic pressure/stroke volume ( EaPV)] and [heart rate × vascular resistance ( EaZ)] during rest, mild treadmill exercise, and MMA (induced via partial reductions in hindlimb blood flow imposed during exercise) in chronically instrumented conscious canines before and after induction of heart failure via rapid ventricular pacing. In healthy animals, MMA elicits significant increases in effective arterial elastance and stroke work that likely maintains ventricular-vascular coupling. In heart failure, Ea is high, and MMA-induced increases are exaggerated, which further exacerbates the already uncoupled ventricular-vascular relationship, which likely contributes to the impaired ability to raise stroke work and cardiac output during exercise in heart failure.
The dominant limb preferentially stabilizes posture in a bimanual task with physical coupling
Authors: Takagi A. , Maxwell S. , Melendez-Calderon A. , Burdet E.
Published: April 2020

We found that subjects prefer to stabilize a bimanually held object by cocontracting their dominant limb, contradicting the established view that the nondominant limb is specialized toward stabilization.
Loss of excitatory amino acid transporter restraint following chronic intermittent hypoxia contributes to synaptic alterations in nucleus tractus solitarii
Authors: Martinez Diana , Rogers Richard C. , Hasser Eileen M. , Hermann Gerlinda E. , Kline David D.
Published: April 2020

Removal of excitatory amino acid transporter (EAAT) restraint increases spontaneous synaptic activity yet decreases afferent [tractus solitarii (TS)]-driven excitatory postsynaptic current (EPSC) amplitude. In the chronic intermittent hypoxia model of obstructive sleep apnea, this restraint is lost due to reduction in EAAT expression and function. Thus EAATs are important in controlling elevated glutamatergic signaling, and loss of such control results in maladaptive synaptic signaling.
Double Effects of Environmental Regulation on Carbon Emissions in China: Empirical Research Based on Spatial Econometric Model
Authors: Yang Yuanhua , Tang Dengli , Zhang Peng
Published: April 2020

This paper theoretically analyzes the direct impact of environmental regulation on carbon emissions and its indirect effects on carbon emissions through foreign direct investment (FDI), energy consumption, industrial structure, and technological innovation. Then, this paper constructs a spatial lag model to empirically test the dual effects of environmental regulation on carbon emissions based on the provincial panel data of 2003–2017 in China. The results show that the average Moran’s I value of carbon emissions during 2003–2017 is 0.2506, passing the significance test at 1% level, and carbon emissions have spatial correlation characteristics. The direct impact of environmental regulation on carbon emissions is significant and positive. Environmental regulation could indirectly influence carbon emissions by influencing FDI, energy consumption, and technological innovation, and meanwhile, FDI, energy consumption, and technological innovation help to reduce carbon emissions under the constraint of environmental regulation, specifically. However, the impact of environmental regulation on carbon emissions through industrial structure is not significant.
Experimental Investigation on Hard Rock Breaking with Fiber Laser: Surface Failure Characteristics and Perforating Mechanism
Authors: Yang Xiaofeng , Zhou Xin , Zhu Hongliang , Zhou Jiaheng , Li Yanhong
Published: April 2020

The rock‐breaking characteristics and the influence factors of laser perforation are investigated in this study. A series of fiber laser perforation experiments on basalt, sandstone, and granite were conducted. Experimental measurements of rock failure morphologies and composition tests showed that the main surface features are thermal cracks and glazed layer formed by the melting and condensing of rock in laser perforation. It is also found that higher quartz content could help reduce the glazed degree of rock. Comprehensive results showed that the laser rock perforation is mainly formed by thermal fractures, the decline of molten pool, and the evaporating and splashing of the special melted rock components. The depth of rock perforation and SE usually increase with the laser irradiation time, while the ROP gradually decreases. With the increase of laser power, the perforation depth and ROP gradually increase, while the SE initially decreases and then increases indicating that there is an optimal power that maximizes perforation efficiency. It is believed that the strength of rock is the main factor affecting laser perforation efficiency, and the lower rock strength resulted in deeper perforation depth, higher ROP, and lower SE.
Multi-UUV Cooperative Dynamic Maneuver Decision-Making Algorithm Using Intuitionistic Fuzzy Game Theory
Authors: Liu Lu , Zhang Lichuan , Zhang Shuo , Cao Sheng
Published: April 2020

