bluuebunny/crossref_metadata_2025 huggingface dataset:
TRPV4 channel mediates adventitial fibroblast activation and adventitial remodeling in pulmonary hypertension
Authors: Cussac Laure-Anne , Cardouat Guillaume , Tiruchellvam Pillai Nichiren , Campagnac Marilyne , Robillard Paul , Montillaud Anaïs , Guibert Christelle , Gailly Philippe , Marthan Roger , Quignard Jean-François , Savineau Jean-Pierre , Ducret Thomas
Published: November 2019

Pulmonary arterial adventitial fibroblasts (PAF), the most abundant cellular constituent of adventitia, act as a key regulator of pulmonary vascular wall structure and function from the outside-in. Previous studies indicate that transient receptor potential vanilloid 4 (TRPV4) channel plays an important role in the development of pulmonary hypertension (PH), but no attention has been given so far to its role in adventitial remodeling. In this study, we thus investigated TRPV4 implication in PAF activation occurring in PH. First, we isolated and cultured PAF from rat adventitial intrapulmonary artery. RT-PCR, Western blot, immunostaining, and calcium imaging (fluo-4/AM) showed that PAF express functional TRPV4 channels. In extension of these results, using pharmacological and siRNA approaches, we demonstrated TRPV4 involvement in PAF proliferation (BrdU incorporation) and migration (wound-healing assay). Then, Western blot experiments revealed that TRPV4 activation upregulates the expression of extracellular matrix protein synthesis (collagen type I and fibronectin). Finally, we explored the role of TRPV4 in the adventitial remodeling occurring in PH. By means of Western blot, we determined that TRPV4 protein expression was upregulated in adventitia from chronically hypoxic and monocrotaline rats, two animal models of PH. Furthermore, morphometric analysis indicated that adventitial remodeling is attenuated in PH-induced trpv4−/− mice. These data support the concept that PAF play an essential role in hypertensive pulmonary vascular remodeling and point out the participation of TRPV4 channel activity in PAF activation leading to excessive adventitial remodeling.
Low-calorie sweeteners cause only limited metabolic effects in mice
Authors: Glendinning John I. , Hart Stephanie , Lee Hyunseo , Maleh Jennifer , Ortiz Gabriella , Ryu Young Sang , Sanchez Abdias , Shelling Sarah , Williams Niki
Published: November 2019

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.
Breathing with fins: do the pectoral fins of larval fishes play a respiratory role?
Authors: Zimmer Alex M. , Mandic Milica , Rourke Kaitlyn M. , Perry Steve F.
Published: November 2019

Convective water flow across respiratory epithelia in water-breathing organisms maintains transcutaneous oxygen (O2) partial pressure (Po2) gradients that drive O2uptake. Following hatch, larval fishes lack a developed gill and the skin is the dominant site of gas transfer, yet few studies have addressed the contribution of convective water flow to cutaneous O2uptake in larvae. We hypothesized that the pectoral fins, which can generate water flow across the skin in larvae, promote transcutaneous O2transfer and thus aid in O2uptake. In zebrafish ( Danio rerio), the frequency of pectoral fin movements increased in response to hypoxia at 4 days postfertilization (dpf), but the response was blunted by 15 dpf, when the gills become the dominant site of O2uptake, and was absent by 21 dpf. In rainbow trout ( Oncorhynchus mykiss), Po2measured at the skin surface of ventilating larvae was lower when the pectoral fins had been surgically removed, directly demonstrating that fins contribute to convective flow that dissipates cutaneous Po2boundary layers. Lack of pectoral fins compromised whole animal O2consumption in trout during hypoxia, but this effect was absent in zebrafish. Overall, our findings support a respiratory role of the pectoral fins in rainbow trout, but their involvement in zebrafish remains equivocal.
How optimal is bimanual tracking? The key role of hand coordination in space
Authors: Mathew James , de Rugy Aymar , Danion Frederic R.
Published: November 2019

When coordinating two hands to achieve a common goal, the nervous system has to assign responsibility to each hand. Optimal control theory suggests that this problem is solved by minimizing costs such as the variability of movement and effort. However, the natural tendency to produce similar movements during bimanual tasks has been somewhat ignored by this approach. We consider a task in which participants were asked to track a moving target by means of a single cursor controlled simultaneously by the two hands. Two types of hand-cursor mappings were tested: one in which the cursor position resulted from the average location of two hands (Mean) and one in which horizontal and vertical positions of the cursor were driven separately by each hand (Split). As expected, unimanual tracking performance was better with the dominant hand than with the more variable nondominant hand. More interestingly, instead of exploiting this effect by increasing the use of the dominant hand, the contributions from both hands remained symmetrical during bimanual cooperative tasks. Indeed, for both mappings, and even after 6min of practice, the right and left hands remained strongly correlated, performing similar movements in extrinsic space. Persistence of this bimanual coupling demonstrates that participants prefer to maintain similar movements at the expense of unnecessary movements (in the Split task) and of increased noise from the nondominant hand (in the Mean task). Altogether, the findings suggest that bimanual tracking exploits hand coordination in space rather than minimizing motor costs associated with variability and effort.

