bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyphenolic flavonoid (Myricetin) upregulated proteasomal degradation mechanisms: Eliminates neurodegenerative proteins aggregation
Authors: Joshi Vibhuti , Mishra Ribhav , Upadhyay Arun , Amanullah Ayeman , Poluri Krishna Mohan , Singh Sarika , Kumar Amit , Mishra Amit
Published: April 2019

Major neurodegenerative disorders are characterized by the formation of misfolded proteins aggregates inside or outside the neuronal cells. Previous studies suggest that aberrant proteins aggregates play a critical role in protein homeostasis imbalance and failure of protein quality control (PQC) mechanism, leading to disease conditions. However, we still do not understand the precise mechanisms of PQC failure and cellular dysfunctions associated with neurodegenerative diseases caused by the accumulation of protein aggregates. Here, we show that Myricetin, a flavonoid, can eliminate various abnormal proteins from the cellular environment via modulating endogenous levels of Hsp70 chaperone and quality control (QC)‐E3 ubiquitin ligase E6‐AP. We have observed that Myricetin treatment suppresses the aggregation of different aberrant proteins. Myricetin also enhances the elimination of various toxic neurodegenerative diseases associated proteins from the cells, which could be reversed by the addition of putative proteasome inhibitor (MG132). Remarkably, Myricetin can also stabilize E6‐AP and reduce the misfolded proteins inclusions, which further alleviates cytotoxicity. Taken together these findings suggested that new mechanistic and therapeutic insights based on small molecules mediated regulation of disturbed protein quality control mechanism, which may result in the maintenance of the state of proteostasis.
Background parenchymal enhancement on breast MRI: A comprehensive review
Authors: Liao Geraldine J. , Henze Bancroft Leah C. , Strigel Roberta M. , Chitalia Rhea D. , Kontos Despina , Moy Linda , Partridge Savannah C. , Rahbar Habib
Published: April 2019

The degree of normal fibroglandular tissue that enhances on breast MRI, known as background parenchymal enhancement (BPE), was initially described as an incidental finding that could affect interpretation performance. While BPE is now established to be a physiologic phenomenon that is affected by both endogenous and exogenous hormone levels, evidence supporting the notion that BPE frequently masks breast cancers is limited. However, compelling data have emerged to suggest BPE is an independent marker of breast cancer risk and breast cancer treatment outcomes. Specifically, multiple studies have shown that elevated BPE levels, measured qualitatively or quantitatively, are associated with a greater risk of developing breast cancer. Evidence also suggests that BPE could be a predictor of neoadjuvant breast cancer treatment response and overall breast cancer treatment outcomes. These discoveries come at a time when breast cancer screening and treatment have moved toward an increased emphasis on targeted and individualized approaches, of which the identification of imaging features that can predict cancer diagnosis and treatment response is an increasingly recognized component. Historically, researchers have primarily studied quantitative tumor imaging features in pursuit of clinically useful biomarkers. However, the need to segment less well‐defined areas of normal tissue for quantitative BPE measurements presents its own unique challenges. Furthermore, there is no consensus on the optimal timing on dynamic contrast‐enhanced MRI for BPE quantitation. This article comprehensively reviews BPE with a particular focus on its potential to increase precision approaches to breast cancer risk assessment, diagnosis, and treatment. It also describes areas of needed future research, such as the applicability of BPE to women at average risk, the biological underpinnings of BPE, and the standardization of BPE characterization.

Level of Evidence: 3

Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:43–61.
Nurturing and Enhancing Creativity of Nursing Students in Taiwan: A Quasi‐Experimental Study
Authors: Liu Hsing‐Yuan , Wang I‐Teng , Huang Ding‐Hau , Hsu Ding‐Yang , Han Hui‐Mei
Published: April 2019

Creativity and innovation are considered important measures of core competence in Taiwan for students of all levels, including nursing students. Integrating creativity with interdisciplinary teaching modules could increase creativity for nursing students; however, this has not been empirically determined. The purpose of this study was to determine if incorporating interdisciplinary teaching into a teaching for creativity module (TCM) could enhance creative thinking and creative abilities of nursing students. Students enrolled in a capstone nursing course for the development of healthcare‐related products were divided into 2 groups. Both groups participated in the 18‐week course; however, one group received creativity training with interdisciplinary teaching during the course, which was taught by nursing faculty who completed a TCM workshop. Students who received the interdisciplinary TCM intervention scored significantly higher than controls on measures of creative thinking. Our findings suggest a TCM program, which incorporates interdisciplinary teaching, and instruction in techniques for creativity, such as brainstorming, attribute listing, assessment matrix, and paired comparison, can stimulate divergent thinking abilities of nursing students.
A novel online prognostic tool to predict long‐term survival after liver resection for intrahepatic cholangiocarcinoma: The “metro‐ticket” paradigm
Authors: Sahara Kota , Tsilimigras Diamantis I. , Mehta Rittal , Bagante Fabio , Guglielmi Alfredo , Aldrighetti Luca , Alexandrescu Sorin , Marques Hugo P. , Shen Feng , Koerkamp Bas G. , Endo Itaru , Pawlik Timothy M.
Published: April 2019

Background

The aim of the current study was to develop an online calculator to predict survival after liver resection for intrahepatic cholangiocarcinoma (ICC) based on the “metro‐ticket” paradigm.

