bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Novel 1‐(5‐(Benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea Derivatives and Evaluation of Their Antimicrobial Activities
Authors: Mannam Madhava Rao , S. Srimurugan , Kumar Pramod , K R. S. Prasad
Published: July 2019

A new series of 1‐(5‐(benzylsulfinyl)‐3‐methyl‐1,3,4‐thiadiazol‐2(3H)‐ylidene)‐thiourea/urea derivatives (1a–j) were designed and synthesized. For the first time, (i) a new process was developed for N‐methylation of 1,3,4‐thiadiazole moiety using dimethyl carbonate an environmentally benign reagent in presence of N,N,N′,N′‐tetramethylethylenediamine and (ii) the sulfide was selectively oxidized to sulfoxide in higher yield by using chlorine (g) in aqueous acetic acid media under mild reaction condition. The synthesized compounds (1a–j) were investigated for their antimicrobial activities. The tested compounds (1a–j) were exhibited moderate to excellent antibacterial activities against both Gram‐positive and Gram‐negative bacterial strains. The same compounds exhibited good antifungal activities against selected fungal strains. Particularly, the compounds 1b, 1d, 1h, and 1i were proved to be promising leads exhibiting both antibacterial and antifungal activities compared with standard drugs, ciprofloxacin, and fluconazole. The presence of 1,3,4‐thiadiazole moiety has a significant role in the display of antimicrobial activity. In addition, the presence of both sulfinyl and thiourea or urea functionalities has enhanced the activity as per obtained antimicrobial activity data.
Socio‐economic Status, Demographic Characteristics and Intimate Partner Violence
Authors: Wilson Nicholas
Published: July 2019

One in three ever‐partnered women worldwide has experienced intimate partner violence (IPV), yet there is little systematic global evidence on the association between socio‐economic status (SES), demographic characteristics and IPV. This paper uses information from more than one‐quarter of one million female respondents age 15–49 in IPV modules from 36 Demographic and Health Surveys to provide detailed evidence on IPV gradients around the developing world. The analysis reveals relatively large negative IPV–SES gradients for respondent years of schooling and household wealth. Marriage and higher age are generally associated with lower IPV, whereas the physical violence–age profile follows an inverted U‐shape. © 2019 John Wiley & Sons, Ltd.
Clinical findings in Brazilian patients with adult GM1 gangliosidosis
Authors: Giugliani Luciana , Steiner Carlos Eduardo , Kim Chong Ae , Lourenço Charles Marques , Santos Mara Lucia Schmitz Ferreira , de Souza Carolina Fischinger Moura , Brusius‐Facchin Ana Carolina , Baldo Guilherme , Riegel Mariluce , Giugliani Roberto
Published: July 2019

GM1 gangliosidosis is a lysosomal storage disorder caused by β‐galactosidase deficiency. To date, prospective studies for GM1 gangliosidosis are not available, and only a few have focused on the adult form. This retrospective cross‐sectional study focused on clinical findings in Brazilian patients with the adult form of GM1 gangliosidosis collected over 2 years. Ten subjects were included in the study. Eight were males and two females, with median age at diagnosis of 11.5 years (IQR, 4‐34 years). Short stature and weight below normal were seen in five out of the six patients with data available. Radiological findings revealed that the most frequent skeletal abnormalities were beaked vertebrae, followed by hip dysplasia, and platyspondyly. Neurological examination revealed that dystonia and swallowing problems were the most frequently reported. None of the patients presented hyperkinesia, truncal hypertonia, Parkinsonism, or spinal cord compression. Clinical evaluation revealed impairment in activities of cognitive/intellectual development and behavioral/psychiatric disorders in all nine subjects with data available. Language/speech impairment (dysarthria) was found in 8/9 patients, fine motor and gross motor impairments were reported in 7/9 and 5/9 patients, respectively. Impairment of cognition and daily life activities were seen in 7/9 individuals. Our findings failed to clearly identify typical early or late alterations presented in GM1 gangliosidosis patients, which confirms that it is a very heterogeneous condition with wide phenotypic variability. This should be taken into account in the evaluation of future therapies for this challenging condition.
Modification of genital kidney nephrons for sperm transport in a plethodontid salamander, Eurycea longicauda
Authors: Hartley Jordan , Gribbins Kevin M. , Siegel Dustin S.
Published: July 2019

Salamanders possess kidneys with two distinct regions: a caudal pelvic portion and cranial genital portion. Nephrons of the pelvic region are responsible for urine formation and transport. Nephrons of the genital region transport sperm from testes to Wolffian ducts; however, nephrons of the genital region possess all the same functional regions found in pelvic kidney nephrons that are involved with urine formation and transport (renal corpuscles, proximal tubules, distal tubules, and collecting ducts). Morphological similarities between pelvic and genital regions stimulated past researchers to hypothesize that nephrons of genital kidneys possess dual function; that is, sperm transport and urine formation/transport. Considering size of glomeruli is directly related to the total amount of blood plasma filtered into the Bowman's space, we tested the hypothesis that nephrons of genital kidneys have reduced urine formation function by comparing glomerular size between nephrons of pelvic and genital kidney regions in Eurycea longicauda with general histological techniques. Light microscopy analysis revealed that glomeruli of pelvic kidneys were significantly larger than those measured from genital kidneys. Transmission electron microscopy analysis also revealed modifications in genital kidney nephrons when compared to pelvic kidney nephrons that suggested a decrease in urine formation function in genital kidneys. Such modifications included a decrease in basal and lateral plasma membrane folding in genital kidney proximal and distal tubules compared to that of pelvic kidney proximal and distal tubules. Genital kidney proximal tubules were also ciliated, which was not observed in pelvic kidney proximal tubules. In conclusion, although structurally similar at the histological level, it appears that nephrons of genital kidneys have decreased urine formation function based on glomerular size comparison and nephron ultrastructure.
Anatomy, histology, and histochemistry of the olfactory organ of the Korean shuttles mudskipper Periophthalmus modestus
Authors: Kim Hyun T. , Yun Seung W. , Park Jong Y.
Published: July 2019

