bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological depletion of retinal neurons prevents vertical angiogenic sprouting without affecting the superficial vascular plexus
Authors: Morita Akane , Yoshizumi Mika , Arima Shiho , Mori Asami , Sakamoto Kenji , Nagamitsu Tohru , Nakahara Tsutomu
Published: October 2020

Background

In mice, a tri‐layered (superficial, intermediate, and deep) vascular structure is formed in the retina during the third postnatal week. Short‐term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor inhibitors delays the formation of superficial vascular plexus and this allows us to investigate the developmental process of superficial and deep vascular plexuses at the same time. Using this model, we examined the effect of pharmacological depletion of retinal neurons on the formation of superficial and deep vascular plexuses.

Results

Neuronal cell loss induced by an intravitreal injection of N‐methyl‐d‐aspartic acid on postnatal day (P) 8 delayed vascular development in the deep layer but not in the superficial layer in mice treated with KRN633, a VEGF receptor inhibitor, on P0 and P1. In KRN633‐treated mice, neuronal cell loss decreased the number of vertical sprouts originating from the superficial plexus without affecting the number of angiogenic sprouts growing in front. Neuronal cell loss did not impair networks of fibronectin and astrocytes in the superficial layer.

Conclusions

Our results suggest that inner retinal neurons play a crucial role in forming the deep vascular plexus by directing the sprouts from the superficial blood vessels to the deep layer.
Relationship between duration of heart failure, patient characteristics, outcomes, and effect of therapy in PARADIGM‐HF
Authors: Yeoh Su E. , Dewan Pooja , Desai Akshay S. , Solomon Scott D. , Rouleau Jean L. , Lefkowitz Marty , Rizkala Adel , Swedberg Karl , Zile Michael R. , Jhund Pardeep S. , Packer Milton , McMurray John J.V.
Published: October 2020

Aims

Little is known about patient characteristics, outcomes, and the effect of treatment in relation to duration of heart failure (HF). We have investigated these questions in PARADIGM‐HF. The aim of the study was to compare patient characteristics, outcomes, and the effect of sacubitril/valsartan, compared with enalapril, in relation to time from HF diagnosis in PARADIGM‐HF.

Methods and results

HF duration was categorized as 0–1, >1–2, >2–5, and >5 years. Outcomes were adjusted for prognostic variables, including N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). The primary endpoint was the composite of HF hospitalization or cardiovascular death. The number of patients in each group was as follows: 0–1 year, 2523 (30%); >1–2 years, 1178 (14%); >2–5 years, 2054 (24.5%); and >5 years, 2644 (31.5%). Patients with longer‐duration HF were older, more often male, and had worse New York Heart Association class and quality of life, more co‐morbidity, and higher troponin‐T but similar NT‐proBNP levels. The primary outcome rate (per 100 person‐years) increased with HF duration: 0–1 year, 8.4 [95% confidence interval (CI) 7.6–9.2]; >1–2 years, 11.2 (10.0–12.7); >2–5 years, 13.4 (12.4–14.6); and >5 years, 14.2 (13.2–15.2); P < 0.001. The hazard ratio was 1.26 (95% CI 1.07–1.48), 1.52 (1.33–1.74), and 1.53 (1.33–1.75), respectively, for >1–2, >2–5, and >5 years, compared with 0–1 year. The benefit of sacubitril/valsartan was consistent across HF duration for all outcomes, with the primary endpoint hazard ratio 0.80 (95% CI 0.67–0.97) for 0–1 year and 0.73 (0.63–0.84) in the >5 year group. For the primary outcome, the number needed to treat for >5 years was 18, compared with 29 for 0–1 year.

Conclusions

Patients with longer‐duration HF had more co‐morbidity, worse quality of life, and higher rates of HF hospitalization and death. The benefit of a neprilysin inhibitor was consistent, irrespective of HF duration. Switching to sacubitril/valsartan had substantial benefits, even in patients with long‐standing HF.
FcγRI plays a critical role in patients with ulcerative colitis relapse
Authors: Li Yan , Zhang Yuan‐Yi , Yang Li‐Teng , Liu Jiang‐Qi , Zhou Chuan , Liu Zhi‐Qiang , Yang Gui , Mo Li‐Hua , Liu Zhi‐Gang , Feng Bai‐Sui , Yang Ping‐Chang
Published: October 2020

Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)‐specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag‐specific IgG amounts in colon biopsies of UC patients. UC patient‐derived Ag‐specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re‐exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC‐like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC.
TLR7 endogenous ligands remodel glycolytic macrophages and trigger skin‐to‐joint crosstalk in psoriatic arthritis
Authors: Van Raemdonck Katrien , Umar Sadiq , Palasiewicz Karol , Romay Bianca , Volkov Suncica , Arami Shiva , Sweiss Nadera , Shahrara Shiva
Published: October 2020

