bluuebunny/crossref_metadata_2025 huggingface dataset:
FN3K expression in COPD: a potential comorbidity factor for cardiovascular disease
Authors: Alderawi Amr , Caramori Gaetano , Baker Emma H , Hitchings Andrew William , Rahman Irfan , Rossios Christos , Adcock Ian , Casolari Paolo , Papi Alberto , Ortega Victor E , Curtis Jeffrey L , Dunmore Simon , Kirkham Paul
Published: November 2020

Introduction

Cigarette smoking and oxidative stress are common risk factors for the multi-morbidities associated with chronic obstructive pulmonary disease (COPD). Elevated levels of advanced glycation endproducts (AGE) increase the risk of cardiovascular disease (CVD) comorbidity and mortality. The enzyme fructosamine-3-kinase (FN3K) reduces this risk by lowering AGE levels.

Methods

The distribution and expression of FN3K protein in lung tissues from stable COPD and control subjects, as well as an animal model of COPD, was assessed by immunohistochemistry. Serum FN3K protein and AGE levels were assessed by ELISA in patients with COPD exacerbations receiving metformin. Genetic variants within the FN3K and FN3K-RP genes were evaluated for associations with cardiorespiratory function in the Subpopulations and Intermediate Outcome Measures in COPD Study cohort.

Results

This pilot study demonstrates that FN3K expression in the blood and human lung epithelium is distributed at either high or low levels irrespective of disease status. The percentage of lung epithelial cells expressing FN3K was higher in control smokers with normal lung function, but this induction was not observed in COPD patients nor in a smoking model of COPD. The top five nominal FN3K polymorphisms with possible association to decreased cardiorespiratory function (p<0.008–0.02), all failed to reach the threshold (p<0.0028) to be considered highly significant following multi-comparison analysis. Metformin enhanced systemic levels of FN3K in COPD subjects independent of their high-expression or low-expression status.

Discussion

The data highlight that low and high FN3K expressors exist within our study cohort and metformin induces FN3K levels, highlighting a potential mechanism to reduce the risk of CVD comorbidity and mortality.
Quality versus risk of bias assessment of palliative care trials: comparison of two tools
Authors: Isenberg Sarina R , Kavalieratos Dio , Chow Ronald , Le Lisa , Wegier Pete , Zimmermann Camilla
Published: November 2020

Background

Randomised controlled trials (RCTs) of palliative care interventions are challenging to conduct and evaluate. Tools used to judge the quality of RCTs do not account for the complexities of conducting research in seriously ill populations and may artificially downgrade confidence in palliative care research.

Objective

To compare assessments from the Palliative Care Trial Assessment Tool (PCTAT) and Cochrane Risk of Bias (RoB) tool.

Design

Reviewers assessed 43 RCTs using PCTAT and RoB. We compared assessments of each trial, assessed overall agreement (weighted kappa (Kw)) and examined (dis)agreement for comparable items. We assessed quality of life at 1–3 months among trials grouped according to RoB or PCTAT score (using meta-analysis) and whether RoB or quality improved over time (Cochran-Armitage trend test).

Results

Of 43 trials, those rated low RoB had a mean PCTAT score of 73 (SD 10); those rated high RoB had a mean PCTAT score of 56 (SD 14). Overall Kwwas 0.33 (95% CI 0.19 to 0.42). Total agreement between comparable items was observed for 56% of trials (24/43) and total disagreement for 21% (8/43). The standardised mean difference in quality of life was statistically significant among RCTs with low RoB and high PCTAT, but not for those with medium/low PCTAT or high/unclear RoB. Quality of reporting improved over time, whereas RoB did not.

Conclusion

Although there was fair agreement between tools, areas of disagreement/non-comparability suggest the tools capture different aspects of bias/quality. A specific tool to evaluate quality of palliative care trials may be warranted.
Errors in prostate core biopsy diagnosis in an era of specialisation and double reporting
Authors: Szecsei Cornelia Margaret , Oxley Jon D
Published: November 2020

Aim

To examine the effects of specialist reporting on error rates in prostate core biopsy diagnosis.

Method

Biopsies were reported by eight specialist uropathologists over 3 years. New cancer diagnoses were double-reported and all biopsies were reviewed for the multidisciplinary team (MDT) meeting. Diagnostic alterations were recorded in supplementary reports and error rates were compared with a decade previously.

Results

2600 biopsies were reported. 64.1% contained adenocarcinoma, a 19.7% increase. The false-positive error rate had reduced from 0.4% to 0.06%. The false-negative error rate had increased from 1.5% to 1.8%, but represented fewer absolute errors due to increased cancer incidence.

Conclusions

Specialisation and double-reporting have reduced false-positive errors. MDT review of negative cores continues to identify a very low number of false-negative errors. Our data represents a ‘gold standard’ for prostate biopsy diagnostic error rates. Increased use of MRI-targeted biopsies may alter error rates and their future clinical significance.
A complex DICER1 syndrome phenotype associated with a germline pathogenic variant affecting the RNase IIIa domain of DICER1
Authors: Pontén Emeli , Frisk Sofia , Taylan Fulya , Vaz Raquel , Wessman Sandra , de Kock Leanne , Pal Niklas , Foulkes William D , Lagerstedt-Robinson Kristina , Nordgren Ann
Published: November 2020

Background

Germline pathogenic variants in DICER1 cause DICER1 syndrome, an autosomal dominant, pleiotropic tumour predisposition syndrome with variable expressivity and reduced penetrance for specific dysplastic and neoplastic lesions. Recently, a syndrome with the acronym GLOW (Global developmental delay, Lung cysts, Overgrowth, Wilms tumour) was described in two children with mosaic missense mutations in hotspot residues of the DICER1 RNase IIIb domain.