The Korean shuttles mudskipper Periophthalmus modestus has paired olfactory organs on its snout, consisting of anterior and posterior nostrils, a single olfactory canal with sensory and nonsensory epithelia, and a single accessory nasal sac. Its sensory epithelium consists of numerous islets forming a pseudostratified layer and contains various cells: olfactory receptor neurons, supporting cells, basal cells, lymphatic cells (LCs), and axon bundles. The sensory epithelium is a stratified squamous layer comprising stratified epithelial cells, mucous cells (MCs) with glycogen, flattened cells (FCs), LCs, and unidentified cells. Specific structures are as follows: (a) a tubular anterior nostril projecting outward, (b) a slit posterior nostril, (c) an elongated olfactory canal, (d) an ethmoidal accessory nasal sac, (e) axon bundles found only in the basal layer of the sensory epithelium, (f) FCs only at the top of the nonsensory epithelium, and (g) glycogen‐containing MCs. Such structures seem to be unique in that they have not been observed in most teleost fishes spending their whole life in water.
Rapid MALDI‐TOF molecular imaging: Instrument enhancements and their practical consequences
Authors: Vestal Marvin , Li Lingjun , Dobrinskikh Evgenia , Shi Yatao , Wang Bowen , Shi Xudong , Li Sicheng , Vestal Christina , Parker Kenneth
Published: July 2019

A new high performance linear MALDI‐TOF mass spectrometer provides both high spatial resolution and high speed. This instrument employs a new ion optics system with a grounded ion source and efficient transfer and detection of ions over a broad mass range. This provides very high sensitivity, precision, and an extended dynamic range for both positive and negative ion detection. Here we demonstrate the capabilities of this system by imaging pancreatic tissue samples from rats and mice.
Electromagnetic hyperthermia on porous model of hepatic cancerous tissue
Authors: Shamekhi Leila , Sayehvand Habib‐Olah , Karami Hamidreza
Published: July 2019

Because the effectiveness of interstitial hyperthermia is related to the temperature distribution achieved during the process, accurate understanding of energy transport within biological organs is necessary. This strongly depends on the complexity of the extended model. Herein, the coupled nonlinear set of transient equations for electromagnetic, momentum, and energy has been extended under two layered porous medium approximation. Maximum temperature value as well as its position has been traced in time by applying local thermal non‐equilibrium (LTNE). The boundary between cancerous and normal tissue has continuously been respected by different properties. The extended model is solved by a new computational approach. The results lead to a special slow and continuous moving antenna to achieve more effective cancerous cell death via normal cell safety.
Toward higher extraction and enrichment factors via a double‐reservoirs microfluidic device as a micro‐extractive platform
Authors: Rezvani Omid , Baraazandeh Maryam , Bagheri Habib
Published: July 2019

In this study, firstly, a double‐reservoir and switchable prototype of a micro‐chip along with the respective holders were fabricated. A cyclic desorption process using microliter volume of organic solvent was adopted to prevent any outdoor contamination. As extractive phases, two identical sheets of electrospun polyamide/polypyrrole/titania nanofibers were synthesized using core–shell electro‐spinning technique and utilized for determination of memantine in plasma samples. Field emission scanning electron microscopy images showed a high degree of porosity and homogeneity throughout the sheet structure. Also, energy dispersive X‐ray analysis confirmed the presence of titania, while the recorded Fourier transform infrared spectra proved the chemical structures of the polymeric mats. The incorporation of titania as well as polypyrrole in the composition of polyamide nanofibers improved both mechanical stability and extraction capacity of the extractive phase and therefore facilitated the extraction/desorption process. The limits of detection and quantification were 0.01 and 0.04 ng/mL, respectively. In addition, the interday and intraday precisions were lower than 6.7% (n = 3). The linearity was in the range of 0.14–75.00 ng/mL, while recoveries were between 94.1 and 98.4% with the regression coefficient of 0.9987.
Antibodies against the DNABII protein integration host factor (IHF) inhibit sinus implant biofilms
Authors: Martyn Lauren , Sethia Rishabh , Chon Rachel , Novotny Laura , Goodman Steven D. , Elmaraghy Charles , Bakaletz Lauren O.
Published: July 2019

Objectives

Chronic rhinosinusitis is a common, costly condition often treated with endoscopic sinus surgery and intraoperative placement of intranasal sinus implant materials. Whereas these materials aid in postoperative healing, they also support bacterial biofilm formation and thus contribute to negative outcomes. This study examined pretreatment of sinus implant materials with antibody against an essential bacterial biofilm structural component, the DNABII family of DNA‐binding proteins, as a strategy to prevent biofilm formation.

