bluuebunny/crossref_metadata_2025 huggingface dataset:
Confident and Understanding Parents (CUPs) – a child nutrition and active play pilot intervention for disadvantaged families attending Supported Playgroups in Victoria, Australia
Authors: Myers Judith , Riggs Elisha , Lee Ju‐Lin , Gibbons Kay , Naughton Geraldine
Published: January 2019

Issue addressed

Health and nutrition inequalities are prevalent among families from socio‐economically disadvantaged backgrounds. However, there is limited evidence of targeted early childhood nutrition and active play approaches due to the methodological challenges in engaging vulnerable families in research.

Methods

The aim of this paper was to report findings from a pilot intervention called Confident and Understanding Parents (CUPs). CUPs aims to improve child nutrition and active play‐related outcomes for children in vulnerable families. The intervention was delivered in six Supported Playgroups (SPs) in two disadvantaged locations in Victoria. Surveys incorporated knowledge and confidence measures and were administered pre‐ and post‐training of SP facilitators along with pre‐, immediately post and and 3 months postintervention to SP facilitators and parents. Qualitative data were collected via debriefing discussions with SP facilitators and ethnographic observations during SP sessions. Thematic analyses of qualitative data and statistical quantitative analyses were conducted.

Results

Nine SP facilitators completed training, of whom six delivered CUPs in SPs with 64 parents of children aged 0 to 4 years from socially disadvantaged backgrounds. Forty‐three parents (66%) attended a minimum of 50% of SP sessions with CUPs delivery. SP facilitators and parents demonstrated improved knowledge and confidence following the pilot. Learnings for implementation were identified.

Conclusion

Overall, the CUPs intervention reached and engaged vulnerable families. A strength of the intervention is the flexibility offered to SP facilitators in selecting key messages and the strong focus on “local” translation of key child nutrition and active play messages within existing early childhood settings. A further strength was the adaptation of evaluation methodology to optimise the engagement of vulnerable families.

So what?

This pilot study provides insights about engaging vulnerable families in a nutrition and active play intervention to promote child health. These promising findings warrant further implementation and rigorous evaluation of CUPs.
Post‐stroke ankle‐foot orthoses: Examining referral trends in the Scottish multi‐disciplinary team
Authors: Morrow Eileen , Bowers Roy
Published: January 2019

Purpose

As per the Best Practice Statement: Use of Ankle‐Foot Orthoses Following Stroke (BPS), members of the stroke multidisciplinary team should refer stroke patients with mobility problems to orthotics. Therefore, the objectives of this study were to (1) assess awareness of the BPS; (2) assess referral patterns and trends; and (3) identify barriers to referral to the Orthotic Service in Scotland.

Methods

An online survey of the stroke MDT, working in Scotland, whose current role involves work with stroke patients. A survey was distributed via the Scottish Stroke Allied Health Professionals Forum, Scottish Stroke Nurses Forum, British Association of Stroke Physicians, and Scottish Stroke Managed Clinical Networks.

Results

Statistically significant association was found between:

Awareness of BPS and NHS Board Area;

Profession and whether clinicians have referred to orthotics;

Confidence in assessment criteria and profession;

Referral to departments other than Orthotics and profession.

Conclusion

Physiotherapists are relied upon by members of the Stroke MDT to identify mobility problems and refer to Orthotics. The BPS should be re‐disseminated, particularly to the East of Scotland and GPs, to improve awareness of referral criteria. Reduced waiting list times and joint physiotherapist‐orthotist clinics may reduce referral barriers to the Orthotic Service.
Applications of SNAP‐tag technology in skin cancer therapy
Authors: Padayachee Eden Rebecca , Adeola Henry Ademola , Van Wyk Jennifer Catherine , Nsole Biteghe Fleury Augustine , Chetty Shivan , Khumalo Nonhlanhla Patience , Barth Stefan
Published: January 2019

Background

Cancer treatment in the 21st century has seen immense advances in optical imaging and immunotherapy. Significant progress has been made in the bioengineering and production of immunoconjugates to achieve the goal of specifically targeting tumors.

Discussion

In the 21st century, antibody drug conjugates (ADCs) have been the focus of immunotherapeutic strategies in cancer. ADCs combine the unique targeting of monoclonal antibodies (mAbs) with the cancer killing ability of cytotoxic drugs. However, due to random conjugation methods of drug to antibody, ADCs are associated with poor antigen specificity and low cytotoxicity, resulting in a drug to antibody ratio (DAR) >1. This means that the cytotoxic drugs in ADCs are conjugated randomly to antibodies, by cysteine or lysine residues. This generates heterogeneous ADC populations with 0 to 8 drugs per an antibody, each with distinct pharmacokinetic, efficacy, and toxicity properties. Additionally, heterogeneity is created not only by different antibody to ligand ratios but also by different sites of conjugation. Hence, much effort has been made to find and establish antibody conjugation strategies that enable us to better control stoichiometry and site‐specificity. This includes utilizing protein self‐labeling tags as fusion partners to the original protein. Site‐specific conjugation is a significant characteristic of these engineered proteins. SNAP‐tag is one such engineered self‐labeling protein tag shown to have promising potential in cancer treatment. The SNAP‐tag is fused to an antibody of choice and covalently reacts specifically in a 1:1 ratio with benzylguanine (BG) substrates, eg, fluorophores or photosensitizers, to target skin cancer. This makes SNAP‐tag a versatile technique in optical imaging and photoimmunotherapy of skin cancer.

