bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the Co‐occurrence of Anxiety and Attention‐Deficit/Hyperactivity Disorder on Intrinsic Functional Network Centrality among Children with Autism Spectrum Disorder
Authors: Wan Bin , Wang Zengjian , Jung Minyoung , Lu Yanchun , He Haoqiang , Chen Qi , Jin Yu
Published: May 2019

Children with autism spectrum disorder (ASD) present with a high co‐occurrence of anxiety and attention‐deficit/hyperactivity disorder (ADHD). However, it remains unclear how the co‐occurrence of anxiety and ADHD in children with ASD alters whole‐brain functional networks. Here, we aimed to examine anxiety‐ and ADHD‐related brain network centrality in children with ASD separately and their relationships with ASD symptoms. Clinical anxiety and ADHD levels in children with ASD, aged 6–13 years old, were assessed. Participants were categorized into four groups: ASD only (n = 28), ASD + anxiety (n = 19), ASD + ADHD (n = 25), and ASD + both anxiety and ADHD (n = 28). Subsequently, we compared voxel‐wise network degree centrality (DC) among the four groups. We found that: (a) compared with ASD only, children with ASD + anxiety showed higher DC in the left middle temporal gyrus, right lingual gyrus, and left cuneus, and lower DC in the right precuneus; (b) children with ASD + ADHD presented higher DC in the right calcarine and left superior frontal gyrus (SFG) compared with ASD only; (c) children with ASD + both displayed higher DC in the right calcarine and lower centrality in the right middle occipital gyrus compared with ASD only; and (d) across all children with ASD, there was a positive correlation between DC of the right calcarine with nonverbal behavior scores, and DC of the left SFG was negatively correlated with social scores. Our findings suggest that the right calcarine, left SFG, and default mode network nodes play important roles in the co‐occurrence of anxiety and ADHD among children with ASD. Autism Res 2019, 12: 1057–1068. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

The co‐occurrence of anxiety and attention‐deficit/hyperactivity disorder (ADHD) has been shown to influence the brain function of children with ASD. In order to gain a better understanding of this, the present study compared degree centrality, the amount of effective brain functional connectivity that reflects the characteristics of brain networks, among four groups: ASD only, ASD + anxiety, ASD + ADHD, and ASD + both anxiety and ADHD. We found that some areas located in the language processing network and primary visual cortex were associated with the co‐occurrence of ADHD, and some other areas located in the default mode network were associated with the co‐occurrence of both anxiety and ADHD. These findings provide more knowledge about the neural basis underlying behavioral changes related to the co‐occurrence of anxiety and ADHD in children with ASD.
Botulinum toxin for the treatment of dystonia and pain in corticobasal syndrome
Authors: Unti Elisa , Mazzucchi Sonia , Calabrese Rosanna , Palermo Giovanni , Del Prete Eleonora , Bonuccelli Ubaldo , Ceravolo Roberto
Published: May 2019

Background

Dystonia is a key symptom in corticobasal syndrome (CBS), and upper limb dystonia is the most common phenotype. Dystonia‐associated pain is frequently reported and can be disabling, with poor benefit from oral treatments.

Aims of the Study

To investigate the role of botulinum toxin A (BoTNA) in the treatment of dystonia and associated pain in CBS.

Methods

Ten consecutive patients with a clinical diagnosis of probable CBS and dystonia with/without associated pain were treated with BoTNA every 3 months. Treatment efficacy was assessed during the first follow‐up visit, three months after the first injection, by means of caregiver impression (CI), evaluation of muscle tone with the Ashworth scale (AS), severity of pain measured with the visual analog scale (VAS).

Results

Nine subjects underwent at least three treatments, four patients discontinued for progressive reduction in efficacy or disease progression, five patients are ongoing with good response, and one completed the 10th treatment. No local or systemic side effects were reported, and levodopa equivalent daily dose remained unchanged in most cases during the observational period. Significant improvement of AS was recorded (from 2.9 ± 0.7 to 2.0 ± 0.5, p = 0.003). CI ranged from mild to moderate benefit. All patients reported efficacy on pain, with a significant reduction of VAS score (from 7.7 ± 1.7 to 1.7 ± 0.7 in the Pain group, p = 0.016).

Conclusions

Our study confirms safety, efficacy, and tolerability of BoTNA in the treatment of dystonia associated with CBS. Local treatment should be considered as a valid alternative to oral treatment modulation mainly in the presence of associated pain.
Designing a holistic process of learning for implementing sustainability: An experience in an engineering doctoral program
Authors: Regueiro Araceli , Crespo Bárbara , Míguez‐Álvarez Carla , Cuevas Miguel
Published: May 2019

Education is a key element of reaching sustainability. The incorporation of sustainability into doctoral programs can be promoted using new learning methods through the practices carried out by the PhD students. These methods include learning by doing, blended learning, collaborative learning, and project based learning, all of which are presented in the practical experience described in this article. This study describes the training that students receive in the doctoral program “Energy Efficiency and Sustainability in Engineering and Architecture,” which is offered in the Engineering School at the University of Vigo. The study includes an analysis of the facility and its operations, the teaching methods used and the students' perceptions of sustainability's incorporation into the program. In this practice, students worked with an experimental facility that could be controlled and supervised both manually and remotely. Students performed numerous tasks, including studying the main problems related to the combustion of biomass and its impact on sustainable development. On the one hand, students have used different measuring devices to control and monitor facilities, and, on the other hand, they have discussed and analyzed data, thereby improving the work capacity with the facility equipment, team work skill and communication with each other effectively. As a conclusion, students showed sincere interest in development of the practice, and they participated actively in each of its phases. The learning methodology used was found to increase student motivation.
MicroRNA‐4286 promotes cell proliferation, migration, and invasion via PTEN regulation of the PI3K/Akt pathway in non‐small cell lung cancer
Authors: Ling Chunhua , Wang Xueting , Zhu Jianjie , Tang Haicheng , Du Wenwen , Zeng Yuanyuan , Sun Lin , Huang Jian‐An , Liu Zeyi
Published: May 2019