Methods

Sinus implant materials were equilibrated in immunoglobulin G (IgG)‐enriched antiserum against the DNABII protein integration host factor (IHF), individually or in combination with amoxicillin‐clavulanate prior to inoculation with nontypeable Haemophilus influenzae (NTHI), a predominant pathogen of chronic rhinosinusitis. After 16 hours, the bacterial burden was quantitated and compared to pretreatment with saline, IgG‐enriched naive serum, or amoxicillin‐clavulanate alone.

Results

NTHI readily formed biofilms on all three materials in vitro. However, pretreatment of each material with IgG‐enriched anti‐IHF resulted in a significant decrease in bacterial burden compared to controls (P ≤ 0.05). Moreover, a significant and synergistic outcome was achieved with a cocktail of anti‐IHF plus amoxicillin‐clavulanate (P ≤ 0.05) with complete inhibition of NTHI biofilm formation on all three materials.

Conclusions

Biofilm formation was well supported in vitro on three sinus implant materials that vary in composition and resorption characteristics; however, pretreatment of each with DNABII protein targeted antibodies in combination with a previously ineffective antibiotic was highly effective to prevent the formation NTHI biofilms. These data demonstrate the potential for clinical utility of pretreatment of sinus implant and additional surgical materials with anti‐DNABII antibodies.

Level of Evidence

NA Laryngoscope, 130:1364–1371, 2020
Economic costs of dysphagia among hospitalized patients
Authors: Allen Jacqui , Greene Monique , Sabido Ismael , Stretton Matthew , Miles Anna
Published: July 2019

Objectives/Hypothesis

Difficulties swallowing may lead to aspiration pneumonia and death. In a hospital setting where patients are admitted for other causes, we hypothesized that the additional burden of a swallow problem would increase length of stay, rate of pneumonia, cost, readmissions, and morbidity compared to those without dysphagia.

Study Design

Retrospective parallel cohort study.

Methods

A study of patients admitted to the hospital with hip/femur fracture was completed. Two groups were identified and compared: those with a coded diagnosis of dysphagia (n = 165) in addition to hip/femur fracture (HF + D), and a group with hip fracture alone (HF‐D) (n = 2,288) (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification). Number of inpatient days, cost per patient, diagnosis of pneumonia, 30‐day readmission, and mortality rates were compared.

Results

For those in the HF + D group, mean age was 85 years compared to 78 years in the HF‐D group (P < .05); length of stay was 32 days, more than twice that of the HF‐D group (14 days) (P < .05). Mortality within 30 days of admission was significantly higher (18% vs. 4%,respectively) but 30‐day readmission rate was similar (8% vs. 11%, respectively). Rate of aspiration pneumonia was 14 times greater in HF + D (9.7%) compared with HF‐D (0.7%). Average admission cost was NZD$36,913 (HF + D) compared with NZD$22,222 (HF‐D) (P < .05).

Conclusions

Complaint of dysphagia, in addition to hip fracture, increases a patient's average admission cost by 60%. It is associated with increased aspiration pneumonia and greater mortality. Dysphagia screening at admission to hospital would allow early identification of swallow compromise and may prevent complications and reduce costs.

Level of Evidence

3b Laryngoscope, 130:974–979, 2020
Tropomodulin 3 modulates EGFR‐PI3K‐AKT signaling to drive hepatocellular carcinoma metastasis
Authors: Zheng Hao , Yang Yuan , Hong Yong‐gang , Wang Meng‐chao , Yuan Sheng‐xian , Wang Zhen‐guang , Bi Feng‐rui , Hao Li‐qiang , Yan Hong‐li , Zhou Wei‐ping
Published: July 2019

The mechanism of hepatocellular carcinoma (HCC) metastasis remains poorly understood. Tropomodulin 3 (TMOD3) is a member of the pointed end capping protein family that contributes to invasion and metastasis in several types of malignancies. It has been found to be crucial for the membranous skeleton and embryonic development, although, its role in HCC progression remains largely unclear. We observed increased levels of Tmod3 in HCCs, especially in extrahepatic metastasis. High Tmod3 expression correlated with aggressive carcinoma and poor patient with HCC survival. Loss‐of‐function studies conducted by us determined Tmod3 as an oncogene that promoted HCC growth and metastasis. Mechanistically, Tmod3 increases transcription of matrix metalloproteinase‐2, ‐7, and ‐9 which required PI3K‐AKT. Interaction between Tmod3 and epidermal growth factor receptor (EGFR) that supports the activation of EGFR phosphorylation, is essential for signaling activation of PI3K‐AKT viral oncogene homolog. These findings reveal that Tmod3 enhances aggressive behavior of HCC both in vitro and in vivo by interacting with EFGR and by activating the PI3K‐AKT signaling pathway.
Targeting cholecystokinin‐2 receptor for pancreatic cancer chemoprevention
Authors: Mohammed Altaf , Janakiram Naveena B , Suen Chen , Stratton Nicole , Lightfoot Stanley , Singh Anil , Pathuri Gopal , Ritchie Rebekah , Madka Venkateshwar , Rao Chinthalapally V
Published: July 2019