Thirty percent of psoriasis patients develop psoriatic arthritis (PsA), nevertheless the mechanism remains unknown. Endogenous GU‐rich miRNAs activate endosomal TLR7 that plays a critical role in autoimmune diseases. We found that endogenous TLR7 ligands, miR‐29 and miR‐Let7b, were markedly increased in PsA compared to osteoarthritis (OA) synovial fluid (SF)s. We showed that intradermal (i.d.) miR‐Let7b injection promoted skin inflammation, which was characterized by amplified Th1 cells, CD68+M1 macrophages, and transcriptional upregulation of glycolytic mediators, GLUT1, C‐MYC, and HIF1α. Expansion of skin Th1 cells driven by miR‐Let7b was also linked to elevated M1‐associated IRFs. Interestingly, i.d. miR‐Let7b administration exacerbated suboptimal joint inflammation along with metabolic reconfiguration of the PsA‐like preclinical model. Moreover, TLR7 agonist, R837, potentiated metabolic reprogramming and expression of IL‐1β, IL‐6, and IL‐12 in murine macrophages, enabling myeloid‐to‐T‐cell crosstalk. Consistently, treatment with glycolytic inhibitors, 2‐DG and/or HIF1αi, reversed R837‐induced metabolic remodeling and disrupted the TLR7‐driven inflammatory phenotype in myeloid and lymphoid cells. Similar to miR‐Let7b, R837 also differentiates progenitor cells into mature osteoclasts, primarily through RANKL induction. Taken together, this study indicates that TLR7‐instigated metabolic rewiring of macrophages and their cross‐regulation of T cells connects skin immunopathology to joint inflammation.
Experimental and Theoretical Studies on the Protective Effect of a Biomass Corrosion Inhibitor (vigna radiata) on Mild Steel in Acidic Medium
Authors: Maduabuchi Chidiebere A. , Njoku Demian I. , Anthony Obike I. , Nwanonenyi Simeon C. , Akalezi Christogonus , Blessing Adindu , Oguzie Emeka E.
Published: October 2020

The scrutiny of the impeding properties of vigna radiata (VR) on mild steel corrosion in sour environs (1 M HCl and 0.5 M H2SO4) was done by means of gravimetric, electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization methods (PDP). Polarization findings revealed that VR retarded the corrosion process in a mixed‐mode manner. Adsorption of the active components of VR was found to be in line with Langmuir adsorption isotherm. The obtained PDP result was complemented by the EIS findings. Scanning electron microscopy (SEM), atomic force microscopy (AFM) and the theoretical technique was used to complement the results.
Metallodendrimer‐sensitised Cytochrome P450 3A4 Electrochemical Biosensor for TB Drugs
Authors: Franke Candice , Ajayi Rachel Fanelwa , Uhuo Onyinyechi , Januarie Kaylin , Iwuoha Emmanuel
Published: October 2020

A cytochrome P450 3A4 (CYP3A4) based enzymatic biosensor was developed with the incorporation of a first‐generation copper polypropyleneimine (CuPPI) metallodendrimer for the detection of anti‐tuberculosis (anti‐TB) drugs. The development of an electrochemical phenotype biosensor for this purpose is still vital since it aids in the ongoing fight against TB by determining metabolic profile. This allows TB treatment to be tailored on an individual patient basis, minimise adverse drug reactions and improve quality of life in TB patients. This simple biosensor was constructed via physical adsorption of CuPPI onto a gold electrode with subsequent electrostatic attachment of CYP3A4. The biosensor was successful in detecting all four first line anti‐TB drugs i. e. isoniazid, ethambutol, pyrazinamide and rifampicin with limits of detection ranging from 0.02244 to 0.1072 nM in 0.1 M phosphate buffer. The developed biosensor was then applied towards “real samples” in the form of spiked synthetic urine and plasma. Calibration curves were carried out in the complex matrices, which were diluted with 0.1 M PB. These yielded good LOD in the range of ultra‐low micromolar concentration i. e. 0.165–0.884 μM across all drugs. Recovery studies were also successful when detecting the real tablets in both plasma and urine with results ranging from 91.5 % to 108.5 %.
Amperometric Detection of Creatinine in Clinical Samples Based on Gold Electrode Arrays Fabricated Using Printed Circuit Board Technology
Authors: Ortiz Mayreli , Botero Mary Luz , Fragoso Alex , O'Sullivan Ciara K.
Published: October 2020

Herein we report a reliable and stable biosensor for the amperometric detection of creatinine through the ammonium produced in its reaction with creatinine deiminase linked to a Nafion®/polyaniline gold coated surface. The gold electrode array was produced using a low cost printed board circuit technology. A linear range of 1–1000 μM was obtained with standard deviations of less than 5 % (n=3) obtained. Stability studies were carried out and 80 % activity was maintained after one month. The sensors were tested with 142 serum samples from patients with renal dysfunction at different stage of the disease and validated using a commercial colorimetric method.
Isolation and identification of O‐ and N‐linked glycoproteins in milk from different mammalian species and their roles in biological pathways which support infant growth
Authors: Kwan Soon Hong , Wan‐Ibrahim Wan Izlina , Juvarajah Thaneswari , Fung Shin Yee , Abdul‐Rahman Puteri Shafinaz
Published: October 2020