Methods

Between 1990 and 2016, patients who underwent liver resection for ICC were identified in an international multi‐institutional database. The final multivariable model of survival was used to develop an online prognostic calculator of survival.

Results

Among 643 patients, actual 5‐year overall survival (OS) after resection for ICC was 42.7%. On multivariable analysis, CA19‐9 > 200 (hazard ratio (HR), 2.62; 95% CI, 2.01‐3.42), sum of the number and largest tumor size >7 (HR, 1.88; 95% CI, 1.46‐2.42), N1 disease (HR, 2.87; 95% CI, 1.98‐4.16), R1 resection (HR, 1.72; 95% CI, 1.21‐2.46), poor/undifferentiated tumor grade (HR, 1.74; 95% CI, 1.25‐2.44), major vascular invasion (HR, 1.47; 95% CI, 1.03‐2.10), and adjuvant chemotherapy (HR, 0.64; 95% CI, 0.45‐0.89) were significantly associated with survival and were included in the online calculator. The predictive accuracy of the model was good to very good as the C‐statistics to predict 5‐year OS was 0.696 in the training dataset and 0.672 with bootstrapping resamples (n = 5000) in the test dataset.

Conclusion

A novel, online calculator was developed to estimate the 5‐year survival probability for patients undergoing resection for ICC. This tool could help provide useful information to guide treatment decision‐making and inform conversations about prognosis.
Family firms’ identity communication and consumers’ product involvement impact on consumer response
Authors: Alonso‐Dos‐Santos Manuel , Llanos‐Contreras Orlando , Farías Pablo
Published: April 2019

The purpose of this study is to determine whether the image transfer theory and the elaboration likelihood model can provide a theoretical framework capable of assessing the influence of consumers’ product involvement and family firms’ identity communication through websites on consumer responses. This research conducted an experiment using an eye‐tracking technique measuring attention to family and nonfamily corporate websites. The procedure involved 120 participants. Consistent with the image transfer theory, family firms’ identity through websites positively impacts attitude toward the website and intention to buy. Additionally, the attitude toward the website affects the relationship between family firms’ identity through websites and the intention to buy. In line with the elaboration likelihood model, consumers’ product involvement negatively impacts the relationship between family firms’ identity through websites and intention to buy.
Antimicrobial resistant and extended‐spectrum β‐lactamase producing Escherichia coli in common wild bird species in Switzerland
Authors: Zurfluh Katrin , Albini Sarah , Mattmann Prisca , Kindle Patrick , Nüesch‐Inderbinen Magdalena , Stephan Roger , Vogler Barbara R.
Published: April 2019

A total of 294 fecal swabs from 294 wild birds in Switzerland were cultivated for antimicrobial resistant (AMR) Escherichia coli. Samples were also subcultivated to detect E. coli with extended‐spectrum β‐lactamases (ESBL), carbapenemases, and plasmid‐mediated aminoglycoside or colistin resistance, respectively. Samples from 17 (5.8%) of the birds contained 19 AMR E. coli, whereof 26.3% were multidrug resistant. Five (1.7%) ESBL‐producing E. coli were detected. The isolates harbored blaCTX‐M‐1 (two isolated from carrion crows and from one great spotted woodpecker, respectively), blaCTX‐M‐15 (originating from a grey heron), blaCTX‐M‐55 (from a carrion crow), and blaCTX‐M‐65 (from a common blackbird). Phylogenetic analysis assigned three isolates to commensal phylogroups A and B1, one to extraintestinal pathogenic group B2, and one to phylogroup F. Multilocus sequence typing identified sequence types (STs) that have been found previously in ESBL E. coli in wild birds (ST58, ST205, ST540). One isolate harboring blaCTX‐M‐55 was assigned to the recently emerged fluoroquinolone‐resistant, extraintestinal pathogenic E. coli clone ST1193. Wild birds have the potential to disperse AMR, including clinically important resistance genes, from anthropogenic‐influenced habitats to diverse areas, including vulnerable natural environments such as surface waters or mountain regions.
Dual DNA topoisomerase 1 and tyrosyl‐DNA phosphodiesterase 1 inhibition for improved anticancer activity
Authors: Zakharenko Alexandra , Dyrkheeva Nadezhda , Lavrik Olga
Published: April 2019

Tyrosyl‐DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that catalyzes the hydrolysis of the phosphodiester bond in the DNA‐topoisomerase 1 (Top1) covalent complex and repairs some other 3′‐end DNA adducts. Currently, Tdp1 functions as an important target in cancer drug design owing to its ability to break down various DNA adducts induced by chemotherapeutics. Tdp1 inhibitors may sensitize tumor cells to the action of Top1 poisons, thereby potentiating their effects. This mini‐review summarizes findings from studies reporting the combined inhibition of Top1 and Tdp1. Two different approaches have been considered for developing such drug precursors.
Drug delivery systems designed to overcome antimicrobial resistance
Authors: Pham Thanh‐Nhat , Loupias Pauline , Dassonville‐Klimpt Alexandra , Sonnet Pascal
Published: April 2019

Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.
Efflux pump inhibitors of clinically relevant multidrug resistant bacteria
Authors: Lamut Andraž , Peterlin Mašič Lucija , Kikelj Danijel , Tomašič Tihomir
Published: April 2019

Bacterial infections are an increasingly serious issue worldwide. The inability of existing therapies to treat multidrug‐resistant pathogens has been recognized as an important challenge of the 21st century. Efflux pumps are important in both intrinsic and acquired bacterial resistance and identification of small molecule efflux pump inhibitors (EPIs), capable of restoring the effectiveness of available antibiotics, is an active research field. In the last two decades, much effort has been made to identify novel EPIs. However, none of them has so far been approved for therapeutic use.

