bluuebunny/crossref_metadata_2025 huggingface dataset:
Toxoplasma gondii excreted‐secreted antigens suppress Foxp3 via PI3K‐AKT‐mTOR signaling pathway
Authors: Chen Jinling , Hu Liang , Wang Jingjing , Cao Yangqing , Zhu Dandan , Chen Liuting , Duan Yinong
Published: May 2019

Toxoplasma gondii excreted‐secreted antigens (ESA) cause spontaneous abortion or fetal teratogenesis during the pregnancy in mice, especially in the early stage. Those adverse pregnancy outcomes are due to the deficit in regulatory T cells (Tregs). Forkhead box P3 (Foxp3), a critical transcription factor, modulates Tregs differentiation and its function. Besides, phosphatidylinositol 3‐kinase‐protein kinase B‐mammalian target of rapamycin (PI3K‐AKT‐mTOR) signaling network is implicated in interfering with Foxp3 induction. We previously demonstrated that ESA diminished the number of Tregs and inhibited its function. And ESA suppressed Foxp3 expression via the attenuation of transforming growth factor β RII/Smad2/Smad3/Smad4 pathway. The current study aimed to investigate whether the PI3K‐AKT‐mTOR signaling network is involved in Foxp3 downregulation induced by ESA. We found that ESA upregulated PI3K, P‐AKT, mTOR, and P‐mTOR. Knockdown of PI3K cooperated with ESA to restore Foxp3 expression mediated by ESA. This suppressive role of ESA on Foxp3 expression was abrogated by AKT inhibitor. In addition, neutralization of Toll‐like receptor 4 could restore the expression of Foxp3, PI3K, and its downstream effectors induced by ESA. Collectively, the findings indicated that ESA inhibited Foxp3 expression via the upregulation of PI3K‐AKT‐mTOR signaling pathway.
MRI‐based radiomics signature for tumor grading of rectal carcinoma using random forest model
Authors: He Bo , Ji Tao , Zhang Hong , Zhu Yun , Shu Ruo , Zhao Wei , Wang Kunhua
Published: May 2019

The present study aimed to construct prospective models for tumor grading of rectal carcinoma by using magnetic resonance (MR)‐based radiomics features. A set of 118 patients with rectal carcinoma was analyzed. After imbalance‐adjustments of the data using Synthetic Minority Oversampling Technique (SMOTE), the final data set was randomized into the training set and validation set at the ratio of 3:1. The radiomics features were captured from manually segmented lesion of magnetic resonance imaging (MRI). The most related radiomics features were selected using the random forest model by calculating the Gini importance of initial extracted characteristics. A random forest classifier model was constructed using the top important features. The classifier model performance was evaluated via receive operator characteristic curve and area under the curve (AUC). A total of 1,131 radiomics features were extracted from segmented lesion. The top 50 most important features were selected to construct a random forest classifier model. The AUC values of grade 1, 2, 3, and 4 for training set were 0.918, 0.822, 0.775, and 1.000, respectively, and the corresponding AUC values for testing set were 0.717, 0.683, 0.690, and 0.827 separately. The developed feature selection method and machine learning‐based prediction models using radiomics features of MRI show a relatively acceptable performance in tumor grading of rectal carcinoma and could distinguish the tumor subjects from the healthy ones, which is important for the prognosis of cancer patients.
Upregulation of AKT1 and downregulation of AKT3 caused by dysregulation of microRNAs contributes to pathogenesis of hemangioma by promoting proliferation of endothelial cells
Authors: Lu Shuo , Chen Lingling , Tang Li
Published: May 2019

This study aimed to verify the differentially expressed miRNAs (microRNAs) in hemangioma, and explore their roles in the pathogenesis of hemangioma in vivo and ex vivo. Real‐time polymerase chain reaction (PCR) and western blot were used to measure reported differentially expressed miRNAs and their potential targets. In‐silicon analysis and luciferase assay were conducted to find the target of miR‐15a and miR‐205. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay and flowcytometry were performed to examine the effect of dysregulation of miR‐15a and miR‐205 on the proliferation and apoptosis of endothelial cells. Among all candidate miRNAs, only miR‐205 level was significantly downregulated whereas miR‐15a was evidently upregulated in the hemangioma group. Accordingly, AKT3 was validated to be the direct target of miR‐15a and miR‐205. Using real‐time PCR, the level of AKT1 was much higher in hemangioma group, whereas level of AKT3 was much lower in the hemangioma group, and in general expression level of ATK was upregulated in the hemangioma group. Furthermore, the ATK1 level of cells transfected with miR‐205 mimics and ATK1 siRNA was substantially downregulated, and anti‐miR‐205 mimic significantly improved the level of AKT1, and meanwhile the level of ATK3 and PTEN were remarkably suppressed after transfection with miR‐15a mimics and ATK3 siRNA, whereas notably overexpressed after introduction of anti‐miR‐15a. And miR‐15a, AKT3 siRNA and anti‐miR‐205 evidently induced viability, and miR‐205, AKT1 siRNA, and anti‐miR‐15a obviously promoted apoptosis of cells.