In this paper, a multi-unmanned underwater vehicle (UUV) cooperative dynamic maneuver decision-making algorithm is proposed based on the combination of game theory and intuitionistic fuzzy sets. Underwater environments with weak connectivity, underwater noise, and dynamic uncertainties are fully considered through intuitionistic fuzzy sets, which solves one of the main problems in making decisions underwater. Subsequently, the intuitionistic fuzzy multiattribute evaluation of a UUV maneuver strategy is conducted, and the intuitionistic fuzzy payment matrix of the cooperative dynamic maneuver game is obtained. Thereafter, the Nash equilibrium condition is proposed to satisfy the intuitionistic fuzzy total order, and the Nash equilibrium maneuver decision-making model under a dynamic underwater environment is established. Meanwhile, the modified particle swarm optimization method is presented to solve the established problem and find the optimal strategy. Finally, an example is used to verify the superiority of the proposed cooperative dynamic maneuver decision-making algorithm.
A Novel Design of a Neural Network-Based Fractional PID Controller for Mobile Robots Using Hybridized Fruit Fly and Particle Swarm Optimization
Authors: Ibraheem Ghusn Abdul Redha , Azar Ahmad Taher , Ibraheem Ibraheem Kasim , Humaidi Amjad J.
Published: April 2020

The design of a swarm optimization-based fractional control for engineering application is an active research topic in the optimization analysis. This work offers the analysis, design, and simulation of a new neural network- (NN) based nonlinear fractional control structure. With suitable arrangements of the hidden layer neurons using nonlinear and linear activation functions in the hidden and output layers, respectively, and with appropriate connection weights between different hidden layer neurons, a new class of nonlinear neural fractional-order proportional integral derivative (NNFOPID) controller is proposed and designed. It is obtained by approximating the fractional derivative and integral actions of the FOPID controller and applied to the motion control of nonholonomic differential drive mobile robot (DDMR). The proposed NNFOPID controller’s parameters consist of derivative, integral, and proportional gains in addition to fractional integral and fractional derivative orders. The tuning of these parameters makes the design of such a controller much more difficult than the classical PID one. To tackle this problem, a new swarm optimization algorithm, namely, MAPSO-EFFO algorithm, has been proposed by hybridization of the modified adaptive particle swarm optimization (MAPSO) and the enhanced fruit fly optimization (EFFO) to tune the parameters of the NNFOPID controller. Firstly, we developed a modified adaptive particle swarm optimization (MAPSO) algorithm by adding an initial run phase with a massive number of particles. Secondly, the conventional fruit fly optimization (FFO) algorithm has been modified by increasing the randomness in the initialization values of the algorithm to cover wider searching space and then implementing a variable searching radius during the update phase by starting with a large radius which decreases gradually during the searching phase. The tuning of the parameters of the proposed NNFOPID controller is carried out by reducing the MS error of 0.000059, whereas the MSE of the nonlinear neural system (NNPID) is equivalent to 0.00079. The NNFOPID controller also decreased control signals that drive DDMR motors by approximately 45 percent compared to NNPID and thus reduced energy consumption in circular trajectories. The numerical simulations revealed the excellent performance of the designed NNFOPID controller by comparing its performance with that of nonlinear neural (NNPID) controllers on the trajectory tracking of the DDMR with different trajectories as study cases.
The Association between Adiponectin Single Nucleotide Polymorphisms and Side Effects of Isotretinoin in Acne Patients
Authors: Garba Munir , Khabour Omar F. , Alzoubi Karem H. , Abu-Siniyeh Ahmed , Al-Qarqaz Firas
Published: April 2020

