bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of novel implant selective laser melting framework design on mechanical durability of acrylic veneer
Authors: Abduo Jaafar , Curtis Michael , Budhwar Vandana , Palamara Joseph 
Published: October 2018

AbstractBackgroundA novel implant framework design is proposed to improve the mechanical durability of acrylic veneer.PurposesComparing the mechanical durability of acrylic veneer on implant frameworks fabricated from selective laser melting (SLM) with novel design against conventional computer numeric controlled (CNC) milled frameworks.Materials and MethodsImplant titanium frameworks with distal cantilever were fabricated by SLM (n = 10) and CNC milling (n = 10). The CNC frameworks had multiple vertical pins, while the SLM frameworks had 3D metal networks of horizontal beams connected by vertical struts. All the frameworks were veneered with acrylic teeth and resin material and were subjected to a static load‐to‐failure test at the cantilever region. The load‐to‐failure readings and the pattern of prosthesis damage were recorded for each prosthesis.ResultsThe CNC and SLM prostheses failed at statistically similar loads. The acrylic veneer around the CNC frameworks tend to initially crack around the distal implant followed by acrylic chipping. Six SLM prostheses failed at the framework connector on the mesial implant by separation of the screw seat. After reloading these prostheses, they failed by acrylic veneer chipping. The SLM prostheses had significantly less incidence of acrylic flexure and severity of acrylic veneer chipping than CNC prostheses.ConclusionsThe SLM framework with novel design is efficient in reinforcing acrylic veneering. However, the SLM frameworks appeared weak in thin sections, such as the screw seat.
Evaluating Supervision Models in Functional Family Therapy: Does Adding Observation Enhance Outcomes?
Authors: Robbins Michael S. , Waldron Holly Barrett , Turner Charles W. , Brody Janet , Hops Hyman , Ozechowski Timothy 
Published: October 2018

This study examined the effects of observation‐based supervision Building Outcomes with Observation‐Based Supervision of Therapy (BOOST therapists = 26, families = 105), versus supervision as usual (SAU therapists = 21, families = 59) on (a) youth externalizing behavior problems and (b) the moderating effects of changes in family functioning on youth externalizing behaviors for adolescents receiving Functional Family Therapy (FFT). Exploratory analyses examined the impact of supervision conditions on youth internalizing problems. In 8 community agencies, experienced FFT therapists (M = 1.4 years) received either BOOST or SAU supervision in a quasi‐experimental design. Male (59%) or female (41%) adolescents were referred for the treatment of behavior problems (e.g., delinquency, substance use). Clients were Hispanic (62%), African American (19%), Non‐Hispanic White (12%), or Other (7%) ethnic/racial origins. Therapists (female, 77%) were Hispanic 45%, African American (19%), White Non‐Hispanic (30%), or other (4%) ethnic/racial backgrounds. Analyses controlled for the presence or absence of clinically elevated symptoms on outcome variables. Clinical outcomes were measured at baseline, 5 months, and 12 months after treatment initiation. Clients with externalizing behavior above clinical thresholds had significantly greater reductions in problem behaviors in the BOOST versus the SAU conditions. Clients below thresholds did not respond differentially to conditions. Supervisors in BOOST had more experience with the FFT model; as such, the observed results may be a result of supervisor experience. The BOOST supervision was associated with improved outcomes on problem behaviors that were above clinical thresholds. The findings demonstrate the importance of addressing client case mix in implementation studies in natural environments.
Social Services Professionals' Views of Barriers to Supporting Homeless Noncustodial Fathers
Authors: Rogers Tiana N. , Rogers Charles R. 
Published: October 2018