Gastrin signaling mediated through cholecystokinin‐2 receptor (CCK2R) and its downstream molecules is altered in pancreatic cancer. CCK2R antagonists, YF476 (netazepide) and JNJ‐26070109, were tested systematically for their effect on pancreatic intraepithelial neoplasia (PanIN) progression to pancreatic ductal adenocarcinoma (PDAC) in KrasG12D mice. After dose selection using wild‐type mice, six‐week‐old p48Cre/+‐LSL‐KrasG12D (22‐24 per group) genetically engineered mice (GEM) were fed AIN‐76A diets containing 0, 250, or 500 ppm JNJ‐26070109 or YF‐476 for 38 weeks. At termination, pancreata were collected, weighed, and evaluated for PanINs and PDAC. Results demonstrated that control‐diet‐fed mice showed 69% (males) and 33% (females) incidence of PDAC. Administration of low and high dose JNJ‐26070109 inhibited the incidence of PDAC by 88% and 71% (P < .004) in male mice and by 100% and 24% (P > .05) in female mice, respectively. Low and high dose YF476 inhibited the incidence of PDAC by 74% (P < .02) and 69% (P < .02) in male mice and by 45% and 33% (P > .05) in female mice, respectively. Further, transcriptome analysis showed downregulation of Cldn1, Sstr1, Apod, Gkn1, Siglech, Cyp2c44, Bnc1, Fmo2, 623169, Kcne4, Slc27a6, Cma1, Rho GTPase activating protein 18, and Gpr85 genes in JNJ‐26070109‐treated mice compared with untreated mice. YF476‐treated mouse pancreas showed downregulation of Riks, Zpbp, Ntf3, Lrrn4, Aass, Skint3, Kcnb1, Dgkb, Ddx60, and Aspn gene expressions compared with untreated mouse pancreas. Overall, JNJ‐26070109 showed better chemopreventive efficacy than YF476. However, caution is recommended when selecting doses, as the agents appeared to exhibit gender‐specific effects.
Fully automated identification of skin morphology in raster‐scan optoacoustic mesoscopy using artificial intelligence
Authors: Moustakidis Serafeim , Omar Murad , Aguirre Juan , Mohajerani Pouyan , Ntziachristos Vasilis
Published: July 2019

Purpose

Identification of morphological characteristics of skin lesions is of vital importance in diagnosing diseases with dermatological manifestations. This task is often performed manually or in an automated way based on intensity level. Recently, ultra‐broadband raster‐scan optoacoustic mesoscopy (UWB‐RSOM) was developed to offer unique cross‐sectional optical imaging of the skin. A machine learning (ML) approach is proposed here to enable, for the first time, automated identification of skin layers in UWB‐RSOM data.

Materials and methods

The proposed method, termed SkinSeg, was applied to coronal UWB‐RSOM images obtained from 12 human participants. SkinSeg is a multi‐step methodology that integrates data processing and transformation, feature extraction, feature selection, and classification. Various image features and learning models were tested for their suitability at discriminating skin layers including traditional machine learning along with more advanced deep learning algorithms. An support vector machines‐based postprocessing approach was finally applied to further improve the classification outputs.

Results

Random forest proved to be the most effective technique, achieving mean classification accuracy of 86.89% evaluated based on a repeated leave‐one‐out strategy. Insights about the features extracted and their effect on classification accuracy are provided. The highest accuracy was achieved using a small group of four features and remained at the same level or was even slightly decreased when more features were included. Convolutional neural networks provided also promising results at a level of approximately 85%. The application of the proposed postprocessing technique was proved to be effective in terms of both testing accuracy and three‐dimensional visualization of classification maps.

Conclusions

SkinSeg demonstrated unique potential in identifying skin layers. The proposed method may facilitate clinical evaluation, monitoring, and diagnosis of diseases linked to skin inflammation, diabetes, and skin cancer.
Molecular indicators of denervation in aging human skeletal muscle
Authors: Soendenbroe Casper , Heisterberg Mette F. , Schjerling Peter , Karlsen Anders , Kjaer Michael , Andersen Jesper L. , Mackey Abigail L.
Published: July 2019

Introduction

Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation.

Methods

Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65–94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn), and neural cell adhesion molecule (NCAM).

Results

Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65–94 years) was negatively associated with AchRγ mRNA.

Discussion

Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.
Magnetic resonance Spectrum simulator (MARSS), a novel software package for fast and computationally efficient basis set simulation
Authors: Landheer Karl , Swanberg Kelley M. , Juchem Christoph
Published: July 2019

The aim of this study was to develop a novel software platform for the simulation of magnetic resonance spin systems, capable of simulating a large number of spatial points (1283) for large in vivo spin systems (up to seven coupled spins) in a time frame of the order of a few minutes. The quantum mechanical density‐matrix formalism is applied, a coherence pathway filter is utilized for handling unwanted coherence pathways, and the 1D projection method, which provides a substantial reduction in computation time for a large number of spatial points, is extended to include sequences of an arbitrary number of RF pulses. The novel software package, written in MATLAB, computes a basis set of 23 different metabolites (including the two anomers of glucose, seven coupled spins) with 1283 spatial points in 26 min for a three‐pulse experiment on a personal desktop computer. The simulated spectra are experimentally verified with data from both phantom and in vivo MEGA‐sLASER experiments. Recommendations are provided regarding the various assumptions made when computing a basis set for in vivo MRS with respect to the number of spatial points simulated and the consideration of relaxation.
Organizational sensegiving: Indicators and nonprofit signaling
Authors: Levine Daniel Jamie , Eckerd Adam
Published: July 2019

