bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and clinical characterisation of pregnant women with eating disorders
Authors: Bye Amanda , Nath Selina , Ryan Elizabeth G. , Bick Debra , Easter Abigail , Howard Louise M , Micali Nadia
Published: January 2020

Objective

To estimate prevalence of lifetime and current eating disorders (ED) in a sample of pregnant women in South‐East London and to describe their sociodemographic and clinical characteristics.

Method

Secondary analysis of data from a cross‐sectional survey. Using a stratified sampling design, 545 pregnant women were recruited. Diagnostic interviews were administered to assess lifetime and current ED, depression, anxiety, and borderline personality disorder. Data were extracted from maternity records to assess identification of ED in antenatal care. Estimates of population prevalence of ED were obtained using sampling weights to account for the stratified sampling design.

Results

Weighted prevalence of lifetime ED was 15.35% (95% confidence interval [CI] [11.80, 19.71]), and current ED was 1.47% (95% CI [0.64, 3.35]). Depression, anxiety, and history of deliberate self‐harm or attempted suicide were common in pregnant women with ED. Identification of ED in antenatal care was low.

Conclusions

Findings indicate that by early pregnancy, a significant proportion of pregnant women will have had ED, although less typically during pregnancy, and psychiatric comorbidity is common. Yet ED were poorly recognised in antenatal care. The findings highlight the importance of increasing awareness about maternal ED to improve identification and response to the healthcare needs of pregnant women with ED.
Study of gas emission law at the heading face in a coal‐mine tunnel based on the Lattice Boltzmann method
Authors: Wang Qifei , Li Chengwu , Zhao Yuechao , Ai Dihao
Published: January 2020

Gas distribution ahead of the coal tunnel is the key risk factor controlling coal and gas outburst. Based on an analysis of the influence of the stress state on the porosity of the coal seam, an improved quartet structure generation set (QSGS) random porous media generation tool is used to reconstruct the coal structure. Adopting the reconstructed pore structure of the coal as the boundary of the flow field, the Lattice Boltzmann method (LBM) is used to simulate the gas dynamic distribution law ahead of the coal tunnel. The gas pressure of the coal seam decreases obviously in the fracture zone only, and the change in gas pressure is very small in the stress concentration zone and ahead of the coal seam. This research is of significance for gas drainage and the prevention of coal and gas outburst hazards in the working face during coal tunneling.
Numerical and Experimental Investigation of the Asymmetric Humidification and Dynamic Temperature in Proton Exchange Membrane Fuel Cell
Authors: Liu Y. , Bai S. , Wei P. , Pei P. , Yao S. , Sun H.
Published: January 2020

The relative humidity is an important parameter reflecting the performance of proton exchange membrane (PEM) fuel cells, which is often accompanied by changes in heat and temperature. In order to study the different humidification effects on the performance of PEM fuel cells, a temperature and heat transfer (T&HT) model is presented. The innovation of this paper is to study the performance of fuel cell (FC) from the perspective of temperature heat transfer by asymmetric humidification. Firstly, symmetrical humidification experiments are performed at three operating temperatures. After that, a three‐dimensional (3D) structure is built using fluent and T&HT model is imported through custom functions. Secondly, the asymmetric humidification experiment is put into practice with 60 °C operating temperature. Furthermore, the Taguchi method is used to optimize the performance of fuel cells in the crossover experiment. Finally, the experimental and numerical results are compared by the contours and polarization curves. The results show that T&HT model is in agreement with the experiment, and asymmetric humidification is more reasonable and flexible than symmetrical humidification. When the cathode relative humidity is 50% and the anode relative humidity is 75%, the maximum optimization rate of system efficiency is 17%.
The Histone Methyltransferase G9a Promotes Cholangiocarcinogenesis Through Regulation of the Hippo Pathway Kinase LATS2 and YAP Signaling Pathway
Authors: Ma Wenbo , Han Chang , Zhang Jinqiang , Song Kyoungsub , Chen Weina , Kwon Hyunjoo , Wu Tong
Published: January 2020

Background and Aims

Cholangiocarcinoma (CCA) is a highly malignant epithelial tumor of the biliary tree with poor prognosis. In the current study, we present evidence that the histone‐lysine methyltransferase G9a is up‐regulated in human CCA and that G9a enhances CCA cell growth and invasiveness through regulation of the Hippo pathway kinase large tumor suppressor 2 (LATS2) and yes‐associated protein (YAP) signaling pathway.

Approach and Results

Kaplan‐Meier survival analysis revealed that high G9a expression is associated with poor prognosis of CCA patients. In experimental systems, depletion of G9a by small interfering RNA/short hairpin RNA or inhibition of G9a by specific pharmacological inhibitors (UNC0642 and UNC0631) significantly inhibited human CCA cell growth in vitro and in severe combined immunodeficient mice. Increased G9a expression was also observed in mouse CCA induced by hydrodynamic tail vein injection of notch intracellular domain (NICD) and myr‐Akt. Administration of the G9a inhibitor UNC0642 to NICD/Akt‐injected mice reduced the growth of CCA, in vivo. These findings suggest that G9a inhibition may represent an effective therapeutic strategy for the treatment of CCA. Mechanistically, our data show that G9a‐derived dimethylated H3K9 (H3K9me2) silenced the expression of the Hippo pathway kinase LATS2, and this effect led to subsequent activation of oncogenic YAP. Consequently, G9a depletion or inhibition reduced the level of H3K9me2 and restored the expression of LATS2 leading to YAP inhibition.