Methods

Whole genome sequencing, exome sequencing, Sanger sequencing, digital PCR and a review of Wilms tumours with DICER1 RNase III domain mutations were performed.

Results

A de novo heterozygous c.4031C>T (p.S1344L) variant in the sequence encoding the RNase IIIa domain of DICER1 was detected. Clinical investigations revealed a phenotype that resembles the GLOW subphenotype of DICER1 syndrome.

Conclusion

The phenotypic overlap between patients with p.S1344L mutation and GLOW syndrome provide clinical support for recent discoveries that RNase IIIa-Ser1344 site mutations impede miRNA-5p biogenesis analogous to DICER1 hotspot mutations in the RNase IIIb domain. We show that an individual with a heterozygous germline p.S1344L mutation has a severe form of DICER1 syndrome (‘DICER1 syndrome plus’), with notable features of intellectual disability, macrocephaly, physical abnormalities, Wilms tumour and a well-differentiated fetal adenocarcinoma of the lung.
Is there room for privacy in medical crowdfunding?
Authors: Snyder Jeremy , Crooks Valorie A
Published: November 2020

When people use online platforms to solicit funds from others for health-related needs, they are engaging in medical crowdfunding. This form of crowdfunding is growing in popularity, and its visibility is increasing as campaigns are commonly shared via social networking. A number of ethical issues have been raised about medical crowdfunding, one of which is that it introduces a number of privacy concerns. While campaigners are encouraged to share very personal details to encourage donations, the sharing of such details may result in privacy losses for the beneficiary. Here, we explore the ways in which privacy can be threatened through the practice of medical crowdfunding by exploring campaigns (n=100) for children with defined health needs scraped from the GoFundMe platform. We found specific privacy concerns related to the disclosure of private details about the beneficiary, the inclusion of images and the nature of the relationship between campaigner, funding recipient and beneficiary. For example, it was found that identifying personal and medical details about the beneficiary, including symptoms (n=52) and treatment history (n=43), were often mentioned by campaigners. While the privacy concerns identified are problematic, they are also difficult to remedy given the strong financial incentive to crowdfund. However, crowdfunding platforms can enhance privacy protections by, for example, requiring those campaigning on behalf of child beneficiaries to ensure consent has been obtained from their guardians and providing additional guidelines for the inclusion of personal information in campaigns made on behalf of those not able to give their consent to the campaign.
Terrible choices in the septic child: a response to the PALOH trial round table authors
Authors: Parker Joshua , Wright David
Published: November 2020

In this response article, we challenge a core assumption that lies at the centre of a round table discussion regarding the Pharmacogenetics to Avoid Loss of Hearing trial. The round table regards a genetic test for a variant (mt.1555A>G) that increases the risk of deafness if a carrier is given the antibiotic gentamicin. The idea is that rapid testing can identify neonates at risk, providing an opportunity to prevent giving an antibiotic that might cause deafness. We challenge the assumption that a positive test unequivocally guides antibiotic choice because, aside from the risk of deafness, all antibiotics for neonatal sepsis are equivalent. We argue that this assumption is faulty and has particularly troubling moral consequences. We claim that giving an alternative to gentamicin is potentially providing inferior treatment and thereby may increase the risk of death. Parents and doctors are faced with a terrible choice as a result of positive point-of-care testing (POCT): give gold-standard treatment and risk deafness or give second line care and risk death. While we do not indicate an answer to this choice, what we do argue is that such a deep and difficult choice is one that may make parents wish genetic testing was never undertaken, and therefore, contra some authors in the round table, provides a reason to gain specific consent for POCT.
Cerebral microhaemorrhage in COVID-19: a critical illness related phenomenon?
Authors: Dixon Luke , McNamara Cillian , Gaur Pritika , Mallon Dermot , Coughlan Charles , Tona Francesca , Jan Wajanat , Wilson Mark , Jones Brynmor
Published: November 2020

Background

Cerebral microhaemorrhages are increasingly being recognised as a complication of COVID-19. This observational retrospective study aims to further investigate the potential pathophysiology through assessing the pattern of microhaemorrhage and clinical characteristics of patients with COVID-19 and microhaemorrhage. By comparing with similar patterns of microhaemorrhage in other non-COVID-19 disease, this study aims to propose possible common pathogenic mechanisms.

Methods

A retrospective observational case series was performed identifying all patients with COVID-19 complicated by cerebral microhaemorrhage on MRI. The distribution and number of microhaemorrhages were recorded using the microbleed anatomical scale, and patients’ baseline characteristics and salient test results were also recorded.

Results

Cerebral microhaemorrhages were noted to have a predilection for the corpus callosum, the juxtacortical white matter and brainstem. All patients had a preceding period of critical illness with respiratory failure and severe hypoxia necessitating intubation and mechanical ventilation.