Milk serves as the sole nutrition for newborns, as well as a medium for the transfer of immunological components from the mother to the baby. This study reveals different glycoprotein profiles obtained from human, bovine, and caprine milk and their potential roles in supporting infant growth. Proteins from these three milk samples are separated and analyzed using two‐dimensional gel electrophoresis (2‐DE). Glycosylated proteins from all samples are enriched by affinity chromatography using lectins from the seeds of Artocarpus integer before analysis using LC/MS‐QTOF. The glycoproteome profiling demonstrates that glycosylated proteins are higher in caprine milk compared to other samples. Analysis using LC/MS‐QTOF identified 42 O‐glycosylated and 56 N‐glycosylated proteins, respectively. Among those identified, human milk has 17 glycoproteins, which are both O‐ and N‐glycosylated, whereas caprine and bovine have 10 and 1, respectively. Only glycoproteins from human milk have shown positive matching to important human biological pathways, such as vesicle‐mediated transport, immune system and hemostasis pathways. Human milk remains unique for human babies with the presence of antibodies in the form of immunoglobulins that are lacking in ruminant milk proteomes.
Politics and administration in times of crisis: Explaining the Swedish response to the COVID‐19 crisis
Authors: Petridou Evangelia
Published: October 2020

The Swedish response to the COVID‐19 pandemic is different not only to the response of other European countries, but also to other Scandinavian countries, which are geographically proximate and culturally similar. The question that emerges from an analysis of the Swedish case concerns the reasons why the country chose to take such a relatively liberal crisis response to the onset of the pandemic compared to the rest of Europe. In this paper, I treat the national response to the pandemic as the outcome variable, which I seek to explain through an analysis of the intersection of dualism in the model of Swedish public administration and the devolved governance system that bestows operational autonomy on public agencies and local public authorities. The duality that characterizes the relationship between politics, policy, and administration in Sweden resulted in a response that was necessarily decentralized. The decentralized response in conjunction with high political trust among the citizenry necessitated, and was conducive to, broad guidelines. I conclude the article with a discussion placing the Swedish response in perspective for further comparative research.

摘要

瑞典对新冠肺炎大流行的响应不仅不同于其他欧洲国家，还不同于其他斯堪的纳维亚国家，后者在地理和文化上都与瑞典相似。浮现的问题则有关于瑞典选择自由式危机响应的原因。本文中，我将国家对大流行的响应作为结果变量，试图通过分析瑞典公共行政与下放治理体系（将操作自治权交予公共机构与地方公共机构）模式中二者的交集，对该变量进行诠释。瑞典政治、政策与行政之间的关系的双重性导致对危机的响应必然是去中心化的。去中心化响应加上全体公民高度的政治信任，不仅使广泛的指南成为必需，同时有益于该指南。我以一项探讨作为本文结论，这项探讨诠释了瑞典的危机响应对进一步比较研究的重要性。
The State Kindergarten Entry Assessment Digital Technology Landscape
Authors: Ackerman Debra J.
Published: October 2020

Over the past 8 years, U.S. kindergarten classrooms have been impacted by policies mandating or recommending the administration of a specific kindergarten entry assessment (KEA) in the initial months of school as well as the increasing reliance on digital technology in the form of mobile apps, touchscreen devices, and online data platforms. Using a sample of KEAs used in 29 states in Fall 2019, in this report I examine the KEA digital technology landscape. Of particular interest was the extent to which states with similar KEA item types incorporated such technology as well as the potential impact of these technology inputs on the role of the kindergarten teacher in the KEA administration, scoring, and report‐generating processes. Analyses of the study's data demonstrated that all 29 states incorporate digital technology into their KEAs. However, differences among states' technological inputs suggested four different models of KEAs along a continuum of supplanting versus retaining teachers' active roles in the administration, scoring, and report‐generating processes. These findings have implications for short‐term research agendas aimed at supporting KEA validity, reliability, and utility.
Emerging markets financial sector debt: A Markov‐switching study of interest rate sensitivity
Authors: Gubareva Mariya , Keddad Benjamin
Published: October 2020

We provide an empirical study on the sensitivity of capital gains of emerging market financial sector debts to the U.S. Treasury market in a three‐state Markov‐switching framework. Specifically, we model the capital gains change in a debt portfolio consisting of emerging market bonds as a linear regression of the capital gains change in a portfolio consisting of U.S. Treasury bonds in which the regression coefficients are allowed to switch between three regimes. Our analysis spans the period 2003–2016. We identify three regimes corresponding to positive sensitivity, insensitivity and negative sensitivity and provide economic explanations of our findings. We find that negative sensitivity regimes mostly occurred during the financial crisis. Our research advances understanding of the financial economics that governs the interdependence of interest rate risk and credit risk. By reassessing interest rate risk management through the prism of the downside risk hedge, our results shed light on how financial institutions may better withstand adverse financial conditions.
Did reduction in corporate tax rate attract FDI in Pakistan?
Authors: Nazir Mian Sajid , Hafeez Qaisar , U‐Din Salah
Published: October 2020

Foreign direct investment (FDI) is a very important factor for economic growth because of its associated benefits such as advanced technology, employment, and economic development for the developing host countries. The factors of lower corporate tax rate, social peace, consistent energy supply, better infrastructure, skilled labor, political stability and business openness are very important for foreign investors. Therefore, this study investigates the impact of corporate tax reduction, terrorism, energy shortfall, availability of labor, infrastructure and degree of business openness on the FDI in Pakistan. Further, it compares democratic and autocratic regimes to evaluate their impact on attracting FDI in Pakistan. A vector error correction (VEC) model is used on the secondary data of the period 1989–2016. The results of the study show that corporate tax rate, terrorism, and energy shortfall have significant negative impact on FDI. The study results also confirm that autocratic period was more favorable to attract FDI providing openness to the economy when compared to democratic period. The findings of this study could be used by policy makers for future FDI policy of Pakistan.
Foreign financial flows, human capital and economic growth in African developing countries
Authors: Dinh Su Thanh , Phuc Nguyen Canh
Published: October 2020