ObjectiveTo investigate barriers to service for homeless noncustodial fathers from the perspective of social service professionals who work directly to assist men with securing housing while meeting the demands of fatherhood.BackgroundThe population of homeless fathers in the United States is increasing. Longitudinal studies show that although homeless noncustodial fathers and mothers face similar risk factors and barriers to services, research on minimizing risk factors and barriers for noncustodial fathers is limited compared with that for noncustodial mothers.MethodThe sample included 7 administrators and 12 direct service professionals engaged with fathers transitioning from homelessness. Data were collected via face‐to‐face, semistructured interviews and analyzed using a qualitative inductive approach. Multiple‐cycle coding was used to capture emerging themes.ResultsThree major themes, encompassing emotional, relational, and systemic factors, emerged regarding participants' experiences serving homeless noncustodial fathers.ConclusionEffective approaches to supporting fathers require empathy, relationship building, and collaboration between service providers and policymakers.ImplicationsFuture policies and interventions should be based on input from direct service professionals and homeless noncustodial fathers themselves, with the aim of best supporting their efforts toward securing housing while meeting the demands of fatherhood.
Transnationalism, diaspora, and development: A purposive review of the literature
Authors: Tan Yan , Liu Xuchun , Rosser Andrew , Yeoh Brenda , Guo Fei 
Published: October 2018

AbstractIn view of the observation of some scholars and policymakers that contemporary international migration and its developmental effects are better understood from a transnational perspective, this paper attempts a systematic review of the impact of the transnational perspective on the relationship between migration and development in the fields of migration studies, population studies, and demography. Based on a study of 666 publications on transnationalism, diaspora, and development derived using keyword searches of the Web of Science database and a more in‐depth review of a subset of 60 influential papers on transnational linkages, the paper discusses five types of transnational linkages—familial, political, economic, sociocultural, and subjective. While the influence of transnationalism has been profound, stimulating an innovative body of work on changing migration patterns, the linkages between diaspora and their homelands, and the impact of these linkages on development, the review also identified significant gaps, namely, the inadequate attention to generating evidence of the developmental impact of transnational migration, particular in the Global South; the lack of consideration for the way diaspora from single homelands is internally differentiated and distributed across multiple transnational social spaces; and the need to identify data sources for more robust quantitative analyses of the multiple linkages between diaspora and development.
Moral dilemmas reflect professional core values of pharmacists in community pharmacy
Authors: Kruijtbosch Martine , Göttgens-Jansen Wilma , Floor-Schreudering Annemieke , van Leeuwen Evert , Bouvy Marcel L 
Published: October 2018

AbstractObjectivesThe aim was to recognise the professional core values in the moral dilemmas of pharmacists in community pharmacy and to customise the descriptions of these values for community pharmacy practice.MethodsThe narratives of 128 moral dilemmas, collected from Dutch PharmD students and early career pharmacists who experienced these dilemmas in practice, were qualitatively analysed. An expert panel deductively coded relevant portions of these narratives with the core values as formulated by the Royal Dutch Pharmacists Association. Other values that emerged were inductively coded and if possible used to further customise the respective core values.Key findingsThe expert panel identified all four professional core values, that is, commitment to the patient’s well-being (117, 91.4%), reliable and caring (116, 90.6%), pharmaceutical expertise (72, 56.2%) and responsibility to society (30, 23.4%) in the 128 moral dilemma narratives. Thirteen other values that emerged in the analysis could all be used for the customisation of the professional core values in descriptions that better reflect community pharmacy practice.ConclusionsProfessional core values were identified in moral dilemma narratives of pharmacists in community pharmacy and customised for their practice. These customised core values can enable pharmacists to better recognise moral dilemmas in practice. This can add to the advancement of the profession as a pharmaceutical care practice.
HMGB1 deficiency reduces H2O2‐induced oxidative damage in human melanocytes via the Nrf2 pathway
Authors: Mou Kuanhou , Liu Wei , Miao Yi , Cao Fang , Li Pan 
Published: October 2018