Conclusion

miR‐15a and miR‐205 had different expression in hemangioma, may be novel therapeutic targets in the treatment of hemangioma by targeting AKT3 and AKT1.
RECK suppresses interleukin‐17/TRAF3IP2‐mediated MMP‐13 activation and human aortic smooth muscle cell migration and proliferation
Authors: Mummidi Srinivas , Das Nitin A. , Carpenter Andrea J. , Yoshida Tadashi , Yariswamy Manjunath , Mostany Ricardo , Izadpanah Reza , Higashi Yusuke , Sukhanov Sergiy , Noda Makoto , Siebenlist Ulrich , Rector Randy S. , Chandrasekar Bysani
Published: May 2019

Sustained inflammation and matrix metalloproteinase (MMP) activation contribute to vascular occlusive/proliferative disorders. Interleukin‐17 (IL‐17) is a proinflammatory cytokine that signals mainly via TRAF3 Interacting Protein 2 (TRAF3IP2), an upstream regulator of various critical transcription factors, including AP‐1 and NF‐κB. Reversion inducing cysteine rich protein with kazal motifs (RECK) is a membrane‐anchored MMP inhibitor. Here we investigated whether IL‐17A/TRAF3IP2 signaling promotes MMP‐13‐dependent human aortic smooth muscle cell (SMC) proliferation and migration, and determined whether RECK overexpression blunts these responses. Indeed, IL‐17A treatment induced (a) JNK, p38 MAPK, AP‐1, NF‐κB, and CREB activation, (b) miR‐21 induction, (c) miR‐27b and miR‐320 inhibition, (d) MMP‐13 expression and activation, (e) RECK suppression, and (f) SMC migration and proliferation, all in a TRAF3IP2‐dependent manner. In fact, gain of TRAG3IP2 function, by itself, induced MMP‐13 expression and activation, and RECK suppression. Furthermore, treatment with recombinant MMP‐13 stimulated SMC migration in part via ERK activation. Importantly, RECK gain‐of‐function attenuated MMP‐13 activity without affecting its mRNA or protein levels, and inhibited IL‐17A‐ and MMP‐13‐induced SMC migration. These results indicate that increased MMP‐13 and decreased RECK contribute to IL‐17A‐induced TRAF3IP2‐dependent SMC migration and proliferation, and suggest that TRAF3IP2 inhibitors or RECK inducers have the potential to block the progression of neointimal thickening in hyperplastic vascular diseases.
Genome‐wide analysis reveals alcohol dehydrogenase 1C and secreted phosphoprotein 1 for prognostic biomarkers in lung adenocarcinoma
Authors: Shen Xiao‐Yan , Liu Xiao‐Ping , Song Cong‐Kuan , Wang Yu‐Jin , Li Sheng , Hu Wei‐Dong
Published: May 2019

To seek out novel promising biomarkers for predicting lung adenocarcinoma (LUAD) prognosis, we conducted this study. First, 279 upregulated and 37 downregulated differentially expressed genes were obtained from LUAD and para‐carcinoma tissues by the Affymetrix GeneChip Human Transcriptome Array. Then, we randomly classified samples of LUAD data set GSE31210 as training and testing sets in a 1:1 ratio. Alcohol dehydrogenase 1C (ADH1C) and secreted phosphoprotein 1 (SPP1) were finally identified correlating with the LUAD survival through least absolute shrinkage and selection operator penalized Cox proportion hazards regression model, and applied to build a 2‐gene signature related to prognosis in training set. Univariate and multivariable survival analyses suggested that overall survival (OS) and relapse‐free survival (RFS) in the 2‐gene signature low‐risk group were better than the high‐risk group. Kaplan–Meier curves proved that elevated ADH1C expression and reduced SPP1 expression were related to better OS and RFS. Besides, the SPP1 expressed higher in LUAD than para‐carcinoma tissues using quantitative reverse transcription polymerase chain reaction assay. Finally, the association between the two genes and clinicopathological parameters in 80 LUAD were analyzed, it is suggested that SPP1 was relevant to epidermal growth factor receptor mutation. These findings indicated that ADH1C and SPP1 might be novel promising biomarkers for predicting LUAD prognosis.
Pharmacokinetics of Lapatinib, a Nonrenally Cleared Drug, in Patients With End‐Stage Renal Disease on Maintenance Hemodialysis
Authors: Pai Sudhakar M. , Chaikin Philip , Berg Jolene Kay
Published: May 2019

Lapatinib, a tyrosine kinase inhibitor, is approved for the treatment of breast cancer. The literature shows that it is metabolized by CYP3A4 and eliminated predominantly (>90%) by the fecal route, with minimal (<2%) renal elimination in healthy subjects (dose of 250 mg); in cancer patients, renal elimination is minimal at therapeutic doses. For nonrenally cleared drugs, while there is ample evidence of pharmacokinetic alterations secondary to renal impairment‐induced effects on drug metabolizing enzymes and/or transporters, the effect of end‐stage renal disease (ESRD) on lapatinib pharmacokinetics has not been determined. Rather, as stated in the drug's label, the expectation is lack of effect of renal impairment on lapatinib pharmacokinetics based on its minimal renal elimination. The current report addresses this gap with pharmacokinetic data (obtained in a 1‐way drug interaction study) in ESRD patients (n = 11) on maintenance hemodialysis and compared with published data in 37 healthy subjects in 3 separate studies. Following a 250‐mg oral dose in ESRD patients, the median tmax was 3.0 hours, and geometric mean (95%CI) values for Cmax, AUCinf, and t1/2 were 349 ng/mL (245–499 ng/mL), 4410 ng·h/mL (2960–6580 ng·h/mL), and 14.8 hours (9.7–22.5 hours), respectively. These parameters approximated published values in healthy subjects and demonstrated that renal impairment and hemodialysis did not affect lapatinib pharmacokinetics. The results of the present study in this renally impaired population, the only such information available to date, support the drug's label and are valuable in view of the recognized difficulties in enrolling organ‐impaired patients in oncology trials.
Dapivirine vaginal ring for HIV prevention: modelling health outcomes, drug resistance and cost‐effectiveness
Authors: Glaubius Robert , Ding Yajun , Penrose Kerri J , Hood Greg , Engquist Erik , Mellors John W , Parikh Urvi M , Abbas Ume L
Published: May 2019

Introduction

A vaginal ring containing dapivirine is effective for HIV prevention as pre‐exposure prophylaxis (PrEP). We evaluated the potential epidemiological impact and cost‐effectiveness of dapivirine vaginal ring PrEP among 22‐ to 45‐year‐old women in KwaZulu‐Natal, South Africa.