This study investigates the relationship between foreign financial flows (i.e., FDI inflows, ODA, and remittances), human capital, and economic growth in African developing countries. Along with the two‐step system GMM estimator, fixed effect panel quantile regression is applied as a robustness check for the sample of 38 African countries over the period 2002–2017. First, FDI inflows emerge with different impacts on economic growth, depending on the level: negative and positive effects at low and high levels, respectively. Interestingly, these effects are moderated by the human capital of hosting countries. Second, ODA and remittances are found as negative factors for economic growth; notably, higher human capital accumulation of receiving countries reduces these negative impacts. Overall, the results imply that foreign financial flows are correlated differently with human capital in influencing economic growth among African countries. Nevertheless, the significant implications are that more attention must be paid to human capital in these countries, and more feasible policies are urgently needed for better absorption of external capital flows.
Nonparametric variational learning of multivariate beta mixture models in medical applications
Authors: Manouchehri Narges , Bouguila Nizar , Fan Wentao
Published: October 2020

Clustering as an essential technique has matured into a capable solution to address the gap between the growing availability of data and deriving the knowledge from them. In this paper, we propose a novel clustering method “variational learning of infinite multivariate Beta mixture models.” The motivation behind proposing this technique is the flexibility of mixture models to fit the data. This approach has the capability to infer the model complexity and estimate model parameters from the observed data automatically. Moreover, as a label‐free method, it could also address the problem of high costs of medical data labeling, which can be undertaken just by medical experts. The performance of the model is evaluated on real medical applications and compared with other similar alternatives. We demonstrate the ability of our proposed method to outperform widely used methods in the field as it has been shown in experimental results.
Prediction of acute inhalation toxicity using cytotoxicity data from human lung epithelial cell lines
Authors: Lim Seong Kwang , Yoo Jean , Kim Haewon , Lim Yeon‐Mi , Kim Woong , Shim Ilseob , Kim Ha Ryong , Kim Pilje , Eom Ig‐chun
Published: October 2020

Recent research on in vitro systems has focused on mimicking the in vivo situation of cells within the respiratory system. However, few studies have predicted inhalation toxicity using conventional and simple submerged two‐dimensional (2D) cell culture models. We investigated the conventional submerged 2‐D cell culture model as a method for the prediction of acute inhalation toxicity. Median lethal concentration (LC50) (rat, inhalation, 4 h) and half maximal inhibitory concentration (IC50) (lung or bronchial cell, 24 h) data for 59 substances were obtained from the literature and by experiments. Cytotoxicity assays were performed on 44 substances with reported LC50, but without IC50, data to obtain the IC50 values. A weak correlation was observed between the IC50 and LC50 of all substances. Semi‐volatile organic compounds (SVOCs) and non‐VOCs (NVOCs) (16 substances) with a water solubility of ≥1 g/L were strongly correlated between 24‐h IC50 and 4‐h LC50, and this had an excellent predictive ability to distinguish between Categories 1–3 and 4 (Globally Harmonized System classification for acute inhalation toxicity). Our results suggest that the submerged 2‐D cell culture model may be used to predict in vivo acute inhalation toxicity for substances with a water solubility of ≥1 g/L in SVOCs and NVOCs.
The long noncoding RNA PDK1‐AS/miR‐125b‐5p/VEGFA axis modulates human dermal microvascular endothelial cell and human umbilical vein endothelial cell angiogenesis after thermal injury
Authors: Zhou Situo , Liang Pengfei , Zhang Pihong , Zhang Minghua , Huang Xiaoyuan
Published: October 2020

Our previous study confirmed the critical role of miR‐125b and vascular endothelial growth factor (VEGF) in burn wound repair., The present study was aimed to identify the role of long noncoding RNAs (lncRNAs) related to the function of miR‐125b and VEGF in burn wound repair and the underlying mechanism. First, we found that lncRNA PDK1‐AS and VEGFA expression was significantly increased in heat‐denatured dermal tissue samples and in human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) after thermal injury. PDK1‐AS knockdown significantly inhibited cell viability, cumulative tube length, cell migratory ability, and cell invasion of thermally injured HDMECs and HUVECs. PDK1‐AS knockdown decreased VEGFA protein levels in HDMECs and HUVECs. While overexpression of PDK1‐AS showed the opposite effects. Online tools prediction and luciferase assay confirmed that miR‐125b‐5p targeted PDK1‐AS and VEGFA 3′‐untranslated region. miR‐125b‐5p inhibition significantly increased VEGFA protein levels and enhanced viability, cumulative tube length, migratory ability, and invasion of HUVECs and HDMECs. Furthermore, the effects of PDK1‐AS knockdown on VEGFA protein levels in the two cell lines were partially reversed by miR‐125b‐5p inhibition. Finally, in the tissue samples, PDK1‐AS and VEGFA expression was increased, while miR‐125b‐5p expression was decreased in heat‐denatured dermal tissues; the expression of miR‐125b‐5p had a negative correlation with PDK1‐AS and VEGFA, respectively, and PDK1‐AS and VEGFA were positively correlated with each other in tissue samples. In conclusion, PDK1‐AS relieves miR‐125b‐5p‐induced inhibition on VEGFA by acting as a endogenous RNA, therefore modulating HDMEC and HUVEC angiogenesis after thermal injury.
Black‐Blood Contrast in Cardiovascular MRI
Authors: Henningsson Markus , Malik Shaihan , Botnar Rene , Castellanos Daniel , Hussain Tarique , Leiner Tim
Published: October 2020