Conclusions

Our findings provide evidence for an important role of G9a in cholangiocarcinogenesis through regulation of LATS2‐YAP signaling and suggest that this pathway may represent a potential therapeutic target for CCA treatment.
A Single Infusion of Zoledronate in Postmenopausal Women Following Denosumab Discontinuation Results in Partial Conservation of Bone Mass Gains
Authors: Everts-Graber Judith , Reichenbach Stephan , Ziswiler Hans Rudolf , Studer Ueli , Lehmann Thomas
Published: January 2020

Discontinuation of denosumab is associated with a rapid return of bone mineral density (BMD) to baseline and an increased risk of multiple vertebral fractures. No subsequent treatment regimen has yet been established for preventing either loss of BMD or multiple vertebral fractures after denosumab discontinuation. The aim of this 8-year observational study was to investigate the effect of a single zoledronate infusion, administered 6 months after the last denosumab injection, on fracture occurrence and loss of BMD. We report on 120 women with postmenopausal osteoporosis who were treated with 60 mg denosumab every 6 months for 2 to 5 years (mean duration 3 years) and then 5 mg zoledronate 6 months after the last denosumab injection. All patients were evaluated clinically, by dual-energy X-ray absorptiometry (DXA) and vertebral fracture assessment (VFA), before the first and after the last denosumab injection and at 2.5 years (median) after denosumab discontinuation. During this off-treatment period, 3 vertebral fractures (1.1 per 100 patient-years) and 4 nonvertebral fractures (1.5 per 100 patient-years) occurred. No patients developed multiple vertebral fractures. Sixty-six percent (confidence interval [CI] 57% to 75%) of BMD gained with denosumab was retained at the lumbar spine and 49% (CI 31% to 67%) at the total hip. There was no significant difference in the decrease of BMD between patients with BMD gains of >9% versus <9% while treated with denosumab. Previous antiresorptive treatment or prevalent fractures had no impact on the decrease of BMD, and all bone loss occurred within the first 18 months after zoledronate infusion. In conclusion, a single infusion of 5 mg zoledronate after a 2- to 5-year denosumab treatment cycle retained more than half of the gained BMD and was not associated with multiple vertebral fractures, as reported in patients who discontinued denosumab without subsequent bisphosphonate treatment. © 2020 American Society for Bone and Mineral Research.
The Loss of Profilin 1 Causes Early Onset Paget's Disease of Bone
Authors: Scotto di Carlo Federica , Pazzaglia Laura , Esposito Teresa , Gianfrancesco Fernando
Published: January 2020

Paget's disease of bone (PDB) is a late-onset disorder frequently caused by mutations in the SQSTM1 gene, leading to hyperactive osteoclasts and resulting in bone pain, deformities, and fractures. However, some more severe forms of PDB—negative for SQSTM1 mutations—have been described, in which the disease degenerates into bone cancers and shows a poor prognosis. Osteosarcoma is the most frequent and aggressive tumor arising in PDB (OS/PDB), with a 5-year survival rate almost nil, but the underlying molecular mechanism is unknown. Here, we investigated an extended pedigree with 11 individuals affected by early onset and polyostotic PDB, mainly interesting the appendicular skeleton. Interestingly, three members also developed secondary osteosarcoma. We performed exome sequencing and identified a 4-bp deletion in the PFN1 gene, resulting in the degradation of the mutant protein. Copy number screening on 218 PDB individuals of our biobank disclosed that four of them (~2%) carry a germline heterozygous deletion of PFN1. The identification of these subjects, who exhibit a particularly severe form of disease, emphasizes the diagnostic value of this genetic screening to identify PDB individuals predisposed to develop osteosarcoma. In fact, we detected allelic imbalance at PFN1 locus also in 8 of 14 (57%) sporadic OS/PDB, further proving its causative role. in vitro experiments also confirmed PFN1 involvement in this form of PDB. Indeed, CRISPR-Cas9-mediated Pfn1 knockout in pre-osteoclasts resulted into enhanced osteoclast differentiation and resorption, with the formation of large osteoclasts never described before in PDB. In addition, Pfn1 lacking pre-osteoblasts lost their differentiation capability and failed to efficiently mineralize bone. Moreover, they acquired features of malignant transformation, including loss of focal adhesions and increased invasion ability. In conclusion, these findings disclose PFN1 haploinsufficiency as the pathological mechanism in OS/PDB. © 2020 American Society for Bone and Mineral Research.
Differential effects of N‐TiO2 nanoparticle and its photo‐activated form on autophagy and necroptosis in human melanoma A375 cells
Authors: Mohammadalipour Zahra , Rahmati Marveh , Khataee Alireza , Moosavi Mohammad A.
Published: January 2020