Background. Acne is a common condition of pilosebaceous follicle especially among young. Clinically, the most used medication in the treatment of moderate to severe acne is oral isotretinoin. However, interindividual variability in therapeutic response to isotretinoin and many side effects such as musculoskeletal pain, headache, and alteration in lipid profile can be seen with this treatment. Aim. In this study, the effect of genetic polymorphisms, rs2241766 and rs1501299, of the adiponectin gene was investigated in relation to the side effects of isotretinoin-treated young adult acne patients (n = 230). Methods. Several biochemical parameters were measured at baseline and after treatments with isotretinoin. The ADIPOQ gene SNPs, rs2241766 and rs1501299, were genotyped in 230 patients. Results. Alterations in lipid profile with a significant increase of ALT (P=0.007) were detected after isotretinoin treatment. Moreover, percentage change in HDL following isotretinoin treatment was significantly associated with rs1501299 (P=0.008). On the other hand, no associations between examined SNPs and side effects of isotretinoin and other lipid parameters (total cholesterol, LDL, and triglycerides) or liver function enzymes (ALT and AST) were detected. Conclusions. Current findings showed that rs1501299 of the ADIPOQ gene might be associated with changes in HDL level in acne patients following treatment with isotretinoin.
Nested Saturation Function Control of a Magnetic Levitation System
Authors: Gutiérrez-Frías Octavio , Lozada-Castillo Norma , Aguirre-Anaya J. Alejandro , Flores-Hernández Diego A.
Published: April 2020

The trajectory tracking task of a magnetic levitation system connected to a beam mechanism is solved by means of a nested saturation control with a feedforward term. The flatness property of the system allows to use the nested saturation control technique and the feedforward control to stabilize the output tracking error around the equilibrium. The closed-loop error dynamics is proven to be locally exponentially stable. Numerical simulations prove the effectiveness of the proposal.
Transfer of MicroRNA via Macrophage-Derived Extracellular Vesicles Promotes Proneural-to-Mesenchymal Transition in Glioma Stem Cells
Authors: Zhang Zongpu , Xu Jianye , Chen Zihang , Wang Huizhi , Xue Hao , Yang Chunlei , Guo Qindong , Qi Yanhua , Guo Xiaofan , Qian Mingyu , Wang Shaobo , Qiu Wei , Gao Xiao , Zhao Rongrong , Guo Xing , Li Gang
Published: April 2020

Proneural-to-mesenchymal transition (PMT) is a common process in glioblastoma (GBM) progression that leads to increased radiotherapy resistance. However, the mechanism underlying PMT is poorly understood. Here, we found that tumor-associated macrophages triggered PMT in glioma stem cells (GSC) via small extracellular vesicles (sEV). sEVs from monocyte-derived macrophages transferred miR-27a-3p, miR-22-3p, and miR-221-3p to GSCs, and these miRNAs promoted several mesenchymal phenotypes in proneural (PN) GSCs by simultaneously targeting CHD7. We found that CHD7 played a critical role in the maintenance of the PN phenotype, and CHD7 knockdown significantly promoted PMT in GSCs via the RelB/P50 and p-STAT3 pathways. The induction of PMT by sEVs containing miR-27a-3p, miR-22-3p, and miR-221-3p in a xenograft nude mouse model exacerbated radiotherapy resistance and thus decreased the benefits of radiotherapy. Collectively, these findings identified macrophage-derived sEVs as key regulators of PMT in GSCs and demonstrated that CHD7 is a novel inhibitor of PMT.
Platelet Dysfunction and Its Role in the Pathogenesis of Psoriasis
Authors: Fan Zhijia , Wang Li , Jiang Haoqin , Lin Yong , Wang Zhicheng
Published: April 2020

Background: Psoriasis is an immune-mediated inflammatory skin disease in conjunction with the systemic inflammatory process. It appears to be related to increased risks of cardiovascular disease events, especially in severe cases. The hemostatic balance is disrupted due to the prothrombotic bias in psoriasis, which might be mainly preserved by platelet hyperactivity. Platelets are also immune cells that initiate and regulate immune and inflammatory processes, except as the principal mediator of hemostasis and thrombosis, and platelet dysfunction is deeply involved in the pathogenesis of psoriasis. Summary: The aim of this study is to perform a review that expounds abnormal platelet function in psoriasis and explains the important role of platelets in the pathogenic mechanism of psoriasis in order to provide new targets for comprehensive medical treatment.
Dynamic-Ventilatory Digital Radiography in Air Flow Limitation: A Change in Lung Area Reflects Air Trapping
Authors: Ohkura Noriyuki , Kasahara Kazuo , Watanabe Satoshi , Hara Johsuke , Abo Miki , Sone Takashi , Kimura Hideharu , Takata Munehisa , Tamura Masaya , Matsumoto Isao , Nakade Yusuke , Sanada Shigeru , Tanaka Rie
Published: April 2020