NEW & NOTEWORTHY When two hands are coordinated to achieve a common goal, optimal control theory proposes that the brain assigns responsibility to each hand by minimizing movement variability and effort. Nevertheless, we show that participants perform bimanual tracking using similar contributions from the dominant and nondominant hands, despite unnecessary movements and a less accurate nondominant hand. Our findings suggest that bimanual tracking exploits hand coordination in space rather than minimizing motor costs associated with variability and effort.
The mammalian spinal commissural system: properties and functions
Authors: Maxwell David J. , Soteropoulos Demetris S.
Published: November 2019

Commissural systems are essential components of motor circuits that coordinate left–right activity of the skeletomuscular system. Commissural systems are found at many levels of the neuraxis including the cortex, brainstem, and spinal cord. In this review we will discuss aspects of the mammalian spinal commissural system. We will focus on commissural interneurons, which project from one side of the cord to the other and form axonal terminations that are confined to the cord itself. Commissural interneurons form heterogeneous populations and influence a variety of spinal circuits. They can be defined according to a variety of criteria including, location in the spinal gray matter, axonal projections and targets, neurotransmitter phenotype, activation properties, and embryological origin. At present, we do not have a comprehensive classification of these cells, but it is clear that cells located within different areas of the gray matter have characteristic properties and make particular contributions to motor circuits. The contribution of commissural interneurons to locomotor function and posture is well established and briefly discussed. However, their role in other goal-orientated behaviors such as grasping, reaching, and bimanual tasks is less clear. This is partly because we only have limited information about the organization and functional properties of commissural interneurons in the cervical spinal cord of primates, including humans. In this review we shall discuss these various issues. First, we will consider the properties of commissural interneurons and subsequently examine what is known about their functions. We then discuss how they may contribute to restoration of function following spinal injury and stroke.
Lack of mutant huntingtin in cortical efferents improves behavioral inflexibility and corticostriatal dynamics in Huntington’s disease mice
Authors: Estrada-Sánchez Ana María , Blake Courtney L. , Barton Scott J. , Howe Andrew G. , Rebec George V.
Published: November 2019

Abnormal communication between cerebral cortex and striatum plays a major role in the motor symptoms of Huntington’s disease (HD), a neurodegenerative disorder caused by a mutation of the huntingtin gene ( mHTT). Because cortex is the main driver of striatal processing, we recorded local field potential (LFP) activity simultaneously in primary motor cortex (M1) and dorsal striatum (DS) in BACHD mice, a full-length HD gene model, and in a conditional BACHD/Emx-1 Cre (BE) model in which mHTT is suppressed in cortical efferents, while mice freely explored a plus-shaped maze beginning at 20 wk of age. Relative to wild-type (WT) controls, BACHD mice were just as active across >40 wk of testing but became progressively less likely to turn into a perpendicular arm as they approached the choice point of the maze, a sign of HD motor inflexibility. BE mice, in contrast, turned as freely as WT throughout testing. Although BE mice did not exactly match WT in LFP activity, the reduction in alpha (8–13 Hz), beta (13–30 Hz), and low-gamma (30–50 Hz) power that occurred in M1 of turning-impaired BACHD mice was reversed. No reversal occurred in DS. In fact, BE mice showed further reductions in DS theta (4–8 Hz), beta, and low-gamma power relative to the BACHD model. Coherence analysis indicated a dysregulation of corticostriatal information flow in both BACHD and BE mice. Collectively, our results suggest that mHTT in cortical outputs drives the dysregulation of select cortical frequencies that accompany the loss of behavioral flexibility in HD.

NEW & NOTEWORTHY BACHD mice, a full-length genetic model of Huntington’s disease (HD), express aberrant local field potential (LFP) activity in primary motor cortex (M1) along with decreased probability of turning into a perpendicular arm of a plus-shaped maze, a motor inflexibility phenotype. Suppression of the mutant huntingtin gene in cortical output neurons prevents decline in turning and improves alpha, beta, and low-gamma activity in M1. Our results implicate cortical networks in the search for therapeutic strategies to alleviate HD motor signs.
A Novel Power‐Driven Grey Model with Whale Optimization Algorithm and Its Application in Forecasting the Residential Energy Consumption in China
Authors: Zhang Peng , Ma Xin , She Kun
Published: November 2019

Along with the improvement of Chinese people’s living standard, the proportion of residential energy consumption in total energy consumption is rapidly increasing in China year by year. Accurately forecasting the residential energy consumption is conducive to making energy programming and supply plan for the administrative departments or energy companies. By improving the grey action quantity of traditional grey model with an exponential time term, a novel power‐driven grey model is proposed to forecast energy consumption as reference data for decision makers. The nonlinear parameter of power‐driven grey action quantity is a crucial factor to influence the prediction precision. To promote the prediction accuracy of the power‐driven grey model, whale optimization algorithm is adopted to seek for the optimal value of the nonlinear parameter. Two validations on real‐world datasets are conducted, and the results indicate that the power‐driven grey model has significant advantages on the aspect of prediction performance compared with the other seven classical grey prediction methods. Finally, the power‐driven grey model is applied in forecasting the total residential energy and the thermal energy consumption of China.
Stepwise Adipogenesis of Decellularized Cellular Extracellular Matrix Regulates Adipose Tissue-Derived Stem Cell Migration and Differentiation
Authors: Zhang Ziang , Qu Rongmei , Fan Tingyu , Ouyang Jun , Lu Feng , Dai Jingxing
Published: November 2019

Microenvironmental factors can modulate the cellular status of adipose tissue-derived stem cells (ASCs). In response to microenvironmental changes, cells can remodel extracellular matrix (ECM) proteins, which play an important role in regulating cell behaviors. During adipogenic differentiation, ECM components secreted from ASCs remodel dramatically. To evaluate the role of stepwise adipogenesis-induced cellular secretion of ECM on the behavior of ASCs, we cultured ASCs in growth and adipogenic media, and ECM secreted from cells was characterized and decellularized. The ASCs were then reseeded on decellularized ECM (d-ECM) to determine the regulatory effects of ECM on cellular behaviors. During adipogenesis, cell-secreted ECM underwent remodeling characterized by conversion from fibronectin-rich ECM to laminin-rich ECM. The cellular status of ASCs was tested after reseeding on decellularized ECM. When reseeded on growth d-ECM, ASCs exhibited greater migration ability. In contrast, ASCs seeded on adipogenic d-ECM underwent adipogenic differentiation. In addition, integrin subunitαv and integrinsα6 andα7 were detected at significantly greater levels in ASCs cultured on growth and adipogenic d-ECM, respectively, suggesting that integrins play an important role in ASC migration and adipogenesis. This study demonstrated that stepwise adipogenesis-induced ECM production plays an important role in ASC migration and differentiation. In addition, this study provided a strategy to achieve precise regulation of stem cell function in adipose tissue engineering.
Load Transfer Characteristics of a Cable Bolt in DEPT
Authors: Li Xuwei
Published: November 2019

Cable bolts help surrounding rock masses of underground excavations to form internal rock structure and thus self‐stabilize through effective load transfer between rock masses and cable bolts. The load transfer characteristics of cable bolt play the most significant role in cable selection for support design. There are many factors potentially affecting the load transfer characteristics of cable bolt via strengthening or weakening load contributors such as cable bonding, mechanical interlocking, frictional resistance at cable‐grout interface and grout‐rock interface, and shearing of grout anchorage. Double embedment pull test (DEPT) is an effective, reliable, and repeatable test method of investigating the load transfer characteristics of cable bolt and thus was selected in this study. With DEPT, the influence of factors such as cable rotation, grout age, grout anchorage annulus thickness, cable wire profile, and failure mode on the load transfer characteristics of cable bolt were investigated in terms of tensile strength and stiffness in different loading stages. Conclusions drawn from the study can be used to improve cable installation quality and to select appropriate cable bolting technique.
Validation of a New Cognitive Screening Method for Stroke Patients
Authors: Saar Katri , Nyrkkö Hannu , Tolvanen Asko , Kuikka Pekka , Poutiainen Erja , Aro Tuija
Published: November 2019

Objective. Two million adults under fifty years of age have a cerebral stroke every year worldwide. Neuropsychological assessment is the best way to identify poststroke cognitive dysfunction, but it is often time-consuming and can be tiring for the patient, and hospitals vary in their availability of neuropsychological expertise. A valid and reliable cognitive screening method could be advantageous in identifying patients who need comprehensive neuropsychological examination. Our purpose in this study was to validate a newly developed cognitive screening method as an identifier of cognitive dysfunction after stroke in working-aged patients. Methods. We analyzed new cognitive screening method concurrent validity by comparing it in two groups formed on the basis of a comprehensive neuropsychological examination for 77 stroke patients. We identified the best balance of sensitivity and specificity by using receiver operating characteristic curve analysis and investigated the impact of the sociodemographic variables to the screening method total score variation. Results. We found a significant correlation between the method’s total score and performance in neuropsychological examination. The cognitive method’s internal consistency was strong; Cronbach’s alpha for all items was .818. The best balance of sensitivity (88%) and specificity (50%) was found at a total score cut point of 138. Subjects’ age and length of education were each responsible for 10% of total score variation. Conclusions. This study shows promising results for this new cognitive screening tool’s ability to identify poststroke cognitive decline and patients’ need for further detailed neuropsychological examination.
Oral Lichenoid Reaction: An Uncommon Side Effect of Rituximab
Authors: Giudice Amerigo , Liborio Francesco , Averta Fiorella , Barone Selene , Fortunato Leonzio
Published: November 2019

Oral lichenoid reactions (OLR) can be caused by systemic drug exposure. To the best of our knowledge, this is the second report describing a case of OLR induced by rituximab administration in a patient with a diagnosis of non-Hodgkin B-cell lymphoma. After 5 doses of rituximab, a typical pattern of OLP was identified with bilateral and symmetrical lesions on the buccal mucosa and on the right lingual margin. This temporal relationship suggested a probable association between oral lesions and drug therapy. The clinical diagnosis of a rituximab-induced OLR was confirmed by an incisional biopsy reporting a histopathological result of lichenoid mucositis consistent with oral lichen planus. Because of the increasing use of rituximab, it is necessary to know and recognize this uncommon side effect.
Antimicrobial Resistance Factors of Extended-Spectrum Beta-Lactamases Producing Escherichia coli and Klebsiella pneumoniae Isolated from Cattle Farms and Raw Beef in North-West Province, South Africa
Authors: Montso Kotsoana Peter , Dlamini Sicelo Beauty , Kumar Ajay , Ateba Collins Njie
Published: November 2019

Background. Extended spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae cause severe infections in humans which leads to complicated diseases. There is increasing evidence that cattle contribute to the development and spread of multidrug resistant pathogens and this raises public health concern. Despite this, data on the concurrence of ESBL producing pathogens in cattle, especially in the North-West province are rare. Therefore, the aim of the present study was to isolate, identify and characterise ESBL producing E. coli and K. pneumoniae species from cattle faeces and raw beef samples. Results. A total of 151 samples comprising 55 faeces samples and 96 raw beef samples were collected and 259 nonreplicative potential isolates of Enterobacteriaceae were obtained. One hundred and ninety-six isolates were confirmed as E. coli (114; 44%) and K. pneumoniae (82; 32%) species through amplification of uspA and uidA and ntrA gene fragments, respectively. Antimicrobial susceptibility test revealed that large proportions (66.7–100%) of the isolates were resistant to Amoxicillin, Aztreonam, Ceftazidime, Cefotaxime, and Piperacillin and were multidrug resistant isolates. Cluster analysis of antibiotic inhibition zone diameter data revealed close similarities between isolates from different sources or species thus suggested a link in antibiotic exposures. The isolates showing phenotypic resistance against ESBL antimicrobial susceptibility tests were screened for the presence of ESBL gene determinants. It was observed that 53.1% of the isolates harboured ESBL gene determinants. The blaTEM, blaSHV and blaCTX-M genes were detected in E. coli isolates (85.5%, 69.6%, and 58%, respectively) while blaCTX-M and blaOXA were detected in K. pneumoniae (40% and 42.9%, respectively). All the genetically confirmed ESBL producing E. coli and K. pneumoniae isolates were subjected to Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR analysis. Fingerprinting data revealed great similarities between isolates from different areas and sources which indicates cross-contamination between cattle and beef. Conclusion. This study revealed that cattle and its associated food products, beef in particular, harbour ESBL producing pathogens. And this warrants a need to enforce hygiene measures and to develop other mitigation strategies to minimise the spread of antibiotic resistant pathogens from animals to human.
MC4R Single Nucleotide Polymorphisms Were Associated with Metabolically Healthy and Unhealthy Obesity in Chinese Northern Han Populations
Authors: Gao Luying , Wang Linjie , Yang Hongbo , Pan Hui , Gong Fengying , Zhu Huijuan
Published: November 2019

Melanocortin-4 receptor (MC4R) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients. Therefore, we aimed to study single nucleotide polymorphisms (SNPs) in the MC4R gene associated with metabolically healthy and unhealthy obesity in Chinese Northern Han populations. A total of 1100 Chinese Northern Han subjects were recruited and divided into four groups according to the criteria of the Adult Treatment Panel-III (ATP-III) and World Health Organization (WHO): MUHO (n = 300), MHO (n = 196), metabolic unhealthy normal weight (MUH-NW) (n = 303), and metabolic healthy normal weight (MH-NW) (n = 301). DNA samples were extracted, and six SNPs of the MC4R gene, including rs2331841, rs656710, rs17782313, rs571312, rs12970134, and rs11872992, were genotyped with the matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) method. Among the six SNPs of the MC4R gene, rs2331841 (A/G) was the most significant and could account for 0.9% of obesity etiology. Compared with the normal weight group, rs2331841 of the MC4R gene was associated with obesity (P=0.032). The obesity risk of subjects with the AG genotype in the rs2331841 site was 82% higher than the risk of those with the GG genotype (β = 0.60, OR = 1.82, P=0.030). After adjusting for sex and age, the frequency of the A allele in the rs2331841 site was higher in the MUHO group than in the MH-NW group (27.9% vs. 21.1%, respectively, OR = 1.49, 95% CI 1.14–1.96, P=0.005) and in the MUHO group than in the MHO group (27.9% vs. 22.3%, respectively, OR = 1.39, 95% CI 1.02–1.92, P=0.039). Among the three genotypes of rs2331841, the subjects with the AA/AG genotype had higher diastolic blood pressure (DBP) than those with the GG genotype. Our data first suggest that SNPs in the rs2331841 site of the MC4R gene are closely related to obesity and its related metabolic disorders in Chinese Northern Han populations. The participants with an A allele of rs2331841 had a higher risk of obesity and MUHO than other participants.
Efficacy of Weikang Pian in Patients with Functional Dyspepsia: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial
Authors: Yan Lijing , Yu Lijin , Zhao Linlin , Wang Dongsheng , Qin Dilan , Fan Haiwei , Cheng Ling , Qiu Musen , Chen Xiao , Zhou Lu , Qiu Juan , Yao Jiamei , Wang Wenbo , Qiu Xinjian
Published: November 2019

Background. FD (functional dyspepsia) is a common functional gastrointestinal disorder, which lacks effective and safe treatment. Chinese herbal medicine (CHM) has been applied in FD treatment for thousands of years with satisfactory clinical outcomes. Zhishi is a classical traditional Chinese medicine used to treat FD. Weikang pian (WKP) is made of flavonoids extracted from zhishi which could effectively alleviate the symptoms of FD. This research aimed to assess the efficacy and safety of WKP in FD treatment. Methods. This was a randomized, double-blinded and placebo-controlled clinical trial. The patients were diagnosed as FD according to RomeIII criteria. Then, FD patients were selected and assigned randomly to either WKP or placebo group. The subjects randomly received WKP or placebo for 4 weeks with 4 tablets each time, 3 times daily. The single dyspepsia symptom (SDS) scale and the gastric emptying function were measured before and after the treatment. Moreover, the safety of the trial and patient compliance were evaluated. Results. A total of 60 FD patients were eventually enrolled in the trial, among them 45 patients in the WKP group and 15 patients in the placebo group. The primary outcome was the SDS scale, including assessments of postprandial distension, early satiety, epigastric burning, and pain. The secondary outcome was the gastric emptying function. Compared with the placebo group, the symptoms of FD in the WKP group were relieved after 4 weeks of treatment (P<0.05). Some minor changes appeared in the four groups, but there were no significant differences in gastric emptying parameters of GER (2-hour gastric emptying rate) and GET/2 (gastric semiempty time) (P>0.05). Severe adverse events were absent. The compliance to treatment was 94%–96%, and there was no significant difference between the groups. Conclusion. WKP can relieve FD symptoms to some extent. This trial is registered with Chinese Clinical Trial Registry (ChiCTR): CTR 20132482.
Research on FBG-Based Sensor Networks and Their Coexistence with Fiber Optical Transmission Systems
Authors: Senkans Ugis , Braunfelds Janis , Lyashuk Ilya , Porins Jurgis , Spolitis Sandis , Bobrovs Vjaceslavs
Published: November 2019

Market forecasts and trends for the usage of fiber optical sensors confirm that demand for them will continue to increase in the near future. This article focuses on the research of fiber Bragg grating (FBG) sensor network, their applications in IoT and structural health monitoring (SHM), and especially their coexistence with existing fiber optical communication system infrastructure. Firstly, the spectrum of available commercial optical FBG temperature sensor was experimentally measured and amplitude-frequency response data was acquired to further develop the simulation model in the environment of RSoft OptSim software. The simulation model included optical sensor network, which is combined with 8-channel intensity-modulated wavelength division multiplexed (WDM) fiber optical data transmission system, where one shared 20 km long ITU-TG.652 single-mode optical fiber was used for transmission of both sensor and data signals. Secondly, research on a minimal allowable channel spacing between sensors’ channels was investigated by using MathWorks MATLAB software, and a new effective and more precise determination algorithm of the exact center of the sensor signal’s peak was proposed. Finally, we experimentally show successfully operating coexistence concept of the spectrum-sliced fiber optical transmission system with embedded scalable FBG sensor network over one shared optical fiber, where the whole system is feed by only one broadband light source.
Age-Related Changes in the Fraction of Cervical Intraepithelial Neoplasia Grade 3 Related to HPV Genotypes Included in the Nonavalent Vaccine
Authors: Giannella Luca , Delli Carpini Giovanni , Di Giuseppe Jacopo , Prandi Sonia , Tsiroglou Dimitrios , Ciavattini Andrea
Published: November 2019

Objective. The prevalence of some human papillomavirus (HPV) genotypes has been shown to change with age. So, also the distribution of HPV genotypes included in the nonavalent vaccine may not be the same at all ages, and this could mean that vaccine protection against cervical cancer may be affected by age. The present study aimed to evaluate whether there are age-related changes in the fraction of high-grade cervical intraepithelial neoplasia (CIN) attributable to HPV genotypes included in the nonavalent vaccine. Methods. Two hundred four consecutive women undergoing conization with a histological diagnosis of CIN3 were retrospectively analyzed. All included women had a preconization HPV genotyping (HPV Sign® Genotyping Test). The women were divided into three groups according to age: <35, 35–44, and ≥45 years of age. Based on HPV genotypes detected in cervical lesions, the age-related changes in the expected vaccine protection were evaluated by the Cochran–Armitage test for trend. Results. The fraction of CIN3 attributable to HPV genotypes included in the nonavalent vaccine showed a significant negative trend with increasing age, with potential vaccine protection of 82% after the age of 45 (p=0.006). The rate of HPV-16 and HPV-33, included in the vaccine, showed a negative trend with age (p=0.047 and p=0.044, respectively). Among HPV genotypes not covered by the vaccine, the rate of non-high-risk HPVs (genotypes: 53-54-70-73-82-85-87) showed a significant positive trend with increasing age (p=0.018). Conclusions. Although the fraction of CIN3 attributable to genotypes included in the nonavalent HPV vaccine was high even after age 45, older women appeared to be more at risk of high-grade CIN related to HPV genotypes not included in the vaccine. Interestingly, older women showed a higher rate of precancerous cervical lesions associated with non-high-risk HPV. The present findings seem to raise the question about the management of cervical pathology at a later age in a future postvaccination era.
Compound Kushen Injection as an Adjunctive Therapy for the Treatment of Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Pu Liu , Chen Wei-hao , Cao Lu-xi , Wu Kun-ji , Chen Shu-lian , Lin Ji-huan , Li Cheng-lu , Wang Shi-qi , Zhu Ming-min , Zhang Yi-min
Published: November 2019

Objectives. To evaluate the efficacy and safety of compound Kushen injection (CKI) combined with chemo treatment (chemo) for non-small-cell lung cancer (NSCLC). Methods. We systematically searched the literature published in seven databases, including Embase, PubMed, central, MEDLINE, CNKI, Wanfang, and VIP, from their inception to April 2019 for all randomized controlled trials (RCTs) comparing CKI plus chemo with chemo alone in patients with NSCLC. Our main end point was clinical efficiency and the secondary outcomes were Karnofsky performance score (KPS), immune function, and adverse events. The Cochrane risk of bias tool was applied for quality assessment. Results. 10 studies involving 1019 participants were included. The clinical response rate (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.06 to 1.37; P=0.003), KPS (RR = 2.18, 95% CI: 1.49 to 3.17; P<0.0001), immune function (mean differences (MD) = 0.82, 95% CI: 0.12 to 1.52; P=0.02) and adverse effects (RR = 0.67, 95% CI: 0.60 to 0.74; P<0.00001) in the CKI plus chemo group showed significant differences when compared with chemo alone. Conclusions. CKI combined with chemo can improve clinical efficiency, KPS, and immune function and reduce adverse reactions in patients with NSCLC when compared with chemo alone. However, more rigorously designed RCTs are needed to validate this benefit, as some of the included RCTs are of low methodological quality.
Mass‐Stiffness Combined Perturbation Method for Mode Shape Monitoring of Bridge Structures
Authors: Zhang Liye , Xia Ye , Lozano-Galant Jose A. , Sun Limin
Published: November 2019

Identification of the mode shapes through monitoring is one of the key problems in damage diagnosis based on modal parameters especially for damaged structures. In order to obtain mode shapes of damaged structures easily and accurately, the mass‐stiffness combined perturbation (MSCP) method is proposed in this paper. To do so, the relationship between the stiffness perturbation mode shapes of damaged and intact structures is firstly derived and established. Then, the principle of similar frequency is applied to optimize the objective function of the most suitable mass perturbation model. Both numerical analyses and experimental tests on simple and complex structures demonstrate that the proposed MSCP method achieves higher precision than traditional mode shape identification methods. The additional advantages of the MSCP method include (i) lower requirement on the frequency analysis of only damaged structures and (ii) higher effectiveness for minor damage scenarios. In fact, the lower the damage, the higher the precision achieved by the MSCP method. As illustrated in the paper, the proposed technique has excellent applications in mode shapes identification and structural health monitoring.
Influence of Hydrophobic Coating on Freeze-Thaw Cycle Resistance of Cement Mortar
Authors: Song Zijian , Lu Zhongyuan , Lai Zhenyu
Published: November 2019

Due to the porous characteristics of cement-based materials, they are often corroded by salt solutions, which results in decreased durability, especially against damage under freeze-thaw cycles (FTCs). Improving surface properties is an effective way to improve the durability of these materials. In this study, a hydrophobic coating was applied to the surface of cement mortar by chemical modification of low surface energy materials. Fourier transform infrared spectroscopy (FT-IR) showed that low surface energy substances are linked to hydration products through chemical bonds. A water contact angle test indicates that the surface of cement mortar changed from hydrophilic (θ = 14°) to hydrophobic (θ = 140°) after chemical modification. The cumulative water uptake of hydrophobic samples decreased by 90%. Meanwhile, the wear resistance of the hydrophobic coatings was excellent. Compared with the baseline sample, mass loss rate, flexural strength, and compressive strength of hydrophobic coating samples increased several-fold in the FTC test. Microstructural changes of the mortar were characterized by scanning electron microscopy. The results show that a hydrophobic coating can significantly improve the freeze-thaw resistance of cement-based materials. The formation of a hydrophobic layer on the surface of cement-based materials can improve their durability. The research results not only have applications in civil engineering but will also have great impact in the restoration of historic structures.
Chromosomal Aberrations in Pediatric Patients with Developmental Delay/Intellectual Disability: A Single-Center Clinical Investigation
Authors: Hu Ting , Zhang Zhu , Wang Jiamin , Li Qinqin , Zhu Hongmei , Lai Yi , Wang He , Liu Shanling
Published: November 2019

Introduction. Chromosomal microarray analysis (CMA) has currently been considered as the first-tier genetic test for patients with developmental delay/intellectual disability (DD/ID) in many countries. In this study, we performed an extensive assessment of the value of CMA for the diagnosis of children with ID/DD in China. Methods. A total of 633 patients diagnosed with DD/ID in West China Second University Hospital, Sichuan University, were recruited from January 2014 to March 2019. The patients were classified into 4 subgroups: isolated DD/ID, DD/ID with multiple congenital anomalies (MCA), isolated autism spectrum disorders (ASDs), and DD/ID with epilepsy. CMA was performed on Affymetrix 750K platform. Results. Among the 633 patients, 127 cases were identified as having pathogenic copy number variations (pCNVs) with an overall positive rate of 20.06%. Of the 127 cases with abnormal results, 76 cases had 35 types of microdeletion/microduplication syndromes (59.84%) including 5 cases caused by uniparental disomy (UPD), and 18 cases had unbalanced rearrangements (14.17%) including 10 cases inherited from parental balanced translocations or pericentric inversions. The diagnostic yields of pCNVs for the subgroups of isolated DD/ID, DD/ID with MCA, isolated ASD, and DD/ID with epilepsy were 18.07% (60/332), 34.90% (52/149), 3.70% (3/81), and 16.90% (12/71), respectively. The diagnostic yield of pCNVs in DD/ID patients with MCA was significantly higher than that of the other three subgroups, and the diagnostic yield of pCNVs in isolated ASD patients was significantly lower than that of the other three subgroups (p<0.05). Conclusion. Microdeletion/microduplication syndromes and unbalanced rearrangements are probably the main genetic etiological factors for DD/ID. DD/ID patients with MCA have a higher rate of chromosomal aberrations. Parents of DD/ID children with submicroscopic unbalance rearrangements are more likely to have chromosome balanced translocations or pericentric inversions, which might have been missed by karyotyping. CMA can significantly improve the diagnostic rate for patients with DD/ID, which is of great value for medical management and clinical guidance for genetic counseling.
Vitamin D–VDR Signaling Inhibits Wnt/β-Catenin–Mediated Melanoma Progression and Promotes Antitumor Immunity
Authors: Muralidhar Sathya , Filia Anastasia , Nsengimana Jérémie , Poźniak Joanna , O'Shea Sally J. , Diaz Joey M. , Harland Mark , Randerson-Moor Juliette A. , Reichrath Jörg , Laye Jonathan P. , van der Weyden Louise , Adams David J. , Bishop D.T. , Newton-Bishop Julia
Published: November 2019

1α,25-Dihydroxyvitamin D3 signals via the vitamin D receptor (VDR). Higher serum vitamin D is associated with thinner primary melanoma and better outcome, although a causal mechanism has not been established. As patients with melanoma commonly avoid sun exposure, and consequent vitamin D deficiency might worsen outcomes, we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D–VDR signaling and replicated the findings in The Cancer Genome Atlas metastases. VDR expression was independently protective for melanoma-related death in both primary and metastatic disease. High tumor VDR expression was associated with upregulation of pathways mediating antitumor immunity and corresponding with higher imputed immune cell scores and histologically detected tumor-infiltrating lymphocytes. High VDR–expressing tumors had downregulation of proliferative pathways, notably Wnt/β-catenin signaling. Deleterious low VDR levels resulted from promoter methylation and gene deletion in metastases. Vitamin D deficiency (<25 nmol/L ∼ 10 ng/mL) shortened survival in primary melanoma in a VDR-dependent manner. In vitro functional validation studies showed that elevated vitamin D–VDR signaling inhibited Wnt/β-catenin signaling genes. Murine melanoma cells overexpressing VDR produced fewer pulmonary metastases than controls in tail-vein metastasis assays. In summary, vitamin D–VDR signaling contributes to controlling pro-proliferative/immunosuppressive Wnt/β-catenin signaling in melanoma and this is associated with less metastatic disease and stronger host immune responses. This is evidence of a causal relationship between vitamin D–VDR signaling and melanoma survival, which should be explored as a therapeutic target in primary resistance to checkpoint blockade.

Significance:

VDR expression could potentially be used as a biomarker to stratify patients with melanoma that may respond better to immunotherapy.
Capping Protein Regulator and Myosin 1 Linker 3 Is Required for Tumor Metastasis
Authors: Wang Huan , Wang Chao , Peng Guang , Yu Doudou , Cui Xin-Gang , Sun Ying-Hao , Ma Xiaojing
Published: November 2019

Metastasis accounts for 90% of deaths caused by solid tumors, but the multitude of mechanisms underlying tumor metastasis remains poorly understood. CARMIL1 and 2 proteins are capping protein (CP) interactants and multidomain regulators of actin-based mobility. However, CARMIL3′s function has not been explored. Through bioinformatic metadata analysis, we find that high CARMIL3 expression correlates with poor survival of patients with breast and prostate cancer. Functional studies in murine and xenograft tumor models by targeted diminution of CARMIL3 expression or forced expression demonstrate that CARMIL3 is vitally important for tumor metastasis, especially for metastatic colonization. Consistent with a predominantly cell-intrinsic mode of action, CARMIL3 is also crucial for tumor cell migration and invasion in vitro. Coimmunoprecipitation coupled with mass spectrometric analyses identifies a group of CARMIL3-interacting proteins, including capping protein, that are involved in actin cytoskeletal organization, which is required for cell polarization and focal adhesion formation. Moreover, molecular pathway enrichment analysis reveals that lack of CARMIL3 leads to loss of cell adhesions and low CARMIL3 expression in breast cancer patient specimens is implicated in epithelial–mesenchymal transition. We also find that CARMIL3 sustains adherens junction between tumor cells. This is accomplished by CARMIL3 maintaining E-cadherin transcription downstream of HDACs through inhibiting ZEB2 protein level, also via protecting β-catenin from ubiquitination-mediated degradation initiated by the destruction complex.

Implications:

This study uncovers CARMIL3 as a novel and critical regulator of metastatic progression of cancers and suggests therapeutic potentials to target CARMIL3.
Influence of Temperature on the Determination of
Enzyme Activities in Human Serum
Authors: Jung K. , Liese W.
Published: November 2019

Optimum reaction conditions for determination of 7-glutamyl transferase were
studied at 25, 30 and 37 °C using a kinetic test and 7-glutamyl-3-carboxy-4-nitranilide as substrate.
There was no dependence on temperature for half saturation constants of 7-glutamyl-3-carboxy-
4-nitranilide. The corresponding constants for glycylglycine were influenced by temperature and
the pH. The pH optimum showed a dependence upon temperature. In Arrhenius’ plot, a deviation
from straight line can be observed only above 35 °C. The influence of temperature on the
determination of enzyme activities in human serum are discussed.
Effect of Cofactor Depletion on Liver Tyrosine
Aminotransferase Expression
Authors: Shuler John K. , Tryfiates George P.
Published: November 2019

Hepatic tyrosine aminotransferase (L-tyrosine: 2-oxoglutarate aminotransferase,
EC 2.6.1.5) was partially purified from pyridoxine depleted and control rats and subsequently
resolved by electrophoresis on polyacrylamide gels. Enzyme activity was detected histochemically
in situ on the gel. Six enzymatically active forms were detected. Cofactor depletion effected
further resolution of the enzyme into seven active forms as revealed by the bifurcation of the
major active peak.
Identification of Asthma-COPD Overlap, Asthma, and Chronic Obstructive Pulmonary Disease Phenotypes in Patients with Airway Obstruction: Influence on Treatment Approach
Authors: Romem Ayal , Rokach Ariel , Bohadana Abraham , Babai Polina , Arish Nissim , Azulai Hava , Glazer Mendel , Izbicki Gabriel
Published: November 2019

Background: Many studies have described asthma-COPD overlap (ACO) among patients diagnosed with asthma or chronic obstructive pulmonary disease (COPD), but less so in broad populations of patients with chronic airway obstruction. Objective: This study aimed to (i) examine the prevalence of ACO, asthma, and COPD phenotypes among subjects referred for pulmonary function testing (PFT), who had airway obstruction in spirometry (forced expiratory volume in 1 s [FEV1]/forced vital capacity [FVC] <0.7); and (ii) delineate the therapeutic approach of each group. Methods: Cross-sectional study of patients who were referred for PFT at the Rokach Institute, in Jerusalem. Working definitions were as follows: (a) COPD: post-bronchodilator (BD) FEV1/FVC <0.70; (b) asthma: physician-diagnosed asthma before age 40 and/or minimum post-BD increase in FEV1 or FVC of 12% and 200 mL; and (c) ACO: the combination of the 2. Demographics, smoking habits, episodes of exacerbation, health-related quality of life (HRQL), and respiratory medication utilization were analyzed. Results: Of 3,669 referrals from January 1 to April 30, 2017, 1,220 had airway obstruction of which 215 were included. Of these, 82 (38.1%) had ACO, 49 (22.8%) asthma, and 84 (39.1%) COPD. ACO subjects tended to (a) be predominantly female; (b) be older than asthmatics, (c) be smokers; (d) have worse HRQL in the activity domain; and (d) have more exacerbations. Treatment of ACO and COPD patients differed from that of asthmatics, but not from each other, in the proportion of subjects on maintenance treatment, use of LABA, LAMA, and ICS, alone or in combination, and in the number of inhaler devices used by patients. Conclusion: ACO represented >1/3 of patients referred for PFT. Despite a clearly identifiable phenotype, ACO patients received treatment similar to COPD patients, suggesting poor ACO identification. Our data emphasize the need to raise the awareness of ACO among clinicians, in order to guide better recognition and appropriate treatment in individual patients.
Breastfeeding and Atopic Dermatitis Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies
Authors: Lin Bingjiang , Dai Ru , Lu Lingyi , Fan Xin , Yu Yingzhe
Published: November 2019

Objectives: The effect of breastfeeding on atopic dermatitis (AD) remains controversial. To determine the association ­between breastfeeding and AD, we conducted an updated meta-analysis of prospective cohort studies. Methods: A comprehensive search of PubMed, EMBASE, MEDLINE and Cochrane Library was conducted. Studies meeting the predetermined criteria were evaluated by 2 authors independently. The pooled relative risk (RR) adjusted for confounders with its 95% CI was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis and meta-regression. Results: A total of 27 studies were included for meta-analysis. The pooled estimates for the effect of total and exclusive breastfeeding on AD were 1.01 (95% CI 0.93–1.10) and 0.99 (95% CI 0.88–1.11), respectively. Heterogeneity was substantial across studies (total: p < 0.01 or I2 = 65.2%; exclusive: p < 0.01 or I2 = 72.3%). There was a weak evidence for a protective effect of breastfeeding against AD in cohorts with atopic heredity (total: RR 0.85, 95% CI 0.74–0.98; exclusive: RR 0.83, 95% CI 0.70–0.97). In cohorts without atopic heredity, the effect shifted to the risk side when limited to exclusive breastfeeding (RR 1.19, 95% CI 1.02–1.40) while it dropped towards null when limited to total breastfeeding (RR 1.11, 95% CI 0.94–1.31). Conclusions: There is no association between AD and breastfeeding, regardless of total or exclusive breastfeeding patterns. There is some evidence for a protective function of exclusive and total breastfeeding in a cohort with atopic heredity. The effect shifts to the risk side in cohorts without atopic heredity. However, these findings should be interpreted with caution because heterogeneity is evident.