Discussion

This study demonstrates a pattern of cerebral microhaemorrhage that is similar to the pattern reported in patients with non-COVID-19 related critical illness and other causes of severe hypoxia. This raises questions regarding whether microhaemorrhage occurs from endothelial dysfunction due the direct effect of SARS-CoV-2 infection or from the secondary effects of critical illness and hypoxia.
Electroacupuncture Improves Motor Symptoms of Parkinson’s Disease and Promotes Neuronal Autophagy Activity in Mouse Brain
Authors: Hsu Wei-Ti , Chen Yi-Hung , Yang Han-Bin , Lin Jaung-Geng , Hung Shih-Ya
Published: November 2020

Autophagic defects are a hallmark of neurodegenerative disorders, such as Parkinson’s disorder (PD). Enhancing autophagy to remove impaired mitochondria and toxic protein aggregation is an essential component of PD treatment. In particular, activation of autophagy confers neuroprotection in cellular and preclinical models of neurodegenerative diseases. In this study, we investigated the therapeutic mechanisms of electroacupuncture (EA) treatment in mice with established PD and evaluated the relationship between EA, autophagy, and different neurons in the mouse brain. We report that EA improves PD motor symptoms in mice and enhances (1) autophagy initiation (increased Beclin 1), (2) autophagosome biogenesis (increased Atg5, Atg7, Atg9A, Atg12, Atg16L, Atg3, and LC3-II), (3) autophagy flux/substrate degradation (decreased p62), and (4) mitophagy (increased PINK1 and DJ-1) in neurons of the substantia nigra, striatum, hippocampus, and cortex (affected brain areas of PD, Huntington disease, and Alzheimer’s disease). EA enhances autophagy initiation, autophagosome biogenesis, mitophagy, and autophagy flux/substrate degradation in certain brain areas. Our findings are the first to show that EA regulates neuronal autophagy and suggest that this convenient, inexpensive treatment has exciting therapeutic potential in neurodegenerative disorders.
Data-Driven Intelligent Port Management Based on Blockchain
Authors: Wang Shuaian , Zhen Lu , Xiao Liyang , Attard Maria
Published: November 2020

This paper proposes a blockchain-based framework to improve the efficiency of ship traffic in port. In the framework, ship agents, terminals, tug company, pilot station, and government share information and the information is stored in a blockchain. Based on the shared information, we discuss three categories of data-driven models that can improve the operations management of the above five parties. The first category is decisions made by a single party. The second category involves decisions of at least two ship agents. The third category relates to multi-party decision-making under uncertainty. This study hopes to stimulate maritime practitioners to embrace blockchain technology and data-driven approaches to enhance the competitiveness of the industry.
Symmetry reduction and new interaction solutions for the negative-order potential KdV equation
Authors: Hu Hengchun , Zhang Zhenya
Published: November 2020

New soliton–cnoidal interaction solutions for the negative-order potential KdV equation are studied with the help of the consistent tanh expansion method. The non-local symmetry for the negative-order potential KdV equation is derived from the truncated Painlevé expansion method. The non-local symmetry is transformed into the standard Lie point symmetry by introducing new dependent variables and the finite symmetry transformation is also presented to construct new exact solutions with non-zero seed solution. The similarity solutions of the enlarged negative-order potential KdV system are obtained through different constant selections.
Complementary equitably totally disconnected equitable domination in graphs
Authors: Nataraj P. , Sundareswaran R. , Swaminathan V.
Published: November 2020

In a simple, finite and undirected graph [Formula: see text] with vertex set [Formula: see text] and edge set [Formula: see text], a subset [Formula: see text] of [Formula: see text] is said to be a degree equitable dominating set if for every [Formula: see text] there exists a vertex [Formula: see text] such that [Formula: see text] and [Formula: see text], where [Formula: see text] denotes the degree of [Formula: see text] in [Formula: see text]. The minimum cardinality of such a dominating set is denoted by [Formula: see text] and is called the equitable domination number of [Formula: see text]. In this paper, we introduce Complementary Equitably Totally Disconnected Equitable domination in graphs and obtain some interesting results. Also, we discuss some bounds of this new domination parameter.
Security analysis of SMS as a second factor of authentication
Authors: Jover Roger Piqueras
Published: November 2020

The challenges of multifactor authentication based on SMS, including cellular security deficiencies, SS7 exploits, and SIM swapping.
Enabling AI at the edge with XNOR-networks
Authors: Rastegari Mohammad , Ordonez Vicente , Redmon Joseph , Farhadi Ali
Published: November 2020

In recent years we have seen a growing number of edge devices adopted by consumers, in their homes (e.g., smart cameras and doorbells), in their cars (e.g., driver assisted systems), and even on their persons (e.g., smart watches and rings). Similar growth is reported in industries including aerospace, agriculture, healthcare, transport, and manufacturing. At the same time that devices are getting smaller, Deep Neural Networks (DNN) that power most forms of artificial intelligence are getting larger, requiring more compute power, memory, and bandwidth. This creates a growing disconnect between advances in artificial intelligence and the ability to develop smart devices at the edge. In this paper, we present a novel approach to running state-of-the-art AI algorithms at the edge. We propose two efficient approximations to standard convolutional neural networks: Binary-Weight-Networks (BWN) and XNOR-Networks. In BWN, the filters are approximated with binary values resulting in 32x memory saving. In XNOR-Networks, both the filters and the input to convolutional layers are binary. XNOR-Networks approximate convolutions using primarily binary operations. This results in 58x faster convolutional operations (in terms of number of the high precision operations) and 32x memory savings. XNOR-Nets offer the possibility of running state-of-the-art networks on CPUs (rather than GPUs) in real-time. Our binary networks are simple, accurate, efficient, and work on challenging visual tasks. We evaluate our approach on the ImageNet classification task. The classification accuracy with a BWN version of AlexNet is the same as the full-precision AlexNet. Our code is available at: urlhttp://allenai.org/plato/xnornet.
Controlled Synthesis of ZnO Nanorods Using Different Seed Layers
Authors: Biehler Erik , Whiteman Rachel , Lin Pengtao , Zhang Kai , Baumgart Helmut , Abdel-Fattah Tarek M.
Published: November 2020