Conclusion

SNAP‐tag technology has the potential to contribute greatly to a broad range of molecular oncological applications because it combines efficacious tumor targeting, minimized local and systemic toxicity, and noninvasive assessment of diagnostic/prognostic molecular biomarkers of cancer.
Mesoscopic approach for steady‐state free convection in a diamond array
Authors: Chaabane Raoudha , Askri Faouzi , Jemni Abdelmajid
Published: January 2019

The purpose of the present paper is testing an in‐house efficiency algorithm based on lattice Boltzmann method (LBM) and using it to resolve the obtained coupled nondimensional governing equations to analyze two‐dimensional free convection inside a cold outer cavity subjected to a heated cylindrical diamond array. Steady state or oscillatory results are obtained using the Bhatnagar‐Gross‐Krook collision model associated to the thermal LBM. Both the velocity and temperature fields are solved using the D2Q9 models. With different Rayleigh numbers (Ra), the tested free convection can either achieve to steady state or oscillatory. We extended our in house Fortran 90 code using curved boundary conditions and implemented them into a cavity with a diamond array. The numerical simulations were done using distinct Ra (106 and 10
7) and distances between the four neighboring circular cylinders aligned in a diamond array. The effects of several physical parameters, including Ra and position of the hot body array on flow and heat transfer characteristics are investigated. The obtained results are highlighted in the form of streamlines, isotherms, and velocities plots. We show in this paper the stability and the efficiency of the LBM to deal with a complex geometry and its ability to reach suitable convergence criteria for high Ra (10
6 and 10
7). The numerical results indicate that LBM can simulate numerical problems with a high Ra reaching a steady state where we can depict the change of the flow pattern and enhancement of the heat transfer in the presence of heated diamond array.
No evidence so far of a major role of AKT1 and GSK3B in the pathogenesis of antipsychotic‐induced tardive dyskinesia
Authors: Levchenko Anastasia , Vyalova Natalya , Pozhidaev Ivan V. , Boiko Anastasiia S. , Osmanova Diana Z. , Fedorenko Olga Yu. , Semke Arkadiy V. , Bokhan Nikolay A. , Wilffert Bob , Loonen Anton J.M. , Ivanova Svetlana A.
Published: January 2019

Objective

AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic‐induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic‐treated patients with schizophrenia.

Methods

DNA samples from 449 patients from several Siberian regions (Russia) were genotyped, and the results were analyzed using chi‐squared tests and analyses of variance.

Results

Antipsychotic‐induced TD was not associated with either of the tested functional polymorphisms (rs334558, rs1130214, and rs3730358).

Conclusions

Despite regulation of AKT1 and GSK3B by DRD2, we found no evidence that these two kinases play a major role in the pathogenesis of antipsychotic‐induced TD. These results agree with previously published data and necessitate further exploration of other pathogenic mechanisms, such as neurotoxicity due to excessive dopamine metabolism.
Highly conservative behaviour of bed sediment‐associated metals following extreme flooding
Authors: Hurley Rachel R. , Woodward Jamie C. , Rothwell James J.
Published: January 2019

On December 26, 2015 (Boxing Day), an exceptional flood event occurred in the Irwell catchment, United Kingdom, when the neighbouring Mersey catchment experienced a much more typical winter run‐off event. This provided an opportunity to examine the influence of high‐magnitude hydrological processes on the behaviour of fine‐grained metal‐contaminated bed sediments. Forty sites across the two catchments were sampled for channel bed fine sediment storage and sediment‐associated metal(loid) concentrations prior to, and following, the flooding. Sediments were analysed for total As, Cr, Cu, Pb, and Zn and then subjected to a five‐step sequential extraction procedure. Despite a significant reorganisation of fine‐grained (<63 μm) sediment storage, metal(loid) concentrations demonstrated markedly conservative behaviour with no significant difference observed between pre‐flooding and post‐flooding values across both catchments. Estimates of the channel bed storage of sediment‐associated metal(loid)s also showed minimal change as a result of the flooding. The metal partitioning data reveal only minor changes in the mobility of bed sediment‐associated metal(loid)s, indicating that such flood events do not increase the availability of sorbed contaminants in these catchments. Post‐flooding bed sediment metal(loid) loadings remain high, indicating persistent and long‐lasting sources of contamination within the Irwell and upper Mersey fluvial network.
Marine omega‐3 fatty acid intake and survival of stage III colon cancer according to tumor molecular markers in NCCTG Phase III trial N0147 (Alliance)
Authors: Song Mingyang , Ou Fang‐Shu , Zemla Tyler J. , Hull Mark A. , Shi Qian , Limburg Paul J. , Alberts Steven R. , Sinicrope Frank A. , Giovannucci Edward L. , Van Blarigan Erin L. , Meyerhardt Jeffrey A. , Chan Andrew T.
Published: January 2019