It is well‐known that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor which negatively regulates PI3K/AKT signaling and is activated widely in non‐small cell lung cancers (NSCLC). However, genetic alterations in PTEN genes are rare, suggesting an undefined mechanism(s) for their suppression. Notably, growing evidence indicates that PTEN can be regulated by microRNAs involved in cancer progression. In this study, we discover that the miR‐4286 is overexpressed in NSCLC and negatively regulates the expression of PTEN. Furthermore, we found that miR‐4286 reduces PTEN expression by directly binding to PTEN 3′‐untranslated region (UTR), thereby inhibiting NSCLC cell proliferation and mobility. Moreover, mechanistic investigations revealed that miR‐4286 overexpression was a result of PTEN‐mediated activation of the PI3K/AKT pathway. Taken together, our findings elucidate that miR‐4286 promotes the tumorigenesis of NSCLC by interacting with PTEN. This miR‐4286‐mediated upregulation of PTEN might lead to new therapeutic strategies for NSCLC.
Toward automatic prediction of EGFR mutation status in pulmonary adenocarcinoma with 3D deep learning
Authors: Zhao Wei , Yang Jiancheng , Ni Bingbing , Bi Dexi , Sun Yingli , Xu Mengdi , Zhu Xiaoxia , Li Cheng , Jin Liang , Gao Pan , Wang Peijun , Hua Yanqing , Li Ming
Published: May 2019

To develop a deep learning system based on 3D convolutional neural networks (CNNs), and to automatically predict EGFR‐mutant pulmonary adenocarcinoma in CT images. A dataset of 579 nodules with EGFR mutation status labels of mutant (Mut) or wild‐type (WT) was retrospectively analyzed. A deep learning system, namely 3D DenseNets, was developed to process 3D patches of nodules from CT data, and learn strong representations with supervised end‐to‐end training. The 3D DenseNets were trained with a training subset of 348 nodules and tuned with a development subset of 116 nodules. A strong data augmentation technique, mixup, was used for better generalization. We evaluated our model on a holdout subset of 115 nodules. An independent public dataset of 37 nodules from the cancer imaging archive (TCIA) was also used to test the generalization of our method. Conventional radiomics analysis was also performed for comparison. Our method achieved promising performance on predicting EGFR mutation status, with AUCs of 75.8% and 75.0% for our holdout test set and public test set, respectively. Moreover, strong relations were found between deep learning feature and conventional radiomics, while deep learning worked through an enhanced radiomics manner, that is, deep learned radiomics (DLR), in terms of robustness, compactness and expressiveness. The proposed deep learning system predicts EGFR‐mutant of lung adenocarcinomas in CT images noninvasively and automatically, indicating its potential to help clinical decision‐making by identifying eligible patients of pulmonary adenocarcinoma for EGFR‐targeted therapy.
Prognosis of three histological subtypes of colorectal adenocarcinoma: A retrospective analysis of 8005 Chinese patients
Authors: Li Chao , Zheng Hongtu , Jia Huixun , Huang Dan , Gu Weilie , Cai Sanjun , Zhu Ji
Published: May 2019

Background and objectives

To evaluate the effect of the varied histological subtypes on clinical outcomes and to determine the prognostic implications of mucinous adenocarcinomas (MAC) and signet ring cell carcinomas (SRCC) compared with classic adenocarcinomas (AC).

Methods

A total of 8005 patients, including 7502 AC, 428 MAC and 75 SRCC, who underwent definitive surgery between 2007 and 2015 at Fudan University Shanghai Cancer Center were remained for analysis in this study.

Results

MAC and SRCC were more common in right‐sided colon cancer, in males and in young patients, compared to AC; moreover, MAC and SRCC led to a higher probability to develop lymph node metastasis, lymphovascular invasion and perineural invasion. For survival outcomes, we found that the 5‐year overall survival (OS) of SRCC was significantly lower than that of MAC and AC, while the 5‐year OS of MAC is much lower than that of AC. However, in multivariable analysis, the difference in survival between SRCC, MAC and AC was no longer significant, especially when stratified by N stage.

Conclusions

MAC and SRCC are rare subtypes of colorectal cancer with a higher T stage, N stage as well as higher incidence of lymphovascular and nerve invasion. However, neither MAC nor SRCC was an independent predictor of decreased survival in multivariate analysis.
Cerebral Embolism due to a Large Papillary Fibroelastoma arising from the Coumadin Ridge
Authors: Kamimura Teppei , Tanaka Kanta , Yamagami Hiroshi , Koga Masatoshi
Published: May 2019

A 70‐year‐old woman developed acute cerebral infarction. Transthoracic echocardiography showed a large mobile mass in the left atrium, suggesting cardiac myxoma as the most likely diagnosis. Surgical exploration revealed a papillary fibroelastoma originating from the coumadin ridge, which is fairly rare but important as a source of cerebral embolization.
New Size‐Expanded Fluorescent Thymine Analogue: Synthesis, Characterization, and Application
Authors: Hirashima Shingo , Han Ji Hoon , Tsuno Hitomi , Tanigaki Yusuke , Park Soyoung , Sugiyama Hiroshi
Published: May 2019