In this article, we explore different structural families of currently known EPIs for multidrug resistance efflux systems in the most extensively studied pathogens (NorA in Staphylococcus aureus, AcrAB‐TolC in Escherichia coli, and MexAB‐OprM in Pseudomonas aeruginosa). Both synthetic and natural compounds are described, with structure‐activity relationship studies and optimization processes presented systematically for each family individually. In vitro activities against selected test strains are presented in a unifying manner for all the EPIs described, together with the most important toxicity, pharmacokinetic and in vivo efficacy data. A critical evaluation of lead‐likeness characteristics and the potential for clinical development of the most promising inhibitors of the three efflux systems is described. This overview of EPIs is a good starting point for the identification of novel effective antibacterial drugs.
The frequency of CNVs in a cohort population of consecutive fetuses with congenital anomalies after the termination of pregnancy
Authors: Rudolf Gorazd , Lovrečić Luca , Tul Nataša , Teran Nataša , Peterlin Borut
Published: April 2019

Background

The implementation of molecular karyotyping has resulted in an improved diagnostic yield in the genetic diagnostics of congenital anomalies, detected prenatally or after the termination of pregnancy. However, the systematic epidemiologic ascertainment of copy number variations in the etiology of congenital anomalies has not yet been sufficiently explored.

Methods

Consecutive fetuses, altogether 204, with major single or multiple congenital anomalies were ascertained by using the SLOCAT registry for the period from 2011 to 2015. After excluding aneuploidies by using conventional karyotyping or Quantitative Fluorescence‐Polymerase Chain Reaction, array comparative genomic hybridization was performed for the detection of copy number variations.

Results

We identified pathogenic or likely pathogenic copy number variations in 14 fetuses (6.8%); 2.9% in fetuses with isolated, and 3.9% in fetuses with multiple congenital anomalies. Additionally, aneuploidies and major structural chromosomal abnormalities were detected in 40.2%.

Conclusion

Our systematic approach of ascertaining congenital anomalies resulted in explaining the etiology of congenital anomalies in 47% of fetuses after the termination of pregnancy. By using array comparative genomic hybridization, we found that copy number variations represent an important part in the etiology of multiple, as well as isolated congenital anomalies, which indicates the importance of analyzing copy number variations in the diagnostic approach of fetuses with congenital anomalies after the termination of pregnancy.
Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low‐pass whole‐genome sequencing
Authors: Yu Dongyi , Zhang Kai , Han Meiyan , Pan Wei , Chen Ying , Wang Yunfeng , Jiao Hongyan , Duan Ling , Zhu Qiying , Song Xiaojie , Hong Yan , Chen Chen , Wang Juan , Hui Feng , Huang Linzhou , Chen Chongjian , Du Yang
Published: April 2019

Background

Expanding noninvasive prenatal testing (NIPT) to include the detection of fetal subchromosomal copy number variations (CNVs) significantly decreased the sensitivity and specificity. Developing analytic pipeline to achieve high performance in the noninvasive detection of CNVs will largely contribute to the application of CNVs screening in clinical practice.

Methods

We developed the Noninvasively Prenatal Subchromosomal Copy number variation Detection (NIPSCCD) method based on low‐pass whole‐genome sequencing, and evaluated its efficacy in detecting fetal CNVs and chromosomal aneuploidies with 20,003 pregnant women.

Results

Totally, NIPSCCD identified 36 CNVs, including 29 CNVs consistent and 7 CNVs inconsistent with amniocytes tests. Additionally, seven fetal CNVs identified by amniocytes testing were undetected by NIPSCCD. The sensitivities for detecting CNVs > 10 Mb, 5 Mb–10 Mb, and CNVs < 5 Mb were 91.67%, 100.00%, and 68.42%, respectively. Moreover, NIPSCCD identified 103/ true positive trisomy 21/18/13 cases and 21 false positives, producing an overall 100.00% sensitivity and 99.89% specificity.

Conclusion

NIPSCCD showed a good performance in detecting fetal subchromosomal CNVs, especially for CNVs >10 Mb, and can be incorporated into the routine NIPT chromosomal aneuploidies screening with high sensitivity and specificity.
Resveratrol Treatment Ameliorates Leptin Resistance and Adiposity Programed by the Combined Effect of Maternal and Post‐Weaning High‐Fat Diet
Authors: Yu Hong‐Ren , Sheen Jiunn‐Ming , Tiao Mao‐Meng , Tain You‐Lin , Chen Chih‐Cheng , Lin I‐Chun , Lai Yun‐Ju , Tsai Ching‐Chou , Lin Yu‐Ju , Tsai Ching‐Chang , Chang Kow‐Aung , Huang Li‐Tung
Published: April 2019

Scope

Prenatal high‐fat (HF) and postnatal HF diet are both associated with obesity and metabolic disturbances in adults. Leptin resistance induced by obesity limits its biological effects. The anti‐obesity mechanism of resveratrol in visceral adiposity is investigated here.