Single-crystal, low-cost, low-temperature, hydrothermal synthesis ZnO nanorods were grown on ZnO fine grained random nanocrystalline seed layers prepared by atomic layer deposition (ALD) and benchmarked against spin coating techniques for seed layers. As the growth temperature increased to 90 °C, more nanorods were observed on the samples. Increasing the growth time from 16 h to 24 h resulted in higher nanorod density for the ALD seeded samples, but less nanorods for the spin-coated seeded samples. Our work demonstrates that the final density of ZnO nanorods and their shape and size are primarily influenced by the characteristics of the ZnO seed layer, such as composition, morphology, grain size, impurity content and thickness, as well as the time spent heated. At ∼10 nm the ALD generated random polycrystalline seed layer grains were one order of magnitude smaller compared to the spin coating generated seed layer grains which appear structurally different as ∼100 nm columnar grains. This morphological seed layer difference caused the ZnO nanorods grown on spin coated seed layers to reach only ∼34% of the average nanorod length achieved on ALD seeds with comparable rod diameter and can also account for the diminished nanorod density. The exact mechanism of how the seed layer affects nucleation and subsequent nanorod growth is unknown, but results suggest that there is a significant impact. Future research can be directed to investigating the ability of metal nanoparticles to self-assemble on these nanorods and to further nanoscale catalysis.
Communication—Magnetic Properties of Fe/Na2SiO3/Fe3O4 Soft Magnetic Composite by Two-Stage Ball Milling
Authors: Zhang Guodong , Chen Jiaqi , Liu Yao
Published: November 2020

Iron-based soft magnetic composites (SMCs) were prepared by two-step ball milling with sodium silicate and ferroferric oxide. The presence of the precoated silicate layer has increased the resistivity of the powder surface, which also improved the agglomeration of ferroferric oxide. The addition of magnetic ferroferric oxide improves the dilution effect. Combining the advantages of both sodium silicate and ferroferric oxide, the prepared soft magnetic composite material has excellent performance. After annealing at 400 °C, the core loss is 214.5 W Kg−1 (1 T, 1000 Hz), and the saturation magnetic induction is 1.33 T.
The Electronic and Physical Structure Evaluation of MoS2(1−x)Te2x Alloy Fabricated with Co-Sputtering and Post-Deposition Annealing in Chalcogen Ambient
Authors: Hibino Yusuke , Yamazaki Kota , Hashimoto Yusuke , Otsuka Yosuke , Sawamoto Naomi , Machida Hideaki , Ishikawa Masato , Sudoh Hiroshi , Wakabayashi Hitoshi , Ogura Atsushi
Published: November 2020

In recent years, the fabrication of transition metal dichalcogenide (TMD) alloys is drawing attention due to their controllable bandgap. Fabrication of MoS2(1−x)Te2x
is expected to be difficult due to its thermal instability although it shows wide tunable bandgap range. In this study, MoS2(1−x)Te2x
fabrication is carried out by sputtering and post-deposition thermal treatment in chalcogen ambient. Films without phase separation were successfully fabricated. It was revealed that the band structure changes according to the chalcogen ratio. The valence band maximum shifted non-linearly showing bowing effect, while the conduction band minimum remained almost unchanged. It was considered that such bowing behavior of valence band minimum is attributed to the electronegativity difference between S and Te. The invariant nature of the conduction band was attributed to the fact that there is no such competition of electronegativity for the metal side whose electron orbitals mainly contribute to the conduction band formation. The maximum shift in the valence band maximum was as large as 0.5 eV. It was also revealed that suppressing the chalcogen deficiency may prevent phase separation. The wide tunability in the band structure and the possibility of realizing the uniform alloy promises the materials high applicability to different electronic devices.
Extracellular BMP1 is the major proteinase for COOH-terminal proteolysis of type I procollagen in lung fibroblasts
Authors: N’Diaye Elsa-Noah , Cook Ryan , Wang Hua , Wu Ping , LaCanna Ryan , Wu Cong , Ye Zhengmao , Seshasayee Dhaya , Hazen Meredith , Lin WeiYu , Tyagi Tulika , Hotzel Isidro , Tam Lucinda , Newman Robert , Roose-Girma Merone , Wolters Paul J. , Ding Ning
Published: November 2020

Proteolytic processing of procollagens is a central step during collagen fibril formation. Bone morphogenic protein 1 (BMP1) is a metalloprotease that plays an important role in the cleavage of carboxy-terminal (COOH-terminal) propeptides from procollagens. Although the removal of propeptides is required to generate mature collagen fibrils, the contribution of BMP1 to this proteolytic process and its action site remain to be fully determined. In this study, using postnatal lung fibroblasts as a model system, we showed that genetic ablation of Bmp1 in primary murine lung fibroblasts abrogated COOH-terminal cleavage from type I procollagen as measured by COOH-terminal propeptide of type I procollagen (CICP) production. We also showed that inhibition of BMP1 by siRNA-mediated knockdown or small-molecule inhibitor reduced the vast majority of CICP production and collagen deposition in primary human lung fibroblasts. Furthermore, we discovered and characterized two antibody inhibitors for BMP1. In both postnatal lung fibroblast and organoid cultures, BMP1 blockade prevented CICP production. Together, these findings reveal a nonredundant role of extracellular BMP1 to process CICP in lung fibroblasts and suggest that development of antibody inhibitors is a viable pharmacological approach to target BMP1 proteinase activity in fibrotic diseases.
Pregnancy-related plasticity of gastric vagal afferent signals in mice
Authors: Li Hui , Clarke Georgia S. , Christie Stewart , Ladyman Sharon R. , Kentish Stephen J. , Young Richard L. , Gatford Kathryn L. , Page Amanda J.
Published: November 2020