The manipulation of autophagy provides a new opportunity for highly effective anticancer therapies. Recently, we showed that photodynamic therapy (PDT) with nitrogen‐doped titanium dioxide (N‐TiO2) nanoparticles (NPs) could promote the reactive oxygen species (ROS)‐dependent autophagy in leukemia cells. However, the differential autophagic effects of N‐TiO2 NPs in the dark and light conditions and the potential of N‐TiO2‐based PDT for the treatment of melanoma cells remain unknown. Here we show that depending on the visible‐light condition, the autophagic response of human melanoma A375 cells to N‐TiO2 NPs switches between two different statuses (ie., flux or blockade) with the opposite outcomes (ie., survival or death). Mechanistically, low doses of N‐TiO2 NPs (1‐100 µg/ml) stimulate a nontoxic autophagy flux response in A375 cells, whereas their photo‐activation leads to the impairment of the autophagosome‐lysosome fusion, the blockade of autophagy flux and consequently the induction of RIPK1‐mediated necroptosis via ROS production. These results confirm that photo‐controllable autophagic effects of N‐TiO2 NPs can be utilized for the treatment of cancer, particularly melanoma.
Mitochondria‐targeted antioxidant mito‐TEMPO alleviate oxidative stress induced by antimycin A in human mesenchymal stem cells
Authors: Barzegari Abolfazl , Nouri Mohammad , Gueguen Virginie , Saeedi Nazli , Pavon‐Djavid Graciela , Omidi Yadollah
Published: January 2020

The cell therapy of damaged tissue, which is linked to hypoxia condition might fail, in large part due to the emergence of oxidative stress (OS) and/or mitochondrial dysfunctions. Thus, the invigoration of stem cells against oxidative stress could be a reliable strategy to improve the cell therapy outcome. Of various antioxidants, mito‐Tempo (mito‐T) is one of the potent antioxidants that could target and neutralize the mitochondrial oxidative stress. In this study, for the induction of hypoxia and oxidative stress in mitochondria of the mesenchymal stem cells (MSCs) isolated from human adipose tissue, antimycin A (AMA) was used and then several parameters were analyzed, including cell viability and cell cycle arrest of MSCs exposed to AMA, mito‐T, antioxidant potential, redox homeostasis, and signaling pathways in MSCs under oxidative stress. Based on our findings, the treated MSCs were found to impose a high resistance to the OS‐induced apoptosis, which correlated with the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway required to manage OS. Upon exposure of the MSCs to high oxidative stress conditions using AMA, the cells failed to scavenge. The use of mito‐T was found to alleviate the damage induced by oxidative stress through both direct functions of the free radical scavenging and the interplay in terms of cell signaling pathways including the upregulation of the Nrf2 pathway. These findings may pave the way in the stem cell therapy for the hypoxia‐mediated tissue damage.
Real‐time measurement of E2: ERα transcriptional activity in living cells
Authors: Cipolletti Manuela , Leone Stefano , Bartoloni Stefania , Busonero Claudia , Acconcia Filippo
Published: January 2020

Kinetic analyses of diverse physiological processes have the potential to unveil new aspects of the molecular regulation of cell biology at temporal levels. 17β‐estradiol (E2) regulates diverse physiological effects by binding to the estrogen receptor α (ERα), which primarily works as a transcription factor. Although many molecular details of the modulation of ERα transcriptional activity have been discovered including the impact of receptor plasma membrane localization and its relative E2‐evoked signaling, the knowledge of real‐time ERα transcriptional dynamics in living cells is lacking. Here, we report the generation of MCF‐7 and HeLa cells stably expressing a modified luciferase under the control of an E2‐sensitive promoter, which activity can be continuously monitored in living cells and show that E2 induces a linear increase in ERα transcriptional activity. Ligand‐independent (e.g., epidermal growth factor) receptor activation was also detected in a time‐dependent manner. Kinetic profiles of ERα transcriptional activity measured in the presence of both receptor antagonists and inhibitors of ERα plasma membrane localization reveal a biphasic dynamic of receptor behavior underlying novel aspects of receptor‐regulated transcriptional effects. Finally, analysis of the rate of the dose‐dependent E2 induction of ERα transcriptional activity demonstrates that low doses of E2 induce an effect identical to that determined by high concentrations of E2 as a function of the duration of hormone administration. Overall, we present the characterization of sensitive stable cell lines were to study the kinetic of E2 transcriptional signaling and to identify new aspects of ERα function in different physiological or pathophysiological conditions.
Molecular mechanism underlying the difference in proliferation between placenta‐derived and umbilical cord‐derived mesenchymal stem cells
Authors: Feng Xudong , Liu Jingqi , Xu Yanping , Zhu Jiaqi , Chen Wenyi , Feng Bing , Pan Qiaoling , Yu Jiong , Shi Xiaowei , Yang Jinfeng , Li Yang , Li Lanjuan , Cao Hongcui
Published: January 2020