MRI is a versatile technique that offers many different options for tissue contrast, including suppressing the blood signal, so‐called black‐blood contrast. This contrast mechanism is extremely useful to visualize the vessel wall with high conspicuity or for characterization of tissue adjacent to the blood pool. In this review we cover the physics of black‐blood contrast and different techniques to achieve blood suppression, from methods intrinsic to the imaging readout to magnetization preparation pulses that can be combined with arbitrary readouts, including flow‐dependent and flow‐independent techniques. We emphasize the technical challenges of black‐blood contrast that can depend on flow and motion conditions, additional contrast weighting mechanisms (T1, T2, etc.), magnetic properties of the tissue, and spatial coverage. Finally, we describe specific implementations of black‐blood contrast for different vascular beds.

Level of Evidence

5

Technical Efficacy Stage

5
Interpretive discrepancies caused by target values inter‐batch variations in chemiluminescence immunoassay for SARS‐CoV‐2 IgM/IgG by MAGLUMI
Authors: Selingerova Iveta , Valik Dalibor , Gescheidtova Lenka , Sramek Vladimir , Cermakova Zdenka , Zdrazilova‐Dubska Lenka
Published: October 2020

Plasma specimens from coronavirus disease 2019 patients were double‐tested for anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies by two different batches of MAGLUMI 2019‐nCov immunoglobulin M/immunoglobulin G (IgM/IgG) assays to evaluate IgM/IgG levels, qualitative interpretation, antibody kinetics, and linearity of diluted specimen. Here we show that (i) high‐level IgM specimens need to be diluted with negative human plasma but not kit diluents and (ii) measured anti‐SARS‐CoV‐2 IgM/IgG concentrations are substantially higher with later marketed immunoassay batch leading to (iii) the change of qualitative interpretation (positive vs. negative) in 12.3% of specimens measured for IgM, (iv) the informative time‐course pattern of antibody production only when data from different immunoassay batches are not combined.
Evaluating Bayesian Radiocarbon‐dated Event Count (REC) models for the study of long‐term human and environmental processes
Authors: Carleton W. Christopher
Published: October 2020

Chronological uncertainty complicates attempts to use radiocarbon dates as proxies for processes such as human population growth/decline, forest fires and marine ingression. Established approaches involve turning databases of radiocarbon‐date densities into single summary proxies that cannot fully account for chronological uncertainty. Here, I use simulated data to explore an alternative Bayesian approach that instead models the data as what they are, namely radiocarbon‐dated event counts. The approach involves assessing possible event‐count sequences by sampling radiocarbon date densities and then applying a Markov Chain Monte Carlo method to estimate the parameters of an appropriate count‐based regression model. The regressions based on individual sampled sequences were placed in a multilevel framework, which allowed for the estimation of hyperparameters that account for chronological uncertainty in individual event times. Two processes were used to produce simulated data. One represented a simple monotonic change in event‐counts and the other was based on a real palaeoclimate proxy record. In both cases, the method produced estimates that had the correct sign and were consistently biased towards zero. These results indicate that the approach is widely applicable and could form the basis of a new class of quantitative models for use in exploring long‐term human and environmental processes.
Precursor carboxy‐silica for functionalization with interactive ligands. I. Carbodiimide‐assisted preparation of silica‐bonded stationary phases with octadecyl, naphthyl, and anthracenyl ligands: Comparison of their selectivity and retentivity
Authors: Paranamana Nilushi , El Rassi Ziad
Published: October 2020

A precursor carboxy‐silica support was introduced for grafting retentive ligands for use in high‐performance liquid chromatography. This support was prepared by sequentially reacting 5 μm silica particles with vinyltrimethoxysilane and then thioglycolic acid. The carboxy‐silica thus obtained was subsequently functionalized with octadecylamine, 2‐naphthylamine, or 2‐aminoanthracene by on‐column reactions via a carbodiimide conjugation reaction. The carbodiimide with its zero‐length carboxyl‐to‐amine coupling ability works by activating the surface carboxyl groups of the precursor support for direct reaction with the primary amines of octadecylamine, 2‐naphthylamine, or 2‐aminoanthracene via amide bond formation. These reactions series, which are applied for the first time in high‐performance liquid chromatography column fabrication, yielded the octadecyl‐, naphthyl‐, and anthracenyl‐silica columns. The three columns were evaluated for their reversed‐phase chromatography retention properties with alkylbenzenes, alkylphenyl ketones, nitroalkanes, benzene and toluene derivatives, polyaromatic hydrocarbons, and nitro‐substituted amino acids. The naphthyl‐ and anthracenyl‐silica exhibited a good selectivity and efficiency toward most of the aromatic analytes when compared to the octadecyl‐silica. Nitro‐substituted amino acids containing electron withdrawing groups showed greater selectivity than other analytes on the aromatic‐based columns than the C18 column. This is because of the ability of the π electron system of the analyte to accept electrons from the aromatic‐based stationary phase (a Lewis base).
Examination of the Factor Structure and Correlates of the Perceived Military Healthcare Stressors Scale
Authors: Hale Willie J. , Moore Brian A. , Straud Casey L. , Baker Monty T. , Peterson Alan L.
Published: October 2020