Marine omega‐3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease‐free survival (DFS) and overall survival according toKRASandBRAFV600Emutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3‐year DFS forKRASwild‐type tumors (77%vs. 73%; HR: 0.84; 95% CI: 0.67–1.05) but notKRAS‐mutant tumors (64%vs. 70%; HR: 1.30; 95% CI: 0.97–1.73;Pinteraction= 0.02). Similar heterogeneity was found by MMR (Pinteraction= 0.14): higher MO3PUFA was associated with better 3‐year DFS for tumors with deficient MMR (72%vs. 67%) but not proficient MMR (72%vs. 72%). No heterogeneity was found byBRAFV600Emutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild‐typeKRASand deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.
An MBSE Eco‐System for Performing Trade‐off Analysis
Authors: Hause Matthew
Published: January 2019

A trade‐off study consists of “comparing the characteristics of each system element and of each candidate system architecture to determine the solution that best globally balances the assessment criteria. The various characteristics analyzed are gathered in cost analysis, technical risks analysis, and effectiveness analysis (NASA 2007).” Trade‐off analysis is the set of techniques by which the “best” solution is found for the customer weighing up cost, risk, effectiveness, and other parameters. The weighting or importance of these parameters depends on the system goals and priorities, which are derived from stakeholder needs, which are gathered from stakeholders. As always, good system solutions are derived from good systems engineering. Defining a decision framework that reflects competing goals, needs, priorities, parameters, and architectures in a clear and understandable way. Orthogonal Variability Modeling (OVM) provides the ability to model systems and software products, their variation points, mutual exclusions, and product dependencies resulting in product lines. OVM was developed by the University Duisburg‐Essen, PALUNO Institute [Paluno 2005], and is now ISO standard ISO 26550: 2013, Reference Model for System and Software Product Line Engineering and Management (ISO, 2013). Through this modeling technique, fully supported by the MBSE toolsets, engineers can see their options and conflicts (if any exist), and to pick their end desired product. Variation Points, Variants (options), and Dependencies can be defined, and relationships parametrized. Variable Elements can be linked to express required and excluded relationships. (ISO, 2013). Options can then be selected based on user goals, a configuration generated, and trade‐off analysis can take place on the resulting model.
Stabilization of Heavy Metals in Contaminated Sediments Using Organic Chelating Agents
Authors: Xu Ying , Fang Sheng‐Rong
Published: January 2019

A stabilization treatment for heavy metals in sediments was developed using the heavy metal chelators ammonium dipropyl dithiophosphate (ADD) and potassium diisopropyl dithiophosphate (PDD). The results indicate that 7% ADD and 7% PDD achieved Pb and Cu stabilization rates of up to 99%, Cd stabilization rates of 78% and 95%, and Zn stabilization rates of 21 and 51%, respectively. At pH levels ranging from 2 to 12, the amount of heavy metals in leachate from the stabilized product using the chelating agents were significantly less than those using Na2S and Na3PO4. After treatment, the chelating agents were mainly bound to the exchangeable fraction of heavy metals in the sediment and formed stable bonds with organic matter, thus significantly reducing the biological risks of heavy metals in sediment.
Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress
Authors: Chen Jiamao , Yang Ting , Long Jimin , Ding Yanhuai , Li Juan , Li Xianqiang , Cao Yi
Published: January 2019

We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini‐NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress‐apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini‐NRs and palmitate (PA) to THP‐1 macrophages. PA influenced the zeta potential and solubility of ZnO NRs and ZnO Mini‐NRs in water, which indicated a change of colloidal stability. Exposure to ZnO NRs and Mini‐NRs dose‐dependent decreased cellular viability and release of soluble monocyte chemotactic protein 1 (sMCP‐1), and these effects were significantly promoted with the presence of PA. However, ZnO NR‐ and Mini‐NR‐induced intracellular Zn ions or reactive oxygen species were not significantly affected by PA. ZnO NRs and ZnO Mini‐NRs significantly promoted the expression of ER stress genes HSPA5, DDIT3, XBP‐1s and apoptotic gene CASP3, whereas PA also modestly promoted the expression of HSPA5, DDIT3 and CASP3. Interestingly, the ER stress inducer thapsigargin showed a similar effect as PA to promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs. It is suggested that PA might promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs possibly by promoting ER stress.
Effects of High-Fat Diet and Body Mass on Bone Morphology and Mechanical Properties in 1100 Advanced Intercross Mice
Authors: Silva Matthew J , Eekhoff Jeremy D , Patel Tarpit , Kenney-Hunt Jane P , Brodt Michael D , Steger-May Karen , Scheller Erica L , Cheverud James M
Published: January 2019

Obesity is generally protective against osteoporosis and bone fracture. However, recent studies indicate that the influence of obesity on the skeleton is complex and can be detrimental. We evaluated the effects of a high-fat, obesogenic diet on the femur and radius of 1100 mice (males and females) from the Large-by-Small advanced intercross line (F34 generation). At age 5 months, bone morphology was assessed by microCT and mechanical properties by three-point bending. Mice raised on a high-fat diet had modestly greater cortical area, bending stiffness, and strength. Size-independent material properties were unaffected by a high-fat diet, indicating that diet influenced bone quantity but not quality. Bone size and mechanical properties were strongly correlated with body mass. However, the increases in many bone traits per unit increase in body mass were less in high-fat diet mice than low-fat diet mice. Thus, although mice raised on a high-fat diet have, on average, bigger and stronger bones than low-fat-fed mice, a high-fat diet diminished the positive relationship between body mass and bone size and whole-bone strength. The findings support the concept that there are diminishing benefits to skeletal health with increasing obesity. © 2019 American Society for Bone and Mineral Research.
Marketing of Professional Counselors: A Q‐Sort Study of Best Practices
Authors: Sheperis Donna S. , Korani Komal , Milan‐Nichols Marsha , Sheperis Carl J.
Published: January 2019