Methods

Using mathematical modelling, we studied dapivirine vaginal ring PrEP implementation, either unprioritized, or prioritized based on HIV incidence (≥3% per year), age (22 to 29 years) or female sex worker status, alongside the implementation of voluntary medical male circumcision and antiretroviral therapy scaled‐up to UNAIDS Fast‐Track targets. Outcomes over the intervention (2019 to 2030) and lifetime horizons included cumulative HIV infections, life‐years lived, costs and cost‐effectiveness. We assessed the incremental cost‐effectiveness ratios against the revealed willingness to pay ($500) and the standard (2017 per capita gross domestic product; $6161) cost‐effectiveness thresholds for South Africa.

Results

Compared to a reference scenario without PrEP, implementation of dapivirine vaginal ring PrEP, assuming 56% effectiveness and covering 50% of 22 to 29‐year‐old or high‐incidence women, prevented 10% or 11% of infections by 2030 respectively. Equivalent, unprioritized coverage (30%) prevented fewer infections (7%), whereas 50% coverage of female sex workers had the least impact (4%). Drug resistance attributable to PrEP was modest (2% to 4% of people living with drug‐resistant HIV). Over the lifetime horizon, dapivirine PrEP implementation among female sex workers was cost‐saving, whereas incidence‐based PrEP cost $1898 per life‐year gained, relative to PrEP among female sex workers and $989 versus the reference scenario. In a scenario of 37% PrEP effectiveness, PrEP had less impact, but prioritization to female sex workers remained cost‐saving. In uncertainty analysis, female sex worker PrEP was consistently cost‐saving; and over the lifetime horizon, PrEP cost less than $6161 per life‐year gained in over 99% of simulations, whereas incidence‐ and age‐based PrEP cost below $500 per life‐year gained in 61% and 49% of simulations respectively. PrEP adherence and efficacy, and the effectiveness of antiretroviral therapy for HIV prevention, were the principal drivers of uncertainty in the cost‐effectiveness of PrEP.

Conclusions

Dapivirine vaginal ring PrEP would be cost‐saving in KwaZulu‐Natal if prioritized to female sex workers. PrEP's impact on HIV prevention would be increased, with potential affordability, if prioritized to women by age or incidence.
Subversion of host immune responses by otopathogens during otitis media
Authors: Parrish James M , Soni Manasi , Mittal Rahul
Published: May 2019

Otitis media (OM) is one of the most common ear diseases affecting humans. Children are at greater risk and suffer most frequently from OM, which can cause serious deterioration in the quality of life. OM is generally classified into two main types: acute and chronic OM (AOM and COM). AOM is characterized by tympanic membrane swelling or otorrhea and is accompanied by signs or symptoms of ear infection. In COM, there is a tympanic membrane perforation and purulent discharge. The most common pathogens that cause AOM are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis whereas Pseudomonas aeruginosa and Staphylococcus aureus are commonly associated with COM. Innate and adaptive immune responses provide protection against OM. However, pathogens employ a wide arsenal of weapons to evade potent immune responses and these mechanisms likely contribute to AOM and COM. Immunologic evasion is multifactorial, and involves damage to host mucociliary tract, genetic polymorphisms within otopathogens, the number and variety of different otopathogens in the nasopharynx as well as the interaction between the host's innate and adaptive immune responses. Otopathogens utilize host mucin production, phase variation, biofilm production, glycans, as well as neutrophil and eosinophilic extracellular traps to induce OM. The objective of this review article is to discuss our current understanding about the mechanisms through which otopathogens escape host immunity to induce OM. A better knowledge about the molecular mechanisms leading to subversion of host immune responses will provide novel clues to develop effective treatment modalities for OM.
Survey of quality of life, phenotypic expression, and response to treatment in Krabbe leukodystrophy
Authors: Langan Thomas J. , Barczykowski Amy , Jalal Kabir , Sherwood Laura , Allewelt Heather , Kurtzberg Joanne , Carter Randy L.
Published: May 2019

Objectives

To develop a quality of life (QOL) survey for Krabbe disease (KD), and to thereby improve understanding of its phenotypic expression and response to treatment.

Methods

The survey, the Leukodystrophy Quality of Life Assessment (LQLA) and the Vineland Adaptive Behavior Scales were co‐administered to 33 patients or their caretakers. These included the phenotypes of early infantile KD (EIKD; 0‐6 months old at onset), late infantile cases (LIKD; 7‐12 months old at onset), and cases that emerged after 12 months old, late onset (LOKD). The sample included cases with and without stem cell transplantation (SCT). Reliability and concurrent validity were assessed for overall and subscale scores. Analysis of variance tested differences in QOL between phenotypes and transplant groups (none, pre‐, post‐symptom).