The current study evaluated the factor structure, reliability estimates, correlates, and predictive utility of the Perceived Military Healthcare Stressor Scale (PMHSS) in a sample of active duty military medical personnel (N = 1,131) deployed to Joint Base Balad in Iraq. The sample was composed of an approximately even split of male (51.2%) and female (48.8%) participants who ranged in age from 18 to 60 years. The PMHSS is a 21‐item measure that was designed to assess the impact of specific medical stressors that military healthcare providers may encounter while deployed. An exploratory factor analysis of the PMHSS revealed the presence of two distinct factors: trainable and futility stressors. Confirmatory factor analysis showed that a bifactor model best represented the data, with all items loading higher on the general factor relative to their specific subscale factors. Evidence of partial scalar invariance by gender was found. The PMHSS was significantly correlated with several convergent measures, including assessments of posttraumatic stress disorder (PTSD), depression severity, distress due to both combat exposure and general deployment‐related concerns, and positive affect, rs = .30–.59. PMHSS scores were more strongly correlated with PTSD and depression in women than in men, and they provided incremental validity in predicting convergent measures over and above other related constructs. Healthcare–specific stressors are an understudied area, and this study provides new insights into how deployment‐related caregiving stress may impact deployed military medical personnel independently of the impact of combat experiences.
Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer
Authors: Morimoto Nobuyuki , Oishi Yoshifumi , Yamamoto Masaya
Published: October 2020

Fast intracellular migration and controlled localization of molecules represent significant challenges for future applications of drug discovery and related fields. In this study, thermoresponsive sulfobetaine polymers with pyridinium cations are evaluated as biocompatible and mitochondria‐localizing agents. Among the polymers, poly(3‐(4‐(2‐methacrylamido)ethyl pyridinio‐1‐yl)propane‐1‐sulfonate), P(E‐PySMAAm)14k (Mn = 14 000 g mol−1) exhibit thermoresponsiveness with an upper critical solution temperature like behavior in cell culture medium containing serum with minimal cytotoxicity. Upon the addition of P(E‐PySMAAm)14k to HeLa cells at temperatures above the clearing point at 37 °C, effective localization is observed in mitochondria. However, increased intensity but nonspecific localization is observed below the clearing point at 4 °C. Doxorubicin is conjugated to the P(E‐PySMAAm) and achieves effective mitochondrial delivery while maintaining drug efficacy. Such sulfobetaine polymers represent promising tools for intracellular delivery of molecules.
Campaign Theme: When Unions Turn on Their Own
Authors: Wich Scott
Published: October 2020

During this election season, politicians across the country are looking to gain votes by making promises for the future and delivering negative messages about their opponents. Empty promises and negative campaigning can turn off many voters, but regardless of the public's distaste for these methods, politicians continue to use them because they are effective. Employers seeking to prevent unionization can learn from these practices.
Antifungal polymers for medical applications
Authors: Velazco‐Medel Marlene Alejandra , Camacho‐Cruz Luis Alberto , Lugo‐González José Carlos , Bucio Emilio
Published: October 2020

Fungi‐associated infections are very common diseases in humans, and these have increased in immunocompromised population and hospitalized patients. Fungi grow almost in any environment, and they reproduce easily in dirt and wet spaces, and thus, the development of antifungal materials is focused on avoiding fungal infections or inhibiting growth. Polymers used for medical devices are susceptible to microorganism adhesion. Therefore, they have been treated and modified for the inhibition of fungi growth. There are two pathways to deal with these microorganisms, firstly, the synthesis of versatile polymeric materials with antifouling properties, and, secondly, the development of materials for controlled fungicide release. These two approaches have been used in the crafting of food packaging. Additionally, sophisticated polymeric drug delivery systems have allowed the systematic and localized administration of fungicides reducing doses with a prolonged delivery. This general purpose has been accomplished by the synthesis of polymeric composites, grafted polymers or the modification of polymeric fungicides, by the coupling of cationic moieties on polymers, using metallic salts and nanoparticles, and by the loading of fungicides in micelles and metallic nanoparticles. Most of the materials presented on this review are still at an early stage of development. This compilation intends to be a frame of reference for researchers willing to explore this topic since clinical applications of these materials are starting to be increasingly relevant.
Facial nerve transfer for facial reanimation with parotidoplasty approach
Authors: Wehrle Chase J. , Sinkler Margaret A. , Brown Jimmy J. , Ritter Edmond F.
Published: October 2020

Background

Facial paralysis has a profound impact on quality of life in affected individuals, primarily through loss of verbal and nonverbal communication. Common facial nerve reanimation techniques include coaptation to the masseteric or hypoglossal nerve. Most techniques require nerve grafts to achieve a tension‐free neurorrhaphy. Our report aims to show a surgical adaption to current facial reanimation procedures using a partial parotidoplasty approach in order to avoid challenges caused by interpositional nerve grafts through primary neurorrhaphy.