AbstractOxidative stress leads to melanocyte death and has been implicated in the pathogenesis of vitiligo. The nuclear factor, E2‐related factor 2 (Nrf2), is a critical transcription factor in protecting cells from oxidative damage. High‐mobility group box 1 (HMGB1) is a chromatin‐associated nuclear protein and an extracellular damage‐associated molecular pattern molecule. Extracellular HMGB1 released from activated immune cells, necrotic or injured cells, becomes a proinflammatory mediator through binding to cell‐surface receptors of responding cells. In this study, we investigated the role of HMGB1 from melanocytes in the response to oxidative stress and the mechanism involved. We showed that HMGB1 is expressed by primary normal human epidermal melanocytes (NHEMs). H2O2 treatment increased cytoplasmic translocation and extracellular release of HMGB1. HMGB1 knockdown by small interfering RNA (siRNA) led to decreased apoptosis of NHEMs. HMGB1 inhibition enhanced the expression of Nrf2 and its target genes. The expression of Nrf2 and its downstream antioxidant genes was downregulated after the supernatant of H2O2‐treated NHEMs was added to HMGB1‐deficient cells. HMGB1 knockdown by siRNA suppressed the expression of the autophagosome marker, LC3, and enhanced p62 expression. Coimmunoprecipitation with Keap1 showed a reduced Nrf2‐Keap1 interaction and an increased p62‐Keap1 interaction under oxidative stress. These data demonstrated that external stimuli (eg, oxidative stress) may trigger autocrine HMGB1 translocation and release by melanocytes, suppressing the expression of Nrf2 and downstream antioxidant genes to induce melanocyte apoptosis, and thereby participate in the pathological process of vitiligo.
MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling
Authors: Ye Dan , Lou Guohua , Zhang Tianbao , Dong Fengqin , Liu Yanning 
Published: October 2018

AbstractThe aberrant expression of Pknox1 is associated with hepatic glucose and lipid dysmetabolism status of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism causing Pknox1 overexpression in this pathological status remains unclear. By using miRNA target prediction programs, we found that the 3′‐UTR of the Pknox1 mRNA sequence contains highly conserved target sites of miR‐17 family. In a rat model of streptozotocin and high‐fat diet‐induced T2DM and NAFLD complication, the increased hepatic expression of Pknox1 was consistent with decreased expressions of miR‐17 family, especially miR‐17 and miR‐20a. Furthermore, an inverse correlation was observed between Pknox1 and miR‐17 and miR‐20a in free fatty acids‐induced hepatocyte steatosis. Dual‐luciferase reporter assay further showed that Pknox1 was a valid target gene of miR‐17 family. The ectopic expression of miR‐17 or miR‐20a could markedly suppress Pknox1 expression in hepatocytes. MiR‐17 or miR‐20a overexpression also resulted in significantly enhanced insulin sensitivity and reduced hepatocyte steatosis in HepG2 and L02 cells, which were determined by altered phosphorylation on insulin receptor signaling pathway proteins and decreased intracellular triglyceride and lipid accumulation, respectively. These data implicate the upregulated hepatic expression of Pknox1 in T2DM complicated with NAFLD may be caused by the reduced expression of miR‐17 family, indicating that developing miRNA‐mediated regulation strategies on Pknox1 may provide new therapeutic options for metabolic disease.
The applications of CRISPR/Cas system in molecular detection
Authors: Zhou Li , Peng Rongxue , Zhang Rui , Li Jinming 
Published: October 2018

AbstractThe Streptococcus pyogenes CRISPR/Cas system has found widespread applications as a gene‐editing and regulatory tool for the simultaneous delivery of the Cas9 protein and guide RNAs into the cell, thus making the recognition of specific DNA sequences possible. The recent study that shows that Cas9 can also bind to and cleave RNA in an RNA‐programmable manner is suggestive of potential utility of this system as a universal nucleic‐acid recognition tool. To increase the signal intensity of the CRISPR/Cas system, a signal amplification technique has to be exploited appropriately; this requirement is also a challenge for the detection of DNA or RNA. Furthermore, the CRISPR/Cas system may be used to detect point mutations or single‐nucleotide variants because of the specificity of the recognition between the target sequence and the CRISPR/Cas system. These lines of evidence make this technique capable of detecting pathogens during infection via analysis of their DNA or RNA. Thus, here we summarize applications of the CRISPR/Cas system to the recognition and detection of DNA and RNA molecules as well as the signal amplification. We also describe its potential ability to detect mutations and single‐nucleotide variants. Finally, we sum up its applications to testing for pathogens and potential barriers for its implementation.
Systematic identification and analysis of dysregulated miRNA and transcription factor feed‐forward loops in hypertrophic cardiomyopathy
Authors: Shi Hongbo , Li Jiayao , Song Qiong , Cheng Liang , Sun Haoran , Fan Wenjing , Li Jianfei , Wang Zhenzhen , Zhang Guangde 
Published: October 2018

AbstractHypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Although some genes and miRNAs related with HCM have been studied, the molecular regulatory mechanisms between miRNAs and transcription factors (TFs) in HCM have not been systematically elucidated. In this study, we proposed a novel method for identifying dysregulated miRNA‐TF feed‐forward loops (FFLs) by integrating sample matched miRNA and gene expression profiles and experimentally verified interactions of TF‐target gene and miRNA‐target gene. We identified 316 dysregulated miRNA‐TF FFLs in HCM, which were confirmed to be closely related with HCM from various perspectives. Subpathway enrichment analysis demonstrated that the method was outperformed by the existing method. Furthermore, we systematically analysed the global architecture and feature of gene regulation by miRNAs and TFs in HCM, and the FFL composed of hsa‐miR‐17‐5p, FASN and STAT3 was inferred to play critical roles in HCM. Additionally, we identified two panels of biomarkers defined by three TFs (CEBPB, HIF1A, and STAT3) and four miRNAs (hsa‐miR‐155‐5p, hsa‐miR‐17‐5p, hsa‐miR‐20a‐5p, and hsa‐miR‐181a‐5p) in a discovery cohort of 126 samples, which could differentiate HCM patients from healthy controls with better performance. Our work provides HCM‐related dysregulated miRNA‐TF FFLs for further experimental study, and provides candidate biomarkers for HCM diagnosis and treatment.
Upregulation of AMPK by 4‐O‐methylascochlorin promotes autophagy via the HIF‐1α expression
Authors: Seok Ji‐Young , Jeong Yun‐Jeong , Hwang Soon‐Kyung , Kim Cheorl‐Ho , Magae Junji , Chang Young‐Chae 
Published: October 2018

Abstract4‐O‐methylascochlorin (MAC) is a derivative of ascochlorin, a prenyl‐phenol compound antibiotic isolated from the fungus Ascochyta viciae. MAC induces caspase/poly (ADP‐ribose) polymerase‐mediated apoptosis in leukemia cells. However, the effects of MAC on autophagy in cancer cells and the underlying molecular mechanisms remain unknown. Here, we show that MAC induces autophagy in lung cancer cells. MAC significantly induced the expression of autophagy marker proteins including LC3‐II, Beclin1, and ATG7. MAC promoted AMP‐activated protein kinase (AMPK) phosphorylation and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream signalling proteins P70S6K and 4EBP1. The AMPK activator AICAR upregulated LC3‐II expression through the AMPK/mTOR pathway similar to the effects of MAC. MAC‐induced LC3‐II protein expression was slightly reduced in AMPK siRNA transfected cells. MAC upregulated hypoxia‐inducible factor‐1α (HIF‐1α) and BNIP3, which are HIF‐1α‐dependent autophagic proteins. Treatment with CoCl2, which mimics hypoxia, induced autophagy similar to the effect of MAC. The HIF‐1α inhibitor YC‐1 and HIF‐1α siRNA inhibited the MAC‐induced upregulation of LC3‐II and BNIP3. These results suggest that MAC induces autophagy via the AMPK/mTOR signalling pathway and by upregulating HIF‐1α and BNIP3 protein expression in lung cancer cells.
Detecting early‐warning signals of influenza outbreak based on dynamic network marker
Authors: Chen Pei , Chen Ely , Chen Luonan , Zhou Xianghong Jasmine , Liu Rui 
Published: October 2018