This study provides first evidence that gastric vagal afferent signaling is attenuated during pregnancy and inversely associated with meal size. Growth hormone attenuated mechanosensitivity of gastric vagal afferents, adding support that increases in maternal growth hormone may mediate adaptations in gastric vagal afferent signaling during pregnancy. These findings have important implications for the peripheral control of food intake during pregnancy.
Looking at the developing lung in single-cell resolution
Authors: Mižíková I. , Thébaud B.
Published: November 2020

Lung development is a complicated and delicate process, facilitated by spatially and temporarily coordinated cross talk of up to 40 cell types. Developmental origin and heterogeneity of lung cell lineages in context of lung development have been a focus of research efforts for decades. Bulk RNA and protein measurements, RNA and protein labeling, and lineage tracing techniques have been traditionally employed. However, the complex and heterogeneous nature of lung tissue presents a particular challenge when identifying subtle changes in gene expression in individual cell types. Rapidly developing single-cell RNA sequencing (scRNA-seq) techniques allow for unbiased and robust assessment of complex cellular dynamics during biological processes in unprecedented ways. Discovered a decade ago, scRNA-seq has been applied in respiratory research to understand lung cellular composition and to identify novel cell types. Still, very few studies to date have addressed the single-cell transcriptome in healthy or aberrantly developing lung. In this review, we discuss principal discoveries with scRNA-seq in the field of prenatal and postnatal lung development. In addition, we examine challenges and expectations, and propose future steps associated with the use of scRNA-seq to study developmental lung diseases.
Consuming sucrose solution promotes leptin resistance and site specifically modifies hypothalamic leptin signaling in rats
Authors: Harris Ruth B. S.
Published: November 2020

Rats consuming 30% sucrose solution and a sucrose-free diet (LiqS) become leptin resistant, whereas rats consuming sucrose from a formulated diet (HS) remain leptin responsive. This study tested whether leptin resistance in LiqS rats extended beyond a failure to inhibit food intake and examined leptin responsiveness in the hypothalamus and hindbrain of rats offered HS, LiqS, or a sucrose-free diet (NS). Female LiqS Sprague-Dawley rats initially only partially compensated for the calories consumed as sucrose, but energy intake matched that of HS and NS rats when they were transferred to calorimetry cages. There was no effect of diet on energy expenditure, intrascapular brown fat tissue (IBAT) temperature, or fat pad weight. A peripheral injection of 2 mg of leptin/kg on day 23 or day 26 inhibited energy intake of HS and NS but not LiqS rats. Inhibition occurred earlier in HS rats than in NS rats and was associated with a smaller meal size. Leptin had no effect on energy expenditure but caused a transient rise in IBAT temperature of HS rats. Leptin increased the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in the hindbrain and ventromedial hypothalamus of all rats. There was a minimal effect of leptin in the arcuate nucleus, and only the dorsomedial hypothalamus showed a correlation between pSTAT3 and leptin responsiveness. These data suggest that the primary response to leptin is inhibition of food intake and the pattern of sucrose consumption, rather than calories consumed as sucrose, causes leptin resistance associated with site-specific differences in hypothalamic leptin signaling.
Skeletal muscle extracellular matrix remodeling with worsening glycemic control in nonhuman primates
Authors: Ruggiero Alistaire D. , Davis Ashley , Sherrill Chrissy , Westwood Brian , Hawkins Gregory A. , Palmer Nicholette D. , Chou Jeff W. , Reeves Tony , Cox Laura A. , Kavanagh Kylie
Published: November 2020

Type 2 diabetes (T2D) development may be mediated by skeletal muscle (SkM) function, which is responsible for >80% of circulating glucose uptake. The goals of this study were to assess changes in global- and location-level gene expression, remodeling proteins, fibrosis, and vascularity of SkM with worsening glycemic control, through RNA sequencing, immunoblotting, and immunostaining. We evaluated SkM samples from health-diverse African green monkeys ( Cholorcebus aethiops sabaeus) to investigate these relationships. We assessed SkM remodeling at the molecular level by evaluating unbiased transcriptomics in age-, sex-, weight-, and waist circumference-matched metabolically healthy, prediabetic (PreT2D) and T2D monkeys ( n = 13). Our analysis applied novel location-specific gene differences and shows that extracellular facing and cell membrane-associated genes and proteins are highly upregulated in metabolic disease. We verified transcript patterns using immunohistochemical staining and protein analyses of matrix metalloproteinase 16 (MMP16), tissue inhibitor of metalloproteinase 2 (TIMP2), and VEGF. Extracellular matrix (ECM) functions to support intercellular communications, including the coupling of capillaries to muscle cells, which was worsened with increasing blood glucose. Multiple regression modeling from age- and health-diverse monkeys ( n = 33) revealed that capillary density was negatively predicted by only fasting blood glucose. The loss of vascularity in SkM co-occurred with reduced expression of hypoxia-sensing genes, which is indicative of a disconnect between altered ECM and reduced endothelial cells, and known perfusion deficiencies present in PreT2D and T2D. This report supports that rising blood glucose values incite ECM remodeling and reduce SkM capillarization, and that targeting ECM would be a rational approach to improve health with metabolic disease.
In vivo Ca2+ dynamics during cooling after eccentric contractions in rat skeletal muscle
Authors: Takagi Ryo , Tabuchi Ayaka , Asamura Tomoyo , Hirayama Seiya , Ikegami Ryo , Tanaka Yoshinori , Hoshino Daisuke , Poole David C. , Kano Yutaka
Published: November 2020