Patients and Methods

The modified surgical approach was performed on four patients, aged 30–67. Length of paralysis ranged from 6 to 13 months. Cause of paralysis included one patient with Bell's palsy in one patient, prior surgery in two patients, and traumatic fracture in the remaining patient. A modified Blair approach is used to expose the parotid capsule. The facial nerve is dissected proximally toward the stylomastoid foramen and distally toward the masseter. The parotid gland substance is sectioned overlying each branch of the facial nerve using ultrasonic dissection or hemostatic scalpel, allowing mobilization of the proximal segment and upper and lower divisions of the facial nerve. The superficial lobe of the parotid is preserved in most cases. The House–Brackmann (H–B) functional scale was used to assess facial nerve function pre‐ and post‐operatively.

Results

All patients showed H–B score V or greater prior to reanimation. Follow‐up was conducted at 3‐, 6‐, and 12‐months in all patients with resultant improvement of H–B scores of I in three patients and II in the remaining patient. Only one complication was noted, with one patient developing a right postauricular hematoma that was adequately managed without sequelae. All remaining patients experienced an uncomplicated post‐operative course.

Conclusion

Our modified approach to facial nerve reanimation works well with a planned parotidoplasty allowing for successful reanimation outcomes without the need for interpositional grafting. This technique may be considered in masseteric and hemi‐hypoglossal nerve transfers for the reinnervation of facial muscles.
Constructing a variational quasi‐reversibility method for a Cauchy problem for elliptic equations
Authors: Anh Khoa Vo , Truong Hoang Nhan Pham
Published: October 2020

In the recent developments of regularization theory for inverse and ill‐posed problems, a variational quasi‐reversibility (QR) method has been designed to solve a class of time‐reversed quasi‐linear parabolic problems. Known as a PDE‐based approach, this method relies on adding a suitable perturbing operator to the original problem and consequently, on gaining the corresponding fine stabilized operator, which leads us to a forward‐like problem. In this work, we establish new conditional estimates for such operators to solve a prototypical Cauchy problem for elliptic equations. This problem is based on the stationary case of the inverse heat conduction problem, where one wants to identify the heat distribution in a certain medium, given the partial boundary data. Using the new QR method, we obtain a second‐order initial value problem for a wave‐type equation, whose weak solvability can be deduced using a priori estimates and compactness arguments. Weighted by a Carleman‐like function, a new type of energy estimates is explored in a variational setting when we investigate the Hölder convergence rate of the proposed scheme. Besides, a linearized version of this scheme is analyzed. Numerical examples are provided to corroborate our theoretical analysis.
The rigorous derivation of unipolar Euler–Maxwell system for electrons from bipolar Euler–Maxwell system by infinity‐ion‐mass limit
Authors: Zhao Liang
Published: October 2020

In the paper, we consider the local‐in‐time and the global‐in‐time convergence of infinity‐ion‐mass limit for bipolar Euler–Maxwell systems by setting the mass of an electron
and letting the mass of an ion mi → +∞. We use the method of asymptotic expansions to handle the local‐in‐time convergence problem and find that the limiting process from bipolar models to unipolar models is actually decoupling but not the vanishing of equations for the corresponding the other particle. Moreover, when the initial data are sufficiently close to the constant equilibrium state, we also establish the corresponding global‐in‐time convergence.
Countable and separable elementary soft topological space
Authors: Altıntaş İsmet , Taşköprü Kemal , Selvi Betül
Published: October 2020

This paper is an introduction to countable and separable elementary soft topological spaces, which includes concepts such as dense soft set, first countability, second countability, separability and Lindelöf properties and some basic properties of them in the elementary soft topological spaces.
Texture analysis for chemotherapy response evaluation in osteosarcoma using MR imaging
Authors: Baidya Kayal Esha , Kandasamy Devasenathipathy , Khare Kedar , Bakhshi Sameer , Sharma Raju , Mehndiratta Amit
Published: October 2020

The efficacy of MRI‐based statistical texture analysis (TA) in predicting chemotherapy response among patients with osteosarcoma was assessed. Forty patients (male: female = 31:9; age = 17.2 ± 5.7 years) with biopsy‐proven osteosarcoma were analyzed in this prospective study. Patients were scheduled for three cycles of neoadjuvant chemotherapy (NACT) and diffusion‐weighted MRI acquisition at three time points: at baseline (t0), after the first NACT (t1) and after the third NACT (t2) using a 1.5 T scanner. Eight patients (nonsurvivors) died during NACT while 34 patients (survivors) completed the NACT regimen followed by surgery. Histopathological evaluation was performed in the resected tumor to assess NACT response (responder [≤50% viable tumor] and nonresponder [>50% viable tumor]) and revealed nonresponder: responder = 20:12. Apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM) parameters, diffusion coefficient (D), perfusion coefficient (D*) and perfusion fraction (f) were evaluated. A total of 25 textural features were evaluated on ADC, D, D* and f parametric maps and structural T1‐weighted (T1W) and T2‐weighted (T2W) images in the entire tumor volume using 3D TA methods gray‐level cooccurrence matrix (GLCM), neighborhood gray‐tone‐difference matrix (NGTDM) and run‐length matrix (RLM). Receiver‐operating‐characteristic curve analysis was performed on the selected textural feature set to assess the role of TA features (a) as marker(s) of tumor aggressiveness leading to mortality at baseline and (b) in predicting the NACT response among survivors in the course of treatment. Findings showed that the NGTDM features coarseness, busyness and strength quantifying tumor heterogeneity in D, D* and f maps and T1W and T2W images were useful markers of tumor aggressiveness in identifying the nonsurvivor group (area‐under‐the‐curve [AUC] = 0.82‐0.88) at baseline. The GLCM features contrast and correlation, NGTDM features contrast and complexity and RLM feature short‐run‐low‐gray‐level‐emphasis quantifying homogeneity/terogeneity in tumor were effective markers for predicting chemotherapeutic response using D (AUC = 0.80), D* (AUC = 0.80) and T2W (AUC = 0.70) at t0, and D* (AUC = 0.80) and f (AUC = 0.70) at t1. 3D statistical TA features might be useful as imaging‐based markers for characterizing tumor aggressiveness and predicting chemotherapeutic response in patients with osteosarcoma.
A bio‐safe cyclophosphazene derivative flame retardant for polylactic acid composites: Flammability and cytotoxicity
Authors: Xue Qingxia , Wu Quan , Yao Yuan , Li Xinjian , Sun Jun , Gu Xiaoyu , Song Weiguo , Yan Fang , Zhang Sheng
Published: October 2020

An efficient bio‐safe cyclophosphazene flame retardant, 1,5,9,13,16,20‐Hexaoxa‐7,14,21‐triaza‐6λ4,8λ4,5λ4‐triphosphatrispiro[5.1.5.1.5.1]heneicosa‐6,8(14),15(21)‐triene (HCPO), was synthesized, and then was incorporated into polylactic acid (PLA) to improve the fire safety. The chemical structure of HCPO was confirmed by Fourier‐transformed infrared spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy. The thermal stability of the compound was characterized by thermogravimetric (TG) analyzer. The cytotoxic effects of HCPO to cells were evaluated. Fire behavior and thermal stability of PLA composites were investigated by vertical burning, limiting oxygen index (LOI), TG analysis, and cone calorimeter. The morphology of residual charring was observed by scanning electron microscope. The results showed HCPO was bio‐safe, and highly effective to enhance the flame retardancy of PLA composites. The LOI value was increased from 18.4 to 27.5 and UL‐94 grade achieved V‐0 for the PLA composite containing only 2% HCPO and 2% pentaerythrotol. It was demonstrated that intermolecular cross‐linking reaction between pentaerythrotol and HCPO in high temperature range could accelerate the formation of compact char layers.
A systematic review and meta‐analysis of the use of renin‐angiotensin system drugs and COVID‐19 clinical outcomes: What is the evidence so far?
Authors: Kurdi Amanj , Abutheraa Nouf , Akil Lina , Godman Brian
Published: October 2020

Conflicting evidence exists about the effect of angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID‐19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID‐19‐related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta‐analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID‐19 were included. Studies’ quality was appraised using the Newcastle‐Ottawa Scale. Data were analyzed using the random‐effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I2 statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID‐19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15), and hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization among USA studies (OR:1.59; 95%CI:1.03,2.44), peer‐reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID‐19 infection (OR:0.24; 95%CI: 0.17,0.34). In conclusion, high‐quality evidence exists for the effect of ACEIs/ARBs on some COVID‐19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.
Dissecting the roles of FTZ‐F1 in larval molting and pupation, and the sublethal effects of methoxyfenozide on Helicoverpa armigera
Authors: Zhang Wanna , Ma Long , Liu Xiangya , Peng Yingchuan , Liang Gemei , Xiao Haijun
Published: October 2020

BACKGROUND

In holometabolous insects, the major developmental transitions – larval molting and pupation – are triggered by a pulse of 20‐hydroxyecdysone (20E) and coordinated by juvenile hormone. Methoxyfenozide (MF), an ecdysteroid agonist, represents a new class of insect growth regulators and is effective against lepidopteran pests. Fushi‐tarazu factor 1 (FTZ‐F1) is an ecdysone‐inducible transcription factor. To date, the effect of MF on 20E‐response genes remains unclear, and we speculate the involvement of FTZ‐F1 in MF's growth regulating effect.

RESULTS

MF at LC25 and LC10 caused severe ecdysis failure in Helicoverpa armigera, extended their larval duration, lowered their pupal weight, and reduced the respiratory, pupation and emergence rates. Furthermore, sublethal doses of MF inhibited ecdysteroidogenesis and lowered the intrinsic 20E titer, but showed an inductive effect on 20E‐response genes including HaFTZ‐F1. HaFTZ‐F1, predominantly expressed in larval epidermis, was markedly upregulated before or right after larval ecdysis, and maintained a high level in prepupal stage. Knockdown of HaFTZ‐F1 in 4th‐instar larvae severely impaired larval ecdysis, whereas its knockdown in final‐instar larvae caused abnormal pupation. Moreover, knocking down HaFTZ‐F1 downregulated three critical ecdysteroidogenesis genes, lowered 20E titer, and suppressed the expression of 20E receptors and 20E‐response genes. The introduction of 20E into HaFTZ‐F1‐RNAi larvae partly relieved the negative effects on the 20E‐induced signaling cascade.

CONCLUSION

Our findings reveal the adverse effects of sublethal doses of MF on the development of H. armigera and elucidate the resulting perturbations on the 20E‐induced signaling cascade; we propose that HaFTZ‐F1 regulates ecdysis and pupation by mediating 20E titer and its signaling pathway. © 2020 Society of Chemical Industry