The placenta and umbilical cord are pre‐eminent candidate sources of mesenchymal stem cells (MSCs). However, placenta‐derived MSCs (P‐MSCs) showed greater proliferation capacity than umbilical cord‐derived MSCs (UC‐MSCs) in our study. We investigated the drivers of this proliferation difference and elucidated the mechanisms of proliferation regulation. Proteomic profiling and Gene Ontology (GO) functional enrichment were conducted to identify candidate proteins that may influence proliferation. Using lentiviral or small interfering RNA infection, we established overexpression and knockdown models and observed changes in cell proliferation to examine whether a relationship exists between the candidate proteins and proliferation capacity. Real‐time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence assays were conducted to elucidate the mechanisms underlying proliferation. Six candidate proteins were selected based on the results of proteomic profiling and GO functional enrichment. Through further validation, yes‐associated protein 1 (YAP1) and β‐catenin were confirmed to affect MSCs proliferation rates. YAP1 and β‐catenin showed increased nuclear colocalization during cell expansion. YAP1 overexpression significantly enhanced proliferation capacity and upregulated the expression of both β‐catenin and the transcriptional targets of Wnt signaling, CCND1, and c‐MYC, whereas silencing β‐catenin attenuated this influence. We found that YAP1 directly interacts with β‐catenin in the nucleus to form a transcriptional YAP/β‐catenin/TCF4 complex. Our study revealed that YAP1 and β‐catenin caused the different proliferation capacities of P‐MSCs and UC‐MSCs. Mechanism analysis showed that YAP1 stabilized the nuclear β‐catenin protein, and also triggered the Wnt/β‐catenin pathway, promoting proliferation.
Circular RNA circTET3 mediates migration of rat vascular smooth muscle cells by targeting miR‐351‐5p
Authors: Yao Qing‐Ping , Liu Ze , Yao Ai‐Hong , Liu Ji‐Ting , Jiang Jun , Chen Yi , Li Shan‐Shan , Han Yue , Jiang Zong‐Lai , Qi Ying‐Xin
Published: January 2020

Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are the pathological basis of hyperplasia during vein graft disease. It remains unknown if circular RNAs (circRNAs) are involved in vein graft disease. In the present study, a rat vein graft model was constructed by the “cuff” technique, and whole transcriptome deep sequencing was applied to identify differential circRNAs in the grafted vein compared to the control. We identified a novel circRNA, named circTET3, whose structure was verified by Sanger sequencing and RNase R digestion. CircTET3 was increased in the grafted vein and stably located in the cytoplasm as detected by fluorescence in situ hybridization. Knockdown of circTET3 suppressed VSMC migration by acting as an endogenous miR‐351‐5p sponge detected by RNA pull‐down and dual‐luciferase reporter assays. PTPN1 was the targeted gene due to the competitive binding of circTET3 to miR‐351‐5p. This regulatory pathway may serve as a potential therapeutic avenue against intimal hyperplasia in vein graft disease.
Therapeutic targeting of neutrophil exocytosis
Authors: Catz Sergio D. , McLeish Kenneth R.
Published: January 2020

Dysregulation of neutrophil activation causes disease in humans. Neither global inhibition of neutrophil functions nor neutrophil depletion provides safe and/or effective therapeutic approaches. The role of neutrophil granule exocytosis in multiple steps leading to recruitment and cell injury led each of our laboratories to develop molecular inhibitors that interfere with specific molecular regulators of secretion. This review summarizes neutrophil granule formation and contents, the role granule cargo plays in neutrophil functional responses and neutrophil-mediated diseases, and the mechanisms of granule release that provide the rationale for development of our exocytosis inhibitors. We present evidence for the inhibition of granule exocytosis in vitro and in vivo by those inhibitors and summarize animal data indicating that inhibition of neutrophil exocytosis is a viable therapeutic strategy.
Machine Learning for Predicting Complications in Head and Neck Microvascular Free Tissue Transfer
Authors: Formeister Eric J. , Baum Rachel , Knott P. Daniel , Seth Rahul , Ha Patrick , Ryan William , El‐Sayed Ivan , George Jonathan , Larson Andrew , Plonowska Karolina , Heaton Chase
Published: January 2020

Objectives/Hypothesis

Machine learning (ML) is a type of artificial intelligence wherein a computer learns patterns and associations between variables to correctly predict outcomes. The objectives of this study were to 1) use a ML platform to identify factors important in predicting surgical complications in patients undergoing head and neck free tissue transfer, and 2) compare ML outputs to traditionally employed logistic regression models.

Study Design

Retrospective cohort study.

Methods

Using a dataset of 364 consecutive patients who underwent head and neck microvascular free tissue transfer at a single institution, 14 clinicopathologic characteristics were analyzed using a supervised ML algorithm of ensemble decision trees to predict surgical complications. The relative importance values of each variable in the ML analysis were then compared to logistic regression models.

Results

There were 166 surgical complications, which included bleeding or hematoma in 30 patients (8.2%), fistulae in 25 patients (6.9%), and infection or dehiscence in 52 patients (14.4%). There were 59 take‐backs (16.2%), and six total (1.6%) and five partial (1.4%) flap failures. ML models were able to correctly classify outcomes with an accuracy of 65% to 75%. Factors that were identified in ML analyses as most important for predicting complications included institutional experience, flap ischemia time, age, and smoking pack‐years. In contrast, the significant factors most frequently identified in traditional logistic regression analyses were patient age (P = .03), flap type (P = .03), and primary site of reconstruction (P = .06).

Conclusions

In this single‐institution dataset, ML algorithms identified factors for predicting complications after free tissue transfer that were distinct from traditional regression models.