Results

Good concurrent validity with the Vineland was shown for total, communication, daily activity, social, and motor scales and good reliability was observed. LOKD cases had better communication skills than either EIKD or LIKD and better overall QOL than EIKD. Analyses of individual items showed that communication items, mostly, contributed significantly to phenotype differences. Presymptomatic SCT significantly improved QOL compared to postsymptomatic SCT or no treatment. Presymptomatically treated patients had near‐normal total scores.

Conclusions

The LQLA is valid and reliable. Despite small sample size, phenotypic demarcation was determined to be due mainly to differences in communication skills. There was a relative enhancement of QOL in LOKD patients, and in those who had presymptomatic SCT. These results apply to the current controversy about recommendations for newborn screening for this condition.
Prevalence, risk factors and clinical characteristics of respiratory syncytial virus–associated lower respiratory tract infections in Kelantan, Malaysia
Authors: Teck Kew Seih , Mac Guad Rhanye , Van Rostenberghe Amin Hans , Hua Gan Siew
Published: May 2019

Respiratory syncytial virus (RSV) is a common pathogen affecting the respiratory tract in infants. To date, there is limited data on RSV occurrence in Malaysia especially in the northeast of Peninsular Malaysia which is significantly affected by the rainy (monsoon) season. This study aimed to determine the prevalence, risk factors (the presence of a male sibling and older school‐age siblings, parental education level, monthly income, chronic lung disease, immunocompromised, being a passive smoker, multipara, breastfeeding, prematurity, congenital heart disease, nursery attendance, and rainy season) as well as clinical manifestations of RSV in hospitalized infants and children with lower respiratory tract infection (LRTI). Patients' nasopharyngeal aspirates were tested for RSV antigen, questionnaires, and seasonal variations were used to assess RSV infection. Approximately 22.6% of children were infected with RSV; mean age 7.68 ± 5.45 months. The peak incidence of RSV as a causative agent for LRTI in infants was less than or equal to 1‐year old (83%) with approximately 50.5% of the affected children in the younger age group (6 months amd below). RSV infection was significantly but independently associated with the rainy season (odds ratio, 3.307; 95% confidence interval, 1.443‐3.688; P < 0.001). The infection was also associated (
P < 0.05) with a higher number of severe clinical courses, poor feeding, vomiting, increased need for medical care and a shorter mean duration of symptoms before hospital admission. Our study suggested administration of the passive prophylaxis for RSV to high‐risk infants during the rainy season in the months of October to January.
Synthesis and Properties of Novel Phenylenediamine Gemini Surfactants
Authors: Xu Hujun , Wang Chen , Lin Liangliang , Xu Jin
Published: May 2019

In the present work, a two‐step method was adopted to synthesize a series of novel Gemini surfactants using N,N‐dimethylalkyl amines (alkyl length = C12, C16 and C18), epichlorohydrin, and n‐phenyllenediamine as starting materials. The products were characterized using mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (1H NMR). Systematic experiments were conducted to evaluate their surface activity, foaming properties, and antibacterial performance. Results showed the critical micelle concentrations (CMC) of the C12‐based, C16‐based, and C18‐based phenylenediamine surfactants were 3.295 × 10−3, 2.532 × 10−4, and 3.140 × 10−4 mol L−1 at 298 K, respectively, with corresponding surface tension (γcmc) values of 28.24, 31.95, and 35.06 mN m−1 under the same conditions. The Gemini surfactants showed not only good surface activity and foaming properties, but also demonstrated good antimicrobial performance against Gram‐positive and Gram‐negative bacteria and fungi.
Optimization of heteroatom doped graphene oxide by deep eutectic solvents and the application for pipette‐tip solid‐phase extraction of flavonoids
Authors: Sun Liping , Deng Qilin , Zhu Tao
Published: May 2019

In order to improve the permeation and adsorption properties of graphene oxide, heteroatoms and deep eutectic solvent were introduced in this study. After being modified, the structural properties of graphene oxide were improved and the materials were applied to the determination of myricetin and rutin in tea sample by pipette‐tip solid‐phase extraction method. The materials were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, X‐Ray diffractomer, energy dispersive spectroscopy, atomic force microscope, and specific surface area by Brunauer–Emmett–Teller N2 adsorption desorption analysis. Meanwhile, they were tested by static and dynamic adsorption. The result showed that the materials after modifying had better adsorption amount for myricetin and rutin than graphene oxide. The calibration graphs of myricetin and rutin in MeOH were linear over 0.10–500.00 µg/mL, and the limits of detection and quantification were in the range of 0.00546–0.0182 µg/mL and 0.00741–0.0247 µg/mL, respectively. A reliable analytical method was developed for recognition targets in tea sample by DES modified nitrogen‐doped graphene oxide with satisfactory extraction recoveries (myricetin 99.77%, rutin 98.14%). It was potential for the rapid purification of myricetin and rutin in tea sample combined with the pipette‐tip solid‐phase extraction.
Enhancing the hospitality customer experience of families with children on the autism spectrum disorder
Authors: Freund Daniela , Cerdan Chiscano Monica , Hernandez-Maskivker Gilda , Guix Mireia , Iñesta Ana , Castelló Montserrat
Published: May 2019