Methods and results

During mating and lactation, Sprague–Dawley dams are fed either control or a HF diet. Subsequently, the offspring are fed chow or an HF diet. A fifth group that received maternal/postnatal HF diet and resveratrol after weaning (HHR) is used to study the effects of resveratrol treatment. Resveratrol treatment alleviates adiposity programed by maternal and postnatal HF diet by decreasing feed intake or inducing metabolic changes. Resveratrol treatment is also found to ameliorate the decrease in SIRT1 abundance observed in retroperitoneal adipose tissue, programed by maternal and postnatal HF diet. Moreover, resveratrol therapy decreases plasma leptin level and increases leptin receptor expression in retroperitoneal adipose tissue through DNA methylation modification.

Conclusion

These results suggest that resveratrol can alleviate peripheral leptin resistance programed by the combined effect of prenatal and postnatal HF diet through epigenetic regulation of genes coding leptin and its receptor. It provides insights into a novel mechanism explaining the beneficial effects of resveratrol in obesity management.
Conditional generative adversarial network for 3D rigid‐body motion correction in MRI
Authors: Johnson Patricia M. , Drangova Maria
Published: April 2019

Purpose

Subject motion in MRI remains an unsolved problem; motion during image acquisition may cause blurring and artifacts that severely degrade image quality. In this work, we approach motion correction as an image‐to‐image translation problem, which refers to the approach of training a deep neural network to predict an image in 1 domain from an image in another domain. Specifically, the purpose of this work was to develop and train a conditional generative adversarial network to predict artifact‐free brain images from motion‐corrupted data.

Methods

An open source MRI data set comprising T2*‐weighted, FLASH magnitude, and phase brain images for 53 patients was used to generate complex image data for motion simulation. To simulate rigid motion, rotations and translations were applied to the image data based on randomly generated motion profiles. A conditional generative adversarial network, comprising a generator and discriminator networks, was trained using the motion‐corrupted and corresponding ground truth (original) images as training pairs.

Results

The images predicted by the conditional generative adversarial network have improved image quality compared to the motion‐corrupted images. The mean absolute error between the motion‐corrupted and ground‐truth images of the test set was 16.4% of the image mean value, whereas the mean absolute error between the conditional generative adversarial network‐predicted and ground‐truth images was 10.8% The network output also demonstrated improved peak SNR and structural similarity index for all test‐set images.

Conclusion

The images predicted by the conditional generative adversarial network have quantitatively and qualitatively improved image quality compared to the motion‐corrupted images.
Proton exchange in aqueous urea solutions measured by water‐exchange (WEX) NMR spectroscopy and chemical exchange saturation transfer (CEST) imaging in vitro
Authors: Stabinska Julia , Neudecker Philipp , Ljimani Alexandra , Wittsack Hans‐Jörg , Lanzman Rotem Shlomo , Müller‐Lutz Anja
Published: April 2019

Purpose

To characterize the proton exchange in aqueous urea solutions using a modified version of the WEX II filter at high magnetic field, and to assess the feasibility of performing quantitative urea CEST MRI on a 3T clinical MR system.

Methods

In order to study the dependence of the exchange‐rate constant of urea as a function of pH and T, the WEX‐spectra were acquired at 600 MHz from urea solutions in a pH range from 6.4 to 8.0 and a temperature range from to . The CEST experiments were performed on a 3T MRI scanner by applying a train of 50 Gaussian‐shaped pulses, each 100‐millisecond long with a spacing of 100 milliseconds, for saturation. Exchange rates of urea were calculated using the (extended) AREX metric.

Results

The results showed that proton exchange in aqueous urea solutions is acid and base catalyzed with the rate constants: l/(mol·s) and l/(mol·s), respectively. Since the urea protons undergo a slow exchange with water protons, the CEST effect of urea can be observed efficiently at 3T. However, in neutral solutions the exchange rate of urea is minimal and cannot be estimated using the quantitative CEST approach.

Conclusions

By means of the WEX‐spectroscopy, the kinetic parameters of the proton exchange in urea solutions have been determined. It was also possible to estimate the exchange rates of urea in a broad range of pH values using the CEST method at a clinical scanner.
A Statewide Evaluation of Florida Bass Genetic Introgression in Tennessee
Authors: Hargrove John S. , Rogers Mark W. , Kacmar Phillip T. , Black Pat
Published: April 2019