Level of Evidence

2c Laryngoscope, 2020
Thistle crops in marginal lands after compost addition: Plant biomass and effect on soil physical, chemical and biological properties
Authors: Domínguez María T. , Panettieri Marco , Madejón Engracia , Madejón Paula
Published: January 2020

The growing interest in bioenergy crops that do not compete with food production for land use has promoted the implementation of low‐input crops on marginal lands. However, these crops can be highly limited by the low soil nutrient and water availability in these lands. In this work, biosolid compost (BC) was applied to improve the quality of a degraded, C‐poor soil under Mediterranean conditions. We evaluated the effects of BC addition on soil physical, chemical and biochemical properties in a field experiment with two native species with potential as bioenergy crops (Cynara cardunculusandSilybum marianum). The addition of BC significantly increased soil C content from <0.9% to >1%, and produced a two‐fold increase in soil P availability. Respiration rates and microbial activity were only slightly improved by BC, while significant increases in the PLFA molar content assigned to general classes of bacteria were recorded. The beneficial effects of BC triggered the percentage of seed germination inS. marianum(from 64% in control plots to 85% in the compost treatment) as well as the production of biomass in both species (two‐fold increase in the second year).Application of BC led to increases in energy yield of 58% forC. cardunculusand of 71% forS. marianum. Considering the low economic cost of BC, its application on marginal soils in combination withC. cardunculuscrops, producing much larger biomass thanS. marianum, could be considered as an option for degraded Mediterranean soils.
Efficacy of Fractional CO2 Laser, Promestriene, and Vaginal Lubricant in the Treatment of Urinary Symptoms in Postmenopausal Women: A Randomized Clinical Trial
Authors: Aguiar Luiza Borges , Politano Carlos Alberto , Costa‐Paiva Lúcia , Juliato Cássia Raquel Teatin
Published: January 2020

Background and Objectives

Evaluating the efficacy of the fractional CO2 laser, promestriene, and vaginal lubricant to treat urinary symptoms in women with genitourinary syndrome of menopause.

Study Design/Materials and Methods

We conducted a randomized clinical trial with 72 postmenopausal women aged 50 years or older. The participants were randomized to one intervention each in three treatment groups fractional CO2 laser, promestriene, and vaginal lubricant. Urinary symptoms were assessed prior to treatment and 2 weeks after treatment completion using validated questionnaires, the International Consultation on Incontinence Questionnaire (ICIQ‐UI SF), and the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ‐OAB).

Results

There was a significant reduction in the total ICIQ‐UI SF score in the intragroup comparison (baseline vs. week 14) of the CO2 laser group (P = 0.004). This group also showed a statistically significant reduction in nocturia (1.33 ± 0.87 vs. 1.00 ± 0.76, respectively; P = 0.031). In the intergroup comparison after treatment, nocturia in the lubricant group had worsened compared with that of the other two groups (P = 0.002). Regarding the total ICIQ‐OAB score, the results of the CO2 laser group were superior to those of the lubricant group in the intergroup comparison (7.76 ± 3.36, P = 0.020; analysis of variance P = 0.038).

Conclusion

The results were significantly different between the intravaginal fractional CO2 laser and topical estrogen groups for treating urinary symptoms related to the genitourinary syndrome of menopause. Further controlled and randomized studies are needed. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.
Understanding the intention to buy secondhand clothing on sharing economy platforms: The influence of sustainability, distance from the consumption system, and economic motivations
Authors: Ek Styvén Maria , Mariani Marcello M.
Published: January 2020

Sharing economy (SE) platforms are increasingly providing an effective means of connecting providers and users of secondhand goods. While media seem to emphasize that the trend of selling/buying secondhand has been growing due to the consolidation and development of peer‐to‐peer (P2P) sharing platforms, a comprehensive identification of the antecedents of buying secondhand on SE platforms is virtually missing. This study addresses this gap by (a) identifying different sets of motivations and attitudes leading consumers to adopt SE platforms for secondhand buying and (b) testing a model on a sample of UK consumers in the context of P2P sharing platforms for secondhand clothing. This study reveals that there are three major antecedents of consumers' attitude towards buying secondhand clothes on P2P–SE platforms: perceived sustainability, economic motivations, and taking a distance from the consumption system. Perceived sustainability and economic motivations influence positively attitude toward buying secondhand, as well as motivations in the form of distance from the consumption system. Attitude toward buying secondhand is positively influenced also by distance from the system and, in turn, has a strong positive influence on behavioral intention to buy secondhand clothes. Moreover, past experience of buying secondhand online has a positive moderating effect on the relationship between perceived sustainability and distance from the consumption system.
CD2AP inhibits metastasis in gastric cancer by promoting cellular adhesion and cytoskeleton assembly
Authors: Xie Wangkai , Chen Chao , Han Zheng , Huang Jingjing , Liu Xin , Chen Hongjun , Zhang Teming , Chen Sian , Chen Chenbin , Lu Mingdong , Shen Xian , Xue Xiangyang
Published: January 2020

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2‐associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F‐actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
Survey of Ehlers‒Danlos Patients’ ophthalmic surgery experiences
Authors: Louie Anita , Meyerle Catherine , Francomano Clair , Srikumaran Divya , Merali Farhan , Doyle Jefferson J. , Bower Kraig , Bloom Lara , Boland Michael V. , Mahoney Nicholas , Daoud Yassine , Singman Eric L.
Published: January 2020

Background

Ehlers‒Danlos Syndrome (EDS) is a rare disease affecting approximately 1 in 5,000 people. Although ophthalmic conditions associated with EDS have been described, little data exist concerning ophthalmic surgical outcomes experienced by EDS patients.