The purpose of this study is to examine intention to travel to accessible accommodations by families of children diagnosed with autism spectrum disorder (ASD), the influence of travel constraints (intrinsic, interactive, and environmental), the severity of disorder, and the families' strategies for coping with such constraints. A structured survey targeted at Spanish families (N = 117) indicated that the intrinsic dimension and the severity of disorder positively influence their intention to travel. The study contributes to extend knowledge about travel constraints related to accessible tourism and provides insights to accommodation providers on how to better enhance the customer experience of families travelling with a child diagnosed with ASD.
GUEST EDITORIAL—SPECIAL ISSUE: Mapping and modelling soil erosion to address societal challenges in a changing world
Authors: Smetanová Anna , Nunes João Pedro , Symeonakis Elias , Brevik Eric , Schindelwolf Marcus , Ciampalini Rossano
Published: May 2019

Special issue Mapping and Modelling Soil Erosion to Address Societal Challenges in a Changing World presents advances in interdisciplinary methodologies for the study of the soil erosion/land management/climate change nexus, with a focus on societal challenges linked to land degradation. Contribution of 22 research teams active in 17 countries all over the world provided a global perspective on how soil erosion research contributes to meet societal challenges of our time. The authors conclude that (a) inclusive representation of non‐linear system feedback between erosion and land management; (b) combination of mapping, measuring, monitoring, and modelling methods on different temporal and spatial scales; and (c) inclusive, cooperative interdisciplinary research approaches are inevitable to support management aiming for land degradation neutrality.
The mechanism(s) of action of antioxidants: From scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites
Authors: Hunyadi Attila
Published: May 2019

Small molecule, dietary antioxidants exert a remarkably broad range of bioactivities, and many of these can be explained by the influence of antioxidants on the redox homeostasis. Such compounds help to modulate the levels of harmful reactive oxygen/nitrogen species, and therefore participate in the regulation of various redox signaling pathways. However, upon ingestion, antioxidants usually undergo extensive metabolism that can generate a wide range of bioactive metabolites. This makes it difficult, but otherwise a need, to identify the ones responsible for the different activities of antioxidants. By better understanding their ways of action, the use of antioxidants in therapy can be improved.

This review provides a summary on the role of the in vivo metabolic changes and the oxidized metabolites on the mechanisms behind the bioactivity of antioxidants. A special attention is given to metabolites described as products of biomimetic oxidative chemical reactions, which can be considered as models of free radical scavenging. During such reactions a wide variety of metabolites are formed, and they can exert completely different specific bioactivities as compared to their parent antioxidants. This implies that exploring the free radical scavenging‐related metabolite fingerprint of each antioxidant molecule, collectively defined here as the scavengome, will lead to a deeper understanding of the bioactivity of these compounds.

Furthermore, this paper aims to be a working tool for systematic studies on oxidized metabolic fingerprints of antioxidants, which will certainly reveal an often‐neglected segment of chemical space that is a treasury of bioactive compounds.
Flow‐based in vivo NMR spectroscopy of small aquatic organisms
Authors: Soong Ronald , Liaghati Mobarhan Yalda , Tabatabaei Maryam , Bastawrous Monica , Biswas Rajshree Ghosh , Simpson Myrna , Simpson Andre
Published: May 2019

NMR applied to living organisms is arguably the ultimate tool for understanding environmental stress responses and can provide desperately needed information on toxic mechanisms, synergistic effects, sublethal impacts, recovery, and biotransformation of xenobiotics. To perform in vivo NMR spectroscopy, a flow cell system is required to deliver oxygen and food to the organisms while maintaining optimal line shape for NMR spectroscopy. In this tutorial, two such flow cell systems and their constructions are discussed: (a) a single pump high‐volume flow cell design is simple to build and ideal for organisms that do not require feeding (i.e., eggs) and (b) a more advanced low‐volume double pump flow cell design that permits feeding, maintains optimal water height for water suppression, improves locking and shimming, and uses only a small recirculating volume, thus reducing the amount of xenobiotic required for testing. In addition, key experimental aspects including isotopic enrichment, water suppression, and 2D experiments for both 13C enriched and natural abundance organisms are discussed.
Body composition in patients with congenital myotonic dystrophy
Authors: Ceballos‐Sáenz Delia , Zapata‐Aldana Eugenio , Singeris Stephanie , Hicks Rhiannon , Johnson Nicholas , Campbell Craig
Published: May 2019

Introduction

Congenital myotonic dystrophy (CDM) is a rare neuromuscular disorder characterized by severe hypotonia and muscle weakness at birth that tends to improve with age. Understanding lean body and bone mass in this population has important research and clinical implications. The main objective of this study was to determine whether older children with CDM had muscle mass similar to healthy controls.

Methods

Thirty‐five patients with CDM (3‐13 years old) were enrolled. We analyzed lean body mass (LBM) and bone mineral content using the mechanostat framework, which allows calculation of z‐scores for sex, age, and height.

Results

All patients had low LBM z‐scores (muscle mass); however, higher LBM z‐score was positively correlated with age (r = 0.45, P = 0.006), showing that it is closer to normal in older patients.

Discussion

Unlike other neuromuscular diseases, older children with CDM have a muscle mass closer to age‐matched controls, consistent with the clinical profile of increasing strength in childhood. Muscle Nerve 60: 176–179, 2019
Variation in Bluegill Catch Rates and Total Length Distributions among Four Sampling Gears Used in Two Wisconsin Lakes Dominated by Small Fish
Authors: Sullivan Christopher J. , Embke Holly S. , Perales K. Martin , Carpenter Stephen R. , Vander Zanden M. Jake , Isermann Daniel A.
Published: May 2019

Many Bluegill Lepomis macrochirus populations are dominated by fish ≤125 mm total length (TL) that may be underrepresented when using standard sampling gears. To identify efficient sampling methods for these populations, we compared catch per unit effort (CPUE) and TL frequency distributions of Bluegill captured in cloverleaf traps, boat electrofishing, mini-fyke nets, and beach seine hauls from two northern Wisconsin lakes supporting populations dominated by fish ≤125 mm TL. Mean Bluegill CPUE ranged from 41 (SE = 11) fish per cloverleaf trap lift to 16 (SE = 8) fish per beach seine haul. Cloverleaf traps generally captured smaller Bluegill relative to other gears and were the only gear to consistently capture Bluegill ≤80 mm TL. Conversely, boat electrofishing captured the widest TL range of Bluegill, and fish ≥80 mm TL composed a greater proportion of catch (37%) relative to other gears. With few exceptions, the effort required to detect 10% or 25% changes in Bluegill CPUE was >100 units of effort regardless of lake, sampling gear, or month. Furthermore, there was no consistency between lakes or months in terms of which sampling gear required the fewest number of samples to detect a 50% change in CPUE. Estimated units of effort needed to detect 10% or 25% changes in mean Bluegill TL were ≤16 for all sampling gears on the lake with consistently higher CPUE (i.e., more fish to measure per unit). In the lake with lower CPUE, cloverleaf traps consistently required less effort to detect changes in mean TL. We note that comparing sample size requirements among gears is not straightforward because gears are sampling differing segments of the Bluegill population. Our study emphasizes the importance of evaluating gear biases and sampling efficiency so that fisheries managers can develop suitable sampling protocols.
Numerical modeling of fracturing in permeable rocks via a micromechanical continuum model
Authors: Eghbalian Mahdad , Wan Richard , Pouragha Mehdi , Fung Larry S.
Published: May 2019

The paper presents a micromechanical approach to describe the failure of low‐permeability brittle rocks as a multiscale fracturing process based on a poroelastic microcrack‐damage model. Failure is formulated deep down at the fine pore scale as a material degradation phenomenon driven by microcrack growth that also impacts upon hydromechanical properties. A set of damage tensors describes the effect of dual‐scale porosities (nanopores and microcracks) on both the hydraulic and poroelastic rock properties. Essentially, the multiscale model reconstructs the coupling effect of hydromechanical forces at the continuum level from the ground up through the upscaling of multiphase interactions at the fundamental structural level of the material. As a result, many macroscopic characteristics emerge naturally such as friction angle, fracture properties, and most importantly, Biot's coefficient taking on a tensorial form that is generally anisotropic. The model is validated within the framework of finite elements to illustrate various baseline constitutive features such as the effect of microcrack growth on the nonlinear stress‐strain response and the induced anisotropy in the context of lab experimental tests and boundary value problems. Heterogeneities of the rock samples were incorporated by choosing material properties to be stochastic following Weibull and lognormal distributions. Numerical results appropriately replicated typical experimental observations where fracture localization and propagation are shown to be a multiscale phenomenon emerging from microcrack growth and coalescence at the microscale, with concomitant enhancement in fluid conductivity.
Chronic high‐fat diet decreased detrusor mitochondrial respiration and increased nerve‐mediated contractions
Authors: Powers Shelby A. , Ryan Terence E. , Pak Elena S. , Fraser Matthew O. , McClung Joseph M. , Hannan Johanna L.
Published: May 2019

Aims

To assess the impact of chronic high‐fat diet (HFD) on behavioral voiding patterns, detrusor contractility, and smooth muscle mitochondrial function in male mice.

Materials and Methods

Male C57BL/6J mice (6 weeks) were fed a control or HFD for 20 weeks. Bladder function was assessed by void spot assays. Bladders were collected and detrusor contractility to carbachol (10−9‐10−5 M), and electrical field stimulation (EFS, 0.5–32 Hz) in the presence and absence of atropine was measured. Homogenized detrusor samples were placed in oxygraphs to assess the rate of oxygen consumption of the mitochondria within the detrusor in the presence of different substrates. Mitochondrial hydrogen peroxide (H2O2) emission was measured fluorometrically. Detrusor citrate synthase activity was measured via enzyme activity kit and Western blots assessed the electron transport chain (ETC) protein content.

Results

HFD significantly increased body weight, adiposity, and blood glucose levels. HFD mice demonstrated increased voiding frequency and increased EFS‐induced detrusor contractility. There were no changes in detrusor relaxation or cholinergic‐medicated contraction. Mitochondrial respiration was decreased with HFD and H2O
2 emission was increased. The relative amount of mitochondria in the detrusor was similar between groups. However, ETC complexes V and III were increased following HFD.

Conclusions

Chronic HFD increased adiposity, lead to more frequent voiding, and enhanced EFS‐mediated detrusor contractions. Mitochondrial respiration was decreased and H2O
2 emission increased following HFD. Further research is required to determine if alterations in mitochondrial function could play a role in the development of HFD‐induced bladder dysfunction.
Heterogeneous impacts of community forestry on forest conservation and poverty alleviation: Evidence from Indonesia
Authors: Santika Truly , Wilson Kerrie A. , Budiharta Sugeng , Kusworo Ahmad , Meijaard Erik , Law Elizabeth A. , Friedman Rachel , Hutabarat Joseph A. , Indrawan Tito P. , St. John Freya A. V. , Struebig Matthew J.
Published: May 2019

Community forestry is a participatory approach aiming to achieve sustainable forest management while also reducing poverty among rural communities. Yet, evidence of the impacts of community forestry programmes on both forest conservation and poverty alleviation is scarce, and there is limited understanding of impacts across different social and biophysical contexts.

We applied a matching method to assess the extent to which deforestation has decreased and village well‐being has improved as a result of Indonesia's community forestry scheme, Hutan Desa (Village Forest). We assessed five dimensions of well‐being: basic (living conditions), physical (access to health and education), financial (income support), social (security and equity) and environmental (natural hazard prevention).

We found that Hutan Desa was associated with reduced deforestation and poverty. ‘Win‐win’ outcomes were found in 51% of cases, comprising (a) positive outcomes for both forests and poverty, (b) a positive outcome for one aspect and a negligible outcome for the other, or (c) a positive outcome for poverty in areas where natural forest had already been lacking prior to Hutan Desa tenure. Benefits to forests and people systematically differed depending on land‐use zones, reflecting subtle interactions between anthropogenic pressures and community livelihood characteristics.

In Watershed Protection Zones, which are dominated by subsistence‐based forest livelihoods, community forestry provided mild conservation benefits, but resulted in the greatest improvements in well‐being through improved land tenure. In Limited Production Zones, community forestry provided modest benefits for both conservation and well‐being because restrictions on timber harvest due to Hutan Desa designation reduced the financial well‐being of logging communities. The greatest conservation benefits were experienced in Permanent or Convertible Production Zones, but well‐being improvements were minimal. Here, living conditions and environmental well‐being were reduced due to pressure to intensify agricultural production under increased land scarcity in these predominantly cash crop‐oriented communities.

Our results highlight the spatial and contextual variation in impacts of community forestry policies on poverty alleviation and forest conservation outcomes. Crucially, our study provides vital objective information for future policy development in Indonesia and other tropical countries implementing community forestry schemes.

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Biocompatible hydrogel for cartilage repair with adjustable properties
Authors: Abou‐Okeil Ashraf , Aly Amal Ahmed , Amr Ahmed , Soliman Ahmed Abdel‐ Fattah
Published: May 2019

Synthesis of hydrogel at mild conditions is considered one most important challenge, especially if the hydrogel will be used for hosting bioactive materials or drugs. The procedure of hydrogel preparation should have no effect on the properties of the hosted materials. Hyaluronic acid (HA) was modified by adding dialdehyde groups to its structure to facilitate formation of hydrogel at very mild conditions. Dialdehyde HA (DHA) was prepared through oxidation of HA using sodium metaperiodate as oxidizing agent. The prepared DHA was characterized by Fourier‐transform infrared (FTIR) spectroscopy and X‐ray diffraction (XRD) and aldehyde content. A hydrogel was prepared using different chitosan/DHA molar ratio and fixed amount of glutaraldehyde at 25°C. The prepared hydrogel has tunable properties and pores size depending on the chitosan/DHA molar ratio. Sodium diclofenac was loaded on the hydrogel as a model drug. The hydrogel was characterized by FTIR spectroscopy, swelling rate, gel fraction, drug release profile, and cytotoxicity. The results obtained indicated that the properties of the prepared hydrogel, including gelling time, gel fraction, swelling, pores size, and drug release profile are highly tuned depending on the chitosan/DHA molar ratio. The drug loading efficiency was in the range of 70% to 85%. The cytotoxicity results reveal that the prepared hydrogel has a very low toxicity in presence and absence of sodium diclofenac.
Phenolic resin/polyhedral oligomeric silsesquioxane (POSS) composites: Mechanical, ablative, thermal, and flame retardant properties
Authors: Dong Yubing , He Jiyu , Yang Rongjie
Published: May 2019

Three different polyhedral oligomeric silsesquioxanes (POSS), trisilanolphenyl polyhedral oligomeric silsesquioxane (T‐POSS), octaaminophenyl polyhedral oligomeric silsesquioxanes (OAPS), and octaphenyl polyhedral oligomeric silsesquioxanes (OPS) were incorporated into phenolic resin (PR), respectively; PR/POSS composites were successfully prepared, and the properties of PR/POSS composites were studied. The limiting oxygen index (LOI), cone calorimeter, and thermal gravimetric analysis (TGA) were used for the estimation of flame retardancy and thermal stability. Oxyacetylene flame test and flexural strength test were used to study the ablative and mechanical properties of the PR/POSS composites. The results indicated that T‐POSS was more effective in improving the flame retardancy of PR than OAPS or OPS. Meanwhile, compared with pure PR, the second line ablation rates of PR/4% T‐POSS, PR/4% OAPS, and PR/4% OPS were significantly reduced by 53.3%, 61.9%, and 40.0%, respectively. In addition, the thermal stability and flexural strength of PR/4% T‐POSS were significantly higher than that of all other PR composites.
Observer‐based event‐triggered control for singularly perturbed systems with saturating actuator
Authors: Yan Yifang , Yang Chunyu , Ma Xiaoping , Zhou Linna
Published: May 2019

This paper investigates an observer‐based event‐triggered control problem of singularly perturbed systems with saturating actuator. A strategy that consists of an observer‐based controller (OBC) and an event‐triggered mechanism (ETM) is considered. Firstly, sufficient conditions, which guarantee that the saturated SPSs are asymptotically stable excluding Zeno phenomenon, are derived via constructing an ε‐dependent Lyapunov‐Krasovskii functional. Then, the OBC and ETM are designed simultaneously based on the aforementioned criteria. Furthermore, an estimate of the basin of attraction and an ε‐bound are given by solving an optimization problem in the form of LMIs. Finally, an electric circuit system and a numerical example are presented to demonstrate the merits of the obtained method.
Straightforward Access to 3,4‐Dihydro‐2H‐1,2,4‐benzothiadiazine 1,1‐dioxides and Quinazolines via Iron‐Catalyzed Aerobic Oxidative Condensation of Amines
Authors: Gopalaiah Kovuru , Tiwari Ankit , Choudhary Renu , Mahiya Kuldeep
Published: May 2019

A novel and straightforward approach for constructing 3,4‐dihydro‐2H‐1,2,4‐benzothiadiazine 1,1‐dioxides from 2‐aminobenzenesulfonamide and benzylamines via oxidative condensation has been explored. Abundant and cheap iron salt as a catalyst and air as an oxidant were employed, which makes the process more practical and economical. This reaction protocol was further applied to synthesize diverse functionalized quinazolines through oxidative condensation of 2‐aminobenzylamines with benzylamines. Besides this, the use of amino acid such as phenylglycine as benzylamine surrogate has also been tested for the construction of 3,4‐dihydro‐2H‐1,2,4‐benzothiadiazine 1,1‐dioxide and quinazoline derivatives. The proposed mechanistic pathway has been validated by isolating the key intermediates.
Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer
Authors: Li Guangzhi , Lei Qifang , Wang Fei , Deng Dashi , Wang Shupeng , Tian Longlong , Shen Wanwan , Cheng Yiyun , Liu Zhuang , Wu Song
Published: May 2019

Surgical intervention combined with intravesical instillation of chemotherapeutics to clear residual cancer cells after operation is the current standard treatment method for bladder cancer. However, the poor bioavailability of active pharmaceutical ingredients for bladder cancer cells on account of the biological barriers of bladder mucosa, together with significant side effects of currently used intravesical medicine, have limited the clinical outcomes of localized adjuvant therapy for bladder cancer. Aiming at improved intravesical instillation therapy of bladder cancer, a fluorinated polyethylenimine (F‐PEI) is employed here for the transmucosal delivery of an active venom peptide, polybia‐mastoparan I (MPI), which shows selective antiproliferative effect against various bladder cancer cell lines. Upon simple mixing, MPI and F‐PET would coassemble to form stable nanoparticles, which show greatly improved cross‐membrane and transmucosal penetration capacities compared with MPI alone or nonfluorinated MPI/PEI nanoparticles. MPI/F‐PEI shows higher in vivo tumor growth inhibition efficacy for local treatment of a subcutaneous tumor model. More excitingly, as further demonstrated in an orthotopic bladder cancer model, MPI/F‐PEI offers remarkably improved therapeutic effects compared to those achieved by free MPI or the first‐line bladder cancer drug mitomycin C. This work presents a new transmucosal delivery carrier particularly promising for intravesical instillation therapy of bladder cancer.
Nanosilica‐Confined Synthesis of Orthogonally Active Catalytic Metal Nanocrystals in the Compartmentalized Carbon Framework
Authors: Lee Seon Hee , Kumari Nitee , Dutta Soumen , Jin Xing , Kumar Amit , Koo Jung Hun , Lee In Su
Published: May 2019

Multifunctionalized porous catalytic nanoarchitectures are highly desirable for a variety of chemical transformations; however, selective installation of different catalysts with spatial and functional precision working synergistically and predictably, is highly challenging. Here, a synthetic strategy is developed toward the customizable combination of orthogonally reactive metal nanocrystals within interconnected carbon‐cavities as a compartmentalized framework by employing aminated‐silica‐directed thermal solid‐state nanoconfined synthesis of metal nanocrystals and endotemplating concomitant carbonization‐mediated interlocking, as key processes. The main advantage of the strategy is the facility to choose any combination of metals, which can be further employed according to the desired application. The strategically synthesized compartmentalized multifunctional catalytic architectures of Pd‐Pt@Com‐CF regulate the O2‐mediated selective cascade oxidation reaction converting alcohol to acid with high yield and selectivity; and another Pt‐Ir@Com‐CF platform is demonstrated as a bifunctional electrocatalyst for oxygen reduction/evolution reactions.
Large‐Range HS‐AFM Imaging of DNA Self‐Assembly through In Situ Data‐Driven Control
Authors: Nievergelt Adrian P. , Kammer Christoph , Brillard Charlène , Kurisinkal Eva , Bastings Maartje M. C. , Karimi Alireza , Fantner Georg E.
Published: May 2019

Understanding hierarchical self‐assembly of biological structures requires real‐time measurement of the self‐assembly process over a broad range of length‐ and timescales. The success of high‐speed atomic force microscopy (HS‐AFM) in imaging small‐scale molecular interactions has fueled attempts to introduce this method as a routine technique for studying biological and artificial self‐assembly processes. Current state‐of‐the‐art HS‐AFM scanners achieve their high imaging speed by trading achievable field of view for bandwidth. This limits their suitability when studying larger biological structures. In ambient conditions, large‐range scanners with lower resonance frequencies offer a solution when combined with first principle model–based schemes. For imaging molecular self‐assembly processes in fluid, however, such traditional control techniques are less suited. In liquid, the time‐varying changes in the behavior of the complex system necessitate frequent update of the compensating controller. Recent developments in data‐driven control theory offer a model‐free, automatable approach to compensate the complex system behavior and its changes. Here, a data‐driven control design method is presented to extend the imaging speed of a conventional AFM tube scanner by one order of magnitude. This enables the recording of the self‐assembly process of DNA tripods into a hexagonal lattice at multiple length scales.