AbstractThe seasonal outbreaks of influenza infection cause globally respiratory illness, or even death in all age groups. Given early‐warning signals preceding the influenza outbreak, timely intervention such as vaccination and isolation management effectively decrease the morbidity. However, it is usually a difficult task to achieve the real‐time prediction of influenza outbreak due to its complexity intertwining both biological systems and social systems. By exploring rich dynamical and high‐dimensional information, our dynamic network marker/biomarker (DNM/DNB) method opens a new way to identify the tipping point prior to the catastrophic transition into an influenza pandemics. In order to detect the early‐warning signals before the influenza outbreak by applying DNM method, the historical information of clinic hospitalization caused by influenza infection between years 2009 and 2016 were extracted and assembled from public records of Tokyo and Hokkaido, Japan. The early‐warning signal, with an average of 4‐week window lead prior to each seasonal outbreak of influenza, was provided by DNM‐based on the hospitalization records, providing an opportunity to apply proactive strategies to prevent or delay the onset of influenza outbreak. Moreover, the study on the dynamical changes of hospitalization in local district networks unveils the influenza transmission dynamics or landscape in network level.
Advanced glycation end products‐related modulation of cathepsin L and NF‐κB signalling effectors in retinal pigment epithelium lead to augmented response to TNFα
Authors: Sharif Umar , Mahmud Nur Musfirah , Kay Paul , Yang Yit C. , Harding Simon P. , Grierson Ian , Kamalden Tengku Ain , Jackson Malcolm J. , Paraoan Luminita 
Published: October 2018

AbstractThe retinal pigment epithelium (RPE) plays a central role in neuroretinal homoeostasis throughout life. Altered proteolysis and inflammatory processes involving RPE contribute to the pathophysiology of age‐related macular degeneration (AMD), but the link between these remains elusive. We report for the first time the effect of advanced glycation end products (AGE)—known to accumulate on the ageing RPE's underlying Bruch's membrane in situ—on both key lysosomal cathepsins and NF‐κB signalling in RPE. Cathepsin L activity and NF‐κB effector levels decreased significantly following 2‐week AGE exposure. Chemical cathepsin L inhibition also decreased total p65 protein levels, indicating that AGE‐related change of NF‐κB effectors in RPE cells may be modulated by cathepsin L. However, upon TNFα stimulation, AGE‐exposed cells had significantly higher ratio of phospho‐p65(Ser536)/total p65 compared to non‐AGEd controls, with an even higher fold increase than in the presence of cathepsin L inhibition alone. Increased proportion of active p65 indicates an AGE‐related activation of NF‐κB signalling in a higher proportion of cells and/or an enhanced response to TNFα. Thus, NF‐κB signalling modulation in the AGEd environment, partially regulated via cathepsin L, is employed by RPE cells as a protective (para‐inflammatory) mechanism but renders them more responsive to pro‐inflammatory stimuli.
Cardiac‐specific Mst1 deficiency inhibits ROS‐mediated JNK signalling to alleviate Ang II‐induced cardiomyocyte apoptosis
Authors: Cheng Zheng , Zhang Mingming , Hu Jianqiang , Lin Jie , Feng Xinyu , Wang Shanjie , Wang Tingting , Gao Erhe , Wang Haichang , Sun Dongdong 
Published: October 2018

AbstractApoptosis is associated with various myocardial diseases. Angiotensin II (Ang II) plays a central role in the pathogenesis of RAAS‐triggered cardiac apoptosis. Our previous studies showed that mammalian Ste20‐like kinase 1 (Mst1) aggravates cardiac dysfunction in cardiomyocyte under pathological conditions, but its role in Ang II‐mediated cardiomyocyte apoptosis is not known. We addressed this in the present study by investigating whether cardiac‐specific Mst1 knockout can alleviate Ang II‐induced cardiomyocyte apoptosis along with the underlying mechanisms. In vitro and in vivo experiments showed that Ang II increased intracellular reactive oxygen species (ROS) production and cardiomyocyte apoptosis; these were reversed by administration of the ROS scavenger N‐acetylcysteine and by Mst1 deficiency, which suppressed c‐Jun N‐terminal kinase (JNK) phosphorylation and downstream signaling. Interestingly, Mst1 knockout failed to alleviate Ang II‐induced phosphorylation of extracellular signal‐regulated kinase 1/2, and inactivated apoptosis signal‐regulating kinase1 (ASK1) by promoting its association with thioredoxin (Trx), which reversed the Ang II‐induced activation of the ASK1–JNK pathway and suppressed Ang II‐induced cardiomyocyte apoptosis. Thus, cardiac‐specific Mst1 knockout inhibits ROS‐mediated JNK signalling to block Ang II‐induced cardiomyocyte apoptosis, suggesting Mst1 as a potential therapeutic target for treatment of RAAS‐activated heart failure.