Methods

Patients with EDS were surveyed via the EDS Society and asked about their ophthalmic surgical experiences including procedure, complications, and the timing with respect to receiving the EDS diagnosis. Complications were confirmed as such by subspecialists.

Results

Of 579 respondents, 467 reported confirmed EDS, and 112 of those had an ophthalmic procedure, including refractive surgery, cataract/lens surgery, retinal surgery, strabismus surgery, oculoplastic surgery, corneal surgery, and laser surgery for glaucoma. The rate of confirmed complications was: 23%‐refractive, 33%‐lens/cataract, 33%‐retina, 59%‐strabismus, 23%‐ oculoplastics, 0%‐cornea, and 25%‐glaucoma laser. In addition, 76% of patients underwent surgery prior to the EDS diagnosis.

Conclusions

Patients with EDS may have elevated risk of postoperative ophthalmic surgical complications. It would seem reasonable to systemically and prospectively explore how patients with EDS respond to ophthalmic surgery. Furthermore, it would seem circumspect to ask surgical candidates patients about whether they carry a diagnosis of EDS or have signs and symptoms of EDS prior to surgery.
In vivo Glx and Glu measurements from GABA‐edited MRS at 3 T
Authors: Bell Tiffany , Boudes Elodie S. , Loo Rachelle S. , Barker Gareth J. , Lythgoe David J. , Edden Richard A.E. , Lebel R. Marc , Wilson Martin , Harris Ashley D.
Published: January 2020

In vivo quantification of glutamate (Glu) and γ‐aminobutyric acid (GABA) using MRS is often achieved using two separate sequences: a short‐echo point resolved spectroscopy (PRESS) acquisition for Glu and a Mescher‐Garwood PRESS (MEGA‐PRESS) acquisition for GABA. The purpose of this study was to examine the agreement of Glu and Glx (the combined signal of glutamate + glutamine) quantified from two different GABA‐edited MEGA‐PRESS acquisitions (GABA plus macromolecules, GABA+, TE = 68 ms, and macromolecule suppressed, MMSup, TE = 80 ms) with Glu and Glx quantified from a short‐echo PRESS (PRESS‐35, TE = 35 ms) acquisition. Fifteen healthy male volunteers underwent a single scan session, in which data were acquired using the three acquisitions (GABA+, MMSup and PRESS‐35) in both the sensorimotor and anterior cingulate cortices using a voxel size of 3 × 3 × 3 cm3. Glx and Glu were quantified from the MEGA‐PRESS data using both the OFF sub‐spectra and the difference (DIFF) spectra. Agreement was assessed using correlation analyses, Bland–Altman plots and intraclass correlation coefficients. Glx quantified from the OFF sub‐spectra from both the GABA+ and MMSup acquisitions showed poor agreement with PRESS‐35 in both brain regions. In the sensorimotor cortex, Glu quantified from the OFF sub‐spectra of GABA+ showed moderate agreement with PRESS‐35 data, but this finding was not replicated in the anterior cingulate cortex. Glx and Glu quantified using the DIFF spectra of either MEGA‐PRESS sequence were in poor agreement with the PRESS‐35 data in both brain regions. In conclusion, Glx and Glu measured from MEGA‐PRESS data generally showed poor agreement with Glx and Glu measured using PRESS‐35.
Health system challenges for improved childhood pneumonia case management in Lagos and Jigawa, Nigeria
Authors: Shittu Funmilayo , Agwai Imaria C. , Falade Adegoke G. , Bakare Ayobami A. , Graham Hamish , Iuliano Agnese , Aranda Zeus , McCollum Eric D. , Isah Adamu , Bahiru Solomon , Ahmed Tahlil , Burgess Rochelle A. , King Carina , Colbourn Tim , on behalf of the INSPIRING Project Consortium
Published: January 2020

Background

Case fatality rates for childhood pneumonia in Nigeria remain high. There is a clear need for improved case management of pneumonia, through the sustainable implementation of the Integrated Management of Childhood Illnesses (IMCI) diagnostic and treatment algorithms. We explored barriers and opportunities for improved case management of childhood pneumonia in Lagos and Jigawa states, Nigeria.

Methods

A mixed‐method analysis was conducted to assess the current health system capacity to deliver quality care. This was done through audits of 16 facilities in Jigawa and 14 facilities in Lagos, questionnaires (n = 164) and 13 focus group discussions with providers. Field observations provided context for data analysis and triangulation.

Results

There were more private providers in Lagos (4/8 secondary facilities) and more government providers in Jigawa (4/8 primary, 3/3 secondary, and 1/1 tertiary facilities). Oxygen and pulse oximeters were available in two of three in Jigawa and six of eight in Lagos of the sampled secondary care facilities. None of the eight primary facilities surveyed in Jigawa had oxygen or pulse oximetry available while in Lagos two of three primary facilities had oxygen and one of three had pulse oximeters. Other IMCI and emergency equipment were also lacking including respiratory rate timers, particularly in Jigawa state. Health care providers scored poorly on knowledge of IMCI, though previous IMCI training was associated with better knowledge. Key enabling factors in delivering pediatric care highlighted by health care providers included accountability procedures and feedback loops, the provision of free medication for children, and philanthropic acts. Common barriers to provide care included the burden of out‐of‐pocket payments, challenges in effective communication with caregivers, delayed presentation, and lack of clear diagnosis, and case management guidelines.