The effect of cooling on in vivo intracellular calcium ion concentration [Ca2+]i after eccentric contractions (ECs) remains to be determined. We tested the hypothesis that cryotherapy following ECs promotes an increased [Ca2+]i and induces greater muscle damage in two muscles with substantial IIb and IIx fiber populations. The thin spinotrapezius (SPINO) muscles of Wistar rats were used for in vivo [Ca2+]i imaging, and tibialis anterior (TA) muscles provided greater fidelity and repeatability of contractile function measurements. SPINO [Ca2+]i was estimated using fura 2-AM and the magnitude, location, and temporal profile of [Ca2+]i determined as the temperature near the muscle surface post-ECs was decreased from 30°C (control) to 20°C or 10°C. Subsequently, in the TA, the effect of post-ECs cooling to 10°C on muscle contractile performance was determined at 1 and 2 days after ECs. TA muscle samples were examined by hematoxylin and eosin staining to assess damage. In SPINO, reducing the muscle temperature from 30°C to 10°C post-ECs resulted in a 3.7-fold increase in the spread of high [Ca2+]i sites generated by ECs ( P < 0.05). These high [Ca2+]i sites demonstrated partial reversibility when rewarmed to 30°C. Dantrolene, a ryanodine receptor Ca2+ release inhibitor, reduced the presence of high [Ca2+] sites at 10°C. In the TA, cooling exacerbated ECs-induced muscle strength deficits via enhanced muscle fiber damage ( P < 0.05). By demonstrating that cooling post-ECs potentiates [Ca2+]i derangements, this in vivo approach supports a putative mechanistic basis for how postexercise cryotherapy might augment muscle fiber damage and decrease subsequent exercise performance.
ATP-mediated increase in H+ flux from retinal Müller cells: a role for Na+/H+ exchange
Authors: Tchernookova Boriana K. , Gongwer Michael W. , George Alexis , Goeglein Brock , Powell Alyssa M. , Caringal Hannah L. , Leuschner Thomas , Phillips Anna G. , Schantz Adam W. , Kiedrowski Lech , Chappell Richard , Kreitzer Matthew A. , Malchow Robert Paul
Published: November 2020

Glial cells are known to regulate neuronal activity, but the exact mechanism(s) whereby these “support” cells modulate synaptic transmission remains unclear. Small changes in extracellular levels of acidity are known to be particularly powerful regulators of neurotransmitter release. Here, we show that extracellular ATP, known to be a potent activator of glial cells, induces H+ efflux from retinal Müller (glial) cells and that the bulk of the H+ efflux is mediated by Na+/H+ exchange.
Amylase-Dependent Regulation of Glucose Metabolism and Insulin/Glucagon Secretion in the Streptozotocin-Induced Diabetic Pig Model and in a Rat Pancreatic Beta-Cell Line, BRIN-BD11
Authors: Pierzynowska Kateryna , Oredsson Stina , Pierzynowski Stefan
Published: November 2020

The current study was aimed at highlighting the role of blood pancreatic amylase in the regulation of glucose homeostasis and insulin secretion in a porcine model of streptozotocin- (STZ-) induced diabetes and in a rat pancreatic beta-cell line, BRIN-BD11. Blood glucose, plasma insulin, and glucagon levels were measured following a duodenal glucose tolerance test (IDGTT), in four pigs with STZ-induced type 2 diabetes (T2D pigs) and in four pigs with STZ-induced type 1 diabetes (T1D pigs). Four intact pigs were used as the control group. The effect of amylase supplementation on both acute and chronic insulin secretion was determined in a BRIN-BD11 cell line. The amylase infusion had no effect on the glucose utilization curve or glucagon levels in the healthy pigs. However, a significant lowering of insulin release was observed in healthy pigs treated with amylase. In the T2D pigs, the glucose utilization curve was significantly lowered in the presence of amylase, while the insulin response curve remained unchanged. Amylase also significantly increased glucagon release during the IDGTT in the T2D and T1D pigs, by between 2- and 4-fold. Amylase did not affect the glucose utilization curve in the T1D pigs. Amylase supplementation significantly decreased both acute and chronic insulin secretion in the BRIN-BD11 cells. These data confirm our previous observations and demonstrate the participation of pancreatic amylase in glucose absorption/utilization. Moreover, the present study clearly highlights the direct impact of pancreatic blood amylase on insulin secretion from pancreatic beta-cells and its interactions with insulin and glucagon secretion in a porcine model.
Spleen Stiffness Predicts Survival after Transjugular Intrahepatic Portosystemic Shunt in Cirrhotic Patients
Authors: Zhu Hao , Guo Huiwen , Yin Xiaochun , Yang Jian , Yin Qin , Xiao Jiangqiang , Wang Yi , Zhang Ming , Han Hao , Zhuge Yuzheng , Zhang Feng
Published: November 2020

Objectives. Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications. Little is known about the ability of spleen stiffness (SS) for predicting the survival of cirrhotic patients undergoing TIPS. This study is to evaluate the influence of SS detected by point shear wave elastography (pSWE) in predicting survival after TIPS. Methods. This retrospective cohort study screened consecutive patients who underwent TIPS and reliable pSWE measurement between October 2014 and September 2017 from our prospectively maintained database. SS values were measured before TIPS. The primary endpoint was the overall survival after TIPS. The Cox regression analysis model was used for univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to calculate the sensitivity, specificity, and positive and negative predictive values. Results. A total of 89 patients were involved in the final analysis. 24 patients (27.0%) died during a median follow‐up time of 31 m. Multivariable Cox regression analysis confirmed that higher SS value (P < 0.001), LS value (P = 0.008), diameter of shunt (P = 0.001), and older age (P < 0.001) were independent prognostic factors of survival after TIPS. The risk of death rose 57.440‐fold for each SS unit (m/s) increase. SS was also correlated with liver failure after TIPS. ROC analysis showed that the best SS cutoff value was 3.60 m/s for predicting survival, with a sensitivity of 54.2% and specificity of 90.8%. Conclusions. The SS value determined by pSWE in cirrhotic patients was an independent predictive factor for survival after TIPS.
Cloud-Fog Computing-Based Distributed Event-Triggered Consensus Predictive Compensation for Optimal Energy Management in Microgrid under DoS Attack
Authors: Wang Lvhang , Pang Yongheng , Zhou Bowen , Jin Shuowei
Published: November 2020

A cloud-fog computing-based event-triggered distributed energy optimization management method based on predictive attack compensation is proposed to address the problem of denial of service (DoS) attack, the complexity of computation, and the bandwidth constraint on the communication network in microgrids. Firstly, in order to optimize the energy supply of microgrid and maximize the profit, the minimum cost function of maintaining the balance of supply and demand is given considering the power loss of microgrid. Secondly, considering the problem of bandwidth-constrained communication, a distributed event-triggered consensus algorithm is proposed based on fog computing. Thirdly, a model predictive compensation algorithm based on cloud computing is proposed, which uses the mismatched power between supply and demand at the historical time before the attack to predict and compensate the missing data of the agent power at the current time and many times after attack. Finally, the effectiveness of the proposed method is verified by simulation results.
A Multilayer Genetic Algorithm for Automated Guided Vehicles and Dual Automated Yard Cranes Coordinated Scheduling
Authors: Zhao Qianru , Ji Shouwen , Zhao Wenpeng , De Xinling
Published: November 2020

At present, a lot of studies on automatic terminal scheduling are aimed at the shortest operating time. An effective way to reduce the operating time is to increase the amount of operating equipment. However, people often ignore the additional costs and energy consumption caused by increasing the amount of equipment. This paper comprehensively considers the two aspects of the equipment operation time and equipment quantity matching. With the minimum total energy consumption of the operating equipment as the objective function, a cooperative scheduling model of Automated Guided Vehicles (AGVs) and dual Automated Yard Cranes (AYCs) is established. In the modelling process, we also considered the interference problem between dual Automated Yard Cranes (AYCs). In order to solve this complex model, this paper designs an improved multilayer genetic algorithm. Finally, the calculation results from CPLEX and a multilayer genetic algorithm are compared, and the effectiveness of the model and algorithm is proved by experiments. In addition, at the same time, it is proved that it is necessary to consider the interference problem of dual Automated Yard Cranes (AYCs), and the optimal quantity matching scheme for the equipment and the optimal temporary storage location is given.
Cancer Vaccines: Toward the Next Breakthrough in Cancer Immunotherapy
Authors: Igarashi Yuka , Sasada Tetsuro
Published: November 2020

Until now, three types of well-recognized cancer treatments have been developed, i.e., surgery, chemotherapy, and radiotherapy; these either remove or directly attack the cancer cells. These treatments can cure cancer at earlier stages but are frequently ineffective for treating cancer in the advanced or recurrent stages. Basic and clinical research on the tumor microenvironment, which consists of cancerous, stromal, and immune cells, demonstrates the critical role of antitumor immunity in cancer development and progression. Cancer immunotherapies have been proposed as the fourth cancer treatment. In particular, clinical application of immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 antibodies, in various cancer types represents a major breakthrough in cancer therapy. Nevertheless, accumulating data regarding immune checkpoint inhibitors demonstrate that these are not always effective but are instead only effective in limited cancer populations. Indeed, several issues remain to be solved to improve their clinical efficacy; these include low cancer cell antigenicity and poor infiltration and/or accumulation of immune cells in the cancer microenvironment. Therefore, to accelerate the further development of cancer immunotherapies, more studies are necessary. In this review, we will summarize the current status of cancer immunotherapies, especially cancer vaccines, and discuss the potential problems and solutions for the next breakthrough in cancer immunotherapy.
Long Noncoding RNA HOTAIR Functions as a Competitive Endogenous RNA to Regulate Connexin43 Remodeling in Atrial Fibrillation by Sponging MicroRNA-613
Authors: Dai Weiran , Chao Xiaoying , Li Shanshan , Zhou Shuang , Zhong Guoqiang , Jiang Zhiyuan
Published: November 2020

Several studies have indicated that long noncoding RNAs (lncRNAs)-HOX transcript antisense RNA (HOTAIR) is involved in some cardiovascular diseases by regulating gene expression as a competitive endogenous RNA (ceRNA). GJA1 encoding Cx43 is one potential target gene of microRNA-613 (miR-613). Meanwhile, there is a potential target regulatory relationship between HOTAIR and miR-613. The present study is aimed at investigating whether HOTAIR functions as a ceRNA to regulate the Cx43 expression in atrial fibrillation (AF) by sponging miR-613. The expressions of HOTAIR, miR-613, and Cx43 were detected in the right atrial appendages of 45 patients with heart valve disease, including 23 patients with chronic AF. The HOTAIR overexpressed and underexpressed HL-1 cell model were constructed to confirm the effect of HOTAIR on Cx43. Then, the Cx43 expression was detected to testify the interplay between HOTAIR and miR-613 after cotransfecting HOTAIR and miR-613. Furthermore, luciferase assays were performed to verify that HOTAIR could regulate Cx43 remolding as a ceRNA by sponging miR-613. The expression of HOTAIR and Cx43 was significantly downregulated in chronic AF group. HOTAIR regulated positively the Cx43 expression in HL-1 cells. The upregulated effect of HOTAIR on the Cx43 expression could be remarkably attenuated by miR-613. Moreover, the inhibitory effect of miR-613 on the Cx43 expression could be obviously mitigated by HOTAIR. At last, luciferase assays confirmed HOTAIR functioned as a ceRNA in the Cx43 expression by sponging miR-613. Our study suggests that HOTAIR, functioning as a ceRNA by sponging miR-613, is an important contributor to Cx43 remolding in AF.
Immunomodulatory Effects of Hydrolyzed Seawater Pearl Tablet (HSPT) on Th1/Th2 Functionality in a Mice Model of Chronic Obstructive Pulmonary Disease (COPD) Induced by Cigarette Smoke
Authors: Chen Zhenxing , Yan Qiangqiang , Zhang Zhongmin , Lan Taijin , Liu Peng , Han Siyin , Lin Yong , Lin Jiang
Published: November 2020

Chronic obstructive pulmonary disease (COPD) is predicted to become the third leading cause of death around the world. The present study is designed to investigate whether hydrolyzed seawater pearl tablet (HSPT) has immunoregulatory effects on the Th1/Th2 functionality in cigarette smoke‐induced COPD model mice. The determination of the amino acid composition of HSPT was carried out by high‐performance liquid chromatography (HPLC) with precolumn phenylisothiocyanate (PITC) derivatization. COPD model mice were constructed by cigarette smoking (CS) treatment and HSPT was administered. HSPT inhibited the infiltration of inflammation in the airway of the lung, reduced influx of eosinophils (EOSs), lymphocytes (LYMs), neutrophils (NEUs), and macrophages (MACs) in the bronchoalveolar lavage fluid (BALF), decreased the levels of IFN‐γ, IL‐2, IL‐4, and IL‐10 in the serum and lung, and decreased the expression of aforementioned cytokines in the spleen and lung in CS‐treated mice. Besides, HSPT also had the ability to reduce the amount of CD3+CD4+ T cells and modulate the Th1/Th2 balance. Taken together, this study supports the consensus that CS is a critical factor to induce and aggravate COPD. HSPT could regulate the balance of Th1/Th2 in CS‐induced COPD model mice, indicating its effects on inhibiting the development of COPD.
Adaptive Backlash Compensation Method Based on Touch State Observation for a Solid Ducted Rocket
Authors: Wang An , Zeng Qinghua , Ma Likun , Wang Hongfu
Published: November 2020

A hysteresis model was built to describe the backlash of the flow regulator in a solid ducted rocket, and its influence on the engine control was also analyzed in this study. An adaptive backlash compensation method was proposed under two challenges: limited information and backlash state variation caused by the harsh environment in the gas generator. The touch state is designed and its observation is used to get the state of backlash, and a compensation control method using the existing information was carried out combined with the motion intention. This method greatly shortened the time during the transition and reduced the hysteresis effect on the control system. Furthermore, the compensation method is improved and acquires a self-learning ability, the compensation parameter changes adaptively during the process of flow regulation, and it is able to meet the challenge of an unknown and variable state of backlash. Finally, the validation of the compensation method was carried out with two simulations.
Driver Fatigue Detection Based on Convolutional Neural Networks Using EM-CNN
Authors: Zhao Zuopeng , Zhou Nana , Zhang Lan , Yan Hualin , Xu Yi , Zhang Zhongxin
Published: November 2020

With a focus on fatigue driving detection research, a fully automated driver fatigue status detection algorithm using driving images is proposed. In the proposed algorithm, the multitask cascaded convolutional network (MTCNN) architecture is employed in face detection and feature point location, and the region of interest (ROI) is extracted using feature points. A convolutional neural network, named EM-CNN, is proposed to detect the states of the eyes and mouth from the ROI images. The percentage of eyelid closure over the pupil over time (PERCLOS) and mouth opening degree (POM) are two parameters used for fatigue detection. Experimental results demonstrate that the proposed EM-CNN can efficiently detect driver fatigue status using driving images. The proposed algorithm EM-CNN outperforms other CNN-based methods, i.e., AlexNet, VGG-16, GoogLeNet, and ResNet50, showing accuracy and sensitivity rates of 93.623% and 93.643%, respectively.