Objective: The aim of this study was to determine the utility of dynamic-ventilatory digital radiography (DR) for pulmonary function assessment in patients with airflow limitation. Methods: One hundred and eighteen patients with airflow limitation (72 patients with lung cancer before surgery, 35 patients with chronic obstructive pulmonary disease [COPD], 6 patients with asthma, and 5 patients with asthma-COPD overlap syndrome) were assessed with dynamic-ventilatory DR. The patients were instructed to inhale and exhale slowly and maximally. Sequential chest X-ray images were captured in 15 frames per second using a dynamic flat-panel imaging system. The relationship between the lung area and the rate of change in the lung area due to respiratory motion with respect to pulmonary function was analyzed. Results: The rate of change in the lung area from maximum inspiration to maximum expiration (Rs ratio) was associated with the RV/TLC ratio (r = 0.48, p < 0.01) and the percentage of the predicted FEV1 (r = –0.33, p < 0.01) in patients with airflow limitations. The Rs ratio also decreased in an FEV1-dependent manner. Conclusion: The rate of change in the lung area due to respiratory motion evaluated with dynamic DR reflects air trapping. Dynamic DR is a potential tool for the comprehensive assessment of pulmonary function in patients with COPD.
De las Malvinas al corralito: Entrevista con Sergio Balardini
Authors: Feixa Carles
Published: April 2020

Resumen (analítico): Sergio Balardini es uno de los pioneros de la «juvenología» argentina
y latinoamericana. El texto se basa en una conversación mantenida por los autores en Buenos Aires en agosto de 2017 y recorre las tres vidas del protagonista: su biografía como joven, como militante político y como investigador. Empieza con sus recuerdos de adolescencia y juventud en la Argentina de los años setenta; sigue con re#exiones sobre la guerra de las Malvinas de 1982 como «marca generacional»; recorre su militancia política en las "las socialistas en la década de los ochenta y noventa, durante la transición a la democracia, y se centra en su descubrimiento de la juvenología y su trabajo por institucionalizarla en instituciones como Flacso, el GT Juventud de Clacso y la Fundación Friedrich Ebert, con la crisis político económica que condujo al corralito de 2001 como parteaguas.
Ambivalências humanas e não humanas em “Meu tio o Iauaretê”, de Guimarães Rosa
Authors: Silva Gustavo De Castro e , Moraes Vanessa Daniele De
Published: April 2020

Problematização dos limites humano/animal a partir do conto “Meu tio o Iauaretê” de Guimarães Rosa. Ao explorar a noção de limite e a análise de mitologias que abordam o humano/animal, pretendemos circunscrever a presença da cultura indígena latino-americana e dessa mitologia no conto de Rosa. Analisaremos a presença do imaginário do jaguar nessa cultura e, para tanto, utilizaremos uma metodologia descritiva e interpretativa. Nossas conclusões apontam para a superação e a ultrapassagem desses limites pelos personagens rosianos no conto em questão
Sereias
Authors: Meneses Adelia Bezerra de
Published: April 2020

No recorte de um estudo do mito odisseico em contraponto com a literatura brasileira, a proposta foi trabalhar o tema das Sereias (na Odisseia e no romance Uma aprendizagem ou O livro dos prazeres, de Clarice Lispector, com uma breve incursão pela Lorelei, de Heine). Na sequência de uma leitura adorniana da Odisseia, aborda-se a sereia de um viés menos explorado na diluição desse mito, que é a inquietante relação entre sedução e saber, ou melhor: a sedução pelo conhecimento. Isso levou, inevitavelmente, a um paralelo com o mito bíblico de Adão e Eva e a Árvore do Conhecimento, e consequente superposição das imagens da sereia e da serpente (curiosamente presente no mito indígena da Mãe d’Água).