This quantitative Q‐sort research was designed to evaluate representations of counselor qualifications and to determine which configurations account for the variance in consumer preference and selection. The sample consisted of 161 graduate and undergraduate students in a regional university in Texas. An iterative inverse factor analysis produced 3 distinct factors that accounted for 65.85% of the variance in the data, explaining a majority of the differences in how consumers perceive counselor credentials.
A Constructive Approach to Help Counselors Work With Clients Who Express Discriminatory Views
Authors: Guiffrida Douglas , Tansey Mathew , Miller Daniel
Published: January 2019

Although much has been written to help counselors understand the potential impact of their own biases toward clients from traditionally marginalized groups, much less attention has been given to assist counselors working with clients who express discriminatory views that counselors may find offensive. In this article, the authors briefly outline how constructive clinical supervision can be integrated with aspects of relational–cultural theory and moral foundations theory to help counselors work with clients who espouse discriminatory views.
Generalized Prediction of Enthalpies of Formation Using DLPNO‐CCSD(T) Ab Initio Calculations for Molecules Containing the Elements H, C, N, O, F, S, Cl, Br
Authors: Mielczarek Detlev Conrad , Nait Saidi Chourouk , Paricaud Patrice , Catoire Laurent
Published: January 2019

The prediction of thermochemical properties such as enthalpies of formation is of crucial importance, both in research and industrial applications, especially for systems involving not well‐characterized molecules, such as biomass systems (bio‐oils), or systems involving new compounds (new‐generation refrigerants). It is highly desirable to obtain an efficient method by which these values can be predicted. Ab initio‐based calculations can be very accurate for predicting gas phase thermochemical properties and are usually more versatile than group contribution methods. In this work, we propose a general extension of the work of Paulechka and Kazakov, using very accurate and efficient domain‐based local pair natural orbital‐coupled cluster theory ab initio calculations, to determine the enthalpies of formation of a broad variety of molecules. New sets of regressed atomic contributions are proposed for a larger group of elements: H, C, N, O, F, S, Cl, and Br. Excellent predictions are obtained for the most studied compounds (bio‐oil compounds and refrigerants). © 2019 Wiley Periodicals, Inc.
Intrapersonal and social–contextual factors related to psychological well‐being among youth experiencing homelessness
Authors: Stewart Katricia , Townley Greg
Published: January 2019

Homeless youth are adolescents and young adults who do not have stable dwellings but instead live on the streets, in shelters, or in other unstable situations. Although researchers have begun examining well‐being among this population, little is known about components of well‐being that are relevant to homeless youth or which factors predict differences in well‐being. This study examined psychological well‐being and its associations with demographic characteristics, intrapersonal factors (mental health, optimism, and self‐esteem), and social–contextual factors (social support, sense of community, and empowerment) among 100 youth experiencing homelessness. All of the intrapersonal and social–contextual variables were associated with well‐being at the bivariate level. In the full regression model, only self‐esteem and psychological distress remained significant. Findings inform future research and program development at homeless service centers.
KCNQ1 rescues TMC1 plasma membrane expression but not mechanosensitive channel activity
Authors: Harkcom William T. , Papanikolaou Maria , Kanda Vikram , Crump Shawn M. , Abbott Geoffrey W.
Published: January 2019

Transmembrane channel‐like protein isoform 1 (TMC1) is essential for the generation of mechano‐electrical transducer currents in hair cells of the inner ear. TMC1 disruption causes hair cell degeneration and deafness in mice and humans. Although thought to be expressed at the cell surface in vivo, TMC1 remains in the endoplasmic reticulum when heterologously expressed in standard cell lines, precluding determination of its roles in mechanosensing and pore formation. Here, we report that the KCNQ1 Kv channel forms complexes with TMC1 and rescues its surface expression when coexpressed in Chinese Hamster Ovary cells. TMC1 rescue is specific for KCNQ1 within the KCNQ family, is prevented by a KCNQ1 trafficking‐deficient mutation, and is influenced by KCNE β subunits and inhibition of KCNQ1 endocytosis. TMC1 lowers KCNQ1 and KCNQ1‐KCNE1 K+ currents, and despite the surface expression, it does not detectably respond to mechanical stimulation or high salt. We conclude that TMC1 is not intrinsically mechano‐ or osmosensitive but has the capacity for cell surface expression, and requires partner protein(s) for surface expression and mechanosensitivity. We suggest that KCNQ1, expression of which is not thought to overlap with TMC1 in hair cells, is a proxy partner bearing structural elements or a sequence motif reminiscent of a true in vivo TMC1 hair cell partner. Discovery of the first reported strategy to rescue TMC1 surface expression should aid future studies of the TMC1 function and native partners.
Novel cellular mechanism that mediates the collecting duct formation during postnatal renal development
Authors: del Valle Guaytima Edith , Brandán Yamila Romina , Favale Nicolás Octavio , Sterin‐Speziale Norma B. , Márquez María Gabriela
Published: January 2019

We have previously demonstrated that kidney embryonic structures are present in rats, and are still developing until postnatal Day 20. Consequently, at postnatal Day 10, the rat renal papilla contains newly formed collecting duct (CD) cells and others in a more mature stage. Performing primary cultures, combined with immunocytochemical and time‐lapse analysis, we investigate the cellular mechanisms that mediate the postnatal CD formation. CD cells acquired a greater degree of differentiation, as we observed that they gradually lose the ability to bind BSL‐I lectin, and acquire the capacity to bind Dolichos biflorus. Because CD cells retain the same behavior in culture than in vivo, and by using DBA and BSL‐I as markers of cellular lineage besides specific markers of epithelial/mesenchymal phenotype, the experimental results strongly suggest the existence of mesenchymal cell insertion into the epithelial CD sheet. We propose such a mechanism as an alternative strategy for CD growing and development.
Identification of several cell cycle relevant genes highly correlated with the progression and prognosis of human bladder urothelial tumor
Authors: Wang Lu , Chen Song , Luo Yongwen , Yuan Lushun , Peng Tianchen , Qian Kaiyu , Liu Xuefeng , Xiao Yu , Wang Xinghuan
Published: January 2019

The incidence of bladder cancer (BCa) in China is the highest among genitourinary system tumors, and its progression is affected by multitudinous pathways, of which cell cycle progress plays an important role. This study screened and enriched differentially expressed genes (DEGs) from four gene expression profiles using bioinformatics analysis methods. The enrichment and analysis of gene function showed that these genes were highly correlated with cell cycle regulation. Identification of candidate small molecules was conducted to evaluate the application of clinical transformation in these DEGs. Prognostic and stage‐related expression analysis further sorted five highly expressed genes associated with worse prognosis and higher stages in patients with BCa. Further analysis revealed their interaction in cell cycle regulation and genetical alteration. Meanwhile, we validated the elevated expression of these genes through transcription and translation levels. Taking the results together, we could infer that these five genes are valuable in diagnosis, prediction, and providing candidate therapeutic targets for patients with BCa in different stages.
Pseudogene CHIAP2 inhibits proliferation and invasion of lung adenocarcinoma cells by means of the WNT pathway
Authors: Shang Jun , Wang Zhongyu , Chen Wenjie , Yang Zuyi , Zheng Liping , Wang Sihua , Li Shikang
Published: January 2019

Recently, pseudogenes have emerged as critical regulators in the onset of human neoplasia. Here, we present a comprehensive analysis of pseudogene alterations at transcriptional levels in lung adenocarcinoma (LUAD) from The Cancer Genome Atlas. By combinations of differential expression analysis, survival analysis, and univariate and multivariable Cox proportional hazards regression models, we identified four dysregulated pseudogenes, whose expression level was closely related to LUAD patients' prognosis and the four pseudogene signature could act as an independent prognostic indicator for LUAD patients. We further characterized CHIAP2, one of those four pseudogenes, whose expression level was the most closely linked to LUAD patients' prognosis. Consistent with our analysis, the expression of CHIAP2 was abnormally downregulated in LUAD tissues compared with that in normal tissues in our 50 pairs of clinical samples. Functional assays demonstrated that upregulation of CHIAP2 significantly impaired cell proliferation and invasion. After performing RNA sequencing (RNA‐seq) and small RNA‐seq between CHIAP2 overexpression and negative control LUAD cell lines, we identified differentially expressed messenger RNAs and microRNAs (miRNAs), among which six miRNAs were downregulated. Target genes of six downregulated miRNAs were predicted with online miRNA target prediction tools and significant pathways including the WNT signal pathway were identified with Gene Set Enrichment Analysis. By combining predictor genes of six downregulated miRNAs and dysregulated genes of the WNT pathway, we inferred that overexpression of CHAP2 may inhibit LUAD cell proliferation and invasion via modulation of NFATC2 or GSK3B (WNT signal pathway) targeted by miR‐3614‐5p or miR‐873‐3p.
Arecoline N‐oxide regulates oral squamous cell carcinoma development through NOTCH1 and FAT1 expressions
Authors: Kuo Tzer‐Min , Nithiyanantham Srinivasan , Lee Chi‐Pin , Hsu Hui‐Ting , Luo Shun‐Yuan , Lin You‐Zhe , Yeh Kun‐Tu , Ko Ying‐Chin
Published: January 2019

Areca nut has been evaluated as a group I carcinogen to humans. However, the exact compounds of areca nut causing oral cancer remain unproven. Previous findings from our lab revealed that arecoline N‐oxide (ANO), a metabolite of arecoline, exhibits an oral fibrotic effect in immune‐deficient NOD/SCID mice. The aim of this study is to investigate the oral potentially malignant disorders (OPMD) inductive activity between areca‐alkaloid arecoline and its metabolite ANO in C57BL/6 mice. Our findings show that ANO showed higher activity in inducing hyperplasia with leukoplakia and collagen deposition in C57BL/6 mice compared with the arecoline treated groups. Importantly, immunohistochemical studies showed significant upregulation of NOTCH1, HES1, FAT1, PCNA, and Ki67 expressions in the pathological hyperplastic part. In addition, in vitro studies showed that upregulation of NOTCH1 and FAT1 expressions in ANO treated HGF‐1 and DOK cell models. We found that NOTCH1 regulates TP53 expression from NOTCH1 knockdown oral cancer cells. The DNA damage was significantly increased after arecoline and ANO treatment. Further, we found that arecoline‐induced H2AX expression was regulated by FMO3. Altogether, our findings show that ANO exhibited higher toxicity in OPMD activity and play a significant role in the induction of areca nut mediated oral tumorigenesis.
Nix/BNIP3L‐dependent mitophagy accounts for airway epithelial cell injury induced by cigarette smoke
Authors: Zhang Ming , Shi Rong , Zhang Yeli , Shan Hu , Zhang Qiuhong , Yang Xia , Li Yali , Zhang Jie
Published: January 2019

Cigarette smoke‐induced airway epithelial cell mitophagy is an important mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Mitochondrial protein Nix (also known as BNIP3L) is a selective autophagy receptor and participates in several human diseases. However, little is known about the role of Nix in airway epithelial cell injury during the development of COPD. The aim of the present study is to investigate the effects of Nix on mitophagy and mitochondrial function in airway epithelial cells exposed to cigarette smoke extract (CSE). Our present study has found that CSE could increase Nix protein expression and induce mitophagy in airway epithelial cells. And Nix siRNA significantly inhibited mitophagy and attenuated mitochondrial dysfunction and cell injury when airway epithelial cells were stimulated with 7.5% CSE. In contrast, Nix overexpression enhanced mitophagy and aggravated mitochondrial dysfunction and cell injury when airway epithelial cells were incubated with 7.5% CSE. These data suggest that Nix‐dependent mitophagy promotes airway epithelial cell and mitochondria injury induced by cigarette smoke, and may be involved in the pathogenesis of COPD and other cigarette smoke‐associated diseases.
Mechanisms of statin‐induced new‐onset diabetes
Authors: Paseban Maryam , Butler Alexandra E. , Sahebkar Amirhossein
Published: January 2019

Statins, with their lipid‐lowering properties, are a first‐line therapy for the prevention of cardiovascular diseases. Recent evidence, however, suggests that statins can increase the risk of new‐onset diabetes (NOD). The molecular mechanisms of statin‐induced NOD are not precisely known, although some pathophysiologic mechanisms have been suggested. Specific to the beta cell, these mechanisms include alterations in insulin secretion, changes in ion channels, modulation of signaling pathways, and inflammation/oxidative stress. Outwith the beta cell, other suggested mechanisms involve adipocytes, including alterations in adipocyte differentiation and modulation of leptin and adiponectin, and genetic and epigenetic mechanisms, including alterations in microRNA. The evidence supporting these and other mechanisms will be discussed. Greater understanding of the underlying mechanisms linking the onset of diabetes to statin therapy is essential and clinically relevant, as it may enable novel preventative or therapeutic approaches to be instituted and guide the production of a new generation of statins lacking this side effect.
mTOR and Beclin1: Two key autophagy‐related molecules and their roles in myocardial ischemia/reperfusion injury
Authors: Shi Binhao , Ma Mengqing , Zheng Yitian , Pan Yanyan , Lin Xianhe
Published: January 2019

Autophagy is the general term of lysosomal degradation of substances in cells, which is considered the key to maintaining the normal structure and function of the heart. It also has a correlation with several heart diseases, in particular, myocardial ischemia/reperfusion (I/R) injury. At the stage of myocardial ischemia, autophagy degrades nonfunctional cytoplasmic proteins providing the critical nutrients for the critical life activities, thereby suppressing cell apoptosis and necrosis. However, autophagy is likely to affect the heart negatively in the reperfusion stage. Mammalian target of rapamycin (mTOR) and Beclin1 are two vital autophagy‐related molecules in myocardial I/R injury playing significant roles in different stages. In the ischemia stage, mTOR plays its roles through AMPK/mTOR and phosphoinositide 3‐kinase/Akt/mTOR pathway, whereas Beclin1 plays its roles through its upregulation in the reperfusion stage. A possible interaction between mTOR and Beclin1 has been reported recently, and further studies need to be done to find the underlying interaction between the two molecules in myocardial I/R injury
A Mechanism‐Based Population Pharmacokinetics Model of Erythropoietin in Premature Infants and Healthy Adults Following Multiple Intravenous Doses
Authors: D'Cunha Ronilda , Widness John A. , Yan Xiaoyu , Schmidt Robert L. , Veng‐Pedersen Peter , An Guohua
Published: January 2019

The objective of the current study was to develop a population pharmacokinetics (PK) model for erythropoietin (Epo) in premature infants and healthy adults to characterize the variation in PK, and to study the differences in Epo PK in these 2 populations. Thirteen very low‐birth‐weight premature infants (<1500 g at birth), and 10 healthy adults received up to 4 intravenous doses of Epo that ranged from 10 to 500 U/kg. The final model had a target‐mediated saturable, nonlinear, elimination pathway that incorporated the mechanism of Epo binding to its receptors along with a parallel linear, central elimination pathway. Epo clearance was found to be significantly higher in preterm infants compared to adults. Epo clearance via the nonlinear pathway was found to be much higher in infants; they had an Epo receptor capacity of 133 pM vs 86.6 pM in adults, which is most likely due to the higher erythroid progenitor cell mass per kilogram of body weight in infants. The parallel linear elimination was found to be more dominant in adults, reaching 91% of the total clearance with a 500‐U/kg dose compared to just 6.1% of the total clearance following the same dose in preterm infants. Thus, this mechanism‐based population PK model revealed that receptor‐based nonlinear elimination is the dominant Epo elimination pathway in premature infants, and parallel linear elimination is dominant in adults.
Population Pharmacokinetic Analyses and Model Validation of Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease
Authors: Lanke Shankar , Shoaf Susan E.
Published: January 2019

Tolvaptan is the first approved drug treatment to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease (ADPKD). The objective is to develop (1091 subjects, 7335 observations) and validate (678 subjects, 3012 observations) a population pharmacokinetic model to describe tolvaptan pharmacokinetics in ADPKD subjects. The final model was evaluated with a bootstrapping method. The final model was internally and externally evaluated using visual predictive checks (VPC). Pharmacokinetics was best described by a 1‐compartmental model with 0‐order absorption, nonlinear relative bioavailability (F1), and first‐order elimination. Accounting for changes in F1 significantly improved the model: as the dose increased from 15 mg to 120 mg, F1 decreased by 36%. Population estimates for clearance/F (CL/F), volume of distribution/F (Vd/F), duration of absorption (D1), the highest dose at which F1 is lowest, and the amount of dose at which F1 is 50% were 12.6 L·h‐1, 110 L, 0.58 hour, 182 mg, and 166 mg, respectively. The interindividual variability was 64% in CL/F, 70% in Vd/F, and 238% in D1. Residual variability was described by a combined‐error model. The VPC (500 data sets simulated) showed that 76% to 92% of the observed data fell within the 90% prediction intervals. The model stability assessed by a 1000‐run bootstrap analysis showed that the mean parameter estimates of data were within 10% of those obtained with the final model. The developed model is robust and stable. Internal and external validation confirmed the model ability to describe the data optimally.
Comparison of Cognitive Impairments After Intensive Care Unit Sedation Using Dexmedetomidine and Propofol Among Older Patients
Authors: Wang Wenhao , Liu Yi , Liu Yunfeng , Liu Feifei , Ma Yuxia
Published: January 2019

Despite the high prevalence of cognitive impairment among older adults, little is known about the association of the selection of dexmedetomidine and propofol on cognitive functions of patients after a critical illness. Patients aged ≥70 years who received intensive care unit (ICU) care from Cangzhou Central Hospital between 2013 and 2016 were enrolled and randomized into a dexmedetomidine group and a propofol group with matched demographic and clinical characteristics. At discharge from the ICU and 4 weeks later, the cognitive status of patients was assessed and compared using the Montreal Cognitive Assessment system. There were 164 patients included in the dexmedetomidine group and 159 patients in the propofol group. No significant difference was observed between the 2 groups in terms of age, female sex, body weight, educational level, ICU and hospital stay, comorbidities, and medications. Further, patients from the 2 groups at ICU discharge did not demonstrate significant difference on the Montreal Cognitive Assessment component scores, which showed significant differences between the 2 groups 4 weeks later (P < .05). Moreover, dexmedetomidine and propofol showed different levels of impacts on the cognitive function of patients discharged from the postanesthesia care unit, neurological ICU, and medical ICU. This study demonstrated that patients discharged from the ICU who received propofol for sedation showed less impairment on the cognitive functions when compared with patients who received dexmedetomidine during ICU care 4 weeks after discharge. Despite some limitations, this study provides insights to the decision‐making process in the selection of appropriate sedation strategy, especially for the elderly patients.
One hour enzymatic synthesis of structure lipids enriched unsaturated fatty acids from silkworm pupae oil under microwave irradiation
Authors: Wang Jin‐Zheng , Liu Xi , Li Wen‐Jing , Song Wen‐Miao , Herman Richard Ansah , Sheng Sheng , Wu Fu‐An , Wang Jun
Published: January 2019

BACKGROUND

The silkworm pupae of Bombyx mori L. are considered to be a valuable unsaturated fatty acids (UFAs) resource. Enzymatic transesterification, which can produce structured lipids (SLs), is regarded as a desirable approach to utilize this resource, but requires long reaction time. A method to reduce the reaction time and obtain novel SLs is thus desirable. Hence, microwave irradiation was employed to reduce the reaction time and obtain novel SLs. In addition, high‐performance liquid chromatography with an evaporative light scattering detector was employed to investigate the contribution of the fatty acids (FAs) after microwave irradiation.

RESULTS

One hour was required for a 1:5 substrate ratio of silkworm pupae oil (SPO):oleic acid (OA) using a solvent‐free system catalysed by Lipozyme RM IM (7%) at 60 °C with microwave irradiation at 50 W to obtain the novel SLs. The relative content of polyunsaturated FAs glyceride increased from 51.1% to 81.0%, and the relative content of glycerol trioleate (OOO) in SPO obtained in the microwave reactor was twice as high as that in the shaker reactor. In addition, the relative content of OA was increased from 3.9% to 35.8% in total compared with the products from the shaker reactor. Furthermore, the changes of α‐helix relative content of Lipozyme RM IM were observed after the reaction under the microwave irradiation.

CONCLUSION

The results indicated that variations in the FA distribution of enzymatic transesterification reactions caused by microwave irradiation could aid the addition of OA and enrichment of UFAs. © 2019 Society of Chemical Industry
Synthesis and characterization of ZnZr composites for the photocatalytic degradation of phenolic molecules: addition effect of ZrO2over hydrozincite Zn5(OH)6(CO3)2
Authors: Tzompantzi‐Flores Clara , Castillo‐Rodríguez Julio Cesar , Gómez Ricardo , Tzompantzi Francisco , Pérez‐Hernández Raúl , De la Luz Tlapaya Verónica , Santolalla‐Vargas Carlos Eduardo
Published: January 2019

BACKGROUND

The composite materials ZrO2/Zn5(OH)6(CO3)2were prepared in only one step by chemical co‐precipitation and thermal hydrolysis of urea. ZrO2was added at 5, 8 and 10 mol%. The samples were dried at 80 °C and characterized by adsorption–desorption of N2isotherms, X‐ray diffraction (XRD) and scanning electron microscopy (SEM) techniques, and diffuse reflectance (DRS), UV–visible, Fourier‐transform infrared (FTIR) and X‐ray photoelectron (XPS) spectroscopies. The materials were assessed in the photodegradation of phenol and polychlorinated phenolic molecules under UV‐light irradiation. The possible mechanism was discussed from studies that corroborated or discarded the formation of the species •OH, •O2−and h+.

RESULTS

The addition of ZrO2to Zn5(OH)6(CO3)2resulted in a composite material with high photoactivity. The material containing 8 mol% of ZrO2(ZnZr‐8.0%) was the sample with the best percentages of photodegradation and mineralization. The photodegradation enhancement was achieved partly by an increment in the specific surface area and principally due to localized states originating in the composite interphase which improved charge transfer. XPS study revealed that the ZrO2addition increases the oxygen vacancies which enhanced the organic molecule photodegradation via direct hole attack.

CONCLUSION

The ZnZr composite system constitutes an excellent alternative for the photodegradation of persistent organic pollutants due to the low cost, high stability and null toxicity of the support Zn5(OH)6(CO3)2. © 2019 Society of Chemical Industry
Preliminary design of a phenols purification plant
Authors: Zagklis Dimitris P , Paraskeva Christakis A
Published: January 2019

BACKGROUND

Phenols are compounds found in agricultural by‐products, with high antioxidant activity and positive impact on human health. As a result, their isolation and purification is of interest for the production of cosmetics, nutritional and pharmaceutical supplements.

A preliminary design for a plant with a treatment capacity of 1.1 m3 h−1 of liquid by‐products or extracts is presented herein, based on experiments carried out with three materials rich in phenolic compounds. The proposed process for the separation of phenols implements physicochemical methods such as solvent extraction, filtration through membranes, adsorption/desorption on resins and vacuum evaporation. The materials tested were olive mill wastewater (OMW), grape marc and olive leaves.

RESULTS

The final products of the proposed process were rich in phenolic compounds, with the OMW final concentrate containing 378 g L−1 phenols in gallic acid equivalents, 84.8 g L−1 being hydroxytyrosol (61% of the initial amount of hydroxytyrosol was retrieved in the final concentrate in 0.05% of the initial OMW volume). The final concentrate of olive leaf extract contained 98 g L−1 phenols in gallic acid equivalents, and the final concentrate of grape marc phenols 190 g L−1 in gallic acid equivalents, containing 4.7 g L−1 catechin (25% of the initial amount of catechin was retrieved in the final concentrate in 0.04% of the initial extract volume).

CONCLUSIONS

The combination of the proposed techniques proved to be effective for the separation and purification of phenols contained in agro‐industrial by‐products. As a result, a new process was designed for their separation and purification. © 2019 Society of Chemical Industry
Ventricular septal rupture with right ventricular wall dissection after inferior ventricular infarction: A case report and literature review
Authors: Li Tan , Kong Fan‐Xin , Wang Jun‐Li , Yang Jun , Ma Chun‐Yan
Published: January 2019

Right ventricular (RV) wall dissection following ventricular septal rupture related to inferior myocardial infarction (MI) is an extremely rare complication with a high mortality rate. We report the case of a 61‐year‐old man who was admitted to our hospital because of syncope and intermittent chest pain with a precordial murmur. Transthoracic echocardiography showed a rupture at the basal infero‐posterior septum and RV free‐wall dissection forming an echolucent cavity that extended beyond the septum and subsequently re‐entered into RV chamber. The patient's overall cardiac and renal functions deteriorated and he died 24 days after the diagnosis. We present a literature review of the published cases of complex dissecting tracts through the septum and RV wall in ischemic context.