Here, the synthesis, photophysical characterization, and application of a new size‐expanded thymine nucleoside, dioxT, is described. dioxT has desirable qualities as a T surrogate, including excellent quantum yield (0.36) and high environmental sensitivity. When incorporated into single‐ and double‐stranded DNA, dioxT showed excellent photophysical characteristics including a high quantum yield (average 0.20), and unlike BgQ, demonstrated dependence on neighboring bases without significant destabilization of the duplex. Interestingly, the matched base pair of adenine (A) and dioxT has the unique property that it exhibits higher fluorescence than mismatched base pairs, and dioxT has self‐quenching effects. As one example of the possible applications of these promising features, single nucleoside polymorphism typing is demonstrated for discrimination of A by using dioxT. The results suggest that dioxT can be used for a broad range of applications in chemical biology.
Fluorescent Nitric Oxide Photodonors Based on BODIPY and Rhodamine Antennae
Authors: Parisi Cristina , Failla Mariacristina , Fraix Aurore , Rolando Barbara , Gianquinto Eleonora , Spyrakis Francesca , Gazzano Elena , Riganti Chiara , Lazzarato Loretta , Fruttero Roberta , Gasco Alberto , Sortino Salvatore
Published: May 2019

Two novel NO photodonors (NOPDs) based on BODIPY and Rhodamine antennae activatable with the highly biocompatible green light are reported. Both NOPDs exhibit considerable fluorescence emission and release NO with remarkable quantum efficiencies. The combination of the photoreleasing and emissive performance for both compounds is superior to those exhibited by other NOPDs based on similar light‐harvesting centres, making them very intriguing for image‐guided phototherapeutic applications. Preliminary biological data prove their easy visualization in cell environment due to the intense green and orange‐red fluorescence and their photodynamic action on cancer cells due to the NO photo‐liberated.
Presence of Streptococcus dentisani in the dental plaque of children from different Colombian cities
Authors: Angarita‐Díaz María P. , Díaz Jaime A. , Tupaz Herlinto A. , López‐López Arantxa , Forero Diana , Mira Alex , Dávila Fernando , Cerón Ximena A. , Ochoa‐Acosta Emilia M. , Goméz Olga L. , Gonzalez Gladys
Published: May 2019

Streptococcus dentisani has been identified as an oral cavity probiotic due to its beneficial characteristics. One of its beneficial features is the production of bacteriocins, which inhibit the growth of cariogenic bacteria, and another is its buffering capacity through the production of ammonium from arginine. The purpose of this study was to determine the presence of S. dentisani in the dental plaque of Colombian children and whether the presence of this bacterium is related to oral health and other conditions. Dental plaque and information on diet and oral hygiene habits were collected from children between 6 and 12 years of age from four Colombian cities, divided into caries‐free children (International Caries Detection and Assessment System [ICDAS] 0, Decayed Missing Filled Teeth index [DMFT] 0), children with ICDAS 1 and 2, and children with ICDAS >3. Plaque DNA was extracted and quantified, and real‐time polymerase chain reaction was performed using specific primers. This bacterium was identified in all samples, with a median of 0.46 cells/ng DNA (interquartile range [IQR] 0.13–1.02), without finding significant differences between the groups (P > 0.05). In caries‐free children, a median of 0.45 cells/ng DNA (IQR 0.14–1.23) was found. In children with ICDAS 1 and 2, the median was 0.49 cells/ng DNA (IQR 0.11–0.97), and in children with ICDAS >3, the median was 0.35 cells/ng DNA (IQR 0.12–1.07). However, statistically significant differences were found in the origin of children (P < 0.01), the use of fluoride‐containing products (P < 0.01), and the frequency of food intake (P < 0.05). In conclusion, the presence of S. dentisani was quantified in children from four Colombian cities, without finding significant differences in oral health status. Nevertheless, three conditions showed a possible relationship with S. dentisani.
Conscious sedation in Spanish dental schools: Current situation
Authors: Vela María Inmaculada , Arregui María , Giner Lluis , Jiménez Esther
Published: May 2019

The current Spanish curricula for degrees in dentistry include conscious sedation (CS) as a basic training competency. However, is the CS training delivered by Spanish dental schools a consensus‐based educational framework enabling students to use this anesthetic technique after graduation? To answer this research question, a study was designed aiming to identify the strategies used to teach this competency in Spanish dental schools and the characteristics of teaching. The authors reviewed legislation concerning officially established requirements for a degree in dentistry as well as curricula currently taught in Spain. Our analysis identified clear discrepancies among the schools of dentistry studied. The only overlap was observed in reference to the level of proficiency imparted, which prevents Spanish dentistry students from using this anesthetic technique after graduation. Specific features of the normative framework and of the Spanish legislative system underlying the design of the present curricula of degrees in dentistry would explain the discrepancies in CS competencies taught at our schools of dentistry. Almost 10 years since its implementation and in light of the new demands of the complex society in which we live, Spanish universities must unify their educational criteria regarding CS training to ensure the appropriate qualification of our new dentists in this technique.
Design of band elimination filter for PMSM vector control operable in overmodulation region of inverter
Authors: Nakayama Yosuke , Doki Shinji
Published: May 2019

This paper proposes a filter design for improving the control performance of the current control system of permanent magnet synchronous motors (PMSMs) using the overmodulation region of an inverter. The control performance of a vector control system for PMSMs using the overmodulation region of an inverter can be improved by suppressing harmonic components that are generated in this region. This paper utilizes band elimination filter (BEF) to eliminate harmonic components; however, unsuitable BEF setting leads to generation of large current oscillation at the resonant frequency of current feedback loop with BEF. In order to deal with these problems, the proposed filter design focuses on gain setting at the cutoff frequency of BEF. The proposed filter design can prevent the generation of current oscillation at the resonant frequency of the system, and can improve current control performance without complex adjustments. Simulations and experiments are carried out to show the effectiveness of the proposed BEF setting.
Two sequential layers of antibody‐mediated control of Legionella pneumophila infection
Authors: Weber Stefan S. , Stoycheva Diana , Nimmerjahn Falk , Oxenius Annette
Published: May 2019