The Largemouth Bass (LMB) Micropterus salmoides is one of the most popular freshwater sport fish in the United States, and managers in southeastern states have stocked its subspecies, the Florida Bass (FLB) M. salmoides floridanus, outside of the subspecies’ natural range to increase the size structure of existing LMB populations. In Tennessee, fisheries for LMB are concentrated in reservoirs of the Cumberland and Tennessee River systems; however, FLB stockings have to date been restricted to two reservoirs of the Tennessee River and have varied significantly in extent and duration. We quantified levels of genetic admixture between FLB and LMB by using 38 species-diagnostic single-nucleotide polymorphisms for 979 fish sampled from 14 reservoirs within the Cumberland and Tennessee River systems. We tested for differences in genetic admixture across river systems and evaluated the relative importance of fish stockings in explaining observed levels of genetic admixture. Levels of admixture and associated variation were higher in Tennessee River reservoirs (average percentage of FLB alleles: range = 6.3–30.4%) than in Cumberland River reservoirs (range = 5.7–13.4%), but admixture was not solely related to stocking rates. The highest levels of FLB introgression were detected in Chickamauga Reservoir, the most extensively stocked reservoir in the state. Linear models identified fish stocked as a significant overall predictor of admixture, but we also observed stocked and unstocked reservoirs with similar levels of admixture, suggesting that factors other than stocking influence population genetics. Our statewide assessment of reservoir-level patterns of hybridization among black bass was performed prior to the recent expansion of FLB stocking efforts in Tennessee and thus represents a baseline for evaluation of future stocking.
Metabolic Risk Factors Associated with Visceral and Subcutaneous Adipose Tissue in a Sex‐Specific Manner in Seven‐Year‐Olds
Authors: Kjellberg Emma , Roswall Josefine , Andersson Jonathan , Bergman Stefan , Karlsson Ann‐Katrine , Svensson Pär‐Arne , Kullberg Joel , Dahlgren Jovanna
Published: April 2019

Objective

This study aimed to investigate how visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes were associated with metabolic risk factors in 7‐year‐old children.

Methods

A total of 81 children (52% girls) from a Swedish birth cohort were studied. At 6 years of age, anthropometric data, fasting insulin, glucose, cholesterol, and blood pressure were collected on 53 children with normal weight and 28 children with overweight or obesity, and insulin resistance was estimated. At 7 years of age, magnetic resonance imaging quantified VAT and SAT. Sex and regression analyses were conducted.

Results

SAT was more strongly associated with metabolic risk factors than VAT. The associations between VAT and metabolic risk factors were stronger in girls (P < 0.05). When VAT was adjusted for birth weight and maternal BMI and education, it accounted for 51% of insulin variance (β = 11.72; P = 0.001) but only in girls. The key finding of this study was that adjusted SAT accounted for 63% of the fasting insulin variance in girls (β = 2.76; P < 0.001). Waist circumference was the best anthropometric marker for insulin resistance.

Conclusions

Insulin resistance was associated with abdominal adipose tissue and its associated metabolic risk factors in children as young as 7 years old.
Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans
Authors: Yoshino Jun , Patterson Bruce W. , Klein Samuel
Published: April 2019

Objective

Connective tissue growth factor (CTGF) is an important regulator of fibrogenesis in many organs. This study evaluated the interrelationship among adipose tissue CTGF expression, fat mass, and insulin resistance in humans.

Methods

This study examined (1) CTGF gene expression in human subcutaneous preadipocytes before and after inducing adipogenesis; (2) relationships among abdominal subcutaneous adipose tissue CTGF gene expression, body fat mass, and indices of insulin sensitivity, including the hepatic insulin sensitivity index and the hyperinsulinemic‐euglycemic clamp procedure in conjunction with stable isotope glucose tracer infusion, in 72 people who had marked differences in adiposity and insulin sensitivity; (3) localization of CTGF protein in subcutaneous adipose tissue; and (4) effect of progressive (5%, 11%, and 16%) weight loss on adipose tissue CTGF gene expression.

Results

CTGF was highly expressed in preadipocytes, not adipocytes. Adipose tissue CTGF expression was strongly correlated with body fat mass and both skeletal muscle and liver insulin sensitivity, and CTGF‐positive cells were predominantly found in areas of fibrosis. Progressive weight loss caused a stepwise decrease in adipose tissue CTGF expression.

Conclusions

It was concluded that increased CTGF expression is associated with adipose tissue expansion, adipose tissue fibrosis, and multi‐organ insulin resistance in people with obesity.
Role of Leptin in the Association Between Body Adiposity and Persistent Asthma: A Longitudinal Study
Authors: Li Zhen , Leynaert Bénédicte , Dumas Orianne , Diaz Gil Oscar , Garcia‐Aymerich Judith , Fito Colomer Montserrat , Le Moual Nicole , Pison Christophe , Romieu Isabelle , Siroux Valérie , Camargo Carlos A. , Varraso Raphaëlle , Nadif Rachel
Published: April 2019

Objective

Obesity is a likely risk factor for asthma. However, underlying mechanisms by which obesity affects asthma activity remain poorly understood. This study aimed to investigate the role of leptin, an adipocyte‐derived proinflammatory protein, as a mediator in the association between body adiposity (assessed using BMI, waist circumference, and body fat percentage) and persistent asthma.

Methods

A causal approach to mediation analysis was used to disentangle total and direct effects and the indirect effect mediated by leptin, using data from the French prospective French Epidemiological Study on the Genetics and Environment of Asthma (EGEA) (baseline: 2003‐2007; follow‐up: 2011‐2013; mean follow‐up time: 7 years). A total of 331 participants with current asthma at baseline were included.

Results

Per 1‐SD increment in BMI, waist circumference, and body fat percentage, the adjusted odds ratios of the total effect were 1.59 (95% CI: 0.95‐2.97), 2.06 (1.06‐4.00), and 3.25 (1.01‐9.41), respectively; the odds ratios of the indirect effect mediated by leptin were 1.68 (1.09‐2.46), 1.55 (0.99‐2.57), and 1.99 (0.94‐4.83), respectively.

Conclusions

Leptin partly (> 60%) mediated the association between high body adiposity and persistent asthma over time. Using a newly developed analytic approach, this longitudinal study brought new insight into one mechanism by which obesity may affect asthma activity.
Effects of interphase regions and filler networks on the viscosity of PLA/PEO/carbon nanotubes biosensor
Authors: Zare Yasser , Rhee Kyong Yop
Published: April 2019

The present work suggests a simple model for viscosity of polymer carbon nanotubes (CNT) biosensor assuming CNT concentration, CNT dimensions, interphase thickness, and network size. CNT concentration, CNT size, and interphase thickness express the effective filler concentration and the percolation threshold, which determine the fraction of networked CNT in nanocomposite biosensors. The experimental results of viscosity for the prepared samples containing poly(lactic acid) (PLA), poly(ethylene oxide) (PEO), and carbon nanotubes (CNT) are measured to approve the suggested model. Moreover, the developed model presents the roles of all parameters in the viscosity to confirm the predictions. The predictions properly agree with the experimental data of samples demonstrating the predictability of the developed model. Thin and large CNT (high aspect ratio) mainly increase the viscosity, while thick or short CNT produce very low viscosity. A high CNT concentration and thick interphase significantly enhance the viscosity, while a low content of CNT or a thin interphase cause an extremely low viscosity. In addition, the percentage of CNT in the networks directly manipulates the viscosity. POLYM. COMPOS., 40:4135–4141, 2019. © 2019 Society of Plastics Engineers
Pressure support ventilation, sigh adjunct to pressure support ventilation, and neurally adjusted ventilatory assist in infants after cardiac surgery: A physiologic crossover randomized study
Authors: Bonacina Daniele , Bronco Alfio , Nacoti Mirco , Ferrari Floriana , Fazzi Francesco , Bonanomi Ezio , Bellani Giacomo
Published: April 2019

Objectives

We sought to compare gas exchange, respiratory mechanics, and asynchronies during pressure support ventilation (PSV), sigh adjunct to PSV (PSV SIGH), and neurally adjusted ventilatory assist (NAVA) in hypoxemic infants after cardiac surgery.

Design

Prospective, single‐center, crossover, randomized physiologic study.

Setting

Tertiary‐care pediatric intensive care unit.

Patients

Fourteen hypoxemic infants (median age 11.5 days [8.7‐74]).

Interventions

The protocol begins with a 1 hour step of PSV, followed by two consecutive steps in PSV SIGH and NAVA in random order, with a washout period of 30 minutes (PSV) between them.

Main Results

Three infants presented an irregular Eadi signal because of diaphragmatic paralysis and were excluded from analysis. For the remaining 11 infants, PaO2/FiO
2 and oxygenation index improved in PSV SIGH compared with PSV (P < 0.05) but not in NAVA compared with PSV. PSV SIGH showed increased tidal volumes and lower respiratory rate than PSV (P < 0.05), as well as a significant improvement in compliance with respiratory system indexed to body weight when compared with both PSV and NAVA (P < 0.01). No changes in mean airway pressure was registered among steps. Inspiratory time resulted prolonged for both PSV SIGH and NAVA than PSV (P < 0.05). NAVA showed the higher coefficient of variability in respiratory parameters and a significative decrease in asynchrony index when compared with both PSV and PSV SIGH (P < 0.01).

Conclusions

The adjunct of one SIGH per minute to PSV improved oxygenation and lung mechanics while NAVA provided the best patient‐ventilator synchrony in infants after cardiac surgery.
Function and solution structure of the Arabidopsis thaliana RALF8 peptide
Authors: Frederick Ronnie O. , Haruta Miyoshi , Tonelli Marco , Lee Woonghee , Cornilescu Gabriel , Cornilescu Claudia C. , Sussman Michael R. , Markley John L.
Published: April 2019

We report the recombinant preparation from Escherichia coli cells of samples of two closely related, small, secreted cysteine‐rich plant peptides: rapid alkalinization factor 1 (RALF1) and rapid alkalinization factor 8 (RALF8). Purified samples of the native sequence of RALF8 exhibited well‐resolved nuclear magnetic resonance (NMR) spectra and also biological activity through interaction with a plant receptor kinase, cytoplasmic calcium mobilization, and in vivo root growth suppression. By contrast, RALF1 could only be isolated from inclusion bodies as a construct containing an N‐terminal His‐tag; its poorly resolved NMR spectrum was indicative of aggregation. We prepared samples of the RALF8 peptide labeled with 15N and 13C for NMR analysis and obtained near complete 1H, 13C, and 15N NMR assignments; determined the disulfide pairing of its four cysteine residues; and examined its solution structure. RALF8 is mostly disordered except for the two loops spanned by each of its two disulfide bridges.
Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
Authors: Schneider Benjamin K. , Boyer Arnaud , Ciccolini Joseph , Barlesi Fabrice , Wang Kenneth , Benzekry Sebastien , Mochel Jonathan P.
Published: April 2019

Bevacizumab‐pemetrexed/cisplatin (BEV‐PEM/CIS) is a first‐line therapeutic for advanced nonsquamous non‐small cell lung cancer. Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV‐PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV‐PEM/CIS pharmacodynamic modeling in non‐small cell lung cancer–bearing mice to estimate the optimal gap in the scheduling of sequential BEV‐PEM/CIS. We predicted the optimal gap in BEV‐PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulations suggest that the efficacy loss in scheduling BEV‐PEM/CIS at too great of a gap is much less than the efficacy loss in scheduling BEV‐PEM/CIS at too short of a gap.
Theoretical study of the photophysical processes of a styryl‐bodipy derivative eliciting an AND molecular logic gate response
Authors: Tzeli Demeter , Petsalakis Ioannis D. , Theodorakopoulos Giannoula
Published: April 2019

We study, via density functional theory and time dependent DFT calculations, the photophysical processes of a styryl‐bodipy derivative, which acts as a three metal‐cation‐receptor fluorophore in order to (a) gain information on the appropriate computational approach for successful prediction of molecular logic gate candidates, (b) rationalize the available experimental data and (c) understand how the given combination of three different receptors with the BODIPY fluorophore presents such interesting optoelectronic responses. The fluorophore (1), its monometallic complexes (1‐Ca
2+, 1‐Zn
2+, and 1‐Hg
2+), and its trimetallic complex (2) are studied. The calculated λmax values for absorption and emission are in excellent agreement with experimental data. It was found that the observed quenching of emission of 1 and of the monometallic complexes is attributed to the fact that their first excited state is a charge‐transfer state whereas this does not happen for the complex 2. It should be noted that for the correct ordering of the excited states, the inclusion of corrections to the excitation energies for nonequilibrium solvent effects is required; while in the case of 1‐Ca
2+, the additional explicit inclusion of the solvent is necessary for the quenching of the emission spectra.
Mapping the underside of an iceberg with a modified underwater glider
Authors: Zhou Mingxi , Bachmayer Ralf , deYoung Brad
Published: April 2019

Icebergs pose many challenges to offshore operations in the Arctic Ocean and sub‐arctic regions. They could damage underwater infrastructure such as pipelines, and disrupt marine transportation. The below‐water shape of an iceberg is a key factor for iceberg management in the North Atlantic Ocean because it affects the iceberg towing plans and iceberg drift patterns. In recent years, unmanned platforms have been proposed as potential candidates for underwater iceberg mapping. Compared to a conventional ship‐based iceberg survey, using unmanned platforms is more efficient and safer. In this paper, we present research using a hybrid underwater glider to measure the underwater shape of an iceberg. The vehicle is equipped with a mechanical scanning sonar for range sensing and iceberg mapping, and a guidance system is designed to use the sonar measurements for guiding the vehicle to circumnavigate an iceberg at the desired standoff distance. Several field experiments have been conducted on an iceberg to evaluate the system performance. With repeated observations, the underside of the target iceberg was successfully reconstructed, and iceberg shape comparisons are presented.
Optimizing Donor Cellular Dissociation and Subretinal Injection Parameters for Stem Cell-Based Treatments
Authors: Scruggs Brittni A. , Jiao Chunhua , Cranston Cathryn M. , Kaalberg Emily , Wang Kai , Russell Stephen R. , Wiley Luke A. , Mullins Robert F. , Stone Edwin M. , Tucker Budd A. , Sohn Elliott H.
Published: April 2019

Subretinal delivery of stem cell-derived retinal cells as a strategy to treat retinal degenerative blindness holds great promise. Currently, two clinical trials are underway in which human fetal retinal progenitor cells (RPCs) are being delivered to patients by intravitreal or subretinal injection to preserve or restore vision, respectively. With the advent of the induced pluripotent stem cell (iPSC), and in turn three-dimensional derivation of retinal tissue, it is now possible to generate autologous RPCs for cell replacement. The purpose of this study was to evaluate the effect of commonly used cell isolation and surgical manipulation strategies on donor cell viability. iPSC-RPCs were subjected to various conditions, including different dissociation and isolation methods, injection cannula sizes, and preinjection storage temperatures and times. The effects of commonly used surgical techniques on both host and donor cell viability were evaluated in Yucatan mini-pigs (n = 61 eyes). We found a significant increase in cell viability when papain was used for RPC isolation. In addition, a significant decrease in cell viability was detected when using the 41G cannula compared with 31G and at storage times of 4 hours compared with 30 minutes. Although 96.4% of all eyes demonstrated spontaneous retinal reattachment following injection, retinal pigment epithelium (RPE) abnormalities were seen more frequently in eyes receiving injections via a 31G cannula; interestingly, eyes that received cell suspensions were relatively protected against such RPE changes. These findings indicate that optimization of donor cell isolation and delivery parameters should be considered when developing a subretinal cell replacement strategy. Stem Cells Translational Medicine  2019;8:797–809
Fates of antibiotic resistance genes in a distributed swine wastewater treatment plant
Authors: Yuan Qing‐Bin , Zhai Yi‐Fan , Mao Bu‐Yun , Schwarz Cory , Hu Nan
Published: April 2019

This study explores the prevalence, emission, and reduction of five ARGs (sulI, tetA, mphB, qnrD, and mcr‐1) and integron (intI) through a distributed swine wastewater purification facility and the effluent‐receiving environment. Typical metal resistance genes (MRGs), pathogenic bacterial indicators, the bacterial community, and wastewater properties were also explored to determine their effects on the fates of ARGs. Results indicated that the purification process could hardly effectively remove ARGs’ prevalence. 3.1 × 104–7.1 × 108 copies/L were present after purification, and 4%–57% of them persisted in the subsequent creek and adjacent soil. 16S rRNA sequencing suggested that the discharge of wastewater significantly changed the bacterial community in receiving creek and soil. Molecular ecological networks analysis detected the wide co‐occurrence among ARGs, MRGs, and PBGs, which could further facilitate the propagation of antibiotic resistance. ARG incidence and specific bacterial genera were closely correlated, suggesting an extensive hosting relationship. Redundancy analyses showed wastewater organics and nutrients showed positive correlation to most ARGs’ abundance, but negatively correlated to their relative abundance.

Practitioner points

Fate of five ARGs and intI was studied in a swine wastewater treatment system.

The treatment process could not effectively reduce ARGs’ abundance.

ARGs and pathogens in wastewater were transferred to the receiving creek and soil.

The network analysis found wide co‐occurrence among ARGs, metal resistance genes, and pathogens.

Wastewater nutrients positively correlated to ARG's abundance but negatively correlated to their relative abundance.
A Methodology for Global Sensitivity Analysis of Activated Sludge Models: Case Study with Activated Sludge Model No. 3 (ASM3)
Authors: Fortela Dhan Lord B. , Farmer Kyle , Zappi Alex , Sharp Wayne W. , Revellame Emmanuel , Gang Daniel , Zappi Mark
Published: April 2019

The main objective of this study was to demonstrate a computational approach of global sensitivity analysis (GSA) integrated with functional principal component analysis (fPCA) for activated sludge models through aggregation of time‐dependent model response patterns into time‐independent coefficients of functional principal components (PCs). This proposed approach addresses the main issue of time‐varying character of GSA indices when calculated solely on the time‐dependent model outputs. The GSA‐fPCA methodology was implemented using the rigorous model Activated Sludge Model No. 3 (ASM3) as case study. The approach transforms the time‐dependent model outputs into functional PCs prior to calculation of GSA indices to remove the time‐varying character of the calculated GSA indices. This work focused on the evaluation of the following key computational factors that may significantly influence the performance of the GSA‐fPCA methodology: (a) model parameter sampling range, (b) model simulation period, (c) basis functions system, and (d) state of the system being modeled—batch or continuous activated sludge process. Results show that first few functional PCs capture up to 100% of the curve patterns in the time‐dependent model outputs. The sensitivity indices calculated from the PC scores via Morris’ GSA technique elucidated parameter sensitivity patterns inherent to the complex mathematical structure of ASM3.

Practitioner points

Functional principal components‐mediated GSA technique to remove time‐varying character of sensitivity indices derived from time‐dependent dynamical models.

Technique amenable to improving efficiency of capturing response patterns into few functional principal components through various basis functions.

Identifying priority parameters for ASM3 model calibration requires specification of target model outputs to which parameter sensitivities are calculated.

GSA‐fPCA offers a comprehensive numerical approach to manipulating models depending on the intended applications: simple fast‐responding models to complex models.
Disinfection of anaerobic/aerobic sanitary effluent using ozone: Formaldehyde formation
Authors: Slompo Nathalie Dyane Miranda , da Silva Gustavo Henrique Ribeiro
Published: April 2019

The scarcity of natural resources supports the perspective of reusing treated effluents, mainly in agriculture, where the reduction in the demand of drinking water and the provision of alternative sources for nutrients are important. However, the process of disinfection, essential to the protection of human health, generates deleterious by‐products to both humans and the environment. This research aimed to evaluate the use of ozone as a disinfectant for wastewater treated by anaerobic/aerobic baffled reactor for later agricultural reuse. Disinfection tests were conducted by applying ozone, in batch, with applied dosages of 5, 8, and 10 mg O3/L and contact time of 7 min. All the tests led to formaldehyde formation, therefore within the standard suggested by the World Health Organization. For the indicators total coliforms and Escherichia coli, the ozone was considered effective, satisfying the criteria for agricultural reuse according to the World Health Organization of a dosage of 8 mg O3/L.

Practitioner Points

Proposal of decentralized system (anaerobic/aerobic baffled reactor + ozone disinfection) for effluent treatment for agricultural reuse.

Formation of formaldehyde dependent on applied ozone dose.

Demand of ozone consumed preferentially for the formation of by‐products, with low removal of COD.

High formaldehyde formation (high ozone demand) can impair the inactivation of pathogens.

System promotes effluent that meets the standards established by the World Health Organization (WHO) for agricultural reuse.