Resource acquisition depends upon the agreement between an organization's sense of identity and the perceptions of organizational identity held by resource providers. To smooth the flow of resources and buffer against potential issues, organizations seek to manage external perceptions and, to the extent possible, control their organizational identity. Using exploratory factor analysis, we examine the data from 300 GuideStar profiles to develop a sense of how nonprofit organizations “give sense” to resource providers and attempt to manage their organizational identity. We find evidence of three sensegiving strategies. We then use a seemingly unrelated regression model to examine the relationship between these strategies and revenue outcomes, finding evidence that (a) nonprofit organizations demonstrate intentional sensegiving, and (b) different sensegiving approaches are related to different income streams.
Experimental investigation of surface defects in low‐power CO2 laser engraving of glass fiber‐reinforced polymer composite
Authors: Prakash Shashi
Published: July 2019

Glass fiber‐reinforced polymers (GFRP) possess excellent structural qualities making it superior to steels and various allied materials in terms of strength and durability. The machining of GFRPs is relatively tough and slow on conventional machining systems. Also, tool life can be significantly reduced while working on such advanced materials with conventional machining processes. Lasers have been proved as a very efficient machine tool for cutting of several newly developed engineering materials. Low‐power lasers can be effectively used for ablating a thin layer or inducing customized surface structures on the target surfaces. Polymer‐reinforced composites act as a multilayered material having significant difference in melting and vaporization temperature between glass fibers and polymer matrix. In this experimental work, GFRP was used as a substrate material and a low‐power CO2 laser was utilized for engraving over a GFRP surface at different amounts of energy deposition. Unidirectional GFRPs were engraved by laser‐engraving process at three different defocusing positions with the overall objective to investigate the surface quality and engraving depth. To study anisotropic effects of the material, laser engraving was performed into two different directions, that is, along the fiber and perpendicular to fiber. Surface roughness and machined depth were investigated as a function of fiber direction. It was observed that surface roughness as well as ablation depth of the laser‐engraved surface hugely depend on fiber direction. It was also found that defocusing results in adverse surface conditions unlike other materials. Based on the results obtained, simple regression‐based mathematical models have been developed to predict engraved depth as a function of energy deposition. The developed models were validated for engraving depth up to 300 μm.
The comparative effectiveness of fourth‐line drugs in resistant hypertension: An application in electronic health record data
Authors: Sinnott Sarah‐Jo , Smeeth Liam , Williamson Elizabeth , Perel Pablo , Nitsch Dorothea , Tomlinson Laurie A. , Douglas Ian J.
Published: July 2019

Purpose

To examine the utility of electronic health records from a routine care setting in assessing comparative effectiveness of fourth‐line anti‐hypertensive drugs to treat resistant hypertension.

Methods

We conducted a cohort study using the Clinical Practice Research Datalink: a repository of electronic health records from UK primary care. We identified patients newly prescribed fourth‐line anti‐hypertensive drugs (aldosterone antagonist , beta‐blocker, or alpha‐blocker). Using propensity score–adjusted Cox proportional hazards models, we compared the incidence of the primary outcome (composite of all‐cause mortality, stroke, and myocardial infarction) between patients on different fourth‐line drugs. AA was the reference drug in all comparisons. Secondary outcomes were individual components of the primary outcome, blood pressure changes, and heart failure. We used a negative control outcome, Herpes Zoster, to detect unmeasured confounding.

Results

Overall, 8639 patients were included. In propensity score–adjusted analyses, the hazard ratio for the primary outcome was 0.81 (95% CI, 0.55‐1.19) for beta‐blockers and 0.68 (95% CI, 0.46‐0.96) for alpha‐blockers versus AA. Findings for individual cardiovascular outcomes trended in a more plausible direction, albeit imprecise. A trend for a protective effect for Herpes Zoster across both comparisons was seen.

Conclusions

A higher rate of all‐cause death in the AA group was likely due to unmeasured confounding in our analysis of the composite primary outcome, supported by our negative outcome analysis. Results for cardiovascular outcomes were plausible, but imprecise due to small cohort sizes and a low number of observed outcomes.
Preparation of transparent nanocomposites from UV‐ and thermo‐curable epoxyacrylate and graphene oxide for the application of corrosion protection coatings
Authors: Syu Cian‐Fan , Lin Yen‐Ting , Yeh Yih‐Chang , Don Trong‐Ming
Published: July 2019