Protective immunity against intracellular pathogens, including bacteria, usually relies on cellular immunity. However, antibodies are also implicated in mediating protection against intracellular bacteria. In case of airway infection with Legionella pneumophila (Lpn), the causative agent of Legionnaires' disease, pre‐existing Lpn‐specific antibodies were shown to afford protection within two days of infection. Here we dissected the early kinetics of Ab‐mediated protection against airway Lpn infection and observed two kinetically and mechanistically distinct phases of protection by passively administered antibodies. Within the first hour of infection, Lpn‐opsonizing antibodies provided almost 10‐fold protection in an antibody Fc‐dependent, but FcR‐independent manner. Later on, by two days post infection, Lpn‐specific Ab‐mediated protection strictly involved FcγR, Syk kinase activity in alveolar macrophages and induction of reactive oxygen species (ROS). The findings presented here contribute to the understanding of the mechanisms of Ab‐mediated control of Lpn infection in actively or passively immunized individuals.
Mechanistic Studies on the Reaction of [FeIII(edta)(H2O)]– with Piloty′s Acid as Source for HNO
Authors: Muthig André , Polaczek Justyna , van Eldik Rudi
Published: May 2019

In earlier work performed in our laboratories, the reaction of [FeII(edta)(H2O)]2– with ·NO(g) was studied as a trap for ·NO(g) and found to be very efficient with a formation constant of ca. 106 M–1 at 25 °C. The formed nitrosyl complex was shown to have substantial FeIII‐NO–, i.e. nitroxyl, character in line with detailed computational studies performed before. In recent years, we developed an interest in the chemistry of HNO/NO– (nitroxyl) and decided to use [FeIII(edta)(H2O)]– as starting material to see whether the reaction of this complex would lead directly to the formation of the nitroxyl complex by using a source for HNO. In the present study, Piloty's acid (benzenesulfonylhydroxamic acid) was used as source for HNO, since it cleanly hydrolysis in basic aqueous solution to release HNO. The results of our studies clearly indicate that the same reaction product as found for the reaction of [FeII(edta)(H2O)]2– with ·NO(g), was formed in the reaction of [FeIII(edta)(H2O)]– with Piloty's acid. A detailed spectroscopic and mechanistic study of the latter reaction is reported.
Tin‐Carboxylate MOFs for Sugar Transformation into Methyl Lactate
Authors: Murillo Beatriz , Zornoza Beatriz , de la Iglesia Oscar , Wang Sujing , Serre Christian , Téllez Carlos , Coronas Joaquín
Published: May 2019

With the purpose of improving the production of methyl lactate (ML) from sugars (glucose and sucrose), a new metal‐organic framework (MOF) denoted as UZAR‐S10, containing Sn ions and ligand 2‐aminobenzene‐1,4‐dicarboxylate was synthesized. The SEM and PXRD characterization revealed that UZAR‐S10 was highly crystalline. The empirical formula of UZAR‐S10 is [(NH2‐BDC)Sn]·(NH2‐BDC)0.5, i.e., per Sn atom, with one structural ligand molecule and half ligand molecule trapped in the MOF structure. The removal of the trapped ligand by either solvent extraction or thermal treatment damaged the structure of UZAR‐S10, not enabling its activation. The performance of UZAR‐S10 in the production of ML was compared to those achieved with different types of carboxylate MOFs, especially with that of Sn partially substituted Ti tetracarboxylate MOF denoted MIP‐177‐LT (MIP‐177‐LT(Ti/Sn)). The highest ML yields achieved from sucrose were 29.5 % and 42.0 % for UZAR‐S10 and MIP‐177‐LT(Ti/Sn), respectively. For comparison, other carboxylate type MOFs (MIL‐53(Al), NH2‐MIL‐53(Al), UiO‐66, MIL‐101(Cr) and HKUST‐1) were tested at the same conditions with worse performance than the two Tin‐containing MOFs.
Water‐Soluble, Disulfonated alpha‐Diimine Rhodium(I) Complexes: Synthesis, Characterisation and Application as Catalyst Precursors in the Hydroformylation of 1‐Octene
Authors: Omosun Nikechukwu N. , Smith Gregory S.
Published: May 2019

The synthesis and characterisation of two new water‐soluble RhI mononuclear 1,4‐diazabutadiene (DADs) complexes of general formula: [Rh(DADs‐R)(COD)], where (DADs = sulfonated‐tagged–1,4‐diazabutadiene, COD = cyclooctadiene; and R = H or C10H8), are described. The rhodium(I) complexes were obtained via a complexation reaction of [Rh(COD)(MeCN)2]BF4 with the sulfonated α‐diimine (DAD) ligands, which were previously obtained from a Schiff base condensation reaction of 4‐aminophenol with either 1,2‐ethanedione or acenapthenequinone. All rhodium complexes and their precursor ligands were characterised using 1H NMR, 13C NMR, FT‐IR spectroscopy and mass spectrometry. Their performance as catalyst precursors in the hydroformylation of 1‐octene was assessed and compared to those of the non‐sulfonated RhI mononuclear 1,4‐diazabutadiene (DAD) complexes. Utilisation of the water soluble [Rh(DADs‐R)(COD)] lead to high conversions and regioselectivity (linear/branched aldehyde ratio) in the aqueous biphasic hydroformylation of 1‐octene. Additionally, the catalysts were recovered by phase separation and are reusable over four consecutive catalytic runs without significant loss in catalytic activity.
IT for the informal sector in developing countries: A broader perspective
Authors: Seetharaman Priya , Cunha Maria Alexandra , Effah John
Published: May 2019

Although the informal sector's presence in the developed world is by no means meagre, the themes and issues related to information technology (IT) for this sector in the developing country contexts seem stark and deeply contrasted with those relating to the informal sector in developed countries. Solutions which attempt to exploit the potential of IT for the informal sector have thus far been either knee‐jerk, ad‐hoc, or have mimicked those targeted at the formal sector. However, technology tools available today can accelerate, catalyze, and go beyond the conventional straight‐jacketed technology, economic, and policy solutions for the informal sector. The papers in this special issue reflect this theme and attempt to present a glimpse of the possibilities for achieving and the challenges in effecting such solutions.
Nonalcoholic Fatty Liver Disease in The Rotterdam Study: About Muscle Mass, Sarcopenia, Fat Mass, and Fat Distribution
Authors: Alferink Louise Johanna Maria , Trajanoska Katerina , Erler Nicole Stephanie , Schoufour Josje Dorothea , de Knegt Robert Jacobus , Ikram M. Arfan , Janssen Harry Leonardus Antonius , Franco Oscar H. , Metselaar Herold J. , Rivadeneira Fernando , Darwish Murad Sarwa
Published: May 2019

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide. Obesity is a major risk factor for NAFLD and recently, low skeletal muscle mass emerged as additional risk factor for NAFLD. However, the different contributions of body mass index (BMI) to the risk of NAFLD are not yet well-known. We therefore studied body composition and muscle function with NAFLD in an elderly population-based study. Participants of European descent underwent dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography. NAFLD was defined as liver steatosis in absence of secondary causes for steatosis. Skeletal muscle index (SMI) was defined as appendicular lean mass/height2 and (pre)sarcopenia was defined using the European Working Group on Sarcopenia in Older People (EWGSOP) consensus guidelines. All analyses were stratified by sex and BMI (cut point: 25 kg/m2) and adjusted for age, weight, height, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, and android-fat-to-gynoid-fat ratio (AGR). We included 4609 participants, of whom 1623 had NAFLD (n = 161 normal-weight and n = 1462 overweight). Presarcopenia and sarcopenia prevalence was low (5.9% and 4.5%, respectively) and both were not associated with NAFLD. SMI was associated with less NAFLD in normal-weight women (OR, 0.48; 95% CI, 0.29 to 0.80). A similar association for SMI and NAFLD was seen in normal-weight men, but significance dissipated after adjustment for AGR (OR, 0.63; 95% CI, 0.39 to 1.02). Generally, fat mass was a better predictor for NAFLD than lean mass. In particular, android fat mass was associated with all NAFLD subgroups (OR from 1.77 in overweight men to 8.34 in normal-weight women, pmax = 0.001), whereas substitution of gynoid fat mass for other body components had a significant protective association with NAFLD in every subgroup, but normal-weight men. Likewise, AGR was the best performing predictor for NAFLD prevalence (OR from 1.97 in normal-weight men to 4.81 in normal-weight women, pmax < 0.001). In conclusion, both high fat mass and low SMI were associated with normal-weight NAFLD. However, fat distribution (as assessed by AGR) could best predict NAFLD prevalence. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Circular RNA rno_circ_0004002 regulates cell proliferation, apoptosis, and epithelial‐mesenchymal transition through targeting miR‐342‐5p and Wnt3a in anorectal malformations
Authors: Qu Yuan , Liu Dan , Jia Huimin , Yang Zhonghua
Published: May 2019

Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have regulatory functions in varieties of diseases. The purpose of this study was to investigate the potential role of circRNAs in anorectal malformations (ARM). With sequencing analysis, 78 circRNAs were identified to be differentially expressed on gestational day (GD) 19 in ARM and normal anorectal tissues, including 41 upregulated and 37 downregulated circRNAs. Among the downregulated circRNAs, rno_circ_0004002 was selected as the candidate circRNA. Functionally, silencing of rno_circ_0004002 was correlated with suppression of proliferation, and promotion of apoptosis and epithelial‐mesenchymal transition (EMT) in anorectal development. For the mechanism investigation, bioinformatic prediction and luciferase reporter assay revealed that rno_circ_0004002 was proved to be a sponge of miR‐342‐5p, and miR‐342‐5p could target 3'‐UTR of Wnt3a to negatively regulate its expression. The quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results showed that the expression of miR‐342‐5p was significantly increased in ARM anorectal tissues compared with normal tissues on GD19 and GD21, and the expression of Wnt3a demonstrated the opposite on GD21. In addition, rescue assays disclosed that miR‐342‐5p inhibitor could reverse the role of rno_circ_0004002 knockdown on the repression of anorectal development. In summary, our study shed light on the regulatory mechanism of rno_circ_0004002 in cell proliferation, apoptosis, and EMT via sponging miR‐342‐5p, which downregulated the Wnt3a expression in anorectal development. We also suggested that GD19 and GD21 was the crucial time in the progression of ARM, and rno_circ_0004002/miR‐342‐5p/Wnt3a might serve as potential therapeutic targets for ARM.
Gene expression profile of the hippocampus of rats subjected to traumatic brain injury
Authors: Huang Guo‐Hui , Cao Xiang‐Yuan , Li Yuan‐Yuan , Zhou Cheng‐Cheng , Li Lei , Wang Ke , Li Hong , Yu Peng , Jin Yi , Gao Liang
Published: May 2019

Traumatic brain injury (TBI) is a serious public health problem as well as a leading cause of severe posttraumatic disability. Numerous studies indicate that the differentially expressed genes (DEGs) of neural signaling pathways are strongly correlated with brain injury. To further analyze the roles of the DGEs in the central nervous system, here we systematically investigated TBI on the hippocampus and its injury mechanism at the whole genome level. On the basis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Analyses, we revealed that the DEGs were involved in many signaling pathways related to the nervous system, especially neuronal survival‐related pathways. Finally, we verified the microarray results and detected the gene expression of neuronal survival‐related genes in the hippocampus by using real‐time quantitative polymerase chain reaction. With Western blot and axon growth assay, the expression of P2rx3 was upregulated in rats subjected to TBI, and overexpression of P2rx3 promoted neurite growth of NG108 cells. Our results suggested that the DEGs (especially P2rx3) and several signaling pathways might play a pivotal role in TBI. We also provided several targeted genes related to TBI for future investigation.
Quantitative assessment of the association between TAP2 rs241447 polymorphism and cancer risk
Authors: Liu Rongzeng , Ma Yan , Chen Xiafei
Published: May 2019

The findings regarding the relation of transporter associated with antigen processing (TAP) to cancer risk have been inconsistent. The aim of this study was to comprehensively evaluate the association between TAP2 rs241447 polymorphism and cancer susceptibility. A meta‐analysis of nine investigations with 2800 cases and 1620 controls was conducted to gain a better understanding of the effect of TAP2 rs241447 polymorphism on cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of the correlation between TAP2 gene polymorphism and cancer susceptibility. The pooled results from TAP2 rs241447 polymorphism showed a decreased risk of cancer in two dominant genetic models (GG + AG vs AA: OR = 0.86, 95% CI, 0.75‐0.99; AG vs AA: OR = 0.85, 95% CI, 0.73‐0.99). From the subgroup analysis, decreased cancer susceptibility was found in Caucasians (GG + AG vs AA: OR = 0.82, 95% CI, 0.68‐0.99), especially among the subgroup of cervical carcinoma (GG + AG vs AA: OR = 0.82, 95% CI, 0.69‐0.96; AG vs AA: OR = 0.83, 95% CI, 0.70‐0.99). Overall, the results suggest that TAP2 rs241447 polymorphism contributes to decreased cancer susceptibility.
miRNA expression profiling uncovers a role of miR‐302b‐3p in regulating skin fibroblasts senescence
Authors: Tan Jingyong , Hu Longyuan , Yang Xin , Zhang Xin , Wei Canshen , Lu Qing , Chen Zhilin , Li Jing
Published: May 2019

Numbers of emerging evidence suggest that variable microRNA (miRNA) expression facilitates the aging process. In this study, we distinguished aberrant miRNA expression in aged skin and explored the biological functions and potential mechanism of upregulated miR‐302b‐3p. At first, miRNA microarray analysis was examined to explore miRNA expression profiling in the skin of aging mice model by D‐galactose (d‐gal) injection. We identified 29 aberrant miRNAs in aged mice skin. Next, KEGG enrichment analysis was conducted with DIANA‐miPath v3.0, which was revealed that enrichment pathways involved in such processes as extracellular matrix‐receptor interaction, MAPK signaling pathway, and mammalian target of rapamycin (mTOR) signaling pathway. The target genes of deregulated miRNAs were predicted from four bioinformatic algorithms (miRDB, Targetscan, miRwalk, and Tarbase). The interaction network of miRNAs and their targets were visualized using Cytoscape software. As a result, we found that some hub genes (including JNK2, AKT1/2/3, PAK7, TRPS1, BCL2L11, and IKZF2) were targeted by 12 potential miRNAs (including miR‐302b‐3p, miR‐291a‐5p, miR‐139‐3p, miR‐467c‐3p, miR‐186‐3p, etc.). Subsequently, we identified five upregulated miRNA via quantitative polymerase chain reaction and all of them were confirmed increased significantly in aged skin tissues compared with young control tissues. Among them, high expression of miR‐302b‐3p was verified in both aged skin tissues and senescence fibroblasts. Furthermore, miR‐302b‐3p mimic accelerated skin fibroblast senescence and suppressed the longevity‐associated gene Sirtuin 1(Sirt1) expression, whereas miR‐302b‐3p inhibitor could delay skin fibroblast senescence and contribute Sirt1 expression. In addition, we demonstrated that c‐Jun N‐terminal kinase 2(JNK2) is a direct target of miR‐302b‐3p by a luciferase reporter assay. An inverse correlation was verified in fibroblasts between miR‐302b‐3p and JNK2. Most importantly, siRNA JNK2 confirmed that low expression of JNK2 could accelerate fibroblasts senescence. In conclusion, our results indicated that overexpressed miR‐302b‐3p plays an important biological role in accelerating skin aging process via directly targeting JNK2 gene.
LncRNA ANCR is positively correlated with transforming growth factor‐β1 in patients with osteoarthritis
Authors: Li Qingsong , Zhang Zhenxiang , Guo Shuguang , Tang Genlin , Lu Wei , Qi Xin
Published: May 2019

Transforming growth factor‐β (TGF‐β) signaling plays pivotal roles in the pathogenesis of osteoarthritis, while TGF‐β signaling in certain diseases models is regulated by the long noncoding RNA (lncRNA) antidifferentiation noncoding RNA (ANCR). Therefore, ANCR may also participate in osteoarthritis. In this study, the expression of ANCR and TGF‐β1 in the plasma of osteoarthritis patients and healthy controls was detected by real‐time quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively. The diagnostic value of ANCR for osteoarthritis was evaluated by receiver operating characteristic receiver operating characteristic (ROC) curve analysis. The correlation between the plasma levels of ANCR and TGF‐β1 was analyzed by the Pearson correlation coefficient. The ANCR expression vector was transfected into cells of the human chondrocyte cell line CHON‐001 (ATCC CRL‐2846), and the effect on TGF‐β1 expression and cell proliferation was detected by Western blot and cell counting kit‐8 assay, respectively. We observed that the plasma levels of ANCR were significantly lower, while the plasma levels of TGF‐β1 were significantly higher in osteoarthritis patients than those in healthy controls. Downregulation of ANCR effectively distinguished osteoarthritis patients from healthy controls. ANCR and TGF‐β1 expression was negatively correlated in osteoarthritis patients but not in healthy controls. ANCR overexpression promoted the proliferation of chondrocytes and inhibited TGF‐β1 expression. We concluded that ANCR might participate in osteoarthritis by downregulating TGF‐β1 and promote the proliferation of chondrocytes.
Sweroside‐mediated mTORC1 hyperactivation in bone marrow mesenchymal stem cells promotes osteogenic differentiation
Authors: Ding Yan , Jiang Huaji , Meng Biying , Zhu Biao , Yu Xiao , Xiang Guangda
Published: May 2019

This paper aims to probe into the effect of sweroside (SOS) in osteoporosis (OP) and explains mechanisms of its molecular. Applying the ovariectomized (OVX) mouse model investigates the preventive effect of SOS against postmenopausal OP after 3 months of SOS treatment (120 mg/kg/day). Using hematoxylin and eosin (HE) staining and micro computed tomography (CT) observed the morphology of OP in each group. Immunohistochemical staining (IHC) was used to examine osteoblast markers. Experiments in vitro, bone marrow mesenchymal stem cells (BMSCs) from C57/BL6 mice were treated with SOS for 14 days. The staining of alizarin red and alkaline phosphatase activity were measured, and the presentation of osteoblast markers was detected by quantitative reverse transcription PCR. BMSCs were also treated with 1 μg/mL SOS with or without rapamycin, the expression of protein S6 (PS6), P‐mTOR, runt‐related transcription factor 2 (RUNX2), OSX, and osteocalcin (OCN) was detected by Western blotting. Experiments in vivo, HE results show that SOS can alleviate OP, CT results show that there are lower trabecular thickness, bone mineral density, and trabecular number in control OVX mice than those in the OVX + SOS group. IHC results showed that SOS can promote the expression of osteogenic markers and immunofluorescent results show that SOS can promote mTORC1 signal activation. Experiments in vitro revealed that SOS stimulated the activation of the mTORC1 signaling pathway and upregulated RUNX2, OSX, and OCN, rapamycin can reverse it. Our findings demonstrated that differentiated BMSCs into osteoblasts can be promoted by SOS via upregulating the expression of P‐mTOR, PS6, RUNX2, OSX, and OCN. SOS effectively prevented OP by hyperactivation of the mTORC1/PS6 signaling pathway.
C1q/tumor necrosis factor‐related protein‐3 improves renal fibrosis via inhibiting notch signaling pathways
Authors: Chen Xinpan , Wu Yiru , Diao Zongli , Han Xue , Li Dishan , Ruan Xiongzhong , Liu Wenhu
Published: May 2019

C1q/tumor necrosis factor‐related protein‐3 (CTRP3) has been extensively reported as an important role involved in antifibrosis, antiapoptosis, and anti‐inflammation. However, the role of CTRP3 involved in renal fibrosis remains unclear. Our current study explored the role of CTRP3 in renal fibrosis and its underlying mechanisms by using serums and renal biopsy specimens from renal fibrosis patients and control subjects, rats models with the surgery of unilateral ureteral obstruction (UUO) and human renal proximal tubular epithelial cells (HRPTEpiCs). We found that circulating levels of CTRP3 had no significant difference between renal fibrosis patients and healthy subjects; however, renal CTRP3 expression was markedly downregulated in the fibrotic region with an abundant expression of collagen‐I. In UUO rat models, circulating levels of CTRP3 have not changed with the prolonged obstruction of the kidney; renal CTRP3 expression was decreased with the severity of renal fibrosis; adenovirus‐mediated CTRP3 treatment inhibited renal interstitial fibrosis. In vitro experiments revealed that CTRP3 attenuates TGF‐β1 induced tubular epithelial cells fibrotic changes; CTRP3 knockdown facilitates the expression of fibrotic markers in TGF‐β1‐induced HRPTEpiCs; recombinant CTRP3 or adenovirus‐mediated CTRP3 overexpression significantly inhibited the Notch signaling pathway‐associated factors, and knockdown of CTRP3 increased TGF‐β1‐mediated activation of the Notch signaling pathways. Collectively, our current study found that CTRP3 could improve renal fibrosis, to some extent, through inhibiting the Notch pathway.
Effects of CXCL4/CXCR3 on the lipopolysaccharide‐induced injury in human umbilical vein endothelial cells
Authors: Wang Xiaolin , Zhao Zhenzhen , Zhu Kaimin , Bao Rui , Meng Yan , Bian Jinjun , Wan Xiaojian , Yang Tao
Published: May 2019

Chemokines and inflammatory response of endothelial cells is crucial in the development and progression of inflammatory disease. Lipopolysaccharide (LPS) is a well‐known factor to trigger inflammatory response and induce damage of endothelial cells. The present study used lipopolysaccharide (LPS)‐treated human vascular endothelial cells (HUVECs) to investigate the function of chemokine CXC chemokine ligand 4 (CXCL4) and its receptor CXC chemokine receptor 3 (CXCR3) in inflammatory‐induced endothelial injury. LPS exposure (50, 100, 200 ng/ml) to HUVECs induced a dose‐ and time‐dependent increase in CXCL4 and CXCR3 expression at both mRNA and protein levels. The LPS‐induced endothelium hyperpermeability was inhibited by the addition of CXCL4 neutralizing antibody. Moreover, the addition of CXCL4 neutralizing antibody abolished the effects of LPS on tight junction (TJ) protein expression (occludin claudin‐4 and Zonula occluden‐1[ZO‐1]) and p38 phosphorylation, which is supported by the observation of increased TJ protein expression and decreased p38 phosphorylation in LPS‐treated HUVECs. SB203580, a p38 inhibitor, protected HUVECs from CXCL4‐stimulated damage. In conclusion, CXCL4/CXCR3, which was enhanced by LPS, may be involved in endothelial proliferation, apoptosis, and permeability via the p38 signaling pathway.
Appetite and food intake results from phase I studies of anamorelin
Authors: Blum Robert A. , Mair Stuart , Duus Elizabeth M.
Published: May 2019

Background

Loss of appetite and body weight are potentially devastating, highly prevalent cancer complications. The ghrelin receptor is a mediator of appetite and metabolism, and anamorelin is a novel, orally administered ghrelin receptor agonist. Effects on appetite and food intake may influence body‐weight gain but can be difficult to measure in multi‐site studies. Here, we summarize two single‐centre trials.

Methods

Both trials were phase I, randomized, double‐blind, placebo‐controlled, partly/wholly crossover studies of healthy young adults. Study 102 tested single anamorelin doses of 1–20 mg. Assessments included post‐dose self‐ratings on 100 mm visual analogue scales for hunger, anticipated eating pleasure, and anticipated quantity of food consumption. Study 101 tested single 10, 25, and 50 mg doses. Assessments included the same scales plus caloric intake beginning 4 h post‐dose.

Results

Study 102 treated 16 male subjects (mean age, 26.3 years). Mean hunger scores generally increased after all treatments, with significant differences from placebo (P < 0.05) in the 5 mg anamorelin group at 0.5 and 1 h post‐dose (+8.2 and +13.2 mm). Results for other scales were similar. Study 101 treated nine male subjects (mean age, 26.3 years). Pooled findings for anamorelin 25 and 50 mg vs. placebo showed significant mean increases in hunger scores at all but 1 pre‐prandial time point, including the first assessment, 0.5 h post‐dose (+10.9 vs. +0.7 mm, P = 0.0077), and the last assessment, 4 h post‐dose (+32.7 vs. +7.0 mm, P = 0.0170), with a significant mean 18.4% increase vs. placebo in caloric intake (P = 0.0148).

Conclusions

In single‐centre studies of healthy adults, single anamorelin doses of 1–20 mg elicited modest increases in hunger, and single doses of 25 and 50 mg achieved significant increases in hunger and caloric intake. The findings are consistent with dose‐related weight gain reported in a prior phase I study as well as multi‐centre findings in cachectic cancer patients and expand the evidence supporting anamorelin as a potential intervention.
Microwave pyrolysis of sludge for potential use as land application and biofuel
Authors: Lin Kuo‐Hsiung , Zeng Jun‐Yan , Chiang Hung‐Lung
Published: May 2019

BACKGROUND

A microwave pyrolysis was conducted to treat two sludge cakes for the production of liquid oil and sludge residues. The application of pyrolysis technology, the safety of land disposal of pyrolysis residue, and the quality of the derived biofuel were evaluated.

RESULTS

Results indicated that the total pore volume increased with increases in the mesopore size range in the case of both sludge residues after increasing the pyrolysis temperature. Low carbon, hydrogen, and sulfur content and high nitrogen content were observed in the oil derived from the chemical industry sludge. As a result, the pyrolysis liquid chemical sludge oils had heat values of 9600 to 9700 kcal kg−1 at 673–1073 K, which was slightly lower than the 9800–10 000 kcal kg−1 found for the petrochemical sludge.

CONCLUSION

After pyrolysis, the amount of 16 polyaromatic hydrocarbons (PAHs) in the residue and oil were significantly reduced in both the chemical sludge and petrochemical sludge at 673–1073 K. The high pyrolysis liquid oil heat values for both types of sludge indicated their potential for use as a biofuel to produce energy. The 16 PAH content in the pyrolysis residues was higher than the European standard of 6 mg kg−1, and they were thus not acceptable for soil and agricultural applications. However, as reported in the literature, using a pyrolysis temperature above 1073 K may further reduce the PAH content of the pyrolysis residue to meet regulatory standards. © 2019 Society of Chemical Industry
Soluble recombinant pyruvate oxidase production in Escherichia coli can be enhanced and inclusion bodies minimized by avoiding pH stress
Authors: Zhang Jianguo , Lu Junwen , Su Erzheng
Published: May 2019

BACKGROUND

Recombinant pyruvate oxidase (pod) is in high demand owing to its broad application in biochemical analysis and low yield from wild microbial strains. Recombinant Escherichia coli harboring pET28a‐pod is an efficient producer of pod, facilitating its production in high yield. Optimizing cultivation using shake flasks is necessary for high‐level soluble pod production.

RESULTS

During recombinant E. coli cultivation, 96.9% of pod activity was lost, and 3.1% of residual pod activity remained in a 25 mL working volume in 250 mL flasks owing to accumulation of pod in insoluble inclusion bodies. pH stress was the factor responsible for this phenomenon based on investigating dissolved oxygen and carbon source addition. Residual pod activity was increased to 43.3, 88.0 and 61.5% by maintaining the pH at 5.0, 6.0 and 7.0 respectively during the induction phase, which decreased inclusion body formation and increased production of soluble pod. Glycerol addition increased the cell density and volumetric pod activity to 21 243.3 U L−1 at pH 6.0 after 64 h induction.

CONCLUSION

Soluble pod is converted to inclusion bodies under pH stress conditions, and this can be avoided by pH maintenance. © 2019 Society of Chemical Industry