Conclusion

There is an urgent need to improve how the prevention and treatment of pediatric pneumonia is directed in both Lagos and Jigawa. Priority areas for reducing pediatric pneumonia burden are training and mentoring of health care providers, community health education, and introduction of oximeters and oxygen supply.
Sultiame pharmacokinetic profile in plasma and erythrocytes after single oral doses: A pilot study in healthy volunteers
Authors: Dao Kim , Thoueille Paul , Decosterd Laurent A. , Mercier Thomas , Guidi Monia , Bardinet Carine , Lebon Sébastien , Choong Eva , Castang Arnaud , Guittet Catherine , Granier Luc‐André , Buclin Thierry
Published: January 2020

A pilot study was conducted aiming at specifying sultiame's pharmacokinetic profile, completed by in vitro assays evaluating the intraerythrocytic transfer of sultiame and by a pharmacokinetic model assessing its distribution. Single oral doses of sultiame (Ospolot® 50, 100, and 200 mg) were administered in open‐label to four healthy volunteers. Serial plasma, whole blood, and urine samples were collected. A spiking experiment was also performed to characterize sultiame's exchanges between plasma and erythrocytes in vitro. Pharmacokinetic parameters were evaluated using standard noncompartmental calculations and nonlinear mixed‐effect modeling. The plasma maximal concentrations (Cmax) showed striking nonlinear disposition of sultiame, with a 10‐fold increase while doses were doubled. Conversely, whole blood Cmax increased less than dose proportionally while staying much higher than in plasma. Quick uptake of sultiame into erythrocytes observed in vivo was confirmed in vitro, with minimal efflux. A two‐compartment model with first‐order absorption, incorporating a saturable ligand to receptor binding, described the data remarkably well, indicating apparent plasma clearance of 10.0 L/h (BSV: 29%) and distribution volume of 64.8 L; saturable uptake into an intracellular compartment of 3.3 L with a maximum binding capacity of 111 mg accounted for nonlinearities observed in plasma and whole blood concentrations. Pharmacokinetic characteristics of sultiame are reported, including estimates of clearance and volume of distribution that were so far unpublished. The noticeable nonlinearity in sultiame disposition should be taken into account for the design of future studies and the interpretation of therapeutic drug monitoring results.
High‐Temperature Operation of AlxGa1−xN (x > 0.4) Channel Metal Oxide Semiconductor Heterostructure Field Effect Transistors with High‐k Atomic Layer Deposited Gate Oxides
Authors: Mollah Shahab , Hussain Kamal , Floyd Richard , Mamun Abdullah , Gaevski Mikhail , Chandrashekhar MVS , Ahmad Iftikhar , Simin Grigory , Wheeler Virginia , Eddy Charles , Khan Asif
Published: January 2020

Due to their superior breakdown fields compared with GaN and SiC and high thermal conductivity, AlxGa1−xN (x > 0.4) channel high‐electron‐mobility transistors (HEMTs) will find applications in extreme environments such as power electronics. Herein, the high‐temperature operation of ultrawide‐bandgap (UWBG) Al0.65Ga0.35N/Al0.4Ga0.6N metal oxide semiconductor heterostructure field effect transistors (MOSHFETs) with atomic layer‐deposited (ALD) high‐k gate dielectrics TiO2, Al2O3, and ZrO2 is reported. As compared with similar geometry HFETs, these devices exhibit a simultaneous reduction in gate‐leakage current by ≈104 and a positive shift of the threshold voltage as much as 4 V. This positive threshold shift indicates the introduction of negative charges at the oxide/barrier interface and within the thin oxide, attributed to the pre‐ALD plasma treatment. The gate leakage increases weakly with temperature up to 250 °C, whereas the peak drain currents decrease from ≈0.5 to 0.3 A mm−1. An analysis of the C–V and I–V characteristics reveals that this drain current decrease is due to a reduction in channel electron mobility. The potential mechanisms responsible for this are discussed. Up to the measured temperature of 250 °C, the devices withstand repeated temperature cycles without catastrophic degradation or breakdown, underscoring the promise of these materials.
Protective effects of beet (Beta vulgaris) leaves extract against oxidative stress in endothelial cells in vitro
Authors: da Silva Luiz Guilherme Salvino , Morelli Ana Paula , Pavan Isadora Carolina Betim , Tavares Mariana Rosolen , Pestana Nathalie Fortes , Rostagno Mauricio Ariel , Simabuco Fernando Moreira , Bezerra Rosângela Maria Neves
Published: January 2020

Beetroot is an herb used worldwide as a food product, raw material for food industry, ethanol production and source of food coloring. Beet leaves are an unconventional food with antioxidant properties, which might neutralize reactive oxygen species (ROS) induced by oxidized Low‐Density Lipoprotein (LDL) present in dyslipidemias. This study aimed to elucidate the effects of beet leaves on the suppression of LDL oxidative processes. Beet leaves extract was produced, characterized, and tested for its antioxidant capacity using endothelial cells in vitro. A model of human umbilical vein endothelial cells was used in various tests, including viability assay, molecular analysis of antioxidant genes, ROS labeling, and macrophage adhesion assay. The extract improved the antioxidative protection of endothelial cells against different agents including oxidized LDL‐cholesterol and H2O2. It acted on ROS directly due to its high content of natural antioxidants, but also due to the activation and improvement of cellular defenses such as Superoxide dismutase 1, Superoxide dismutase 2, and catalase. The inhibition of LDL‐mediated oxidative effects on endothelial cells may turn this unconventional food a functional food with great potential for phytotherapy of atherosclerosis as an adjuvant for medicinal treatments.
Sustainable development and corporate social responsibility in Japanese manufacturing companies
Authors: Goto Mika , Sueyoshi Toshiyuki
Published: January 2020