In this study, we report UV‐ and thermo‐curable epoxyacrylate/graphene oxide (EA/GO) nanocomposites that present good transparency, excellent pencil hardness and promising improvement in corrosion protection. A dual‐curable EA oligomer with one terminal epoxide and one double bond at the other end was synthesized by reaction of diglycidyl ether of bisphenol‐A and acrylic acid. After mixing EA and GO with the curing agents and reactive diluent followed by UV cure and thermo‐cure, the resulting EA/GO films on a glass slide with GO loading up to 3 phr exhibited over 86% light transmittance. Furthermore, the pencil hardness was enhanced from 3H for EA to 6H for the EA/GO composite at 2 phr GO loading. The corrosion protection of the EA/GO coatings was evaluated by a potentiodynamic polarization technique and electrochemical impedance spectra. The corrosion potential (Ecorr) of the EA/GO‐coated steel increased with increasing GO loading. Meanwhile, Nyquist and Bode plots indicated that the higher the GO content in the EA/GO coating was, the higher was the coating resistance and also the charge transfer resistance after immersion in salt solution. All these results proved that the GO had positive effects on enhancement of the corrosion resistance. The improved corrosion protection by the EA/GO coatings was mainly due to the enhanced hydrophobicity, the deviation of electron transfer and the increased tortuosity of the diffusion path. The improved corrosion protection and hardness together with the useful dual‐curability make the EA/GO nanocomposite a competitive candidate for corrosion protection coatings. © 2019 Society of Chemical Industry
Development of an Analytical Method for the Metaproteomic Investigation of Bioaerosol from Work Environments
Authors: Piovesana Susy , Capriotti Anna Laura , Foglia Patrizia , Montone Carmela Maria , La Barbera Giorgia , Zenezini Chiozzi Riccardo , Laganà Aldo , Cavaliere Chiara
Published: July 2019

The metaproteomic analysis of air particulate matter provides valuable information about the properties of bioaerosols in the atmosphere and their influence on climate and public health. In this work, a new method for the extraction and analysis of proteins in airborne particulate matter from quartz microfiber filters is developed. Different protein extraction procedures are tested to select the best extraction protocol based on protein recovery. The optimized method is tested for the extraction of proteins from spores of ubiquitous bacteria species and used for the metaproteomic characterization of filters from three work environments. In particular, ambient aerosol samples are collected in a composting plant, in a wastewater treatment plant, and in an agricultural holding. A total of 179, 15, 205, and 444 proteins are identified in composting plant, wastewater treatment plant, and agricultural holding, (cow stable and blending plant), respectively. In agreement with the major categories of primary biological aerosol particles, all identified proteins originated primarily from fungi, bacteria, and plants. The paper is the first metaproteomic study applied to bioaerosol samples collected in occupationally relevant environmental sites and, even though not aimed at monitoring the risk exposure of workers, it provides information on the possible exposure in the working environmental sites.
Engaging with plants in an urban environment through street art and design
Authors: Sachdev Geetanjali
Published: July 2019

Societal Impact Statement

Engaging people with botanical street art and design is a good way to draw attention to the botanical world. Here, the importance of plants to people's everyday life in India is highlighted through street art and design. By focusing on the plant motifs present in everyday urban environments, educators can shine a light on the deep historical and cultural connections that we share with plants. This could be a vital tool for those wishing to draw attention to plants in urban settings and highlight their importance for human existence and life on Earth, and as a possible route to counteract plant blindness in urban settings.

Summary

This article explores plant motifs in street art and design artifacts in India, in order to gain insights toward a pedagogical framework for studying plants in the context of higher education in art and design. The study was carried out as a visual ethnography of the representational use of plants in the public environment, in street art and design artifacts; theoretical implications are drawn from the findings of the ethnographic work for a public pedagogy concerning plants. Across India, street art and craft practices engage with plant representations and plant motifs through diverse materials, techniques, and media. Plant motifs are encountered across personal, professional, and official contexts. Their presence is, in many cases, explained by beliefs in Hinduism, the dominant religion in India. Several historical and culturally meaningful motivations could thereby be established for the use of botanical themes by street artists and craftspeople, which are readily available as a resource for public pedagogy about plants. Plant motifs are common in street art and design artifacts in India. Clear motivations for the public use of these motifs are outlined in the article. The combination of widespread plant motifs and the rich tapestry of motivations for presenting them in the public space offers good scope for a public pedagogy curriculum that highlights the traditional and culturally rich symbolic function of plants in people's lives in this region.
The viability of a breeding programme for ash in the British Isles in the face of ash dieback
Authors: Plumb William J. , Coker Timothy L. R. , Stocks Jonathan J. , Woodcock Paul , Quine Christopher P. , Nemesio‐Gorriz Miguel , Douglas Gerry C. , Kelly Laura J. , Buggs Richard J. A.
Published: July 2019

Societal Impact Statement

The current ash dieback epidemic in Europe caused by Hymenoscyphus fraxineus poses a key question to policy makers: whether or not to commit time and resources to the initiation of a breeding programme for the development of more resistant ash, as a long‐term policy of adaptation to the epidemic. Here we review current evidence on the potential viability of such a programme, from a biological perspective. We conclude that a breeding programme for ash aimed at resistance to current strains of H. fraxineus in the British Isles is biologically feasible.

To evaluate the viability and feasibility of a future breeding programme to produce trees resistant to an emerging pest or pathogen, it is helpful to ask the following questions: How much variation in resistance exists in tree populations? To what extent is this resistance heritable? How many genetic loci are involved? What level of resistance is found in other species of the same genus? Here, we survey current knowledge of these issues in relation to the degree of resistance of European ash (Fraxinus excelsior) to H. fraxineus, the fungus causing ash dieback (ADB). Several studies have found a low frequency of heritable resistance in F. excelsior populations, which seems to be determined by many genetic loci. This suggests that a breeding programme is viable and that natural selection may also increase the mean resistance of populations over time. More research is needed on the genetic basis of resistance to ADB to understand how quickly natural selection can operate in woodlands and what acceleration may be possible in breeding programmes, including via use of genetic markers. Hybrid breeding programmes may also be a possibility, as some ash species appear to be more resistant to ADB than is F. excelsior, but more research is needed on this issue. We do not yet know if it will be possible to breed F. excelsior to have resistance to both ADB and the emerging threat of emerald ash borer. We recommend short‐term mitigation measures for the ADB epidemic and future research directions.
Conditions for connectivity of incomplete block designs
Authors: Godolphin Janet
Published: July 2019

In experimental situations where observation loss is common, it is important for a design to be robust against breakdown. For incomplete block designs, with one treatment factor and a single blocking factor, conditions for connectivity and robustness are developed using the concepts of treatment and block partitions, and of linking blocks. Lower bounds are given for the block breakdown number in terms of parameters of the design and its support. The results provide guidance for construction of designs with good robustness properties.
A proposed variable parameter control chart for monitoring the multivariate coefficient of variation
Authors: Chew XinYing , Khoo Michael Boon Chong , Khaw Khai Wah , Yeong Wai Chung , Chong Zhi Lin
Published: July 2019

An efficient process monitoring system is important for achieving sustainable manufacturing. The control charting technique is one of the most effective techniques to monitor process quality. In certain processes where the process mean and variance are not independent of one another, the coefficient of variation (CV), which measures the ratio of the standard deviation to the mean, should be monitored. In line with industrial settings, where at least two or more variables are monitored simultaneously in most processes, this paper proposes a variable parameter (VP) chart to monitor the multivariate CV (MCV). Formulae and algorithms to optimize the various performance measures are discussed. The proposed VP MCV chart is designed based on a Markov chain approach. The performance comparison shows that the proposed VP MCV chart prevails over the existing MCV charts, in terms of the average time to signal (ATS), standard deviation of the time of signal (SDTS), and expected average time to signal (EATS) criteria. An example is presented to illustrate the implementation of the proposed VP MCV chart.
Neurofibromatosis type 1‐associated malignant peripheral nerve sheath tumour carcinomatous pleurisy: an autopsy case
Authors: Furukawa Marie , Ota Hiroki , Nakamura Yasuhiko , Nihonyanagi Yasuhiro , Tochigi Naobumi , Homma Sakae
Published: July 2019

A 57‐year‐old man with neurofibromatosis type 1 (NF‐1) and intrathoracic meningoceles was admitted to hospital after presenting with neck pain and progressive dyspnoea. On admission, a chest computed tomography scan demonstrated right pleural effusion, neck tumour, intrathoracic meningoceles, and rib metastasis. The myelography showed no transportation between the intrathoracic meningoceles and pleural cavity. As a result, these radiological finding indicated the potential for malignant transformation. The appearance of the right pleural effusion was bloody and had no malignant cells. We biopsied the neck tumour, and the tissue showed glass‐like materials but no malignant cells. At 1 month after admission, he developed bladder–rectal disorder, syndrome of inappropriate secretion of antidiuretic hormone, and paralysis of both legs and later died. An autopsy demonstrated glass‐like material in the neck tumour, which was surrounded by malignant cells. NF‐1 appears to have progressed to a malignant peripheral nerve sheath tumour in this patient.
Habitat metrics based on multi‐temporal Landsat imagery for mapping large mammal habitat
Authors: Oeser Julian , Heurich Marco , Senf Cornelius , Pflugmacher Dirk , Belotti Elisa , Kuemmerle Tobias
Published: July 2019

Up‐to‐date and fine‐scale habitat information is essential for managing and conserving wildlife. Studies assessing wildlife habitat commonly rely on categorical land‐cover maps as predictors in habitat models. However, broad land‐cover categories often do not adequately capture key habitat features and generating robust land‐cover maps is challenging and laborious. Continuous variables derived directly from satellite imagery provide an alternative for capturing land‐cover characteristics in habitat models. Improved data availability and processing capacities now allow integrating all available images from medium‐resolution sensors in compositing approaches that derive spectral‐temporal metrics at the pixel level, summarizing spectral responses over time. In this study, we assessed the usefulness of such metrics derived from Landsat imagery for mapping wildlife habitat. We categorize spectral‐temporal metrics into habitat metrics characterizing different aspects of wildlife habitat. Comparing the performance of these metrics against categorical land‐cover maps in habitat models for lynx, red deer and roe deer, we found that models using habitat metrics consistently outperformed models based on categorical land‐cover maps, with average improvements of 13.7% in model AUC and 9.7% in the Continuous Boyce Index. Performance increases were larger for seasonal habitat models, indicating that the habitat metrics capture intra‐annual variability in habitat conditions better than land‐cover maps. Comparing suitability maps to ancillary data further revealed that our habitat metrics were sensitive to fine‐scale heterogeneity in habitat associated with forest structure. Overall, our study highlights the considerable potential of Landsat‐based spectral temporal metrics for assessing wildlife habitat. Given these metrics can be derived directly and in an automatized fashion from globally and freely available Landsat imagery, they open up new possibilities for monitoring habitat dynamics in space and time.
Application of surface science techniques to study a gilded Egyptian funerary mask: A multi‐analytical approach
Authors: Gard Faramarz Sahra , Daizo Maria Belén , Santos Diego Maximiliano , Halac Emilia Betty , Freire Eleonora , Reinoso María , Bozzano Patricia Beatriz , Dominguez Silvia Adriana , Montero Ricardo Jesús
Published: July 2019

A wide range of analytical techniques has been used to study an Egyptian funerary mask of the Ptolemaic period (305‐30 bc). Secondary electron (SE) and back‐scattering (BS) images, recorded by a scanning electron microscope (SEM), provided a detailed representation of the metallurgical techniques used to construct the gilded mask. It is confirmed, that the golden leaf used to cover the mask is the product of an antique refinery practice, so called, cementation process of naturally occurring alloy of gold and silver, namely electrum. Complementary results of SEM‐electron dispersion spectroscopy (EDS) and electron probe microanalysis (EPMA)–wavelength dispersion spectroscopy (WDS) provided chemical compositions of the golden leaf as well as in the plaster base of the mask. X‐ray photoemission spectroscopy (XPS) revealed the presence of Au, Ag, Si, S, Cl, Ca, and N, in addition to O and C. Relative concentration of Au/Ag at the surface has been measured by XPS to be 70% to 30%. XPS depth profiling verified silver‐enrichment at the surface, as ratio of gold to silver is measured to be 80% to 20% at the depth of 15 nm. XPS chemical mapping images of gold and silver confirmed a rather inhomogeneous character of Au/Ag relative concentration at the surface. The main diffraction peaks in the X‐ray diffraction (XRD) spectrum coincide with diffraction peaks of pure gold, silver metals, and magnesium calcite Mg0.03Ca0.97CO3. Whereas, Raman spectroscopy results implied the existence of Ag2S, a tarnishing compound, on the golden area of the mask.
Dynamic human contact prediction based on naive Bayes algorithm in mobile social networks
Authors: Zeng Feng , Yao Lan , Wu Baoling , Li Wenjia , Meng Lin
Published: July 2019

Human contact prediction is a challenging task in mobile social networks. The existing prediction methods are based on the static network structure, and directly applying these static prediction methods to dynamic network prediction is bound to reduce the prediction accuracy. In this paper, we extract some important features to predict human contacts and propose a novel human contact prediction method based on naive Bayes algorithm, which is suitable for dynamic networks. The proposed method takes the ever‐changing structure of mobile social networks into account. First, the past time is partitioned into many periods with equal intervals, and each period has a feature matrix of all node pairs. Then, with the feature matrixes used for classifiers training based on naive Bayes algorithm, we can get a classifier for each time period. At last, the different weights are assigned to the classifiers according to their importance to contact prediction, and all classifiers are weighted combination into the final prediction classifier. The extensive experiments are conducted to verify the effectiveness and superiority of the proposed method, and the results show that the proposed method can improve the prediction accuracy and TP Rate to a large extent. Besides, we find that the size of time interval has a certain impact on the clustering coefficient of mobile social networks, which further affects the prediction accuracy.
Esculetin induces cell cycle arrest and apoptosis in human colon cancer LoVo cells
Authors: Choi Yong J. , Lee Chang M. , Park See‐Hyoung , Nam Myeong J.
Published: July 2019

We investigated the anti‐cancer effects of ESC in human colon cancer LoVo cells. Cell counting assay results showed that ESC inhibited the proliferation of LoVo cells. Cell cycle arrest results showed that cell cycle was arrested during the G0/G1 phase in the ESC‐treated LoVo cells. Western blot results showed that the cell cycle inhibitory proteins p53, p27, and p21 were increased, and cyclin D1, the cell cycle progressive protein, was decreased. Sp1 is a transcription factor regulating cell proliferation, was decreased in the ESC‐treated LoVo cells. Annexin V/propidium iodide staining results showed that ESC induces apoptosis in LoVo cells. Western blot results showed that Bax, cleaved caspase ‐3, ‐7, ‐9, and poly(ADP‐ribose) polymerase, which are proapoptotic proteins, were increased and the antiapoptotic protein Bcl‐2 was decreased. Taken together, ESC induced apoptosis and has an anti‐cancer effect in LoVo cells.
Current perspectives on biosimilars
Authors: Agbogbo Frank K , Ecker Dawn M , Farrand Allison , Han Kevin , Khoury Antoine , Martin Aaron , McCool Jesse , Rasche Ulrike , Rau Tiffany D , Schmidt David , Sha Ma , Treuheit Nicholas
Published: July 2019

In this work, an overview of the biosimilars market, pipeline and industry targets is discussed. Biosimilars typically have a shorter timeline for approval (8 years) compared to 12 years for innovator drugs and the development cost can be 10–20% of the innovator drug. The biosimilar pipeline is reviewed as well as the quality management system (QMS) that is needed to generate traceable, trackable data sets. One difference between developing a biosimilar compared to an originator is that a broader analytical foundation is required for biosimilars and advances made in developing analytical similarity to characterize these products are discussed. An example is presented on the decisions and considerations explored in the development of a biosimilar and includes identification of the best process parameters and methods based on cost, time, and titer. Finally factors to consider in the manufacture of a biosimilar and approaches used to achieve the target-directed development of a biosimilar are discussed.