Many firms are now conscious about engaging in corporate social responsibility (CSR) for managing their business operations. The CSR is an approach that comprises a wide range of components such as corporate governance and workforce diversity. Among them, environmental protection has emerged as an important business issue in recent decades. This study focuses on the environmental protection from corporate efforts measured by CSR and socially responsible investment (SRI) that may serve as a proxy of CSR. This study considers that the level of sustainable development is measured by two unified (operational and environmental) efficiencies. To examine the sustainable development of Japanese manufacturing firms, we utilize a data set consisting of 110 manufacturing companies during 2013–2015. All the companies examined in this study are listed in the first section of the Tokyo Stock Exchange. This research first applies data envelopment analysis intermediate approach as a holistic method to assess their two efficiency measures. Then, we apply the panel data Tobit estimation to examine whether CSR and/or SRI influence their unified efficiency measures. This research finds that the SRI incorporation increases the efficiencies, enhancing their sustainable developments. However, the compliance with various CSR standards does not have such a direct influence probably because it increases complexity within firms.
Bayesian hierarchical meta‐analytic methods for modeling surrogate relationships that vary across treatment classes using aggregate data
Authors: Papanikos Tasos , Thompson John R. , Abrams Keith R. , Städler Nicolas , Ciani Oriana , Taylor Rod , Bujkiewicz Sylwia
Published: January 2020

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their predictive value of clinical benefit by investigating the surrogate relationship between treatment effects on the surrogate and final outcomes using meta‐analytic methods. When surrogate relationships vary across treatment classes, such validation may fail due to limited data within each treatment class. In this paper, two alternative Bayesian meta‐analytic methods are introduced which allow for borrowing of information from other treatment classes when exploring the surrogacy in a particular class. The first approach extends a standard model for the evaluation of surrogate endpoints to a hierarchical meta‐analysis model assuming full exchangeability of surrogate relationships across all the treatment classes, thus facilitating borrowing of information across the classes. The second method is able to relax this assumption by allowing for partial exchangeability of surrogate relationships across treatment classes to avoid excessive borrowing of information from distinctly different classes. We carried out a simulation study to assess the proposed methods in nine data scenarios and compared them with subgroup analysis using the standard model within each treatment class. We also applied the methods to an illustrative example in colorectal cancer which led to obtaining the parameters describing the surrogate relationships with higher precision.
Experimental study on flexural behavior of new type of prestressed reactive powder concrete sound barrier for high‐speed rail
Authors: Cao Xia , Yang Zhen‐Xuan , Zhu Wan‐Xu , Peng Han‐Ze , Fu Feng , Wang Long , Qian Kai
Published: January 2020

In this paper, four‐point bending tests of six prestressed reactive powder concrete (RPC) sound barrier unit panels were performed, the flexural behavior, deflection, and failure modes of both in situ and prefabricated panels were studied. The results show that the major failure modes for in situ panels were bending failure. Prestressing the panels can effectively increase the cracking loads and improve the stiffness of the in situ panels, but it cannot improve the ultimate flexural capacities. The ductility of the in situ panels decreased with the increase of prestressing degree. The stiffness of the prefabricated panels was improved by prestressing. Increasing the thickness of back and front plates, the ductility of the panels decreased accordingly, and the ductility of the prefabricated panels decreased more obviously than that of in situ panels. Based on the test results, considering tensile strength of RPC and prestressing stress, a modified formula for flexural capacity of in situ panels was established. In the meantime, considering the “bridge” effect of steel fiber, the formulae to calculate the crack width and deflection at service limit state were also developed for future design.
TRIM25 and its emerging RNA‐binding roles in antiviral defense
Authors: Choudhury Nila Roy , Heikel Gregory , Michlewski Gracjan
Published: January 2020

The innate immune system is the body's first line of defense against viruses, with pattern recognition receptors (PRRs) recognizing molecules unique to viruses and triggering the expression of interferons and other anti‐viral cytokines, leading to the formation of an anti‐viral state. The tripartite motif containing 25 (TRIM25) is an E3 ubiquitin ligase thought to be a key component in the activation of signaling by the PRR retinoic acid‐inducible gene I protein (RIG‐I). TRIM25 has recently been identified as an RNA‐binding protein, raising the question of whether its RNA‐binding activity is important for its role in innate immunity. Here, we review TRIM25's mechanisms and pathways in noninfected and infected cells. We also introduce models that explain how TRIM25 binding to RNA could modulate its functions and play part in the antiviral response. These findings have opened new lines of investigations into functional and molecular roles of TRIM25 and other E3 ubiquitin ligases in cell biology and control of pathogenic infections.

This article is categorized under:

RNA in Disease and Development > RNA in Disease

RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications

RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition